Research

The prevalence of hepatitis C in patients admitted with acute hepatitis to Fairfield Infectious Diseases Hospital, 1971-1975 Jennifer A Thomson, Alison J Rodger, Sandra C Thompson, Damien Jolley, Amanda Byrne, Susan J Best and Nick Crofts MJA 1998; 169: 360-363 Abstract - Introduction - Methods - Results - Discussion - Acknowledgements - References - Authors' details - - More articles on Infectious diseases and parasitology - ©MJA1998 Abstract Objective: To identify and determine trends in the prevalence of hepatitis C virus (HCV) antibody in stored sera from 1971 to 1975 and to determine associations with HCV seropositivity, including markers for other hepatitis infections and possible routes of transmission. Design: A retrospective cross-sectional study. Patients and setting: 1511 adults admitted to Fairfield Infectious Diseases Hospital, Victoria, with a clinical and biochemical diagnosis of hepatitis between 1 January 1971 and 31 December 1975. Main outcome measures: Prevalence over study period of hepatitis A virus antibody (anti-HAV) IgM, hepatitis B core antibody (anti-HBc), hepatitis B surface antigen (HBsAg) and hepatitis C virus antibody (anti-HCV) in stored sera; sociodemographic data and risk factors for blood-borne viruses documented in original medical records. Results: Anti-HCV was detected in 17% of adults admitted with hepatitis from 1971 through 1975. Prevalence increased significantly over this period. Most cases were in young men who had a history of injecting drug use. HCV seropositivity was also significantly associated with markers for hepatitis B infection. Conclusions: Given the 20-30-year period between infection with hepatitis and the development of liver disease, our findings predict significant liver-related morbidity in Australia in the next decade. The increase in prevalence over the five years studied suggests rapid spread of HCV through susceptible populations, principally injecting drug users. Introduction Hepatitis C is an important public health problem in Australia. Approximately 150 000 people in this country are currently infected with the virus, predominantly as a result of injecting drug use.1,2 Acute hepatitis C virus (HCV) infection is generally benign; less than 25% are estimated to be icteric.3 The main significance of HCV infection is that it is strongly associated with the development of chronic liver disease. After 20 to 30 years a significant proportion of those infected will have chronic hepatitis, cirrhosis, liver failure and primary hepatocellular carcinoma.4 In view of this 20-30-year latency period, estimating the prevalence of HCV in the Australian community during the early 1970s may give an indication of the morbidity to be expected from this infection over the next decade. We thus aimed to determine the prevalence of hepatitis C antibody in stored sera from people with acute viral hepatitis admitted to Fairfield Infectious Diseases Hospital (FIDH), Victoria, from 1971 to 1975, to identify possible associations with HCV seropositivity and to detect trends in HCV prevalence over that time. Methods Ethical approval for the study was obtained from the ethics committees at FIDH and the Australian Institute of Health and Welfare. We chose the period 1971 to 1975 because systematic storage of sera began in 1971, the same year diagnostic coding was standardised at FIDH (with the introduction of International classification of diseases, ninth revision coding), and because a previous study had identified HCV antibody in stored sera from that time.5We included all patients admitted to FIDH with biochemical and clinical evidence of hepatitis between 1 January 1971 and 31 December 1975. Those for whom there was no original serum sample for testing and those for whom medical records could not be found were excluded. Patients aged under 16 years at the time of admission were also excluded as they were generally admitted for hepatitis A infection, which was endemic at that time.6 Multiple serum samples had been stored for many patients. For each individual, we tested the last available serum sample associated with their final hepatitis admission and which was adequate for testing. Sera were tested for all hepatitis markers at the Victorian Infectious Diseases Reference Laboratory and the National Serology Reference Laboratory, Australia by the following commercially available immunoassays: hepatitis A virus antibody (anti-HAV) IgM, IMX assay and HAVAB M enzyme immunoassay; hepatitis B core antibody (HBcAb), CORAB radioimmunoassay; hepatitis B surface antigen (HBsAg), AUSRIA II radioimmunoassay; and hepatitis C antibody (HCVAb), second generation enzyme immunoassay (all assays manufactured by Abbott Diagnostics, Abbott Park, Illinois, USA). Results were designated reactive or non-reactive by the laboratories. As previous studies of frozen sera stored for long periods suggested a stringent classification was required to avoid overestimating the prevalence of antibody to HCV,7,8 we used twice the manufacturer's recommended cutoff (as recommended in the literature7) to further increase the specificity of the HCV antibody test. Individuals with weakly positive results (ie, a ratio of 1-2 of sample optical density determined by enzyme-linked immunosorbent assay [ELISA] to cutoff optical density) were recorded as equivocal and excluded to minimise misclassification bias. Medical records were located and information collected on sociodemographics and risk factors for hepatitis. For patients with multiple admissions over the study period, information on risk factors was summarised from all admissions preceding the date of the last available serum sample. We compared our test results for the stored serum samples with the original results recorded for HBsAg at the time the samples were taken using K 9 to measure agreement. In addition, we traced a subset of patients in 1996 and 1997 and obtained information on risk factors before their FIDH admission. Traced patients were also retested for hepatitis B and C markers in 1996 and 1997. The results of tests on their original stored serum samples were compared with these follow-up results for hepatitis C virus antibody (anti-HCV) and hepatitis B core antibody (anti-HBc). Statistical analysis We used the Statistical Package for Social Sciences (SPSS)10 for data analysis, which included descriptive statistics, unpaired t test, chi-squared test, Fisher's exact test, chi-squared test for trend, and measures of risk and agreement. Results Patients aged over 16 and admitted to FIDH with hepatitis during the study period numbered 1798. Medical records were found for 1737 (97%) and 5% were noted to have been admitted with hepatitis more than once over the study period. Serum specimens were found for 1559 of these patients (90%) and testing for all the measured hepatitis markers was completed for 1511 (87%). We were able to trace a subset of 161 patients for follow-up in 1996 and 1997. The distribution of optical density ratios indicating anti-HCV status for the 1511 patients in the study is shown in Box 1. Seven per cent (99) had equivocal anti-HCV results and were excluded. Of the remaining 1412, 17% (238) were anti-HCV positive. Only 15% (37) of those who were anti-HCV positive had no evidence of other hepatitis markers. Those who were anti-HCV positive were significantly more likely to have markers for hepatitis B virus (Box 2), and the sensitivity and specificity of anti-HBc as a surrogate marker for HCV infection were 77% and 57%, respectively. The trends in prevalence of each of the measured hepatitis markers were significant (P < 0.05). The prevalence of anti-HCV increased fourfold, with the biggest increase between 1974 and 1975. The prevalence of anti-HBc and HBsAg also increased, while the prevalence of anti-HAV IgM declined (Box 3). In patients who were HCV seropositive, the prevalence of markers of hepatitis A and B did not change significantly over the study period. Validation of serological tests For the 161 patients we traced, comparing the results of serological testing of their stored sera for anti-HBc and anti-HCV with those of follow-up tests in 1997 showed good overall agreement, with complete agreement for anti-HBc of 91% (K, 0.79; 95% CI, 0.67-0.91) and, for anti-HCV, of 88% (K, 0.74; 95% CI, 0.66-0.82). For all patients, there was moderate agreement between HBsAg results recorded at the time of original admission and our results for the stored sera, with complete agreement for 65% (K, 0.58; 95%CI, 0.43-0.72). Sociodemographic data and risk behaviours Sociodemographic data were available from medical case records for all patients. The 238 individuals who were positive for anti-HCV were significantly younger than those who were anti-HCV negative (mean age at time of original admission, 22 years; SD, 5.3 years v. 29.5 years; SD, 12 years; P < 0.001). Anti-HCV-positive individuals were also significantly more likely to have been born in Australia (80% v. 69%; RR, 1.5; 95% CI, 1.4-1.8; P < 0.001) and to be male (62% v. 52%; RR, 1.4; 95% CI, 1.1-1.9; P < 0.001). Information on risk factors was incompletely recorded in medical records. Only 40% had information recorded for injecting drug use, 69% for contact with someone with hepatitis, 36% for transfusion, 15% for tattooing and 11% for travel. A history of injecting drug use and of contact with someone with hepatitis were the only risk factors significantly associated with HCV seropositivity (Box 2). There was good agreement between original records of injecting drug use in case records on admission and follow-up information obtained from the 161 patients traced in 1996 and 1997 (k, 0.83; 95% CI, 0.74-0.92). Discussion Our findings confirm the presence of anti-HCV among adults admitted with acute hepatitis to FIDH in Victoria in the early 1970s and also that its prevalence increased markedly from 1971 through 1975. Most cases were in young men who had a history of injecting drug use. Most individuals with HCV appear to have been admitted because of subsequent infection with hepatitis A or B. While the actual proportion is unclear, it is likely to be significant as only 16% of HCV-seropositive individuals had no evidence of other acute hepatitis markers. As this implies that individuals with subclinical acute HCV infection were admitted and therefore included in the study, the HCV seropositive group would appear to be reasonably representative of community-acquired HCV infection in Melbourne in the 1970s. The significant association between the presence of HCV antibody and documented contact with a person with clinical hepatitis infection probably results from a spurious association with the hepatitis A or hepatitis B infection that precipitated admission. This also suggests that those infected with HCV were likely to have risk behaviours that exposed them to other hepatitis viruses, in particular to hepatitis B. Significant misclassification of hepatitis status appears unlikely as there was moderate to good agreement between original results for hepatitis A and B with our results. In addition, we used a more stringent cutoff to classify anti-HCV status, to increase specificity and reduce misclassification bias. Another source of potential bias in our study was loss of samples as a result of our exclusion criteria, but given the large sample size this should not have significantly affected our findings. The risk factor information in the original case records was also incomplete and may have been subject to bias. However, the results of follow-up assessment of risk factors in patients we were able to trace equate well with risk factor information documented at the time of original admissions, in particular the presence or absence of a history of injecting drug use. In addition, the association between injecting drug use and HCV seropositivity -- documented in many other studies in the 1990s1,2,11-14 -- was very clear. We did not identify the presence of tattoos and a history of blood transfusion as significant risk factors for HCV seropositivity, and this probably reflects the low prevalence of HCV in the general population in the 1970s. The significant increase in the prevalence of HCV seropositivity over the five-year study period suggests that infection became firmly established within the Australian community, particularly the injecting drug user population, as early as the mid 1970s. Most of the estimated 150 000 people in Australia currently infected with HCV are thought to have become infected in the past two decades, implying that the population of injecting drug users expanded dramatically in the late 1970s and early 1980s.1 Our finding of a twofold increase in the recording of injecting drug use among patients admitted with viral hepatitis from 1971 through 1975 supports this. Given the 20-30-year latency period before the development of liver-related complications, it is likely that the rapid increase in prevalence of HCV infection from the mid 1970s will translate into a rapid increase in HCV-positive individuals presenting with liver disease over the next decade. Health service planning and resource allocation should take this into account. Further research is now urgently required on the natural history of community-acquired, as opposed to transfusion-acquired, HCV infection in the Australian population and on factors that predict the development of hepatic sequelae. Acknowledgements We thank Anna Lanigan (MBCMR), Dr Alan Breschkin, Dr Mike Catton and Associate Professor Steven Locarnini (Victorian Infectious Diseases Reference Laboratory) and Dr Elizabeth M Dax (National Serology Reference Laboratory, Australia). The National Health and Medical Research Council (NHMRC) Public Health and Development Committee provided funding for the study, and Dr J Thomson was an NHMRC PHRDC Research Fellow. Dr Nick Crofts was funded from the Research Fund of the Macfarlane Burnet Centre and Dr Alison Rodger partly funded by the Victorian Health Promotion Foundation. References Crofts N, Jolley D, Kaldor J, et al. Epidemiology of hepatitis C virus infection among injecting drug users in Australia. J Epidemiol Community Health 1997; 51: 692-697. MacDonald M, Crofts N, Kaldor J. Transmission of hepatitis C virus rates, routes, and cofactors. Epidemiol Rev 1996; 18: 137-148. Alter HJ. To C or not to C? These are the questions. Blood 1995; 85: 1681-1695. Seeff L. Natural history of Hepatitis C. Hepatology 1997; 26: 21-28. Moaven L, Crofts N, Locarnini SA. Hepatitis C virus infection in Victorian injecting drug users in 1971. Med J Aust 1993; 158: 574. Lehmann NI, Gust ID. The prevalence of antibody to hepatitis A virus in two populations in Victoria. Med J Aust 1977; 2: 731-732. Lok AS, Ma OC, Chan TM, et al. Overestimation of the prevalence of antibody to hepatitis C virus in retrospective studies on stored sera. Hepatology 1991; 14: 756-762. Moaven L, Cunningham T. Hepatitis C serology. Aust Microbiologist 1994; 12: 321-323. Fleiss J. Statistical methods for rates and proportions. 2nd ed. London: Wiley; 1981. SPSS [computer program]. Version 8. Chicago, Ill.: SPSS Inc, 1998. Van Beek I, Buckley R, Stewart M, et al. Risk factors for hepatitis C virus infection among injecting drug users in Sydney. Genitourin Med 1994; 70: 321-324. Crofts N, Aitken, CK. Incidence of and risk behaviours for blood-borne viruses in a cohort of injecting drug users in Victoria, 1990-1995. Med J Aust 1997; 167: 17-20. Galeazzi B, Tufano A, Barbierato E, et al. Hepatitis C virus infection in Italian intravenous drug users: epidemiological and clinical aspects. Liver 1995; 15: 209-212. Van den Hoek JA, van Haastrecht HJ, Goudsmit J, et al. Prevalence, incidence, and risk factors of hepatitis C virus infection among drug users in Amsterdam. J Infect Dis 1990; 162: 823-826. (Received 3 Feb, accepted 3 Aug, 1998) Authors' details Epidemiology and Social Research Unit, The Macfarlane Burnet Centre for Medical Research, Melbourne, VIC. Jennifer A Thomson, PhD, FAFPHM, Research Fellow; Alison J Rodger, MRCP(UK), MFPHM(UK), Research Fellow; Sandra C Thompson, PhD, FAFPHM, Research Associate; Amanda Byrne, BSc(Hons), MSc, Research Assistant; Nick Crofts, MPH, FAFPHM, Head. Department of Public Health & Community Medicine, The University of Melbourne, Melbourne, VIC. Damien Jolley, MSc(Epidemiol), MSc(Stats), Senior Lecturer in Epidemiology and Biostatistics. National Serology Reference Laboratory, Australia, Melbourne, VIC. Susan J Best, DipMedTech, Senior Scientist. Reprints will not be available from the authors. Correspondence: Dr A J Rodger, The Macfarlane Burnet Centre for Medical Research, PO Box 254, Fairfield, VIC 3078. E-mail: rodgerATburnet.edu.au - Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Jennifer A Thomson · Alison J Rodger · Sandra C Thompson · Amanda Byrne · Susan J Best · Nick Crofts

Re-engineering the elective surgical service of a tertiary hospital: a historical controlled trial Gideon A Caplan, Ann Brown, Philip J Crowe, Su-Jen Yap and Shaune Noble MJA 1998; 169: 247-251 For editorial comment, see Hillman Abstract - Introduction - Methods - Patients - Outcome measures - Control group--existing system - Postintervention group--the perioperative system - Operative complications - Statistical analysis - Results - Outcomes - Complications - Patient satisfaction - Discussion - Acknowledgements - References - Authors' details - Figure 1 - Figure 2 - - - ©MJA1998 Abstract Objective: To study the clinical effects of re-engineering the processes associated with elective surgery. Design: A prospective, historical controlled trial. Control patients were enrolled from March 1995 to January 1996, and postintervention patients from February 1996 to October 1996. Setting: A major teaching, tertiary care hospital (Prince of Wales Hospital, Sydney). Patients: 224 patients (123 before and 101 after the intervention) undergoing elective herniorrhaphy or laparoscopic cholecystectomy who lived in the local area. Intervention: Introduction of a re-engineered surgical service consisting of preadmission assessment and education, admission on day of surgery, and postacute care after discharge. There were no changes to the operative methods or infection control procedures. Main outcome measures: Length of stay, operative complications, pain scores and patient satisfaction. Results: The risk of a patient suffering one or more complications was reduced in the postintervention group (postintervention v. control patients: 25.7% v. 38.2%; relative risk [RR], 0.66; 95% confidence interval [CI], 0.44-0.98; P = 0.035) because of a reduced risk of wound infections (5.0% v. 16.3%; RR, 0.30; 95% CI, 0.12-0.78; P = 0.0075). Other complications (perioperative or postoperative) and pain scores were unchanged. Patients treated by the re-engineered service had a significantly shorter length of stay, reported a higher level of satisfaction with the preoperative and postdischarge care, and were more likely to say that they would have the same treatment again (92.9% v 82.6%; P = 0.037). Conclusions: Re-engineering surgical services, with an associated reduction in length of stay, does not lead to a deterioration in care and may decrease postoperative complications and increase patient satisfaction. MJA 1998; 169: 247-251 Introduction Financial pressures from insurance companies1 and governments2 are driving changes in the healthcare systems of many countries. One of the most visible changes is shorter hospital stay, especially for elective surgery.3 Organisational changes include preadmission clinics, enhanced patient education, increased use of day surgery, improved discharge planning and postacute care at home; and clinical changes include less invasive surgical techniques and improved anaesthetic drugs.4 The introduction of a package of these organisational changes amounts to a re-engineering of elective surgery.5Many of these changes have been introduced with little scientific evaluation of their effect on patients, and perceptions of detrimental effects on patient care can make such changes unpopular.1,2 Studies of healthcare changes so far6-10 have focused on changes in surgical procedures and have been unable to identify any clinical effects of initiatives, such as preadmission clinics, patient education, reduction in length of stay, and postacute care. Moreover, in these studies, control patients underwent different procedures,6,7 significant results were not obtained,8,9 or there were worse outcomes in the postintervention group.10 We studied the effects of re-engineering our elective surgical service using a prospective, historical, controlled trial. Our re-engineered service comprised a perioperative unit, preadmission anaesthetic assessment based on self-reported questionnaires, admission on the day of surgery, enhanced patient education, use of clinical pathways, and postacute care (Box 1). 1: A re-engineered surgical service Admission coordinated by Perioperative Unit, which sends out, receives and reviews patients' self-reported health questionnaires, and arranges preadmission assessment, if indicated. Patients admitted to Perioperative Unit on day of surgery. After surgery, day-only patients return to Perioperative Unit, others to the ward. Patient information specific for each operation distributed by the surgeon. Nurses reinforce patients' knowledge. Clinical pathways followed. These provide a diagnosis-specific plan for the episode of care and the role of each member of the multidisciplinary team. Postacute care continues at home after discharge, if required. Methods Patients To minimise variation and ensure adequate patient numbers, we studied prospectively a cohort of patients having one of two general surgical procedures (inguinal herniorrhaphy and laparoscopic cholecystectomy). Patients in the control group were treated before and compared with patients treated after the new elective surgical service was commissioned. Patients who lived outside the local area or were admitted as an emergency were excluded. All patients gave informed consent, and the study was approved by the South Eastern Sydney Area Health Service (Eastern Branch) Ethics Committee. Outcome measures Information collected for comparing the control and postintervention groups included length of hospital stay, level of pain (assessed by a linear analogue pain scale), complications of the operation, and patient satisfaction (assessed by a self-reported questionnaire). Control group -- existing system Patients booked for surgery from the surgeon's rooms or surgical outpatients clinic; Patient information and education provided according to individual surgeon's protocols; Patients admitted to the ward on the day before the procedure, clerked by the surgical intern and assessed by the anaesthetist; Postsurgical care given in the surgical ward; and Discharge plans made by ward staff, subject to individual surgeon's decision. A total of 123 control patients were enrolled prospectively from March 1995. (We had planned to enrol 100, but a delay in commissioning the new system extended the enrolment period.) Eligible patients booked for surgery each day were visited by the study nurse on admission to the ward. After surgery, the nurse obtained patient data, including a pain score on Day 1 after the operation, and arranged to contact the patient by telephone on Day 7. Before discharge, patients were given an anonymous, self-reported patient satisfaction survey, based on the Australian model.11 They were asked to rate their overall treatment, the information provided, preoperative treatment, the operation and care after discharge from hospital on a five-point Likert scale from "very satisfactory" to "very unsatisfactory". They were also asked whether they would have the procedure the same way again, and were given a further copy of the pain scale, and asked to complete both documents on Day 7 after the operation and return them in the prepaid envelope provided. The telephone call on Day 7 reminded patients to return their satisfaction surveys and pain scores. Postintervention group -- the perioperative system A more coordinated system was developed, based on the perioperative system (Box 1).12 The surgeons, nursing staff, operating theatre location and organisation and infection control practices did not change. Although surgical registrars changed surgical units during the study period, they worked with other surgeons whose patients were also studied. The Perioperative Unit included a preadmission anaesthetic clinic where patient health questionnaires were completed, and patients with significant comorbidity were fully assessed. Based on the information provided by the questionnaires, 70% of elective surgery patients were seen by an anaesthetist for the first time on the day of surgery, 15% of patients were seen as outpatients before the day of surgery because of anaesthetist preference, and the remaining 15% required further anaesthetic consultation and one (usually) additional outpatient visit for review. All patients, both day-only and those transferring to the surgical ward after the operation, went to theatre from a day-surgery ward within the Perioperative Unit. Patient care was guided by a clinical pathway developed by the multidisciplinary team to drive and support the system. The role of every member of the multidisciplinary team is specified for each day, with alternative plans available if a patient's condition changes. Improved patient educational material was developed for distribution by the surgeons, and patients' comprehension of the material was reviewed by the study nurse at the preadmission anaesthetic clinic or on the day of surgery. If doubts existed about the safety and suitability of a patient's accommodation for postsurgical recovery, the study nurse made a preadmission home visit. After surgery, study patients were transferred to the surgical ward and an existing postacute care service arranged early discharge with follow-up at home. The new system was introduced at the end of January 1996 and enrolment of the 101 patients in the postintervention group commenced in February 1996. A pain scale was completed on Day 1 after operation. The timing of discharge was entirely at the surgeons' discretion, and the study nurse arranged to visit the patient at home within 24 hours of hospital discharge to assess pain control, wound care needs and general postsurgical progress. This visit generally lasted less than half an hour, and occasional further visits were arranged, as clinically indicated. A contact phone number was provided for use in the event of any complications or concerns. Patients in the postintervention group were also asked to complete the self-reported patient satisfaction survey. Operative complications Data on all complications were collected prospectively and crosschecked with the patients' clinical records. The criteria for wound infections were those of the Centers for Disease Control and Prevention (CDC),13 notably that the infection involves only the skin and subcutaneous tissue of the incision, and at least one of the following: purulent drainage from the superficial incision; organisms isolated from aseptically obtained culture of fluid or tissue from the superficial incision; at least one of the following signs or symptoms of infection -- pain or tenderness; localised swelling; redness or heat; and superficial incision is deliberately opened by the surgeon, unless incision is culture negative; diagnosis of superficial incisional surgical site infection by the surgeon or attending physician. Statistical analysis Statistical calculations were performed using SPSS for Windows.14 Normally distributed continuous variables were compared by t tests, dichotomous variables by χ2 tests. Ordinal variables were compared with the Mann-Whitney U test. Logistic regression was used to obtain a multivariate analysis of factors predictive of wound infection. Results From March 1995 to October 1996, 224 patients were enrolled in the study. Baseline characteristics of the two groups were not statistically significantly different (Box 2). 2: Baseline characteristics of elective surgery patients Postintervention group* (n = 101) Control group* (n = 123) Laparoscopic cholecystectomy 57 (56.4%) 65 (52.8%) Herniorrhaphy 44 (43.6%) 58 (47.2%) Mean time in operating theatre (min, SEM) 100.3 (4.2) 102.1 (3.5) Female : male ratio 46 : 55 54 : 69 Mean age (range) (years) 54.4 (21-85) 54.0 (18-90) Smoker 27 (26.7%) 25 (20.3%) Ischaemic heart disease 8 (7.9%) 9 (7.3%) Requires an interpreter 8 (7.9%) 4 (3.3%) Lives alone 19 (18.8%) 23 (18.7%) Lives upstairs (no lift) 37 (36.6%) 39 (31.7%) *Differences were not statistically significant Outcomes The postintervention group had a significantly shorter length of stay, but there was no difference in pain scores between the two groups (Box 3). 3: Outcomes in the postintervention and control groups Outcome Postintervention group Control group Mean length of stay in days (range) 2.2 (1-8) 3.2 (1-9)* For herniorrhaphy 1.8 (1-4) 3.1 (2-7)þ For laparoscopic cholecystectomy 2.5 (1-8) 3.3 (1-9)§ Postoperative pain score mean (SEM) Day 1 21.7 (1.2) 22.6 (0.9) Day 7 9.4 (1.1) 8.4 (1.0) Number of deaths 0 1 (0.8%) Number readmitted 5 (5.0%) 4 (3.3%) Postintervention v. control group: *P < 0.001; þ P < 0.001; § P = 0.020. Complications The postintervention group had a lower risk of suffering any complication (complications in postintervention v. control patients -- 26 [25.7%] v. 48 [38.2%]; relative risk [RR], 0.66; 95% confidence interval [CI], 0.44-0.98; P = 0.035) because of a lower risk of wound infection (Figure 1). There was no significant difference between postintervention and control patients in intraoperative complications or other postoperative complications (Figure 1). Figure 1: Proportion of patients with each type of complication in the postintervention and control groups, including relative risk (RR) and 95% confidence interval (CI) for comparison between the groups. Intraoperative complications were bile/stone spillage (4 v. 5), conversion to open cholecystectomy (4 v. 1) and, in the control group, one each of cystic duct damaged, cystic artery damaged, unsuccessful exploration of common bile duct, local anaesthetic converted to general anaesthetic, penis injured by towel clips, and aspiration into lungs. Postoperative complications are listed in Box 4. Eight patients suffered two complications and one three complications, so that the total for all types of complications exceeds the number of patients who suffered a complication. 4: Postoperative complications Complication Postintervention group (n = 22) Control group (n = 42) Wound infection 5 20 Cerebrovascular accident, died 0 1 ERCP after operation 2 4 Haematoma/haemorrhage/ooze 4 1 Shoulder tip pain 1 2 Scrotal pain or swelling 2 2 Nausea and vomiting 2 0 Constipation (> 4 days) 2 2 Urinary retention requiring indwelling catheter 1 1 Unstable INR after operation, delayed discharge 0 2 Rash (due to antibiotics) 0 1 Fall Day 1 after operation, low blood pressure 0 1 Delirium 0 1 Difficulty mobilising 0 1 Respiratory infection 3 3 ERCP = endoscopic retrograde cholangiopancreatography. INR = International Normalised Ratio. Multivariate analysis using logistic regression found that the only variables significantly predictive of having a wound infection were being in the control group, length of stay (Figure 2) and the patient having a carer (a proxy for functional dependence). Figure 2: Proportion of patients with wound infection in the postintervention and control groups, by length of stay. Patient satisfaction Completed responses to the satisfaction survey were received from 85 postintervention patients (84.2%) and 89 controls (72.4%). Analysis showed that patients in the postintervention group were more satisfied with both the preoperative (P = 0.0094) and the postdischarge treatment (P = 0.0001), as well as the operation, and were also more likely to want to have the procedure done the same way next time, if required (postintervention v. control: 92.9% v 82.6%; difference, 10.3%; 95% CI, 0.8%-19.8%; P = 0.037). There was no difference between the groups in their ratings of the overall treatment or of the information supplied preoperatively. Although the difference in response rates between the control and postintervention groups was significantly different (P < 0.05), there were no significant differences between respondents and non-respondents in terms of age, sex, type of operation, pain scores, complications, comorbidity, living arrangements, occupational or smoking status. Discussion Patients having elective surgery after a re-engineered system of coordinated care for elective surgery was introduced had shorter hospital stays, a lower risk of wound infection and reported higher levels of satisfaction. Previous studies, rather than focusing on the outcomes of the process, as we did, have examined the impact of elements of our re-engineered service (particularly preadmission clinics) on the efficiency of the elective surgical process.15 Our study found a higher rate of wound infection than is generally reported in surgical series, although the rate was within the range of prevalence of nosocomial infections (3%-21%) in a World Health Organization survey,16 and comparable with rates in an Australian survey which also actively followed up patients for wound infections after discharge.17 Surveys may also identify widely varying wound infection rates if different definitions of infections are used.18 Definitions of wound infections which require the presence of pus19 tend to underestimate the true prevalence, given that most doctors institute antibiotic therapy for earlier signs of infection. With decreasing lengths of hospital stay, most wound infections occur after discharge from hospital, where they are often diagnosed and treated by general practitioners (GP) and not surgeons.17 Thus, it is not surprising for series of laparoscopic cholecystectomies to report infection rates which vary from 1% to 17%.6,17 The 70% reduction in the risk of surgical nosocomial infections which we found is relatively large. We used the CDC definition of infection, and found that most infections were diagnosed and treated by GPs before the wounds developed purulent drainage and without waiting for a positive culture result. The study nurses collected the data in the same manner (ie, prospectively during planned follow-up of patients), but the diagnosis of wound infection was left to the treating GP or surgeon. We tested the observation that there is a dose-effect relationship between iatrogenic complications and length of stay in hospital. A relationship between length of stay and risk of nosocomial infection has been observed in a number of studies.18,19 Cruse and foord retrospectively also found that risk of infection increases with length of preoperative stay,19 but previous studies have not prospectively examined the possibility that decreasing the length of stay will result in lower wound infection rates. Our data demonstrate that a reduction in hospital stay as part of a re-engineered surgical service can decrease the wound infection risk. From the near-parallel slope of the lines in Figure 2, it would appear that the difference between the two groups is due to some factor that occurs early in the admission, most likely through decreasing exposure to hospital microbial flora on the night before surgery, resulting in a shift of the curve to the right. Our study design was a prospective, sequential, before-and-after comparison. Randomised controlled trials are generally considered to be the reference standard for evaluating new treatments. However, when the intervention is a coordinated system of care involving a "culture change" in an organisation, there may be a "Hawthorne effect" -- that is, behaviour changes due to an awareness of being in a study -- and leakage of elements of the "culture change" into the control group, thus reducing the power of a randomised controlled trial.20 Our sequential enrolment of patients more closely mimics the situation in hospital when a surgical service is re-engineered, and makes the study results more relevant. Our study had the active collaboration of the hospital administration, and hospital policy was revised at the start of the treatment phase to require all elective surgery patients to be admitted through the Perioperative Unit. The surgeons and operating theatre location and organisation were unchanged, although junior medical staff were rotated. There was no change in antibiotic prophylaxis or hospital infection control policies, thereby minimising any differences in enrolment patterns and other factors between the two arms of the trial. Our patient satisfaction survey suggested that patients were more satisfied with a shorter length of stay combined with the appropriate support after hospital discharge. A previous study in which surgical patients were not similarly supported after early hospital discharge found patients to be less satisfied with the treatment.21 We have demonstrated that changes in the organisation of elective surgery can produce improved health outcomes and patient satisfaction. This does not mean that any reduction in length of stay results in improved outcomes, but that reduced in-hospital support may be replaced with carefully planned and supervised preadmission assessment, education and postdischarge care, without detriment to the quality of patient care. Acknowledgements We would like to acknowledge the invaluable assistance of the staff of Post Acute Care Services, the Perioperative Unit, and the Departments of Surgery and Anaesthetics, without whose help this study would not have been possible. This study was supported by a grant from the Commonwealth Department of Health and Family Services Hospital Access Program. References Sawyer RB. General surgeons in the world of gatekeepers. Am J Surg 1995; 170: 528-531. Maxwell RJ. Why rationing is on the agenda. Br Med Bull 1995; 51: 761-768. Hoare J. Medicine for managers: day surgery. Health Services Management 1992; June: 12-14. Maddern GJ. The changing pattern of surgery [editorial]. Br J Surg 1996; 83: 145-146. Speer TL. With an eye to the future. Hospitals and Health Networks 1996; 70: 43. Barkun JS, Barkun AN, Sampalis JS, et al. Randomised controlled trial of laparoscopic versus mini cholecystectomy. Lancet 1992; 340: 1116-1119. Stoker ME, Vose J, O'Mara P, Maini BS. Laparoscopic cholecystectomy: a clinical and financial analysis of 280 operations. Arch Surg 1992; 127: 589-595. Adler MW, Waller JJ, Creese A, Thorne SC. Randomised controlled trial of early discharge for inguinal hernia and varicose veins. J Epidemiol Community Health 1978; 32: 136-142. Ruckley CV, Cuthbertson C, Fenwick N, et al. Day care after operations for hernia or varicose veins: a controlled trial. Br J Surg 1978; 65: 456-459. Russell IT, Devlin HB, Fell M, et al. Day case surgery for hernias and haemorrhoids: a clinical, social and economic evaluation. Lancet 1977; 1: 844-847. Hill S, Draper M. The role of patient satisfaction surveys in a national approach to hospital quality management. Canberra: AGPS, 1995. Kerridge R, Lee A, Latchford E, et al. The perioperative system: a new approach to managing elective surgery. Anaesth Intens Care 1995; 23: 591-596. Centers for Disease Control and Prevention, US Department of Health and Human Services. National Nosocomial Infections Surveillance Manual. Atlanta, Ga: USDHHS, May 1994. SPSS for Windows [computer program], version 6.0. Chicago: SPSS Inc, 1993. Kahan E, Carel RS, Hart J. Comparison of two pre-admission testing methods for elective surgery patients. Isr J Med Sci 1991; 27: 141-144. Ayliffe GAJ. Surveys of nosocomial infections. Med J Aust 1988; 149: 571-572. Hardy KJ, Miller H, Fletcher DR, et al. An evaluation of laparoscopic versus open cholecystectomy. Med J Aust 1994; 160: 58-62. Freeman J, McGowan JE. Differential risks of nosocomial infection. Am J Med 1981; 70: 915-918. Cruse PJE, foord R. The epidemiology of wound infection: a 10-year prospective study of 62,939 wounds. Surg Clin North Am 1980; 60: 27-40. Bouchet C, Guillemin F, Briancon S. Nonspecific effects in longitudinal studies: impact on quality of life measures. J Clin Epidemiol 1996; 49: 15-20. Michaels JA, Reece-Smith H, Faber RG. Case control study of patient satisfaction with day-case and inpatient inguinal hernia repair. J R Coll Surg Edinb 1992; 37: 99-100. (Received 5 Jun 1997, accepted 18 May 1998) Authors' details Prince of Wales Hospital, Sydney, NSW. Gideon A Caplan, MB BS, FRACP, Director, Post Acute Care Services. Ann Brown, RN, Nurse Manager, Post Acute Care Services. Philip J Crowe, MB BS, FRACS, Surgeon, Department of Surgery. Su-Jen Yap, MB BS, FANZCA, Director, Perioperative Unit, Prince of Wales Hospital. South Eastern Sydney Area Health Service, Sydney, NSW. Shaune Noble, BHA, MPH, Health Services Development Unit. Reprints: Dr GA Caplan, Director, Post Acute Care Services, Prince of Wales Hospital, Randwick, NSW 2031. E-mail: G. CaplanATunsw.edu.au - Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Gideon A Caplan · Ann Brown · Philip J Crowe · Su-Jen Yap · Shaune Noble

Rotavirus infection and rates of hospitalisation for acute gastroenteritis in young children in Australia, 1993-1996 John B Carlin, Patty Chondros, Paul Masendycz, Helen Bugg, Ruth F Bishop and Graeme L Barnes For editorial comment, see Ferson MJA 1998; 169: 252-256 Abstract - Introduction - Methods - Results - Discussion - Acknowledgments - References - Authors' details - Figure 1 - Figure 2 - - - ©MJA1998 Abstract Objective: To determine rates of hospitalisation of young children for acute gastroenteritis in Australia, and to estimate the proportion of these admissions caused by rotavirus infection. Design: Analysis of hospital admission records, and parallel, prospectively collected data on rotavirus-positive admissions. Setting: Hospitals admitting young children in all Australian States and Territories in 1993-1996. Patients: All children under five years admitted to hospital for acute gastroenteritis (International Classification of Diseases, ninth revision principal diagnosis codes 003.0, 004.0-009.3 and 558.9). Main outcome measures: Rate of hospital admission per 1000 children per year by State, and the proportion of admissions caused by rotavirus infection. Results: There were almost 20 000 hospital admissions annually in Australia for acute gastroenteritis in children under five years, at an average rate of 15/1000. An estimated 50% of these were attributable to rotavirus infection, implying a rate of hospitalisation for rotavirus-related gastroenteritis of 7.5/1000/year. Among children under two years this rate was 11.6/1000. Rotavirus incidence rates generally followed a typical seasonal pattern in temperate regions of the country, with sharp peaks in mid to late winter. Rates of hospitalisation varied markedly, even between States with apparently similar patterns of disease, while the incidence in the Northern Territory was 3-5 times higher than other States. Conclusions: Rotavirus-related gastroenteritis is a major cause of hospital admissions in young children, and large savings to the healthcare system are possible if it can be prevented at reasonable cost. Variation in treatment practices between States may be worth studying in greater detail as another source of potential savings. MJA 1998; 169: 252-256 Introduction Rotavirus is a major cause of severe gastroenteritis in young children. Although discovered only 25 years ago,1 the role of this virus in the huge burden of diarrhoeal disease in developing countries was recognised quickly, and in 1985 it was estimated to be responsible for 870 000 deaths annually.2 In developed countries, mortality from gastroenteritis is low, but many studies have documented the large burden of morbidity caused by rotavirus.3-7Precise estimates of rotavirus-related morbidity are difficult to obtain from routine hospital data because stool samples for microbiological testing are not obtained from all children admitted to hospital with diarrhoea. Even when testing is performed, the findings may not be recorded or coded in the medical record. There was no specific category in the International Classification of Diseases, ninth revision (ICD-9-CM) for rotavirus diarrhoea until 1993, and since then the specified code (008.61) has not been used consistently. However, many studies have shown that at least 30% of hospital admissions for acute gastroenteritis in young children are the result of rotavirus infection and, further, that the incidence of rotavirus infection has a distinctive cyclical pattern with a peak in winter (this is unique to rotavirus among all major pathogens associated with gastroenteritis).3,4,6,8-10 While other Australian studies have examined aspects of rotavirus gastroenteritis,5,11 there are no national population-based estimates of the incidence of hospital admission for acute gastroenteritis in young children. Such estimates are important in assessing preventive measures, and in evaluating the cost-effectiveness of rotavirus vaccines currently under development.12,13 We aimed to provide the first national data on rates of hospitalisation of young children for acute gastroenteritis in Australia, and to estimate the proportion of these admissions that could be ascribed to rotavirus infection. Our results will be used in a later study to estimate the cost-effectiveness of rotavirus vaccination. Methods State and Territory health departments provided computer files with unidentified records for the years 1993 through 1996 of all hospital admissions of children under the age of five with a principal diagnosis in the medical record of acute gastroenteritis. In our analysis, we combined data from the Australian Capital Territory with those from New South Wales. Acute gastroenteritis was identified as ICD-9-CM codes in the range 003-009 (covering infectious gastroenteritis of various known and unknown origins) or code 558.9 ("other and unspecified noninfectious gastroenteritis"). This last code was included for consistency with other studies in the expectation that it might comprise a substantial number of cases of infectious gastroenteritis. Similar files of admission records were obtained from participating paediatric hospitals in each of the States (see Box 1). Records from the Royal Children's Hospital (RCH), Melbourne, and Princess Margaret Hospital (PMH), Perth, also included an identifying hospital record number. 1: Participating hospitals Royal Children's Hospital, Melbourne (VIC) Princess Margaret Hospital, Perth (WA) Women's and Children's Hospital, Adelaide (SA) Alice Springs Hospital (NT) Royal Darwin Hospital (NT) Royal Hobart Hospital (TAS) Sydney Children's Hospital (formerly Prince of Wales Children's Hospital) (NSW) New Children's Hospital, Sydney (Royal Alexandra Hospital for Children) (NSW) Westmead Hospital, Sydney (NSW) Royal Brisbane Hospital (QLD) Microbiology departments at participating hospitals were asked to forward all rotavirus-positive faecal specimens obtained from children under five years who were admitted for acute gastroenteritis to laboratories at RCH, where rotavirus infection was confirmed by enzyme immunoassay.14 All participating hospitals provided specimens over the entire study period, except that Westmead Hospital participated in the study for the first two years only, and was replaced by Sydney Children's Hospital in 1995. Seasonal, temporal, and geographic variation in strains of rotaviruses will be reported elsewhere. We estimated the proportion of gastroenteritis admissions that were caused by rotavirus infection both by direct and indirect means. The direct method involved a linked analysis of admissions and rotavirus data. Admission and laboratory records from RCH (Melbourne) and PMH (Perth) were linked by means of hospital unit record number and date of admission/date of specimen, thus identifying the proportion of admissions that we could directly confirm as involving rotavirus infection. This analysis was supplemented with information from each hospital's pathology records, as it became clear that not every rotavirus-positive specimen was being sent on to our laboratory (usually owing to insufficient size of samples). Further, it was possible to omit patients for whom no faecal test was performed, to give a more appropriate denominator for estimating the fraction admitted because of rotavirus infection (calculated as rotavirus fraction = number of admissions with positive rotavirus test result/number of admissions with faecal specimen tested). The indirect statistical estimation of the rotavirus fraction and the rationale behind this method are described in Box 2. The study was approved by ethics committees in each of the participating hospitals. 2: Statistical estimation of the rotavirus fraction We assumed (i) that rotavirus is the only major cause of childhood gastroenteritis admissions that shows significant seasonal variation; and (ii) that the total number of admissions due to rotavirus in a State is a constant multiple of the number seen in our participating hospital(s). Thus, total admissions per month were expressed as the sum of a constant number (representing non-rotavirus causes) and varying numbers of rotavirus admissions. The resulting linear regression model for the number of admissions in a State in each month was used to estimate the rotavirus fraction (the proportion of hospital admissions for acute gastroenteritis resulting from rotavirus infection). This is shown mathematically below, where: Ni = number of acute gastroenteritis admissions in the State in month i; ni = number of "rotavirus-positive" admissions in the State's participating (index) hospital(s); = monthly number of admissions statewide not caused by rotavirus; and = scaling factor relating the number of "rotavirus-positive" admissions in the State to that in the index hospital(s). The regression model (in which i = random error) is: Ni = + ni + i , which leads to: We followed earlier practice4,5 and used ordinary least squares to estimate , despite the fact that the model does not fit the usual assumptions of linear regression (in particular, the variance of i cannot be expected to be constant). As the assumption that there is perfect correlation between rotavirus incidence recorded at the index hospital and total rotavirus numbers at all hospitals in the State is inevitably untrue, there will be an underestimation of in this model, and consequently some underestimation of the rotavirus fraction. On the other hand, if the assumption that rotavirus is the only agent responsible for seasonal variation is wrong, then the estimation may be biased in either direction. The estimate is also potentially subject to other biases relating to the completeness and regularity of coverage of the contributed rotavirus samples. These biases are likely to outweigh random error, so that conventional confidence intervals would not provide a reliable indicator of uncertainty. Results Total numbers and estimated rates of acute gastroenteritis admissions are shown in Box 3. Of all admissions, 65.7% involved children under the age of two years, with approximately equal numbers in each of the first two years of life, and declining numbers in each of the subsequent three years to age five. The age breakdown was similar in all States except the Northern Territory, where a substantially larger proportion were aged under two (86.1%). Length of stay was also considerably longer in the Northern Territory. There were slightly more boys than girls (53.1% overall), consistent across all States. Of all admissions, 29.4% were coded 558.9, although this proportion declined sharply over the four years of the study as coding practices apparently changed. 3: Acute gastroenteritis in children aged less than five years, 1993-1996. Number and rate of hospital admissions, rate ratio relative to the Victorian rate, and average length of stay (95% confidence intervals in parentheses) State or TerritoryAverage annual admissionsAnnual rate per 1000 children under 5 yearsRate ratio relative to VictoriaAnnual rate per 1000 children under 1 yearAnnual rate per 1000 children aged 1-2 yearsAverage length of stay Victoria29159.2 (9.0-9.3)1.00 14.6 (14.1-15.1)14.4 (13.9-14.8) 1.93 days (1.90-1.96) Tasmania3199.3 (8.8-9.8) 1.01 (0.96-1.07) 15.0 (13.6-16.4) 15.1 (13.7-16.6) 1.79 days (1.71-1.87) Western Australia178614.2 (13.9-14.5) 1.55 (1.51-1.60) 25.3 (24.3-26.2) 24.9 (24.0-25.9) 3.13 days (3.03-3.23) Queensland377316.0 (15.7-16.2) 1.74 (1.70-1.79) 24.0 (23.3-24.7) 26.4 (25.6-27.1) 2.15 days (2.11-2.18) New South Wales*786617.1 (16.9-17.3) 1.87 (1.83-1.91) 25.5 (25.0-26.0) 27.5 (27.0-28.1) 2.11 days (2.09-2.13) South Australia189519.2 (18.8-19.7) 2.10 (2.04-2.16) 32.0 (30.7-33.2) 30.7 (29.5-31.9) 2.09 days (2.03-2.15) Northern Territory85449.8 (48.2-51.4) 5.44 (5.24-5.65) 106.2 (101.0-111.3) 108.1 (102.9-113.3) 9.18 days (8.88-9.47) Total1940815.0 (14.9-15.1) 23.9 (23.6-24.2) 25.0 (24.7-25.3) * Including Australian Capital Territory. Box 4 shows the temporal pattern of all admissions and of rotavirus admissions in index hospitals in the five largest States and the Northern Territory. The seasonal peaks in the eastern States (New South Wales, Victoria, Queensland, and South Australia) were generally coincident and occurred regularly in the colder months from July to September (except for the unusual final year in South Australia). In contrast, the weaker and less regular peaks in Western Australia occurred earlier than in the eastern States, and there was no discernible seasonal pattern in the Northern Territory. Even where the seasonal pattern was less distinct, the peaks in statewide admissions were reflected in peaks in the numbers of rotavirus- positive specimens. 4: Monthly incidence of hospital admission for acute gastroenteritis in children under five years of age in Australian mainland States and the Northern Territory, 1993-96 (solid line) and number of rotavirus-positive specimens received from participating hospitals in that State, rescaled from the hospital to the State level (dashed line), by the "regression method" For the data linkage method, among 1732 children admitted for whom a specimen was tested, we received 767 rotavirus-positive specimens from RCH (Melbourne) and found another 205 admissions with hospital records showing a positive rotavirus test, giving an estimated rotavirus fraction of 56%. The corresponding totals from PMH (Perth) were 1631, 626 and 161, respectively, giving a rotavirus fraction of 49%. Regression estimates of the rotavirus fraction ranged from a low of 22% for the Northern Territory (based on a total of 598 rotavirus-positive specimens) to a high of 41% for Victoria (984 specimens). When data from all States were combined, the correlation between rotavirus numbers and admissions increased, because a more accurate representation of the relationship between total admissions and rotavirus numbers in participating hospitals was obtained by pooling. The resulting estimated rotavirus fraction was 50% (based on 4634 specimens received). Separate estimates obtained for children aged under one year, one year to less than two years, and at least two years were 34%, 60% and 48%, respectively. Discussion This national four-year study has shown that there are almost 20 000 hospital admissions annually in Australia for acute gastroenteritis in children aged under five years -- an average rate of 15 per 1000, 50% of which appear to be attributable to rotavirus infection. The annual rate of hospitalisation for rotavirus-related gastroenteritis in children under five is therefore about 7.5 per 1000. Among children under two years, combining estimates for the two one-year age brackets, the corresponding rate is 11.6 per 1000, or just over one in every 100 children. Of the two methods we used to estimate the proportion of admissions that were caused by rotavirus, the method involving direct linkage of hospital admission records and stool specimen tests is likely to be the more accurate. Estimates of 56% (Melbourne) and 49% (Perth) were obtained for the two centres where it was available. These estimates may be too low, as enzyme immunoassay can fail to detect up to 10% of rotavirus-positive specimens.15 Conversely, they might be too high on a population-wide basis, as they were based on tertiary referral centres where the severity of admitted cases -- and therefore the likelihood of rotavirus involvement -- might be higher (although this was only weakly supported by our data on mean length of stay [LOS], which showed a small difference between RCH [mean LOS 1995-1996, 2.15 days] and the whole of Victoria [1.87 days], and no difference between PMH and WA averages [2.80 v. 2.85]). Our second method, based on a regression model, was subject to statistical fluctuations and assumptions that imply it might produce an underestimate of the rotavirus fraction (see Box name="box2"2). In particular, the coverage of rotavirus specimen collection varied between States and also, at times, within States. For example, only a relatively small number of specimens (457) were ascertained from New South Wales, implying that the rotavirus fraction for that State might be considerably underestimated. In fact, when the regression method was applied to the pooled national data, we found reasonable convergence between the two methods, and believe they both support the conclusion that 50% of all gastroenteritis admissions in this age group are due to rotavirus. A reasonable range of possible alternative estimates around this value would be from 40% to 60%. In other studies, estimates of the proportion of hospital admissions in children under five years attributable to rotavirus have ranged from around 30% to as high as 66%.3,4,6,8,9,16 United States studies from the Centers for Disease Control have estimated this proportion both by a simple "residual" method based on assuming that all diarrhoea admissions in the winter seasonal peaks are rotavirus-related,17 and a more direct method based on an eight-year series of children admitted to a Washington DC hospital.6 Both methods indicated that rotavirus was responsible for about one-third of admissions, and the corresponding annual rate of hospitalisation for rotavirus-related gastroenteritis in children under five years was 2.8 per 1000. In the United Kingdom, estimates have been based on laboratory surveillance and hospital discharge data, with a similar statistically based estimation procedure to ours.4 It was found that 43% of admissions in children under five years could be attributed to rotavirus, corresponding to 5.3 per 1000 admissions per year. A New South Wales study by Ferson also used a regression method, based on a larger sample of rotavirus surveillance data than ours, and estimated an annual rate of hospital admission of 8.7 per 1000.5 Using the 1993-1996 NSW hospital admission rates (Box name="box3"3), this corresponds to a rotavirus fraction of 51%, very consistent with our national estimate. Ferson's study found over twice the rate of rotavirus gastroenteritis in the second year of life compared with the first, a slightly greater difference than suggested by our data. The findings of both studies are consistent with a detailed investigation of children with gastroenteritis over 13 years at RCH Melbourne, which found that no pathogen could be identified in a substantially greater proportion of infants under six months than in older children.18 There were substantial differences in hospital admission rates between the States, with NSW, Queensland and South Australia having almost twice the rate of hospitalisation of Victoria. It seems very unlikely that these differences are the result of different disease patterns, especially as the seasonal patterns in these States were very similar. Nor are they likely to be explained by differences in coding, as our incidence figures are based on an inclusive selection of principal diagnosis ICD-9-CM codes. In particular, the inclusion of code 558.9 ("non-infectious gastroenteritis") identified a substantial number of apparently miscoded cases of viral diarrhoea, consistent with findings in other reports.4,5 The differences may reflect variations in patterns of primary care influencing the numbers of children who present to hospital emergency departments, and/or differences in hospital admission policies. The relative importance of each of these factors warrants further study, as it appears likely that substantial savings could be made if hospitalisation rates nationally could be reduced. There were no major seasonal differences in gastroenteritis incidence between States, except in the Northern Territory and Western Australia, where the relative importance of rotavirus in the gastroenteritis disease burden may be somewhat reduced. There is little evidence in our data of a progressive spread of the rotavirus epidemic across the country each year, in the manner that has been described in North America,19 apart from the fact that the annual peak of rotavirus activity in Western Australia appears generally to precede that in the eastern States. The Northern Territory was the most clearly distinct of all the regions, not only in its substantially higher hospital admission rate and lack of seasonal pattern, but also in the dramatically longer length of stay of patients. Average length of stay in this study (2.2 days, excluding the Northern Territory) was substantially shorter than that reported in the United States (3.9 days20), but very similar to British findings.4 Given the higher admission rates in Australia, shorter length of stay may reflect a less severe spectrum of illness, or possibly better management involving more widespread use of oral rehydration solution. Our results imply that 10 000 hospital admissions occur annually in Australia for rotavirus gastroenteritis. The direct cost of this hospital care is at least $12 million, based on an (Australian national diagnosis-related group-based) estimate of $1244 per admission,21 and may be as high as $15-$18 million (preliminary analysis, RCH [Melbourne] costing data). A successful rotavirus vaccine -- depending on its cost -- could result in substantial savings to the healthcare system. Acknowledgments The study was funded by the Public Health Research and Development Committee of the National Health and Medical Research Council. It would not have been possible without the generous cooperation of numerous individuals in all State and Territory health authorities, and in medical records and hospital information units at the participating hospitals, or without the participation and skilled assistance of the following microbiologists and paediatricians: G Davidson, P Goldwater, T Kok, A Lawrence, L Micken, S Weir (Adelaide); G Clift, J Erlich, J Hagger, R Matters, F Morey (Alice Springs); J Faogali, J Farrah, R Shepherd, M Witt (Brisbane); G Lum, A Lowe, A Ruben, B Way, K Withnall (Darwin); A Carmichael, A Claridge, K Dahlenburg, R Fang, R Tucker (Hobart); B Crawford, G Hogg, B Ross, R Schnagl, P Ward (Melbourne); B Dwyer, R Hill, A May, G O Connor, B Wild (Perth); P Amin, T Borg, A Cunningham, J MacRae, P McIntyre, C McIvor, K McPhie, J Mitchell, J Montgomery, G Sandico (Sydney). References Bishop RF, Davidson GP, Holmes IH, Ruck BJ. Virus particles in epithelial cells of duodenal mucosa from children with acute non-bacterial gastroenteritis. Lancet 1973; 2: 1281-1283. Bern C, Glass RI. Impact of diarrheal diseases worldwide. In: Kapikian AZ, editor. Viral infections of the gastrointestinal tract. New York: Marcel Dekker, 1994: 1-26. Glass RI, Kilgore PE, Holman RC, et al. The epidemiology of rotavirus diarrhea in the United States: surveillance and estimates of disease burden. J Infect Dis 1996; 174 (Suppl 1): S5-S11. Ryan MJ, Ramsay M, Brown D, et al. Hospital admissions attributable to rotavirus infection in England and Wales. J Infect Dis 1996; 174 (Suppl 1): S12-S18. Ferson MJ. Hospitalisations for rotavirus gastroenteritis among children under five years of age in New South Wales. Med J Aust 1996; 164: 273-277. Brandt CD, Kim HW, Rodriguez WJ, et al. Pediatric viral gastroenteritis during eight years of study. J Clin Microbiol 1983; 18: 71-78. Matson DO, Estes MK. Impact of rotavirus infection at a large pediatric hospital. J Infect Dis 1990; 162: 598-604. Konno T, Suzuki H, Imai A, et al. A long-term survey of rotavirus infection in Japanese children with acute gastroenteritis. J Infect Dis 1978; 138: 569-576. Spence L, Singer O, Kibsey P, Fauvel M. Rotavirus infection in children with diarrhoea admitted to a general hospital in metro Toronto. Can J Pub Health 1985; 76: 17-20. Lewis HM, Parry JV, Davies HA, et al. A year's experience of the rotavirus syndrome and its association with respiratory illness. Arch Dis Child 1979; 54: 339-346. Liddle JLM, Burgess MA, Gilbert GL, et al. Rotavirus gastroenteritis: impact on young children, their families and the health care system. Med J Aust 1997; 167: 304-307. Smith JC, Haddix AC, Teutsch SM, Glass RI. Cost-effectiveness analysis of a rotavirus immunization program for the United States. Pediatrics 1995; 96: 609-615. Barnes GL, Lund JS, Adams L, et al. Phase 1 trial of a candidate rotavirus vaccine (RV3) derived from a human neonate. J Paediatr Child Health 1997; 33: 300-304. Coulson BS, Unicomb LE, Pitson GA, Bishop RF. Simple and specific enzyme immunoassay using monoclonal antibodies for serotyping human rotaviruses. J Clin Microbiol 1987; 25: 509-515. Husain M, Seth P, Broor S. Detection of group A rotavirus by reverse transcriptase and polymerase chain reaction in feces from children with acute gastroenteritis. Arch Virol 1995; 140: 1225-1233. Donelli G, Ruggeri FM, Tinari A, et al. A three-year diagnostic and epidemiological study on viral infantile diarrhoea in Rome. Epidemiol Infect 1988; 100: 311-320. Ho MS, Glass RI, Pinsky PF, Anderson LJ. Rotavirus as a cause of diarrheal morbidity and mortality in the United States. J Infect Dis 1988; 158: 1112-1116. Barnes GL, Uren E, Stevens KB, Bishop RF. Etiology of acute gastroenteritis in hospitalized children in Melbourne, Australia, from April 1980 to March 1993. J Clin Microbiol 1998; 36: 133-138. LeBaron CW, Lew J, Glass RI, et al. Annual rotavirus epidemic patterns in North America: Results of a 5-year retrospective survey of 88 centers in Canada, Mexico, and the United States. JAMA 1990; 264: 983-988. Jin S, Kilgore PE, Holman RC, et al. Trends in hospitalizations for diarrhea in United States children from 1979 through 1992: estimates of the morbidity associated with rotavirus. Pediatr Infect Dis J 1996; 15: 397-404. Australian casemix report: on hospital activity, 1995-96. Canberra: Department of Health and Family Services, 1997. (Received 30 Oct 1997, accepted 4 May 1998) Authors' details Clinical Epidemiology and Biostatistics Unit, Royal Children's Hospital, Melbourne, VIC. John B Carlin, BSc(Hons), PhD, Deputy Head, and Associate Professor, Department of Paediatrics, University of Melbourne; Patty Chondros, BSc(Hons), Research Assistant. Department of Gastroenterology and Clinical Nutrition, Royal Children's Hospital, Melbourne, VIC. Paul Masendycz, BAppSc, Research Assistant; Helen Bugg, BSc, Research Assistant; Ruth F Bishop, AO, DSc, PhD, Senior Principal Research Fellow (NHMRC, and Professor, Department of Paediatrics, University of Melbourne; Graeme L Barnes, MD, FRACP, Senior Gastroenterologist, and Associate Professor, Department of Paediatrics, University of Melbourne. Reprints: Associate Professor G L Barnes, Department of Gastroenterology and Clinical Nutrition, Royal Children's Hospital, Parkville, VIC 3052. E-mail: barnesgATcryptic.rch.unimelb.edu.au - Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

John B Carlin · Patty Chondros · Paul Masendycz · Helen Bugg · Ruth F Bishop · Graeme L Barnes

Interval breast cancers in an Australian mammographic screening program Mary T Rickard, Richard J Taylor, Mohamed A Fazli and Nadima El Hassan MJA 1998; 169: 184-187 For editorial comment, see Rodger & Kavanagh Abstract - Introduction - Methods - Results - Discussion - Acknowledgements - References - Authors' details - - ©MJA1998 Abstract Objective: To determine the incidence of interval cancers which occurred in the first 12 months after mammographic screening at a mammographic screening service. Design: Retrospective analysis of data obtained by crossmatching the screening Service and the New South Wales Central Cancer Registry databases. Setting: The Central & Eastern Sydney Service of BreastScreen NSW. Participants: Women aged 40-69 years at first screen, who attended for their first or second screen between 1 March 1988 and 31 December 1992. Main outcome measures: Interval-cancer rates per 10 000 screens and as a proportion of the underlying incidence of breast cancer (as estimated by the underlying rate in the total NSW population). Results: The 12-month interval-cancer incidence per 10 000 screens was 4.17 for the 40-49 years age group (95% confidence interval [CI], 1.35-9.73) and 4.64 for the 50-69 years age group (95% CI, 2.47-7.94). Proportional incidence rates were 30.1% for the 40-49 years age group (95% CI, 9.8-70.3) and 22% for the 50-69 years age group (95% CI, 11.7-37.7). There was no significant difference between the proportional incidence rate for the 50-69 years age group for the Central & Eastern Sydney Service and those of major successful overseas screening trials. Conclusion: Screening quality was acceptable and should result in a significant mortality reduction in the screened population. Given the small number of cancers involved, comparison of interval-cancer statistics of mammographic screening programs with trials requires age-specific or age-adjusted data, and consideration of confidence intervals of both program and trial data. Introduction The principal aim of a mammographic screening service is to reduce mortality from breast cancer. As this outcome cannot be measured effectively for many years after the establishment of screening, and as it applies to spatially defined populations, a range of interim measures are used to evaluate screening services and to determine the likelihood of mortality reduction. Interim measures include screen-detected cancer rates and the rates of prognostic indicators for these cancers, such as size, nodal status and grade.1 Another interim measure of screening performance is the interval-cancer rate.2,3 As survival among women with interval cancers is similar to that among unscreened women, then as the incidence of interval cancers approaches that of the underlying incidence of breast cancer the benefit of screening disappears.3 Interval-cancer rates can be compared with background or underlying rates to better assess the effectiveness of screening. Further, comparing the rate of interval cancers with the underlying rate allows comparison between different screening programs in populations with different incidences of breast cancer. Our aim was to evaluate first-year interval breast cancers after screening at the Central & Eastern Sydney Service of BreastScreen NSW (a mammographic screening and assessment service). We report the incidence and proportional incidence of interval breast cancers during the 12 months after both the first and second rounds of screening, over five years. Methods The Central & Eastern Sydney Service of BreastScreen NSW is located in inner Sydney, and started screening in March 1988 as one of the first pilot mammography screening programs in Australia. Any woman aged 40 years or more was eligible to attend, although during the study period only 50-69-year-old residents in the Central Sydney Area Health Service were actively recruited for two-yearly screening. Since the progressive introduction of systematic, government-funded, population-based screening from 1991, the Service has become a regional component of BreastScreen NSW and BreastScreen Australia.4The study population comprised women who attended the Service for mammographic screening between 1 March 1988 and 31 December 1992. These women were all screened by two-view mammography. The technical quality of the Service's screening mammograms met all requirements for accreditation by BreastScreen Australia.5 All films were read independently by two radiologists and were reported as "normal" for routine rescreen or as "suspicious" and requiring assessment. The design of the screening and assessment Service has been previously described.6 Screen-detected cancers The definition of primary breast cancer used for this study includes invasive cancer and ductal carcinoma-in-situ (DCIS), but excludes lobular carcinoma-in-situ.5 All cases of primary breast cancer diagnosed by the screening and assessment Service in women attending for the first time were classified as prevalent (first-round) screen-detected cancers. Cancers in women attending for their first routine rescreen after two years were classified as second-round screen-detected cancers. Data were analysed according to age at first screen, by 10-year age groups (40-49, 50-59 and 60-69 years). Interval cancers We reviewed the data for interval cancers, defined as primary cancer of the breast diagnosed up to 12 months after a first-round or second-round screening mammogram in women aged 40-69 years at the time of screening. The date of diagnosis of these interval cancers was taken as the date of histological confirmation of cancer. Cases in which clinical and imaging findings were consistent with breast cancer but no surgery had been performed were included in the study and the date of diagnosis was taken as the date of cytological confirmation of cancer. Data were analysed by women's age at their first screen. Some interval cancers were reported to the screening Service and others were identified by linking the Service's screening database with the NSW Central Cancer Registry (NSW CCR), which has operated since 1972 as a population-based registry. Notification of malignant neoplasms has been a statutory requirement for all NSW public and private hospitals, radiotherapy departments and nursing homes since 1972, and for pathology and outpatient departments since 1985. The date of diagnosis used by the NSW CCR was defined as "date of first definitive treatment for cancer" during the period covered by this study, although incidence was designated mostly on the basis of the first notification (usually the biopsy report). We matched records of the screening database with the NSW CCR in late 1994 with the aid of probabilistic linkage7,8 using Automatch.9 Equivocal matches were investigated by individual examination of all details available, and by active follow-up by the screening Service. Positive linkages between the screening database and the cancer registry were investigated by the screening Service to ensure that all data on those interval cancers diagnosed in the first year after a negative screen were available for inclusion in the study. Statistical analysis The age-specific incidence of interval cancers was determined by dividing the number of interval cancers found in women screened between 1988 and 1992 by the age-specific (age at first screen) number of women screened over the same period. Age groups were 40-49, 50-59 and 60-69 years, although the latter two age groups are aggregated for reporting purposes. The underlying incidence of breast cancer from 1988 to 1992 was obtained by dividing NSW reported cases (as reported by the NSW CCR.10,11) by the State female population for the same three 10-year age groups. To express the interval-cancer incidence as a proportion of the underlying breast cancer incidence rate, an indirectly age-standardised incidence ratio12 was calculated using the State age-specific incidences as the standard. Because of small numbers of cases, 95% confidence intervals were derived by the Poisson method.12,13We compared our findings with those of studies from Sweden,3 the Netherlands14 and the United Kingdom15 using the 12-month interval-cancer data from the first two screening rounds for all studies except the UK study, for which only the first-round data were available. Confidence limits for interval-cancer rates from comparison populations were calculated from the published data using the same Poisson method as above. Results During the study period, the Central & Eastern Sydney Service carried out 39 988 first-round and second-round screens on women aged 40-69 years, and 226 screen-detected cancers were diagnosed. In the prevalent (first-round) screens, the screen-detected cancer rates per 1000 screens were 3.0 for women aged 40-49 years, 6.2 for 50-59-year-olds and 9.6 for 60-69-year-olds. Second-round rates were 3.5, 4.2 and 4.6, respectively. Eighteen interval cancers occurred in the first 12 months after screening. All of these interval cancers were invasive. The 12-month interval-cancer incidences are shown in Box 1. The underlying annual breast cancer incidences were 13.8 per 10 000 for the 40-49 years age group and 21.2 per 10 000 for the 50-69 years age group (19.4 for 50-59 years and 23.2 for 60-69 years). The interval-cancer incidences as a proportion of these underlying incidences are shown in Box 2, in which they are compared with those of the Swedish Two-County Study.3 The proportional interval-cancer incidence for women aged 50-69 years in the Central & Eastern Sydney Service (22.0%; 95% CI, 11.7%-37.7%) is compared with that for similar age groups from international studies3,14,15 in Box 3. The proportional interval-cancer incidence point estimate for the Central & Eastern Sydney Service was higher and had wider 95% confidence intervals than that of the Swedish Two-County Study (13.2%; 95% CI, 8.4-19.9), but was lower than that of the UK (31.4%; 95% CI, 24.9-39.1) and Dutch (39.5%; 95% CI, 20.4-69.0) studies. Discussion The screen-detected cancer rates achieved by the Central & Eastern Sydney Service exceed the National Accreditation Requirements and compare favourably with those reported from the Swedish Two-County Study and the other Australian mammographic screening services.5,16,17Our findings indicate that the first 12-month interval-cancer rate (as a proportion of underlying incidence) for women attending the Central & Eastern Sydney Service is higher than that of the Swedish Two-County Study,3 but lower than the rates reported from Nijmegen (the Netherlands)14 and North West Region UK.15 However, there is considerable overlap of 95% confidence intervals, and the conclusion must be that the Central & Eastern Sydney proportional first-year interval-cancer rate is not significantly different from that in these other studies. As a proportion of interval cancers occur because an abnormality has not been detected at the time of screening, the first-year interval-cancer rates reflect the proportion of false negative screens in the screening episode. The Central & Eastern Sydney results therefore indicate acceptable screening sensitivity and, as they are not significantly different from the results of the Two-County Study, they would be expected to indicate a similar future mortality reduction. The interval-cancer data presented in this study are not affected by significant ascertainment bias. Restricting our analysis to interval cancers occurring within the first year after a screen eliminates the difficulties of accurately differentiating interval cancers and screen-detected cancers diagnosed around the 21-27-month rescreen interval. We directed considerable attention to the linkage with the NSW CCR to ensure that no interval cancers were missed. The underlying rate of breast cancer is reliable. This was determined in a population that included the women who were screened. However, during the study period, the Central & Eastern Sydney BreastScreen Service was one of only two pilot mammographic screening and assessment endeavours in New South Wales, and screened a small fraction of the State's female population. Its clientele was not limited to the immediate geographic area. For the busiest years in this period (1991 and 1992) less than 5% of breast cancers in NSW were detected through these two mammographic screening services.18 Completeness of enumeration is difficult to determine precisely for cancer registries, but the standard indicators suggest reasonably good completeness for the NSW CCR,10,19 and its data are accepted for inclusion in Cancer incidence in five continents.20 Comparisons of the Central & Eastern Sydney Service and another pilot mammographic screening service with the NSW CCR for the period 1988-1992 showed 100% enumeration of invasive breast cancer by the NSW CCR (R T, NSW Cancer Council, unpublished data). The design of the Australian mammographic screening program and the comparison studies in this paper differ. The Swedish Two-County Study employed single-view mammography and double reading. The Dutch and UK studies used single-view mammography and single reading. Double-view mammography and double reading, as used in Australia, would be expected to produce better results and fewer interval cancers in the first year than the comparison studies. The confidence intervals of the proportional interval-cancer rates from the Swedish Two-County Study and those reported for North West Region UK do not overlap, and direct statistical testing has shown a significant difference between these rates.15 The authors of the UK article15 and those of the accompanying editorial21 expressed concern that the screening sensitivity in the British National Health Service program may not be sufficient to achieve mortality reduction targets. They noted the increased sensitivity resulting from two-view mammography, good film quality and two independent film readings. These features are part of BreastScreen Australia and of the Central & Eastern Sydney Service. Even when data are collected over reasonable lengths of time, the numbers of interval cancers in many screening services are often small because of the size of the base populations. In the 50-69 years age group, there were 23 interval cancers in the Swedish Two-County Study, compared with 12 in the Nijmegen study and 13 in our study. However, performance can still be evaluated through calculation of interval-cancer rates, provided that interpretation is qualified by consideration of confidence intervals based on exact or Poisson methods. Australian mammography screening services are evaluated by comparison with National Accreditation Requirements standards.5 The point estimate of the Swedish Two-County Study has come to be regarded as a standard, as this study achieved significant mortality reduction. However the Two-County Study did not involve large numbers, and its interval-cancer rates must be interpreted in relation to their statistical confidence intervals. That is, standards cannot be derived from point estimates alone as they emanate from real studies in real populations. Further, comparison of the performance of screening services with such standards also requires that the confidence intervals of the screening service data be taken into account. Evaluations should not be based on point estimates of rates which derive from small numbers with considerable stochastic variation. The standard for Australian National Accreditation Requirements is less than six interval cancers per 10 000 screens occurring in the first 12 months. However, no age range or standardisation is specified, and confidence intervals are not considered. Another consideration in setting performance standards for mammographic screening services is the difference in results from experimental and operational studies. Randomised trials and other specially constructed studies usually attract significant financial resources and interested investigators. It may be more reasonable to derive standards from studies of operational mammographic screening services whose data, when sufficient studies have been reported, could be assessed to determine performance standards which could reasonably be expected. However, until operational mammography screening services have been shown to produce reduced breast cancer mortality in the screened populations, the results of successful trials must set the gold standard. Acknowledgements The Central & Eastern Sydney Service of BreastScreen NSW and BreastScreen Australia is jointly funded by the Commonwealth and the NSW State Governments. The NSW Central Cancer Registry, which is administered by the NSW Cancer Council and funded by the NSW Health Department, provided valuable assistance with data linkage. References Duffy SW, Tabar L, Fagerberg G, et al. Breast screening, prognostic factors and survival -- results from the Swedish two county study. Br J Cancer 1991; 64: 1133-1138. Day NE, Williams DRR, Khaw KT. Breast cancer screening programmes: the development of a monitoring and evaluation system. Br J Cancer 1989; 59: 954-958. Tabar L, Fagerberg G, Day NE, Holmberg L. What is the optimum interval between mammographic screening examinations? An analysis based on the latest results of the Swedish two-county breast cancer screening trial. Br J Cancer 1987; 55: 547-551. Australian Health Ministers' Advisory Council. Breast Cancer Screening Evaluation Committee. Breast cancer screening in Australia: future directions. Australian Institute of Health, Prevention Program Evaluation Series No. 1. Canberra: AGPS, 1990. National Program for the Early Detection of Breast Cancer -- national accreditation requirements: March 1994. Canberra: Commonwealth Department of Human Services and Health, December 1994. Rickard MT, Lee W, Read JW, et al. Breast cancer diagnosis by screening mammography: early results of the Central Sydney Area Health Service Breast X-Ray Program. Med J Aust 1991; 154: 126-131. Fellegi IP, Sunter AB. A theory for record linkage. J Am Statistical Assoc 1969; 64: 1183-1210. Jaro M. Advances in record linkage methodology as applied to matching the 1985 census of Tampa, Florida. J Am Statistical Assoc 1989; 84: 414-420. Jaro M. Automatch. Generalised record linkage system. Silver Spring, Md: Matchware Technologies Inc, USA, 1994. Taylor R, Smith D, Hfyer A, et al. Breast cancer in New South Wales 1972-91. Sydney: NSW Central Cancer Registry and Cancer Epidemiology Research Centre, NSW Cancer Council, September 1994. Coates M, Day P, McCredie M, Taylor R. Cancer in NSW, incidence and mortality 1992. Sydney: NSW Central Cancer Registry and Cancer Epidemiology Research Centre, NSW Cancer Council, 1995. Armitage P, Berry G. Statistical methods in medical research. 3rd ed. Oxford: Scientific Publications, 1994. Lentner C, editor. Geigy scientific tables. Volume 2: Poisson distribution. Basle, Switzerland: Ciba-Geigy, 1982: 152. Peeters PHM, Verbeek ALM, Hendriks JHCL, et al. The occurrence of interval cancers in the Nijmegen screening programme. Br J Cancer 1989; 59: 929-932. Woodman CBJ, Threlfall AG, Boggis CRM, Prior P. Is the three year breast screening interval too long? Occurrence of interval cancers in NHS breast screening programme's north western region. BMJ 1995; 310: 224-226. Rickard MT, Donnellan M. Diagnosis of small sized invasive breast cancer by an Australian mammography screening service: surrogate end points for mortality reduction. Aust N Z J Surg 1998; 68: 426-429. Robinson JI, Crane CEB, King JM, et al. The South Australian Breast X-Ray Service: results from a statewide mammographic screening programme. Br J Cancer 1996; 73: 837-842. Smith D, Oudod V, Supramaniam R, et al. BreastScreen NSW. Statistical Report 1991-1995. Sydney: NSW Cancer Council, 1996. Coates M, McCredie M, Armstrong B. Cancer in NSW, incidence and mortality 1993. Sydney: Cancer Control Information Centre, NSW Cancer Council, 1996. Parkin DM, Muir CS, Whelan SL, et al, eds. Cancer incidence in five continents. Volume VI. World Health Organization (WHO), International Association of Cancer Registries (IACR), International Agency for Research on Cancer (IARC). Lyon: IARC, 1992. (IARC Scientific Publication No. 120.) Field S, Michell M J, Wallis MGW, Wilson ARM. What should be done about interval breast cancers? BMJ 1995; 310: 203-204. (Received 7 Aug 1997, accepted 3 Apr 1998) Authors' details BreastScreen NSW, Central & Eastern Sydney, Sydney, NSW. Mary T Rickard, FRACR, MPH, Director and Radiologist; Mohamed A Fazli, BScEng, ME, Database Manager; Nadima El Hassan, BEc(Hons), Computer Consultant. Department of Public Health and Community Medicine, Faculty of Medicine, University of Sydney, Sydney, NSW. Richard J Taylor, FAFPHM, FRCP, Associate Professor in Public Health. Reprints will not be available from the authors. Correspondence: Dr M T Rickard, BreastScreen NSW, Central & Eastern Sydney, PO Box 1535, Strawberry Hills, NSW 2012. E-mail: MaryATces.bci.org.au - Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Mary T Rickard · Richard J Taylor · Mohamed A Fazli

Decision making in CPR: attitudes of hospital patients and healthcare professionals Ian H Kerridge, Sallie-Anne Pearson, Isobel E Rolfe and Michael Lowe MJA 1998; 169: 128-131 For editorial comment, see Ryan Abstract - Introduction - Methods - Results - Discussion - Acknowledgments - References - Authors' details - - ©MJA1998 Abstract Objective: To examine the opinions of patients and healthcare professionals regarding the process of making decisions about cardiopulmonary resuscitation (CPR). Design and participants: A cross-sectional survey of 511 healthcare professionals (doctors, nurses and allied health professionals) (64% response rate) and 152 patients (58% response rate) at the John Hunter Hospital, Newcastle, New South Wales, in June 1994. Main outcome measures: Opinions on who should be involved in CPR decision making; what issues are important when making the decision; and how these decisions should be communicated. Results: 80% (95% confidence interval [CI], 72%-86%) of patients and 99% (95% CI, 98%-100%) of healthcare professionals (P < 0.001) thought patients' views should be taken into account when making CPR decisions. More patients (29%; 95% CI, 22%-38%) than healthcare professionals (14%; 95% CI, 11%-17%) indicated that doctors should be the main decision makers. Two-thirds of respondents regarded the patient's wishes, diagnosis and quality of life as important factors. Most respondents (82%) felt comfortable discussing CPR, but only 29% (95% CI, 22%-37%) of patients and 57% (95% CI, 52%-61%) of healthcare professionals had actually discussed CPR with others (P < 0.001). More than half of all respondents preferred to express their wishes about CPR in writing (47% [95% CI, 39%-55%] of patients, 69% [95% CI, 64%-73%] of healthcare professionals; P < 0.01); the others preferred to tell a family member or close friend. Most patients (60%; 95% CI, 52%-68%) and healthcare professionals (85%; 95% CI, 81%-88%) wanted their views in their medical records (P < 0.001). Conclusion: Most patients want to be involved in CPR decision making and many want some form of advance directive. Although there are some differences in opinions between patients and healthcare professionals, both perceive decision making at the end of life as a shared process, primarily involving the patient and doctor. Introduction Cardiopulmonary resuscitation (CPR) has been used in hospitals for about 30 years.1 Early studies of CPR in highly selected populations demonstrated its effectiveness and CPR soon became routine for any patient who died in hospital. However, as experience accumulated it became apparent that many patients, particularly those with chronic diseases, did not benefit from CPR. Hospitals responded by developing procedures for withholding CPR through the documentation of "do-not-resuscitate" orders. Decisions to initiate or withhold CPR were originally taken by doctors, but changing attitudes towards the doctor-patient relationship and the rise of medical consumerism have challenged this form of unilateral decision making. Indeed, respect for patient autonomy suggests that patients should have the right to contribute to such decisions. No Australian studies reported to date have examined patient preferences regarding CPR decision making. International studies suggest that most patients do not consider discussions about CPR preferences to be cruel or insensitive,2 and most wish to participate in decisions regarding CPR and other life-sustaining therapies.3 However, many patients are unable to participate during the final stages of life-threatening illnesses.4 The use of advance directives has been proposed as a means by which competent patients may ensure that their wishes will be carried out. Advance directives are written or verbal statements in which patients set out their preferences regarding life-sustaining treatment in case they later become incompetent. Advance directives have received considerable attention in the United States,5 where they have widespread legal recognition,6 but have received less publicity in Australia. In the absence of advance directives, CPR decisions are generally made by healthcare professionals in consultation with patients' families.7 The aim of this study was to compare the opinions of patients and healthcare professionals about several aspects of CPR: who should be involved in making the decision, what issues are considered important, and how these decisions should be communicated. Methods Survey We carried out a cross-sectional survey of healthcare professionals (doctors, nurses and allied health professionals) and patients at the John Hunter Hospital, Newcastle, New South Wales, in June 1994. The John Hunter Hospital is a 700-bed teaching hospital in an urban area. The survey formed part of a larger study that aimed to compare patients' and healthcare professionals' attitudes and knowledge about CPR. Survey questions were developed by reviewing published articles, incorporating questions from previously administered surveys,8,9 and consulting experts in the fields of ethics and questionnaire development. After pilot testing, the questionnaire was modified to incorporate the suggestions of a sample of patients and healthcare professionals at a local district hospital. The questionnaire included questions on sociodemographic information (age, sex, marital status, educational, religious and ethnic background) and self-reported health status. Respondents were then asked: whether doctors should ask patients if they would like CPR should they require it; whether patients have the right to choose or refuse resuscitation; who (from a list of people) should be involved in CPR decision making and who should be the main decision maker; which of eight issues listed were important in CPR decision making; whether discussing CPR was cruel or insensitive; whether they had discussed CPR and, if so, with whom; whether they would like patients' views about CPR to be expressed in writing before or soon after admission to hospital; and whether they would like patients' views about CPR to be included in medical records. The survey was administered to all healthcare professionals working over a two-day period at the John Hunter Hospital and to all eligible inpatients over an adjacent two-day period. Self-complete questionnaires were delivered by hand and collected as soon as they had been completed. Patients were initially screened by one of the principal investigators in consultation with a nursing unit manager and excluded if they were regarded as unable to complete the questionnaire or could not understand English. The remaining patients were asked by trained interviewers to participate. After consent was obtained, a Mini Mental State Examination (MMSE) was carried out to assess cognitive status. Patients with an MMSE score less than 24 were excluded, as this may indicate incompetence.10 Statistical analysis Data were analysed with SPSS for Windows.11 Continuity-corrected chi-square analysis was used to compare the sociodemographic variables and the responses of patients and healthcare professionals for each questionnaire item. Ethical approval The Hunter Area Health Service Research Ethics Committee and the University of Newcastle Research Ethics Committee approved the study. Results Respondents Of the 803 questionnaires delivered to hospital staff, 511 were returned -- a response rate of 64%. Of these respondents, 148 were doctors, 312 were nurses and 51 were from other healthcare professions, including physiotherapy, social work, occupational therapy, speech therapy and nutrition and dietetics. There were 443 adult patients in the John Hunter Hospital at the time of the study; 183 were excluded because of dementia, neurological impairment or delirium (110 of those excluded), incompetence (35), visual problems (24), psychiatric illness (9), or because they were undergoing procedures (5). Of the 260 remaining patients, 152 completed the questionnaire -- a response rate of 58%. Healthcare professionals were more likely than patients to be younger, female, have tertiary qualifications and report being healthy. Healthcare professionals and patients did not differ in terms of marital status, religion or ethnic background. Patient involvement in CPR decision making Patients and healthcare professionals differed significantly in their responses to whether doctors should ask patients if they would like CPR should they require it (P < 0.001): 23% (95% confidence interval [CI], 16%-30%) of patients and less than 1% (95% CI, 0-2%) of healthcare professionals thought that doctors should never ask patients, whereas 30% (95% CI, 22%-37%) of patients and 41% (95% CI, 37%-46%) of healthcare professionals thought that they should always ask patients. The remaining respondents were unsure or thought it depended on the patient's circumstances. There was also a significant difference in the way healthcare professionals and patients responded regarding the right to choose or refuse CPR (P < 0.001): 32% (95% CI, 25%-40%) of patients and 1% (95% CI, 0-2%) of healthcare professionals felt that patients should never have this right. Fewer patients (34%; 95% CI, 26%-42%) than healthcare professionals (67%; 63%-71%) believed that patients should always have the right to choose or refuse resuscitation, and the remaining respondents thought it depended on the patient's circumstances. Who should be involved in decision making More than 80% of patients and healthcare professionals indicated that patients and their doctors are important in CPR decision making (Table). Approximately half the respondents regarded the patient's partner and family members as important, but only a third regarded nursing staff as important decision makers. Interestingly, 47% (95% CI, 41%-52%) of nurses believed that they should be involved, whereas only 23% (95% CI, 16%-31%) of doctors and 24% (95% CI, 13%-37%) of allied health professionals believed that nurses should be involved. A significantly lower proportion of patients than healthcare professionals indicated that patients and their partners are important in making the decision. Approximately two-thirds of respondents identified the patient and less than one-third identified the doctor as the person who should be the main decision maker. There was a significant difference in the way healthcare professionals and patients responded. Fewer patients (55%; 95% CI, 47%-63%) than healthcare professionals (85%; 95% CI, 82%-88%) thought the patient should be the main decision maker, whereas 29% (95% CI, 22%-38%) of patients but only 14% (95% CI, 11%-17%) of healthcare professionals thought the doctor should be the main decision maker. The other respondents identified nurses, partners or family members. Important factors in the decision The patient's wishes, diagnosis and quality of life were identified by at least two-thirds of all respondents as important factors in CPR decision making (Figure). Patients were less likely than healthcare professionals to regard patient's wishes (P < 0.001), diagnosis (P < 0.001) and quality of life (P < 0.001) as important, but were more likely to regard age (P < 0.001), family wishes (P < 0.01), mental state (P < 0.03) and social circumstances (P < 0.01) as important. Discussing CPR Most respondents (82% in both groups) did not think discussing CPR was cruel or insensitive. Although 92% (95% CI, 86%-96%) of patients and 96% (95% CI, 94%-97%) of healthcare professionals (P < 0.001) indicated that they had family members who could make decisions for them if they were unable to, only 29% (95% CI, 22%-37%) of patients and 57% (95% CI, 52%-61%) of healthcare professionals (P < 0.001) had discussed with others whether they would like CPR. For all respondents, any discussions that had taken place were with partners (37%; 95% CI, 33%-41%), and/or family members (26%; 95% CI, 23%-30%) and/or doctors (3%; 95% CI, 2%-4%). Advance directives More than half the respondents (47% [95% CI, 39%-55%] of patients, 69% [95% CI, 64%-73%] of healthcare professionals; P < 0.01) preferred to express their wishes about CPR in writing before or soon after being hospitalised. The remaining respondents preferred to tell a family member or close friend about their wishes. About two-thirds of all respondents indicated that they would like their views about CPR to be part of their medical records. Fewer patients (60%; 95% CI, 52%-68%) than healthcare professionals (85%; 95% CI, 81%-88%) wanted their views in their medical records (P < 0.001). The remaining respondents were either uncertain or did not wish to have their views as part of their records. Discussion We found that many patients want to be involved in CPR decision making and many want some form of advance directive. Patients and healthcare professionals generally think that decisions about CPR should be shared by doctors and patients, with patients more likely to feel that doctors should be the main decision maker in such circumstances. This study has several flaws. The study uses a self-report questionnaire, and the low response rate among patients suggests that the group may not have been representative of the population as a whole. Indeed, there is likely to have been a systematic bias towards those who were willing to discuss CPR. Despite this, the findings of this study are of interest, particularly as the study sampled inpatients and had methodological strengths, including a process for the assessment of patient competence and the use of trained interviewers who were not members of the patients' own healthcare team, and thus less likely to influence their participation in the study or their responses to the questions about CPR. International studies have demonstrated that most patients would like to be involved in CPR decision making.12 Layson et al, reviewing international published studies, found that 52%-87% of patients had considered their preferences for life-sustaining therapy (CPR and admission to intensive care) and wished to discuss their preferences with their doctors, but few did so.13 We found that 80% of patients believed they should be involved in CPR decisions, but only 29% had discussed CPR with their doctors or their families. Forty-seven per cent of patients in this study would have liked to express their wishes regarding CPR in writing, either before admission or shortly after. The remainder preferred to tell a family member or a close friend. However, very few patients reported giving advance directives. There are few data to validate routine use of advance directives in hospitals. In the largest study to date that looked at the introduction of advance directives in routine care, their use did not affect patient-physician communication, physician's knowledge of patient preferences, the number of patients receiving ventilation or the use of hospital resources.14 Interestingly, that study was based upon the extensive use of nurses to assess patient preferences and communicate these results to physicians. Hospital staff appear to place more importance upon the role of patients in CPR decision making than patients do. This has been noted in previous studies of patient preferences about decision making,15,16 leading commentators such as Ende et al to suggest that the current emphasis upon patient autonomy arises more from normative ethical reasoning than from patients' actual preferences.16 Other researchers suggest that this is a misconception arising from combining several different aspects of decision making into a single question. Deber and Baumann suggest that shared decision making has two parts:17 problem solving, in which an expert identifies diagnostic and treatment options and expected risks and benefits, and decision making per se, in which the doctor and patient together determine an appropriate course of action.18 According to Deber et al, "given the choice between abiding by the decisions of a paternalistic provider and being handed a stack of medical books and being told to figure out what they wish to do, most patients unsurprisingly opt to hand over control to a trusted provider".18 Both these options are probably inappropriate, and if given a wider choice patients are unlikely to opt for unilateral decision making. Our study suggests that, despite differences between the views of healthcare professionals and patients, the overwhelming majority of both groups support patient and doctor involvement in shared decision making about CPR. Who else should be involved in CPR decision making? Both patients and healthcare professionals believe that partners and some family members should be involved. Surprisingly, only 36% of patients believed that nurses should be involved in these decisions. The reasons for this are likely to be complex. There is no doubt that nurses have a genuine stake in discussions about resuscitation. When a patient has a cardiac arrest, nurses are faced with an ethical decision: to follow their own ethical standards, or to follow the protocols documented in patient notes and hospital procedures, if such documentation exists. Within this context it is interesting to note that in a recent study of American critical care nurses 16% reported that they had participated in euthanasia or assisted suicide, many without the knowledge of physicians, patients or patients' surrogates, and 4% reported that they had hastened a patient's death by only pretending to apply life-sustaining treatment ordered by a physician.19 Nurses are independent moral agents, and there are good reasons for nurses to be involved in CPR decision making. However, there are considerable practical difficulties as nurses care for patients in shifts, and it is not possible to involve every nurse who looks after a patient. It is clearly inadequate to include only one nurse, and then to document "nursing staff in agreement". Perhaps some of this uncertainty filters through to patients. Without continuity of nursing care, patients are unlikely to consider nurses to be major participants in CPR decision making. In addition, the professional image of nurses as moral agents in their own right may not have been communicated adequately to patients or other healthcare professionals. Either way, this finding challenges the notion of "nurse as patient advocate". Differences between staff and patients in preferences about CPR decision making may influence the way decisions are made in hospital and limit the capacity for healthcare professionals to act as patient advocates. This suggests that the proper role for advance directives and the process of CPR decision making requires further study. The effect of determinants such as age, health status, education and religion on CPR decision making also requires further research. Simplistic assertions of autonomy or of the theoretical moral or legal value of advance directives without consideration of the importance of care, compassion or clinical context are clearly inappropriate. This study suggests that both healthcare professionals and patients see decision making at the end of life as a complex, shared process rather than a sterile abstraction of expert information disclosure followed by patient self-determination. Acknowledgements We wish to acknowledge student research assistants from the Faculty of Medicine and Health Sciences for their assistance with data collection and the staff and patients of the John Hunter Hospital for their generous participation in this study. References Robertson GS. Resuscitation and senility: a study of patients' opinions. J Med Ethics 1993; 19: 104-107. Stolman CJ, Gregory OJ, Dunn D, Levine JL. Evaluation of patient, physician, nurse and family attitudes toward do not resuscitate orders. Arch Intern Med 1990; 150: 653-658. Reilly BM, Magnassen R, Ross J, et al. Can we talk? Inpatient discussions about advance directives in a community hospital. Arch Intern Med 1994; 154: 2299-2308. Bedell SE, Pelle D, Maher PL, et al. Do-not-resuscitate orders for critically ill patients in the hospital: how are they used and what is their impact? JAMA 1986; 256: 233-237. Council on Ethical and Judicial Affairs. American Medical Association. Guidelines for the appropriate use of do-not-resuscitate orders. JAMA 1991; 265: 1868-1871. Fisher RH, Meslin EM. Should living wills be legalised? CMAJ 1990; 142: 23-26. Hare J, Pratt C, Nelson C. Agreement between patients and their self-selected surrogates on difficult medical decisions. Arch Intern Med 1992; 152: 1049-1054. Frankl D, Oye RK, Bellamy P. Attitudes of hospitalised patients toward life support: a survey of 200 inpatients. Am J Med 1989; 86: 645-648. Murphy DJ, Burrows D, Santilli S, et al. The influence of the probability of survival on patient's preferences regarding cardiopulmonary resuscitation. N Engl J Med 1994; 330: 545-549. Folstein MF, Folstein SE, McHugh PR. Mini-mental state. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975; 12: 189-198. SPSSx statistical package for the social sciences [computer program]. Version 6.0. Chicago, Ill: SPSS Inc, 1990. Morgan R, King D, Prajapati C, Rowe J. Views of elderly patients and their relatives on cardiopulmonary resuscitation. BMJ 1994; 308: 1677-1678. Layson RT, Adelman HM, Wallach PM, et al. Discussions about the use of life-sustaining treatments: a literature review of physicians' and patients' attitudes and practices. J Clin Ethics 1994; 5: 195-199. The SUPPORT Principle Investigators. A controlled trial to improve care for seriously ill hospitalised patients. JAMA 1995; 274: 1591-1592. Strull WM, Lo B, Charles G. Do patients want to participate in medical decision making? JAMA 1984; 252: 2990-2994. Ende J, Kazis L, Ash AB. Measuring patients' desire for autonomy: decision making and information seeking preferences among medical patients. J Gen Intern Med 1989; 4: 23-30. Deber RB, Baumann AO. Clinical reasoning in medicine and nursing: decision-making versus problem-solving. Teach Learn Med 1992; 4: 140-146. Deber RB, Kraetschmer N, Irvine J. What role do patients wish to play in treatment decision making? Arch Intern Med 1996; 156: 1414-1420. Asch DA. The role of critical-care nurses in euthanasia and assisted suicide. N Engl J Med 1996; 334: 1374-1379. (Received 14 Jul 1997, accepted 1 Apr 1998) Authors' details Faculty of Medicine and Health Sciences, University of Newcastle, NSW. Ian H Kerridge, BMed, MPhil, Lecturer in Clinical Ethics, Clinical Unit in Ethics and Health Law, and Haematology Registrar, John Hunter Hospital; Sallie-Anne Pearson, BSc(Hons), Professional Officer, Programme Evaluation Committee; Isobel E Rolfe, FRACP, MRCP, Senior Lecturer in Medical Education; Michael Lowe, BMed, Tutor in Clinical Ethics, and Medical Registrar, John Hunter Hospital. Reprints will not be available from the authors. Correspondence: Dr I H Kerridge, Clinical Unit in Ethics and Health Law, John Hunter Hospital, Locked Bag 1, Hunter Regional Mail Centre, Newcastle, NSW 2310. E-mail: ikerridgeATmail.newcastle.edu.au - Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Ian H Kerridge · Sallie-Anne Pearson · Isobel E Rolfe · Michael Lowe

The stress of metropolitan general practice Peter L Schattner and Greg J Coman MJA 1998; 169: 133-137 For editorial comment, see Douglas & Sibthorpe Abstract - Introduction - Methods - Results - Sex differences - Discussion - Acknowledgements - References - Authors' details - - ©MJA1998 Abstract Objective: To identify the work-related stressors of Australian metropolitan general practitioners (GPs). Design and setting: A descriptive postal survey of metropolitan GPs from all States and Territories selected at random from the Health Insurance Commission database. Participants: 296 of 464 GPs (64%) surveyed in June 1996; 67% were male; 87% worked full-time (more than 6 sessions per week). Main outcome measures: Frequency and severity of work stresssors in general practice; overall feelings of stress at work in the past 12 months; effects of the stressors on work satisfaction; contribution of work stress to overall life stress; responses to the 12-item General Health Questionnaire (GHQ) as potential correlates of occupational stress. Results: "Time pressure to see patients" was the most frequently reported stressor. Threat of litigation was perceived as the most severe stressor. Of the top 10 severe stressors, seven were also in the top 10 for stressor frequency. Work was the major stressor in GPs' lives. The GHQ scores did not correlate significantly with major stress outcome measures, but 12.8% of GPs had scores indicative of severe psychiatric disturbance. Fifty per cent of respondents had considered leaving their current workplace and 53% had considered abandoning general practice because of occupational stress. GPs working 6 or more sessions per week were more likely to be moderately or severely stressed than those working part-time (P < 0.02, Fisher's exact test). Those who had considered leaving their current workplace or careers were also more likely to be moderately or severely stressed (P < 0.0001, Fisher's exact test). Conclusions: The most frequent and relatively severe stressful events in general practice involved time pressures. There are implications for government, which, through remuneration policies, might influence GPs to work at a rate beyond their capacity to cope. Strategies are required to manage or prevent stress in metropolitan GPs. Introduction Stress has been defined as a response to challenging events.1 It is usually thought of as "distress" or an inability to cope with an external factor (the "stressor"). In the workplace it is generally referred to as occupational stress. Australian and international studies suggest that general practice is a stressful occupation.2-7 The extent to which GPs feel stressed by various aspects of their occupation may affect the quality of patient care and may also affect practitioners' health. Health problems experienced by GPs include alcohol and drug abuse,8-10 marital disruption and divorce,3,11,12 anxiety,3,13 burnout,14 depression,15 as well as suicide and attempted suicide.16,17 The specific characteristics that make general practice so stressful are largely unknown, although anecdotal evidence would suggest that time and financial issues are major stress factors for Australian GPs. In our study we aimed to identify the sources, frequency and severity of occupational stress experienced by metropolitan GPs; the importance of occupational stress compared with other life stressors; the effects of the work stressors on GPs' job satisfaction; and the possible effects of these stressors on GPs' psychological health. Rural GPs were not included, as factors such as isolation and difficulty in obtaining locum relief suggest this group should be studied separately.18 Methods General practitioner recruitment and survey distribution A list of 500 potential survey participants was obtained from the Health Insurance Commission database of the Commonwealth Department of Human Services and Health (now the Department of Health and Family Services). Potential participants were randomly selected from the population of GPs in all States and Territories who had capital city practices only and more than 1500 consultations annually (the number generally accepted by the General Practice Evaluation Programme as the definition of "active" GPs). The Department advised that potential participants had not recently been surveyed through this database. Questionnaires were mailed to all 500 GPs in June 1996. Non-respondents to the first mailout were sent a second questionnaire in July 1996, and non-respondents to this prompter were telephoned to request their participation in August 1996. Survey instrument We used a four-part questionnaire to collect data on:(1) GPs' demographic and practice information. (2) The frequency and severity of potentially stressful events in general practice, using a 28-item list developed from an extensive literature review which included validated stress-screening instruments,4,5,6,18 and input from a Melbourne-based GP focus group. A four-point Likert-like scale was used, with 3 representing "frequently, at least weekly"; 2, "occasionally, at least monthly"; 1, "rarely, a few times a year"; and 0, "does not occur". Another four-point Likert-like scale, with 3 representing "severe stress"; 2, "moderate stress"; 1, "mild stress"; and 0, "no stress", was used to assess stress severity for each item. (3) The effects of stressors on GPs' job satisfaction, including asking them to (a) indicate on a four-point scale (from 0 = none to 4 = severe) their overall work stress levels in the previous 12 months; (b) rank six aspects of general practice in order of contribution to work stress levels, from 1 for the greatest contribution to 6 for the least; (c) distinguish between stressors related to job content (ie, clinical duties) and job context (ie, environmental and organisational factors) (see Box 1); (d) rank six potential sources of life stress in order from 1 for the greatest source of stress to 6 for the least stressful. (4) The 12-item General Health Questionnaire (GHQ),19 used to determine the presence of psychiatric disturbance, anxiety or depression as potential correlates of occupational stress. GHQ items have four response options, which were scored 0, 0, 1 or 1. This provides a GHQ score range from 0 to 12. Using this method, scores of less than four represent negligible psychiatric disturbance, scores between four and eight suggest moderate disturbance, and scores greater than eight indicate severe psychiatric disturbance. Data entry and analysis Data were computer-coded and analysed using the Statistical Package for the Social Sciences for Windows.20 Analyses included cross-tabulations of stress outcome measures with the demographic data shown in Box 2. Non-parametric tests were used to test for significant differences at the P = 0.05 level. Potential work stressors were ranked in order of reported frequency and severity. Ethical approval Ethical approval was granted by the Monash University Standing Committee on Ethics in Research on Humans. Results Characteristics of respondents Of the 500 questionnaires mailed, 36 were returned unopened; 296 of the remaining 464 GPs participated (response rate, 64%). Box 2 shows their demographic characteristics, which are similar to the demographic profile of Australian metropolitan general practice.21 General practice stressors Frequency of general practice stressors The most frequent stressors were related to perceived lack of time. "Time pressure to see patients", "phone interruptions during consultations" and "too much work to do in a limited time" were ranked 1, 3 and 4, respectively, in frequency, with "paperwork" the second most frequent stressor (Box 3). Severity of general practice stressors The threat of litigation (actual involvement in litigation proceedings was not an item), although perceived as one of the most stressful events in general practice, was reported relatively infrequently. However, seven of the 10 most stressful events (Box 4) were also in the top 10 for frequency. The GPs appeared to experience a number of stressors which were perceived as mild to moderate, but which occurred frequently. The mean ratings for the three most severe stressors -- "threat of litigation", "too much work to do in a limited time" and "earning enough money in general practice" -- were between "mild" and "moderate". Effects of stress Overall work stress The Figure shows that most GPs (273/296; 92%) reported some feelings of stress, with 241 (81%) labelling it "mild" or "moderate" and 32 (10.8%) "severe". When asked about levels of stress in the past 12 months, 121 (41%) of GPs said they had increased, 118 (40%) said they had stayed the same, and 33 (11%) said they had decreased. Fifty per cent of GPs surveyed had considered leaving their current workplace, and 157 (53%) had considered abandoning general practice because of occupational stress. Factors associated with high overall work stress levels When the GPs' reported experience of work stress was cross-tabulated with the demographic variables reported in Box 2, the only significant association was that GPs working six or more sessions per week were more likely to be moderately or severely stressed than those working part-time (P < 0.02, Fisher's exact test). Those who had considered leaving their current workplace or abandoning their careers were also more likely to be moderately or severely stressed (P < 0.0001, Fisher's exact test). Six major causes of occupational stress Of the six most stressful aspects of general practice high workload was rated worst, followed, in descending order, by economic factors (income, running a business) and "medicopolitical" factors (involvement with professional associations, government pressures). Clinical factors and the effect of work on outside life were rated fourth and fifth, respectively, and the physical working environment was considered the dimension which contributed the least to the stresses of general practice (Box 5). These rankings were based on the means of rank scores; the first two items ranked significantly ahead of the other factors (P < 0.05). Sixty per cent of the GPs said that their experience of stress arose mainly from "job context" rather than from "job content". Comparisons with other life stresses Work was the major source of overall stress in GPs' lives, followed closely by financial concerns (Box 6). General Health Questionnaire data The 12-item GHQ was used to assess respondents' levels of psychiatric morbidity, especially depression and anxiety. The mean GHQ score was 3.01 (95% confidence interval, 2.66-3.35), suggesting that, on average, GPs experience low levels of psychiatric disturbance. However, almost a third (30.7%) of respondents recorded GHQ scores of 4 or more and 38 (12.8%) recorded scores of 8 or more, suggesting that many GPs are clinically depressed, anxious, or experiencing other psychiatric symptoms. The responses to three GHQ questions were of concern. These were Item 5 ("Have you recently felt constantly under strain?"), to which 7.1% responded "much more than usual"; Item 9 ("Have you recently been feeling unhappy and depressed?"), to which 5.1% responded "much more than usual"; and Item 11 ("Have you recently been thinking of yourself as a worthwhile person?"), to which 6.1% responded "not at all". Box 7 shows that, while significant, correlations between GHQ scores and the stress measures were not high. The highest correlation (0.53) was with GPs' overall perception of stress in the past 12 months. Sex differences There were small but statistically insignificant differences in the responses of men and women. Discussion Our study indicates that, while the worst stressors in general practice are perceived to be of only mild to moderate severity, many occur frequently. The study cannot determine whether there is a cumulative effect, in which a series of minor frustrations leads to a pervasive level of significant stress in GPs, but this may be an explanation as to why so many GPs have considered leaving their practices or abandoning general practice altogether. Apart from the threat of litigation, work overload issues, such as time pressure to see patients, phone interruptions and too much work to do in a limited time, were the most common stressors for GPs. Both GPs and their patients have been reported to be dissatisfied with the amount of time spent in consultations.4,7,22-25 Time pressure may be a reason for patients' reporting that GPs are not listening to what they are saying and not explaining things to them properly.26 Effects of time constraints on GPs may include irritability, frustration and, possibly, mistakes in diagnosis and treatment.4 Practice administration issues, which have not been traditionally taught to undergraduates, were rated as causing much more stress than issues of clinical competence. This may add to the pressure of high patient loads. The intrusion of work on family life was a significant stressor. Presumably, GPs would be less stressed if work did not impinge on family time or if they could see more of their family by working fewer hours. Although our list of potential sources of life stress was not exhaustive, we have not found a similar ranking attempt in the other stress studies reviewed. It would be interesting to see how this group of GPs compares with other occupational groups and the community at large in this regard. Concerns about remuneration and other financial concerns, such as the cost of practice overheads, were considered to be among the most frequent and severe stressors in this study (although they were not rated as highly as some might expect). This should be of interest to governments, which continue to emphasise cost-cutting in healthcare expenditure. It is of concern that almost a third of the respondents (91; 30.7%) had GHQ scores of 4 or more, suggesting moderate psychiatric disturbance, and that 38 (12.8%) scored 8 or more, suggesting severe disturbance. To some extent this is an independent finding; work stress cannot be blamed entirely for the presence of psychiatric disturbance in GPs, although it is likely to be a contributing factor. Our 64% response rate and the similarity of our sample's demographic profile to that of Australian metropolitan general practice21 suggest that the survey results are generalisable to urban GPs. It is possible that highly stressed GPs are under-represented because they were too stressed to comply with yet another demand on their time (the completion of a questionnaire). General practice may be no more or less stressful than many other "caring professions".4 However, the specific stressors highlighted in this study do suggest that government, healthcare policymakers, organisers of vocational training and GPs themselves should be aware of the high levels of stress experienced by doctors who choose this vocation, and steps should be taken to institute stress prevention and management. Acknowledgements Our thanks to the administrative staff at the Department of Community Medicine and General Practice at Monash University, as well as Dr Lynne Ham and Dr Chris Peterson for their expert advice on occupational stress, and Dr Con Tsalamandris for statistical analysis. This project was funded by a grant from the General Practice Evaluation Program of the Department of Human Services and Health. References Selye H. The stress of life. New York: McGraw Hill, 1976. Mawardi B. Satisfactions, dissatisfactions and causes of stress in medical practice. JAMA 1979; 241: 1483-1486. Roeske N. Stress and the physician. Psychiatr Ann 1981; 11: 245-258. Porter A, Howie J, Levinson A. Stress and the general practitioner. In: Payne R, Firth-Cozens J, editors. Stress in health professionals. Chichester: Wiley, 1987: 45-70. Makin P, Rout U, Cooper C. Job satisfaction and occupational stress among general practitioners -- a pilot study. J R Coll Gen Pract 1988; 38: 303-306. Sutherland V, Cooper C. Job stress, satisfaction and mental health among general practitioners before and after introduction of new contract. BMJ 1992; 304: 1545-1548. Sutherland V, Cooper C. Identifying distress among general practitioners: predictors of psychological ill health and job dissatisfaction. Soc Sci Med 1993; 37: 575-581. Ball J. Alcohol and drug use and related problems in the medical profession. Aust Drug Alcohol Rev 1986; 5: 29-32. Baldwin D, Hughes P, Conrad S, et al. Substance abuse among senior medical students. JAMA 1991; 265: 2074-2078. Serry N, Bloch S, Ball R, Anderson K. Drug and alcohol abuse by doctors. Med J Aust 1994; 160: 402-407. Bird H. The physician's marriage: joys and sorrows: life transition points. Facets 1979; Summer: 18-20. Miles J, Krell R, Lin T. The doctor's wife: mental illness and marital pattern. Int J Psychiatry Med 1975; 6: 481-487. Cramond W. Anxiety in medical practice: the doctor's own anxiety. Aust N Z J Psychiatry 1969; 3: 324-328. Lemkau J, Purdy R, Rafferty J, Rudisill J. Correlates of burnout among family practice residents. J Med Educ 1988; 63: 682-691. Smith M, Andrasik F, Quinn S. Stressors and psychological symptoms of family practice residents and spouses. J Med Educ 1988; 63: 397-405. Craig A, Pitts F. Suicide by physicians. Dis Nerv Syst 1968; 219: 763-772. Steppacher R, Mausner J. Suicide in male and female physicians. JAMA 1974; 228: 323-328. Dua J. Development of a scale to assess occupational stress in rural general practitioners. Int J Stress Manage 1996; 3: 117-128. Goldberg D, Williams P. Manual of the General Health Questionnaire. Windsor (UK): Nfer-Nelson, 1988. Statistical Package for the Social Sciences [computer program] release 6.0. SPSS, Chicago, Ill, USA, 1996. Commonwealth Department of Health and Human Services. General practice in Australia: 1996. Canberra: AGPS, 1996. Cartwright A, Anderson R. General practice revisited. London: Tavistock, 1981. Bates E. Doctors and their spouses speak: stress in medical practice. Sociol Health Illness 1982; 4: 25-39. Richardson IM, Howie J, Durno D, et al. A study of general practitioner consultations in North-East Scotland. J R Coll Gen Pract 1973; 23: 132-142. Brooks M, Stewart-Weeks M. Integrating consumer views about quality in general practice. Canberra: Consumers' Health Forum of Australia, 1996. Myerson S. Doctors' methods of dealing with "on going" stress in general practice. Med Sci Res 1991; 19: 267-269. (Received 7 Oct 1997, accepted 31 Mar 1998) Authors' details Department of Community Medicine and General Practice, Monash University, Melbourne, VIC Peter L Schattner, MMed BS, FRACGP, Director, Research Unit; Greg J Coman, GradDipAppPsych, MSc, Psychologist. Reprints will not be available from the authors. Correspondence: Dr P L Schattner, Department of Community Medicine and General Practice, Monash University, 867 Centre Road, East Bentleigh, Melbourne, VIC 3165. E-mail: peter.schattnerATmed.monash.edu.au - Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Peter L Schattner · Greg J Coman

Analysing potential harm in Australian general practice: an incident-monitoring study Alice L Bhasale, Graeme C Miller, Sharon E Reid and Helena C Britt MJA 1998; 169: 73-76 For editorial comment, see Kidd & Veale Abstract - Introduction - Method - Results - Discussion - Acknowledgements - References - Authors' details - - ©MJA1998 Abstract Objective: To collect data on incidents of potential or actual harm to general practice patients and to evaluate the possible causes of these incidents. Design: An observational study of incidents of potential harm based on a modified critical incidents technique. A non-random sample of general practitioners (GPs) anonymously submitted incident reports contemporaneously. Setting and participants: Australian general practices between October 1993 and June 1995. During the study period, 324 GPs participated at some time. Main outcome measures: GP-reported free-text descriptions of incidents and structured responses for preventability, potential for harm, immediate consequences, predicted long-term outcomes, type of incident, contributing factors, mitigating factors, and additional resource use. Results: 805 incidents were reported -- 76% were preventable; 27% had potential for severe harm. No long term harm was predicted for 66% of incidents. Incidents could relate to pharmacological management (51 per 100 incidents), non-pharmacological management (42 per 100 incidents), diagnosis (34 per 100 incidents) or equipment (5 per 100 incidents). The most common contributory factors were poor communication between patients and healthcare professionals and actions of others (23 per 100 incidents each) and errors in judgement (22 per 100 incidents). Conclusion: Human errors and preventable system problems were identified. The incident monitoring technique provided useful data which could be applied to incident prevention strategies. Introduction Increased interest in quality improvement in healthcare has led to greater recognition that errors occur. The Harvard Medical Practice Study1,2 and the Quality in Australian Health Care Study3 retrospectively reviewed hospital medical records to identify and quantify adverse events caused by the hospital care provided. These studies have provided important insight into rates of adverse outcomes. In Australia, around 16% of admissions studied were associated with an adverse event.3Following the success of incident monitoring in anaesthetics,4,5 in 1993 the Commonwealth Review of Professional Indemnity Arrangements for Health Care Professionals initiated pilot incident-monitoring studies in six medical specialties. The aim of this study was to test the incident-monitoring method in general practice. An important difference between studies such as the Harvard Medical Practice Study and incident-monitoring studies is that no claims of generalisability are made in the latter. Incident monitoring cannot estimate prevalence. It provides detailed contextual information about specific processes and situations that can lead to adverse patient outcomes. Such information is then used to make specific recommendations. The objectives of this study were to test a mechanism for obtaining incident reports from GPs; to gain an understanding of the type of incidents occurring in general practice and hence areas of potential harm; and to identify areas which might benefit from intervention. Method The method has been described in detail elsewhere.6 Participating general practitioners reported incidents contemporaneously, on purpose-designed reporting forms. An incident was broadly defined as "an unintended event, no matter how seemingly trivial or commonplace, that could have harmed or did harm a patient". This criterion included "near misses" -- where the harm may have been averted, but the potential for harm existed. All GP members of the Australian Sentinel Practice Research Network and the Central, Southern, Western and Wentworth Area Health Sentinel Networks in Sydney were asked by letter to participate. Others volunteered when reporting was offered as a Quality Assurance option through the Royal Australian College of General Practitioners (RACGP). Reports were anonymous and information was protected from subpoena by the Health Insurance Act 1973 (Cwlth).7 The reporting form included both free text and fixed-response questions. Information requested included GP characteristics and the patient's age, sex and health problems associated with the incident. Free text descriptions were elicited of the incident, its consequences, and contributing and mitigating factors; the outcome; and the GP's opinion of the incident's preventability. Fixed-choice responses included the type of incident, contributing factors, mitigating factors, potential for harm, immediate consequences, and predicted long term outcomes. All fixed-choice questions included an "other" category to allow continuing development of categories. Quantitative descriptive analysis was used to describe the main features of the data for all 805 incidents received, using SAS.8 No significance testing was carried out as it would have been invalid because of the nature of the study and sample. Qualitative analysis of textual data was carried out for 500 incidents. This analysis involved examination of groups of events for common causes, situations and contributing factors. Results GP response Of 510 GPs initially approached, 214 accepted. A further 110 GPs volunteered during the study. Between October 1993 and June 1995, 805 reports were received from 324 enrolled participants. As all reports were anonymous, reporting rates could not be calculated. However, a GP-generated personal identification number on most reports allowed estimation of the number of reports received from each identification number. There were 241 GPs who submitted at least one report, and 82 unidentified reports. The proportion of each sex and the proportion from rural practices among the respondents were equivalent to the overall GP population at that time.9 However, only 16% of respondents had less than 10 years' experience, whereas in a national sample in 1990-1991 about 30% of GPs had less than 10 years' experience.10 Patients Of the 805 incidents, 58% involved female patients. Almost one-third of incidents involved patients over 65 years old (median age, 50 years; range, 0-98 years). Younger patients (0-24 years) were least likely to be involved in incidents (Figure). Compared with the overall age-sex distribution of patients attending GP consultations, women older than 75 years and infants were over-represented in the incidents reported.9 Age and sex of patients involved in reported incidents. Incidents Incidents were categorised as pharmacological, non-pharmacological, diagnostic or equipment events (Box 1). Pharmacological events were most frequent. The most common incident type overall was omitted or delayed treatment. A high degree of overlap between non-pharmacological and diagnostic events was noted -- 79 incidents involved both types. GPs thought 76% of the incidents were preventable (Box 2) and 11% were unpreventable. They were undecided about the remaining 13%. More than one-third of the incidents resulted in additional use of resources. While pharmacological incidents were most often reported, they were also largely considered preventable (79%) and the least harmful potentially and in the long term. In contrast, diagnostic events were less preventable and more harmful (Box 2). Of the 38 deaths reported, 30 involved a diagnostic incident. Major immediate consequences were reported in 17% of incidents, and 4% resulted in the patient's death (Box 2). GPs predicted that most incidents would cause no long term harm, but that 7% would result in the future death of the patient. Mitigating and contributing factors Incident outcomes were more frequently mitigated by chance factors than through systematised fail-safe or preventive procedures. The most frequently reported mitigating factors were good fortune, early intervention by the GP, and the patient's good physical condition (Box 3). Ineffective communication and problems in coordination between healthcare services were frequent contributing factors (Box 4). Actions or involvement of others in caring for patients were also frequently cited. Assessment-related mistakes constituted another cluster of contributing factors (eg, errors in judgement, failure to recognise significant signs and symptoms, and inadequate patient assessment). Insufficient use of standard resources and protocols by the GP was also recognised. GPs reported being tired, rushed or late in 10% of incidents, but GP memory lapses and stressful situations were least frequently cited as contributing factors. There were no obvious associations between specific contributing factors and incident type. Qualitative analysis Qualitative analysis of free-text responses identified four broad problem groups: communication, procedural, clinical and external problems. More comprehensive descriptions are available elsewhere.11,12Communication problems: Most communication problems between GPs and patients occurred when patients did not understand some aspect of their condition, the management plan or the treatment. Patients with mental health problems or lacking English language skills were particularly at risk. Some serious pharmacological incidents occurred when patients misunderstood instructions and took newly prescribed drugs in addition to, rather than instead of, a previously prescribed medication. Poor communication also manifested as clinical error in inadequate history taking. There were also problems with communication between healthcare providers. Clinical information about the outcomes of hospital referrals or admissions, the expected role of the GP in post-discharge care, specialists' recommendations for management and results of tests or investigations was often not communicated between GPs and other healthcare providers, or was too late to be of use. Unclear or uninformative medical records caused a number of incidents, and inadequate records resulted in poor communication within practices. Incorrect or unclear labelling of drugs resulted in administration of the wrong drug, and inappropriate drugs were dispensed because of poor handwriting on prescription forms. Such errors were often compounded by similar medication names (eg, Teldane/Feldene, Microlax/ Murelax). Procedural problems: The main procedural error was failure to check medical records. Diagnostically, procedural error manifested in poor application of the differential diagnosis, when the correct diagnosis was inappropriately rejected because of insufficient or incorrect examination, or was not included in the differential diagnoses and was therefore not evaluated. In non-pharmacological incidents, treatment procedures may have been neglected (eg, not checking for anaesthesia before an excision). In equipment incidents, machines were not properly checked before use (eg, leads or tubes were disconnected) or were not well maintained (eg, unfilled emergency oxyviva equipment). Lack of protocols for ensuring action on results of tests and investigations meant that important results were filed unseen or left until the GP who ordered the test was next in the surgery. Recall systems were often inadequate, preventing recall of patients for follow-up tests and investigations and resulting in missed or delayed diagnosis or management. Clinical problems: These consisted of incidents that could only be attributed to human error. In pharmacological incidents, clinical errors occurred where an inappropriate drug was chosen; in non-pharmacological incidents, where the wrong treatment was chosen; in diagnostic incidents, where symptoms and signs were not recognised (eg, chest pain considered to be musculoskeletal); and in equipment incidents, where equipment was used inappropriately. External problems: External problems involved factors outside the GP's control, such as actions of other healthcare providers, equipment faults or unavailability, disease-related factors, and unpredictable drug effects. Patient-related factors included non-compliance, age, level of comprehension, and psychological condition. Discussion The diversity of incidents reflects the heterogeneous nature of general practice and its context within the healthcare system. Nevertheless, it was possible to isolate recurrent themes and errors and to identify incidents that occurred because of system problems or other preventable factors. Pharmacological incidents were most frequent and could be prevented through clearer prescription writing, double-checking of doses and potential interactions, and improved patient understanding. Unexpected drug reactions (eg, to previously well-tolerated drugs) and idiosyncratic complications were largely beyond GPs' control. However, compilation of this information may be useful to reinforce or add to data collected elsewhere. Diagnostic incidents had the most serious outcomes. While management of test results and lack of recall systems contributed to these incidents, many occurred while the patient was under another medical practitioner's care, or were caused by the diagnostic decision-making processes of GPs. Patient misunderstanding was a factor in many incidents. This might be addressed by improved GP awareness to ensure full patient understanding. However, information management problems require "hard-wired" solutions -- structures and systems that ensure better outcomes. In particular, opportunities for errors may be reduced by better recall systems for follow-up and for regular tests and screening,13 better transfer of medical information between healthcare providers, clearer writing of prescriptions, and better maintenance and use of medical records. Information technology could help by streamlining some of the administrative functions, particularly prescription writing, which appears to be adversely affected when GPs are tired, rushed, or running late. Limitations to the validity of our data include the non-random nature of the sample, limited recognition of incidents, selectivity in reporting incidents, and the lack of an alternative perspective. (We did not seek the patients' perspective because of the controversial nature of the data.) However, issues we identified as important have been described by other researchers. Many of the issues pertaining to pharmacological incidents have been described in a study of adverse drug events in United States hospitals.14 Similarly, the problems of multiple prescribing in the elderly have been well summarised, and opportunities for improvement in the management of polypharmacy have been identified.15 Prescription clarity has also been recognised as an area of potential misunderstanding.16 In critical incident studies, incidents are sampled until "saturation" (until no new incident types are reported).17 While these 805 incidents may not reach saturation, they demonstrate at least some of the types of incidents occurring in Australian general practice. Logically, where inadequate systems are widely used, similar events are likely to occur regularly rather than being related to individual characteristics or techniques. Continued collection and classification of events will elucidate more causal factors, particularly for the less common types of incidents. This study also resulted in a number of suggested interventions.18 Incident monitoring studies are intended to be continually used in improving systems. It is important to use the data for formulating interventions. This study has shown that such data can be collected in general practice, but the translation of findings into active change remains to be addressed. Acknowledgements We gratefully acknowledge the funding provided by the Commonwealth Review of Professional Indemnity Arrangements for Health Care Professionals. The project was conducted under the auspices of the RACGP. Recruitment of GPs and administration of the GP participants was carried out jointly by the Family Medicine Research Unit and the RACGP Research and Health Promotion Unit, South Australia. Other members of the research team made considerable contributions to running the project. Thanks must go to the GP participants for so generously sharing their experiences with us. References Brennan TA, Leape LL, Laird NM, et al. Incidence of adverse events and negligence in hospitalized patients: results of the Harvard Medical Practice Study I. N Engl J Med 1991; 324: 370-376. Leape LL, Brennan TA, Laird NM, et al. The nature of adverse events in hospitalized patients: results of the Harvard Medical Practice Study II. N Engl J Med 1991; 324: 377-384. Wilson RM, Runciman WB, Gibberd RW, et al. The Quality in Australian Health Care Study. Med J Aust 1995; 163: 458-471. Williamson JA, Mackay P. Incident reporting. Med J Aust 1991; 155: 340-343. Webb R, Currie M, Morgan CA, et al. The Australian incident monitoring study: an analysis of 2000 incident reports. Anaesth Intensive Care 1993; 21: 520-528. Britt H, Miller G, Steven I, et al. Collecting data on potentially harmful events: a method for monitoring incidents in general practice. Fam Pract 1997; 14: 101-106. Commonwealth of Australia. Health Insurance Act 1973. Declaration under section 106L. Commonwealth of Australia Gazette 1993; GN 31: 2269-2272. SAS [computer program]. Version 6.11. Cary, North Carolina: SAS Institute, 1995. General Practice Branch. Commonwealth Department of Health and Family Services. General Practice in Australia: 1996. Canberra: Commonwealth of Australia, 1996. Bridges-Webb C, Britt H, Miles DA, et al. Morbidity and treatment in general practice in Australia 1990-1991. Med J Aust 1992; 157 Suppl: S1-S56. Miller G, Britt H, Steven I, et al. Incident monitoring in general practice: a pilot study. Report to the Professional Indemnity Review, Commonwealth Department of Human Services and Health. Sydney: Royal Australian College of General Practitioners, 1995. Bhasale AL. Collecting data on potentially harmful events: evaluation of an incident monitoring technique in Australian general practice [master's thesis]. Sydney: University of Sydney, 1997. Bhasale AL, Norton KJ, Britt H. Tests and investigations. Indicators for better utilisation. Aust Fam Physician 1996; 25: 680-694. Leape LL, Bates DW, Cullen DJ, et al. Systems analysis of adverse drug events. JAMA 1995; 274: 35-43. Teng Liaw S. Drug interactions among the elderly. Aust Fam Physician 1997; 26: 355-357. Liddell MJ, Goldman SP. Attitudes to and use of a modified prescription form by general practitioners and pharmacists. Med J Aust 1998; 168: 322-325. Flanagan JC. The critical incident technique. Psych Bull 1954; 51: 327-359. Bhasale AL, Britt H, Miller G. Developing interventions which could reduce the occurrence of adverse patient incidents in general practice. Report to the Taskforce on Quality in Australian Health Care, Department of Human Services and Health, Canberra. Sydney: Family Medicine Research Unit, University of Sydney, 1995. (Received 4 Aug 1997, accepted 26 Mar 1998) Authors' details Department of General Practice, University of Sydney, Sydney, NSW. Alice L Bhasale, BSc(Psychol), MSc(Med), Senior Research Assistant, Family Medicine Research Unit; Graeme C Miller, MB BS, FRACGP, Medical Director, Family Medicine Research Unit; Sharon E Reid, MB BS, MPH, Lecturer; Helena C Britt, PhD, Director, Family Medicine Research Unit. Reprints will not be available from the authors. Correspondence: Ms A L Bhasale, Acacia House, Westmead Hospital, Westmead, NSW 2145. E-mail: alicebATgenprac.wsahs.nsw.gov.au - Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Alice L Bhasale · Graeme C Miller · Sharon E Reid · Helena C Britt

Suicide among young Australians, 1964-1993: an interstate comparison of metropolitan and rural trends Michael J Dudley, Norman J Kelk, Tony M Florio, John P Howard and Brent G H Waters MJA 1998; 169: 77-80 See also Rosenman Abstract - Introduction - Methods - Results - Discussion - Acknowledgements - References - Authors' details - - ©MJA1998 Abstract Objectives: (i) To compare suicide rates in 15-24 year old men and women; and (ii) for 15-24 year old men, to investigate differences in suicide rates between metropolitan and rural areas, and changes in method-specific suicide rates and, in particular, firearm and hanging suicide rates in rural and metropolitan areas. Design: Retrospective analysis of Australian Bureau of Statistics (ABS) suicide data (1964-1993). Setting: All Australian States. Subjects: Young women and men aged 15-24 years who died by suicide. Results: Male youth suicide rates rose substantially over the 30 years in all Australian States, whereas female rates did not increase. Increases in suicide rates in young men in small rural towns consistently exceeded those in metropolitan areas in all Australian States. Metropolitan rates in 1964 were higher than those in small rural towns, but by 1993 the position was reversed. Medium-sized cities were the only areas where there was no consistent interstate trend. Differences were noted in suicide base rates in different States. High car exhaust suicide rates were noted in Western Australia, and high firearm suicide rates in Tasmania and Queensland. The ratio of firearm suicide rates in small rural areas to those in metropolitan areas rose in all mainland States, but the same ratio for hanging suicide rates changed little. Conclusions: All Australian States reflect national suicide trends in relation to sex and residential area. In some States, particular suicide methods predominate. A decreasing trend in overall firearm suicide rates in young men in all States from 1984 to 1993 conceals substantial increases in firearm suicide rates in small rural areas in all mainland States over the 30-year period. This, together with the marked rate ratio difference in firearm suicides between metropolitan and small rural areas, suggests that particular risk factors for suicide are operating in small rural areas. The fact that hanging rate ratios changed little suggests that more general factors in male youth suicide are also operating in all areas. A better understanding of similarities and differences in health risks faced by metropolitan and rural youth is required. Introduction Suicide rates for 15-24 year old Australian men have trebled since the early 1960s. However, these rate increases have not been uniform. In metropolitan areas they have doubled, but they have increased as much as 12-fold in towns with fewer than 4000 people. The rates for suicide with a firearm in 15-24 year old men have declined overall, and in metropolitan areas since the late 1980s, but they have continued to rise in rural areas. Rates of suicide by hanging have risen in all locations.1We aimed to answer questions about whether these national suicide trends are replicated at the State level. We wanted to know whether the trends for the larger States dominate the national picture, or whether the same fundamental trends are occurring in all States. Interstate analysis is also important, because health, education and welfare services are often organised and funded at a State level. Differences among the States have long been part of the Australian culture, and firearms legislation, in particular, is at present a State prerogative. In this article, we report suicide rates in young men and women (aged 15-24 years) in all Australian States and Territories, as well as suicide rates in young men by method of suicide, and by residential area, in all States, for 1964 to 1993. Methods Our methods are described in more detail elsewhere.1 Data on suicides and corresponding population data for subjects aged 15-24 years were sought from the Australian Bureau of Statistics (ABS) for the years 1964-1993. These data were de-identified, and an undertaking was given not to attempt to identify the subjects or to contact their families. Data concerning usual area of residence were available for all but 219 of 8537 people who had died by suicide. Subjects' usual place of residence was classified as: metropolitan areas of capital cities of each State; cities with populations >100 000; cities with populations >25 000; towns with populations >4000; or towns with populations <400. These cut-offs, chosen after consulting social geographical sources,2,3 approximate Australian urban groupings in order of size. Definitions of "metropolitan" and "rural" also follow guidelines given in these sources. Rates throughout are expressed as numbers of suicides per 100 000 of the at-risk population. Data were aggregated in 5-year epochs to enable longer-term trends to be discerned. Results Sex-specific suicide rates Suicide rates in 15-24 year old men rose substantially over the past 30 years in all Australian States and Territories, but rates in women of the same age did not (Figure 1). We will consider suicide rates in 15-24 year old men only in the remainder of the article. Method-specific suicide rates Considering the whole 30-year period, for 15-24 year old men, a clear trend exists, both nationally and for individual States, of a reduction in firearm suicide rates in the past 10-15 years, and of an increase in hanging suicide rates over the whole period at a substantially greater rate than the increase by all other methods. Car exhaust suicide rates also increased at a greater rate than the overall increase, especially in Western Australia, but to a lesser extent than suicide by hanging. Suicides by poisoning did not increase proportionally in any States or nationally. Hanging is now the most common method of youth suicide in most States, exceeding firearms as a means of suicide in all States except Queensland and Tasmania. In the most recent epoch, firearm suicide rates were highest in Tasmania and Queensland (Figure 2). Residence-specific suicide rates In all States, suicide rates in 15-24 year old men have increased substantially in metropolitan areas, but the greatest increases have been recorded for towns with a population under 4000. In 1964 in four States (New South Wales, Victoria, Queensland, Western Australia), metropolitan suicide rates exceeded those of small rural areas, but by 1993 the position was reversed (Figure 3). New South Wales Suicide rates in 15-24 year old men rose consistently in all residential categories except cities with over 25 000 people. Sydney's rates rose least (1.6-fold), smaller towns (population, <4000) rose the most (9.9-fold), and Newcastle- Wollongong (2.7-fold) and towns with populations over 4000 (3.8-fold) were intermediate. Victoria Suicide rates in 15-24 year old men rose in all residential areas. Melbourne's rates began from a low baseline, and in 1964 rate differences between Melbourne and smaller towns (population, <4000) were less marked than in NSW. Melbourne's rates rose least (4.2-fold), smaller towns with fewer than 4000 people the most (34.5-fold), and Geelong (5.7-fold) and larger towns (population, >4000) (5.5-fold) were intermediate. Queensland Suicide rates in 15-24 year old men in Brisbane trebled, and rates for the Gold Coast and Sunshine Coast, areas with a high population growth, which both now exceed 100 000 people, peaked in the mid 1970s, but then fell. Rates in cities (population, >25 000 and larger towns (population >4000) increased 1.7- and 1.9-fold, respectively, but in smaller towns (population, <4000) the increase was 31.6-fold. South Australia Differences in suicide rates in 15-24 year old men between metropolitan and small rural areas were less marked in States with lower populations. Adelaide's suicide rate for young men rose 2.7-fold, and in towns with populations under 4000 it rose 5.5-fold. Rates in larger towns (population, >4000) increased 1.8-fold. High rates in cities with populations >25 000 were based on small numbers. Western Australia Suicide rates in 15-24 year old men in Perth rose 2.5-fold and rates in smaller towns (population, <4000) rose 7.0-fold. Rates in larger towns (population, >4000) fluctuated, rising 3.2-fold overall. Tasmania Tasmania's suicide rates in 15-24 year old men have been consistently high. While Hobart's rates have more than doubled, rates in smaller towns (population, <4000) have risen 3.6-fold. Trends elsewhere were inconsistent, although high rates have been recorded. Firearm and hanging suicide rates for metropolitan and small rural areas Suicide with firearms or by hanging, the most common methods, account for between a half and two-thirds of suicides in 15-24 year old men in each State, so these have been analysed by place of residence. In all States the ratio of the firearms suicide rate in small rural areas to the firearms suicide rate in metropolitan areas rose substantially over the 30-year period. In contrast, this ratio for suicide rates by hanging remained much the same or rose minimally over the same period. Thus, the national trend for a reduction in firearm suicide rates conceals a continuing rise in firearm suicide rates in rural areas in all States. These increases were especially pronounced in Victoria and Queensland (41.5- and 36.7-fold respectively), while Tasmania's rates remained high throughout the period (Figure 4). Discussion National youth suicide trends according to sex of the subject are reflected in the rates of all the individual States: suicides in 15-24 year old men rose substantially, whereas those in 15-24 year old women did not change in the past 30 years. The disproportionate increase in suicide rates in young men in small rural areas nationally is also occurring consistently in all Australian States. Certain data limitations should be noted. Coroners often must exercise subjective judgements in determining verdicts, which may lead to possible systematic differences in rates between different States and over time; Errors may also arise from unstandardised methods of recording suicides, especially earlier in the study period;1 Population data may fluctuate in minor ways with changing residential area boundaries, notably with some towns being absorbed into larger cities; and The data do not allow inferences about particular local geographical areas (see for comparison National Injury Surveillance Unit data4). However, it is unlikely that changing coronial verdicts account for the magnitude or generality of the changes we noted. Cantor and Coory5 found that Queensland's provincial cities and rural towns of modest size had negligible rate increases compared with metropolitan and major urban areas from 1986 to 1991. They questioned whether there was a rural suicide problem in Queensland. Our study confirms their observations for Queensland cities with populations over 25 000, but notes a massive rate increase in towns with fewer than 4000 people, with substantial numbers supporting this finding. Further, the Queensland picture does not appear to be atypical. There are differences in suicide base rates in the various States. Whether Melbourne's low base rate in 1964 is coincidental, or a result of Victorian coroners showing less willingness to reach a verdict of suicide, requires further investigation. Tasmania's relative isolation, demographically stable population, and easy firearm access may explain its consistently high suicide rates. Suicide methods differ somewhat between States. The high rates for car exhaust suicides in Western Australia may reflect its relative isolation and this method's cultural acceptability. Carbon monoxide sensors, exhaust modifications and changes to catalytic converters may be effective prevention measures.6 High firearm suicide rates among 15-24 year old men in Tasmania and Queensland,7 rising metropolitan firearm suicide rates in those States, and rising rates in small towns (population, <4000) in all States, but especially Victoria and Queensland, probably relate to falling populations in small rural areas with stable or rising suicide numbers, the easy availability of firearms, and the more liberal firearm legislation in Tasmania and Queensland. Applying methods to prevent car exhaust suicide and reducing the availability of guns may reduce suicide rates by these two methods, and possibly total suicide rates.8 While rates for suicide by various methods may differ in different States, residential area trends for firearm and hanging suicides were pronounced in all States. A trend for overall firearm suicide rates to decrease in all States from 1984-1993 conceals substantial firearm rate increases in small rural areas in all mainland States over the 30-year period. Differences in rates between metropolitan and small rural areas, and the fact that the ratio of firearms suicide rates in small rural areas to those in metropolitan areas rose substantially in all mainland States, suggest that particular risk factors (directly and indirectly related to firearms) are operating in small rural areas. Restrictive legislation may differentially affect firearm suicides in metropolitan areas, where availability is lower.9 The rural economic downturn, the strain on small rural communities, and a major population exodus in all States from towns with fewer than 4000 people have meant added health burdens for those communities, with possibly specific risk factors.1 The fact that the equivalent ratio for hanging rates changed little suggests that more general factors are also operating across all areas in relation to suicide in young men. Particular States have local issues which require specific attention, but the fact that all Australian States reflect the national trends in youth suicide in relation to sex and residential area supports a national approach to youth suicide prevention. Effective national approaches will depend in part on acquiring a better understanding of the similarities and differences in health risks faced by metropolitan and rural youth.1 Acknowledgements Thanks are due to Caroline Haski and Margaret Alcock for their painstaking work as research assistants, and to the NSW Institute of Psychiatry, which partly funded this study. References Dudley M, Kelk N, Waters B, et al. Suicide among young rural Australians 1964-1993: a comparison with metropolitan trends. Soc Psychiatry Psychiatr Epidemiol 1997; 32: 251-260. Department of Primary Industries and Energy and Department of Human Services and Health. Rural, remote and metropolitan areas classification, 1991 Census edition. Canberra: AGPS, 1994. Holmes J. In: Jeans D, editor. Space and society. Chapters 2 and 3. Sydney: Sydney University Press, 1988: 24-74. Moller J. An atlas of injury death in Australia 1990-1992. Adelaide: National Injury Surveillance Unit, 1995. Also available online: <www.nisu.flinders.edu.au/data/atlas/atlas.html> Cantor C, Coory M. Is there a rural suicide problem? Aust J Public Health 1993; 17: 382-384. Australian Institute for Suicide Research and Prevention. Access to means of suicide by young Australians; a background report to the Commonwealth Department of Health and Family Services Youth Suicide Prevention Advisory Group. Brisbane: Australian Institute for Suicide Research and Prevention, 1996. Cantor C, Lewin T. Firearms and suicide in Australia. Aust N Z J Psychiatry 1990; 24: 500-509. Cantor C, Baume P. Access to methods of suicide: what impact? Aust N Z J Psychiatry 1998; 32: 8-14. Cantor C, Slater P. The impact of firearm control legislation on suicide in Queensland: preliminary findings. Med J Aust 1995; 162: 583-585. (Received 12 May 1997, accepted 17 Apr 1998) Authors' details University of New South Wales, Sydney, NSW. Michael J Dudley, MB BS, FRANZCP, Lecturer, School of Psychiatry. Norman J Kelk, PhD, Social Worker, School of Community Medicine. Prince of Wales Hospital, Sydney, NSW. Tony M Florio, MPsych, Clinical Psychologist. Macquarie University, Sydney, NSW. John P Howard, PhD, Clinical Psychologist. PO Box 474, Edgecliff, NSW. Brent G H Waters, MD, FRANZCP, Psychiatrist. Reprints will not be available from the authors. Correspondence: Dr M J Dudley, Department of Child and Adolescent Psychiatry, Sydney Children's Hospital, Randwick, NSW 2031. E-mail: m.dudleyATunsw.edu.au - Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Michael J Dudley · Norman J Kelk · Tony M Florio · John P Howard

Prostate-specific antigen testing in Australia and association with prostate cancer incidence in New South Wales David P Smith and Bruce K Armstrong MJA 1998; 169: 17-20 For editorial comment, see McCredie & Cox Abstract - Introduction - Methods - Results - Discussion - Acknowledgements - References - Authors' details - - ©MJA1998 Abstract Objective: To describe patterns and trends in prostate-specific antigen (PSA) testing in Australia and assess its role in the increasing incidence of prostate cancer. Design: Descriptive analysis of (i) Medicare records of PSA testing in Australia, and (ii) prostate cancer recorded incidence in New South Wales. Data: (i) Medicare data for all males who received a Medicare-reimbursed PSA test between August 1989 and December 1996. (ii) NSW Central Cancer Registry data for all males in NSW with prostate cancer diagnosed between 1988 and 1995. Main outcome measures: (i) Number of PSA tests, age-standardised rates of PSA tests by State and Territory, and proportions of males who had a PSA test. (ii) Recorded incidence of prostate cancer in NSW. Results: (i) More than 2.2 million PSA tests were done on more than 1.1 million Australians between 1989 and 1996. The annual number of males tested increased fivefold in this period and peaked in 1995. Twenty-seven per cent of Australian men aged 50 years or over had at least one PSA test in 1995 or 1996; 33% of men aged 60-69 years had a test in this period. (ii) In NSW the number of PSA tests per quarter was highly correlated with the number of new cases of prostate cancer (R2 = 0.92). Conclusions: Although no organised program for prostate cancer screening exists, and despite repeated advice against it, opportunistic screening has been occurring at high rates. There was a high correlation between PSA testing and prostate cancer incidence between 1990 and 1995 in NSW. Introduction Prostate cancer is the most common cancer in Australians after non-melanocytic skin cancers, and accounts for about a third of all newly diagnosed internal cancers in males.1,2 It is the second most common cause of cancer death among Australian males.3 During the late 1980s and early 1990s, recorded prostate cancer incidences increased substantially in Australia, while mortality from prostate cancer remained stable.1,2,4-6 Much of the increase in incidence has been attributed to detection of latent cancers by increased use of the prostate-specific antigen (PSA) test, transurethral resection of the prostate, prostatic biopsy and radical prostatectomy.7There are considerable arguments for8,9 and against10,11 screening for prostate cancer. In 1996 the Australian Health Technology Advisory Committee reviewed the evidence and recommended against screening. However, the committee recognised that de facto screening occurs in the community and stated a need to monitor and review the evidence when important developments occur.12 Data collected by the Health Insurance Commission provide the best available means to monitor trends and patterns in PSA testing. We analysed these data to determine the association between PSA testing and reported incidence of prostate cancer in Australia and in New South Wales. Methods Data PSA tests: The Commonwealth Department of Health and Family Services Medicare Estimates and Statistics Unit provided de-identified data, extracted from the national dataset of all services rendered on a fee-for-service basis for which a Medicare benefit has been paid. The data included all tests itemised under the Medicare Benefits Schedule codes that included PSA tests. PSA tests first appeared in the Schedule in August 1989, but were included with 20 "other" biochemical tests until November 1993. Since then they have been itemised together with prostatic acid phosphatase (PAP) tests. PSA tests could not be differentiated from PAP tests with the available information. To estimate the proportion of non-PSA tests in the dataset, we investigated the patterns of use of the other tests, using data provided by the Commonwealth Department of Health and Family Services. We calculated retrospective projections using exponential regression on the number of tests by age group and annual quarter to give an adjusted number of PSA and PAP tests for the period between August 1989 and November 1993. This study included data for all males who had at least one PSA or PAP test between 1989 and 1996 reimbursed by Medicare. The data included a unique identification number for each person, age, date of service, postcode, and fee charged for the service. The identification number allowed individuals to be linked over time to quantify those who had multiple tests, but was not linkable to any other identifying data. Prostate cancer: Data on prostate cancer incidence in NSW were obtained from the NSW Central Cancer Registry, a population-based register which began collecting data in 1972. Notification of malignant neoplasms has been a statutory requirement for all NSW public and private hospitals, radiation oncology departments and nursing homes since 1972, and for all pathology and outpatient departments since 1985.1 Population: The Australian Bureau of Statistics provided the estimated resident populations of Australia by five-year age group and State or Territory for the years 1989 to 1996.13 Analysis We calculated the rate of testing and the number of males tested by age group, State or Territory, and year from August 1989 to December 1996. We calculated the number of males having multiple tests from January 1995 to December 1996 and the proportion of males tested in each age group in this period. We used a two-year period for these calculations to reduce errors introduced by men moving up age groups. We compared the number of tests carried out in NSW by quarter with the number of prostate cancers diagnosed between 1990 and 1995 (the most recent year for which prostate cancer data were available). All rates, standardised to the total male and female Australian 1991 population, are expressed per 100 000 males. We used SAS software for statistical analysis.14 Results PSA testing in Australia From August 1989 to December 1996 more than 2.2 million PSA or PAP tests were reimbursed by Medicare in Australia. About 1.1 million males were tested during this period. Eighty-eight per cent of the tests were for men aged 50 years or over, with the largest proportion (34%) for men aged 60-69 years (Table 1). Age-standardised rates for males having one or more PSA/PAP tests per year increased fivefold between 1990 and 1996, and the greatest increases occurred between 1993 and 1995. There was substantial variation in the rates of testing by State and Territory (Figure 1). Except in the Australian Capital Territory, the rates peaked in 1995, when the highest rates were in Western Australia (8668 tests per 100 000) and the Australian Capital Territory (8284 tests per 100 000) and the lowest in the Northern Territory (3270 per 100 000). From January 1995 to December 1996, 709 523 Australian males had at least one PSA/PAP test reimbursed by Medicare. Most of those tested (73%) had one test, 17% had two tests, 5% had three tests and 5% had four or more tests. Older men were more likely to have had multiple tests (Table 2). In this period, 27% of Australian men aged 50 years and over had one or more PSA/PAP tests reimbursed by Medicare. This figure peaked at 33% in men aged 60-69 years (Table 3). In 1996 the Medicare schedule fee for a single PSA/PAP test was $19.90 or, where two or more tests were undertaken at the same consultation, $36.65. The overall amount reimbursed by Medicare for PSA/PAP tests in 1996 was $10 675 880 (mean per test, $20.73; mode, $19.90; range, $11.00 to $36.65), not including the fee that may have been charged for the accompanying consultation. PSA/PAP tests and prostate cancer in NSW Between 1990 and 1995, more than 625 000 PSA/PAP tests were carried out in NSW, and 20 120 prostate cancers were diagnosed. The number of tests was highly correlated with the number of prostate cancers diagnosed (R2 = 0.92) (Figure 2). The ratio of number of tests performed to number of new cases of prostate cancer diagnosed increased from about 19 in 1990 to 45 in 1995. In 1995, in NSW, 150 479 males had one or more PSA/PAP tests. Figure 3 shows the age-specific rates of testing and reported incidence of prostate cancer. The number of PSA/PAP tests per prostate cancer detected in 1995 varied between age groups from a high of 579 in men aged 40-49 years to fewer than 24 in men aged 70 years or over. Discussion More than 2.2 million PSA tests were carried out in Australia from 1989 to 1996. More than 1.1 million males were tested in this period, and the annual number of males tested peaked in 1995. Data from this study support the hypothesis that the rising incidence of prostate cancer is associated with increased PSA testing. In NSW, the number of PSA tests was highly correlated with the number of new cases of prostate cancer. The PSA test is a blood test used in diagnosis and monitoring of prostate disease. First used in Australia in the late 1980s to monitor clinically identified disease, it has since been used in the diagnosis of relevant symptoms and as a screening test for asymptomatic men. It was not possible to identify from Medicare data the reasons why the tests were ordered. However, recent research found that 67 of 118 PSA tests (57%) were ordered for screening.15 Although we adjusted for other tests included under the same Medicare Benefits Schedule item from 1989 to 1993, we could not adjust for PAP tests, which are used to monitor the clinical progress of prostate cancer. However, in a continuous six-month period the ratio of PAP tests to PSA tests processed by a large, representative private pathology laboratory in NSW (covering city, suburban and regional centres) was less than 2% (Dr G Caldwell, Pathologist, Douglass Hanly Moir Pathology, personal communication). Data from a large public pathology laboratory in South Australia indicate that the proportion of PAP tests to the total PSA and PAP tests fell from 50% in 1991 to 6% in 1996 (Dr H A Morris, Manager, Endocrine Unit, Institute of Medical and Veterinary Science, personal communication). At their peak in 1995, the rates of PSA/PAP testing in Australian males ranged from 3270 per 100 000 in the Northern Territory to 8668 per 100 000 in Western Australia. These are probably underestimates because Medicare data do not include services provided free to public patients in public hospitals, to Veterans' Affairs patients and to men offered screening under the research activities of centres such as the Perth-based Urological Research Centre. In the one-year period April 1993 to March 1994, 39 626 PSA tests were done on 30 739 veterans.16 Data from the Department of Veterans' Affairs show about 50 000 tests were done each year in Australia between 1994 and 1996, which would have contributed a further 10% to the number of Medicare-reimbursed PSA tests. In South Australia 72 000 PSA tests that would not appear in Medicare statistics were undertaken between 1990 and 1996 by a public laboratory (Dr H A Morris, personal communication). These and the tests done on veterans would have accounted for an approximate under-enumeration of 33% annually in South Australia. Nationally, considering all these extra sources of PSA tests, we estimate that Medicare data underenumerate PSA tests by 14%. In a recent study of self-reported rates of prostate cancer screening in the Central Sydney Area Health Service, about one in five men aged 50 years or over reported being screened in the previous 12 months.17 This agrees quite closely with our results, which show that during the two years 1995 to 1996 about one in four Australian men aged 50 years or over had a PSA test, and in 1995 one in six (17%) had a test. More prostate cancers would result in more PSA tests used for monitoring. However, the overall effect of this on PSA test-ordering is thought to be small. More than 70% of males tested in 1995 and 1996 had only one test, suggesting that most tests were for screening rather than monitoring disease activity. A further possible indication that most tests were undertaken for screening rather than for monitoring or diagnosis is the increase in the ratio of tests to newly diagnosed prostate cancers in New South Wales. This ratio continued to increase in 1995, when the reported incidence of prostate cancer had begun to fall. Increasing recorded incidences of prostate cancer have been reported from the United States,18-22 France23 and elsewhere in Australia.1,2,4-6 Incidence figures began rising earlier in the United States than in Australia, and appeared to peak in 1992 and 1993.20 South Australian and Western Australian age-standardised recorded incidences peaked in 1994 and fell by 22% and 13%, respectively, between 1995 and 1996.2,4,5 The rate of PSA testing peaked in 1995 in both States and fell 10% and 16%, respectively, in 1996. These data and the high correlation between PSA tests and newly diagnosed prostate cancers in NSW support the hypothesis that the rising incidence figures for prostate cancer in the early 1990s were a direct result of screening.7 Based on these trends and correlations, it is likely that the recorded incidence for prostate cancer in most Australian States and Territories will continue to fall after 1995. Given that screening for prostate cancer has never been recommended in Australia, the rates of de facto screening in men aged over 50 years, and especially those aged between 60 and 69 years, are quite remarkable. These findings have important implications for public health policy and for patient and practitioner education aimed at reducing prostate cancer screening. Acknowledgements We would like to thank Mr Ross Saunders, Director of the Medicare Statistics Section of the Department of Health and Family Services, for supplying the data. References Coates M, Armstrong B. Cancer in New South Wales. Incidence and mortality 1994. Sydney: NSW Cancer Council, 1997. South Australian Cancer Registry. Epidemiology of cancer in South Australia. Incidence, mortality and survival 1977 to 1996, incidence and mortality 1996 analysed by type and geographical location. Twenty years of data. Adelaide: South Australian Health Commission, 1997. Australian Bureau of Statistics. Causes of death, Australia, 1995. Canberra: AGPS, 1996. (Catalogue No. 3303.0.) Threlfall T, Whitford M, Thompson J. Cancer incidence and mortality in Western Australia 1992 to 1994. A report of the Western Australian Cancer Registry. Perth: Health Department of Western Australia, 1996. Threlfall T, Thompson J. Cancer incidence and mortality in Western Australia, 1995. A report of the Western Australian Cancer Registry. Perth: Health Department of Western Australia, 1997. Shugg D, Dwyer T, Blizzard L. Cancer in Tasmania. Incidence and mortality 1994. Hobart: Menzies Centre for Population Health Research, 1997. McCredie M, Coates M, Churches T, Rogers J. Rising incidence of prostate cancer in Australia: a result of 'screening'? J Epidemiol Biostatistics 1996; 1: 99-105. Lange PH. Is screening for prostate cancer the current gold standard? -- "Yes". Eur J Cancer 1997; 33: 354-356. Kaye KW. Prostate cancer: enthusiasm for screening. Med J Aust 1995; 162: 540-541. Kramer BS, Gohagan JK, Prorok PC. Is screening for prostate cancer the current gold standard? -- "No". Eur J Cancer 1997; 33: 348-353. Hirst GHL, Ward JE, Del Mar CB. Screening for prostate cancer: the case against. Med J Aust 1996; 164: 285-288. Australian Health Technology Advisory Committee. Prostate cancer screening. Canberra: AGPS, 1996. Australian Bureau of Statistics. Estimated resident population by sex and age: States and Territories of Australia 1996. Canberra: Australian Bureau of Statistics, 1997. (Catalogue no. 3201.0.) SAS [computer program]. Version 6.12. Cary, North Carolina: SAS Institute, 1996. Ward JE, Gupta L, Taylor NJ. Do general practitioners use prostate-specific antigen as a screening test for early prostate cancer? Med J Aust 1998: 169; 29-31. Parkes AJ, Killer GT. Prostate-specific antigen -- is it already being used as a screening test? [letter]. Med J Aust 1994; 161: 722-723. Ward JE, Hughes A-M, Hirst GHL, Winchester L. Men's estimates of prostate cancer risk and self-reported rates of screening. Med J Aust 1997; 167: 250-253. Stephenson RA, Smart CR, Mineau GP, et al. The fall in incidence of prostate carcinoma. On the down side of a prostate specific antigen induced peak in incidence -- data from the Utah Cancer Registry. Cancer 1996; 77: 1342-1348. Jacobsen SJ, Katusic SK, Bergstralh EJ, et al. Incidence of prostate cancer diagnosis in the eras before and after serum prostate-specific antigen testing. JAMA 1995; 274: 1445-1449. Merrill RM, Potosky AL, Feuer EJ. Changing trends in U. S. prostate cancer incidence rates. J Natl Cancer Inst 1996; 88: 1683-1685. Gann PH. Interpreting recent trends in prostate cancer incidence and mortality. Epidemiology 1997; 8: 117-120. Lu-Yao GL, Greenberg R. Changes in prostate cancer incidence and treatment in USA. Lancet 1994; 343: 251-254. Menegoz F, Colonna M, Exbrayat C, et al. A recent increase in the incidence of prostatic carcinoma in a French population: role of ultrasonography and prostatic specific antigen. Eur J Cancer 1995; 31A: 55-58. (Received 28 Nov 1997, accepted 24 Apr 1998) Authors' details Cancer Control Information Centre, New South Wales Cancer Council, Sydney, NSW. David P Smith, BA, MPH, Research Coordinator, Cancer Epidemiology Research Unit; Bruce K Armstrong, DPhil, FRACP, Director. Reprints will not be available from the authors. Correspondence: Mr D P Smith, Cancer Epidemiology Research Unit, NSW Cancer Council, PO Box 572, Woolloomooloo, NSW 2011. E-mail: dsmithATnswcc.org.au Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

David P Smith · Bruce K Armstrong

Prostate cancer in Western Australia: trends in incidence and mortality from 1985 to 1996 Timothy J Threlfall, Dallas R English and Ian L Rouse MJA 1998; 169: 21-24 For editorial comment, see McCredie & Cox Abstract - Introduction - Methods - Results - Discussion - References - Addendum - Authors' details - - ©MJA1998 Abstract Objective: To measure trends in recorded incidence and mortality rates of prostate cancer in Western Australia from 1985 to 1996 and to relate these to prostate-specific antigen (PSA) testing for prostate cancer. Design: Descriptive study based on data from the Western Australian Cancer Registry, the Australian Bureau of Statistics and the Health Insurance Commission. Data: All newly diagnosed cases of prostate cancer and all deaths from prostate cancer in Western Australia from 1985 to 1996. Main outcome measures: Recorded incidences and mortality rates for prostate cancer. Results: After increasing steadily from 42 per 100 000 person-years in 1985 to 61 in 1992, the recorded incidence more than doubled to 134 per 100 000 person-years in 1994, then fell sharply to 87 in 1996. Among men aged 50 years or more, those aged 50-54 years had the largest annual increases: 14% (95% confidence interval [CI], 10%-19%) from 1985 to 1992 and 108% (95% CI, 84%-134%) from 1992 to 1994. They also had the smallest annual decline between 1994 and 1996 (8%; 95% CI, 1% increase to 16% decrease). The mortality rate showed no sudden increases or decreases. In men aged 60 years or older, the mortality rate increased annually by 2.9% (95% CI, 2%-4%) from 1985 to 1996. The number of Medicare reimbursements for PSA tests increased until May 1995, then fell. There was a significant correlation between the monthly number of PSA tests and new cases of prostate cancer (P < 0.01). Conclusions: Following a period of steady increase, the recorded incidence of prostate cancer increased dramatically in 1992 because of screening by PSA testing. From 1994, these incidence figures declined almost as sharply, partly because of reductions in testing. The mortality rate has not shown any systematic deviation from its long-term trend. Introduction In the early 1990s the recorded incidence of prostate cancer increased dramatically in Australia,1,2 several years after a similar increase in the United States.3-7 Testing for the disease among asymptomatic men by measuring plasma prostate-specific antigen (PSA) is believed to be responsible for the increases.1,3,4,7We report here on trends in incidence figures and in the mortality rate for prostate cancer in Western Australia from 1985 to 1996, and their relationship to PSA testing. Methods Data sources We obtained data on prostate cancer cases and deaths from the Western Australian Cancer Registry, and population estimates from the Australian Bureau of Statistics (ABS).8 We standardised rates to the World Standard Population and calculated the risk of men developing prostate cancer before the age of 75 years.9 Because mortality rates based on coding of cause of death by the ABS were not available for 1996, we used 1996 rates from the Registry, which began coding causes of death in 1990; from 1990 until 1995, the two mortality rates were almost identical. Data relating to the number of PSA tests reimbursed by Medicare in Western Australia were obtained from the Health Insurance Commission in July 1997. Socioeconomic status To investigate any effect of socioeconomic status (SES) on recorded incidence we used an index, derived from the 1991 census, in which each census collection district (about 50 households) is assigned a score.10 For Perth patients, addresses at the time of diagnosis were mapped to collection districts for the 1991 census using MapInfo.11 Geographical coordinate data were provided by the Western Australian Valuer General's office and the Department of Land Administration. The SES index was divided into quarters of its distribution. Because population data were available at the collection district level for census years only (ie, 1986 and 1991), we could not calculate SES-specific incidence. To determine whether any changes in numbers of cases by SES might be the result of different changes in population size in areas of different SES, we compared numbers of cases of prostate cancer and lung cancer. Trends in age-specific rates We used Poisson regression in EGRET12 to model age-specific recorded incidences and mortality rates. Analyses of incidence were restricted to men aged 50 years or older and analyses of mortality rate to men aged 60 years or older because there were few events in younger age groups. We analysed recorded incidence for each of the periods January 1985 to December 1992, January 1992 to December 1994 and January 1994 to December 1996. (Because the periods overlap, the results were not independent.) A single analysis of mortality rate was conducted. Likelihood ratio tests were used to obtain P values. We fitted age group as a categorical (ie, factored) variable and year of diagnosis as a continuous variable. The coefficient for year was exponentiated to give an annual percentage increase in the rate (eg, a coefficient of 0.35 when exponentiated is 1.42, equivalent to an annual increase of 42%). Age was added first, followed by the year of diagnosis, and then the interaction between the two. The interaction was fitted with age as a categorical variable and as a continuous variable, and the difference between these models was tested. Fitting the interaction with age as a categorical variable tests whether the secular trend was the same for all age groups; fitting it with age as a continuous variable tests whether there was a greater increase in younger men than in older men (or vice versa). In the analyses of incidence, P values for comparison of the two types of interaction were 0.17 for 1985-1992, 0.32 for 1992-1994 and 0.70 for 1994-1996. As there were no significant differences, the results reported for recorded incidence are from models in which the interaction involved age as a continuous variable. In all analyses, the final models provided good fits to the data -- the smallest P value for goodness-of-fit (for incidence in the period 1992-1994) was 0.09. Prostate-specific antigen testing Medicare began identifying PSA tests, together with prostatic acid phosphatase (PAP) tests, as a separate item during November 1993. Fewer than 1% of these tests would be PAP tests (Dr Glen Edwards, Chemical Pathologist, Western Diagnostic Pathology, personal communication). We plotted the number of tests reimbursed by Medicare each month from December 1993 to December 1996. To investigate the trends in the numbers of tests, we fitted a curve through the data. Results Incidence From 1985 until 1992, the age-adjusted recorded incidence increased steadily from 42 to 61 per 100 000 person-years (Figure 1). In the next two years it more than doubled to 134 per 100 000 person-years, but then fell almost as sharply to 87 in 1996. The risk of prostate cancer before age 75 years was one in 23 in 1985, one in six in 1994 and one in nine in 1996. Age: In men aged over 50 years, the recorded incidence of prostate cancer increased annually by 5% (95% confidence interval [CI], 3%-6%) between 1985 and 1992 (trend, P < 0.001). The largest relative increases in recorded incidence between 1985 and 1992 occurred in the youngest men (Table 1; interaction between year and age, P < 0.001). The largest relative increases between 1992 and 1994 were also seen in the younger age groups (interaction between year and age, P < 0.001), and from 1994 to 1996 the decline was greatest in the oldest men (interaction between year and age, P < 0.001). As a result of the different relative changes in different age groups, the differences in age-specific rates in 1996 were smaller than in earlier years. In 1985, the recorded incidence for men in the oldest age groups was close to 1000 times higher than for men aged 50-54 years, but by 1996 the relative difference was about 100-fold. We also examined the absolute changes in recorded incidence between 1992 and 1996 (Table 2). Between 1992 and 1994, the largest absolute increases were in men aged 65-79 years. Between 1994 and 1996, the largest absolute decreases were in men aged 70 years or older, so that between 1992 and 1996 the overall increases were greatest in men aged 60-69 years. The overall changes in men aged 55-59 years and 70-74 years were similar. The mean age at diagnosis was 73 years in 1985, 74 years from 1986 until 1990, 73 years in 1991 and 1992, 72 years in 1993, 70 years in 1994 and 69 years thereafter. Place of residence: We examined age-standardised recorded incidence for prostate cancer separately for the Perth metropolitan region and the rest of Western Australia. Before 1992, the two rates were similar in all years. During the sudden rise and fall, these incidences were, respectively, 1992: 65 per 100 000 person-years (Perth), 51 per 100 000 person-years (non-metropolitan areas); 1993: 141 per 100 000 person-years, 107 per 100 000 person-years; 1994: 141 per 100 000 person-years, 110 per 100 000 person-years; 1996: 87 per 100 000 person-years, 84 per 100 000 person-years. Socioeconomic status: We mapped 94% of lung cancer and prostate cancer cases in the Perth metropolitan area to a 1991 census collection district, with no apparent trend over time in the proportion mapped. Before 1993, the numbers of prostate cancer cases in the four SES groups were similar (Figure 2). However, the increase in cases in 1993 and 1994 was greatest in areas of highest SES, and the largest declines in numbers of cases from 1994 to 1996 were also in these areas. Over the same period, there was no consistent change in the distribution of lung cancer cases by SES (Figure 2). Mortality rate The age-adjusted mortality rate from 1985 to 1996 showed no sudden increases or decreases (Figure 1). In men aged 60 years or older, the estimated annual increase from 1985 to 1996 was 2.9% (95% CI, 2%-4%; trend, P < 0.001). Adding quadratic (P = 0.78) or cubic (P = 0.92) terms for year did not improve the fit of the Poisson model. Furthermore, models using year as a continuous or a categorical variable fitted equally well (P = 0.14), indicating that year-to-year variations in the trend of the age-adjusted rates could be a result of chance alone. The increase differed across age groups (interaction between age as a categorical variable and year of death, P = 0.03), but the trends by age were inconsistent (Table 1; interaction between age as a continuous variable and year of death, P = 0.96). Prostate-specific antigen testing On average, there were 5337 tests reimbursed each month in Western Australia. The numbers of tests initially increased before falling, although there was substantial monthly variation (Figure 3). A cubic curve fitted the data well (R2 = 0.46) and provided a better fit than a quadratic curve (P < 0.001) or a linear model (P < 0.001). The fitted maximum monthly number of tests occurred in May 1995. Spearman's rank correlation between the monthly number of PSA tests and new cases of prostate cancer was 0.48 (P < 0.01). Discussion After increasing steadily during the 1980s, the age-adjusted recorded incidence of prostate cancer more than doubled between 1992 and 1994. By 1996, it had fallen to a level about 40% higher than that in 1992. In contrast, the mortality rate increased by about 3% per year, with no sudden increases or decreases. The youngest age groups showed the largest relative increases in recorded incidence up to 1994, and the oldest age groups showed the greatest decrease after 1994, causing a substantial compression of the range of age-specific recorded incidence in Western Australia. When the rates rose steeply in 1992, the absolute increases were greatest in men aged 65-79 years. However, men aged 70 years or older had the greatest absolute falls from 1994, so that, between 1992 and 1996, the largest absolute increases were in men aged 60-69 years. The increase appeared first in Perth and the peak was higher in Perth. However, by 1996, Perth and the rest of Western Australia had similar recorded incidences of prostate cancer. Within Perth, the changes were greatest in areas of high SES. Most observers have attributed the increases in recorded incidence of prostate cancer during the 1980s to improved case detection, particularly following transurethral resection of the prostate for benign prostatic hypertrophy.1,13 The sudden rise in incidence figures in about 1993 was observed in all Australian States.1 In the United States, similar dramatic increases were observed first in 1989.3 These increases are almost certainly the result of the introduction of screening by PSA testing.1,3 In Western Australia, free PSA testing during Prostate Awareness Week would have contributed to the increase. Each October from 1993, about 1100 men attended Prostate Awareness Week in Perth for PSA tests (Mr M D'Antuono, Biostatistician, Urological Research Centre, University of Western Australia, personal communication). These tests do not appear in the Medicare figures, although the peaks in Medicare-funded PSA tests in November 1994 and November 1995 might be the result of publicity surrounding Prostate Awareness Week. However, substantially fewer tests were performed at the screening venues than were reimbursed by Medicare each month in Western Australia. Thus, Prostate Awareness Week is unlikely to have greatly increased the recorded incidence in Western Australia. Rapid declines in recorded incidence, such as we found in Western Australia since 1994, have also been reported in some US States.4,6,7,14 Part of the Western Australian decrease is probably the result of reduced screening activity. The most likely explanation for the decrease in Medicare reimbursements that started in 1995 is a reduction in PSA testing for screening. In fact, the reduction in screening tests is probably greater than Figure 3 suggests, because PSA testing is also used for surveillance of men with prostate cancer. Therefore, its overall use will decline less rapidly than its use for screening. Widespread publicity in the media about the controversy surrounding screening for prostate cancer may have contributed to this decline, and the greater declines seen in the oldest men may be because of concerns that screening is unlikely to benefit those with a short expectation of life.15 Recorded incidence is expected to decrease even if screening activity remains constant. After the introduction of screening, recorded incidence increases because the time of diagnosis is advanced and some cases may be diagnosed that would not have become symptomatic. When all prevalent cases are detected, incidence figures will fall until new cancers develop, whereupon they will rise again. If screening detects only those cancers that would eventually have been diagnosed anyway, the recorded incidence will stabilise at its pre-screening level. Otherwise, it will stabilise at a higher level.16 Before 1980, the mortality rate from prostate cancer in Australia was stable for some time.17 Since then it has increased, but more slowly than recorded incidence, indicating that short-term survival, at least, has improved over time. Increasing diagnosis of disease with low potential for metastasis is one explanation for the discrepancy. What changes in mortality rate can we expect? Gann has argued that if screening is effective and covers enough of the population, the mortality rate should eventually decrease.16 It is too early for any effect of screening on mortality rate to be seen, and by the end of 1996 there had been no new trend in the mortality rate in Western Australia. Because of the effect of lead time (the time by which screening advances diagnosis), changes may not occur for some years. We have witnessed extraordinary changes in the recorded incidence of prostate cancer in Western Australia, and we have strong evidence that these changes are the result of medical practice rather than intrinsic changes in the incidence. Surveillance of incidence and mortality rates may help answer the question of whether screening has benefit, although more rigorous scientific evaluations are also needed. References McCredie M. A rising incidence of prostate cancer in Australia: effect of "screening" or more disease? Cancer Forum 1995; 19: 7-12. McCaul KA, Luke CG, Roder DM. Trends in prostate cancer incidence and mortality rates in South Australia, 1977-1993. Med J Aust 1995; 162: 520-522. Lu-Yao GL, Greenberg ER. Changes in prostate cancer incidence and treatment in USA. Lancet 1994; 343: 251-254. Gilliland FD, Welsh DJ, Hoffman RM, Key CR. Rapid rise and subsequent decline in prostate cancer incidence rates for New Mexico, 1989-1993. Cancer Epidemiol Biomarkers Prev 1995; 4: 797-800. Merrill RM, Brawley OW. Prostate cancer incidence and mortality rates among white and black men. Epidemiology 1997; 8: 126-131. Polednak AP. Trends in prostate carcinoma incidence in Connecticut (1988-1994) by age and race. Cancer 1997; 79: 99-103. Newcomer LM, Stanford JL, Blumenstein BA, Brawer MK. Temporal trends in rates of prostate cancer: declining incidence of advanced stage disease, 1974 to 1994. J Urol 1997; 158: 1427-1430. Australian Bureau of Statistics. Estimated Resident Population by age and sex in statistical local areas, Western Australia. Canberra: AGPS, 1996. (Catalogue No. 3203.5.) Parkin DM, Muir CS, Whelan SL, et al, editors. Cancer incidence in five continents. Vol VI. IARC Scientific Publications No. 120. Lyon: International Agency for Research on Cancer, 1992. Australian Bureau of Statistics. Information Paper: 1991 Census socioeconomic indicators for areas. Canberra: AGPS, 1993. (Catalogue No. 2912.0.) MapInfo [computer program]. Version 3. New York: MapInfo Corporation, 1995. EGRET [computer program]. Version 1.02. Seattle: Statistics and Epidemiology Research Corporation, 1995. Potosky AL, Kessler L, Gridley G, et al. Rise in prostatic cancer incidence associated with increased use of transurethral resection. J Natl Cancer Inst 1990; 82: 1624-1628. Stephenson RA, Smart CR, Mineau GP, et al. The fall in incidence of prostate carcinoma. On the down side of a prostate specific antigen induced peak in incidence -- data from the Utah Cancer Registry. Cancer 1996; 77: 1342-1348. Chodak GW, Thisted RA, Gerber GS, et al. Results of conservative management of clinically localized prostate cancer. N Engl J Med 1994; 330: 242-248. Gann PH. Interpreting recent trends in prostate cancer incidence and mortality. Epidemiology 1997; 8: 117-120. Holman CD, James IR, Segal MR, Armstrong BK. Recent trends in mortality from prostate cancer in male populations of Australia and England and Wales. Br J Cancer 1981; 44: 340-348.(Received 30 Sep 1997, accepted 31 Mar 1998) Addendum Since this article was submitted in September 1997, data on the recorded incidence and mortality rate of prostate cancer in the first eight months of 1997 have become available. The age-adjusted recorded incidence of prostate cancer was 64 per 100000 person-years, while the mortality rate was 16 per 100000 person-years. Thus, the recorded incidence was almost the same as in 1992, before the rapid rise and fall. In 1997, men aged 50-69 years had higher recorded incidences of prostate cancer than in 1992, but older men had lower recorded incidences. Authors' details Health Department of Western Australia, East Perth, WA. Timothy J Threlfall, MB BS, MPH, Senior Medical Officer, Western Australian Cancer Registry; Ian L Rouse, PhD, General Manager, Health Information Centre. Department of Public Health, University of Western Australia, Nedlands, WA. Dallas R English, PhD, Senior Lecturer. Reprints: Dr D R English, Department of Public Health, University of Western Australia, Nedlands, WA 6907. E-mail: dallasATdph.uwa.edu.au Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Timothy J Threlfall · Dallas R English · Ian L Rouse

Self-reported prevalence of prostate-specific antigen testing in South Australia: a community study Carole B Pinnock, David P Weller and Villis R Marshall MJA 1998; 169: 25-28 For editorial comment, see McCredie & Cox Abstract - Introduction - Methods - Results - Discussion - Acknowledgements - References - Authors' details - - ©MJA1998 Abstract Objective: To determine the prevalence and other characteristics of self-reported blood testing (prostate-specific antigen [PSA]) for prostate cancer in the community. Design: Interview-based prevalence study. Participants and setting: 695 men aged 40 years and over in the Spring 1996 South Australian Health Omnibus survey of a probability sample of 3011 households, weighted to reflect the age and sex distribution of the South Australian population. Outcome measures: Number of men who had a PSA test in the preceding 12 months; number of first tests; the person initiating and performing the test; knowledge of the next step if test result abnormal; number of men visiting doctor for lower urinary tract symptoms in the preceding 12 months. Results: 20.3% of participants reported having a PSA test in the preceding 12 months; 62.1% were first tests. Prevalence of testing was highest in the age group 70-79 years (35.8%). Most tests were initiated by the general practitioner (41.2%) and by patients (35.7%). Of those tested, 45.3% had inadequate knowledge of the next step. Visiting a doctor for urinary symptoms was significantly associated with PSA testing (P < 0.001): 47.7% of men who visited a doctor for urinary symptoms had been tested compared with only 17.4% of those who did not visit the doctor for this problem. Only age and visiting a doctor for urinary symptoms were significant independent predictors of having a PSA test. Conclusions: Investigation of lower urinary tract symptoms contributed substantially to PSA testing, and those tested did not adequately understand the consequences. Our findings suggest a need for a better framework for PSA testing in general practice, including all important elements of decision-making, such as evidence and patient preference, as well as the means to ensure adequate patient counselling before testing. Introduction Screening for prostate cancer remains a topic of widespread debate. Recent systematic reviews have concluded that there is currently insufficient evidence to establish an overall benefit of prostate cancer screening, and major health agencies have issued conflicting recommendations.1-3 Randomised controlled trials examining this question have begun in the United States and Europe,4,5 but results will not be available for some years. Nevertheless, prostate-specific antigen (PSA) testing of asymptomatic men is thought to be common in Australia,6,7 and the recent doubling in recorded incidence of prostate cancer in this country8,9 has been attributed to PSA testing. Little is known about the circumstances of such testing -- whether it occurs in general practice or other specialties, whether men are truly asymptomatic, whether the test is initiated by the patient or the doctor, and how much information about the test is provided to the patient. Most authors agree that men seeking a test should be informed about the risks as well as the benefits of taking the test,10,11 and that individual preferences should be taken into account.12-15 A community survey of self-reported participation in PSA testing confirmed high rates in the community (25% of men 40 years and over with no history of prostate cancer) and an even higher rate of intention to test (53.9%).16 The strongest predictor of past testing was a visit to a doctor for urinary tract symptoms, and the strongest predictor of intention to test was perceived vulnerability to prostate cancer.16 This study was undertaken in 1996 to expand these findings by establishing the prevalence of self-reported prostate cancer testing (PSA testing) over the preceding 12 months, the incidence of PSA testing (first tests), who initiated the test, who performed it, the association with investigation for urinary symptoms, and whether participants had understood the immediate consequences of taking the test. Methods Survey Questions were included in the Spring 1996 South Australian Health Omnibus survey, a multiple-user household interview survey undertaken on behalf of a number of healthcare organisations in South Australia. The sampling method provides a probability sample of the South Australian population.17,18Participants were asked whether they had visited the doctor for troublesome urinary symptoms in the past 12 months (as in a previous survey17), ever been diagnosed with prostate cancer or had a blood test for prostate cancer (PSA test) in the previous 12 months. Those who had been tested were asked who had initiated the test, who performed it and what they understood to be the next step if the test were abnormal. Question alternatives were derived from a previous qualitative study (who initiated test)19 and expert clinical opinion (who performed it, next step). Questions were tested for comprehensibility and acceptability in 50 pilot interviews before the survey. Analysis Data were weighted by household size, age, sex and geographical region to benchmarks derived from the estimated resident population at 30 June 1995 (Australian Bureau of Statistics). Because of the clustered nature of the sample, confidence limits were calculated after allowing for a design effect of 1.1, calculated using the method of Kish,20 which inflates the standard error. We analysed data for men aged 40 years or older who had not had a diagnosis of prostate cancer, using SPSS for Windows.21 Statistical significances were determined by Pearson c2 tests or Fisher's exact test, and logistic regression by the forced entry method (the contribution is evaluated after removal of effects of all other variables). The contribution of demographic and urinary symptom variables was examined in a logistic regression model to identify independent predictors of having a PSA test in the preceding 12 months. Results Sample In unweighted numbers, from the sampling frame of 4081 households, 3011 interviews were conducted, giving a response rate of 73.8%. The reasons for not participating were refusal (548), no contact could be established (301), selected respondent away for duration of study (108), illness/mental incapacity (65) and respondent unable to speak English (48). Of the 3011 people interviewed, 695 were men 40 years or older and 642 of these had not had a diagnosis of prostate cancer. The average age of these 642 men was 58.3 years (SE, 0.50 years; range, 40-91 years). After weighting, 6.0% (95% confidence interval [CI], 4.45%-7.86%) of men aged 40 years or more reported being diagnosed with prostate cancer. The weighted sample size of men aged 40 years and over with no reported diagnosis of prostate cancer was 716. PSA testing and demographic factors Overall, 20.3% of men older than 40 years reported having a blood test for prostate cancer (PSA test) in the preceding 12 months (Table 1). This varied with age (chi-squared = 48.1; df = 4; P < 0.001), with the highest proportion (35.8%) being in the age group 70-79 years. Nearly two-thirds of tests (62.1%) were first tests, and this proportion was high across all age groups. Men were slightly more likely to be tested if they lived in metropolitan (20.8%; 95% CI, 17.5%-24.1%) than in rural (19.0%; 95% CI, 15.8%-22.1%) areas, but the difference was not significant. Educational attainment was not associated with testing. Lifetime occupation also showed no clear trends (eg, drivers and plant operators had similar rates to managers and administrators), nor did marital status and country of birth. Lower urinary tract symptoms Of 715 men aged 40 years and over who had not had a diagnosis of prostate cancer, 65 (9.1%) had visited a doctor for troublesome lower urinary tract symptoms (LUTS) in the preceding 12 months (46 visited their general practitioner). Of these 65 men, 31 (47.7%) had had a PSA test, compared with only 113/650 (17.4%) of those who did not visit the doctor for such a problem (P < 0.001, Fisher's exact test). A first visit to a doctor for LUTS was significantly associated with a first PSA test (P = 0.018, Fisher's exact test): 15/17 (88.2%) men who had a first visit for LUTS in the previous 12 months also had a first test in that time, compared with only 6/14 (42.9%) men for whom it was not the first visit. Who initiates and performs the test Most testing (70.6%) was performed in general practice, and most tests were initiated by the general practitioner (Table 2). However, patients initiated 35.7% of tests. Tests performed by "other doctor" may reflect those done by pathology services, but could also have been included in other types of medical assessments. Doctors initiated 25 (80.6%) of the tests on the 31 men who visited for LUTS and were tested, but initiated only 51 (45.1%) of the tests on the 113 who were tested but had not visited a doctor for LUTS (chi-squared = 12.3; df = 1; P < 0.001). Knowledge of the "next step" There was wide variability in understanding of the next step if the test were abnormal. The most frequent response was "do not know" (34.0%). Other responses were "operation on the prostate" (10.7%), "no further action" (0.6%), "referral to a specialist" (27.2%), "repeat the test" (6.3%), "biopsy of the prostate" (4.8%) and "other" (16.7%). The first three (do not know, operation on the prostate, no further action), totalling 45.3%, may be considered to reflect poor understanding. Independent predictors of testing The logistic regression model (chi-squared = 89.8; df = 22; P < 0.001) included age, rural/metropolitan residence, country of birth, educational attainment, marital status, lifetime occupation, and doctor visit for LUTS in the past 12 months. Of these, only age and visit to a doctor for LUTS were significant independent predictors of having had a PSA test in the past 12 months (Table 3). Discussion We found a high level of self-reported PSA testing among men in South Australia. Testing was associated with lower urinary tract symptoms and was initiated by the patient or his GP. Nearly half the respondents had an inadequate knowledge of the appropriate next step if the test result were abnormal. Our study was a community-based survey of self-reported testing. Such studies suffer from limitations in that individual recall of past events and comprehension of the research questions may vary. Nevertheless, representative community sampling makes it possible to derive estimates of incidence and prevalence, a benefit over general practice-based studies. The level of self-reported rates of PSA testing observed in this study is higher than that reported in New South Wales across all age groups.7 This may result from a real difference between South Australia and New South Wales or from differences in survey method. The sampling method differed between the two studies (probability sample weighted to reflect age and sex structure of South Australian population versus random telephone number selection from Sydney metropolitan white pages). Older men were under-represented in the New South Wales study compared with 1991 Census data. The interview method (face to face in South Australia versus telephone in New South Wales) may also have contributed to the differences. In our study, the number of men tested increased with age and peaked in the age group 70-79 years, with nearly half the tests in this age group being first tests. The choice to begin PSA testing at this age is of concern, as those least likely to benefit are men who can anticipate less than a decade of life.1 We found no association between PSA testing and socioeconomic factors such as education and occupation, although in the United States participation in prostate cancer screening is reported to be sensitive to socioeconomic factors.22,23 However, our result is consistent with other Australian data.7,16 It is also consistent with the view that testing is initiated more by doctors than patients in this community. There was only a small difference between rural and metropolitan testing rates, which suggests that access to services does not influence the number of men seeking or being offered testing. The role of LUTS in prompting testing for prostate cancer has been reported previously,7 and is important because of the high prevalence of such symptoms in the community. In a recent South Australian survey, 26.4% of men over 18 years reported experiencing troublesome urinary symptoms in the past 12 months, and 10.2% had visited a doctor for this reason. A similar number (8.6%) were substantially dissatisfied with their urinary function.17 The relative proportions of men and their doctor initiating prostate cancer testing have not been reported previously. We found that, in the absence of urinary symptoms, this is roughly equal. However, among those men who had visited a doctor for LUTS, 80% of tests were doctor-initiated. This strong association between doctor as test initiator and LUTS suggests that, while testing may be for case-finding or screening purposes in asymptomatic men, its use may be investigational for those with LUTS. We cannot know, from these and other data,7 whether other indicators for investigational PSA testing (such as abnormal or suspicious digital rectal examination, family history of prostate cancer, or complicated LUTS) were present, and therefore whether testing was appropriate in these cases. The current clinical guidelines for uncomplicated LUTS do not recommend testing for prostate cancer.24 The American College of Physicians maintains that, as no association between LUTS and prostate cancer has been demonstrated, testing in men both with and without LUTS consistent with benign prostatic enlargement constitutes screening.10 Current guidelines focus on when not to use the PSA test, but not when it is appropriate.24 There is no framework for doctors and patients which includes all the important elements of decision-making in this area, including evidence, patient preference and medicolegal issues. PSA testing in general practice is driven in part by concern of patients and in part for investigational purposes. In addition, there is anecdotal evidence that general practitioners are concerned that if a PSA test is not offered, and prostate cancer is later diagnosed, they may be seen as negligent. Clinical guidelines or other measures promoting the appropriate use of the PSA test in general practice need to give consideration to all of these factors. Undoubtedly, providing information about testing for prostate cancer is more complex than for breast cancer or cervical cancer screening. The finding that a large proportion of men tested did not understand the immediate consequences of testing is thus not surprising, but of concern. We cannot tell from these data whether information was not given, not understood, or not recalled. Nevertheless, it is reasonable to assume that if this very basic information is not understood effectively, then more complex information (such as the likelihood of a false positive result, side effects of a biopsy, effectiveness of treatment for early-stage prostate cancer, and the risks of impotence and incontinence resulting from radical surgery for localised cancer) would also not have been understood. Yet this has been suggested as basic information needed by a patient to understand the implications of a PSA test.11,14,15 We therefore see a need for closer examination of the exchange and uptake of information in consultations that result in a PSA test, and the provision of resources for GPs which aid effective counselling. Such resources may need to include longer consultations. Acknowledgements The study was funded through a collaboration of Repatriation General Hospital, Daw Park, the Anti-Cancer Foundation of Australia, and the Department of Evidence Based Care and General Practice, Flinders University of South Australia, under the auspices of the Collaborative Centre for Prostate Health. References Australian Health Technology Advisory Committee. Prostate cancer screening. Canberra: AGPS, 1996. National Health Service. Screening for prostate cancer: effectiveness matters. York, UK: NHS Centre for Reviews and Dissemination, 1997. Mettlin C, Jones G, Avarette H, et al. Defining and updating the American Cancer Society guidelines for cancer-related checkup: prostate and endometrial cancers. CA Cancer J Clin 1993; 43: 42-46. Denis L, Middelheim A. To screen or not to screen? Prostate 1992; Suppl 4: 63-70. Gohagan J, Prorok P, Kramer B, et al. The prostate, lung, colorectal and ovarian screening trial of the National Cancer Institute. Cancer 1995; 75: 1869-1873. Parkes A, Killer G. Prostate-specific antigen -- is it already being used as a screening test? [letter]. Med J Aust 1994; 161: 722-733. Ward JE, Hughes A-M, Hirst GHL, Winchester L. Men's estimates of prostate cancer risk and self-reported rates of screening. Med J Aust 1997; 167: 250-253. McCredie M. A rising incidence of prostate cancer in Australia: effect of "screening" or more disease? Cancer Forum 1995; 19: 7-12. McCaul K, Luke C, Roder D. Trends in prostate cancer incidence and mortality rates in South Australia. Med J Aust 1995; 162: 520-522. American College of Physicians. Screening for prostate cancer. Clinical Guideline: Part III. Ann Intern Med 1997; 126: 480-484. Hirst GH, Ward JE, Del Mar C. Screening for prostate cancer: the case against. Med J Aust 1996; 164: 285-288. Hahn DL, Roberts RG. PSA screening for asymptomatic prostate cancer: truth in advertising. J Fam Pract 1993; 37: 432-436. Woolf SH. Should we screen for prostate cancer? Men over 50 have a right to decide for themselves [editorial]. BMJ 1997; 314: 989-990. Flood AB, Wennberg JE, Nease RF Jr, et al. The importance of patient preference in the decision to screen for prostate cancer. Prostate Patient Outcomes Research Team. J Gen Intern Med 1996; 11: 2342-2349. Wolf AM, Nasser JF, Wolf AM, Schorling JB. The impact of informed consent on patient interest in prostate-specific antigen screening. Arch Intern Med 1996; 156: 1333-1336. Weller D, Pinnock C, Silagy C, et al. Prostate cancer testing in South Australian men: influence of sociodemographic factors, health beliefs and lower urinary tract symptoms. Aust N Z J Public Health 1998; 22: 400-402. Pinnock C, Marshall V. Troublesome lower urinary tract symptoms in the community: a prevalence study. Med J Aust 1997; 167: 72-75. Wilson D, Wakefield M, Taylor A. The South Australian Health Omnibus Survey. Health Prom J Aust 1992; 2: 47-49. Pinnock C, O'Brien B, Marshall V. Older men's concerns about their urological health: a qualitative study. Aust N Z J Public Health 1998; 22: 368-373. Kish L. Estimates of unit variance: design effect. In: Survey sampling. New York: John Wiley and Sons, 1965; 257-263. SPSS for Windows [computer program]. Version 7.5. Chicago, Ill: SPSS Inc, 1996. Robinson SB, Ashley M, Haynes MA. Attitudes of African Americans regarding screening for prostate cancer. J Natl Med Assoc 1996; 88: 241-246. Diefenbach PN, Ganz PA, Pawlow AJ, Guthrie D. Screening by the prostate-specific antigen test: what do the patients know? J Cancer Educ 1996; 11: 39-44. National Health and Medical Research Council. Clinical practice guidelines. The management of uncomplicated lower urinary tract symptoms in men. Canberra: Commonwealth of Australia, 1997. (Received 7 Nov 1997, accepted 7 May 1998) Authors' details Division of Surgery, Repatriation General Hospital, Daw Park, SA. Carole B Pinnock, PhD, Principal Research Scientist. Flinders University of South Australia, SA. David P Weller, FRACGP, FAFPHM, Senior Lecturer, Department of Evidence Based Care and General Practice; Villis R Marshall, MD, FRACS, Professor of Surgery, Department of Surgery, Flinders Medical Centre, and Head, Division of Surgery, Repatriation General Hospital, Daw Park, SA. Reprints will not be available from the authors. Correspondence: Dr C R Pinnock, Division of Surgery, Repatriation General Hospital, Daws Rd, Daw Park, SA 5041. E-mail: spinncbATrgh.edu.au - Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Carole B Pinnock · David P Weller · Villis R Marshall

Abstract Objective: To assess the feasibility of offering the choice of prescribing injectable heroin (diamorphine) or injectable methadone to opiate-dependent injecting drug users and to assess whether there are health and social gains associated with prescribing injectable opiates. Design: A protocol-driven prospective observational study. Type of injectable opiate received was based on self-selection. Setting: A large west London drug clinic. Patients: Fifty-eight patients admitted to the clinic between 1 June 1995 and 31 December 1996, who were long term opiate-dependent injecting drug users, who had previously tried and failed oral methadone and who were apparently unable or unwilling to give up injecting. Main outcome measures: Retention in treatment, illicit drug use, HIV risk behaviour, criminal activity, social functioning, health and psychological status as measured by self-report, urinalysis and doctors' ratings. Results: Thirty-seven patients (64%) chose heroin and 21 (36%) chose injectable methadone. Fifty (86%) were retained in treatment after three months, 40 (69%) after six months and 33 (57 %) after 12 months. Among those in treatment at three months, there were significant reductions in illicit drug use, illicit drug-injecting risk behaviour, and criminal activity, and significant improvements in social functioning, health status and psychological adjustment. Generally, these gains were sustained between three, six and 12 months. Doctors' ratings of health and urinalysis results further supported these findings. Conclusions: Injectable heroin is not always the drug of choice. This intervention retained most patients in treatment with substantial benefits to both patients and the community. Prescribing injectable opiates to long term injecting drug users is a feasible treatment option. Introduction Opiate dependency is a major public health and social problem. Oral methadone treatment is the most common form of treatment for opiate dependency, and its effectiveness has been well demonstrated.1 However, Britain is one of the few countries where doctors can legally prescribe pharmaceutical heroin (diamorphine) and injectable methadone, and injectable opiates have been prescribed for opiate dependency since the 1920s in the case of heroin, and since the 1970s in the case of methadone.2Despite the legality of this practice, numbers of patients receiving such treatment remain small. Methadone accounts for 96% of all opiate prescriptions for treating drug dependency in the United Kingdom;3 injectable heroin accounts for only 2% of the total number of prescriptions for opiates;4 and methadone ampoules make up 9% of all methadone prescriptions.3 While injectable methadone is prescribed by doctors attached to specialist drug services, general practitioners and private doctors, a special licence from the Home Office is required to prescribe injectable heroin, and most doctors with such licences work in specialist drug services.5 Injectable opiate prescribing has not been guided by clinical protocols, but has been characterised by a high level of flexibility in decisions about eligible patients and dosage. The prescribing of injectable opiates has been the source of international controversy and debate. A large research trial has been undertaken in Switzerland6 and, in Australia, a heroin trial was designed to determine the impact of offering the choice of an injectable opiate prescription.7 However, the Australian Federal Government has decided that this trial will not proceed. It has been argued that injectable opiate prescribing may attract resistant opiate-dependent users into, and retain them in, treatment, with potential health and social benefits, including a reduction in crime,8 but there is a lack of scientific evidence on which to base these claims. The Swiss trial found that heroin prescribing retained drug users in treatment, with reductions in crime and improvements in health status.6 However, results of the most influential research carried out in the UK -- a randomised controlled trial comparing maintenance with oral methadone with heroin -- were inconclusive.9 In that study, the heroin group were better retained in treatment, but they continued to inject regularly and use illicit opiates in small amounts, which could lead to increasing clinic caseloads. On the other hand, the oral methadone group were more likely to either drop out of treatment or become abstinent. There were higher arrest rates and higher levels of drug involvement and criminal activity among those who did not become abstinent. Other studies have also found conflicting results.10-12 In this study we aimed to assess the feasibility of offering opiate-dependent injecting drug users the choice of treatment with injectable heroin (diamorphine) or injectable methadone, and to examine possible health and social gains associated with prescribing injectable opiates. Methods This pilot study was carried out at a west London drug treatment clinic. The clinic's protocol aimed to reduce illicit drug use and HIV risk behaviours; to improve physical, psychological and social functioning; and to move patients on to oral methadone treatment en route to abstinence. Eligible patients met the following criteria: aged over 21 years; dependent on opiates; unable or unwilling to give up injecting (defined by injecting for a minimum of three years with consistent injecting over the previous nine months and evidence of injecting over the past three months); previously failing oral methadone treatment (defined by regular continued use of illicit opiates while receiving oral methadone, continuing to inject regularly and receiving doses of oral methadone in excess of 80 mg/day); and problems relating to drug use in areas of health, social functioning or crime. Patients chose treatment with either injectable diamorphine (heroin) or injectable methadone. After a one-month induction period, they were required to stay with their drug of choice. A ceiling dose of 200 mg/day of either drug was set, and the treatment dose was achieved through tolerance testing over one week and stabilisation over the first month; after this time doses could only be reduced. Drugs were dispensed at the clinic daily (Monday to Friday with weekend doses taken home) for the first few weeks and then less frequently (a few times a week or weekly). After their initial tolerance test, patients were not permitted to inject on-site. To reduce the risk of injectable opiates being diverted to others, patients had to return used ampoules (batch numbers were checked) before receiving further ampoules. Criteria for disciplinary discharge from the study were evidence of "double-scripting" (receiving an additional prescription for opiates for drug dependency outside the clinic), dealing in the injectable opiates prescribed in this study, violence in the clinic, continual and persistent evidence of illicit drug use, consistently failing to return used ampoules, and injecting outside the clinic in the hospital grounds. The Australian Opiate Treatment Index (OTI)13 -- a multidimensional scale measuring illicit drug use, HIV risk behaviour, criminal activity, social functioning, physical and psychological health -- was administered to patients at entry and at three-monthly intervals. This instrument, which has been validated in both Australia13 and the UK,14 has a high correlation with doctors' and nurses' reports and with urine results at opiate treatment settings.14 Clinic doctors used standardised instruments to rate patients' health and psychological well-being at entry and at three-monthly intervals. These instruments included a physical rating scale for recording doctors' opinions of patients' physical health, including cardiovascular, respiratory, gastrointestinal, central nervous system and injecting-related health (Tallack F, Metrebian N, The Centre for Research on Drugs and Health Behaviour, London, 1996), and the Brief Psychiatric Rating Scale15 for recording doctors' judgements of patients' psychopathology. In addition, illicit drug use was measured through random urine tests throughout the treatment. Statistical analysis Tests of significance included t tests for related samples, and McNemar's chi-squared tests for dichotomous and ordinal data. Results from parametric and non-parametric tests were compared where normal approximations to the underlying distributions were suspect. We considered a P value of 0.05 to be significant. Results Fifty-eight subjects were recruited to the study. Forty-two (72%) were male, 50 were white (86%), and their median age was 38 years (range, 24-49 years). Their median duration of injecting heroin was 19.5 years (range, 4-30 years), and they had been in opiate treatment a median of four times previously (range, 2-17 times). Thirty-seven (64%) chose to receive diamorphine, 21 (36%) chose methadone. A higher mean dose of diamorphine was prescribed over three months (diamorphine, 181.43 mg/day [SD, 22.2; range, 120-200] v. methadone, 148.18 mg/day [SD, 45.1; range, 100-200) and over 12 months (185.24 mg/day [SD, 15.7; range, 150-200 v. 161.25 mg/day [SD, 46.4; range, 90-200]). Fifteen of the patients prescribed heroin (71%) reported experiencing night-time withdrawal symptoms as a result of heroin's shorter duration of action and were thus given an additional prescription for oral methadone. The mean dose of additional oral methadone was 24 mg/day (SD, 5.2; range, 20-30). A number of patients were found loitering in the vicinity of the clinic after their prescriptions were dispensed, and one was found injecting the prescription while still on hospital premises. No other major postdispensing problems were reported in the surrounding community. Fifty patients (86%) were still in treatment after three months, 40 (69%) after six months and 33 (57%) after 12 months. Reasons for discontinuing treatment are given in Box 1. Patients still in treatment at three months had significantly reduced their consumption of illicit drugs (with the exception of amphetamines, which did reduce, but not significantly), and made positive changes in all health and social domains. Self-reported criminal behaviour was initially low and further significantly reduced. There were significant improvements in social functioning (employment, housing, relationships and involvement in drug-using networks), health status and psychological adjustment. HIV risk behaviour (injecting and sexual risk behaviour -- the OTI considers any injecting as risk behaviour), and illicit drug-injecting risk behaviour (frequency of injecting and sharing of illicit drugs) reduced significantly. Although not significant, levels of sexual risk behaviour reduced slightly. There were no significant differences in measures of health and social behaviour between three and six months (data not shown), except for illicit drug injecting, which increased, although at six months it was still significantly less than at entry (1.13 [SD, 2.06] v. 5.66 [SD, 4.11]; P < 0.0001). Between six and 12 months, there were significant reductions in HIV risk behaviour, illicit drug-injecting risk behaviour and sexual risk behaviour, but no other significant changes. Results of urinalysis suggest that there were (non-significant) reductions in tranquilliser, amphetamine, and cocaine use between entry and three months, and between three and six months, which were sustained between three and 12 months. Few patients receiving injectable methadone were using illicit opiates. Measures of health and psychological status as reported by clinic doctors suggest health and psychological well-being had significantly improved at three months and these improvements were generally sustained. These findings were similar to measures of self-report. All measures reported at six and 12 months had significantly improved or reduced compared with measures obtained for the same sample at entry, with the exception of HIV risk, sexual risk and doctors' rating of psychological well-being, which had not significantly reduced or improved at six months but did reach significance again at 12 months. There were no differences found in drug use, health or social status reported at entry between those leaving treatment before 12 months and those remaining. Discussion These pilot study findings showed that opiate-dependent injecting drug users with long injecting careers (most started between 1970 and 1982) and for whom opiate treatment had failed multiple times previously were attracted into and retained by therapy with injectable opiates. Compared with drug users in a national UK study of oral methadone maintenance programs,16 our patients were older (38 v. 29 years) and had been injecting for longer (19.5 v. 9 years). While some clinicians17 and drug users' forums perceive a high demand for heroin treatment, our findings suggest that heroin is not always the drug chosen by users, with over one-third choosing injectable methadone. There has been much discussion about the correct dose of heroin.18 Over 12 months doses remained within the limit of 200 mg/day. In the Swiss study patients were stabilised on much higher doses of 500-600 mg/day.19 While interpretation of our findings is limited by the absence of a control group receiving oral methadone therapy and by reliance on self-report data, this is one of few studies to systematically examine the use of injectable opiates in treating opiate dependence, and the results will be used to inform a multicentre randomised controlled trial. In our study, at six months, 31% of patients had left treatment, and 40% of the 25 who left over the full 12 months were discharged because they violated the study protocol. Only two (16%) requested a move to oral methadone therapy and one became abstinent. There was one fatality (from hepatic failure) but no overdoses. By comparison, in the Swiss study of 366 patients receiving injectable heroin,20 18% had left treatment at six months and, of these, 48% switched to another treatment modality (mostly methadone maintenance) and 25% were excluded for threat of violence or other inappropriate behaviour. Four died and there were no overdoses. The retention rate in our study was higher than that reported by a national study of oral methadone maintenance programs at one month15 (86% v. 78%), and similar at six months (69% v. 67%).21 This suggests that the long-term opiate-dependent drug users in our study were well retained in treatment. Other studies have found similar high retention levels.9-11 There are concerns that prescribing injectable opiates might encourage drug users to continue injecting and discourage them from accepting oral methadone treatment or becoming abstinent.9 It is impossible to know whether our patients would have been more likely to move towards abstinence had they received oral methadone. However, these patients were long-term opiate-dependent drug users who had had a median of four previous opiate treatments and had tried and failed at least two oral methadone treatments without achieving abstinence. Our patients made significant health and social gains and experienced significantly reduced drug-related harm in the first three months. These gains were generally sustained between three and six, and six and 12 months. At entry, there were no significant differences in health and social status between patients later discharged from treatment and those who remained in the study. There has been some concern that patients' health might deteriorate while receiving prescribed injectable drugs.10 Previous research has shown little improvement in health and social wellbeing.9-11 The study by Battersby et al10 of drug users at high risk from serious physical illness, including HIV, found one individual developed a life-threatening illness (cervical spine osteomyelitis resulting from intravenous drug use) but survived, several injected into their femoral vein (a highly dangerous practice which carries a high risk of causing deep venous thromboses) and the health of 20% deteriorated. However, the authors concluded that "it was not possible to determine the nature of risk taking that would have occurred ... in the absence of the present treatment intervention". By contrast, we found that, although some patients were also injecting into their femoral vein, two moved to oral methadone because of poor health related to injecting and one died, for those remaining in treatment significant improvements were made in health, psychological adjustment and social functioning. These improvements were seen between entry and three months, and sustained between three, six and 12 months. There was also a reduction in illicit drug-injecting risk behaviour. Doctors' ratings of patients' health and psychological well-being verified these improvements. The problems of vein care associated with injectable opiates need to be weighed up against benefits in client attraction and retention, and in the provision of clean pharmaceutical drugs and injecting equipment, and advice on safer injecting practices and healthcare. Our findings do not support the suggestion that prescribing injectable opiates eliminates illicit drug use and criminal activity,22-24 as both declined significantly, but neither was eliminated. Similar results have been obtained by other studies.9-11 Results of urinalysis corroborated self-reported non-opiate drug use. However, it was not possible to corroborate self-reported opiate use as we could not differentiate between illicit and prescribed heroin. Diversion of prescribed opiates to others is of particular concern when there is no observed on-site injecting. While the clinic attempted to reduce the risk of such diversion, ways of corroborating self-reported compliance with prescription and illicit opiate use are needed. Prescribing injectable opiates is one of many options in a range of treatments for opiate-dependent drug users. In showing that it attracts and retains long term resistant opiate-dependent drug users in treatment and that it is associated with significant and sustained reductions in drug use and improvements in health and social status, our findings endorse the view that it is a feasible option. Further research is needed to examine the potential benefits of this treatment at both an individual and community level. Randomised controlled trials comparing alternative treatments and their relative cost effectiveness are required to fully assess this treatment option. Acknowledgements The Centre for Research on Drugs and Health Behaviour is core funded by the North Thames Office of the NHS Executives Research and Development Directorate. Riverside Mental Health Trust Substance Misuse Service, Ealing, Hammersmith and Hounslow and Kensington, Chelsea and Westminster Health Authorities funded this study. Thanks to all the clients who took part in the research, and to the clinic staff: Colin Small, Mark Lee, Victor Mtutu, Sue Byers, Movena Lucus, Gail Jones, Nicky Meux and Sam Nyeck. References Farrell M, Ward J, Mattick R, et al. Methadone maintenance treatment in opiate dependence: a review. BMJ 1994; 309: 997-1001. Strang J, Gossop M, editors. Heroin addiction and drug policy: the British system. Oxford: Oxford Medical Publications, 1994. Strang J, Sheridan J, Barber N. Prescribing injectable and oral methadone to opiate addicts: results from the 1995 national postal survey of community pharmacies in England and Wales. BMJ 1996; 313: 270-272. Strang J, Sheridan J. Heroin prescribing in the "British System" of the mid 1990s: data from the 1995 national survey of community pharmacies in England and Wales. Drug Alcohol Rev 1997; 16: 7-16. Sell L, Farrell M, Robson P. Prescription of diamorphine, dipipanane and cocaine in England and Wales. Drug Alcohol Rev 1997; 16: 221-226. Uchtenhagen A. Summary of the synthesis report. In: Uchtenhagen A, Gutzwiller F, Dobler-Mikola A, editors. Programme for a medical prescription of narcotics: final report of the research representatives. Zurich: Institute for Social and Preventive Medicine, University of Zurich, 1997. Bammer G. Should the controlled provision of heroin be a treatment option? Australian feasibility considerations. Addiction 1993; 83: 467-475. Metrebian N, Shanahan W, Stimson GV. Heroin prescribing in the UK: an overview. Eur Addict Res 1996; 2: 194-200. Hartnoll RL, Mitcheson MC, Battersby A, et al. Evaluation of heroin maintenance in controlled trial. Arch Gen Psych 1980; 37: 877-883. Battersby M, Farrell M, Gossop M, et al. "Horse trading": prescribing injectable opiates to opiate addicts. A descriptive study. Drug Alcohol Rev 1992; 11: 35-42. McCusker C, Davis M. Prescribing drug of choice to illicit heroin users: the experience of a UK Community Drug Team. J Subst Abuse Treat 1996; 13; 6: 521-531. Stimson GV, Oppenheimer E. Heroin addiction treatment and control in Britain. London: Tavistock Publications, 1982; 229-252. Darke S, Hall W, Wodak A, et al. Development and validation of a multi-dimensional instrument for assessing outcome of treatment among opioid users: the Opiate Treatment Index. Br J Addict 1992; 87: 733-742. Adelekan M, Green A, DasGupta N, et al. Reliability and validity of the Opiate Treatment Index among a sample of opioid users in the United Kingdom. Drug Alcohol Rev 1996; 15: 261-270. Overall JE, Gorham DR. The brief psychiatric rating scale. Psych Rep 1962; 10: 799-812. The Task Force to Review Services for Drug Misusers. Report of an independent review of drug treatment services in England. London: Department of Health, 1996; 61-64. Marks J. Who killed the British System? Druglink 1995; 10: 21. Strang J, Farrell M. Treatment of heroin users [letter]. BMJ 1994; 308: 718. Farrell M, Hall W. The Swiss heroin trials: testing alternative approaches [letter]. BMJ 1998; 316: 639. Uchtenhagen A, Dobler-Mikola A, Gutzwiller F. Medical prescription of narcotics. Eur Addict Res 1996; 2: 201-207. Gossop M, Marsden J, Stewart D, et al. The National Treatment Outcome Research Study in the United Kingdom: six month follow-up outcomes. Psych Addict Behav 1997; 11: 324-337. Beckett D. Prescription of controlled drugs to addicts. BMJ 1983; 287: 127. Connell PH. Drug dependence in Great Britain: a challenge to the practice of medicine. In: Steinberg, editor. Scientific basis of drug dependence. London: Churchill Livingstone, 1969. Marks J. Opium the religion of the people. Lancet 1985; i: 1439-1440. (Received 9 Sep 1997, accepted 24 Apr 1998) Authors' details The Centre for Research on Drugs and Health Behaviour, Department of Social Science and Medicine, Imperial College School of Medicine, London, United Kingdom. Nicky Metrebian, BA(Hons), Research Fellow; Gerry V Stimson, PhD, Professor, and Director. Chelsea and Westminster Drug Treatment Unit, Riverside Mental Health Trust Substance Misuse Service, London, United Kingdom. William Shanahan, MRCPsych, Lead Clinician, and Clinic Director. Riverside Mental Health Trust, London, United Kingdom. Brian Wells, MRCPsych, Trust Medical Director. Reprints: Ms N Metrebian, The Centre for Research on Drugs and Health Behaviour, Department of Social Science and Medicine, Imperial College School of Medicine, 200 Seagrave Road, London SW6 1RQ, United Kingdom. E-mail: n.metrebian@cxwms.ac.uk Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia ".

Nicky Metrebian · William Shanahan · Brian Wells · Gerry V Stimson

Abstract Objective: To define recent trends (1993-1996) in incidence of endstage renal disease (ESRD) among Australian Aboriginal people in the Top End of the Northern Territory (NT). Design: Analysis of hospital and clinical records of the Darwin-based ESRD treatment program from 1993 to 1996 and comparison with data accumulated since 1978. Participants: All people entering the ESRD treatment program from 1978 to 1996. Main outcome measures: Number of patients treated for ESRD; their ethnicity, age and sex; comorbidities in Aboriginal patients; treatment methods and outcomes. Results: More Aboriginal people presented with ESRD between 1993 and 1996 (87) than in the previous 15 years of the program (68). The incidence of ESRD in Aboriginals reached 838 per million in 1996, and is doubling every 4 years. Aboriginal people presenting with ESRD are younger than non-Aboriginal people with ESRD, and, in contrast to non-Aboriginals, ESRD rates are higher in women than men. The numbers and proportions of Aboriginal ESRD patients who have hypertension, type 2 diabetes and cardiac disease are rising. Haemodialysis remains the most common form of treatment, and the number of dialysis treatments is doubling every 2.5 years. Only 9% of Aboriginal patients entering the program in 1993-1996 were treated with chronic ambulatory peritoneal dialysis and only 3% received transplants. Despite their younger age, survival of Aboriginal people on dialysis is low (median 3.3 years v. 6.5 years in non-Aboriginals), and graft survival after transplant is poor (37% at 5 years v. 88% in non-Aboriginals). Survival has not improved in the past 4 years, with fewer deaths from infection offset by more deaths from cardiovascular disease. Conclusions: The predicted doubling of ESRD incidence among Aboriginal people by the year 2000 will add an enormous burden to limited resources. Risk factors for renal disease underlie all the excess morbidity and mortality in NT Aboriginal adults, and arise out of accelerated lifestyle changes and socioeconomic disadvantage. Better living conditions and education, robust and integrated primary healthcare programs, and systematic screening for early renal disease and treatment of those with established disease are all matters of urgency. Introduction The high rate of endstage renal disease (ESRD) in Australian Aboriginal people is attracting increased attention.1-4 The Northern Territory (NT) faces particular challenges in dealing with this problem. It has the lowest population (179 000 people) and tax base of any Australian State, and the highest proportion of Aboriginal people (22% of the population, compared with 5%-6% for Queensland and Western Australia -- the States with the next-highest proportion). It has an area of 1 346 200 km2, and only two dialysis centres, 1500 km apart (one in Darwin and one in Alice Springs), which can scarcely accommodate the increasing numbers of Aboriginal people needing treatment. In a previous article,1 we reported the rising rates of ESRD among Aboriginal people in the Top End of the NT (Figure 1), with an average annual incidence of 440 per million from 1988 to 1993. Aboriginal patients were younger than their non-Aboriginal counterparts and, in contrast to the non-Aboriginal population, more women than men were affected. There was little use of chronic ambulatory peritoneal dialysis (CAPD), and the few transplants gave poor results. Comorbidities were high and there was a shorter survival time on treatment than in non-Aboriginal people. Tiwi people living on Bathurst and Melville islands had especially high rates of ESRD, but for other communities there were too few cases to allow calculation of population-adjusted rates. We present data for ESRD treatment in the Top End of the NT for the period 1993-1996, thus extending the period of analysed data to 19 years. The expanded data allow calculation of regional population-specific rates, and illuminate trends in diagnoses, comorbidities, treatment methods and survival. Methods Study population The total study population comprised all people entering the Top End ESRD treatment program from January 1978 to December 1996 inclusive. Our data sources were dialysis unit records and hospital files. We used Australian Bureau of Statistics aggregate and regional data from the 1987, 1991 and 1995 population censuses for the denominators for calculating ESRD rates for the 4-year intervals 1985-1988, 1989-1992, and 1993-1996.5The 1991 Aboriginal community census was used to calculate individual community rates for the three 4-year intervals. People moving to the NT from other countries or other States and becoming residents are potentially included in the census and thus the denominators. Statistical analysis We calculated age-standardised rates of ESRD with Epi-Info6 using aggregate Australian non-Aboriginal data from the 1996 Australian and New Zealand Dialysis and Transplant Registry (ANZDATA) as the reference population.7χ2 tests with Yates' correction were used to examine differences between groups. Kaplan-Meier survival analyses were performed by SPSS for Windows,8 and the log-rank test was used to compare the differences between the groups. Results In the period 1993-1996, 104 people entered the ESRD treatment program, making a total of 214 for the period 1978-1996. Of the total, 155 (72%) were Aboriginal, and 59 (28%) were non-Aboriginal. Incidence of treated ESRD Figure 2a shows the dramatic increase in incidence of ESRD in Aboriginal people over the three 4-year periods, with an average doubling time of about 4 years. More Aboriginal people (87) presented for treatment in the 4 years 1993-1996 than in the previous 15 years of the program (68). Within this most recent 4-year period, rates have continued to rise at an average of 22% per year, peaking at 838 per million9 in 1996 (compared with 39 per million in non-Aboriginal people in the NT). With age adjustment, the 1993-1996 average annual rate represents a 15-fold increase and the 1996 rate a 21-fold increase over ESRD rates in non-Aboriginal Australians nationwide. NT rates for non-Aboriginals, which did not change over this time period, are lower than Australian aggregate rates (62 per million from 1993-1996) because the NT has a younger population. All regions of the Top End are experiencing the same phenomenon, although current rates vary. Figure 2b shows the changes in incidence in Aboriginal people in the five regions with the highest current rates. The number of Aboriginal people receiving ESRD treatment (the prevalence), including those with functioning transplants, peaked at 2871 per million in 1996 versus 377 per million for non-Aboriginals. Finally, the number of dialysis procedures (which accrue most of the costs) is rising by 28% per year, or doubling every 2.5 years.9 Sex and age distribution of ESRD patients Ninety-three (60%) of the 155 Aboriginals with ESRD were women and 62 (40%) were men, compared with 23 (39%) women and 36 (61%) men among the 59 non-Aboriginal patients. Figure 2c shows the higher ESRD rates in Aboriginal women than men at each time period, resulting, in 1993-1996, in an age-adjusted relative risk of 31 in women versus 16 in men. On average, Aboriginal people were 5 years younger than non-Aboriginal people on entering the program (44 v. 49 years). However, the age distributions were quite different, with Aboriginal people most commonly presenting between the ages of 30 and 49 years, and non-Aboriginals between 50 and 69 years. Figure 3 shows that ESRD rates in Aboriginal people rose in most age groups over the life of the program, so that the average age and age distribution did not change appreciably. The age-specific incidence of ESRD in Aboriginal people peaked at age 50-59 years, and in non-Aboriginals at over 70 years. Renal failure causes and comorbidities in Aboriginals The Table compares the distribution of "causes" of ESRD in the two most recent 4-year intervals in those patients with documented causes. The proportion of ESRD in Aboriginal people attributed to (but not always solely due to) diabetes has almost doubled, that classified as glomerulonephritis has fallen by more than half, and the proportion in the "unknown" category has increased markedly. Aboriginal people with ESRD are more likely than non-Aboriginal people to have type 2 diabetes (48% v. 24%; P = 0.002) and hypertension (52% v. 32%; P = 0.01). Furthermore, these proportions have increased recently: for diabetes from 37% pre-1993 to 60% in 1993-1996 (P < 0.005); and for hypertension from 43% to 57% (P = 0.1); and for people with both diabetes and hypertension from 19% to 38% (P = 0.011). Treatment for ESRD Fifty-one per cent (30) of non-Aboriginal people, but only 17% (26) of Aboriginal people, have received transplants since 1978, and only 3% in the period 1993-1996. Potential reasons for this discrepancy include medical ineligibility, discouraging earlier results, distance to the transplant centre (in Adelaide), underservicing and difficulties in supervision of care in remote areas, lack of living related donors, and difficulties in HLA matching with donor organs. In 1996, only 11% of Aboriginal people with ESRD had functioning transplants versus 65% for non-Aboriginal people. Chronic ambulatory peritoneal dialysis (CAPD) rates in Aboriginal patients remain low, with only 5% of incident cases pre-1993 and 9% in 1993-1996 treated in this manner. Patient and graft survival Despite the younger age of Aboriginal patients with ESRD, their "integrated" survival (with all forms of treatment, ie, dialysis and transplantation) was significantly worse than that of non-Aboriginal people, with median survival times of 3.6 versus 12.3 years (P = 0.0025). This difference was reflected in those with and without diabetes. While survival on dialysis (CAPD and haemodialysis), as shown in Figure 4, tended to be lower in Aboriginal people (median 3.3 v. 6.5 years; P = 0.34), both graft and patient survival after transplantation were clearly worse (Figures 5 and 6). Patient survival at 1 and 5 years after transplantation was 92% and 60% for Aboriginals, compared with 97% and 93% for non-Aboriginals (P < 0.001), and graft survival at 1 and 5 years was 73% and 37% for Aboriginal people, compared with 97% and 88% for non-Aboriginal people (P < 0.001). There has been no improvement in integrated survival, or in dialysis or transplant survival separately, in the period 1993-1996. Causes of death The causes of death in Aboriginal people have changed for the period 1993-1996. Deaths due to cardiac disease have increased from 33% before 1993 to 51% after 1993. Deaths due to voluntary withdrawal from treatment are unchanged (24% and 25%, respectively). In contrast, only one non-Aboriginal patient has ever withdrawn from treatment, and none in the past decade. Discussion These data for 1993-1996 confirm and further define the rise in incidence of renal failure among Aboriginal people in the Top End of the Northern Territory. No community is spared, and this pattern is repeated in Central Australian Aboriginals, who have even higher rates (1400 per million in 1996).4 Current incidence rates are now comparable with those of Afro-Americans and Native Americans (800 and 744 per million, respectively, in 1995); however, age-adjusted rates are much higher in Australian Aboriginals (due to their very youthful population) and are increasing much faster, with a doubling time less than 4 years versus 10 years for the US minority groups.10 These alarming figures are nonetheless underestimates, because some Aboriginal people, especially older people and those from very remote communities, decline treatment for ESRD or are medically unsuited. Most of the increase is real. It is not due to ageing of the Aboriginal population, as it is reflected across every age group; and it is not due to improved ascertainment, at least in the major communities, as awareness has been high since the mid 1980s. The disability and the personal, family and community disruption are great, and the resource requirement will be truly formidable if current rates of increase, which project up to 500 new cases between 1997 and 2004 (exponential progression), are sustained. The data confirm the younger age and female predominance of Aboriginal people with ESRD. The latter might be due, in part, to lower birthweights and the relatively higher adult body weights in women, with more marked insulin resistance and earlier onset of type 2 diabetes.11,12 Both occur also in Central Australia.4 Some of the change in attributed cause of ESRD over the most recent 8-year period reflects subjectivity in assignment criteria, but much reflects reassignment of the common finding of bland glomerulomegaly with absent or minimal inflammation13-15 from the "glomerulonephritis" category to the "unknown" category. The rise in renal failure attributed to diabetes is compatible with the dramatic increase in rates of diabetes and its complications in all Aboriginal communities,16 but clinical and biopsy data show that diabetes is more often a facilitating factor for disease expression and progression rather than the prime or sole cause of the underlying nephropathy.11,14 The increased incidence in all communities of Syndrome X (obesity, hypertension, dyslipidaemia, dysglycaemia and predisposition to cardiovascular disease), which is attributed to insulin resistance, likewise explains the increasing proportions of Aboriginal people presenting for ESRD treatment with diabetes and hypertension as comorbidities.11,16-18 These conditions are already generating more heart attacks, strokes, coronary angioplasties, coronary artery bypass graft procedures and cardiovascular deaths among Aboriginal ESRD patients. As the epidemic grows and the Aboriginal population ages, these complications will become more common, and further increase costs, complicate treatment and compromise survival. The persistently high rate of withdrawal of Aboriginal people from ESRD treatment reflects difficulties with chronic disability, the complex treatment regimen, and loss of social and family support and "land identity" associated with relocation from their community to Darwin for treatment.19,20 Initiatives to move treatment closer to home include attempts to promote CAPD, which has low rates of technical failure and peritonitis, but major problems with exit-site infections;20 a renewed focus on transplant (seven Aboriginal people received transplants in 1997); construction of the first community-based dialysis unit with seven stations on the Tiwi islands; and the possibility of placing haemodialysis stations in clinics in high risk remote areas. However, deliberations about efficient and equitable delivery of ESRD treatment must no longer be allowed to dominate the dialogue. Dialysis in the Top End currently costs $496 per treatment, which is about $75 000 per patient per year. This cost does not include medicines, relocation and housing, transportation and hospitalisations.9 The allocation of resources of this magnitude to people with a median life expectancy of 3.3 years must be balanced by serious and sustained community-based initiatives to prevent and ameliorate the underlying problem. Most renal disease in Aboriginal communities is marked by albuminuria, and all renal failure arises in people with a history of progressive overt albuminuria.11Risk factors for renal failure include low birthweight and infant malnutrition, infections (scabies, poststreptococcal glomerulonephritis), increasing adult weight, high blood pressure, increasing glucose levels, insulin resistance, dyslipidaemia, and heavy drinking.11 Several risk factors can operate simultaneously, progressively compounding the decline in renal function that accompanies increasing age. The current epidemic is probably explained by the confluence of many risk factors over a short time period, associated with dramatic lifestyle changes and serious socioeconomic disadvantage. Ironically, the great fall in infant mortality between the late 1950s and late 1970s, a consequence of better hospital management of sick babies, means that those low birthweight babies now surviving to adult life are at high risk for renal and other chronic diseases.11,21 This multifactorial perspective on renal disease necessitates a rethinking of renal disease classifications.11 There is a need for a stronger focus on community and individual risk factor profiles and on pathophysiological interactions, and some de-emphasis of categorical definitions. It justifies a general preventive health services model, which will also reduce the diabetes, hypertension, cardiovascular disease, chronic lung disease and infections that contribute to the excess mortality in NT Aboriginal adults.17 In addition, screening programs to recognise early and established renal disease, and treatment (including angiotensin-converting enzyme inhibitors) to arrest disease progression, must be incorporated into regular adult healthcare in every Aboriginal community as a matter of urgency.22,23 Acknowledgements This study was supported by the National Health and Medical Research Council of Australia, and the Australian Kidney Foundation. We thank Dr David Pugsley, who led the way with renal services in the Northern Territory, and established the basis of these observations, and Dr Diane Howard and Dr Sid Selva-Nayagam, who have had the longest tenure of care of renal patients. We thank the staff of the Nightcliff Dialysis Unit and the Renal Unit at Royal Darwin Hospital for their excellent care and cooperation. Dr Zhiqiang Wang assisted with statistical analyses, and Ms Susan Jacups with clerical and graphic support. References Hoy WE, Mathews JD, Pugsley DJ. Treatment of end-stage renal disease in the Top End of the Northern Territory: 1978-93. Nephrology 1995; 1: 307-313. Hoy WE, Silva D. NT Top End Aboriginal end stage renal disease data and projections. Darwin, NT: Renal Strategy Committee, Territory Health Services, February 1997. Hoy WE. Renal disease in Aboriginal Australians. Med J Aust 1996; 165: 126-127. Renal disease in Central Australia -- challenges and opportunities for better health. Health Strategies, Deakin. Melbourne: Deakin University, September, 1997. Australian Bureau of Statistics. 1996 Census of population and housing. Aboriginal community profiles, small area data. Canberra: ABS, 1996. (Catalogue No. 2020.0.) Dean AG, Dean JA, Coulombier D, et al. Epi-Info, version 6: a word processing, database and statistics program for epidemiology on microcomputers. Atlanta, Ga: Centers for Disease Control and Prevention, 1994. Disney APS, editor. ANZDATA Report 1996. Nineteenth report of the Australian and New Zealand Dialysis and Transplant Registry. Adelaide: Queen Elizabeth Hospital, 1996. SPSS -- Statistical Package for the Social Sciences [computer program], release 6.1, standard version. Chicago: SPSS Inc, 1988. Margetts C, Morris E. Cabinet submission to the NT Legislature for renal services funding. Darwin: Royal Darwin Hospital, February 1998. United States Renal Data System (USRDS). Annual Data Report. Bethesda, MD: The National Institutes of Health, NIDDK, April 1997. Hoy WE, Mathews JD, McCredie DA, et al. The multidimensional nature of renal disease: findings in a high risk Australian Aboriginal community. Kidney Int 1998. In press. Hoy WE, Norman RJ, Hayhurst B, G Pugsley DJ. A health profile of adults in a Northern Territory Aboriginal community, with an emphasis on preventable morbidities. Aust N Z J Public Health 1997; 21: 121-126. Lloyd ML, Moore L, Pugsley DJ, Seymour AM. Renal disease in an Australian Aboriginal population: a pathologic study. Nephrology 1996; 2: 315-322. Howard DM, Davis J, Pugsley DJ, et al. Morphologic correlates of renal disease in a high risk Aboriginal community. Proceedings of the 31st Annual Scientific Meeting, Australian and New Zealand Society of Nephrology; Perth, WA; March 5-8, 1996. Sydney: Australian and New Zealand Society of Nephrology, 1996. Bertram JH, Young RJ, Seymour AE, et al. Glomerulomegaly in Australian Aborigines. Nephrology 1998. In press. Markey P, Weeramanthri T, Guthridge S. Diabetes in the Northern Territory. Darwin: Diabetes Australia (Northern Territory), 1996. Cunningham J, Condon J. Premature mortality in Aboriginal adults in the Northern Territory, 1979-1991. Med J Aust 1996; 165: 309-312. Reaven GM. Insulin resistance and compensatory hyperinsulinemia: role in hypertension, dyslipidemia, and coronary artery disease. Am Heart J 1991; 121: 1283-1288. Willis J. Fatal attraction: do high technology treatments for end stage renal disease benefit Aboriginal people in Central Australia? Aust J Public Health 1995; 19: 603-609. . Snelling P. I hit beautiful serves -- but my partner keeps putting the ball in the net: renal transplantation in Aboriginal patients. Proceedings of the 10th Dialysis and Transplant Workshop of the Australian Kidney Foundation and the Australian and New Zealand Society of Nephrology; Launceston, Tasmania; October 1997. Sydney: Australian and New Zealand Society of Nephrology, 1997: 62-63 Barker DJP. Mothers and babies and disease in later life. London: BMJ Publishing Group, 1994. Hoy WE. Markers for cardiovascular and renal morbidity: expectations for an intervention program in an Australian Aboriginal community. Clin Exp Pharmacol Physiol 1996; 23 (Suppl 1), S33-S37. Hoy WE. Guidelines for screening and treatment of renal disease in Aboriginal communities. Nephrology 1998. In press. (Received 5 Jan, accepted 10 Mar, 1998) Authors' details Menzies School of Health Research, Darwin, NT. Janine L Spencer, FRACP, DTM&H(Lond), Paediatrician, Australian Kidney Foundation Research Fellow. Wendy E Hoy, BScMed, FRACP, NHMRC Senior Research Fellow, Director of Renal Program; and Renal Community Services Specialist, Territory Health Service. TVW Telethon Institute for Child Health Research, Perth, WA. Desiree T Silva, FRACP, MPH, Paediatrician. Royal Darwin Hospital, Darwin, NT. Paul Snelling, FRACP, Nephrologist, Royal Darwin Hospital, and Territory Health Service. Reprints will not be available from the authors. Correspondence: Dr W E Hoy, Menzies School of Health Research, PO Box 41096, Casuarina, NT 0811. E-mail: wendyATmenzies.su.edu.au Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia ".

Janine L Spencer · Desiree T Silva · Paul Snelling · Wendy E Hoy

Abstract Objective: To determine the prevalence of the Wernicke-Korsakoff syndrome (WKS) in Australia and compare this with previous studies. Design and setting: Prospective autopsy study at the New South Wales Institute of Forensic Medicine, 1996-1997. Methods: Brains of deceased people (aged over 15 years) derived from 2212 sequential autopsies performed between 1 January 1996 and 31 December 1997 were studied macroscopically and microscopically to identify cases of WKS. Main outcome measures: Standard histological criteria for WKS and any available clinical data. Results: Twenty-five cases of WKS were identified (prevalence, 1.1%), mostly among the 5.9% of the 2212 people who had a history suggestive of alcohol abuse. Only four cases (16%) had been diagnosed during life. Conclusions: There has been a significant reduction in the prevalence of WKS in Australia since the introduction of thiamine enrichment of bread flour. While the prevalence is still higher than in most other Western countries, further research is needed before adding thiamine to alcoholic beverages can be recommended. Introduction Wernicke-Korsakoff syndrome (WKS) is a potentially fatal neurological disorder caused by thiamine (vitamin B1) deficiency. It is easily treated by thiamine supplementation, with most people showing dramatic clinical improvement. Biochemical studies in the 1980s showed that 10%-20% of Australians had a low thiamine intake, with those who used alcohol excessively being particularly "at risk",1 and previous autopsy studies had shown that Australia had the highest recorded prevalence of WKS in the world, with most cases occurring among those who abused alcohol.2-5 To address these problems, the Australian Health Ministers' Council recommended the mandatory enrichment of bread flour with thiamine. Consequently, since 1991 bread flour in Australia has contained not less than 6.4 mg of thiamine per kilogram.6 Human thiamine requirements have been estimated to be 1.0-1.5 mg daily.7 The major food sources of thiamine are cereal products. Although thiamine is naturally present in the grains used to produce flour, much is removed during some types of processing, and thiamine enrichment of flour has been practised in a number of countries for many years.8,9 It is a mandatory requirement in the United Kingdom, Canada, and Denmark, while in the United States enrichment is not mandatory, but most flour is enriched. Since the introduction of thiamine enrichment of rice and flour, thiamine deficiency is said to have virtually disappeared in countries such as Japan and the US.10,11 Our aim was to establish whether this safe and simple public health measure has reduced the prevalence of WKS in Australia, and hence to determine whether we need to consider alternative public health measures such as adding thiamine to all flours used in food preparation or even to alcoholic beverages.12 Methods We prospectively studied all sequential autopsies of people aged over 15 years (as WKS is rare in a younger population in Western countries) from the NSW Institute of Forensic Medicine in Sydney during 1996 and 1997. In line with standard autopsy procedures, brains were fixed in 10% formol saline for at least two weeks. After careful external examination and removal of the brainstem and cerebellum, the brain was cut in the coronal plane, the first cut being made at the level of the anterior (ventral) tip of the mammillary bodies. The hemispheres were then cut at 10 mm intervals. The brainstem and cerebellum were separated by dividing the right and left cerebellar peduncles. The cerebellum was sectioned in the sagittal plane through the vermis and through the lateral hemispheres. The brainstem was sectioned in the horizontal plane at 3 mm intervals. The brain slices were examined, paying particular attention to the mammillary bodies and the regions around the third ventricle and the floor of the fourth ventricle. It has been shown that the mammillary bodies are abnormal on microscopic examination in 99%-100% of cases of WKS.3,13 The mammillary bodies were measured in three dimensions and brain slices were photographed if any macroscopic abnormality was noted. Blocks of tissue were taken for paraffin embedding and the preparation of histological sections. The principal block for this study incorporated both of the mammillary bodies and the walls of the third ventricle. Blocks from other regions of the brain were taken according to routine neuropathological protocols of the Institute of Forensic Medicine and the Neuropathology Department.4 These varied depending on the clinical history, cause of death, and general autopsy findings. Sections were cut at 10 mm and stained with haematoxylin and eosin. Brains were stored until each case was completed, so that, if necessary, additional blocks of tissue could be taken for further examination. This was particularly important if an abnormality was identified in the section of the mammillary bodies. A number of other diseases can affect the mammillary bodies, but these can usually be easily differentiated from WKS.5,14 All cases were examined microscopically by a neuropathologist (C H) without knowledge of the relevant clinical history or the macroscopic findings. In all cases in which WKS was suspected, the mammillary body section was also stained with reticulin, Weil myelin, glial fibrillary acidic protein, Perl's iron stain, Bodian silver impregnation, and Nissl stain for neurones. The purposes of these stains are summarised in Box 1. Clinical histories and general pathological data were correlated with the neuropathological findings. Statistical comparisons were made with data from a previous, similar study3 using chisquared statistics with Yates' correction factor and relative risk with 95% confidence intervals. Results We diagnosed 25 forensic cases of WKS from 2212 brains, giving an overall prevalence of 1.1%. Box 2 compares the prevalence data with those of a similar Australian study (including both forensic and hospital cases of WKS) undertaken by one of the authors (C H) from 1973 to 1981,3 and shows that there has been a statistically significant reduction in the prevalence of WKS. The mean age at death of the people with WKS was 55 years; 23 (95%) were men. Hospital medical records, located for 18 of the 25 deceased people with WKS, showed that alcohol appeared to have been a predisposing factor for WKS in 16 (89%). Of the remaining two, one was a man with paraplegia who was totally dependent and required gastrostomy feeding, and the other man had both lung and bowel cancer. Information available at autopsy indicated that 5.9% of the 2212 brains studied were from people with a history which suggested an alcohol problem, giving a prevalence of WKS in an Australian forensic population with a history suggestive of alcohol problems of 19%. A clinical diagnosis of WKS (Korsakoff's psychosis) during life had been made in only four (16%) of the 25 deceased whose WKS was identified at autopsy. However, two others had a diagnosis of alcohol-related brain damage. The hospital records located for 18 deceased people with WKS showed that four had severe amnesia (Korsakoff's psychosis), two others had memory problems and three had ataxia or unsteady gait. None were reported to have ophthalmoplegia or nystagmus, which are commonly described clinical signs in WKS.15 Three had a history of epilepsy. Eight (44%) had been given thiamine (vitamin B1) supplements during one or more of their hospital admissions. The diagnosis of WKS in this study was based on typical pathological abnormalities, which will not be described in detail as this information is available in current neuropathological texts.6 In brief, lesions are seen in a characteristic distribution -- in the mammillary bodies and around the walls of the third and fourth ventricles. Macroscopic findings vary depending on the stage of the disease (see Box 3). There were two acute cases, six acute-on-chronic cases (evidence of both acute and chronic damage to mammillary bodies), and 17 chronic cases. These data are compared with those of a previous study3 in Box 4. Discussion Our findings show a significant reduction in the prevalence of WKS in Australia compared with the findings of a similar study of forensic cases between 1973 and 1981 (see Box 2).3 The two forensic populations were similar, even though these two studies were conducted in different Australian States (New South Wales and Western Australia) and at different times. Laws relating to deaths which must be reported to the Coroner and undergo forensic autopsy are almost identical in these two States. Moreover, one of the authors (J H) was the Director of the Forensic Department in Perth, WA, at the time of the first study and is currently the Director of the NSW Institute of Forensic Medicine, where the current study was carried out; he commented that the profiles of cases in the two autopsy studies were very similar. The high prevalence of WKS at autopsy in Australia2-5 has been reflected in clinical studies, with, for example, 170 cases of WKS being identified among 1100 total inpatients at Queensland's largest hospital for the mentally ill.12 However, a retrospective study of records from 17 major Sydney hospitals from 1978 to 1993 showed that the number of acute cases of WKS was lower in 1992 and 1993 than in any of the other years.16 This suggests that dietary enrichment of bread flour with thiamine may have had an impact on the occurrence of acute cases of WKS. Our finding of fewer cases of acute WKS compared with the earlier WA study also supports this (see Box 4, above). As patients with acute WKS who are treated appropriately with parenteral thiamine respond within days, and signs and symptoms usually resolve completely, not all cases will progress to chronic disease. The development of chronic disease is not fully understood, but many chronic cases of WKS are likely to be the result of recurrent episodes of either clinical or subclinical thiamine deficiency.17 WKS is said in the medical textbooks to have a characteristic clinical picture of mental changes (confusion, obtundation), ataxia, and eye signs (nystagmus, ophthalmoplegia). However, as shown in this study and previously, analysis of clinical signs and symptoms of patients diagnosed with WKS post mortem reveals that a minority of cases have the full clinical picture and about a third exhibit only mental changes.15 Thus, the diagnosis can be easily overlooked. Many authors agree that WKS can develop as a result of repeated "subclinical" episodes of thiamine deficiency,18 so that studies of the prevalence of this disorder based on clinical findings are unsatisfactory and may underestimate the true incidence.15 Given that most of the cases of WKS we identified were chronic, some explanation must be sought for the significant reduction in the prevalence of this disease within six years of the introduction of thiamine enrichment of bread flour. There are four possible explanations: 1. A true reduction in the number of new (acute) cases of WKS as a result of the increase in dietary thiamine, and reduced numbers of "at risk" cases. 2. An improvement in the clinical status of patients who already have WKS and a reduced occurrence of further clinical or "subclinical" episodes of thiamine deficiency.17 This could result in an increase in the longevity of patients with existing WKS -- for example, through a reduction in the sudden unexpected deaths seen among chronic alcoholics. 3. A general improvement in the health status of the Australian population, independent of the introduction of thiamine supplementation. 4. Publication of the high prevalence of WKS in Australia may have led to an increased awareness, particularly among health professionals, of the necessity for thiamine treatment in "at risk" patients. Almost half of the 25 people whose WKS was identified at autopsy had been treated with thiamine in hospital. This increased awareness and therapeutic intervention may have played a role in the reduced prevalence. It is likely that each of these explanations played a part in reducing the prevalence of WKS. However, the relative importance of each will only be clarified with time and further study as the enrichment of bread flour with thiamine, has only been in place for six years. It should be noted that the results of this study may in fact underestimate the beneficial effect of the enrichment of bread flour with thiamine as many of the cases of chronic WKS will have developed before the enrichment program commenced. Further prevalence studies should be carried out in, say, another five years, and this information, together with biochemical studies of the thiamine status of the Australian population, will enable rational decisions to be made with regard to other public health programs, such as fortification of alcoholic beverages with thiamine. Our findings neither support nor confirm the prediction of Price and Theodorous that many people who abused alcohol would not be protected by a flour enrichment program because alcoholic beverages are, "for a hazardously long period of their lives, their only form of caloric intake".12 However, they had suggested, on the basis of this prediction, that thiamine supplementation of alcoholic beverages might be a more effective preventive measure, and in reviewing this proposal Connelly and Price noted that fortification of beverages, rather than bread flour, would be more cost-effective by a factor of 20-40-fold.19 Although there has been a significant decrease in the prevalence of WKS in Australia since the introduction of thiamine enrichment of bread flour in 1991, the rate is still higher than in most other Western countries5 and there is a need to maintain vigilance in the management of patients, particularly those with known or suspected alcohol problems. Acknowledgements This research was supported by the Australian Brewers' Foundation and by the National Health and Medical Research Council (Grant number 943302). We are grateful to all the staff at the NSW Institute of Forensic Medicine for their assistance and cooperation. References Wood B, Breen KJ. Clinical thiamine deficiency in Australia: the size of the problem and approaches to prevention. Med J Aust 1980; 1: 461-464. Harper C. Wernicke's encephalopathy: a more common disease than realised. J Neurol Neurosurg Psychiatry 1979; 42: 226-231. Harper CG. The incidence of Wernicke's encephalopathy in Australia -- a neuropathological study of 131 cases. J Neurol Neurosurg Psychiatry 1983; 46: 593-598. Harper CG, Gold J, Rodriguez M, Perdices M. The prevalence of the Wernicke-Korsakoff syndrome in Sydney, Australia: a prospective necropsy study. J Neurol Neurosurg Psychiatry 1989; 52: 282-285. Harper C, Fornes P, Duyckaerts C, et al. An international perspective on the prevalence of the Wernicke- Korsakoff syndrome. Metab Brain Dis 1995; 10: 17-24. Harper C, Butterworth R, editors. Nutritional and metabolic disorders. 6th ed. London: Arnold, 1997: 601-664. Freeman RM, editor. Rational use of vitamins in practice. Toronto: JB Lippincott, 1979: 115-122. Axford DWE, Williams DA. Flour enrichment around the world. Br Flour Milling Baking Res Assoc 1981; 4: 156-163. Bauerfeind JC. Nutrification of food. In: Shiks ME, Young VR, editors. Modern nutrition in health and disease. 7th ed. Philadelphia: Lea and Febiger, 1988. Figueroa WG, Sargent F, Imperiale L, et al. Lack of avitaminosis amongst alcoholics. J Clin Nutrition 1953; 1: 179-199. Sebrel WH. Enrichment: good gift of yesterday. Cereal Science Today 1966; 11: 228-230. Price J, Theodorus MT. The supplementation of alcoholic beverages with thiamin: a necessary preventative measure in Queensland. Aust N Z J Psychiatry 1979; 13: 315-320. Victor M, Adams RD, Collins GH. The Wernicke- Korsakoff Syndrome. Philadelphia: Davis, 1989. Schubert T, Friede RL. Transneuronal mammillary atrophy. J Neurol 1979; 221: 67-72. Harper CG, Giles M, Finlay-Jones R. Clinical signs in the Wernicke-Korsakoff complex -- a retrospective analysis of 131 cases diagnosed at autopsy. J Neurol Neurosurg Psychiatry 1986; 49: 341-345. Ma JJ, Truswell S. Wernicke-Korsakoff syndrome in Sydney hospitals: before and after thiamine enrichment of flour. Med J Aust 1995; 163: 531-534. Lishman WA. Cerebral disorders in alcoholism. Syndromes of impairment. Brain 1981; 104: 1-20. Lishman WA. Alcohol and the brain. Br J Psychiatry 1990; 156: 635-644. Connelly L, Price J. Preventing the Wernicke-Korsakoff syndrome in Australia: cost-effectiveness of thiamin-supplementation alternatives. Aust N Z J Public Health 1996; 20: 181-187. (Received 7 Aug1997, accepted 16 Feb 1998) Authors' details Department of Pathology, University of Sydney, and Royal Prince Alfred Hospital, Sydney, NSW. Clive G Harper, MD, FRCPA, Professor; Donna L Sheedy, BA, Research Assistant; Ana I Lara, Technical Assistant. Network for Brain Research into Mental Disorders, Prince of Wales Hospital, Sydney, NSW. Therese M Garrick, RN, BNurs, Research Assistant. New South Wales Institute of Forensic Medicine, Sydney, NSW. John M Hilton, MB ChB, FRCPA, Director; Jack Raisanen, MD, Forensic Neuropathologist. Reprints: Professor C G Harper, Department of Pathology, University of Sydney, NSW 2006. E-mail: clivehATpathology.su.oz.au Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia ".

Clive G Harper · Donna L Sheedy · Ana I Lara · Therese M Garrick · John M Hilton · Jack Raisanen

Abstract Objective: To determine the health-related quality of life (HRQOL) of Australian men after radical prostatectomy. Design: Cross-sectional study. Setting: Private and public practices of three urologists in south-east Queensland, July 1989 to June 1995. Participants: 140 men with no evidence of disease recurrence 1 to 6 years after radical prostatectomy. Main outcome measures: Voiding and erectile potency and HRQOL. Recall of preoperative status and status at survey were established by an independently administered multi-item questionnaire. Results: 112 men (80%) completed the study questionnaire. Difficulty with bladder control before the operation was reported by 25 (22%; 95% confidence interval [CI], 15%-31.2%), and the incontinence rate after treatment was 22/112 (20%; 95% CI, 12.7%-28.2%). Men with incontinence after operation were more likely to recall preoperative urinary symptoms. Eighty-four (75%) men were happy or coping with their sexual function after radical prostatectomy despite an erectile potency rate of only 12% (95% CI, 7%-20%). Twenty-eight (25%) had tried penile injections and three have had penile prostheses since their operation. Impotence was reported more frequently (40%) as the treatment-related problem most affecting life, followed by "concern about cancer" (12%) and incontinence (8%). Impotence was also the most common cause given for diminished HRQOL. Conclusions: Loss of sexual function after radical prostatectomy is more commonly perceived as a major problem and is more likely than urinary incontinence to adversely affect HRQOL. Loss of sexual function and its effect on HRQOL needs to be given greater emphasis in counselling before radical prostatectomy. MJA 1998; 168: 483-486 Introduction Prostate cancer is the second most common cause of cancer-related death in Australian men, and in 1989 became the most common cancer in men in New South Wales.1 This increase may be partly attributed to a more health-conscious, ageing population, as well as greater use of "routine" digital rectal examination (DRE) and prostate-specific antigen (PSA) tests.2 PSA tests, together with DRE and transrectal ultrasound-guided prostatic biopsies, have enabled the diagnosis of potentially curable early-stage prostate cancer.3 In particular, increased efforts have been made to identify early-stage prostate cancer in men under 70 years of age, even though a significant survival advantage has yet to be demonstrated. Screening and case detection remain controversial. There is argument about whether the tests are sufficiently sensitive and specific for effective screening, and whether screening affects outcomes enough to be cost effective.4,5Opinions also differ regarding the optimal management of localised prostate cancer.6 In men over 70 years of age, or in those with appreciable co-morbidity, a conservative approach is generally accepted. Healthy younger men are more likely to live long enough to experience progression of their disease, so radical prostatectomy and radiotherapy, as well as "watchful waiting", are options in this group. Judging by current published studies, these options may provide similar outcomes in selected patients: up to 10 years after diagnosis, similar survival rates are seen in patients treated immediately with surgery or radiotherapy, and in patients initially watched and then treated with androgen ablation, transurethral resection or radiotherapy if the disease progresses.7 This has created a significant dilemma for both doctor and patient when selecting appropriate treatment.6 The lack of a clearly superior treatment option makes the impact of treatment on health-related quality of life (HRQOL) of greater importance. The difficulty in selecting appropriate treatment is compounded by a lack of Australasian data on the effect of treatment on HRQOL. Radical prostatectomy has been increasingly used in treating patients with localised prostate cancer and is considered an appropriate option for men who have a life expectancy in excess of 15 years.8 Despite improved surgical technique, postoperative impotence and incontinence may still occur, although the reported incidence varies considerably.9 Our study was undertaken to record patients' perception of HRQOL after radical prostatectomy, to assist patients, families and doctors in their discussions about treatment expectations and outcomes. Methods Sample Surgical audit data were collected prospectively on all patients having radical prostatectomy between July 1989 and June 1995. Three of us (P S H, A N J and L C T) performed the operations. We all receive referrals from other specialist urologists, and perform most of the radical prostatectomies in Queensland. We believe that the patients studied are likely to be representative of the Australian population, although there are no data currently available from other States or Territories. We selected for review patients who had no evidence of recurrent or residual disease to avoid any effect treatment failure may have had on HRQOL. No evidence of disease was defined as a PSA level less than 0.1 µg/L and no abnormal signs and symptoms at the last clinic visit. Men operated on less than a year before the survey were excluded as complications may still resolve during this period.9 As complications are likely to remain stable after one year, we believe the cohort to be homogeneous for the purposes of studying the effects of radical prostatectomy on HRQOL. To minimise recall bias, we included only patients operated on less than six years earlier. Non-surgical factors, such as co-morbidity and ageing, were thought to be unlikely modifiers of HRQOL during this period, so that most of the changes seen could be attributed to the prostatectomy. We decided that post-hoc subgroup analysis of a cross-sectional study with small numbers was of limited value so we included patients in the survey regardless of whether nerve sparing (which may affect postoperative potency) was contemplated or performed. Comparisons with non-surgical therapies may be facilitated by this approach. Definitions We defined urinary incontinence as the need to wear incontinence pads regularly, and defined erectile potency as the ability to achieve an erection firm enough for sex more than once a month. Questionnaire As higher complication rates are usually reported in studies in which patients are reviewed independently of their treating physician,10 our questionnaire was administered independently (by R J B). Each patient was telephoned before the questionnaire and a letter of explanation was mailed. They were assured of confidentiality, that the questionnaire was being administered independently of their treating doctor and that their answers would have no impact on management of their condition. Patients who had not replied within one month were sent one reminder. As there is no current internationally validated HRQOL questionnaire for patients with prostate cancer,11 two of us (D L N and R J B) developed the questionnaire. The initial questions collected demographic data; there were 16 items about bladder and sexual function, with similar questions to check for internal consistency; and another five items assessed postoperative therapies (such as penile injections and prostheses) and satisfaction with treatment. As our questionnaire is a new tool, only some sections have been validated.10,12-14 The questionnaire assessed men's perceptions of their urinary, sexual and overall function during the month before receipt of the questionnaire. (This is a recognised method used in other validated scoring systems.15,16) Urinary symptoms and erectile function, at the time of the survey and before surgery, were assessed on a five-point scale and included severity, effect and bothersomeness of symptoms. Satisfaction with treatment and willingness to have the same treatment again were also assessed on a five-point scale. An edited version of the Functional Assessment of Cancer Therapy Scale was used to assess health, social life and satisfaction with life.14 Statistical analysis We calculated exact confidence intervals (CI) and Fisher's exact tests using the STATA statistics package.17 Results Respondents Of 185 men having radical prostatectomy, 140 had no evidence of disease at last review. One of these 140 died in a motor vehicle accident and three more were lost to follow-up. Completed questionnaires were received from 112 (80%) men whose ages at the time of survey were normally distributed around the mean of 64 years (range, 54-73). Urinary incontinence There were 22 (20%; 95% CI, 12.7%-28.2%) respondents with postoperative urinary incontinence (Box). Those with more severe incontinence were more likely to report urge incontinence or mixed stress and urge incontinence. Twenty-five respondents (22%; 95% CI, 15%-31.2%) recalled "trouble with bladder control" before surgery, although none required pads. Seventeen of the 25 (68%; 95% CI, 46.5%-85%) were incontinent after the operation, compared with only 5 of the 87 (6%; 95% CI, 2%-13%) who did not recall having problems before surgery. That is, men with urinary incontinence after radical prostatectomy were much more likely to recall preoperative urinary symptoms. There was no statistically significant association between age and postoperative continence, nor was there any association with level of education or area of residence (Fisher's exact test). Urinary symptoms did not interfere with daily activities in 93 (83%; 95% CI, 75%-85%) respondents, and 89 (79%; 95% CI, 71%-86%) were either very happy or happy with their present bladder function. Erectile potency Of the 112 respondents, 99 (88%; 95% CI, 81%-94%) recalled preoperative erectile potency, but only 14 (12%; 95% CI, 7%-20%) described erectile potency at survey. Although only 14 were potent, 23 (20.5%; 95% CI, 13.5%-29%) were happy and 61 (54.5%; 95% CI, 45%-64%) were coping with their level of sexual function. Since surgery, 28 of the respondents (25%) have tried penile injections and three (2.7%) now have a penile prosthesis. Of the 13 men who were impotent before surgery, two have tried penile injections and one has had a penile prosthesis. There was no statistically significant association between postoperative impotence and age, level of education or place of residence (Fisher's exact test). Health-related quality of life Most respondents enjoyed a high HRQOL -- 104 (93%) were satisfied with their life and with their social life. Nearly all respondents reported good general health. The most common problem affecting their lives was impotence (44 men; 40%), followed by "concern about cancer" (13 men; 12%) and "bladder problems" (9 men; 8%). Despite the high prevalence of impotence, 104 (93%; 95% CI, 80.5%-97%) respondents were satisfied with their treatment and 98 (88%; 95% CI, 80%-93%) would opt for the same treatment again. Impotence was the most common reason given for treatment dissatisfaction (7/8) and reluctance to have the same treatment again (8/14). A final section asked about "any other problems related to your surgery which affects your quality of life". One man had a problem with a lack of pad-disposal facilities in golf club toilets, and one, although potent, said that loss of ejaculation left him unsatisfied. Discussion Our questionnaire was designed to examine specific problems of incontinence, impotence and patients' perception and satisfaction with treatment and feeling of well-being after radical prostatectomy. We found impotence to be the most common cause of diminished HRQOL, followed by "concern about cancer" and then incontinence. The preoperative urinary difficulty and impotence rates in our study are similar to those in other published prospective series,18,19 and our postoperative results lie within the range of the results of other published studies,10 suggesting that our questionnaire and study design are valid. Differences between our results and those of others may be explained by our case selection and independent data collection. In Australia, initial presentation of men with prostate problems during the study period was usually prompted by lower urinary tract symptoms. Men with troublesome urinary symptoms are more likely to have detrusor instability, a factor that commonly predisposes them to incontinence after radical prostatectomy.20 Our respondents reported a 20% incontinence rate and 22% recalled preoperative urinary difficulties. In contrast, Steiner et al reported an 8% incontinence rate after radical prostatectomy,21 but the more widespread screening for prostate cancer in the United States2-5 makes it likely that their patients were referred after screening and may not have had incontinence problems. The methods by which data are collected may also affect reporting of incontinence. Other studies that also used independent data collection15,22 have reported higher rates of incontinence (31% and 47%, respectively). We found that men with postoperative incontinence were much more likely to recall preoperative symptoms. However, we advise caution in interpreting this apparent strong association because of the limitations of cross-sectional studies (such as only measuring subjects' status once and not taking account of variation in patients' condition, including only those with successful treatments, and not yielding true relative risks) and the potential effects of recall bias. Patients with incontinence after surgery may have thought more about their predicament and been more likely to recall preoperative urinary symptoms; and, conversely, those continent after the operation may have had urinary symptoms before the operation but did not recall being troubled by them. Nevertheless, specific enquiry regarding urinary symptoms is advised when discussing treatment options with patients with localised prostate cancer, and those with urinary symptoms need to be informed of the association with urinary incontinence after radical prostatectomy. Lack of preoperative symptoms, however, does not guarantee postoperative continence as 6% of this group were incontinent after the operation. The preoperative impotence rate in our patient group is similar to that reported by Jonler et al. Men in their study were of similar age, and data were collected prospectively in a community setting.19 After the operation 12% of our respondents were potent, which is similar to the rates Jonler et al22 and Fowler et al10 reported (16% and 11%, respectively), but lower than the 70% found by Quinlan et al.23 Recall bias, case selection and independent data collection, as discussed for incontinence, are also plausible explanations for these differences. Impotence was much more likely to be reported as a major quality-of-life problem than incontinence, which is consistent with other series.12,24 Loss of potency as a cause of diminished HRQOL is not specific to radical prostatectomy, as Jonler et al concluded in their study of 1680 men attending a cancer screening program "impotent men have a lower QOL than potent men".19 Many men are prepared to trade off survival for sexual potency,25 so some men may choose a treatment with possibly lower long-term survival to increase their chance of remaining potent. The impact of radical prostatectomy and other treatments on potency should be discussed in detail when counselling patients with localised prostate cancer before therapy. However, erectile potency and a happy sex life do not go hand-in-hand, as 75% of respondents were happy or coping with their sexual function but only 12% claimed postoperative potency. This may be because people who have made a treatment decision are likely to believe, and want others to believe, that they have made the right choice,24 especially if they are disease free, as this group were. References Coates M, McCredie M, Armstrong BK. Cancer in New South Wales. Incidence and mortality, 1993. Sydney: NSW Cancer Council; 1996. McCredie M, Coates M, Churches T, Rogers J. The rising incidence of prostate cancer in Australia -- a result of "screening"? J Epidemiol Biostat 1996; 1: 99-105. McCaul KA, Luke CG, Roger DM. Trends in prostate cancer incidence and mortality rates in South Australia, 1977-1993. Med J Aust 1995; 162: 520-522. Hirst GHL, Ward JE, Del Mar CB. Screening for prostate cancer: the case against. Med J Aust 1996; 164: 285-288. Kaye KW. Prostate cancer: enthusiasm for screening. Med J Aust 1995; 162: 540-541. Whitmore WF Jr. Management of clinically localized prostatic cancer -- an unresolved problem [editorial]. JAMA 1993; 269: 2676-2677. Chodak GW, Thisted RA, Gerber GS, et al. Results of conservative management of clinically localized prostate cancer. N Engl J Med 1994; 330: 242-248. Freedman G, Hanlon M, Lee W, Hanks G. Young patients with prostate cancer have an outcome justifying their treatment with external beam radiation. Int J Radiat Oncol Biol Phys 1996; 35: 243-250. Madsen F, Bruskewitz R. Functional results of radical prostatectomy. Curr Opin Urol 1995; 5: 246-248. Fowler JF Jr, Barry MJ, Lu-Yao G, et al. Patient-reported complications and follow-up treatment after radical prostatectomy. The National Medicare Experience: 1988-1990 (updated June 1993). Urology 1993; 42: 622-629. Borghede G, Karlsson J, Sullivan M. Quality of life in patients with prostate cancer: results from a Swedish population study. J Urol 1997; 158: 1477-1486. Brickman AL, Soloway MS. Quality of life 12 months after radical prostatectomy. Br J Urol 1995; 75: 48-53. Herr HW. Quality of life of incontinent men after radical prostatectomy. J Urol 1994; 151: 652-654. Cella DF, Tulsky DS, Gray G, et al. The Functional Assessment of Cancer Therapy Scale: development and validation of the general measure. J Clin Oncol 1993; 11: 570-589. O'Leary MP, Barry MJ, Fowler FJ Jr. Hard measures of subjective outcomes: validating symptom indexes in urology. J Urol 1992; 148: 1546-1548. Barry MJ, Fowler FJ Jr, O'Leary MP, et al. Correlation of the American Urological Association symptom index with self-administered versions of the Madsen-Iversen, Boyarsky and Maine medical assessment program symptom indexes. J Urol 1992; 148: 1558-1563. STATA statistics package [computer program]. Version 5.0. Texas: Stata Corp; 1996. Diokno A, Brock BM, Brown M, Herzog A. Prevalence of urinary incontinence and other urological symptoms in the non-institutionalised elderly. J Urol 1986; 136: 1022-1025. Jonler M, Moon T, Brannan W, et al. The effect of age, ethnicity and geographical location on impotence and quality of life. Br J Urol 1995; 75: 651-655. Goluboff E, Chang D, Olsson C, Kaplan S. Urodynamics and the etiology of post prostatectomy urinary incontinence: the initial Colombia experience. J Urol 1995; 153: 1034-1037. Steiner MS, Morton RA, Walsh PC. Impact of radical prostatectomy on urinary continence. J Urol 1991; 145; 512-515. Jonler M, Messing EM, Rhodes RR, Bruskewitz RC. Sequelae of radical prostatectomy. Br J Urol 1994; 74: 352-358. Quinlan DM, Epstein JI, Carter BS, Walsh PC. Sexual function following radical prostatectomy: influence of preservation of neurovascular bundles. J Urol 1991; 145: 998-1002. Litwin MS, Hays RD, Fink A, et al. Quality of life outcomes in men treated for localized prostate cancer. JAMA 1995; 273: 129-135. Singer PA, Tasch E, Stocking C, et al. Sex or survival: trade-offs between quality and quantity of life. J Clin Oncol 1991; 9: 328-334. (Received 7 Apr 1997, accepted 24 Feb 1998) Authors' details Princess Alexandra Hospital, Brisbane, QLD. Peter S Heathcote, FRACS, Urologist; Peter N Mactaggart, FRACS, Urologist; Robyn J Boston, MB BS, Urology Registrar; Leslie C Thompson, FRACS, Urologist; David L Nicol, FRACS, Urologist. Royal Brisbane Hospital, Brisbane, QLD. Anthony N James, FRACS, Urologist. Reprints will not be available from the authors. Correspondence: Dr D L Nicol, Department of Urology, Princess Alexandra Hospital, Ipswich Road, Brisbane, QLD 4102. E-mail: D. NicolATmailbox.uq.edu.au Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia ".

Peter S Heathcote · Peter N Mactaggart · Robyn J Boston · Anthony N James · Leslie C Thompson · David L Nicol

Abstract Objective: To ascertain the effectiveness of a home vaccination service for children behind in their vaccination schedule. Design: Randomised controlled trial of nurse-administered vaccination at home. Children were allocated at random to the intervention or the control group before any contact with the parents was made. Setting: 10 council areas in north-west metropolitan Melbourne defined by 56 postcode zones. Six-week intervention period from November 1996. Participants: 405 children -- all those in the study area (n = 2610) 90 days late (age 9 months) for their third diphtheria-tetanus-pertussis/poliomyelitis/Haemophilus influenzae type B (DTP/OPV/Hib) vaccination, or 120 days late (age 16 months) for their measles-mumps-rubella (MMR) vaccination, according to the Australian Childhood Immunisation Register. Main outcome measures: Number of children completing DTP/OPV/Hib or MMR during the intervention period, and number up to date before intervention. Results: Verification of vaccination status with the parents revealed that 123 (60%) of the children in the intervention group and 113 (56%) of those in the control group were up to date with their vaccinations, leaving a study population of 81 (intervention group) and 88 (control group). Vaccination was achieved in 46 (57%) intervention children and 24 (27%) control children (risk ratio [RR], 2.08; 95% CI, 1.4-3.1; P < 0.001). For DTP/OPV/Hib, 18/32 (56%) intervention children and 12/36 (33%) control children were vaccinated (P = 0.06). For MMR, 28/49 (57%) and 12/52 (23%) children were vaccinated, respectively (P < 0.001). Home vaccinations were completed with 26 families (including five siblings). The average cost per child vaccinated as a result of the home program was $92.52. Conclusion: Home vaccination for children behind in their immunisation schedule is an effective, acceptable and relatively cheap method of completing recommended vaccinations. We recommend that a home vaccination program be widely implemented and made available, particularly for disadvantaged families. Introduction In Australia, incomplete immunisation of children under 2 years of age remains an important public health problem. Many children never complete their immunisation schedule or are many months overdue.1 Uptake rates are lowest for measles-mumps-rubella vaccination at age 12 months and the diphtheria-tetanus-pertussis booster at 18 months.1-3 Being late for a primary course is predictive of being late for or missing subsequent vaccinations.3,4Parents' beliefs about the seriousness of the vaccine-preventable illnesses and the safety and efficacy of vaccines are important predictors of vaccination uptake.5 However, there are other barriers to children being vaccinated -- frequent minor childhood illnesses, parental forgetfulness, and advice from health providers to delay vaccinations.6-10 A current strategy to overcome barriers to vaccination is to make vaccination more accessible, but parents are still required to bring their children to be vaccinated. For some families, however, it may be more effective to take the vaccination service to the child. We have explored (i) the effectiveness of offering a home vaccination service to children at greatest risk of not completing their immunisation schedule by age 2 years; and (ii) the usefulness of the Australian Childhood Immunisation Register (ACIR) for identifying these at-risk children. Method Participants The Australian Childhood Immunisation Register provided identifying information for children living in 10 local council areas in north-west metropolitan Melbourne (defined by 56 postcode zones) who were either born January 1996 and 90 days late for their third diphtheria-tetanus-pertussis/poliomyelitis/Haemophilus influenzae type B vaccination (DTP/OPV/Hib; 1st milestone), or born June 1995 and 120 days late for their measles-mumps-rubella vaccination (MMR; 2nd milestone). The intervention period comprised six weeks from November 1996. Making contact to verify vaccination status before randomisation would have in itself constituted an intervention. Therefore, before any contact was made with the parents, the children were allocated at random (by computer) to the intervention or the control group. Contact We made initial contact with the intervention group by letter, then by telephone one to three weeks later to verify vaccination status, to organise an appointment, and to administer a pre-vaccination health check as recommended by the National Health and Medical Research Council's Australian immunisation handbook.11 This health check was to ensure that the child did not require special medical attention and could be vaccinated at home. If no telephone contact could be made, two follow-up letters were sent. As local councils and maternal and child health nurses provide a substantial number of childhood vaccinations in Victoria and maintain vaccination records, we checked these (possible) providers for vaccination details if parents could not be contacted. Children were confirmed as either overdue for vaccination or up to date with vaccination if parents, the local council or the maternal and child health nurse provided a record of the vaccination. Intervention The study was approved by the Royal Children's Hospital Ethics in Human Research Committee. Parents signed a consent form to participate in the study and a standard State Government vaccination consent form. A nurse administered vaccination in the child's home at a time convenient to the parents. Siblings were also vaccinated if they were due for vaccination. The nurse providing the vaccination had completed a standard Victorian Government Department of Human Services immunisation course. A resuscitation kit (including adrenalin) was taken on each home visit, and the cold chain was maintained by transporting vaccines in a temperature-monitored car refrigerator. Before vaccination, the nurse administered a pre-vaccination health checklist11 to confirm the child's medical history, as obtained during the initial telephone contact, and to assess the child's health on the day of vaccination. Vaccines that were due were verified from the parent-held Child Health Record. The child's temperature was taken if he or she was hot or appeared unwell (a temperature > 38.58c precludes vaccination11). Paracetamol was offered to all children before vaccination. The nurse remained with the family for more than 20 minutes after vaccination. The visits included time for parents to complete questionnaires about immunisation service use, reasons for the delay in vaccination, education level, family size and whether the family had a Health Care Card. (A Health Care Card is a Federal Government card available to low income families, including those receiving government pensions, to obtain concessions for health and medical expenses; ie, it is an indicator of disadvantage or poverty.) Neither written consent nor sociodemographic information was obtained from parents who chose to have their child vaccinated by another provider, or whose child was up to date with immunisation, or who refused to take advantage of the home service. Follow-up of control children Two months after the intervention period, and based on updated information from the Australian Childhood Immunisation Register, we sent letters to parents of control children for whom neither the Register nor local councils had recorded a third DTP/OPV/Hib or an MMR vaccination. We followed the letters with a telephone call to verify vaccination status and to offer, in this case, vaccination at the Royal Children's Hospital. Parents of control children were also informed of local vaccination services offered by the maternal and child health nurse or of the schedules of mobile vaccination vans provided by local councils. No sociodemographic information was collected from the parents of control children. Cost analysis Costs included travel, estimated at $0.50 per kilometre, nursing time at $25 per hour, consumables (excluding vaccines) as charged by the Royal Children's Hospital and clerical work at $17 per hour for 18 days. Statistical analysis Sample size was estimated assuming that 35% of intervention children would accept vaccination and 6% of control children would be immunised. This would require 30 in each group, with a set at 0.05 and statistical power 80%. Statistical associations were assessed with chi-squared tests. Confidence intervals and risk ratios were calculated with the STATA program.12 Results Subjects There were 2610 children born in June 1995 or January 1996 in the study area and registered with the Australian Childhood Immunisation Register. Of these, 416 children (16%) were identified by the Register as overdue for their third DTP/OPV/Hib or MMR. The Figure shows the number of children on the Register meeting the study criteria, the number excluded and the vaccination status of the children in the intervention and control groups at the time of contact. On verification of vaccination status with parents, 123 (60%) of the intervention children and 113 (56%) of the control children were confirmed as being up to date with their immunisation schedule, and therefore were ineligible for the intervention, leaving 81 children in the intervention group and 88 control children. Those whose status could not be verified were assumed for analysis to be unvaccinated. In total, 2430 (93%) children were up to date with their vaccinations at the beginning of the study period: 1219 (95%; 95% confidence interval [CI], 93.6%-96.0%) 9-month-old children and 1211 (92%; 95% CI; 90.8%- 93.8%) 16-month-old children. Intervention Table 1 shows the number of children vaccinated during the intervention period. To estimate the effect of the intervention on uptake for the full cohort, the cohort was divided into two equal groups (n = 1305 each). The number of children immunised in the group with the intervention children increased from 1220 (93.5%) before intervention to 1266 (97%) after intervention. The group with the control children increased from 1210 (93%) to 1234 (95%). Using similar logic, but dividing for type of vaccine, in the group with intervention children the rate for 1st milestone vaccination increased to 98% and for 2nd milestone to 97%, whereas the rates for the group with control children increased to 96% and 94%, respectively. The mean (SD) age for DTP/ OPV/Hib vaccination for intervention and control children was 10 (0.2) months and 11.5 (0.3) months, respectively (which was significantly different; P < 0.001), compared with 7 (1.3) months for children having DTP vaccination before study commencement. The mean (SD) age for MMR vaccination for intervention and control children was 17.2 (0.1) months and 19 (0.3) months (P < 0.001), compared with 14 (1.7) months for those having MMR vaccination before study commencement. In the intervention group 26 children were immunised by the study nurse and 19 by their doctor or local council service. One child who had a severe egg allergy was vaccinated at the Royal Children's Hospital Immunisation Adverse Events Clinic. Ten children due for MMR were also given their 18-month DTP/Hib boosters and five siblings were brought up to date with their vaccination schedule. In all, 82 vaccines were administered to study children and siblings. On the day of vaccination 13 children had colds or were taking antibiotics; none had a fever. All were vaccinated as arranged. Two families refused the service because they were against immunisation and 22 families preferred to use their own doctor. As mentioned, 19 did so within the study period. One mother changed her mind about home vaccination because of concern about her child's egg intolerance. The child was vaccinated a month after the intervention by her doctor. Table 2 summarises the demographic information of those immunised at home and major reasons given by parents for delayed vaccinations. Costs The mean cost per child vaccinated in the intervention group was $92.52, and the mean cost per visit per vaccine was $52. These costs excluded cost of visits to the general practitioner by those being vaccinated by their own doctor. Fifty-one per cent of the cost was attributable to clerical time needed to verify vaccination status. Travel costs were 12% of total costs and 33% of nurses' costs. Discussion We have shown that offering home vaccination is an effective method of bringing children (and their siblings) up to date with their immunisation schedule. Importantly, we used information from a population-based register, and thus provided vaccinations for children in socially disadvantaged families. Such families have been identified previously by the Australian Bureau of Statistics13 and others14 as being most at risk of not completing the scheduled childhood immunisations. A major finding of this study was the unexpectedly high proportion of children already vaccinated at the commencement of the study. This proportion was substantially higher than expected from previous statewide estimates -- 95% v. 84% for 1st milestone vaccination and 92% v. 78% for 2nd milestone vaccination2 -- and exceptionally high given that our study was conducted in a socially disadvantaged area. Data for our study on children's vaccination status were from Australian Childhood Immunisation Register enrolments, which are derived from Medicare data and miss about 2% of children; however, this would have had a minimal impact on these vaccination estimates. It is also unlikely that substantial misclassification of vaccination status occurred. While we did not formally cross-check vaccination dates, when dates were obtained from two sources 85% matched. When dates differed it cannot be assumed that Register dates were correct. In some cases vaccinations reported to the Register by us were incorrectly recorded or missing. Thus, we found the usefulness of the Australian Childhood Immunisation Register as a source of accurate information to be limited. However, our study was undertaken in the first year of the Register's existence and it is expected that accuracy of the Register will improve. Limitations of this study arise from the need to randomise the population sample before verification of immunisation status. This has the potential to introduce bias because of the possibility of differences in response between the intervention and control groups. Another limitation was the number of children in each group with whom no contact was made. However, these limitations are unlikely to have caused substantial bias. In both groups a similar number of control (56%) and intervention children (60%) were excluded because they were up to date with vaccinations, and likewise the proportion of control (15%) and intervention children (14%) who could not be contacted to determine immunisation status was similar. There is also no reason to suppose that any differences in vaccination rates between these two uncontacted groups would be sufficient to bias the estimate of the intervention effect. Assuming that 50% of the children in each group who could not be contacted were vaccinated, the risk ratio for vaccination would be 1.67 (95% CI, 1.3-2.2; P < 0.001). Itinerancy is a risk factor for incomplete and late vaccination,3,15 making it not surprising that a considerable number considered overdue for vaccination could not be contacted. We have shown that those who can be contacted can be vaccinated. A similar program that accesses vaccination information at a local level may be more efficient at targeting families who move frequently. It is obvious that a home service will cost more than mass vaccination programs. The cost per vaccine, taking into account only nurses' time and travel costs, was about $23, which compares favourably with the £8 reported by an outreach program in the United Kingdom.16 The costs of the service would be reduced with improved accuracy of Australian Childhood Immunisation Register information (clerical costs would be reduced by 50%), by offering a local rather than a centralised service (travelling costs would be reduced by 30%), and by incorporating the vaccination service into a broader home visiting program to promote child health and support disadvantaged families in this endeavour. As indicated by many studies,17-22 a barrier to age-appropriate immunisation is often not parental unwillingness to have their child vaccinated, but immunisation providers failing to provide a service. About a third of the parents of children behind in their vaccinations reported having recently consulted a doctor. In almost all these cases the child could have been vaccinated at that time. To prevent diseases such as measles, immunisation rates need to exceed 95%.23 Even the high uptake rates found at the commencement of our study are below this level. Innovative and proactive methods are necessary to attain these high levels and have been found to be effective.15,24 Acknowledgements This study was funded by National Health and Medical Research Council (NHMRC) project grant number HS371. Lyndal Bond was funded by an NHMRC Scholarship. We would like to thank the research nurse (Michelle Wills), the Royal Children's Hospital Immunisation Adverse Events Clinic for providing a service for children in the intervention and control groups, and local council health departments for their cooperation. References Australian Bureau of Statistics. Children's immunisation Australia. Canberra: ABS, April 1995, 1996. (Catalogue No. 4352.0.) Lester R, Norris P. 1994/5 Pre-school immunisation coverage. Notifications for Victoria, July-September 1995. Health Protection Update (Public Health Division, Department of Human Services, VIC) 1995; 3: 10-13. Hanna CJ, Wakefield JE, Doolan CJ, Messner JL. Childhood immunisation factors associated with failure to complete the recommended schedule by two years of age. Aust J Public Health 1994; 18: 15-24. Li J, Taylor B. Factors affecting uptake of measles, mumps, and rubella immunisation. BMJ 1993; 307: 168-171. Peckham C, Bedford H, Senturia J, Ades A. The Peckham Report National Immunisation Study: factors influencing immunisation uptake in childhood. Horsham: Action Research For The Crippled Children, 1989. Jones K, Fasher B, Hanson R, et al. Immunisation status of casualty attenders: risk factors for non- compliance and attitudes to "on the spot" immunisation. J Paediatr Child Health 1992; 28: 451-454. Miles TA, Merrell WH. An outbreak of measles in the Hunter area of New South Wales. Aust J Public Health 1992; 16: 302-304. New SJ, Senior ML. "I don't believe in needles": qualitative aspects of a study into the uptake of infant immunisations in two English health authorities. Soc Sci Med 1991; 33: 509-518. Harding GC. How can the uptake of vaccines be increased? J Inst Health Educ 1984; 22: 5-11. Adjaye N. Measles immunisation: some factors affecting non-acceptance of vaccine. Public Health 1981; 95: 185-188. National Health and Medical Research Council. The Australian immunisation handbook. 6th ed. Canberra: AGPS, 1997. Stata Statistical Software [computer program], Release 5.0. College Station, Tex: Stata Corporation, 1997. Australian Bureau of Statistics. 1989-90 National Health Survey children's immunisation, Australia. Canberra: AGPS, 1992. Bazeley P, Kemp L. Childhood immunisation: the role of parents and service providers. A review of the literature. Canberra: National Immunisation Programme, Commonwealth Department of Human Services and Health, AGPS, 1994. Pearson M, Makowiecka K, Gregg J, et al. Primary immunisations in Liverpool II: is there a gap between consent and completion? Arch Dis Child 1993; 69: 115-119. Jefferson N, Sleight G, MacFarlane A. Immunisation of children by a nurse without a doctor present. BMJ 1987; 294: 423-424. MacIntyre R, Nolan T. Attitudes of Victorian vaccine providers to pertussis vaccine. Med J Aust 1994; 161: 295-299. Burgess MA. Pertussis vaccine -- time to stop the confusion. Med J Aust 1994; 161: 293-294. Begg NT, Nicholl A. Immunisation. BMJ 1994; 309: 1073-1075. Stevens D, Baker R, Hands S. Failure to immunise against whooping cough. Arch Dis Child 1986; 61: 382-387. Kinder J, Teare L, Rao M, et al. False contraindications to childhood immunisation. Br J Gen Pract 1992; 42: 160-161. Askew GL, Finelli L, DeGraaf J, et al. Beliefs and practices regarding childhood vaccination among urban pediatric providers in New Jersey. Pediatrics 1995; 96: 889-892. Nolan T. Measles -- eradication or procrastination? Med J Aust 1990; 152: 449-450. Birkhead GS, LeBaron CW, Parsons P, et al. The immunisation of children enrolled in the special supplemental food program for women, infants and children (WIC). JAMA 1995; 274: 312-316. (Received 29 Sep 1997, accepted 6 Apr 1998) Authors' details Clinical Epidemiology and Biostatistics Unit, Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Melbourne, VIC. Lyndal M Bond, MA(ApplPsych), NHMRC Scholar. Terry M Nolan, PhD, FRACP, FAFPHM, Head, Clinical Epidemiology and Biostatistics Unit. Department of Human Services, Melbourne, VIC. Rosemary A Lester, MB BS, MPH, FAFPHM, Head, Infectious Diseases Unit. Reprints: Ms Lyndal Bond, Clinical Epidemiology and Biostatistics Unit, Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Parkville, VIC 3052. E-mail: bondATcryptic.rch.unimelb.edu.au Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia ".

Lyndal M Bond · Terry M Nolan · Rosemary A Lester

Asthma and other atopic diseases in Australian children Australian arm of the International Study of Asthma and Allergy in Childhood Colin F Robertson, Marita F Dalton, Jennifer K Peat, Michelle M Haby, Adrian Bauman, J Declan Kennedy and Louis I Landau MJA 1998; 168: 434-438 Abstract - Introduction - Methods - Results - Discussion - Acknowledgements - References - Authors' details - - ©MJA1998 Abstract Objective: To determine the prevalence of asthma, eczema and allergic rhinitis in Australian schoolchildren using the protocol of the International Study of Asthma and Allergy in Childhood (ISAAC). Design: Questionnaire-based survey. Setting: Melbourne, Sydney, Adelaide (in winter-spring, 1993) and Perth (in winter-spring, 1994). Subjects: All children in school years 1 and 2 (ages 6-7 years) or in year 8 (ages 13-14 years), attending a random sample of 272 schools, stratified by age and city. Main outcome measures: Parent-reported (for 6-7 year olds) or self-reported (for 13-14 year olds) symptoms of atopic disease in the previous 12 months, or ever; treatment of asthma; and country of birth. Results: 10 914 questionnaires were completed for 6-7 year olds and 12 280 for 13-14 year olds (84% and 94% response rates, respectively). Prevalence of wheeze in the past 12 months was 24.6% for the 6-7 year olds and 29.4% for the 13-14 year olds, and, among 6-7 year olds, was significantly higher in boys (27.4%) than girls (21.7%). Children born in Australia were more likely to report current wheeze than those born elsewhere (6-7 year olds: odds ratio [OR], 1.82; 95% confidence interval [CI], 1.55-2.15; and 13-14 year olds: OR, 1.88; 95% CI, 1.68-2.11). Prevalences of current eczema and allergic rhinitis were 10.9% and 12.0%, respectively, for the 6-7 year olds, and 9.7% and 19.6%, respectively, for the 13-14 year olds. Asthma, eczema and rhinitis coexisted in 1.8% of 6-7 year olds and 2.8% of 13-14 year olds. Conclusion: This study provides evidence that asthma prevalence in Australian schoolchildren is continuing to increase and is higher among Australian-born children than among those born elsewhere. Asthma, eczema and allergic rhinitis coexist to a lesser extent than expected. These results form the basis for future Australian and international comparisons. Introduction There is now substantial evidence that the prevalence of asthma and other atopic disorders is increasing worldwide.1,2 While the prevalence of asthma has been documented in the past 30 years, variation in methods and lack of uniform diagnostic criteria make direct comparison between studies difficult. Little is known about the prevalence of the other atopic disorders -- eczema and allergic rhinitis -- both throughout the world and particularly in Australia. The International Study of Asthma and Allergy in Childhood (ISAAC) is a collaborative project which has developed a standardised methodology to describe the prevalence and severity of asthma, rhinitis and eczema in children throughout the world.3 Such data will provide a framework for aetiological research into lifestyle, environmental and genetic factors affecting these disorders. Phase 1 of ISAAC is to determine the prevalence of the disorders throughout the world. Phases 2 and 3 will be more comprehensive, using more detailed questionnaires and objective measures to confirm the differences seen in Phase 1 and to identify important aetiological factors. Our study was part of Phase 1 of ISAAC. It aimed to determine the prevalence of asthma and other atopic diseases in Australian schoolchildren, to determine the burden of atopic disease in this country, and to provide a basis for international comparison. Methods We used the protocol of ISAAC3 to survey two age groups: 6-7 year olds (school years 1 and 2) and 13-14 year olds (school year 8). Subjects were all children in the relevant years of a random sample of primary and secondary schools. The sample comprised about 10% of all government, Catholic and independent schools in the metropolitan areas of Adelaide and Perth; the area within a radius of 20 km from the GPO in Melbourne; the area within a radius of 10 km from the GPO in Sydney for primary schools (school years 1 and 2); and the Western Region of Sydney for secondary schools (school year 8). Previous studies have shown these areas of Sydney and Melbourne to be representative of the metropolitan areas of these cities.4,5 A five-page questionnaire was issued by teachers for completion by parents of the 6-7 year olds, and by the 13-14 year olds in the classroom under examination conditions. The questionnaires contained the three standard ISAAC modules, asking about symptoms of asthma, eczema and allergic rhinitis3 (see Box 1 for definitions), an additional module about treatment of asthma, and two extra questions about the children's and mothers' country of birth. No translations were provided. If the first questionnaire was not returned by the 6-7 year olds, a second was issued. A second visit was made to the secondary schools, if necessary, to recruit students absent at the initial visit. Data were analysed with the statistical package SPSS-X.9 Results were adjusted for cluster effect, and chi-squared tests were used to compare prevalences, while significance of odds ratios (OR) was assessed with 95% confidence intervals (CIs). Results Details of schools and subjects surveyed are shown in Box 2; 201 primary schools and 71 secondary schools participated, comprising 7%-42% of schools in the sampling area; 9% of schools selected declined to participate. A total of 12 952 questionnaires were issued to the 6-7 years age group (response rate, 84%) and 13 078 to the 13-14 years age group (response rate, 94%). Prevalence of atopic diseases in the two age groups is shown in Box 3. Asthma Prevalence of current wheeze was 24.6% for the 6-7 year olds (95% CI, 23.8-25.4), and 29.4% for the 13-14 year olds (95% CI, 29.1-29.7) (Box 3). In the younger group, current wheeze was significantly more common in boys than in girls (OR, 1.36; 95% CI, 1.25-1.49), but this sex difference was reversed in the older group (OR 0.82; 95% CI, 0.76-0.89). Figure 1 (below) compares the prevalence of atopic diseases between the four cities. For the 6-7 year olds, there was no significant difference in prevalence of current wheeze between cities, but for the 13-14 year olds prevalence was slightly higher in the western cities (Adelaide and Perth: 32.3%) than in the eastern cities (Sydney and Melbourne: 25.9%) (OR, 1.37; 95% CI, 1.26-1.48). There was a similar difference between west and east in percentage of 13-14 year olds who had had more than 12 episodes of wheeze per year (4.1% versus 3.1%) and who had attended the emergency department (3.5% versus 2.9%) (data not shown). The prevalence of current wheeze was generally higher in the older age group. The spectrum of asthma among children who reported current wheeze is shown in Box 4. While most children in both age groups reported only one to three asthma episodes in the previous 12 months, 8.0% of 6-7 year olds and 12.2% of 13-14 year olds reported more than 12 episodes. Sleep disturbance due to asthma was common, with 11.2% of 6-7 year olds and 9.8% of 13-14 year olds reporting sleep disturbance on one or more nights per week. About 7% of both age groups reported a hospital admission for asthma in the previous 12 months. Patterns of asthma treatment are shown in Box 5. Regular b2-agonists were taken as sole therapy by 5.5% of 6-7 year olds and 7.4% of 13-14 year olds with current wheeze, while regular inhaled steroids were taken by 21.1% of 6-7 year olds and 14.6% of 13-14 year olds, rising to 49.7% and 36.9% for those with more than 12 episodes per year. While overall 26.5% of 6-7 year olds with current wheeze and 15.8% of 13-14 year olds had a written asthma management plan, this increased to 46.5% and 25.9% in those who reported 12 or more attacks in the past 12 months. Most children attended a doctor at least once during a wheezy episode throughout the year, but only 42.2% of 6-7 year olds and 31.3% of 13-14 year olds visited a doctor for a regular check-up. Eczema Prevalence of current eczema did not vary significantly between the cities (Box 3). Eczema was less common in boys than in girls in both age groups (6-7 year olds: OR, 0.81; 95% CI, 0.72-0.92; 13-14 year olds: OR, 0.57; 95% CI, 0.51-0.65). Sleep disturbance due to itching was common among those with current eczema; it was reported to occur at least weekly by 7.9% of 6-7 year olds and 13.4% of 13-14 year olds, and at a lesser frequency by 27% of 6-7 year olds and 30.4% of 13-14 year olds. Allergic rhinitis The prevalence of current allergic rhinitis was significantly higher in Adelaide and Perth than in Sydney and Melbourne (6-7 year olds: OR, 1.62; 95% CI, 1.44-1.82; 13-14 year olds: OR, 1.53; 95% CI, 1.40-1.68). Like wheeze, rhinitis was more common in boys than girls in the younger group (boys versus girls: OR, 1.19; 95% CI, 1.06-1.33), while this sex difference was reversed in the older group (boys versus girls: OR, 0.64; 95% CI, 1.40-1.68). Among those with current rhinitis, 71% of 6-7 year olds and 76% of 13-14 year olds reported that it interfered with their daily activity to some extent (troublesome rhinitis), while 18.5% of 6-7 year olds and 19.1% of 13-14 year olds described this interference as moderate to "a lot". Atopic disease and country of birth Children born in Australia were more likely to report current wheeze than those born elsewhere (6-7 year olds: OR, 1.81; 95% CI, 1.54-2.14; 13-14 year olds: OR 1.89; 95% CI, 1.69-2.12). This trend was similar for children whose mothers were born in Australia compared with those whose mothers were born elsewhere (6-7 year olds: OR, 1.29; 95% CI, 1.18-1.42; 13-14 year olds: OR, 1.58; 95% CI, 1.45-1.71). When children born outside Australia were analysed by region of birth (United Kingdom, Central Europe, South-East Asia or the Middle East), there was no difference in the prevalence of wheeze between regions. Eczema and rhinitis were also more common in children born in Australia than those born elsewhere. For eczema the OR was 1.31 (95% CI, 1.06-1.63) for 6-7 year olds and 1.36 (95% CI, 1.14-1.61) for 13-14 year olds. For rhinitis, the OR was 1.79 (95% CI, 1.42-2.26) for 6-7 year olds and 1.5 (95% CI, 1.32-1.70) for 13-14 year olds. The proportion of children born outside Australia was higher in the eastern cities among 13-14 year olds (23%) than in the western cities (15%). Similarly, the proportion of mothers born outside Australia was higher in the eastern cities (54%) than in the western cities (39%). When the odds ratio comparing prevalence of wheeze among 13-14 year olds in western versus eastern cities was adjusted for child's country of birth, it fell from 1.37 to 1.25 (95% CI, 1.15-1.36). Interrelations of atopic diseases Figure 2 (below) shows the overlap of asthma, eczema and allergic rhinitis. While 35.2% of 6-7 year olds reported having at least one of these conditions in the past 12 months, only 1.8% reported having all three. Corresponding figures for 13-14 year olds were 41% with at least one condition and 2.8% with all three. Among those with current wheeze, only 19% of 6-7 year olds and 18% of 13-14 year olds reported coexistent current eczema, with no apparent age effect in the relationship. Discussion This study describes the burden of atopic disease in Australian schoolchildren. The prevalence of current wheeze was similar to that reported in recent epidemiological studies in Australia.10 However, comparison with results of a similar questionnaire given to Melbourne schoolchildren in 1990 suggests that, although the spectrum of asthma remains unchanged, the prevalence of recent wheeze has increased from 23.1% in 1990 (95% CI, 21.7-24.5)4 to 27.2% in 1993 (95% CI, 25.6-28.8) (P < 0.01). The rate of increase (1.4% per annum) is similar to that reported in an earlier Australian study (1.24%)10 and higher than that reported in European studies (0.1%-0.4%).1 Morbidity due to asthma remains significant, with high levels of symptoms, emergency department attendances and hospital admissions. Asthma is the second most common reason for admission to a paediatric hospital bed in Victoria (after otolaryngological conditions), with a rate in children of 738 per 100 000 population in 1994-1995.11 The total annual cost to the community associated with asthma management in Australia was estimated in 1989 as $627 million, or $769 per asthmatic person.12 These costs are likely to have increased because of the increases in medication costs and asthma prevalence. There was a significant difference in the prevalence of current wheeze and current rhinitis between the eastern and western States. A possible explanation is the difference in patterns of immigration, with more children in the eastern cities born outside Australia than in the western cities. Indeed, the odds ratio comparing prevalence of wheeze among 13-14 year olds in western versus eastern cities fell from 1.37 to 1.25 after adjustment for country of birth. Internationally, ISAAC has collected data on over half a million children from 120 centres in 48 countries. Australia ranks third-highest in prevalence of current wheeze for 13-14 year olds and second-highest for 6-7 year olds.13 For "current rhinitis", Australia ranks fifth and, for eczema, eleventh. Australia's high ranking for asthma prevalence is supported by data for asthma mortality. This was not collected by ISAAC, but comparison of available data from 11 developed countries shows Australia had the highest mortality rate due to asthma in 1990.14 We found evidence from throughout Australia for continuing lack of effective treatment of asthma. Among children with more than 12 episodes of wheeze per year, only 64% of 6-7 year olds and 43% of 13-14 year olds were taking regular preventive treatment. Further, 5.5% and 7.4% of those reporting "current wheeze" used regular b -agonists in the absence of any preventive therapy, despite the cumulative evidence against the practice. Sodium cromoglycate was used by 19% of the 6-7 year olds and 11% of the 13-14 year olds who reported taking regular preventive therapy, showing some support for the Australian paediatric asthma guidelines, which recommend cromoglycate as first-line therapy for mild to moderate persistent asthma.15 We also found eczema and rhinitis to be common and to cause significant morbidity among Australian schoolchildren. Eczema was less common in boys than in girls in both age groups, a trend seen throughout the world.16 It is not life-threatening, but may cause considerable physical and psychological disability (including discomfort from itching, which may result in sleep loss and secondary infection, as well as the psychological effects of a visible skin disease). Treatment can be expensive and time consuming. Recent Australian estimates of the cost to the family were $330 to $1255 a year, depending on eczema severity.17 Additional costs to the community for consultations ranged from $209 to $642 a year for each child. Allergic rhinitis also carries significant morbidity. The effect on quality of life of perennial rhinitis has been estimated to be similar to, or worse than, mild to moderate asthma.18 In adults, hayfever is estimated to cause, on average, the loss of a third of a day from work each year, in addition to loss of productivity through symptoms or the sedating effects of some drug treatments.18 There are no precise estimates for the cost of therapy, as many sufferers do not consult a medical practitioner,8 and most treatment is available "over the counter". The higher prevalence of "current wheeze" found among 13-14 year olds compared with 6-7 year olds should be interpreted with caution, as the respondents differed between the two groups (parents for the 6-7 year olds and the children themselves for the 13-14 year olds). In an earlier study of Melbourne 7-year-olds and 15-year-olds, in which parents completed the questionnaire for both age groups, prevalence of "current wheeze" was lower among the 15-year-olds (18.6%) than among the 7-year-olds (23.1%).4 Further, comparison of adolescent and parent responses to an Australian asthma morbidity questionnaire showed that the adolescents reported a higher incidence of symptoms than their parents.19 The correlation between the three atopic diseases was less than anticipated. Atopy is usually associated with increased serum levels of IgE and positive skin reactivity to common allergens and has a strong genetic basis. The factors that determine the phenotypic expression of atopy and direct it to asthma, eczema or hayfever are unclear. This diverse expression of the genotype needs to be considered when studying the genetics of asthma. In conclusion, Australia has a high prevalence of atopic disorders, ranking among the highest in the world. Our study, part of a much larger international study, provides an opportunity to gain new insights into the causes and natural history of these disorders. Acknowledgements We would like to thank the schools, parents and children who participated, the research assistants who helped collect the data, and the State departments of education that approved the study. In Adelaide, the study was supported by Rotary, in Perth by the Asthma Foundation of Western Australia, and in Melbourne and Sydney by internal department funds. References Magnus P, Jaakkola JJK. Secular trends in the occurrence of asthma among children and young adults: critical appraisal of repeated cross sectional surveys. BMJ 1997; 314: 1795-1799. Wuthrich B. Epidemiology and natural history of atopic dermatitis. Allergy Clin Immunol Int 1996; 83: 77-82. Asher I, Kiel U, Anderson HR, et al. International study of asthma and allergies in childhood (ISAAC): rationale and methods. Eur Resp J 1995; 8: 483-491. Robertson CF, Heycock E, Bishop J, et al. Changes in prevalence of asthma in Melbourne schoolchildren over 26 years. BMJ 1991; 302: 1116-1118. Peat JK, Toelle BG, Gray EJ, et al. Prevalence and severity of childhood asthma and allergic sensitisation is seven regions of New South Wales. Med J Aust 1995; 163: 22-26. Jenkins MA, Clarke JR, Carlin JB, et al. Validation of questionnaire and bronchial hyperresponsiveness against respiratory physician assessment in the diagnosis of asthma. Int J Epidemiol 1996; 25: 609-616. Williams HC, Burney PGJ, Pembroke AC, Hay RJ. Validation of the UK diagnostic criteria for atopic dermatitis in a population setting. Br J Dermatol 1996; 135: 12-17. Sibbald B, Strachan DP. Epidemiology of rhinitis. In: Busse WW, Holgate ST, editors. Mechanisms in asthma and rhinitis: implications for diagnosis and treatment. Oxford: Blackwell Scientific Publications, 1994: 32-43. Norusis MJ. SPSS/PC+ Advanced Statistics. V5.0 [computer program]. Chicago, Ill:SPSS Inc, 1992. Peat JK, van den Berg RH, Green WF, et al. Changing prevalence of asthma in Australian children. BMJ 1994; 308: 1591-1596. Information Analysis Unit, Acute Health, Victorian Department of Human Services. Victorian inpatient mordibity database. Melbourne: Department of Human Services. Sighted Oct 1997. Toelle BG, Peat JK, Mellis CM, Woolcock AJ. The cost of childhood asthma to Australian families. Pediatr Pulmonol 1995; 19: 330-335. Beasley R, Keil U, von Mutius E, et al. Worldwide variation in the prevalence of symptoms of asthma, allergic rhinoconjunctivitis and atopic eczema: the international study of asthma and allergies in childhood (ISAAC). Lancet 1998. In press. Robertson CF, Sennhauser F, Mallol J. The change in prevalence and severity of asthma in developed and developing countries. Phelan PD (ed). Baillieres Clin Paediatr 1995; 3: 253-275. National Asthma Campaign. Asthma management handbook. 3rd edition. Melbourne: National Asthma Campaign, 1996. Williams HC, Robertson CF, Stewart AW, et al. Worldwide variation in the prevalence of symptoms of atopic eczema in the International Study of Asthma and Allergies in Childhood. J Allergy Clin Immunol 1998. In press. Su JC, Kemp AS, Varigos GA, Nolan TM. Atopic eczema: its impact on the family and financial cost. Arch Dis Child 1997; 76: 159-162. Juniper EF. Measuring health-related quality of life in rhinitis. J Allergy Clin Immunol 1997; 99: S742-S749. Bishop J, Robertson CF, Caust J, et al. Concordance between adolescent and parent response to an asthma morbidity questionnaire. Am Rev Respir Dis 1993; 147: A373. Received 30 Oct 1997, accepted 10 Mar 1998 Authors' details Department of Thoracic Medicine, Royal Children's Hospital, Melbourne. Colin F Robertson, MSc, FRACP, Deputy Director; Marita F Dalton, Assoc Dip Med Rec, Research Assistant. Department of Medicine, University of Sydney, Sydney. Jennifer K Peat, PhD, Senior Research Fellow; Michelle M Haby, MAppSc, Research Assistant. School of Community Medicine, University of New South Wales, Sydney. Adrian Bauman, PhD, FAFPHM, Associate Professor. Department of Respiratory Medicine, Women's and Children's Hospital, Adelaide. J Declan Kennedy, MD, FRCP, Physician. Department of Respiratory Medicine, Princess Margaret Hospital for Children, Perth. Louis I Landau, MD, FRACP, Professor of Paediatrics. Reprints will not be available from the authors. Correspondence: Dr C F Robertson, Department of Thoracic Medicine, Royal Children's Hospital, Flemington Road, Parkville, VIC 3054. E-mail: cfrobATcryptic.rch.unimelb.edu.au Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/> © 1998 Medical Journal of Australia.

Colin F Robertson · Marita F Dalton · Jennifer K Peat · Michelle M Haby · Adrian Bauman · Louis I Landau

Severe cervical spinal cord injuries related to rugby union and league football in New South Wales, 1984-1996 Tai R Rotem, James S Lawson, Stephen F Wilson, Stella Engel, Sue B Rutkowski and Chris W Aisbett MJA 1998; 168: 379-381 For editorial comment see Yeo Correction note: This article was published online with a typographic error that was corrected on 15 June 1998: A P value of 0.06 was misprinted as 0.6. Jump to corrected par. Abstract - Introduction - Methods - Results - Discussion - Acknowledgement - References - Authors' details - - ©MJA1998 Abstract Objective: To determine the frequency and circumstances of serious cervical cord injuries associated with rugby union and league football in New South Wales. Design: Retrospective review of patients with rugby football-related cervical spinal cord injuries. Setting: The two central spinal units in NSW, from January 1984 to July 1996. Outcome measures: Admission to spinal units; injury resulting in permanent tetraplegia. Results: During the review period, 115 rugby football players (56 union and 59 league) were admitted to the spinal units because of cervical spinal cord injuries. 49 patients had resultant permanent neurological deficits (complete tetraplegia [quadriplegia]) -- 26 associated with rugby union and 23 with rugby league. Two patients died of injury sequelae within two weeks of admission. There was no significant change in the rate of football-related admissions to spinal units for either code. There was a small decline in the number (from 15 in 1984 to 1987 to 7 in 1992 to 1996) and incidence (from 1.2 to 0.5 per 10 000 participants) of patients with tetraplegia associated with rugby union. When this decline was tested as a trend over the years, it was found to be statistically significant (P = 0.06). No significant trend was found in the tetraplegia data associated with rugby league. Cervical spinal cord injuries leading to complete tetraplegia were most commonly associated with scrum-like plays in union and with tackles in league. Conclusion: Serious cervical spinal injuries associated with both codes of rugby continue to occur in NSW. Rugby football in its various forms is still an inherently dangerous game. Introduction Injury to the cervical spinal cord sustained while playing rugby union or league football has tragic personal consequences, with subsequent high demands on community resources.1 During the 1970s and early 1980s there was an approximately twofold increase in the incidence of such injuries in many countries,2-4 possibly because of the development of more powerful scrums and tackles (see Box for terms). In response, between 1984 and 1996, new rules were introduced intermittently, existing rules were more strictly enforced, and "safety" programs were offered -- these included exercises for strengthening players' neck muscles and the banning of players with long thin necks from taking dangerous positions, such as the front row of scrums. We report the findings of a survey of rugby union- and league-related cervical spinal cord injuries in New South Wales (NSW) for the period 1984 to 1996. Methods We retrospectively reviewed the medical records of all patients admitted to the two central spinal units in NSW (at the Royal North Shore Hospital and Prince Henry Hospital, Sydney) because of cervical spinal cord injuries associated with rugby union and rugby league football from January 1984 to December 1996. Patients transferred from outside NSW were excluded from the analysis. Almost all patients (more than 95%) with spinal injuries that occur in NSW are admitted to these two units. Additional information about the circumstances of the injuries, including eyewitness reports of the events leading to them, was obtained from the NSW Sporting Injuries Committee -- a statutory authority which administers an insurance scheme for people permanently injured while playing sports. We also estimated the number of participants in rugby union and league football in NSW per year in the review period, based on the Committee's data5 plus surveys of NSW schoolboy football participants.6 As some of these data were incomplete and there was some duplication, these estimates are broad approximations only. Statistical analysis The number of cervical spinal cord injury cases is small, so any statistical analysis necessarily lacks power. To develop valid conclusions from this study, we analysed cases of cervical spinal cord injuries according to: total number of admissions to the two spinal units; permanent neurological deficits (ie, complete tetraplegia); and trends during the review period. When there are large numbers of participants and the risk of cervical spinal cord injury to any particular player is very low over a short time period -- and the injury is permanent and will not allow a return to the game -- the number of injuries in each year is assumed to follow a Poisson distribution. In the absence of data on hours of playing football or training for football, we assumed that the total number of hours devoted to the game for each code and grade did not vary from year to year. The null hypothesis for each test we performed was that there was no change in aggregated risk of cervical spinal injury against the alternative that the risk had decreased. All tests were based on the null-hypothesis assumption that the best estimate of annual rate of injuries was the average rate of injuries. We then fitted a simple linear regression, of time, to a probability transformation of the injury data. The number of injuries for each year was converted to the probability of observing, at most, that number of injuries in a particular year. These values were then converted to their corresponding standard normal score. The tests were based only on the regression slopes, which were tested to see if they were negative. The critical level of significance for these tests was 0.1. All calculations were performed using Microsoft Excel. The function POISSON was used to calculate the cumulative probabilities; the function NORMINV was used to calculate the standard normal scores; the function LINEST was used to calculate the slope and its standard error; and the function TDIST (one-tailed 11 degrees of freedom) was used to obtain the significance of the results. The Random Number Generator was used in a small simulation study to confirm the size of the testing procedure. Results During the 13-year period of the review, 117 rugby football players (56 union and 59 league players, plus one "backyard" and one "touch" player) were admitted to the spinal units because of cervical spinal cord injuries. The injuries were associated with permanent neurological deficits which led to complete tetraplegia (quadriplegia) in 26 union and 23 league players and in both the "backyard" and the "touch" football players. (The touch and backyard football players were not included in this analysis because they were not playing according to official union or league rules [Table 1].) The 23 "unspecified" admissions shown in Table 1 could not be included in the formal analysis because the football code was omitted from their clinical records. Two patients died of pneumonia within 14 days of sustaining the cervical spinal cord injuries. The age range of the injured players from both codes was 15-37 years (median, 22 years); all were male. The number of patients admitted per year to the spinal units because of cervical spinal cord injuries varied widely: from one to nine per year for league and one to eight per year for union. The number of players who had permanent tetraplegia varied from none to five per year for league and none to six for union (Table 1). Incidence and trends There were about 106 000 participants in rugby league and about 31 000 in rugby union in NSW during each year of the review.5,6 Trends in rates of admissions and incidence of permanent neurological deficits per 10 000 participants are shown in Table 2. Using the data shown in Table 1, there was no decline in the number (and hence the rate) of admissions for union (P = 0.21) or league (P = 0.33) players. There was a small but significant decline for union in the number and hence the incidence (P = 0.06) of players with permanent neurological deficits, but no significant decline for league (P = 0.16). Type of play associated with severe cervical spinal cord injuries Although detailed self-reports and eyewitness accounts of the events surrounding the injuries were available for 43 of the 49 patients with complete tetraplegia, no consistent patterns of play or events could be identified other than that the injury occurred in scrum-like plays (scrums, mauls and rucks; n = 23) or tackles (n = 26). Repeatedly, eyewitnesses observed that a player was found paralysed on the ground, without an obvious causal explanation, while the general play moved on. This lack of a specific, out-of-the-ordinary event was supported by two video recordings of cervical spinal cord injuries that occurred during scrums. The injuries were most common in scrum-like plays in union and in tackles in league. The most common level of spinal cord damage was C4-5 (Table 3). Discussion Despite its limitations as a retrospective study (such as the use of records created for other purposes), the findings of this review are disturbing. While for union players there was a small reduction in both the number and incidence of those with permanent neurological deficits leading to tetraplegia, there were no such changes for league players. Nor were there any changes for either code in the number of players admitted or rates of admission to spinal units. While any fall in the number and incidence of permanent neurological deficits among union players is pleasing and may well be a consequence of rule changes and safety measures,7 the unchanged rate of admissions to spinal units suggests that such improvements may not be sustained. In those players admitted to spinal units who do not experience permanent neurological deficits, the injuries can be regarded as "near misses" (ie, possible damage to the vertebral column without spinal cord injury).7 While evacuation procedures for suspected cervical and other spinal cord injuries may vary, such "near misses" included in the admission rates offer a useful indicator of the risks of such injuries associated with rugby union and league football.8 Our observation that cervical spinal cord injuries are more common in scrum-like plays in union and tackles in league is similar to recent findings in New Zealand.7 However, there is insufficient information in this review and in the New Zealand7 and other reviews9 of rugby football-associated spinal cord injury upon which to base sound recommendations for detailed changes to the rules or other safety measures. These reviews confirm the obvious -- that both rugby union and league are inherently dangerous games. There appear to be several options: Maintain the status quo and accept that each year several union and league players in NSW (and elsewhere) will suffer cervical spinal cord injuries which will leave them permanently paralysed below the neck; For rugby union, change the rules so as to substantially reduce the number of scrum-like plays and change the organisation of the scrum; For rugby league, introduce changes to the rules aimed at substantially altering the nature of the tackle. Acknowledgement This study was conducted with a grant from the NSW Sporting Injuries Committee. Disclaimer of conflict of interest: Apart from providing access to their own case files, the NSW Sporting Injuries Committee was in no way involved with the collection or analysis of data and did not have the right to disapprove or influence the contents of the manuscript. References Yeo JD. Prevention of spinal cord injuries in an Australian study (NSW). Paraplegia 1993; 31: 759-763. Taylor TKF, Coolican MRJ. Spinal cord injuries in Australian footballers, 1960-1985. Med J Aust 1987; 147: 112-118. Silver JR. Injuries of the spine sustained during rugby. BMJ 1984; 288: 37-43. Silver JR, Stewart D. The prevention of spinal injuries in rugby football. Paraplegia 1994; 32: 442-453. NSW Sporting Injuries Scheme. Annual reports of the NSW Sporting Injuries Committee. Sydney 1984 to 1995. Sydney: NSW Sporting Injuries Committee, 1984-1995. Northern Sydney Area Health Service. NSW Youth Sports Injury Report. July 1997. Sydney: Northern Sydney Area Health Service, 1997. Armour KS, Clatworthy BJ, Bean AR, et al. Spinal injuries in New Zealand rugby and rugby league -- a twenty-year survey. N Z Med J 1997; 110: 462-465. Noakes T, Jakoet I. Spinal cord injuries in rugby union players: How much longer must we wait for proper epidemiological studies? BMJ 1995; 310: 1345-1346. Kew T, Noakes TD, Kettles AN, et al. A retrospective study of spinal cord injuries in Cape Province rugby players, 1963-1989. S Afr Med J 1991; 80: 127-133. (Received 18 Sep 1997, accepted 27 Jan 1998) Authors' details School of Health Services Management, Faculty of Medicine, University of NSW, Sydney, NSW. Tai R Rotem, BSocSci, Research Fellow; James S Lawson, MD, MHA, Professor; Chris W Aisbett, BSc, Visiting Fellow. Department of Aged Care and Rehabilitation, Royal North Shore Hospital, Sydney, NSW. Stephen F Wilson, MB BS, FAFRM(RACP), Senior Staff Specialist. Department of Rehabilitation, Prince Henry Hospital, Sydney, NSW. Stella Engel, DPRM, FAFRM(RACP), Director. Spinal Injuries Unit, Royal North Shore Hospital, Sydney, NSW. Sue B Rutkowski, MB BS, Director. Reprints will not be available from the authors. Correspondence: Professor J S Lawson, School of Health Services Management, Faculty of Medicine, University of NSW, Sydney, NSW 2052. - Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Tai R Rotem · James S Lawson · Stephen F Wilson · Stella Engel · Sue B Rutkowski · Chris W Aisbett

Attitudes to and use of a modified prescription form by general practitioners and pharmacists Merilyn J Liddell and Sue P Goldman MJA 1998; 168: 322-325 For editorial comment see Roberts Abstract - Introduction - Methods - Results - Discussion - Acknowledgements - References - Authors' details - - ©MJA1998 Abstract Objective: To evaluate the rate of use and acceptance of a new prescription form designed to provide more information to pharmacists and patients. Design: Prospective descriptive study. Setting: A semi-rural community outside Melbourne, Victoria, in November 1994. Participants: GPs and pharmacists working three or more sessions per week in the locality, and 21 consumers who formed two consumer focus groups. Intervention: An education session for GPs and pharmacists, followed by a one-month trial of new prescription forms which included notations to facilitate interprofessional communication. Main outcome measures: Rate of use and acceptability of the new prescription notations. Results: Eighteen GPs and 10 pharmacists participated; 3600 forms were issued and 2521 prescriptions, including 3464 prescription items, were analysed. GPs and pharmacists used at least one of the new prescription notations in 45% (1559) of prescription items; 35% of prescription items (1222) were notated with the general purpose of the medication. Qualitative findings suggested that GPs, pharmacists and consumers considered the new prescription form to be beneficial and useful. Conclusions: A modified prescription form to increase communication between GPs and pharmacists is acceptable in clinical practice. Introduction Over recent years professional standards for prescribing have emphasised the need for a more patient-centred approach,1 as shown in such documents as the National Health and Medical Research Council's guidelines for medical practitioners on providing information to patients,2 the Policy on the Quality Use of Medicines developed by the Commonwealth Government,3 and regulations on the provision of written consumer information with dispensed medication.4 Research on how to provide more patient-centred pharmaceutical information and counselling shows that closer collaboration between general practitioners (GPs) and pharmacists would help to ensure that medication information is both comprehensive and relevant for consumers.5,6 A joint working party of the Royal Australian College of General Practitioners (RACGP) Victoria Faculty and the Victorian Branch of the Pharmaceutical Society of Australia (PSA) was formed in 1993 to consider how to improve communication between GPs, pharmacists and consumers. A series of recommendations were developed and endorsed by the national executives of the RACGP and the PSA, and published in a joint statement.7 The major recommendation was the use of a new prescription form to aid communication between GPs, pharmacists and patients. Here, we describe a pilot study to determine the rate of use of, and the attitudes of GPs, pharmacists and patients to, a modified prescription form for use in normal clinical practice. No similar study has been reported in the literature (based on the following searches: MEDLINE, January 1982 - June 1997; International Pharmaceutical Abstracts, January 1970 - December 1996; HEALTH, January 1975 - December 1996; EMBASE, January 1994 - December 1996; Pharmaceutical News Index, January 1974 - December 1996). Methods Ethical approval for this study was received from the Monash University Standing Committee on Ethics in Research on Humans and all subjects gave informed consent for their par ticipation. The study was conducted in November 1994 in a semi-rural community on the outskirts of Melbourne with a population of 25 000. All 24 GPs and 13 pharmacists working three or more sessions per week in the locality were invited to participate; 18 GPs and 10 pharmacists agreed. Twenty-one consumers from existing heart and arthritis support groups at the local community health centre were recruited for two focus groups of eight and 13 participants. Before the intervention, the 18 participating GPs and 10 pharmacists completed separate questionnaires (29 questions for pharmacists and 28 for GPs), which covered demographics and assessed (on a scale of 1 to 5) attitudes to professional roles, interprofessional collaboration and consumers' needs for medication information and counselling. Intervention The intervention began with an educational session for GPs and pharmacists to introduce the modified prescription form on which GPs could notate the purpose of prescribed medications, changes to existing medications and specific patient needs. Some of these notations were unprompted, requiring freehand additions to the prescription, while others were prompted, appearing as abbreviations on the form which could be circled when appropriate (see Box 1). A glossary of the new prescription notations was provided. Box 1 shows the glossary which was provided to pharmacists. During the education sessions, the new notations were explained as follows. The major change was that GPs were encouraged, where they considered it appropriate, to indicate the purpose of each prescribed medication as part of the written directions. For example, -adrenoceptor blocking agents might be notated as "for arrhythmias" or "for blood pressure". Pharmacists could then ensure that their medication counselling was relevant to that particular indication and would include the medication's purpose on the medication label for the patient's information. There was provision for GPs to request that the purpose not be written on the medication label by the pharmacist in certain circumstances (such as to preserve patients' privacy if the nature of their illness was not known to family members). GPs were also encouraged to indicate to the pharmacist if therapy with an ongoing medication was to cease (enabling pharmacists to update their computer records to show that a drug was no longer to be taken, and attempt to withdraw any unpresented repeats from circulation), or if the directions intentionally specified an unusual dosage or quantity to be dispensed. Finally, GPs could circle abbreviations printed on the prescription form to indicate specific patient needs or changes in the medication regimen. Pharmacists could then check the patient had understood changes to directions and amend the computer records accordingly. At the end of the educational session, 200 triplicate prescription forms were issued to each GP for use over one month. The third copy of each prescription dispensed (minus identifying patient details) was collected to determine the use of the new notations. After one month, individual one-hour open-ended, semi-structured interviews were conducted with all participating GPs and pharmacists, covering their overall views on the reformatted prescription, specific issues of practical application and suggested changes. Two separate one-and-a-half-hour focus group discussions with consumers dealt with aspects of the use of the reformatted prescription which would directly affect patients. Data analysis For frequency analysis of the questionnaires and of the prescription data, we used, respectively, the statistical package Genstat8 and the computer database program Access.9 Transcripts of interview data and focus group discussions were coded according to emerging themes around the prescription format and particular notations. The analysis, with the NUDIST program for qualitative analysis,10 concentrated on direct testimonies of views held about the new prescription form. Results The median age of the 18 GPs was 35 years (range, 20-29 to >70 years) and 14 were male. Their median workload was 175 patients per week (range, 50-99 to >200) and 13 had postgraduate qualifications. The GPs' age and sex distribution was similar to that of respondents in a national general practice population survey.11 The median age of the 10 pharmacists was 40 years (range, 20-29 to 50-59 years) and eight were male. Their median workload was 125 prescriptions dispensed per day (range, 50-99 to >200) and three had postgraduate qualifications. Attitudes to interprofessional communication In the questionnaire, 16 GPs (89%) and all of the pharmacists stated that they were in favour of more collaboration with one another. GPs had a reasonably high regard for the local pharmacists -- 13 (72%) did not agree that pharmacists' advice conflicted with their own; 17 (94%) agreed they had a good working relationship with the pharmacists, and none believed that pharmacists contacted them unnecessarily. Seven pharmacists (70%) stated that they enjoyed a comfortable working relationship with GPs; only three (30%) agreed that GPs were not always receptive to inquiries about prescriptions, and five (50%) expected the GP to be responsive to contact about a potential drug interaction. Before the intervention, the concept of including the general purpose of a medication on the prescription was not recognised by seven GPs (39%) and seven pharmacists (70%) as useful or necessary for the pharmacist. However, nine pharmacists (90%) stated that to counsel patients adequately they often needed to ask a patient for more information than was on the prescription. Use of the new prescription form Of a total 3600 prescription forms distributed to the GPs, 70% (2521 prescriptions for 3464 individual prescription items) were collected and analysed. Forty-five per cent of individual prescription items (1559) included one of the new notations. The rate of use of the new notations by the GPs is shown in Box 2. The purpose of the medication was notated for 35.3% of all prescription items (1222), with use of this notation by individual GPs ranging from 1% for the lowest user to 92% for the highest user. In only 0.3% (range, 0-4.5%) of cases where this notation was used did doctors request that the information be omitted from the label of the medication container. Attitudes to the new prescription form Overall, the new system was positively received by most GPs and pharmacists, and they suggested it should be widely implemented. Also, most GPs and pharmacists saw indicating the purpose of the medication on the prescription as the most substantial and important focus of the new prescription notations, and suggested that this would enhance the quality of information provided to consumers and minimise irrelevant or inappropriate advice. Further, some suggested that compliance may be improved because patients would receive consistent advice from GPs and pharmacists. Most GPs and pharmacists considered it useful to note when therapy with a long term medication was to be ceased, as patients may forget verbal instructions by the GP. Although the need did not often arise in practice, both GPs and pharmacists were in favour of specifically informing the pharmacist when an unusual dosage or a special quantity of medication was being prescribed. Most GPs and pharmacists thought it appropriate to indicate a new treatment, primarily for ongoing management. Noting a change of directions was considered useful by doctors and pharmacists alike, particularly with elderly patients or those who might still have unused prescriptions. The pharmacist could then be sure the change was intended, check the patient had understood the change, amend any unpresented repeats available, and note the change in the pharmacy computer record. Many GPs, pharmacists and consumers regarded preprinted abbreviations for specific patient needs as unnecessary; it was suggested that longhand could always be used for these or other specific requests to the pharmacist. The abbreviation for noting when separate written instructions had been given to the patient was considered a simple and useful quality control mechanism by doctors, pharmacists and consumers. The consumer focus groups indicated that pharmacists needed to know why someone was being prescribed a medication to enable them to provide appropriate counselling. They expressed reservations about conditions of a very personal nature; in such cases they expected the doctor to either ask their permission or omit the information from the prescription. In general, they considered it both appropriate and helpful to have the purpose of the medication included on the medication label. Discussion In this study the questionnaire findings gave basic data about pre-existing attitudes of the GPs and pharmacists to their respective roles, while the qualitative data explored, in much more depth, the strengths and weaknesses of the new innovation. A 70% return rate of prescriptions was satisfactory, as non-redemption of prescriptions can range from 5%-20%.12 Our most notable finding was the utilisation rate of the new notations, with 35% of prescription items indicating the purpose of the medication to the pharmacist. This was somewhat unexpected, as such a strategy had not previously been considered necessary by GPs or pharmacists. Further, such a high utilisation rate requires considerable behaviour change, and behaviour change strategies generally have much more modest outcomes (eg, 6% for minimal intervention smoking cessation programs13 and 8%-25% for group counselling14). The benefits of asking GPs to indicate the purpose of the medication on the prescription were supported by the qualitative data suggesting that when this strategy was employed it was highly valued. Both GPs and pharmacists indicated that the new prescription form would improve the quality of information given to patients by ensuring that information given by pharmacists was consistent with the advice already given by the GP. It would also enable more information to be given to patients on the medication label. It was of particular interest that, while some of the GPs and pharmacists had very high workloads, they were able to use the new prescription conventions easily in their normal daily practice. There was a high level of utilisation of the new prescription form as a whole, with some notations being used frequently, and others barely at all. This is to be expected as the appropriate circumstance for the use of some notations (such as unusual dosage) would be infrequent. The notation to pharmacists that drug therapy was to be ceased was not widely used, possibly because this affected only a small number of patients, but more likely because there was no specific reminder on the prescription form itself and doctors may have simply forgotten to use it. While some variation in the use of notations may have related to differing perceptions of their value, it was probably also a result of the difficulty of altering ingrained behaviour. Some participants stated that they would try to increase their use of the strategies if they were implemented in the future. Indicating the purpose of the medication is easily misinterpreted as being the same as including the diagnosis, and thereby providing unnecessarily detailed and confidential information to the pharmacist. Participating GPs, however, reported that they provided general information at an appropriate level for the pharmacist and, subsequently, the patient. From the pharmacists' perspective, information about the purpose of a medication was most useful for drugs with multiple indications. It enabled them to target their information appropriately without asking questions to ascertain the precise indication for a particular patient. Generally, consumers thought that including the purpose of the medication on the container label was likely to enhance patients' understanding of their own medication. Confidentiality needs always to be considered, but there are clear advantages in having a drug's purpose included on the label in most situations. As we used only two small consumer focus groups, they could provide only a limited indication of what consumers may think of the proposed system. However, consumers did suggest that the new system would help them gain access to appropriate information and advice. Any future implementation should be made with adequate consumer input, to ensure attention to their requirements. In conclusion, this study showed that it is possible to modify the prescription form to include more information in a way that is acceptable to GPs and pharmacists in their daily practice. GPs, pharmacists and consumers found such changes worthwhile and believed they could lead to better medication management and patient care. Acknowledgements We thank the Royal Australian College of General Practitioners and the Victorian Branch of the Pharmaceutical Society of Australia, and the members of the joint working party -- Val Constable, John Daffey, David Dammery, Chris Hogan, Alistair Lloyd, Mary Murray and Denise Ruth -- as well as the GPs, pharmacists and consumers in the study. Finally, we thank the Department of Health, Housing, Local Government and Community Services for financial support for the project. References Liddell M. Rational prescribing and professional standards. Med J Aust 1994; 160: 564-567. Working Party of the Health Care Committee, National Health and Medical Research Council. General guidelines for medical practitioners on providing information to patients. Canberra: National Health and Medical Research Council, 1993. Commonwealth Department of Health, Housing and Community Services, in conjunction with the Pharmaceutical Health and Rational Use of Medicines (PHARM) Working Party. A policy on the quality use of medicines. Canberra: Commonwealth Department of Health, Housing and Community Services, 1992. Part 2A, Schedule 12 of the Therapeutic Goods Regulations under the Therapeutic Goods Act 1989, Section 63. Murphy B, Ruth D, Murray-Hodge M. The use of qualitative research in the development of the HEARTWISE program for general practitioners. Med J Aust 1993; 158: 626-628. Ruth D, Hodge M, Murphy B. Improving the relationship between general practitioners and pharmacists. Aust Fam Physician 1994; 23: 1536-1540. Royal Australian College of General Practitioners and the Pharmaceutical Society of Australia. General practitioners' and pharmacists' interprofessional communication. Aust Fam Physician 1994; 23: 1544-1546. Genstat [computer program]. Version 5 Release 3.1. Lawes Agricultural Trust (Rothamstead Experimental Station, UK), 1993. 9. Access [computer program]. Version 2.0. Redmond, Wa.: Microsoft Corporation, 1994. Richards T, Richards L. The NUDIST qualitative data analysis system. Qual Sociol 1991; 14: 307-325. Bridges-Webb C, Britt H, Miles D, et al. Morbidity and treatment in general practice in Australia 1990-1991. Med J Aust 1992; 157 Suppl Oct 19: 14. Beardon P, McGilchrist M, McKendrick A, et al. Primary non-compliance with prescribed medication in primary care. BMJ 1993; 307: 846-848. Kottke T, Battista R, DeFrieze G, et al. Attributes of successful smoking cessation interventions in medical practice: a meta-analysis of 39 controlled trials. JAMA 1988; 259: 2882-2889. Curry S, Marlatt G, Gordon J, et al. A comparison of alternative theoretical approaches to smoking cessation and relapse. Health Psychol 1988; 7: 545-556. (Received 5 Jun, accepted 10 Nov, 1997) Authors' details Department of Community Medicine and Department of General Practice, Monash University, Melbourne, VIC. Merilyn J Liddell, MB BS, FRACGP, Senior Lecturer; Sue P Goldman, BEd, GradDipSoc, Research Fellow. Reprints will not be available from the authors. Correspondence: Dr M J Liddell, 867 Centre Road, East Bentleigh, VIC 3165. E-mail: merilyn.liddell AT med.monash.edu.au Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Merilyn J Liddell · Sue P Goldman

Use of systematic reviews of randomised trials by Australian neonatologists and obstetricians Christopher F C Jordens, Penelope Hawe, Les M Irwig, David J Henderson-Smart, Margaret Ryan, Deborah A Donoghue, Roger G Gabb and Ian S Fraser MJA 1998; 168: 267-270 For editorial comment see Phillips Abstract - Introduction - Methods - Results - Discussion - Acknowledgements - References - Authors' details - - ©MJA1998 Abstract Objective: To determine what proportion of Australian neonatologists and obstetricians report using systematic reviews of randomised trials. Design: Cross-sectional survey using structured telephone interviews. Setting: Australian clinical practice in 1995. Participants: 103 of the 104 neonatologists in Australia (defined as clinicians holding a position in a neonatal intensive care unit); a random sample of 145 members of the Royal Australian College of Obstetricians and Gynaecologists currently practising in Australia. Main outcome measures: Information sources used in clinical practice; reported awareness of, access to and use of systematic reviews, and consequent practice changes. Results: Response rates were 95% (neonatologists) and 87% (obstetricians); 71 neonatologists (72%) and 55 obstetricians (44%) reported using systematic reviews, primarily for individual patient care. Databases of systematic reviews were used with a median frequency of once per month. Among neonatologists, systematic reviews were used more commonly by those who were familiar with computers, attended professional meetings, and had authored research papers. Among obstetricians, they were used more commonly by those who were familiar with computers, had less than 10 years' clinical experience, attended more deliveries, and were full-time staff specialists in public hospitals. Of neonatologists who reported using systematic reviews, 58% attributed some practice change to this use. For obstetricians, the corresponding figure was 80%. Conclusions: There is evidence that Australian neonatologists and obstetricians use systematic reviews and modify their practice accordingly. Dissemination efforts can benefit from knowledge of factors that predict use of systematic reviews. Introduction Randomised controlled trials are widely accepted as the best method of evaluating the effectiveness of medical interventions. However, their findings are slow to change medical opinion and practice.1,2 The communication of clinically important research findings is hampered by the volume and geometric growth of the medical literature.3 Reviews address this problem, but conventional review methodology is unscientific4,5 and open to selection biases inherent in the publication process.5,6 This has led to the development of systematic reviews. A properly conducted systematic review begins with an exhaustive search for published and unpublished randomised trials addressing a well defined research question. The second step is to identify trials of adequate quality to contribute to decision-making. The results of included trials are then pooled, or "meta-analysed", to arrive at a quantitative estimate of the benefits and harms of treatment. Systematic reviews published by the Cochrane Collaboration are also continuously updated by specialist review groups.7 Systematic reviews in pregnancy and childbirth have been available for some years. In 1988 a comprehensive trial register became commercially available in database form as the Oxford database of perinatal trials.8 Effective care in pregnancy and childbirth, 9 a textbook based on this research synthesis, was published the following year, with a guide for non- specialist readers.10 A companion textbook, Effective care of the newborn infant,11 appeared in 1992. From 1993, systematic reviews relating to pregnancy and childbirth were available electronically in the Cochrane pregnancy and childbirth database.12 All these reviews are currently being updated for The Cochrane library.13 These new publications represent prototypes for future publications in other fields of practice. However, their impact on clinical practice remains uncertain, despite several surveys to ascertain the extent of their dissemination and uptake.14-18 To make a practical difference, systematic reviews must be readily available to clinicians who are aware of them, who use them, and who implement their findings. To ascertain whether this is occurring in Australia, we conducted a survey of neonatologists and obstetricians with the aims: To gauge awareness of, access to, and use of the Oxford database, Cochrane database, and Effective care textbooks; To place these resources in the context of other information sources that inform practice in obstetrics and neonatology; and To ascertain how often and why these resources are consulted, predictors of their use, and whether their use has led to reported changes in clinical practice. Methods Participants Clinicians who held a position in one of Australia's 23 neonatal intensive care units were eligible for the survey. The Australian and New Zealand Neonatal Network (ANZNN), which covers all neonatologists, provided a current listing. The Royal Australian College of Obstetricians and Gynaecologists (RACOG) drew a simple random sample of 20% of Fellows from its membership. Those sampled were eligible if they were currently practising obstetrics. Any clinicians not currently practising in Australia, not on the telephone network, or who were involved in designing this survey, were ineligible. Eligible clinicians were sent an introductory letter, telephoned, and invited to schedule a confidential, 10-minute telephone interview about information sources used in clinical practice. Systematic reviews were not mentioned until the interview was under way. Interviews An existing interview schedule15,16 was modified in consultation with the ANZNN and the RACOG. Respondents were first asked to name the three main sources of information they used for keeping up with new developments in their field, and for dealing with uncertainty about a specific treatment decision. They were also asked which of the three information sources they considered the most important or useful for each task. Respondents were then asked about their access to and use of computers, and asked directly whether they had heard of, had access to, and used the Cochrane database, Oxford database, and Effective care of the newborn infant (neonatologists) or Effective care in pregnancy and childbirth (obstetricians). Those who reported using any of these resources were asked what a systematic review was, how often they consulted that resource, what they used it for, whether they thought using it had made any difference to their clinical practice and, if so, whether they could name a treatment policy they had altered in response to evidence from a systematic review. To count as users of systematic reviews, respondents had to mention randomised trials or meta-analysis in their description of a systematic review. The final questions sought demographic information on clinical experience, place of education, attendance at professional meetings, research publications, academic appointments, and qualifications. A research degree was defined as a doctorate, relevant master's degree, or bachelor's degree of science in medicine, held in addition to basic medical and specialty qualifications. Reports of authorship were verified by searching MEDLINE and by screening abstracts. For neonatologists it was noted whether they held full- or part-time positions, whether they worked in a hospital with an obstetric unit, whether they headed a neonatal unit, and in which unit they worked. For obstetricians, it was noted whether they held a position as a full-time staff specialist in a public hospital. They were asked how many deliveries they attended each year, and whether they worked at any hospital with an accredited RACOG training post. The interview schedule was modified after a pilot study with seven neonatologists in New Zealand. The main survey was conducted between August and December 1995, with ethics approval from the ANZNN, RACOG and the University of Sydney. All interviews were conducted by the first author (C F C J). Analysis Confidence intervals for the proportion of obstetricians who reported using systematic reviews were calculated with a finite population correction. Confidence intervals were not calculated for the corresponding proportion of neonatologists, as this was ascertained for all Australian neonatologists. Descriptive and c 2 analyses were conducted. Then, using a backwards stepwise modelling procedure, a multivariate logistic regression analysis was used to determine which study factors predicted the reported use of systematic reviews. With the neonatology data, this modelling procedure was repeated using binomial generalised estimating equations to adjust for clustering of respondents within neonatal units.19 Results Of 106 listed neonatologists, three were ineligible (one had retired, one was not practising in Australia, and one was involved in designing this survey). Of the 103 eligible clinicians remaining, 98 completed interviews (95% response). From a sample of 210 obstetricians, 65 were ineligible for the survey (51 no longer practised obstetrics, 13 were not practising in Australia, and one could not be located on the telephone network). Of 145 eligible obstetricians, 126 completed interviews (87% response). Respondent characteristics are shown in Box 1, with comparative data on computer use. For the purpose of keeping up with new clinical developments, respondents favoured journals, conferences and meetings, colleagues and MEDLINE (in that order) over systematic reviews. For the purpose of clinical problem-solving, colleagues, MEDLINE, journals, and other printed medical literature were favoured over systematic reviews as sources of information. Although the percentages favouring each source varied between the two specialties and according to whether the respondent was simply nominating the resource or nominating it as the most important resource, the rank order of the resources remained consistent. In each specialty, 21% of respondents mentioned systematic reviews without prompting from the interviewer when naming the information sources they used, or when describing their computer use. When questioned directly about systematic reviews, 71 neonatologists (72%) and 55 obstetricians (44%; 95% confidence interval, 36%-51%) reported using them in either electronic database or textbook form. The confidence interval indicates the reliability of the sample prevalence as an estimate of the population prevalence. The Figure shows reported levels of awareness of, access to and use of systematic reviews by specialty. Predictors of use of systematic reviews Results of the multivariate analysis are shown in Box 2. Among neonatologists, three factors significantly (P<0.05) and independently predicted use of systematic reviews: attendance at meetings of the Australian Perinatal Society, authorship of at least one research paper, and familiarity with computers (our index of this was use of a computer for word-processing). Results from cluster analysis agreed with those from logistic regression. Among obstetricians, four factors sig nificantly and independently predicted use of systematic reviews: familiarity with computers, mode of practice (full-time staff specialists were more likely to use systematic reviews than others), clinical experience (recent graduates were more likely to use systematic reviews), and number of deliveries per year (likelihood of using systematic reviews increased with this number). Descriptors of use of systematic reviews Both neonatologists and obstetricians reported using databases of systematic reviews with a median frequency of once per month. The main purpose for using systematic reviews (irrespective of their format) reported by respondents from both specialties was individual patient care. Systematic reviews were also said to be used for (in rank order of frequency of reporting) teaching, preparing a pre sentation, reviewing current management or developing evidence-based protocols or guidelines, settling disputes, background information, reviewing a topic, research, as a source of references, and patient information. Of the 71 neonatologists who reported using systematic reviews, 58% said that this had changed their clinical practice in some way, and 44% gave at least one example of a treatment policy they had altered in response to a systematic review. The most common examples were treatment of respiratory disorders, and use of steroids and indomethacin. Corresponding percentages for obstetricians who reported using systematic reviews were 80% (reported a change in practice) and 71% (gave at least one example). The most common example was use of steroids in management of preterm rupture of membranes. Discussion We found that 72% of neonatologists and 44% of obstetricians reported consulting systematic reviews, primarily for the purpose of individual patient care. Databases of systematic reviews were used at a median frequency of once per month. Systematic reviews were used more commonly by those who were familiar with computers in both specialties, by those who attended professional meetings and had authored research papers among neonatologists, and by those who had had less than 10 years' clinical experience, attended more deliveries, and who had a position as a full-time staff specialist among obstetricians. The findings of this survey are based on self-reporting. Although the survey was designed to minimise over-reporting, it was still subject to imprecision in respondents' recall about (for example) the frequency with which they used systematic reviews, and to difficulties in attributing practice changes to their use. Nevertheless, this was the first study of the use of systematic reviews by Australian clinicians, and the findings have immediate and practical relevance for organisations such as universities, government agencies and specialty colleges that are trying to improve access to the best available evidence and to promote its use.20-23 The association between use of systematic reviews and attendance at Australian Perinatal Society meetings among neonatologists could reflect greater receptiveness to innovations among clinicians who attend professional meetings. However, it also supports the perception (reported elsewhere13 ) that professional organisations play an important role in disseminating research findings. Future dissemination efforts could usefully concentrate on these organisations. In both specialties, familiarity with computers predicted use of systematic reviews. Better access to digital information technology and training in its use is therefore likely to enhance uptake of these reviews. This might include improved access to The Cochrane library and the Internet, and training workshops for searching specialist databases. The remaining predictors of use of systematic reviews, as well as the overall contrast between neonatology and obstetrics, suggest that specialists practising primarily in public hospitals are more likely to use systematic reviews than those working primarily in private practice. Special efforts are therefore needed to reach the latter. As systematic reviews do not appear to rank highly among the information sources used in clinical practice, it is important to stress their relative advantages. Uptake of this innovation appears more likely among recent graduates, with senior clinician researchers acting as "product champions".24 Although debate persists as to whether practising clinicians accept the innovations of evidence-based medicine,25 our survey found evidence that Australian neonatologists and obstetricians use systematic reviews, and appear to modify their practice accordingly. Efforts are needed to enhance the use of these reviews, and to conduct further evaluations of their influence on clinical practice. In attempting to improve practice standards, it is important to pursue methods which have been shown to be effective.26 Acknowledgements We would like to thank the many clinicians who gave up their time to participate in this survey. Infrastructure support for this project was provided by the Department of Public Health and Community Medicine at the University of Sydney. Special thanks are due to Petra Macaskill, who conducted the cluster analysis, and Jeanette Ward and Mary Osborne, from the Central Sydney Area Health Service Needs Assessment and Health Outcomes Unit, who provided helpful advice on survey procedures. References Antman EM, Lao J, Kupelnick B, et al. A comparison of results of meta-analyses of randomized control trials and recommendations of clinical experts: treatments for myocardial infarction. JAMA 1992; 268: 240-248. Stross JK, Harlan WR. The dissemination of new medical information. JAMA 1979; 241: 2622-2624. Warren KS. From papyrus to parchment to paper to pixels: information technology and the future of biomedical publishing. In: Lock S, editor. The future of medical journals. London: BMJ, 1991: 127-146. Mulrow CD. The medical review article: state of the science. Ann Intern Med 1987; 106: 485-488. Light RJ, Pillemer DB. Summing up: the science of reviewing research. Cambridge: Harvard University Press, 1984. Dickersin K, Berlin JA. Meta-analysis: state-of-the-science. Epidemiol Rev 1992; 14: 154-176. Sackett DL. The Cochrane Collaboration. ACP J Club 1994; 120 Suppl 3: A-11. Chalmers I, editor. Oxford database of perinatal trials. Version 1.2, disk issue 7 (Spring). Oxford: Oxford University Press, 1992. Chalmers I, Enkin M, Keirse MJNC. Effective care in pregnancy and childbirth. Oxford: Oxford University Press, 1989. Enkin M, Keirse MJNC, Chalmers I. A guide to effective care in pregnancy and childbirth. Oxford: Oxford University Press, 1989. Sinclair JC, Bracken MB. Effective care of the newborn infant. Oxford: Oxford University Press, 1992. Enkin MW, Keirse MJNC, Renfrew MJ, Neilson JP, editors. Cochrane pregnancy and childbirth database. Oxford: Update Software, 1993. The Cochrane Library [database on disk and CD-ROM]. The Cochrane Collaboration. Oxford: Update Software; 1996. Updated quarterly. Lomas J. Retailing research: increasing the role of evidence in clinical services for childbirth. Milbank Q 1993; 71: 439-475. Stocking B. Implementing the findings of effective care in pregnancy and childbirth in the United Kingdom. Milbank Q 1993; 71: 497-523. Paterson-Brown S, Fisk NM, Wyatt JC. Uptake of meta-analytical overviews of effective care in English obstetric units. Br J Obstet Gynaecol 1995; 102: 297-301. Paterson-Brown S, Wyatt JC, Fisk NM. Are clinicians interested in up to date reviews of effective care? BMJ 1993; 307: 1464. Hyde C. Who uses the Cochrane pregnancy and childbirth database? BMJ 1995; 310: 1140-1141. Zeger SL, Liang K-Y. Longtitudinal data analysis for discrete and continuous outcomes. Biometrics 1986; 42: 121-130. Rychetnik L. Evidence-based medicine in the GMP (Graduate Medical Program). Focus: graduate medical degree news and events. Sydney: 1995: 1-2. Liddle J, Williamson M, Irwig L. Method for evaluating research and guideline evidence. Sydney: NSW Department of Health, 1996. National Health and Medical Research Council. Clinical practice guidelines: the management of early breast cancer. Canberra: NHMRC, 1995. Commonwealth Department of Human Services and Health. Guidelines for the development and implementation of clinical practice guidelines. Canberra: the Department, 1995. Rogers EM. Diffusion of innovations. New York: MacMillan, 1983. Miles A, Bentley P, Polychronis A, Grey J. Evidence-based medicine: why all the fuss? J Evaluation Clin Pract 1997; 2: 83-85. Grimshaw JM, Russell IT. Effect of clinical guidelines on medical practice: a systematic review of rigorous evaluations. Lancet 1993; 342: 1317-1322. (Received 11 Jun, accepted 11 Sep, 1997) Authors' details University of Sydney, Sydney, NSW. Christopher F C Jordens, MPH, Postgraduate Student, Department of Public Health and Community Medicine; now Researcher, Centre for Values, Ethics and the Law in Medicine, Department of Surgery, University of Sydney; Penelope Hawe, MPH, Senior Lecturer, Department of Public Health and Community Medicine; Les M Irwig, FFPHM, PhD, Associate Professor, Department of Public Health and Community Medicine; David J Henderson-Smart, PhD, FRACP, Professor, and Director, NSW Centre for Perinatal Health Services Research, and Department of Neonatal Medicine, Royal Prince Alfred Hospital, Sydney, NSW; Deborah A Donoghue, RN, BSocSc, Senior Research Assistant, Australian Institute of Health and Welfare National Perinatal Statistics Unit; Ian S Fraser, MD, FRACOG, Professor in Reproductive Medicine, Department of Obstetrics and Gynaecology, Queen Elizabeth II Research Institute for Mothers and Infants. Royal Australian College of Obstetricians and Gynaecologists, Melbourne, VIC. Margaret Ryan, MSW, PhD, Research Officer. Centre for Professional Development, Victoria University of Technology, Melbourne, VIC. Roger G Gabb, PhD, Professor, and Director. Reprints: Mr C F C Jordens, Department of Surgery, Blackburn Building D06, University of Sydney, NSW 2006. E-mail: cjordens AT surgery.usyd.edu.au Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Penelope Hawe · Les M Irwig · David J Henderson-Smart · Margaret Ryan · Deborah A Donoghue

Smoking behaviours of Australian adults in 1995: trends and concerns David J Hill, Victoria M White and Michelle M Scollo MJA 1998; 168: 209-213 For editorial comment see Gray Abstract - Introduction - Methods - Results - Discussion - References - Authors' details - - ©MJA1998 Abstract Objectives: To estimate the prevalence of smoking among Australian men and women in 1995 and to examine trends in smoking prevalence in Australia over the past 10 years. Design: A representative sample of adults participated in face-to-face interviews conducted by a large market research company. Participants: 2819 men and 2880 women over the age of 16. Main outcome measure: Self-reported smoking behaviours assessed by standard questions. Results: Overall, 27.1% of men and 23.2% of women were smokers of tobacco (factory-made cigarettes, pipes, cigars or roll-your-own cigarettes). This difference in smoking prevalence of men and women was significant. More men (32.1%) than women (21.7%) were past smokers and more women (53.4%) than men (39.3%) had never been regular smokers. On average, male smokers smoked about 20 factory-made cigarettes a day, while women smoked about 18. Occupation and education levels were inversely related to smoking prevalence. Comparisons with earlier data suggest that the decline in smoking prevalence seen in previous surveys has ceased. However, the number of cigarettes consumed daily decreased between 1992 and 1995. In the period between 1983 and 1989, when per capita expenditure on adult antismoking campaigns rose, smoking prevalence declined, but levelled off thereafter in a period when expenditure on campaigns fell. Conclusion: Failure to find a continuing decline in prevalence of smoking among the Australian population is of great concern and indicates the importance of continuing and extending antismoking programs. Introduction Cigarette smoking is still the most important preventable cause of premature death in Australia. Reducing the prevalence of smoking rightly remains a high priority on Australia's public health agenda.1,2 As such, it is important to collect and publish estimates of the prevalence of smoking and its sociodemographic correlates at regular intervals, as indicators of progress towards controlling the virtual epidemic of tobacco-related disease,3 and as a basis for public decisions on action to take. We have published data on national smoking prevalence for the years 1974,4 1976,5 1980,6 1983,7 1986,8 19899 and 1992,10 using a standard method of data collection. Here we report data for 1995. Methods Survey method: A large market research company carried out the sampling and interviewing as part of an omnibus survey in September/October 1995. Procedures were the same as in our previous surveys. In brief, interviews were conducted on the weekend, with respondents within a census collector's district selected at random within specified strata, including State and rural or urban divisions. Within each collector's district an individual residence was chosen at random for the first contact and the adjacent house was contacted next. Further adjacent households were approached until the required number of interviews for that collector's district were obtained (usually eight from about 200 households in each census collector's district). Response rate: Of the households contacted 47% agreed to participate in the survey, 42% refused, and in the remaining 11% either the residents were too old or ill or could not speak English, or call-back was unsuccessful. The response rate for this survey was similar to the rates for the 1992 and 1989 surveys, but it was lower than response rates in earlier years. Thus, if variable response rates influence reported prevalences, this could only have occurred for the period before 1989; recent comparisons are not confounded by response rates. Data collected: Respondents indicated their smoking status by choosing a category from the following list: Current smoker -- cigarettes only, cigarettes plus cigars or pipes, cigars only (ex-cigarettes), pipes only (ex-cigarettes), cigars only (never cigarettes), or pipes only (never cigarettes); Past smoker -- of cigarettes only, of cigarettes plus pipe or cigar, of cigars or pipes only; and Never smoker -- those who had never smoked regularly. Current smokers of factory-made cigarettes indicated the brand usually smoked, the size of the pack usually bought and the number of cigarette packets usually smoked in a week. Respondents' sex, age (in five-year age groups), country of birth, highest level of education achieved, and occupation were recorded, as well as the occupation of the household's main income earner. Analysis of data: We calculated 95% confidence intervals (95% CI) associated with estimates of smoking prevalence among men and women and the difference between estimates. Confidence intervals around prevalence estimates for particular subgroups (eg, men aged 50-59 years) are not given. We used chi-squared tests of association to examine differences in the prevalence of smoking between groups, and logistic regression analyses to explore whether associations between smoking prevalence, educational level, occupation and, for women, country of birth were independent of associations between age and smoking. We used analyses of variance and t tests to examine whether the mean number of cigarettes smoked differed between groups. Finally, to compare the prevalence of smoking across recent years, we age-standardised the data from the 1995, 1992 and 1989 surveys to the age distribution of the 1986 sample. Results Smoking status: Of the 5699 participants, 51% (2880) were women and 49% (2819) were men. A comparison of the distributions of age, occupation, education and country of birth in the sample data with those in the census data indicated no bias in the socio demographic variables in the dataset. Eighty-two per cent of respondents were interviewed on the first visit to their home. The smoking status of these respondents was similar to that of the more hard-to-reach respondents (those who were interviewed on the second or third contact). Cigarettes dominated tobacco use, with only 1% of men and less than 1% of women indicating that they smoked only pipes or cigars. Only 8% of men and 4% of women had smoked roll-your-own cigarettes in the month before the survey. The smoking status of the males and females in the sample is shown in Table 1. Smoking prevalence: In 1995, the estimated prevalence of smoking among Australian men aged 16 years and over was 27.1% (95% CI, 25.6%-28.7%), while among women the prevalence was estimated to be 23.2% (95% CI, 21.7%-24.7%); this difference was significant (3.9%; 95% CI, 1.6%-6.2%). The prevalence of smoking peaked between the ages of 25 and 29 in men (34.7%) and in women (35%), after which age smoking generally decreased among both men and women. Past smoking or non-smoking: More men (32.1%; 95% CI, 30.4%-33.8%) than women (21.7%; 95% CI, 20.2%-23.2%) were past smokers, a highly significant difference (10.4%; 95% CI, 8.1%-12.7%). More women (53.4%; 95% CI, 51.6%-55.2%) than men (39.3%; 95% CI, 37.5%-41.1%) had never been regular smokers, and again this difference was highly significant (14.1%; 95% CI, 11.5%-16.7%). Men and women differed in their age-related patterns of past smoking. Among men, the proportion of past smokers increased with age to reach a peak of 54.4% in those over 70. Although among women the proportion of past smokers peaked at 26% for those over 70, the proportion of past smokers in the other age groups showed little variation from the overall rate of 21.7%. The proportion who had ever smoked was calculated by adding the percentage of those who had smoked in the past to the percentage of current smokers. Overall, 59.2% (95% CI, 57.4%-61.0%) of men and 44.9% (95% CI, 43.1%-46.7%) of women had smoked at some stage in their life. The association between age and ever having smoked differed for men and women. While among men the proportion who had ever smoked increased with increasing age, for women the proportions of ever smokers began to decrease after the age of 35. Quit proportions: The quit proportion (ie, proportion of ever smokers who had given up smoking in each age and sex group) is also shown in Table 1. The overall quit proportion for men (0.54) was slightly higher than that among women (0.48). However, as Table 1 shows, there is little difference in the quit proportions for men and women in most age groups, except for the 16 to 19 years and 60 to 69 years age groups. Factory-made cigarettes: The mean number of factory-made cigarettes smoked per day by smokers was 19.7 (SD, 11.6) for men and 18.1 (SD, 10.8) for women; this difference was statistically significant (t=2.55, df=1238, P=0.01). In 1995, the cigarettes smoked by women had a lower average tar content than the cigarettes smoked by men (t=5.56, df=1022, P<0.001). The average tar content of cigarettes smoked by men was 8.2 mg (SD, 2.8), while for women it was 7.2 mg (SD, 3.0). Education: As in previous reports of this survey series, the prevalence of smoking and the mean number of cigarettes smoked per day differed for people in various sociodemographic groups. As Table 2 shows, smoking prevalence decreased with increased education, so that only 17.0% of men and 14.2% of women who were university graduates smoked. The association between education level and smoking prevalence was significant for both sexes, but was stronger for men (chi-squared=91.3, df=6, P<0.001) than women (chi-squared=35.5, df=6, P<0.001). The proportions of ex-smokers in the different education levels indicate that quitting was common in all groups. However, the greater proportion of never smokers in the better-educated groups indicates that the lower prevalence of smoking among this group was due to their never having smoked in the first place. For both men and women, smokers with more years of formal education smoked fewer cigarettes per day than did those who had fewer years of education (men: F3,618 = 3.15, P<0.05; women: F3,614=8.92, P<0.001). Occupational levels: Respondents were classified into one of four occupation levels based on the occupation of the household's main income earner. Occupational levels differed in the level of skill required for the job, such that unskilled workers (eg, labourers) were classified as "lower blue collar", while skilled workers (eg, plumbers) were classified as "upper blue collar". As occupation status increased, the prevalence of smoking decreased (Table 2). Among men from "upper white collar" households, 18.7% smoked compared with 40.9% of men from "lower blue collar" households. The association between occupation status and smoking was significant for both men (chi-squared=102.3, df=6, P<0.001) and women (chi-squared=46.8, df=6, P<0.001). Among men, the proportion of ex-smokers was slightly lower among "lower blue collar" households than other groups . Among women, the proportion of ex-smokers was similar among all occupation groups. The proportion of never smokers was greatest among higher occupation levels. This pattern of results indicates that the lower prevalence of smoking seen in higher occupation groups is due to the relatively lower rate of taking up smoking among these groups rather than their greater success at quitting. The differences in the mean number of cigarettes consumed per day between occupation groups was not statistically significant for men (F3,618 = 2.0, P=0.12) or women (F3,614=1.4, P=0.24). Country of birth: The prevalence of smoking was lowest among both men and women born in Asian countries. However, while the prevalence of 19.8% among Asian-born men was not significantly different from that found for groups born elsewhere, the prevalence of smoking among Asian-born women was significantly lower than the prevalence of smoking among women born in Australia (chi-squared=7.2, df=1, P<0.01) or the United Kingdom (chi-squared=6.6, df=1, P<0.01). The number of cigarettes smoked per day showed little variation according to place of birth. The overall association between place of birth and cigarette consumption was not significant for either men (F4,617=1.3, P=0.26) or women (F4,614=1.0, P=0.40). However, Asian-born men consumed significantly fewer cigarettes per day than did men born elsewhere (t=2.14, df=620, P<0.05). Logistic regression analyses of demo graphic data: In separate analyses, age was entered before the predictor variable of education level, occupational status or country of birth (for women only), and in each case the association between smoking prevalence and the predictor variable remained significant. Pack size and number of cigarettes smoked: The cigarette packet size most commonly used was 25 (by 36% of smokers), followed by packets of 30 and 40 (19% each), 50 (17%), 20 (6%) and 35 (4%). The number of cigarettes smoked per day was related to packet size (F5,1205=34.93, P<0.001). The mean number of cigarettes smoked per day by those who used packets of 20 was 13, for packets of 25 it was 16, for packets of 30 it was 17, for packets of 40 the mean was 23, and for packets of 50 it was 25. Except for women from lower blue collar households, the packet of 25 cigarettes was the most popular size for all occupation and education groups. After collapsing pack-size categories and combining sexes, 55% of blue collar smokers used pack sizes of 20, 25 or 30 compared with 68% of white collar smokers, and 32% of white collar smokers used packs of 35, 40 or 50 compared with 45% of blue collar smokers (chi-squared=20.0, df=1, P<0.001). Comparisons with previous years Smoking prevalences in Australia from 1986 to 1995 are shown in Figure 1, with a line of best fit superimposed. Of concern from a public health point of view is that the observed prevalence in 1995 is no lower than that in 1992, necessitating an upward adjustment of the projection to 2001 compared with our projection based on the four triennial surveys up to 1992. It was expected that the national prevalence targets for the year 2000 would be bettered.10 Now the trends suggest they will not be met, either for men or women. The results of the 1995 survey also show 5% more men and 3% more women smoking than would have been expected on the basis of the trends to 1992, and, by extrapolation, this means that in 1995, 356 000 more men and 384 500 more women were smoking in Australia than expected . The mean number of cigarettes smoked by men in 1995 was lower than the 22.1 cigarettes smoked per day by men in 1992 (t=3.39, df=1348, P<0.001). Among women, however, the average number of cigarettes smoked per day in 1995 was not significantly less than the number smoked in 1992 (19.1) (t=1.59, df=1322, P=0.113). The legislative and other activity to restrict advertising and promotion of tobacco, as well as expenditure on adult-directed antismoking campigns, between 1989 and 1995 are outlined in Box 1. Discussion This is the first time in eight successive surveys that the reported prevalence of smoking in men was no lower than the previous survey and the first time since 1983 that this was also the case for prevalence of smoking in women. If these data signal an underlying change and the previously falling prevalence of smoking has indeed stabilised, a major public health response is indicated. Attainment of what is arguably the nation's primary public health target1 -- reducing the prevalence of smoking in men and women to 20% by 2000 -- is clearly under threat. Given that this target was and still may be seen as modest, this would be a major public health failure, as the following calculations show. For every percentage point smoking prevalence in Australia exceeds the national goal, nearly 140 000 people are smoking who, had the goal been met, would not have been. So, if the goal is missed by 3%, which would be the case if the prevalence remains stable, nearly 420 000 more people than expected will be smoking. If they remain smokers, according to estimates of Doll et al,15 210 000 will die prematurely as a result of their smoking. Against the above fairly alarming observations must be set some auspicious trends -- smokers are smoking less and are probably less exposed to inhaled carcinogens and this should flow through to modest public health gains. As well as benefiting themselves, it seems plausible that a lower daily consumption by smokers is reducing the passive exposure of others to cigarette smoke, as forgone cigarettes may be some of those previously smoked at work or in public places where others would be exposed to sidestream smoke. Assuming these data indicate a slow-down or stalling in the previous reduction in smoking prevalence, why has this occurred and what needs to be done? Figure 2 suggests one explanation for influences on smoking prevalence. At times when antismoking activity is high, whether it be in the form of policy or programs, smoking declines, but when these abate prevalence stagnates. Clearly, these data call for more extensive and rigorous analysis which might incorporate, in a multivariate analysis, other factors such as price, regulations and pro-cigarette promotions. This could determine the extent to which program expenditure affects smoking prevalence. The trends are extremely worrying. Stasis in public policy and prevention programs paralleled by static smoking levels suggest the importance of continuing to extend antismoking programs in order to restart the reduction in smoking prevalence. The experience of some Scandinavian countries shows that public health authorities cannot rest on their laurels.16 Much remains to be done (Box 2). References Commonwealth Department of Human Services and Health. Better Health Outcomes for Australians. Canberra: AGPS, 1994. Australian Institute of Health and Welfare. Tobacco use and its health impact in Australia. Canberra: AIHW, 1996. English D, Holman CD, Milne E, et al. The quantification of drug caused morbidity and mortality in Australia. Canberra: Commonwealth Department of Human Services and Health, 1995. Gray N, Hill D. Patterns of tobacco smoking in Australia. Med J Aust 1975; 22: 819-822. Gray NJ, Hill D. Patterns of tobacco smoking in Australia II. Med J Aust 1977; 20: 329-330. Hill D, Gray N. Patterns of tobacco smoking in Australia III. Med J Aust 1982; 1: 23-25. Hill D, Gray N. Australian patterns of tobacco smoking and related health beliefs in 1983. Community Health Stud 1983; 8: 307-316. Hill D. Australian patterns of tobacco smoking in 1986. Med J Aust 1988; 149: 6-10. Hill D, White V, Gray N. Australian patterns of tobacco smoking in 1989. Med J Aust 1991; 154: 797-801. Hill D, White V. Australian adult smoking prevalence in 1992. Aust J Public Health 1995; 19: 305-308. Chapman S, Wooward S. Australian court rules that passive smoking causes lung cancer, asthma attacks and respiratory disease. BMJ 1991; 302: 943-945. Schollam v Dept of Health (NSW). District Court (NSW). 25 May 1992, Case 40830/86. Borland R, Mullins R. The increasing prevalence of workplace smoking bans in Victoria. J Occup Health Safety Aust N Z 1994; 10: 35-40. Borland R, Morand M, Mullins R. Prevalence of workplace smoking bans in Victoria. Aust N Z J Public Health 1997; 21: 694-698. Doll R, Peto R, Wheatley K, et al. Mortality in relation to smoking: 40 years' observations on male British doctors. BMJ 1994; 309: 901-911. Rimpela A. Critical analysis of the Finnish Tobacco Act: implementation and legitimacy 1977-89. Tobacco Control 1992; 1: 285-292. (Received 11 Aug 1997, accepted 27 Jan, 1998) Authors' details Centre for Behavioural Research in Cancer, Anti-Cancer Council of Victoria, Melbourne, VIC. David J Hill, PhD, Director; Victoria M White, MA, Behavioural Scientist; Michelle M Scollo, BBSc, GradDipCommHlth, Public Health Consultant. Reprints will not be available from the authors. Correspondence: David J Hill, Director, Centre for Behavioural Research in Cancer, Anti-Cancer Council of Victoria, 1 Rathdowne Street, Carlton South, VIC 3053. E-mail: davidh AT accv.org.au Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

David J Hill · Victoria M White · Michelle M Scollo

Prevalence of tuberculosis infection in Melbourne secondary school students Paul D R Johnson, John B Carlin, Catherine M Bennett, Peter D Phelan Michael Starr, Jane Hulls and Terry M Nolan MJA 1998; 168: 106-110 Abstract - Introduction - Methods - Statistical analysis - Results - Discussion - Acknowledgements - References - Authors' details - - ©MJA1998 Abstract Objective: To estimate the prevalence of asymptomatic Mycobacterium tuberculosis infection in Melbourne secondary school students. Design: Cross-sectional Mantoux testing of a partly random and partly targeted sample of secondary school students, designed to enable estimation of prevalence by region of birth. Setting: Fifty-one State and Catholic secondary schools in metropolitan Melbourne during 1995. Participants: Australian and overseas-born students in Years 9 and 10. Outcome measures: Proportions of students with positive Mantoux reactions (defined as induration at 48 hours of ≥5 mm with a history of recent exposure; ≥10 mm and no prior BCG vaccination; ≥15 mm and prior BCG vaccination). Results: Of 2586 students potentially eligible for testing, evaluable results were obtained from 1274 (49%). The overall prevalence of infection for Melbourne students in Years 9 and 10 was 2.5% (95% CI, 1.1-3.9%). Main predictors of a positive test were birth overseas and number of years residing overseas. Prevalence varied considerably by region of birth, and was very low in students born in Australia (0.7%), "other developed countries" (0.7%), and Southern Europe (0). The highest rates were observed in students born in Indochina (15.9%), other countries in South East Asia (10.2%), and Eastern Europe (10.2%). Conclusions: The risk of a young person becoming infected with M. tuberculosis while living in Melbourne is very low. Our results do not indicate a need for the reintroduction of mass screening in Victorian schools. If targeted screening were to be considered, the group most likely to benefit would be recently arrived migrants from Indochina. Introduction Human infection with Mycobacterium tuberculosis is usually clinically silent, and may then only be detectable by a positive Mantoux skin test. A minority of infected individuals develop active tuberculosis (TB), and those with pulmonary disease are the major source of new human infections. For M. tuberculosis to persist within a community over time, each person with pulmonary TB must infect an average of 20 others.1,2 In developed countries, the transmission rate is much lower than this, and the incidence of tuberculosis has declined steadily for many years.2 In the United States, a 32-year trend of declining TB notifications was reversed in the mid 1980s.3 This resurgence is thought to have resulted in at least 51 000 unexpected cases of the disease, and has been attributed to the impact of AIDS, urban decay, homelessness and high levels of migration from regions where TB is endemic.4 Recent increases in incidence have also been reported from other developed countries, including Denmark, Italy, the Netherlands, Spain, Switzerland, France and the United Kingdom.5 In Australia, the incidence of TB has remained constant during the 1990s (rates per 100 000 population of 5.95 in 1990 and 5.75 in 1995).6 In Victoria, the annual incidence of TB per 100 000 declined from 47 in 1954 to 6.2 in 1992;7 it was 6.35 in 1995.6 In 1970 40% of new cases of active tuberculosis in Victoria were in people born overseas, but by 1990 this figure had risen to 80%. Currently, most new TB patients are migrants from Indochina and South East Asia.7 Although intending adult migrants are screened by chest x-ray before their arrival in Australia, migrant children are generally not screened, partly because childhood tuberculosis is not normally transmissible. In a recent inner-Sydney study, 27% of foreign-born Year 8 students (159 of 580), compared with 2% of those born in Australia (20 of 1221), had positive Mantoux reactions.8 As adolescents appear to have an increased risk (compared with children over three years and adults) of developing active tuberculosis,9 this group may become a source of new, locally acquired infection. During 1995, we conducted a Mantoux survey of healthy metropolitan Melbourne secondary students in Years 9 and 10. Our aim was to estimate the prevalence of asymptomatic TB infection, and to identify specific groups of students by region of birth who may benefit from future targeted screening and intervention programs. Methods The study was a cross-sectional survey of secondary school students in the metropolitan region of Melbourne (population, 3.1 million, with people aged 12 to 17 years comprising approximately 8% [Australian Bureau of Statistics, 1996 Census]). To recruit enough overseas-born students for estimating prevalence by region of birth, we used a combination of targeted and random sampling, aiming to include schools where at least 4% of students were born overseas, plus a 5% random sample of all other schools. The Australian Bureau of Statistics (ABS) provided numbers and country of birth of Melbourne residents aged 12 to 17 years from the 1991 national census. The Directorate of School Education and the Catholic Education Office provided numbers of students at each school speaking a language other than English at home. These data were combined and used to select schools with high enrolments of overseas-born students. Independent schools were not included as they comprised only 18% of all Year 9 and Year 10 students (Directorate of School Education, personal communication), and we assumed that they would have a low proportion of recently arrived overseas-born students. Of 50 purposely selected and seven randomly selected schools approached, six and one, respectively, declined. The randomly selected school was replaced by a neighbouring school, so that 51 schools participated. Parents of all students in Years 9 and 10 at each participating school were provided with an explanatory letter and a short survey (in English and, if appropriate, one of 12 translations). The survey was part of a separate study on asthma, but included a question on country of birth and sought permission to approach students a second time for the TB study. The initial (asthma) survey was distributed to all 13 020 Year 9 and Year 10 students at the 51 schools; 9794 usable responses were obtained (75%). Respondents comprised 85% from purposely selected and 15% from randomly selected schools. From the returned surveys we created 12 notional region-of-birth groups, based partly on geography and partly on numbers of respondents to the first survey, and an additional group comprising Australian-born students with both parents born in Asia (Box 1). We aimed to enrol approximately 200 students from each group to allow us to estimate prevalence within each with a 95% confidence interval of ± 1.9% if the true prevalence were 2%, and ± 6.4% if the true prevalence were 30%. Selection for Mantoux testing was random, except when the number of respondents in a category was less than 200, in which case all respondents from that region were included. Parents of students selected for Mantoux testing were sent information letters, consent forms and a TB survey (in English and one of 14 translations). This survey sought parental consent for Mantoux testing and included questions on parents' country of birth, date of arrival in Australia and history of BCG vaccination. Mantoux testing (by two experienced nurses, with two assistants from the Victorian Tuberculosis Program) was performed at school. Responses on each TB survey were checked for completeness and each student's deltoids, forearms and scapulas inspected for the presence of BCG vaccination scars before testing, which involved intradermal injection of 0.1 mL of a 100 IU/mL solution of purified protein derivative (PPD; CSL Limited, Parkville, Vic.) to the volar aspect of the student's left forearm. A single batch of PPD was used throughout. At between 48 and 72 hours, the extent of transverse palpable induration was measured by ruler and recorded in millimetres. The study was approved by the Ethics in Human Research Committee of the Royal Children's Hospital. Statistical analysis We used the exact binomial method for confidence intervals and the chi-squared test for comparisons between groups. Logistic regression was used to estimate prevalences, adjusted for differences in duration of residence in Australia. As we had deliberately selected schools with high concentrations of foreign-born students, we estimated overall prevalence of infection by direct standardisation to the population distribution of region of birth in students aged 12 to 17 years in metropolitan Melbourne (1991 Census data, ABS). Results Of 2586 students (the results of our efforts to create the 13 groups) sent the TB survey, 620 (24.0%) did not return it, and 692 (27%) returned completed surveys but declined to be tested or were away on the day of testing. Test results were therefore available for 1274 students (49%). To explore the potential for response bias, survey response rates and acceptance of testing were compared between subgroups defined by age, sex and time since arrival in Australia (Box 2). Younger students and females were statistically more likely to return their surveys than older students and males (data not shown), but refusal to be tested did not vary between these subgroups. Proportions of students with Mantoux reactions that were positive by National Health and Medical Research Council criteria (≥5 mm with a history of recent exposure; ≥10 mm and no prior BCG vaccination; ≥15 mm and prior BCG vaccination8,10 ) were compared by region-of-birth group (Box 3). Birth overseas, number of years resident outside Australia (Box 4) and past BCG vaccination were predictors of a positive result. The crude prevalence was 5.3%. After standardisation by region of birth, we estimated that 2.5% of all students in Years 9 and 10 in metropolitan Melbourne had positive Mantoux results (95% CI, 1.1-3.9%). Students born in Australia, "other developed countries" and Southern Europe had the lowest rates (0.7%, 0.7% and 0, respectively). The highest rates were observed in students born in Indochina (15.9%), other countries in South East Asia (10.2%), and Eastern Europe (10.2%) (Box 3). Differences in mean number of years resident overseas between the groups prevented direct statistical comparison, so logistic regression was used to estimate the odds ratio for increase of risk for each year lived overseas (odds ratio per year, 1.15; 95% CI, 1.08-1.24), and to standardise rates by region so they could be compared directly. After this adjustment, statistically significant differences in prevalence by region persisted, but the ranking of some regions, most notably Eastern Europe, was altered (Box 3). Prevalence of TB in the group of Australian-born students with Asian-born parents was 3.6%. None of these students had received a prior BCG vaccination. This prevalence was fivefold higher than the background rate of 0.7% for other students born in Australia, but this difference did not reach statistical significance (P = 0.17, two-tailed Fisher's exact test). The 244 students with a result ≥10 mm and the two with a result ≥5 mm plus a history of exposure to someone known to have TB were referred to a special clinic at the Royal Children's Hospital for chest x-ray and clinical review. However, 10 students with indurations ≥10 mm declined to attend the clinic, five of whom had positive Mantoux reactions. Of the 236 students who attended the clinic, 174 had at least one BCG vaccination scar and/or documentary evidence of BCG vaccination and a Mantoux reaction < 15 mm; these were therefore considered to have negative results. Students with results positive by NHMRC criteria8,10 were offered isoniazid preventive therapy, provided there was no evidence of active disease and they had not been previously treated. Sixty-two students had positive Mantoux reactions. Of these, seven had previously been prescribed isoniazid preventive therapy, two had previously been treated for TB disease, and one (a recently arrived refugee from East Timor) had active pulmonary TB. Five students refused isoniazid therapy, and five were not offered therapy as they were considered to have a reduced risk (recent BCG). Forty-two students with positive Mantoux reactions were offered isoniazid preventive therapy; 38 (90%) completed six months of treatment. Multiple BCG scars (evidence of previous vaccinations) were common in students from Eastern Europe (mean number, 1.6; 33% of students with ≥2 scars) and the Middle East, whereas those from Indochina generally had only one (mean number, 0.9; 11% of students with ≥2 scars). Discussion The risk of a young person becoming infected with M. tuberculosis while living in Melbourne appears to be very low. The major determinant of the size of the Mantoux reaction in this study was birth overseas. However, most students with reactions to testing had also received at least one prior BCG vaccination, which complicates interpretation. Most Australian-born students had not been vaccinated, and the prevalence of infection in this group was very low (0.7%, giving a calculated annual risk of infection of 0.04% per year). The higher prevalence in Australian-born students with Asian-born parents may be the result of low-level transmission within migrant communities, although the apparent difference could have been due to chance. For those born overseas, the number of years spent outside Australia correlated positively with Mantoux results, indicating that the risk of infection increases with duration of residence in an endemic region. The prevalence of infection in Year 9 and Year 10 students in metropolitan Melbourne appeared to be approximately half that identified in a recent survey in Year 8 students in inner Sydney, both overall and within specific migrant subgroups.8 The authors of the Sydney study commented that the prevalence they identified was higher than previously reported in Australia and have since found a slightly lower prevalence in a further survey of younger students.11 Our lower rate may be the result of differing patterns of migration between Melbourne and Sydney, or the selection of our sample from the whole metropolitan region instead of just the inner city. Although only half of eligible students in our study were tested, we do not believe that our results are systematically biased in a way that would have led us to grossly underestimate prevalence. In particular, we found no association between recent arrival in Australia and the likelihood of refusing to be tested, and the group with the lowest participation rate (Eastern Europe) showed the second-highest prevalence. In retrospect, acceptance of testing may have been improved by selecting whole classes rather than individuals within a class for testing, and our two-stage study design allowed ample opportunity for students to withdraw. However, any future targeted screening program would need to select individuals from within a larger group, and part of our study rationale was to investigate the acceptability of such programs. Even if it were assumed that non-participants had twice the prevalence of those tested, the true prevalence would only be 50% greater than our estimates. There is controversy about the influence of BCG vaccination on the results of subsequent Mantoux testing. In countries with a high prevalence of TB infection, a single BCG vaccination is often given shortly after birth, but this is unlikely to influence the result of a Mantoux test 15 years later.12 By contrast, BCG given to older children or given several times during childhood probably does influence Mantoux reaction size.13 Although the current NHMRC guidelines make some allowance for past BCG vaccination, they could be further refined.13 For example, for recently arrived migrants who have received a single BCG vaccination early in life and who have lived for many years in a region of high prevalence it may be appropriate to use ≥10 mm to indicate a positive reaction, while for migrants from countries that routinely give three BCG vaccinations in childhood but have a lower prevalence of infection ≥20 mm may be more appropriate.13 Whether or not such refinements are introduced, the distinction between positive and negative reactions will remain somewhat arbitrary; a more reliable test is urgently required. Mass screening of secondary school students by Mantoux test was discontinued in Victoria over 10 years ago. Our results do not suggest that such programs need to be reintroduced, and recent overseas studies suggest that mass screening at school is unlikely to be cost effective.14-16 However, 24% of overseas-born students in our study had Mantoux reactions ≥10 mm, one of whom had active pulmonary disease and one-quarter of whom were considered eligible for isoniazid preventive therapy. If reactions of ≥10 mm for students born in a high-risk region with a history of having received a single BCG vaccination in infancy were considered positive, the number of students eligible for preventive therapy would increase further. If targeted screening were introduced, the group most likely to benefit would be recently arrived students from Indochina. We offered isoniazid therapy to students who tested positive because adolescents have an increased risk of developing active tuberculosis.9,17 However, we were mindful that isoniazid therapy is not entirely without risk even in young people,18-20 and that the risk of infection progressing to disease in an affluent society with a low prevalence of HIV infection may be much lower than the 10% often quoted.21 We cannot therefore be completely confident that wider use of isoniazid in this way would result in a net benefit to the Australian community. Acknowledgements This study was supported by a grant from the John Burge Estate administered by the Victorian Department of Human Services. We gratefully acknowledge the assistance of the principals, coordinators, teachers, students and parents at the participating schools. We also wish to thank the following individuals: Mary Randall, Mary McColl and staff of the Victorian Tuberculosis Program; Marita Dalton, Colin Powell, Department of Thoracic Medicine; and Susan Sawyer, Centre for Adolescent Health, Royal Children's Hospital. References Bates JH, Stead WW. The history of tuberculosis as a global epidemic. Med Clin North Am 1993; 77: 1205-1217. Styblo K. Recent advances in epidemiological research in tuberculosis. Tuberc Res 1980; 20: 1-63. Centers for Disease Control and Prevention. Tuberculosis morbidity -- United States, 1992. MMWR Morb Mortal Wkly Rep 1993; 42: 696-704. Snider DE Jr, Raviglione M, Kochi A. Global burden of tuberculosis. In: Bloom BR, editor. Tuberculosis: pathogenesis, protection and control. Washington DC: ASM Press, 1994: 3-12. Raviglione MC, Sudre P, Rieder HL, et al. Secular trends of tuberculosis in western Europe. Bull World Health Organ 1993; 71: 297-306. Oliver G, Harvey B. Tuberculosis notifications in Australia, 1995. Commun Dis Intell 1997; 21: 261-269. MacIntyre CR, Dwyer B, Streeton JA. The epidemiology of tuberculosis in Victoria. Med J Aust 1993; 159: 672-677. Alperstein G, Fett MJ, Reznik R, et al. The prevalence of tuberculosis infection among year 8 schoolchildren in inner Sydney in 1992. Med J Aust 1994; 160: 197-201. Comstock GW, Livesay VT, Woolpert SF. The prognosis of a positive tuberculin reaction in childhood and adolescence. Am J Epidemiol 1974; 99: 131-138. National Health and Medical Research Council. Tuberculosis in Australia and New Zealand into the 1990s. Canberra: AGPS, 1990. Alperstein G, Morgan KR, Fett MJ, et al. Prevalence of tuberculosis infection among primary school-entry children in Sydney. A N Z J Pub Health 1996; 20: 123-128. Menzies R, Vissandjee B. Effect of bacille Calmette-Guerin vaccination on tuberculin reactivity. Am Rev Resp Dis 1992; 145: 621-625. Ildirim I, Hacimustafaoglu M, Ediz B. Correlation of tuberculin induration with the number of Bacillus Calmette-GuŽrin vaccines. Ped Infect Dis J 1995; 14: 1060-1063. Driver CR, Valway SE, Cantwell MF, Onorato IM. Tuberculin skin test screening in schoolchildren in the United States. Pediatrics 1996; 98: 97-102. Mohle-Boetani JC, Miller B, Halper M, et al. School-based screening for tuberculous infection: a cost-benefit analysis. JAMA 1995; 274: 613-619. Starke JR. Universal screening for tuberculosis infection: school's out! JAMA 1995; 274: 652-653. Katz J, Kunofsky S. Logistics of chemoprophylaxis of tuberculosis. Chest 1971; 59: 600-605. Gal AA, Klatt EC. Fatal isoniazid hepatitis in a child. Ped Infect Dis J 1986; 5: 490-491. Israel HL, Gottlieb JE, Maddrey WC. Perspective: preventive isoniazid therapy and the liver. Chest 1992; 101: 1298-1301. Millard PS, Wilcosky TC, Reade-Christopher SJ, Weber DJ. Isoniazid-related fatal hepatitis. West J Med 1996; 164: 486-491. Haas DW, Des Prez RM. Mycobacterium tuberculosis . In: Mandell GL, Bennett JE, Dolin R, editors. Principles and practice of infectious diseases. 4th ed. New York: Churchill Livingstone, 1995: 2213-2243. (Received 23 May, accepted 27 Sep, 1997) Authors' details Clinical Epidemiology and Biostatistics Unit, Royal Children's Hospital, Melbourne, VIC. Paul D R Johnson, FRACP, PhD, Research Officer, Royal Children's Hospital Research Institute (also, Infectious Diseases Physician, Department of Infectious Diseases and Clinical Epidemiology, Monash Medical Centre); John B Carlin, BSc(Hons), PhD, Deputy Head (also, Associate Professor, University of Melbourne, Department of Paediatrics); Catherine M Bennett, BSc(Hons), Research Officer; Jane Hulls, RN, Research Nurse; Terry M Nolan, PhD, FRACP, Head (also, Associate Professor, University of Melbourne, Department of Paediatrics). University of Melbourne, Department of Paediatrics, Royal Children's Hospital, Melbourne, VIC. Peter D Phelan, MD, FRACP, Stevenson Professor, and Head (currently, Emeritus Professor of Paediatrics). Department of Microbiology and Infectious Diseases, Royal Children's Hospital, Melbourne, VIC. Michael Starr, MB BS, FRACP, Paediatrician. Reprints: Dr P D R Johnson, Department of Infectious Diseases and Clinical Epidemiology, Monash Medical Centre, Clayton, VIC 3168. E-mail: Paul. Johnson AT med.monash.edu.au Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Paul D R Johnson FRACP, PhD · John B Carlin · Catherine M Bennett · Peter D Phelan · Michael Starr · Jane Hulls · Terry M Nolan

Apolipoprotein screening in Australian children: feasibility and the effect of age, sex, and ethnicity Judith F Lynch, Michelle D Marshall, Xing L Wang and David E L Wilcken MJA 1998; 168: 61-64 Abstract - Introduction - Methods - Results - Discussion - References - Authors' details - - ©MJA1998 Abstract Objectives: (i) To evaluate the feasibility of detecting adverse lipid profiles in schoolchildren by measuring capillary dried blood spot apolipoprotein levels, and (ii) to assess the effect of age, sex and ethnicity on apolipoprotein levels. Design: We measured capillary dried blood spot apolipoproteins B and A-I (apo B and apo A-I); assessed levels in relation to age, sex and ethnicity; and recalled children with elevated levels for a full lipid profile measurement. Participants and setting: 6992 children (3501 boys and 3491 girls), aged 5-13 years, from schools in eastern Sydney, 1991-1995. Main outcome measures: Capillary blood levels of apolipoproteins B and A-I, and serum total cholesterol level. Results: Of the 6951 children who provided an adequate fingerprick blood sample, we recalled 1465 children (21.1%) (640 boys [43.7%] and 825 girls [56.3%]) with elevated apo B levels and/or apo B : apo A-I ratios for further testing, either by us or by their family doctor (overall estimated compliance rate up to 70%). Among the 458 children who returned to us, there was a 90% positive predictive value for a total cholesterol level of over 4.5 mmol/L in those with both elevated apo B levels and high apo B : apo A-I ratios. Girls had higher apo B levels and apo B : apo A-I ratios than boys (P < 0.00001 for both), and in both sexes there was a trend downwards for apo B and upwards for apo B : apo A-I ratio over the age range tested, but levels were relatively stable between the ages of 6 and 10 years. Indian children (1.5% of the screened population) had the highest apo B levels, followed by white children (71.1%); Asian children (9.2%) had the lowest (P < 0.00001 compared with Indian and white children). Conclusions: The high positive predictive value of capillary blood apolipoprotein levels for an adverse lipid profile in children suggests that measuring apolipoprotein levels by this method is a useful initial approach to cardiovascular risk assessment. Introduction Despite a recent decline in cardiac deaths, coronary disease is still the largest single cause of premature death in Australia.1 It is known that atherogenesis, the underlying pathological process, may begin in childhood;2,3 that relevant risk factors may track from childhood to adulthood (particularly elevated levels of total and low-density lipoprotein [LDL] cholesterol and increased body weight); and that these factors tend to aggregate within families.4,5 With these considerations in mind, we explored the feasibility of screening for adverse lipid profiles in a target group of primary schoolchildren, with the aim of implementing family-based coronary prevention by secondarily identifying any parents at risk. We measured levels of apolipoprotein B (apo B), the carrier protein for the atherogenic LDL cholesterol, and apolipoprotein A-I (apo A-I), the principal carrier protein for the antiatherogenic high density lipoprotein (HDL) cholesterol, in capillary dried blood spots from 6992 primary schoolchildren aged 5-13 years. There is increasing evidence that high apo B and low apo A-I levels are as reflective of cardiovascular risk as are their respective lipoproteins.6 We describe here the positive predictive value of high apo B and/or apo B : apo A-I ratio for elevated total cholesterol levels and the effects of age, sex and eth nicity on lipid levels in Australian children. Methods School and population demographics We received permission from 70 schools in eastern Sydney (public primary schools, 45%; Catholic primary schools, 29%; and private fee-paying schools, 26%) to contact parents and offer them the option of their child participating in a "Heart Health Screening Program". Children were given consent forms to take home to their parents. On the forms, we asked for the country of origin of each family, and this information was confirmed by a family history questionnaire (sent to all parents within a week of the testing at school) asking each parent to identify their country of origin. Only 1% of the total declined to answer this question (the "unknown" group) (Table 1). Blood collection and apolipoprotein measurement Testing took place between 1991 and 1995. From each child we obtained a capillary blood sample by fingerprick, which was spotted directly onto filter paper (No. 903: Schleicher & Schuell Inc., Keene, NH, USA), allowed to air dry and stored at 2 70¡C until analysis. Concentrations of dried blood spot apo B, apo A-I and lipoprotein (a) (Lp(a)) were measured within two weeks by our previously described enzyme-linked immunosorbent assay methods,7-9 and from these results an apo B : apo A-I ratio was also calculated. These methods allowed us to carry out all three measurements on one small (minimum, 20 µL sample) capillary dried blood spot. We report here the results obtained for measurement of apo B and apo A-I only. Recall In the first school tested, we established the frequency distribution for apo B levels and apo B : apo A-I ratios and set the level for recall for each of these as at or above the 90th percentile. These cut-off points were adjusted from the apo lipoprotein results obtained from each of the next seven schools. However, a stable cut-off level was reached by the third school. We defined three categories of children for recall: those with an ele vated apo B level only (Criterion 1), those with a combination of elevated apo B level and apo B : apo A-I ratio (Criterion 2), and finally those with an elevated apo B : apo A-I ratio only (Criterion 3). We notified the parents of the children for recall by letter, explaining the results and suggesting that both parents, the child, and any other siblings might come to us for further lipid testing, or attend their family doctor. In those who returned to us, we measured total cholesterol level, as well as HDL cholesterol and triglyceride levels, in a venous blood sample by standard methods. LDL cholesterol level was calculated by the Friedewald formula,10 and we also measured serum apo B, apo A-I and Lp(a) by the methods outlined above.7-9 The parents of children with apo B levels and apo B : apo A-I ratios below the established cut-off points were also sent a letter explaining that their children's levels currently fell below the recall criteria. These families were sent a healthy lifestyle pamphlet specifically directed to maintaining a low level of cardiovascular risk; they were also asked if they would like to volunteer as a healthy control family and have complete lipid profiles measured as above. Statistical analysis As the distributions of age, apo B and apo A-I levels, and apo B : apo A-I ratios were normal, analyses by parametric methods were appropriate. We used one-way analysis of variance (ANOVA) for comparisons of measured quantitative variables when there were more than two groups; for example, when children were divided according to high apo B, high apo B : apo A-I ratio, or both, as categorical variables, and levels of total cholesterol and LDL cholesterol, and total cholesterol to HDL cholesterol ratio as the continuous outcome variables. When the comparison was between two groups -- for example, when lipid values were compared in girls and boys as categorical determinants -- Student's t test was used.11 We employed a chi-squared comparison for assessing associations between categorical variables, and used the SPSS statistical software package for all analyses.12 Ethical approval The study was approved by the ethics committee of the University of New South Wales. Results Initial testing The parental consent rate to initial testing was 63.9%. There were 6992 children aged 5-13 years available for testing, 3501 (50.1%) boys and 3491 (49.9%) girls. Only 41 children (0.6%) failed to provide an adequate finger-prick blood sample on the day, leaving a total population of 6951 children tested. Recall population The cut-off point for apo B level was set at 0.550 g/L or more and for the apo B : apo A-I ratio 1.200 or more. We recalled 1465 children (or 21.1% of the population tested). Of these recalls, 65.3% were for elevated apo B only (Criterion 1), 19.6% for elevated apo B and apo B : apo A-I ratio (Criterion 2), and 15.1% for elevated apo B : apo A-I ratio only (Criterion 3). In all, 458 of the children recalled returned with their families to our laboratory for lipid studies (31.2% compliance rate). To obtain an assessment of how many may have been seen by their family doctor (the other option we suggested), we contacted 205 of the remaining 1007 families. Among these, 118 had seen their family doctor for follow-up, and 89 had either moved or were not interested in further testing. This suggested an overall compliance rate of about 70%, if this sample was representative. Of the non-recalled "normal" population of 5486 (78.9%), only 151 families (2.7%) volunteered for lipid testing, an insufficient number for meaningful statistical analysis. Predictive value We used the results of the 458 children who returned for a full lipid profile to assess the positive predictive value of our screening method. The National Heart Foundation of Australia recommends a total cholesterol level of 4.5 mmol/L as the upper limit for children in this age range.13 With a level of over 4.5 mmol/L as the endpoint, Criterion 1 (elevated apo B only) had a positive predictive value of 84% (95% confidence interval [CI], 80%-88%), and with Criterion 2 (elevated apo B level and apo B : apo A-I ratio combined) the predictive value increased to 90% (95% CI, 85%-95%). However, Criterion 3 (elevated apo B : apo A-I ratio only) yielded only 66% (95% CI, 54%-77%), possibly reflecting children with low HDL cholesterol and normal total cholesterol levels. Raising the cut-off point did not substantially improve the positive predictive value of our screening method. When the cut-off point for apo B was increased from 0.550 g/L to 0.700 g/L, for example, the positive predictive value of Criterion 2, the most strongly predictive, only increased to 94% (95% CI, 91%-97%). ANOVA confirmed the association between high apo B levels from analysis of dried blood spot and an adverse lipid profile, and also that a combined high apo B level and apo B : apo A-I ratio was a stronger predictor. In this analysis, criteria established by high apo B, high apo B : apo A-I ratio and a combination of both were determinant categorical variables, and the total cholesterol and LDL cholesterol levels and total chol es terol to HDL cholesterol ratio were the continuous outcomes. Total (P < 0.0006) and LDL cholesterol (P < 0.0014) levels and the total cholesterol to HDL cholesterol ratio (P < 0.0006) were all significantly higher in Criterion 2 than in Criterion 1 or Criterion 3 (Table 2). Sex, age and ethnicity There was a highly significant difference in the apo B and apo B : apo A-I ratio levels between boys and girls (P < 0.00001 for each) (Figures 1 and 2), but no difference (P = 0.6) in apo A-I levels (data not shown). The girls had consistently higher apo B levels and apo B : apo A-I ratios over the age range studied (Figures 1 and 2). This resulted in a significant difference in the recall rate between girls and boys (chi-squared = 23.362; P < 0.00001). This sex difference was also reflected in the total cholesterol levels of children returning for further lipid tests (data not shown). As shown in Figures 1 and 2, there was a downward trend in apo B level and an upward one in apo B : apo A-I ratio in boys over the age range screened, while the opposite was observed in girls; but levels were relatively consistent in both between the ages of 6 and 10 years. Most of the 6951 children screened were white (71.1%); the remainder were of diverse ethnic origins (Table 1). The mixed-race group (8.3% of the total) included white/Asian (28.2%), white/Arabic (17.8%), white/South American (10.7%), and other combinations (56.7%). As age was a significant contributor to apo B concentrations, we compared the "age adjusted apo B levels" for both boys and girls to assess potential differences between major ethnic groups (Figure 3). Indian children had the highest apo B levels, followed by white children. Asian children had the lowest levels and these were significantly different from those of the Indian, white, mixed-race and South American children (P < 0.00001 for each). We did not include black, Australian Aboriginal or Pacific Islander ethnic groups in this analysis because of small numbers and highly skewed age distributions. In all ethnic groups, girls had higher levels than boys (Figure 3). Discussion We have established previously that apolipoprotein measurements provide a convenient and effective approach to the detection of dyslipidaemia,14 and that apo B levels in children are correlated with the occurrence of coronary events in their grandparents, which highlights the relevance of measurements in children to assessing risk of vascular disease in older family members.15 We have also established a clear-cut association between increased apo B levels and apo B : apo A-I ratios and body mass index in Australian children.16 Here, we extend these find ings by demonstrating the feasibility of screening of schoolchildren's capillary blood apolipoprotein levels as an approach to family-based primary coronary prevention. Although we do not have adequate data to determine the sensitivity or specificity of our screening method, the presence of both an elevated apo B level and raised apo B : apo A-I ratios had a positive predictive value of 90% for the detection of elevated total serum cholesterol level. Raising the apolipoprotein cut-off points only improved the predictive value to 94%. This method identified elevated apolipoprotein levels in 21.1% of our population, of whom 90% had elevated total cholesterol levels. Screening for apolipoprotein levels may be more relevant than screening for total cholesterol levels alone, as total cholesterol level does not show the interrelations between levels of the atherogenic LDL and the antiatherogenic HDL cholesterol.17 In a small number of children (0.48%) apo B levels were elevated without elevation of total cholesterol level.18 These families were also provided with dietary and lifestyle advice as this may also be associated with increased cardio vascular risk. Our findings clearly show highly significant differences between boys and girls at this age, with girls having higher apo B levels and apo B : apo A-I ratios than boys. We suspect this biological difference, which was evident before the onset of puberty in both boys and girls, to be hormonally based, although we have no data to support this. The vari ation in apolipoprotein levels within the age range studied could also be hormonally based. Whatever the mech anisms, these same age-related sex differences have been identified in several other studies in children.19,20 The consistency of these results clearly indicates a need to have different cut-off points in boys and girls for elevated apolipoprotein levels. Our results also define the age range (between 6 and 10 years) when levels are most stable and most appropriate for screening, findings which will be incorporated into future studies. There were uniform sex-related differences in apolipoprotein levels in each of the racial groups in our population, as well as very significant differences in levels between the various ethnic groups, as has also been found in previous studies.21,22 In our population, Indian and white children had the highest apo B and apo B : apo A-I ratios and Asian children had the lowest. It is well established that Chinese and Japanese populations have much lower cholesterol levels than whites and a correspondingly lower prevalence of coronary artery disease. Indian populations have a higher prevalence of cardiovascular disease.23 While these variations may relate to the genetic background of each ethnic group, diet and lifestyle undoubtedly make major contributions, and this is particularly evident in non-Western groups who have moved to live in a Western society. The higher prevalence of coronary disease in Indians living in the United Kingdom, for example, is well documented.24 Ethnic differences may become blurred with time if dietary habits become more uniform, and this has occurred among Asians emigrating to the United States and the United Kingdom; within a generation they acquired local lifestyles and a correspondingly higher prevalence of coronary artery disease than that in the communities they had left.25,26 In conclusion, our study demonstrates the feasibility of conducting a program of measuring apolipoprotein levels in capillary blood samples to assess lipid profiles in children to facilitate family-based coronary prevention. It documents wide acceptance by both schools and parents. Implicit in such a study is the potential for a multiplier effect in that, if a child has an elevated apolipoprotein level and therefore an adverse lipid profile, it is very likely that this will also be seen in at least one parent and other siblings.27 Our ongoing screening program requires the establishment of a concurrent intervention program to improve dietary and lifestyle habits of affected children and their parents. This is of more immediate relevance to affected parents as they are approaching the age of overt coronary disease. However, the program provides an ideal opportunity to establish healthy lifestyles in young children at a time of easy acceptance, and with the potential for preventing a disorder that may have its origins in childhood.28 References Heart and Stroke Facts. A report by the National Heart Foundation of Australia. Canberra: NHFA, 1996. Stary HC. Evolution and progression of atherosclerotic lesions in coronary arteries of children and young adults. Arteriosclerosis 1989; 9(1 Suppl): I19-I32. Tracy RE, Newman WP, Wattigney WA, Berenson GS. Risk factors and atherosclerosis in youth autopsy findings of the Bogalusa Heart Study. Am J Med Sci 1995; 310(Suppl 1): S37-S41. Berenson GS, Wattigney WA, Bao W, et al. Rationale to study the early natural history of heart disease: the Bogalusa Heart Study [review]. Am J Med Sci 1995; 310(Suppl 1): S22-S28. Sanchez-Bayle M, Gonzalez-Requjo A, Ruiz-Jarabo C, et al. Serum lipids and lipoproteins in Spanish children and adolescents: a 5 year follow-up. Acta Paediatr 1996; 85: 292-294. Bao W, Srinivassan SR, Berenson GS. Tracking of serum apolipoproteins A-I and B in children and young adults: the Bogalusa Heart Study. J Clin Epidemiol 1993; 46: 609-616. Wang XL, Dudman NP, Wilcken DE. Enzyme-linked immunosorbent assay of apolipoprotein B in blood spotted onto filter paper, suitable for neonatal screening. Clin Chem 1989; 35: 1000-1004. Wang XL, Dudman NP, Blades BL, Wilcken DE. Changes in the immunoreactivity of apo A-I during storage. Clin Chem 1989; 179: 285-293. Wang XL, Wilcken DE, Dudman NP. An indirect sandwich ELISA for Lp(a) in serum and dried blood spots. Clin Chim Acta 1992; 207: 73-86. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972; 18: 499-502. Norusis MJ. General factorial analysis of variance. SPSS for Windows Advanced Statistics, release 6.0. Chicago: SPSS Inc, 1993: 31-56. McNeil D. Statistical methods II: one-way analysis of variance. In: McNeil D, editor. Epidemiological research methods. New York: John Wiley & Sons, 1996: 66-71. National Diet and Heart Disease Advisory Committee, National Heart Foundation of Australia. Guide to plasma lipids for doctors. Curr Therap 1992; 10(Suppl 1): S1-S8. Wang XL, Wilcken DE, Dudman NP. Apolipoprotein A- I and B and the B/A-I ratio in the first year of life. Pediatr Res 1991; 30: 544-549. Wilcken DEL, Wang XL, Greenwood J, Lynch JF. Lipoprotein (a) and apolipoproteins B and A-I in children and coronary vascular events in their grandparents. J Pediatr 1993; 123: 519-526. Wilcken DE, Lynch JF, Marshall MD, et al. Relevance of body weight to apolipoprotein levels in Australian children. Med J Aust 1996; 164: 22-25. Taylor CJ, Olpin S, Rattenbury J, et al. Familial hyper cholesterolaemia: pilot study to identify children at risk. J Clin Pathol 1993; 46: 730-733. Grundy S. Small LDL. Atherogenic dyslipidaemia and the metabolic syndrome. Circulation 1997; 95: 1-4. Resnicow K, Morley-Kotchen J, Wynder E. Plasma cholesterol levels of 6585 children in the United States: results of the know your body screening in five states. Pediatrics 1989; 84: 969-976. Christensen B, Glueck C, Kwiterovich P, et al. Plasma cholesterol and triglyceride distributions in 13,665 children and adolescents: the Prevalence Study of the Lipid Research Clinics Program. Pediatr Res 1980; 14: 194-202. Zhang W, Evans AE, Cambien F, et al. Distribution of lipid variables in subjects in Belfast, Northern Ireland and Taiyuan, PR China. Atherosclerosis 1993; 102: 175-180. Freedman DS, Lee SL, Byers T, et al. Serum cholesterol levels in a multiracial sample of 7,439 preschool children from Arizona. Prev Med 1992; 21: 162-176. Enas EA, Mehta J. Malignant coronary artery disease in young Asian Indians: thoughts on pathogenesis, prevention, and therapy. Coronary Artery Disease in Asian Indians (CADI) Study [review]. Clin Cardiol 1995; 18: 131-135. Bhatnagar D, Anand IS, Durrington PN, et al. Coronary risk factors in people from the Indian subcontinent living in west London and their siblings in India. Lancet 1995; 345: 405-409. Egusa G, Murakami F, Ito C, et al. Westernized food habits and concentration of serum lipids in the Japanese. Atherosclerosis 1993; 100: 249-255. Robinson D, Kawamura T, Hinohara S, Sakamoto Y. Levels of cardiovascular risk factors in Japanese people living in the UK. J Cardiovasc Risk 1995; 2: 449-458. Shaukat N, de Bono DP, Jones DR. Like father like son? Sons of patients of European or Indian origin with coronary artery disease reflect their parents' risk factor patterns. Br Heart J 1995; 74: 318-323. Resnicow K, Cross D, Lacosse J, Nichols P. Evaluation of a school-site cardiovascular risk factor screening intervention. Prev Med 1993; 22: 838-856. (Received 15 Apr, accepted 15 Oct, 1997) Authors' details Department of Cardiovascular Medicine, Prince Henry and Prince of Wales Hospitals, Sydney; and Community Health Services and Programs, South Eastern Sydney Area Health Service, Royal South Sydney Hospital, Sydney, NSW. Judith F Lynch, HTech, Heart Health Education Program Co-ordinator; Michelle D Marshall, BSc, Scientific Officer; Xing L Wang, PhD, Research Fellow; David E L Wilcken , MD, FRACP, Visiting Professor of Medicine. Reprints will not be available from the authors. Correspondence: Professor D E L Wilcken, Department of Cardiovascular Medicine, Room 163, Clinical Sciences Building, Prince Henry Hospital, Little Bay, Sydney, NSW 2036. Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Judith F Lynch · Michelle D Marshall · Xing L Wang

The impact of catalytic converters on motor vehicle exhaust gas suicides Virginia H Routley and Joan Ozanne-Smith MJA 1998; 168: 65-67 Abstract - Introduction - Methods - Results - Discussion - Acknowledgments - References - Authors' details - - ©MJA1998 Abstract Objective: To examine the trends in motor vehicle exhaust gas suicides since 1970 and to investigate the impact of catalytic converters. Design: Australia-wide database analyses and a retrospective stratified series of 100 Victorian cases. Data sources: Australian Bureau of Statistics, 1970-1995; Australian Institute of Health and Welfare, National Injury Surveillance Unit, 1991/92-1995/96; Victorian Coroner's files, 1994-1996. Results: There were 509 motor vehicle exhaust gas suicides in Australia in 1995, representing 22% of total suicides. Since the 1986 requirements for reduced carbon monoxide emissions from new vehicles (and thus the use of catalytic converters), the absolute numbers and rates of such suicides have increased, and they have come to represent a larger percentage of total suicides. Of 75 Victorian victims' vehicles traced, 36% were manufactured during or after 1986, showing that exhaust gas suicides have occurred in vehicles with catalytic converters. Blood carboxyhaemoglobin levels did not differ between victims using vehicles with or without catalytic converters. Between 1976 and 1991 exhaust gas suicides increased at a faster rate than motor vehicle registrations. Australian hospital admissions for exhaust gas suicide attempts have increased substantially since 1991-1992. Conclusion: Catalytic converters and the associated lower CO emission limits of 9.3 g/km had not, by 1995, resulted in a reduction in numbers, rates or percentages of exhaust gas suicides in Australia. Introduction Suicide is a major problem in Australia, with approximately 2000 deaths from suicide annually in recent years. Since 1990 suicide has become a more common cause of death than motor vehicle crashes. In 1995, suicide by motor vehicle exhaust gas accounted for 509 deaths and was second only to hanging. It was most commonly used by males (85%), especially those aged 20-50 years. Rates of motor vehicle exhaust gas suicide per 100 000 population in Australia were 4.69 for males, 1.02 for females and 2.85 total (Australian Institute for Suicide Research and Prevention, 1996; unpublished data). Further, motor vehicle exhaust gas related self-harm represented a smaller proportion of patients hospitalised for attempted suicide than of successful suicides (2.0% v. 21.6%; Australian Institute of Health and Welfare, National Injury Surveillance Unit, 1996; unpublished data), indicating the high lethality of this means of suicide. Motor vehicle availability has been found to be related to exhaust gas suicides,1 and in Australia the rates of such suicides in different States vary to some extent with motor vehicle registration rates. For example, the Northern Territory has the lowest rates for each, while Western Australia has relatively high rates (Australian Institute of Health and Welfare, National Injury Surveillance Unit, 1996; unpublished data).2 Carbon monoxide (CO), the most toxic component of motor vehicle exhaust gas, is colourless, odourless and tasteless and is produced from the incomplete combustion of organic fuels. Mild CO poisoning produces headache and drowsiness; more severe poisoning leads to collapse, coma and death.3 Other effects can include myocardial infarction, deterioration of personality and impaired memory.4,5 Environmental regulations have required carbon monoxide emission levels from vehicle exhausts to be reduced over past decades. The required maximum levels have been 24.3 g/km from July 1976 (Australian Design Rule [ADR] 27A), 9.3 g/km from 1986 for new passenger vehicles (ADR 37-00) and 2.1 g/km for new models (ADR 37-01) from 1997 and for all new passenger vehicles from 1998. To cope with the unleaded petrol legally required since 1986 to reduce environmental air pollution from exhaust emissions, vehicles usually require catalytic converters (ADR 37-00; Australian Standard 2877). These convert carbon monoxide and other pollutants into the by- products, carbon dioxide and water. The purposes of this study were to examine overall trends in exhaust gas suicides, and to investigate the impact of the 1986 reduction in allowable carbon monoxide emissions (or the effects of catalytic converters) on that suicide rate. Methods To examine the trends in exhaust gas suicide between 1970 and 1995, we analysed Australia-wide data for mortality from motor vehicle exhaust gas suicides and for total suicides by age, sex and State of residence obtained from the Australian Bureau of Statistics (ABS). We examined Australian hospital admissions data from the Australian Institute of Health and Welfare, National Injury Surveillance Unit for admissions related to motor vehicle exhaust gas suicide attempts. Rates for suicide by motor vehicle exhaust gas were obtained from the Australian Institute for Suicide Research and Prevention. Data on vehicle numbers, rates per head of population and year of manufacture were obtained from ABS publications. Australian exhaust gas suicides and motor vehicle registration rates were compared for the ABS Motor Vehicle Census years since 1970. To examine the effects of catalytic converters, we undertook a retrospective stratified case series study of 100 exhaust gas suicides in Victoria between 1 January 1994 and 31 December 1996, noting the year of manufacture of the motor vehicles involved and victims' blood levels of carboxyhaemoglobin (COHb) -- a reflection of carbon monoxide levels. We compared COHb levels in victims whose suicides involved vehicles manufactured before 1986 with those whose vehicles were manufactured from 1986 (when CO emission levels were reduced). Cases of exhaust gas suicide in 1994 were obtained from a Victorian State Coroner's Office publication,6 while those in 1995 and 1996 were obtained from the Victorian Coroner's Facilitation System database. Results Since 1975 there have been approximately 7000 motor vehicle exhaust gas suicides in Australia. Suicides show an increasing trend, with dips in 1979 and 1993 (R2 = 0.58), while motor vehicle registrations follow an exponential trend (R2 = 0.88), showing a steady rise (Figure 1). Between 1979 and 1991 such suicides increased at a faster rate than motor vehicle registrations. Motor vehicle exhaust gas suicides have steadily increased as a percentage of total suicides since at least 1970 (7% in 1970, 13% in 1980 and 22% in 1995). Hospital admissions for Australian motor vehicle exhaust gas suicide attempts have increased steadily in recent years (1994/95 data are not available), with the data showing an exponential trend (R2 = 0.99). Deaths also increased, but show no clear trend (Figure 2). The 100 cases of exhaust gas suicide obtained from the records of the Victorian Coroner comprised 33 of a total of 96 in 1994, 33 of 140 in 1995, and 34 of 136 in 1996. The year of vehicle manufacture had been recorded for only 75 of these cases (25 in each of 1994, 1995 and 1996). Of these 75, 20% in 1994, 56% in 1995 and 32% in 1996 involved vehicles manufactured in 1986 or later. In total, 27 of the 75 vehicles (36%) were 1986 models or later. This proportion is not significantly different (P = 0.62) from the 39% of vehicles manufactured in 1986 or later in the total Victorian fleet of 2 799 310 vehicles in May 1995 (ABS 1995 Motor Vehicle Census).2 For the 74 cases in which both the victim's COHb level and the age of the vehicle was known, 26 involved vehicles manufactured in 1986 or later and 48 involved earlier models. The median COHb level of victims in these two groups was identical (77.1%). Discussion Motor vehicle exhaust gas suicide is a major public health problem in Australia, accounting for 22% of suicides in 1995. Despite the introduction of catalytic converters and the 1986 reduction in CO exhaust limits, motor vehicle exhaust gas suicides have increased in number, rate and as a proportion of total suicides since 1986. Hospitalisations, however, have doubled, suggesting an increase in failed attempts, and the rate curve for successful suicides also appears to be flattening in the 1990s. In 1995, 43% of registered Australian motor vehicles were manufactured in 1986 or later.2 If exhaust gas suicide had been made impossible by catalytic converters and the 1986 reduced CO emission standard of 9.3 g/km, then rates for such suicides should have reduced from 2.08 to about 1.19 per 100 000 population between 1985 and 1995 (assuming a similar distribution of vehicles to that of the Australian fleet and an unchanged number of attempts). In fact, rates per 100 000 population have been about 2.5 for the past five years and peaked at 2.85 in 1995. It is clear from our investigation of the sample from the Victorian Coroner's files that vehicles manufactured since 1986 have been used in exhaust gas suicides. Our finding that there was no difference in median COHb levels between victims who used vehicles with and without catalytic converters is consistent with the results of a New South Wales study.7 Given that CO emissions from vehicles with catalytic converters are lower, it can be deduced that time (and possibly other factors) need further investigation. The few overseas studies which have examined the relationship between suicides and motor vehicle exhaust gas have found that imposing emission controls reduces the incidence of such suicides.8-10 Vehicle emission limits for CO in the US have been lower than those in Australia, being at our 1986 limit (9.3 g/km) as early as 1975 and at just under our 1997 limit (2.1 g/km) in 1981.11 Thus, US trends should shed some light on the Australian situation, especially as the test conditions are similar. However, it should be noted that the average age of vehicles in the US is seven years, compared with 11 years in Australia, which suggests that there would be a longer lag time for exhaust emission changes to affect suicide rates in Australia. Motor vehicle exhaust gas is a less popular method of suicide in the United States than in Australia (1991 rates per 100 000 population being 0.73, compared with 2.78 for Australia).12 Data available for the US to 1991 show a decline in the exhaust gas suicide rate from the years 1963 to 1979, an increase from 1981 to 1987, followed by a decline to below the pre-1982 rates. Exhaust gas suicides in the US have decreased from 8.9% of suicides in 1970 to 7.4% in 1980 and 5.6% in 1991.8,12 Despite some conflicting evidence in Australia and the US as to the reductions in CO exhaust emission levels ne cessary for influencing exhaust gas suicide rates, these emission reductions do not appear to have produced the success suggested by early reports in the international literature.8-10 There are a variety of possible explanations for this. Firstly, exhaust gas suicides usually involve a hose or pipe being used to feed exhaust gas from an idling vehicle into the sealed interior of a vehicle. Clearly, CO emission levels set for environmental reasons may not be particularly relevant in this situation, and if suicides are to be prevented it would be more appropriate to set CO emission limits in relation to each vehicle's cabin volume. Further, testing vehicles for compliance with environmental standards involves three phases, none of which involve engine idling (during which CO emission could be higher) only. Secondly, CO emissions from vehicles with catalytic converters may exceed the legislated limit. Specific examples are: the engine idles from a cold start, with a delay of 1.5-3 minutes before the catalytic converter has warmed up and is operating efficiently (as blood COHb concentration rises most rapidly when first exposed to CO the initial absorption rate would be particularly high3 ); the condition of the catalytic converter has deteriorated or the engine may require tuning (under ADR 37-00 a catalytic converter is required to operate effectively for 80 000 km or five years, whichever occurs first); and for reasons that are unclear, the pollution performance of 4-9-year-old cars has been found to deteriorate faster than that of older cars.13 A 1989 US report noted that, even with reduced CO emission limits and catalytic converters, it is still possible to use car exhaust for suicide.10 If exposure is prolonged, residual CO content would eventually cause death, or suffocation might occur. Also, destruction of the engine management system, by the use of leaded petrol and neglect, or physical disconnection of the engine management system, could increase the CO content, and thus the lethality of this method for suicide.8 Further research needs to be undertaken in this technically complex area. A study of the vehicles used for unsuccessful exhaust gas suicide attempts and of other factors contributing to their failure would assist in understanding the relationship between vehicles and exhaust gas suicides. New regulations in Australia have not yet reduced suicides from motor vehicle exhaust gas. There is a need to monitor the situation, especially in the light of the 1997 reduction in CO to 2.1 g/km, and to review the regulations, vehicle design and testing methods. Acknowledgments The study was funded by the Victorian Health Promotion Foundation through its funding of the Victorian Injury Surveillance System, a project of Monash University Accident Research Centre. We thank the Victorian State Coroner's Office for providing access to relevant records, Associate Professor David Ranson (Victorian Institute of Forensic Medicine), David Lester (Richard Stockton College of New Jersey), Jerry Moller and Stan Bordeaux (Australian Institute of Health and Welfare, National Injury Surveillance Unit) for providing data, Christine Chesterman and Voula Stathakis (Monash University Accident Research Centre) for assisting with data collection and analysis, respectively, and Dr Ella Sugo (formerly of the NSW Institute of Forensic Medicine), Brian Hobsbawn (Environment Australia) and Jerry Moller for providing valuable comment. References Lester D. Car ownership and suicide by car exhaust in nations of the world. Percept Motor Skills 1994; 79: 898. Australian Bureau of Statistics. May 1995, Motor Vehicle Census. Canberra: ABS, 1996. (Catalogue No. 9309.0.) Ernsting J, King P. Aviation medicine. 2nd ed. London: Butterworths, 1988. Willis Hurst J, Schlant R, Rackley C, et al. The heart. 7th ed. New York: McGraw-Hill, 1990. Smith JS, Brandon S. Morbidity from acute carbon monoxide poisoning at three-year follow-up. BMJ 1973; 1: 318-321. Unnatural deaths, 1993/94. Melbourne: Victorian State Coroner's Office, December 1995. Sugo E, Duflou J, Sercombe J, Brown J. Suicidal inhalation of carbon monoxide -- a reappraisal of variables affecting lethal levels. Paper presented at the Annual Scientific Meeting of the Royal College of Pathologists of Australasia;1996 Sep 16-19; Sydney. Sydney: The College, 1996. Lester D. Changing rates of suicide by car exhaust in men and women in the United States after car exhaust was detoxified. Crisis 1989; 10: 164-168. Clarke R, Lester D. Toxicity of car exhausts and opportunity for suicide: comparison between Britain and the USA. J Epidemiol Community Health 1987; 41: 114-120. Lester D, Abe K. Car availability, exhaust toxicity and suicide. Ann Clin Psychiatry 1989; 1: 247-250. Code of Federal Regulations. Title 40: Protection of environment. Part 86 -- control of air pollution from new and in-use motor vehicles and new and in-use motor vehicle engines: certification and test procedures. Washington, DC: Office of the Federal Register National Archives and Records Administration, 1997. Centers for Disease Control and Prevention, National Center for Health Statistics. Vital statistics of the US. Vol. II. Mortality. Part A. Washington: Public Health Service, May 1996. Federal Office of Road Safety. Motor vehicle pollution in Australia. Report on the national in-service vehicle emission study. Canberra: AGPS, 1996. (Received 18 Mar, accepted 27 Sep, 1997) Authors' details Monash University Accident Research Centre, Melbourne, VIC. Virginia H Routley, BEc, GradDipSocStats, Research Fellow; Joan Ozanne-Smith, MB BS, MPH, Professorial Fellow. No reprints will be available. Correspondence: Ms V H Routley, Monash University Accident Research Centre, Wellington Road, Clayton, VIC 3168. Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Virginia H Routley · Joan Ozanne-Smith

Breast cancer mortality trends in Australia: 1921 to 1994 Catherine L Smith, Anne Kricker, Bruce K Armstrong MJA 1998; 168: 11-14 Abstract - Introduction - Methods - Results - Discussion - Conclusions - Acknowledgements - References - Authors' details - - ©MJA1997 Abstract Objective: To analyse breast cancer mortality trends in Australia and to see if mammographic screening has yet led to a reduction in mortality. Design: Retrospective analysis of trends in mortality rates from breast cancer in Australian women between 1921 and 1994, and in potentially explanatory variables such as fertility, body size, age at menarche, and screening. Results: Changes in breast cancer mortality in Australian women could not be explained by chance variation alone. Mortality rose steadily (average annual increase, 1.0%) to 1940-1944, fell to the 1960s and early 1970s, and rose (average annual increase, 0.3%) to the late 1980s. Between 1985-1989 and 1990-1994, breast cancer mortality fell by 3.2% in women 50-69 years of age (the target age group for mammographic screening) and by 4.2% in women 25-49 years of age. There was almost no change ( - 0.2%) in breast cancer mortality in older women in this period. The proportion of women screened in all age groups increased substantially between 1988 and 1994; nearly 65% of women in the target age group had had at least one mammogram by 1994. Decreases in fertility were followed by increases in mortality, and vice versa. Conclusions: Trends in breast cancer mortality have probably been influenced by changing fertility, nutrition and body-size increases among Australian women. Improvements in stage at diagnosis and treatment have probably moderated the upwards pressure on mortality caused by an increasing incidence. Recent falls in mortality could be expected to continue as more women participate in the mammographic screening program. This trend should be more clearly evident in the second half of the 1990s. Introduction Breast cancer mortality in women in most developed countries, including Australia, has levelled off or fallen in recent years.1 In Britain, an important fall in mortality since 1989, considered too early to be the result of mammographic screening, is thought to be the result of improved treatment.2 Similar observations have been made in the United States.3 We examined trends in breast cancer mortality and breast cancer risk factors in Australia between 1921 and 1994 to see if we could explain recent mortality changes and, in particular, to see if mammographic screening has yet led to decreased breast cancer mortality in the target age group for screening (50-69 years). Methods Age-specific and age-standardised mortality rates from breast cancer per 100 000 woman-years, standardised to the world population, were calculated for one four-year period (1921-1924) and 14 five-year periods (1925-1929 to 1990-1994) from annual mortality and population data from the Australian Bureau of Statistics. Rates for 1995 have subsequently been released. Estimates of the number of women who had had at least one mammogram by the end of each year from 1984 to 1994 were obtained as follows: Annual numbers of women by age having a first or subsequent bilateral mammogram (bilateral mammograms being most likely for screening purposes) under Medicare from 1984 to 1994 were estimated from data of the Commonwealth Department of Health and Family Services; Annual numbers of first screens in 10 pilot projects of the national screening program were estimated by age from 1 January 1988 to 30 June 19914-7 (BreastScreen Australia, personal communication) on the assumption, where necessary, that all screens were initial and that rates were constant within and over time periods and age groups; and Similar estimates were made for BreastScreen Australia from 1 July 1991 to December 1994 by applying the age distribution for all screens, initial and subsequent, in Victoria8 (BreastScreen Australia, personal communication) and New South Wales9 to published national screening estimates,9 and by estimating the fraction that were initial screens from State-based proportions of initial screens. These three sets of estimates were totalled to estimate numbers of women who had had at least one mammogram by the end of each year from 1984 to 1994. Total fertility rates by age in Australian women were obtained by year from 1921 to 1994.10,11 Rates of first births by age and year, available only for married women, showed patterns similar to those for total fertility. Results Mortality Breast cancer mortality (Box 1a) increased in Australia between the periods 1921-1924 and 1940-1944 (average annual increase, 1.0%), fell to a post-war low around 1960, and increased slowly again to a peak in 1985-1989. The average annual increase in rates from 1970-1974 to 1985-1989 was 0.3%. Thereafter, rates fell by 0.5% a year between 1985-1989 and 1990-1994. The recent fall in annual age-standardised rates has been from 20.7 per 100 000 woman-years in 1990 and 1991, to 19.6 per 100 000 in 1992, 1993 and 1995, and 19.2 in 1996; in 1994 the mortality rate was 20.3 per 100 000 woman-years. Age-specific mortality rates for women aged 25-49 years showed little change between 1921 and 1994 (Box 2). In women 50 years of age and older, breast cancer mortality rose steadily to reach initial peaks at different times between 1935-1939 and 1950-1954. These peaks occurred in women born between 1865 and 1885. Mortality in women 50 years and older then fell to a post-war low between 1950-1954 and 1985-1989 depending on age group and occurring in women born around 1890 to 1905. Thereafter, mortality rates again rose and appeared to peak in 1980-1984 or 1985-1989 for each age group of women from 50-54 years to 70-79 years. There was little evidence of this later mortality rise in women older than 80 years. In the target age group for mammographic screening (50-69 years), the age-standardised mortality rate increased by 4.0% (95% CI, - 0.1 to 8.3) from 1980-1984 to 1985-1989 and then fell by 3.2% (95% CI, - 6.9 to 0.6) to 1990-1994. In women 25-49 years of age, rates increased by 7.5% (95% CI, 0.4-15.0) from 1980-1984 to 1985-1989 and then fell by 4.2% (95% CI, - 9.9 to 1.9) to 1990-1994. Women 70 years of age and older showed only weak evidence of change from the early to the late 1980s (1.3%; 95% CI, - 3.1 to 6.0) and almost no evidence of a fall in the 1990s ( 2 0.2%; 95% CI, - 4.2 to 4.0). Mammographic screening Our analysis of mammographic screening data is summarised in Box 3. The percentages of women screened between 1988 and 1994 increased in all age groups, most notably in women aged 50-69 years. The beginning of most pilot projects in late 1988 and early 1989 and of the National Program in 1991 led to a substantial change in the age distribution of screening mammograms. There was a nearly sevenfold increase in the cumulative numbers of women in the target age group who had been screened once or more, from around 138 000 in 1988 to nearly one million by 1994. The estimated number of women under 50 years of age who had been screened (which was twice the number in the target group in 1988) increased only 3.7 times (to an estimated 1 140 000) by 1994. By 1994, about 70% of women in their 50s and 58% of women in their 60s had had an initial screen. In all, 54% of women in their 40s and 22% of women younger than 40 were estimated to have been screened once by 1994. In older women, the proportion screened reached 25% at 70-74 years of age and 6% at 80 years and older. Fertility Fertility fell at all ages from 1921-1924 or 1925-1929, to reach a minimum in most age groups in 1930-1934 or 1935-1939 (Box 1b), and then rose to reach a peak between 1945-1949 and 1970-1974. Rates again fell from these peaks. Minima were reached in 1975-1979 or 1980-1984 in those aged between 30 and 44 years, with subsequent rises to 1990-1994. There was little evidence that any of these trends related better to cohort of birth than time period. Discussion Compared with many other countries, breast cancer mortality in Australia has varied little over the past 75 years.1 However, the clear trends we found cannot be explained by chance fluctuation. The recent fall in the early 1990s, while apparently quite definite in women aged 40-69 years, could be a chance occurrence and will need to be shown for several more years for it to be declared a "real" trend. There are three broad classes of explanation for these trends, represented under the subheadings below. Changes in how cause of death is registered and coded can influence reported cause-specific mortality rates, but no substantial changes of this kind are known to have occurred in Australia.1,12 We have specified "real" incidence (below) because recent apparent increases in breast cancer incidence have probably been the result of increased screening.3,13 These increases will not cause increases in mortality because they reflect either earlier diagnosis of breast cancers, or the diagnosis of lesions that would otherwise never have been detected.13 Changes in determinants of real incidence Incidence trends: Whether changes in incidence caused changes in mortality would be most easily determined by comparing incidence and mortality trends. Incidence of breast cancer in New South Wales (representing about one-third of Australian women) changed little from 1972 to 1983, but increased steadily from 1984, and by 1995 was nearly 50% higher than it was in 1983.14 The greatest increase was in women in the target age group for mammographic screening (50-69 years). As there was no parallel increase in mortality during that period, the observed increase in incidence has probably been caused by screening. Incidence was not measured in Australia before 1972. However, it is most likely that incidence rates in Australia, as in several other countries,15-17 were increasing and thus underlie the steady increase in mortality from 1921 to the peak of the mid 1940s. Incidence rates in Australia were probably also increasing in the post-war period, as in other populations of European origin,18,19 when Australian mortality rates were falling or stable. Fertility: Breast cancer is associated with late age at first birth, childlessness and low parity.13 Box 1 shows that Australian trends in rates of mortality from breast cancer moved in the opposite direction from those of fertility rates, with changes in mortality occurring a few years after those in fertility. Australian women born in the 1840s were at the forefront of a transition to lower family sizes in English-speaking countries.10 This falling fertility could have produced the increasing mortality from breast cancer from 1921 onwards. The peak breast cancer mortality in the 1940s occurred in women born before 1885; the highest proportions of unmarried and childless women seen in Australia up to the 1940s were among those born in 1871 to 1876.10 The upward trend in fertility after 1935, which peaked in 1955-1964, started about 10 years before mortality began to fall in the mid 1940s. Fertility again fell in the late 1960s and 1970s to a new low in the 1980s, with a pronounced shift during that period to later childbearing; mortality began to rise again in the 1980s. Body size and age at menarche: Each 5-cm increase in average height in adult women has been estimated to increase breast cancer risk by 10%.13 From the early 1900s to about 1980, net increases of 8-9 cm in height and 10 kg in weight20,21 could have contributed appreciably to increases in mortality in women born from about 1895 to 1935 (evident in overall mortality from breast cancer between 1970-1974 and 1985-1989). A fall in age at menarche is also associated with an increase in breast cancer incidence.13,22 Trends in Australia, probably similar to the 2-3 months' fall per calendar decade seen in the United Kingdom and United States in the 100 years to about 1950,13,22,23 would have been expected to increase breast cancer rates. Younger age at menarche is very likely caused by increased height and body mass index, perhaps because menarche depends on attainment of a critical body mass.22,24 Diet: Dietary changes may have affected breast cancer rates by way of changes in body size, and possibly by other means.25 Alcohol consumption is associated with increased risk of breast cancer, being 35% higher in women who have 2-4 drinks and 67% higher in those who have more than four drinks a day compared with women who drink little or no alcohol.26 The high alcohol consumption among Australian women of the early 1800s was not equalled again until 1989, when more than 50% of women over 18-20 years were consuming up to two drinks a day.26,27 However, it has been estimated that no more than 3% of breast cancers in Australia in 1990 were the result of drinking more than two drinks of alcohol a day.26 Physical activity may reduce risk of breast cancer.27 The proportion of Australian women who participate in any recreational exercise (around 70%) appears not to have changed in recent times.28 Changes over time in the physical activity associated with running a household and in paid employment have not been measured. Migration: Breast cancer rates vary six-fold internationally.29 Migration of women from countries of higher (UK) and lower (eastern Europe, southern Europe, Asia) breast cancer mortality than in Australia has varied, but the net effect of migration on breast cancer mortality rates has probably been small. Oestrogen use: Use of the oral contraceptive pill increased rapidly in Australia after its introduction in 1961.30 If the Pill has caused an increase in breast cancer mortality, it would have done so mainly in younger women who were current or recent users.31 The increase in mortality in the late 1980s, however, was mostly in women over 50 years of age. Falling mortality from breast cancer in the generations of women who first used oral contraceptives in the US, UK and Sweden also suggests no major effects of the Pill on breast cancer rates.32,33 The use of oestrogen replacement therapy, which may increase breast cancer risk, has probably not affected breast cancer incidence appreciably as long term use has been uncommon in Australia. Changes in determinants of stage at diagnosis Trends to smaller breast cancers and fewer axillary node metastases over nearly 100 years34-36 are probably the results of increased access to and use of care. The trend to more localised disease is probably continuing because of increased screening.3,13,37 Such trends would have caused downward pressure on breast cancer mortality. Mortality from breast cancer in Australian women in the target age group for screening (50-69 years) fell by 3.2% between 1985-1989 and 1990-1994. This may be the result of screening, although the same or larger falls in mortality also occurred in younger women, for whom there is little evidence that mammographic screening reduces breast cancer mortality.38 Changes in determinants of probability of survival after diagnosis at a particular stage The effectiveness of radical mastectomy as the primary treatment for breast cancer has probably changed little in the past 100 years. However, advances in anaesthetics and operating conditions38 as well as the recent use of adjuvant chemotherapy and hormonal therapy3,39 have almost certainly increased survival. Conclusions While no certain conclusions can be drawn about the causes of changes in breast cancer mortality since 1921, it is probable that the increase to the mid 1940s was caused mainly by rapidly falling fertility in the latter part of the 19th and the early 20th centuries. Subsequent increased fertility, and earlier diagnosis, may have contributed to the fall in mortality from 1940-1944 to 1960-1964. The increasing mortality in women born between 1895 and 1935 was probably caused by nutritional factors leading to increases in body size and resultant earlier age at menarche. However, this incidence-driven increase in mortality was probably moderated by increasing survival with earlier diagnosis and, more recently, improved treatment. Improved treatment is probably the reason for cross-sectional falls in mortality between 1985-1989 and 1990-1994 in women up to 69 years of age. Early effects of mammographic screening may have contributed to these falls, but should be more clearly evident in the second half of the 1990s. Acknowledgements Australian Bureau of Statistics data on mortality from breast cancer from 1921 to 1994 were supplied by Mr Paul Jelfs from the national mortality database at the Australian Institute of Health and Welfare, Canberra. 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Systemic treatment of early breast cancer by hormonal, cytotoxic, or immune therapy. Lancet 1992; 339: 1-15. (Received 29 Jan, accepted 21 Jul, 1997) Authors' details National Health and Medical Research Council National Breast Cancer Centre, Sydney, NSW. Catherine L Smith, MPH, Statistician; Anne Kricker, PhD, Epidemiologist. Cancer Control Information Centre, NSW Cancer Council, Sydney, NSW. Bruce K Armstrong, DPhil, FRACP, Director. Reprints will not be available from the authors. Correspondence: Dr A Kricker, NHMRC National Breast Cancer Centre, PO Box 572, Kings Cross, NSW 2011. Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. 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Catherine L Smith · Anne Kricker · Bruce K Armstrong