Research

Research Iron deficiency in Australian-born children of Arabic background in central Sydney Margaret A Karr, Michael Mira, Garth Alperstein, Samia Labib Boyd H Webster, Ahti T Lammi and Patricia Beal MJA 2001; 174: 165-168 For editorial comment, see Couper and Simmer Abstract - Methods - Results - Discussion - Acknowledgements - References - Authors' details - - More articles on Public and environmental health Abstract Objectives: To determine the prevalence of iron depletion and deficiency, and iron-deficiency anaemia, along with risk factors for iron depletion, in Australian-born children aged 12-36 months of Arabic-speaking background. Design: Community-based survey. Setting: Central Sydney Area Health Service (CSAHS), NSW, April to August, 1997. Participants: All children born at five Sydney hospitals between 1 May 1994 and 30 April 1996, whose mothers gave an Arabic-speaking country of birth and resided in the area served by the CSAHS. Main outcome measures: Full blood count (haemoglobin, mean corpuscular haemoglobin, mean corpuscular volume), plasma ferritin concentration, haemoglobin electrophoresis, potential risk factors for iron depletion. Results: Families of 641 of the 1161 eligible children were able to be contacted, and 403 agreed to testing (response rate, 62.9% among those contacted). Overall, 6% of children had iron-deficiency anaemia, another 9% were iron deficient without anaemia, and 23% were iron depleted. Multiple logistic regression analysis showed three significant independent risk factors for iron depletion: < 37 weeks' gestation (odds ratio [OR], 5.88, P = 0.001); mother resident in Australia for less than the median time of 8.5 years (OR, 1.96, P = 0.016); and daily intake of > 600 mL cows' milk (OR, 3.89, P = < 0.001). Conclusion: Impaired iron status is common among children of Arabic background, and targeted screening is recommended for this group. Numerous studies have documented the adverse health effects of iron deficiency in infants and preschool children, including growth retardation,1,2 gastrointestinal changes,3 impaired immune function,4 impaired behavioural and mental development5,6 and decline in psychomotor development.7,8 In 1992-1994, a study of Sydney children aged 9-62 months found that 1.1% had iron-deficiency anaemia, while 2.8% were iron deficient without anaemia and another 10.5% were iron depleted.9 The prevalence of iron-deficiency anaemia appeared to be higher among children of Arabic-speaking background, but the small number of these children prevented firm conclusions, and the reasons for any difference were not clear. The most important determinants of iron status in infants are growth rate relative to iron endowment at birth, dietary iron content and bioavailability and gastrointestinal blood loss.10 Risk factors for iron deficiency in infancy and childhood include prematurity, low birth weight,11,12 exclusive breastfeeding beyond six months of age,13 introduction of whole cows' milk before 12 months of age,14 and high intake of cows' milk.15 We examined the prevalence of impaired iron status in a large group of Australian-born children of Arabic-speaking background and evaluated their risk factors for iron depletion. Methods The study was a community-based survey undertaken between April and August 1997. Participants Children were identified from the medical records of five Sydney hospitals, which, according to the Midwives Data Base, account for 92% of deliveries to mothers born in an Arabic-speaking country and residing in the area served by the Central Sydney Area Health Service (CSAHS).16 Eligibility criteria were: birthdate between 1 May 1994 and 30 April 1996; mother gave an Arabic-speaking country of birth on admission; postcode of mother's place of residence was in the area served by the CSAHS. Hospitals were asked to exclude stillbirths and neonatal deaths. Contact details were obtained from the medical records. Survey Parents of all eligible children were sent a letter about the study in both Arabic and English. Five days later, they were telephoned to discuss queries and to invite their child's participation. If they agreed, an appointment was made at a convenient early childhood health centre, or a home visit was arranged. Parents were asked to bring the child's Personal Health Record for assessment of birth weight and gestation. Demographic data were obtained using a structured questionnaire administered by an Arabic-speaking research assistant (S L). Questions were also asked about the child's feeding habits since birth and whether the child had had a fever in the two weeks before the blood test, as fever can elevate plasma ferritin concentration.17 Investigations About 0.75 mL of blood was collected by fingerprick and tested at the Royal Alexandra Hospital for Children (RAHC), Sydney, NSW. Haematological investigations (using a Coulter S+IV, Fullerton, Cal, USA) included measurement of haemoglobin and red cell indices. Plasma ferritin concentration was measured by immunoradiometric assay (Biorad, Hercules, Cal, USA). Haemoglobin electrophoresis was performed on all samples to detect haemoglobinopathies. Definitions of impaired iron status are shown in Box 1. All parents were notified of their children's results. Children with poor iron status or haemoglobinopathy were referred to their general practitioners (GPs). A copy of the laboratory report was sent to the GP and to the parents, if they so requested. Statistical analyses Children found to have a haemoglobinopathy were excluded from the analyses, which were performed using Stata (version 5).21 Statistical tests were performed after adjustment for possible cluster effects both within hospitals and within families (as some families contributed more than one child to the study). Confidence intervals were similarly adjusted. Adjusted χ2 tests were used to examine relationships between iron depletion and demographic and risk factors. Variables found to be significantly associated with iron depletion were then entered into a multivariate logistic regression model. Prevalence of impaired iron status was compared with prevalence in children from the general population of central Sydney assessed in 1992-1994.9 Data from that study were re-examined for children aged 12-38 months, using a ferritin level < 10 µg/L to define iron depletion. To test the representativeness of our sample group, demographic characteristics of the mothers were compared with those of all women who in the 1996 census gave an Arabic-speaking country of birth, resided in the area served by the CSAHS, were aged 15-45 years and had children aged 12-38 months. These data were obtained from the Australian Bureau of Statistics. Ethical approval for all components of this study was obtained from the CSAHS Ethics Review Committee. All participating parents gave informed written consent. Results We were able to contact families of 641 of the 1161 eligible children and tested 403 of these children (63% response rate among those able to be contacted). Haematological testing identified a haemoglobinopathy in 21 children, who were therefore excluded from analysis, although two had other haematological parameters consistent with iron depletion. This left 382 children with a plasma ferritin result, and 315 with complete haematological results (blood volume was insufficient for a complete examination in the other 67). Median age of the 382 children at the time of data collection was 25 months (range, 12-38 months). Age distribution was 12-23 months (149 children), 24-35 months (204), and 36-38 months (29). Just over half the children (53%) were male. Prevalence of impaired iron status Prevalence of impaired iron status is shown in Box 2. Overall, 38% of children with an Arabic background had impaired iron status, comprising 6% with iron-deficiency anaemia, a further 9% with iron deficiency without anaemia and a further 23% with iron depletion. The Box also shows prevalences found in 1992-1994 among children the same age in the general population of central Sydney.9 The proportion of children with impaired iron status was substantially higher among Australian-born children of Arabic-speaking background in 1997 than among children of the same age in the general community in 1992-1994. Among the children of Arabic background, those who were reported as having a fever in the two weeks before the blood test were statistically less likely to fulfil the criteria for iron depletion (19/122 versus 68/260; F1,339 = 5.07; P = 0.025). However, they did not differ significantly in rates of iron deficiency (11/108 versus 16/207; F1,282 = 0.49; P = 0.48) or iron-deficiency anaemia (8/108 versus 12/207; F1,282 = 0.31; P = 0.58). The rate of iron depletion among the 260 children reported not to have had a fever in the two weeks before the blood test was 26% (95% CI, 21%-32%). There were no significant differences in iron status between the sexes or between age groups. Risk-factor analysis Potential risk factors among the 382 children are shown in Box 3. Univariate analysis revealed that prematurity, mother resident in Australia less than the median time of 8.5 years, mother born in a country other than Lebanon, and daily intake of more than 600 mL of cows' milk were significantly associated with iron depletion (Box 4). None of the other variables tested, including age of introduction of cows' milk, were significantly associated with iron depletion. Multivariate logistic regression analysis determined that prematurity, mother resident in Australia less than the median time of 8.5 years, and daily intake of more than 600 mL of cows' milk, but not mother born in a country other than Lebanon, were independently associated with iron depletion (Box 4). Children who had been born prematurely were almost six times more likely to be iron depleted, while those who drank more than 600 mL cows' milk per day were almost four times as likely and those whose mothers had been in Australia less than the median time (8.5 years) were almost twice as likely. Representativeness of sample We compared post-secondary education and time in Australia between the sample group and all women who in the 1996 census gave an Arabic-speaking country of birth, resided in the area served by the CSAHS, were aged 15-45 years and had children aged 12-38 months. In the sample group, 29% (116/403) had post-secondary qualifications (95% CI, 24%-33%), compared with 30.2% in the census group (421/1392). Similarly, 30% (121/401) of our sample had been in Australia for six to 10 years (95% CI, 26%-35%), while the corresponding figure for the census group was 26.4% (368/1392). The 238 parents who declined a blood test for their child were questioned by telephone about the age and sex of the child and the volume of cows' milk consumed daily; 180 parents (76%) responded. There were no significant differences between their children and those who had blood tests in age (P = 0.7), sex (P = 0.6) or reported volume of cows' milk consumed daily (P = 0.17). Among the 382 children tested for iron depletion, 67 had moved place of residence since birth and 315 had not moved. The proportion with iron depletion did not differ between these two groups (OR, 1.31; 95% CI, 0.73-2.36). Nor did it differ between the 67 children who had only ferritin level estimated and the 315 who gave sufficient blood for a full haematological examination (OR, 1.03; 95% CI, 0.53-2.01). Discussion These results indicate a public health problem in Australian-born children of Arabic-speaking background in central Sydney that could indicate a nationwide problem. More than a third of these children had impaired iron status, including 6% with iron-deficiency anaemia and another 9% with iron deficiency without anaemia. These prevalences are higher than those found in children the same age in the general population of central Sydney in 1992-1994.9There are several potential sources of bias in this study. The first was the use of retrospective records and consequent failure to contact about 45% of mothers. This is a common problem in such retrospective studies.22,23 However, the mothers of the children studied did not differ significantly from all women in the 1996 census who were aged 15-45 years with children in the target age range, gave an Arabic-speaking country of birth and resided in the CSAHS, while prevalence of iron depletion did not differ between children who had moved residence since birth and those who had not. It is unlikely that our sample differed substantially from the total study population. A second potential source of bias was non-response. However, children whose parents refused a blood test did not differ significantly from those who had a blood test in age, sex and proportion who drank more than 600 mL cows' milk daily. Finally, children whose blood samples were insufficient for full haematological assessment did not differ significantly in prevalence of iron depletion from those who had a full assessment. In the group of children reported to have had a fever in the two weeks before the blood test, a significantly lower proportion fulfilled the criteria for iron depletion. Therefore, the rate of iron depletion reported may be an underestimate. The definition of iron deficiency used in this study was particularly stringent, requiring abnormal values for three laboratory indicators of iron status. Criteria used by the United States Third National Health and Nutrition Examination Survey were less stringent: individuals were diagnosed as iron-deficient if they had abnormal values for two of three laboratory indicators (serum ferritin, free erythrocyte protoporphyrin or transferrin saturation).18 Nevertheless, that survey found rates of iron deficiency and iron-deficiency anaemia among children aged one to two years less than half the rates found in our study (3% versus 6% in our study). The US rate was similar to the rate found in children in the general population of central Sydney in 1992-1994. Risk of iron depletion in our study was greater in children whose mothers had been in Australia for less than the median time of 8.5 years. About 79% of these mothers spoke Arabic, or mainly Arabic, in the home. Early childhood health centres in central Sydney have specific days on which an Arabic interpreter is present, but anecdotal reports suggest that many mothers do not avail themselves of this service. Newly arrived mothers should be targeted in hospital, immediately postpartum, and given information as to which days an Arabic interpreter will be at their local centre and strongly encouraged to attend on a regular basis. Prematurity is well documented as a risk factor for iron deficiency, and this should be kept in mind by GPs and other healthcare providers. Of particular interest is the risk associated with the volume of cows' milk consumed daily. The National Health and Medical Research Council recommends that children aged under 12 months should not receive cows' milk as the main source of milk, while those aged over 12 months should not receive more than 600 mL per day.24 In the multiple logistic regression model, children who consumed more than 600 mL per day were almost four times as likely to have iron depletion, and targeted screening is strongly indicated based on this dietary history. Cows' milk is a poor source of iron, displaces foods with greater available iron and may also increase gastrointestinal occult blood loss. GPs should be aware of the importance of a dietary history for children of Arabic-speaking background and should enquire particularly about the volume of cows' milk consumed per day after 12 months of age. Acknowledgements We wish to thank the parents and children who participated in this study, the haematology laboratory staff at the Royal Alexandra Hospital for Children, Sydney, and the nurses of the participating Early Childhood Health Centres. The blood collection skills of Mrs Rhonda Dryden were invaluable to this study. The study was funded by the National Health and Medical Research Council Public Health Research Development Committee, Grant No: 97-417-7. References Aukett MA, Parks YA, Scott PH, Wharton BA. Treatment with iron increases weight gain and psychomotor development. Arch Dis Child 1986; 61: 849-857. Prasad AN, Prasad C. Iron deficiency; non-hematological manifestations. Prog Food Nutr Sci 1991; 15: 255-283. Berant M, Khourie M, Menzies IS. Effect of iron deficiency on small intestinal permeability in infants and young children. J Pediatr Gastroenterol Nutr 1992; 14: 17-20. Thibault H, Galtn P, Selz F, et al. The immune response in iron-deficient young children: effect of iron supplementation on cell-mediated immunity. Eur J Pediatr 1993; 152: 120-124. Oski FA, Honig AS, Helu B, Howanitz P. Effect of iron therapy on behavior performance in nonanemic, iron-deficient infants. Pediatrics 1983; 71: 877-880. Lozoff B, Jiminez E, Wolf AW. Long-term developmental outcome of infants with iron deficiency. N Engl J Med 1991; 325: 687-694. Williams J, Wolff A, Daly A, et al. Iron supplemented formula milk related to reduction in psychomotor decline in infants from inner city areas: randomised study. BMJ 1999; 318: 693-697. Walter T, De Andraca I, Chadud P, Perales CG. Iron deficiency anemia: adverse effects on infant psychomotor development. Pediatrics 1989; 84: 7-17. Karr M, Alperstein G, Causer J, et al. Iron status and anaemia in preschool children in Sydney. Aust N Z J Public Health 1996; 20: 618-622. Dallman PR, Siimes MA, Stekel A. Iron deficiency in infancy and childhood [review]. Am J Clin Nutr 1980; 33: 86-118. Gorten MK, Cross ER. Iron metabolism in premature infants: 2. Prevention of iron deficiency. J Pediatr 1964; 64: 509-520. Friel JK, Andrews WL, Matthew JD, et al. Iron status of very-low-birth-weight infants during the first 15 months of infancy. CMAJ 1990; 143: 733-737. Calvo EB, Galindo AC, Aspres NB. Iron status in exclusively breast-fed infants. Pediatrics 1992; 90: 375-379. Penrod JC, Anderson K, Acosta PB. Impact on iron status of introducing cow's milk in the second six months of life. J Pediatr Gastroenterol Nutr 1990; 10: 462-467. Mills AF. Surveillance for anaemia: risk factors in patterns of milk intake. Arch Dis Child 1990; 65: 428-431. NSW Department of Health, NSW Midwives Data Collection, 1994. Sydney: NSW Department of Health, 1995. Elin RJ, Wolff SM, Finch CA. Effect of induced fever on serum iron and ferritin concentrations in man. Blood 1977; 49: 147-153. Looker AC, Dallman PR, Carroll MD, et al. Prevalence of iron deficiency in the United States. JAMA 1997; 277: 973-976. Dallman PR, Siimes MA. Percentile curves for hemoglobin and red cell volume in infancy and childhood. J Pediatr 1979; 94: 26-31. Dallman PR, Looker AC, Johnson CL, Carroll M. Influence of age on laboratory criteria for the diagnosis of iron deficiency anaemia and iron deficiency in infants and children. In: Hallberg L, Asp N-G, editors. Iron nutrition in health and disease. London: J Libbey, 1996: 64-74. Stata statistical software release 5.0 [computer program]. College Station, Texas: Stata Corporation, 1997. McBride WG, Black BP, English BJ. Blood lead levels and behaviour of 400 preschool children. Med J Aust 1982; 2: 26-29. Ranmuthugala G, Karr M, Mira M, et al. Opportunistic sampling from early childhood centres: a substitute for random sampling to determine lead and iron status of pre-school children? Aust N Z J Public Health 1998; 22: 512-514. National Health and Medical Research Council. Dietary guidelines for children and adolescents. Canberra: AGPS, 1995. (Received 2 Mar, accepted 1 Sep, 2000) Authors' details Central Sydney Area Health Service, Sydney, NSW. Margaret A Karr, MPH, MSc(Med), Senior Research Officer, Division of General Practice; Michael Mira, MB BS, PhD, Clinical Professor, Department of General Practice, University of Sydney; Garth Alperstein, FRACP, Paediatrician and Clinical Senior Lecturer, University of Sydney, and Conjoint Senior Lecturer, University of New South Wales, Sydney, NSW; Samia Labib, BA, MEd(Health), Senior Interpreter, Health Interpreter Service. Department of Haematology, Royal Alexandra Hospital for Children, Sydney, NSW. Boyd H Webster, FRCPA, Senior Staff Specialist; Ahti T Lammi, FRACP, FRCPA, Senior Staff Specialist; Patricia Beal, MSc, Senior Hospital Scientist. Reprints will not be available from the authors. Correspondence: Professor M Mira, General Practice Casualty, Balmain Hospital, Booth Street, Balmain, NSW 2041. michaelmira_auATyahoo.co.uk 1: Definitions of impaired iron status used in the survey of children of Arabic background Iron depletion18 Plasma ferritin level Iron deficiency19 Iron depletion plus Mean corpuscular volume plus Mean corpuscular haemoglobin Iron-deficiency anaemia20 Iron deficiency plus Haemoglobin level Back to text 2: Prevalence of impaired iron status among children aged 12-38 months of Arabic background in central Sydney in 1997 Arabic background General population9 Iron status* Number % (95% CI) Number % (95% CI) Iron depletion Iron deficiency Iron-deficiency anaemia 87/382 27/315 20/315 23% (19%-27%) 9% (5%-12%) 6% (4%-9%) 36/381 14/329 5/329 9% (7%-12%) 4% (2%-7%) 2% (0-3%) *Definitions of iron status in children of Arabic background are shown in Box 1. The same definitions were used for children in the general population, except that iron deficiency was defined as iron depletion plus mean corpuscular volume < 70fL (age, 12-23 months) or < 73fL (age, 24-38 months), or red cell zinc protoporphyrin level > 80µmol/mol haem. Back to text 3: Potential risk factors for iron depletion among 382 children aged 12-38 months of Arabic background in central Sydney, 1997 Children with Children without Potential risk factors iron depletion iron depletion P* Born before 37 weeks' gestation 12/87 (14%) 10/295 (3%) 0.001 Birth weight 7/86 (8%) 8/293 (3%) 0.05 Breastfed initially 70/87 (81%) 245/295 (83%) 0.59 Breastfed at time of data collection 4/87 (5%) 9/295 (3%) 0.49 Cows' milk introduced before age of 12 months 32/87 (37%) 76/295 (26%) 0.06 Cows' milk introduced before age of 9 months 15/87 (17%) 36/295 (12%) 0.20 Consume >600mL cows' milk per day 54/83 (65%) 109/287 (38%) Consume ≥1L cows' milk per day 23/83 (28%) 30/287 (11%) Iron-fortified cereal as first solid 38/87 (44%) 149/295 (51%) 0.27 Consume meat 42/87 (48%) 122/295 (41%) 0.26 Receiving vitamin supplement 3/87 (3%) 11/295 (4%) 0.90 Receiving iron-containing supplement 1/87 (1%) 4/295 (1%) 0.88 Mother not born in Lebanon 26/87 (30%) 49/295 (17%) 0.01 Arabic or mainly Arabic spoken at home 58/87 (67%) 180/293 (61%) 0.39 Mother resident in Australia less than median time (8.5 years) 53/86 (62%) 137/294 (47%) 0.02 *By adjusted χ2 test. Back to text 4: Risk factors significantly associated with iron depletion among children aged 12-38 months of Arabic background in central Sydney, 1997 Univariate analysis Multivariate analysis Risk factor Odds ratio (95% CI) P Odds ratio (95% CI) P Gestation ≥37 weeks 1.00 1.00 4.55 (1.70-12.50) 0.003 5.88 (2.22-20.0) 0.001 Years mother in Australia ≥8.5 years 1.00 1.00 1.82 (1.10-3.03) 0.02 1.96 (1.36-3.33) 0.016 Cows' milk consumed daily ≤600mL 1.00 1.00 >600mL 3.04 (1.80-5.13) 3.89 (2.22-6.80) Country of birth Lebanon 1.00 Country other than Lebanon 2.14 (1.18-3.88) 0.01 NS NS=Not significant. Back to text

Margaret A Karr · Michael Mira · Garth Alperstein · Samia Labib · Boyd H Webster · Ahti T Lammi · Patricia Beal

Research Selective versus universal screening for gestational diabetes mellitus: an evaluation of predictive risk factors Richard X Davey and P Shane Hamblin MJA 2001; 174: 118-121 For editorial comment, see Wilson Abstract - Methods - Results - Discussion - Acknowledgements - References - Authors' details - - More articles on Obstetrics & gynaecology and women's health Abstract Objective: To assess whether selective screening for gestational diabetes mellitus (GDM) on the basis of risk-factor assessment is a practicable alternative to universal screening. Design: Case-control study. Setting: A 212-bed regional specialist hospital in Melbourne, providing services in obstetrics and gynaecology, paediatrics, geriatrics and rehabilitation. Subjects: 6032 women who gave birth at the hospital, May 1996 to August 1997 and November 1997 to August 1998; all were screened for GDM, and 313 were diagnosed with the condition. Main outcome measures: Odds ratios (ORs) for risk factors (age, obesity, family history of diabetes mellitus and high-risk racial heritage) in women with GDM compared to those without GDM; proportion of women with GDM whose diagnosis would have been missed by selective screening. Results: ORs were 1.9 for age ≥25 years (95% CI, 1.3-2.7), 2.3 for body mass index ≥27 kg/m2 (95% CI, 1.6-3.3), 2.5 for high-risk racial heritage (95% CI, 2.0-3.2), and 7.1 for family history of diabetes mellitus (95% CI, 5.6-8.9). Other proposed criteria (previous GDM and glycosuria) added no further diagnostic power. Selective screening using the above four criteria would have missed two of 313 cases (0.6%) and could have saved screening up to 1025 women without GDM (17% of all women). Conclusions: Selective screening for GDM based on prior risk assessment can reduce the need for testing, with negligible loss of diagnostic efficiency. Gestational diabetes mellitus (GDM) is officially described as carbohydrate intolerance with onset or first recognition during pregnancy.1 It is associated with increased incidence of maternal hypertension, pre-eclampsia and obstetric intervention; a third of women with GDM develop diabetes mellitus in later life. Babies of mothers with GDM may be either macrosomic or small-for-gestational-age, and may suffer birth trauma, hypoglycaemia and other metabolic disturbances. Potential effects later in the child's life are still debated. In Australia, at least 5% of pregnancies are affected by GDM. However, there is no sharply defined maternal blood glucose level beyond which morbidity invariably ensues in either mother or baby,2 and there is disagreement about how to diagnose GDM and how aggressively to treat it.3In 1998, both the American Diabetes Association (ADA) and the WHO Consultation on diabetes published recommendations on diagnosis and classification of diabetes mellitus that included comments on GDM.4,5 The Australasian Diabetes in Pregnancy Society (ADIPS) has also published GDM guidelines.6 Both the ADA and ADIPS recommendations acknowledge that there are variable levels of risk for GDM and, consequently, that selective rather than universal screening can be considered. Selective screening both reduces costs and, for women deemed not to need screening, eliminates the minor physical inconvenience of the procedure and any anxiety raised by the possibility of suffering diabetes. Both ADA and ADIPS list risk factors for GDM (Box 1). The WHO Consultation's delineation of risk factors for GDM was less clear.5 We tested the hypothesis that selective screening for GDM is a practicable alternative to universal screening. We also investigated the effect of using the different age criteria of ADIPS and ADA as a basis for selective screening. Methods We undertook a case-control study to compare the likelihood of particular risk factors (defined in Box 2) among women with and without GDM. We also determined the proportion of women with GDM whose diagnosis would have been missed by selective screening, based on different sets of risk factors. Study population Sunshine Hospital is a 212-bed regional specialist hospital in Melbourne, Victoria, which provides service in obstetrics and gynaecology, paediatrics, geriatrics and rehabilitation. The study population comprised all 6032 women who gave birth at the hospital over the 26 months May 1996 to August 1997 and November 1997 to August 1998. Women who gave birth in September and October 1997 were excluded, as their laboratory data were incomplete. All women were screened with a 50 g glucose challenge test, according to the ADIPS protocol.6 Those with an abnormal result (defined as plasma glucose level after one hour of ≥7.8 mmol/L) proceeded to a 2 h 75 g oral glucose tolerance test (OGTT); GDM was diagnosed if the fasting plasma glucose level was ≥5.5 mmol/L, or the 2 h level was ≥8.0 mmol/L. Nearly all patients diagnosed with GDM were managed by an endocrinologist (P S H) in conjunction with one of the clinic obstetricians and were offered review and ongoing care from a dietitian and a diabetes nurse educator. Data retrieval Case group: We identified all post-delivery patient separations coded for GDM by computer search of the hospital medical information system, with cross-referencing to laboratory, dietitian and diabetes nurse educator records. Women who gave birth twice in the study period were included only once, using details from their first GDM-affected pregnancy. There were 313 women diagnosed with GDM. Information on risk factors for these women was obtained from medical records containing details of pregnancy management and delivery, endocrinologist's and dietitian's notes and laboratory records (by R X D). If racial heritage was unclear, patients were telephoned at home to obtain more details. Body mass index (BMI) was available for only 290 of the 313 women (93%), but other data were available for over 99%. Control group: For the 5719 women without GDM, information on age was also obtained from the hospital medical records. However, it was impracticable to investigate racial heritage as closely for this group as for the case group. Therefore, if country of birth was recorded as being in Europe, Asia or Central and South America, it was used for risk categorisation (45.5% of women). All other women were allocated to risk groups in the same proportions as found in the case group. While this biases the outcome in favour of the null hypothesis, it is more accurate than making no such allocation at all. BMI and family history were not available for the 5719 women without GDM. Therefore, the BMI comparison used BMI data obtained from 303 consecutive non-diabetic women presenting for a glucose challenge test at about 28 weeks' gestation as part of a 1995 study at Sunshine Hospital.8 As the patient catchment area was unchanged between 1995 and 1998, this group should represent an unbiased sample of women who presented between 1995 and 1998. For the family history comparison, a recent estimate of prevalence of diabetes mellitus in Australia9 was used for the non-GDM patients. Background risk was corrected for the bias caused by the tendency of patients with diabetes to visit their doctors twice as often as non-diabetic patients.10 It was also doubled to give a worst-case estimate, as each parent might pass on heritable risk independently. Statistical analyses and ethics approval Data were analysed using Stata statistical software.11 Odds ratios were calculated from the comparative prevalence in affected and control populations by Cornfield's method. Ethics approval for this study was not required by the Victorian Health Services Act 1988 and was not sought. Data were permanently de-identified after analysis. Results Risk-factor comparison Prevalence of risk factors among women with and without GDM is shown in Box 3, along with odds ratios. Women with GDM were almost twice as likely to be aged 25 years or over compared with those without GDM, more than twice as likely to have a BMI ≥27 kg/m2 or to have a high-risk racial heritage, and more than seven times as likely to have a family history of diabetes mellitus. To determine the value of racial heritage as a predictor of GDM in isolation from family risk, we determined the OR for high-risk racial heritage among women with no family history of diabetes mellitus. This OR was not statistically different from the earlier OR for high-risk racial heritage that included women with a family history. Furthermore, birth in Australia, New Zealand or North America (of non-Indigenous background) does not necessarily equate with low heritable GDM risk. Of the 313 women with GDM, 94 were born in these countries, but 19 of these had high-risk racial heritage. Finally, we also assessed whether glycosuria in pregnancy or previous GDM had any extra value as predictors of GDM. All women with these risk factors qualified for screening on other grounds. Effect of selective screening The numbers of women with GDM who would be screened on the basis of risk factors, using different age thresholds, are shown in Box 4. Only the 290 women with complete data for all risk factors are included. However, all 23 women with incomplete risk-factor data would have undergone screening under these selective screening policies, as all had at least one risk factor (10 had two factors and five had three). Selective screening on the basis of at least one risk factor, using the ADIPS age criterion (≥30 years), would have missed 12 women with GDM (95% CI, 6-19; 4%). Using the ADA age criterion (≥25 years), selective screening would have missed only two women with GDM (95% CI, 0-5; 0.6%). Furthermore, χ2 tests showed that the proportions of women with GDM who had risk factors other than age did not differ significantly between age groups (≥30 years, ≥25 years and all ages); all P values exceeded 0.67. Among the women without GDM, 83% were aged 25 years or over and 48% were aged 30 years or over. A selective screening policy could therefore have saved testing up to 17%-52% of women without GDM, depending on the age threshold used and the presence of risk factors other than age. Discussion We found that selective screening for GDM using the four criteria common to the ADA and ADIPS lists of risk factors -- older age, obesity, family history of diabetes and high-risk racial heritage -- would have missed few women with GDM in our study population. It is clear that the age threshold for screening proposed by ADA (25 years) is diagnostically safer than the ADIPS threshold of 30 years, missing only 0.6% versus 4% of women with GDM. However, our data also show that it is important to examine risk factors other than age even when the lower age threshold is used, as the other factors underlying susceptibility to GDM operate irrespective of age. Family history and heredity are immutable, and obesity may also be partly under genetic control. These observations are also consonant with the theory that pregnancy unmasks diabetes mellitus prematurely.12 We also found that previous GDM and glycosuria in pregnancy added nothing to the above four criteria for screening. However, this does not mean that GDM in a previous pregnancy should be ignored. It is often regarded as a criterion for a full OGTT, without a prior glucose challenge test, earlier than 28 weeks' gestation; the wisdom of this practice is not doubted. Not only are the ADA criteria for screening diagnostically safer than the ADIPS criteria, they are also more precise in their definitions. Australian women would benefit if ADIPS recommendations were brought into line with ADA recommendations. Our conclusions differ from those of Moses and colleagues, who found no benefit from selective screening in their study in the Illawarra region of New South Wales.13,14 Indeed, Moses has championed universal screening.15 However, the Illawarra protocol for GDM screening varied from contemporary practice, as it did not measure fasting glucose level or stringently control the time between the glucose load and blood sampling, making comparison difficult. Its outcomes have been questioned.16,17 In North America, a recent, albeit small, retrospective study of GDM screening in Michigan specifically assessed the ADA selective screening recommendations and concluded that they can be used as they miss "few" (4%) women with GDM.18 A larger study was reported by the Toronto Trihospital Investigators.19 They proposed a scheme that used among its criteria those later published by ADA to differentiate risk levels for GDM, sparing 35% of pregnant women the need for a glucose challenge test. This is at least twice as efficient as using the ADA criteria in our population, which potentially spared up to 17% of women a glucose challenge test (depending on the presence of risk factors other than age). However, an accompanying editorial concluded that the Trihospital criteria were "so hard to discern" that universal screening would continue as the only practicable alternative.20 For busy clinicians, simple systems are essential. Our study differed from the Toronto study in that only women with positive results on a glucose challenge test proceeded to an OGTT, while, in Toronto, all women had a full OGTT. We will have missed the small number of women who would have had positive results on an OGTT despite their negative results on a challenge test -- perhaps 3%, based on the Toronto data. Short of performing a full OGTT on all pregnant women, which is impracticable, this group will always escape detection. The Toronto ORs for risk factors among those with GDM generally accord with ours (1.6 for age ≥35 years [95% CI, 1.1-2.5], 3.2 for BMI ≥25.1 kg/m2 [95% CI, 2.1-4.8], 4.8 for Asian race [95% CI, 3.0-7.6]), but our results differ in two ways. Toronto race groupings, apart from "Asian", are difficult to interpret and, by using "white" and "black", ignore the extreme variation among "white" Europeans. Secondly, family history of diabetes mellitus in Toronto did not correlate significantly with higher risk of GDM, whereas our findings strongly support the inclusion of family history among criteria for a glucose challenge test. Our study, along with the Michigan and Toronto studies, indicates that a selective approach to GDM screening in pregnancy is justifiable. Our simplified algorithm for selective screening is shown in Box 5. In practice, the proportion of women spared a glucose challenge test by selective screening will vary between populations. Consequently, whether selective screening is locally practicable will be a decision for individual groups of obstetricians, endocrinologists and pathologists with local knowledge. It is clear that consideration of a patient's age, rigorous questioning about racial and family history and accurate measurement of height and weight can reduce the need for screening among suitable populations. Selective screening can reduce costs and maternal anxiety, with negligible loss in diagnostic power. Nevertheless, GDM poses still further challenges. Australia needs a better-directed, more organised, totally inclusive approach to follow-up of women who have had GDM. The third who will go on to develop diabetes mellitus need to be tracked, monitored, and managed prospectively into a healthier future. Acknowledgements We thank dietitians Candy d'Menzie-Bunshaw and Ruth Cuttler, specialist diabetes nurse consultant Elizabeth Borg, and health information manager Sianne Banks and her staff at Sunshine Hospital for their invaluable assistance with the study, and Lucy Inocencio for her excellent technical assistance. References Metzger BE, editor. Summary and recommendations of the Third International Workshop-Conference on Gestational Diabetes Mellitus. Diabetes 1991; 40 Suppl 2: 197-201. Sacks DA, Greenspoon JS, Abu-Fadil S, et al. Towards universal criteria for gestational diabetes: The 75-gram glucose tolerance test in pregnancy. Am J Obstet Gynecol 1995; 172: 607-614. Jovanovic L. A tincture of time does not turn the tide [editorial]. Diabetes Care 2000; 23: 1219-1220. The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 1998; 21 (Suppl 1): S5-S19. Alberti KGMM, Zimmet PZ for the WHO Consultation. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1. Diagnosis and classification of diabetes mellitus. Provisional report of a WHO consultation. Diabet Med 1998; 15: 539-553. Hoffman L, Nolan C, Wilson JD, et al, for the Australasian Diabetes in Pregnancy Society. Gestational diabetes mellitus -- management guidelines. Med J Aust 1998; 169: 93-97. Beischer NA, Oats JN, Henry OA, et al. Incidence and severity of gestational diabetes mellitus according to country of birth in women living in Australia. Diabetes 1991; 40: 35-38. Davey R. The glucose challenge test: different drink dilutions. Diabet Med 1996; 13: 917-918. Welborn TA, Reid CM, Marriott G. Australian Diabetes Screening Study: impaired glucose tolerance and non-insulin-dependent diabetes mellitus. Metabolism 1997; 46 (12 Suppl 1): 35-39. Australian Bureau of Statistics. National health survey: diabetes, Australia, 1995. Canberra: AGPS, 1997. (Catalogue No. 4371.0.) StataCorp. 1999. Stata Statistical Software: Release 6. College Station. TX: Stata Corporation. Yue DK, Molyneaux LM, Ross GP, et al. Why does ethnicity affect prevalence of gestational diabetes? The underwater volcano theory. Diabet Med 1996; 13: 748-752. Moses R, Griffiths R, Davis W. Gestational diabetes: do all women need to be tested? Aust N Z J Obstet Gynaecol 1995; 35: 387-389. Moses RG, Moses J, Davis WS. Gestational diabetes: do lean young Caucasian women need to be tested? Diabetes Care 1998; 21: 1803-1806. Moses RG. Diabetes in pregnancy [editorial]. Med J Aust 1998; 169: 68-69. Davey R. Of gestational diabetes, finesse, and an antipodean snark [letter]. Diabetes Care 1999; 22: 873-874. Moses RG, Moses J, Davis WS. Response to Davey [letter]. Diabetes Care 1999; 22: 874. Williams CB, Iqbal S, Zawacki CM, et al. Effect of selective screening for gestational diabetes. Diabetes Care 1999; 22: 418-421. Naylor CD, Sermer M, Chen E, Farine D. Selective screening for gestational diabetes mellitus. N Engl J Med 1997; 337: 1591-1596. Greene MF. Screening for gestational diabetes mellitus [editorial]. N Engl J Med 1997; 337: 1625-1626. (Received 15 May, accepted 21 Sep, 2000) Authors' details Western Hospital, Melbourne, VIC. Richard X Davey, FRCPA, FACB, Clinical Pathologist; P Shane Hamblin, FRACP, Senior Endocrinologist. Reprints will not be available from the authors. Correspondence: Dr R X Davey, Western Hospital, Gordon Street, Footscray, VIC 3011. richard.daveyATwh.org.au Make a comment 1: Risk factors for gestational diabetes mellitus, listed by different sources Risk factor Australasian Diabetes in Pregnancy Society6 American Diabetes Association4 Age Obesity Family history of diabetes mellitus Previous GDM High risk "ethnic" group Glycosuria Previous adverse pregnancy outcome Yes (>30 years) Yes (not defined) Yes Yes Yes (examples given)† Yes Yes Yes (>25 years) Yes (BMI >27kg/m2) Yes (first-degree relative) Not mentioned* Yes (examples given)‡ Not mentioned Not mentioned* GDM=Gestational diabetes mellitus. BMI=Body mass index. *While the ADA did not consider previous GDM or adverse pregnancy outcome as sufficiently significant for women to be included in the high-risk GDM group, it did report them as criteria for diabetes testing in asymptomatic, undiagnosed individuals,4 thereby acknowledging them as markers of early, silent diabetes mellitus. †Including Australian Indigenous, Polynesian, Asian and Middle Eastern women. ‡Including Hispanic-American, Native American, Asian-American, African-American and Pacific Islander women. Back to text 2: Definitions of risk factors used in this study Age: Age was not further defined by ADA or ADIPS; we used age at estimated time of conception — the most conservative calculation. Obesity: As defined by the ADA — body mass index ≥27kg/m2, determined from pre-pregnancy mass and height. Family history of diabetes mellitus: As defined by the ADA — diabetes mellitus affecting a first-degree relative. Racial susceptibility: Termed "ethnic" risk by ADA and ADIPS. We classified a woman as having high-risk racial heritage if she or her parents were born in one of the countries around the Mediterranean (including the Levant, but not the rest of Europe), the Indian subcontinent or Asia, or belonged to the Indigenous populations of Australia, the Pacific or the Americas.7 ADA = American Diabetes Association. ADIPS=Australasian Diabetes in Pregnancy Society. Back to text 3: Prevalence and odds ratios of risk factors for gestational diabetes mellitus (GDM) Prevalence Risk factor Women with GDM (n=313) Women without GDM (variable n*) Odds ratio (95% CI) Age (years) >25 90.1% 82.9% 1.9 (1.3-2.7) >30 58.5% 47.8% 1.5 (1.2-1.9) Body mass index >27 kg/m2 36.2%† 19.8% 2.3 (1.6-3.3) Family history of diabetes mellitus 39.9% 8.6% 7.1 (5.6-8.9) High-risk racial heritage 68.7%‡ 46.4% 2.5 (2.0-3.2) Among women with no family history 71.7%§ 42.8%¶ 2.9 (2.1-4.0) *Sample size varied between risk factors: 5719 (age), 303 (body mass index), 50371 (family history) and 5719 (racial heritage). †Data were available for 290 of the 313 women. ‡High-risk racial heritage: peri-Mediterranean (56 women), Indian subcontinent (20), Asia (124), South America (12), Indigenous populations (3); low risk racial heritage: United Kingdom (61), other European countries (35) and other (2). §n=187. ¶n=5324. Back to text 4: Effect if selective screening were used among 290* women with gestational diabetes mellitus Number of women who would be screened (% of women with GDM) Risk factors† ADIPS age threshold (≥30 years) ADA age threshold (≥25 years) Age ≥ threshold Only risk factor Plus any one other factor Plus any two other factors Plus any three other factors Total 13 (4%) 78 (27%) 54 (19%) 20 (7%) 165 (57%) 23 (8%) 120 (41%) 90 (31%) 27 (9%) 260 (90%) Age ≤ threshold One risk factor Two risk factors Three risk factors Total 60 (21%) 42 (14%) 11 (4%) 113 (39%) 18 (6%) 6 (2%) 4 (1%) 28 (10%) Any risk factor 278 (96%) 288 (99%) *23 women with gestational diabetes mellitus but incomplete data on risk factors are not included. †Risk factors other than age were body mass index ≥27kg/m2, family history of diabetes mellitus and high-risk racial heritage. Back to text Back to text

Richard X Davey

A randomised controlled trial was planned to compare two different treatment strategies — structured problem solving and selective serotonin reuptake inhibitor (SSRI) medication — for patients with mild to moderate major depression. The trial was to be conducted in the primary care setting with all treatment given by general practitioners. When no patients had been recruited into the study after six months, we performed an audit of all patients with depressive symptoms attending the doctors' practices over three weeks. Exclusion criteria were changed to ease entry into the trial, but still no patients were recruited over the following six months. What went wrong? MJA 2001; 174: 144-146 Why did the trial fail? - Acknowledgements - References - Authors' details - - More articles on General practice and primary care The recent National Survey of Mental Health and Wellbeing found that depression was associated with significant disability and that 6.3% of the Australian population was estimated to have suffered a major depressive disorder in the previous 12 months.1 The survey also showed that general practices were the main points of contact for patients with a mental disorder, consistent with previous reports that only 5% of such patients are referred to psychiatrists.2 As most depressed patients will be treated in primary care, the evaluation of treatment in this setting is important. Structured problem solving is emerging as an effective treatment for clinical depression.3-6 This treatment aims to teach patients to use their own resources to deal with their problems and includes skills such as identifying and simplifying problems, "brainstorming" potential solutions, and implementing these solutions. The treatment is brief, has clearly identified stages, and is very suitable for delivery by primary healthcare professionals. However, little research in primary care settings has used general practitioners as the main treatment providers, and thus the degree to which the evidence for the effectiveness of structured problem solving can be generalised to general practice is questionable. For this reason we designed a randomised trial with all treatment conducted by GPs (Box 1). The study was, in part, a replication of an earlier United Kingdom project that showed that problem solving was better than placebo, but equivalent to amitriptyline.4 Six months after the trial commenced no patients had been recruited. Why did the trial fail? In practical terms, the trial should not have failed, as mild to moderate depression is a common presentation in primary care and the research protocol addressed many of the problems identified in previous primary care research failures.9,10 For example: We used GPs who had participated in a Masters program designed to improve the recognition and management of mental disorders in general practice; We involved the participating GPs in the development of the protocols; We made every effort to minimise tasks involved in the study for the GPs; and The chief investigator was responsible for the teaching on the Masters program, and had developed a close working relationship with the GPs. While our original intention was not to address the complexity of conducting randomised trials in clinical practice, the apparent unease of many of the GPs with randomisation raises some potential reasons for the failure (Box 2). Apparent ambivalence towards randomisation in medicine, despite strong support in the scientific literature, has been reported previously.11 Silverman argues that as medicine shifts from the traditional authoritarian stance of "doctor knows best" towards the use of clinical guidelines and standardised treatment protocols, there is an increased discomfort in any approach that might be seen to admit a lack of crucial knowledge on the part of the doctor.11 In other words, asking patients to consent to randomisation between two conditions admits an uncertainty that compromises the traditional doctor-patient relationship. However, it has not been difficult to engage doctors in trials involving randomisation of their patients, and there is evidence that many are prepared to follow simple randomisation protocols.12 For example, one of the first randomised controlled trials of giving aspirin to patients very early after myocardial infarction (to stop or reverse the thrombotic process) enrolled 2500 GPs. These GPs, who were blind to the treatment condition they were offering, agreed to give the allocated capsules (aspirin or placebo) to any patient who presented with chest pain or other symptoms likely to be caused by a myocardial infarct. Two thousand patients were recruited into the trial, suggesting that, in this example, randomisation was not a substantial concern. If it is not randomisation per se that causes reluctance to recruit, then other factors need consideration. In our study, the audit results indicated that one in six patients had been excluded because the GPs lacked confidence that structured problem solving would be of benefit. Perhaps the GPs lacked confidence in their ability to deliver the psychological treatment effectively. If this is the case, the failure of this trial may have been influenced by the inclusion of a psychological treatment. We have argued elsewhere that doctors remain cautious about using non-drug treatments, partly because of the lack of organised promotion of non-proprietary treatments, and partly because of the difficulty in ensuring quality control.13 Yet, these GPs had agreed problem solving was a useful treatment, had demonstrated competence as part of their training, and two GPs in the group had conducted their own research projects where they taught structured problem solving to other doctors. It is also possible that, given the obvious differences between the psychological and pharmacological approaches, the GPs had formed an opinion early in the recruitment process that one or other approach would better suit a particular patient. In this case, exclusion from the trial was based on the presumption that the doctor already knew what treatment was best.11,14 In a disturbing example of "doctor knows best", two-thirds of suitable patients were not enrolled in a randomised trial of antiarrhythmia drugs because their doctors were so convinced of the benefits of the drugs that they did not want their patients allocated to the placebo group.15 The study eventually showed that these drugs were capable of causing fatal arrhythmias, so those doctors were essentially withholding from their patients the 50% chance of being allocated to the safer placebo alternative. Other factors may cause doctors to hesitate when faced with recruiting patients, including the complexities of obtaining informed consent, the need to complete clinical ratings or ask patients to complete self-report questionnaires for measurement of outcome, or the need to work within a specific treatment protocol. Although tasks for the GPs were minimal, it is likely that the necessary role change from practitioner to scientist-practitioner was too great to facilitate a shift in treating behaviour. If this is the case, the inherent contradiction between research and delivery of care in the minds of many clinicians is a basic problem for clinical research.16 Nevertheless, treatments that are efficacious in research settings need to be evaluated under the conditions of routine care, and it may not be sufficient to rely on the use of qualitative methods to evaluate outcome in primary care.17 Perhaps an explicit use of the "uncertainty principle" in randomised controlled trials within routine clinical care will enhance recruitment rates.18 That is, if there is apparent certainty about what treatment is best, it is ethically untenable that patients should have their treatment chosen at random, so only patients for whom there is uncertainty about which treatment would be best should be recruited into a randomised trial. In this way the ethical dilemma for clinicians is solved, and the heterogeneity of the patient sample maintained, as clinicians will differ significantly in the types of patients they will be uncertain about. Financial incentives might increase the involvement of clinicians in research, but have caused public outcry in the United States;19,20 the resulting assertive recruiting can also erode informed consent.21,22 We argue instead that a more fundamental shift in ethos and knowledge of principles that underlie research in clinical practice is required. This argument has parallels in the recent Royal Australian College of General Practitioners report on an implementation strategy for evidence-based clinical practice guidelines.23 The report points to a lack of understanding of the principles underpinning the use of clinical practice guidelines in general practice, and the need to develop a culture in which such guidelines are used and valued. In regard to outcome research, until doctors accept a scientist-practitioner model of practice it is unlikely that they will feel comfortable using conventional research protocols. Clinical research conducted in routine care will help clinicians make informed decisions about what may be the best treatment for their patients based on scientifically derived knowledge. We hope that the questions raised in this article will stimulate debate and research that will directly address this important issue. Acknowledgements This research was supported by a grant from the School of Psychiatry, University of New South Wales. References Andrews G, Henderson S, Hall W. Prevalence, comorbidity, disability and service utilisation; and overview of the Australian national mental health survey. Br J Psychiatry 2001. In press. Gath D, Catalan J. The treatment of emotional disorders in general practice: psychological methods versus medication. J Psychosom Res 1986; 30: 381-386. Mynors-Wallis L, Davies I, Gray A, et al. A randomised controlled trial and cost analysis of problem-solving treatment for emotional disorders given by community nurses in primary care. Br J Psychiatry 1997; 170: 113-119. Mynors-Wallis LM, Gath DH, Lloyd-Thomas AR, Tomlinson D. Randomised controlled trial comparing problem-solving treatment with amitriptyline and placebo for major depression in primary care. BMJ 1995; 310: 441-445. Schulberg HC, Block MR, Madonia MJ, et al. Treating major depression in primary care practice. Eight-month clinical outcomes. Arch Gen Psychiatry 1996; 53: 913-919. Catalan J, Gath DH, Anastasiades P, et al. Evaluation of a brief psychological treatment for emotional disorders in primary care. Psychol Med 1991; 21: 1013-1018. Depression Guideline Panel. Depression in primary care. Vol. 2. Treatment of major depression. Clinical Practice Guideline No. 5. Rockville, MD: Department of Health and Human Services, Public Health Service, Agency for Health Care Policy and Research, April 1993. (AHCPR Publication No. 93-0551.) ICD-10 classification of mental and behavioural disorders. Geneva: World Health Organization, 1992. Foy R, Parry J, McAvoy B. Clinical trials in primary care. BMJ 1998; 317: 1168-1169. Peto V, Coulter A, Bond A. Factors affecting general practitioners' recruitment of patients into a prospective study. Family Practice 1993; 10: 207-211. Silverman W. Equitable distribution of the risks and benefits associated with medical innovations. In: Maynard A, Chalmers I, editors. Non-random reflections on health services research: on the 25th anniversary of Archie Cochrane's effectiveness and efficiency. London: BMJ Publishing Group, 1997: 184-193. Elwood P. Cochrane and the benefits of aspirin. In: Maynard A, Chalmers I, editors. Non-random reflections on health services research: on the 25th anniversary of Archie Cochrane's effectiveness and efficiency. London: BMJ Publishing Group, 1997: 107-121. Andrews G. On the promotion of non-drug treatments. BMJ 1984; 289: 994-995. Segelov E, Tattersall MHN, Coates AS. Redressing the balance -- the ethics of not entering an eligible patient on a randomised trial. Ann Oncol 1992; 3: 103-105. Moore TJ. Deadly medicine. New York: Simon and Schuster, 1995. Tognoni G, Alli F, Avanzini F, et al. Randomised clinical trials in general practice: lessons from a failure. BMJ 1991; 303: 969-971. Miller ML, Crabtree BF. Qualitative analysis: how to begin making sense. Family Practice Res J 1994; 14: 289-297. Collins R, Peto R, Gray R, Parish S. Large-scale randomised evidence: trials and overviews. In: Maynard A, Chalmers I, editors. Non-random reflections on health services research: on the 25th anniversary of Archie Cochrane's effectiveness and efficiency. London: BMJ Publishing Group, 1997: 197-230. Eichenwald K, Kolata G. Drug trials hide conflicts for doctors. New York Times, May 16, 1999; 1,28-29. Eichenwald K, Kolata G. A doctor's drug trials turn into fraud. New York Times, May 17, 1999. Ferguson C. Payment of financial incentives to GPs may invalidate informed consent process. BMJ 1998; 316: 75-76. Shalala D. Protecting research subjects -- what must be done. N Engl J Med 2000; 343: 808-810. Report on consultancy to develop an implementation strategy for CPGs. Sydney: Royal Australian College of General Practitioners, August 2, 2000. Authors' details School of Psychiatry, University of New South Wales, Sydney, NSW. Caroline J Hunt, MPsych, PhD, Lecturer (currently, Senior Lecturer, Department of Psychology, University of Sydney). Gavin Andrews, MD, Professor. Clinical Research Unit for Anxiety Disorders, St Vincent's Hospital, Sydney, NSW. Louise M Shepherd, BA(Hons), MPsych, Clinical Psychologist. Reprints will not be available from the authors. Correspondence: Dr C J Hunt, Department of Psychology (F12), University of Sydney, NSW, 2006. carolineATpsych.usyd.edu.au Make a comment 1: The planned trial Objective: To compare structured problem solving with SSRI medication and non-specific counselling for mild to moderate major depression. Trial development: The trial was initially designed with three treatment arms: structured problem solving, medication and placebo. In 1997, general practitioners in their second year of a two-year part-time Master of Psychological Medicine course were approached for feedback. The GPs indicated that, while they believed the study to be of value, they were uncomfortable with the use of a placebo control, so the placebo arm of the trial was abandoned. Detailed protocols for each treatment were developed, with medications which reflected best prescribing practice (United States Department of Health and Human Services Clinical practice guidelines 7), a treatment period of six months, and a follow-up period to track longer-term changes. The protocols were designed to be simple to use and, to minimise tasks for the GPs, telephone assessments by a clinical psychologist were planned to confirm diagnosis, assess severity, and evaluate outcome. Design: Patients assessed by their GPs as having mild to moderate major depression were to be randomly allocated to: structured problem solving alone; selective serotonin reuptake inhibitor (SSRI) medication and non-specific counselling; or SSRI medication and structured problem solving. Patients were required to meet International classification of diseases - 10th revision 8 criteria for a mild or moderate major depressive episode. Exclusion criteria included current or previous manic (or hypomanic) or psychotic symptoms, current suicidal intent, current drug or alcohol abuse, current pharmacological or psychological treatment for depression, and (to exclude severe depression) current somatic (or melancholic) features. Participating general practitioners: In 1998, the protocols were again reviewed by students in the Masters course, who agreed that they were consistent with current best primary care practice and could be delivered in this setting. Ten GPs agreed to participate - four were current second-year students in the Masters course, and six were graduates of the course. Three current second-year students did not participate because they were not working in general practice, and two because they did not wish to randomly allocate their patients to treatment. All participating doctors had been trained in assessing and managing depression (including structured problem solving), and clinical supervision was offered over the course of the trial. Back to text 2: Why were no patients recruited? Six months after commencement of the trial in 1998, despite frequent reminders and discussions about the trial protocol, no patients had been recruited. This prompted a clinical audit of all patients with depressive symptoms attending the participating doctors' practices over three weeks. Each general practitioner recorded patients presenting with depressive symptoms and the reasons why they considered them unsuitable for the trial on a form we designed for this purpose. Over the three weeks, 114 patients presented with depressive symptoms (12% of all presenting patients), but none were entered in the study. The results of the audit are shown in the Table. The most frequently cited reasons for exclusion were current pharmacological or psychological treatment for depression, or depression of insufficient severity to meet ICD-10 criteria. In an attempt to improve recruitment in the following six months, we dropped the exclusion criteria of current psychological treatment and insufficient severity (these features now to be assessed by the clinical psychologist), yet still no patients were recruited. Reasons for not entering trial No. (%) patients* Depression insufficiently severe to meet ICD-10 criteria 27 (23.6%) Severe depression or criteria met for "somatic syndrome" 13 (11.4%) Prior or current manic, hypomanic or psychotic episode 6 (5.3%) Serious suicidal intent 5 (4.4%) Current drug or alcohol abuse 6 (5.3%) Current pharmacological treatment for depression 38 (33.3%) Current psychological treatment for depression 34 (29.8%) Physical problems precluding use of an SSRI 1 (0.9%) Prior failure to respond to an SSRI 5 (4.4%) Patient refused randomisation 7 (6.1%) General practitioner not confident about using problem solving with this patient 20 (17.5%) Other (eg, dementia, communication difficulties, personality disorders) 22 (19.3%) *There were 114 patients, but general practitioners frequently nominated more than one reason for excluding patients. ICD-10=International classification of diseases - 10th revision.8 SSRI=selective serotonin reuptake inhibitor. Once the trial was formally abandoned, there were discussions with the four GPs still completing their Masters course. These GPs admitted unease with the process of randomisation, despite the demonstrated efficacy of both treatments for this population. Back to text

Caroline J Hunt · Louise M Shepherd · Gavin Andrews

Research The effects of Chinese medicinal herbs on postmenopausal vasomotor symptoms of Australian women A randomised controlled trial Susan R Davis, Esther M Briganti, Run Q Chen Fabien S Dalais, Michael Bailey and Henry G Burger MJA 2001; 174: 68-71 For editorial comment, see Eden Abstract - Methods - Results - Discussion - Acknowledgements - References - Authors' details - - More articles on Obstetrics & gynaecology and women's health Abstract Objective: To evaluate the effects of a defined formula of Chinese medicinal herbs (CMH) on menopausal symptoms. Design: A double-blind randomised placebo-controlled trial. Methods: Between August 1998 and April 1999, 55 postmenopausal Australian women recruited from an urban population completed 12 weeks of intervention with either a defined formula of CMH (n = 28) or placebo (n = 27) taken twice daily as a beverage. Main outcome measures: The primary end-point was change in frequency of vasomotor events (hot flushes and night sweats). The secondary end-points were changes in score for the domains measured in the Menopause Specific Quality of Life (MENQOL) Questionnaire. Results: There was a reduction in average weekly frequency of vasomotor events with CMH (- 15%; 95% CI, - 31% to + 1%) and with placebo (- 31%; 95% CI, - 42% to - 21%). The difference between groups favoured the use of placebo; however, this was not significant (P = 0.09). Although significant reductions in scores for the various domains of the MENQOL Questionnaire were observed for both CMH and placebo, there were no significant differences between the two treatment groups for any domain. There was evidence for effect modification by previous use of natural therapies for the vasomotor, physical and sexual domains of the MENQOL Questionnaire: women with no prior use of natural therapies for their menopausal symptoms responded to therapy, whereas prior users did not. Conclusions: The defined formula of CMH was no more effective than placebo in reducing vasomotor episodes in Australian postmenopausal women, or in improving any of the four symptom domains in the MENQOL Questionnaire. Three of the MENQOL Questionnaire domains were modified by prior use of natural therapies. This finding has implications for future studies. In Australia, more than a third of postmenopausal women are troubled by vasomotor symptoms.1 Although hormone replacement therapy (HRT) eliminates 60% of flushes within three months,2 a significant number of postmenopausal women have absolute or relative contraindications to HRT, or are unwilling to use this therapy.3Chinese herbal medicine has been used for centuries in China for treating menopausal symptoms, and is still in current use. Clinical trials in China have shown significant effects of Chinese herbal medicine in alleviating menopausal symptoms in Chinese women,4,5 but these effects may not be generalisable. We therefore conducted a double-blind, randomised, placebo-controlled study of the effects of a modified traditional formula of Chinese medicinal herbs (CMH) on vasomotor symptoms in Australian postmenopausal women. Methods Study population Approval for the study was obtained from the Human Research and Ethics Committee of Monash Medical Centre. All patients gave written informed consent. The study was conducted between August 1998 and April 1999. Inclusion criteria: Patients were recruited through the Jean Hailes Foundation Newsletter, newspapers, radio station interviews and the Medical Unit of the Jean Hailes Foundation. Non-Asian women aged 45 to 70 years, who had lived in Australia for at least 10 years, were postmenopausal (> 12 months' amenorrhoea and follicle-stimulating hormone level > 25 IU/L), and reported at least 14 hot flushes or night sweats per week were eligible for the study. Exclusion criteria: Women were excluded if they had used HRT, CMH or other natural therapies (evening primrose oil, yam cream, progesterone cream or any other over-the-counter preparation for menopausal symptoms) during the eight weeks before baseline, or if they had preexisting gastrointestinal, renal or liver disease, diabetes mellitus requiring treatment, uncontrolled hypertension, undiagnosed vaginal bleeding, systemic glucocorticosteroid use, or were undergoing cancer therapy. Women who had consumed a high phytoestrogen diet (according to a food frequency questionnaire6) for the four weeks before baseline were also excluded. Randomisation: Subjects were randomised to CMH or placebo using a randomisation chart constructed by randomising numbers 1 to 88 into two groups using Microsoft Excel.7 Study intervention The defined formula of CMH for the active preparation used in the trial is listed in Box 1. Placebo was cornstarch with a bitter taste enhancer. All herbs are listed with the Australian Therapeutic Goods Administration, and were administered within standard dosage levels. All were screened for heavy metal contamination by Ningbo Daekang Herbs Co Ltd (Ningbo, China) and the National Analytical Laboratories in Melbourne. The CMH and placebo were produced by Ningbo Daekang Herbs Co Ltd as granules soluble in warm water, and each dose was prepackaged in identical aluminium foil sachets. Patients were instructed to drink one sachet of granules dissolved in 200 mL of warm water, twice a day. Both solutions had similar unusual tastes. A four-week supply was dispensed at each treatment visit. The design did not accommodate the diagnostic and therapeutic principles of Chinese medicine, but was for analysing the therapeutic efficacy of the herbs. Outcome measures Demographics, body mass index (kg/m2), medical history, gynaecological history, and use of previous HRT or natural therapies for menopausal symptoms were documented at baseline. The primary end-point of the study was the effect of treatment on the frequency of vasomotor symptoms. Each woman completed a daily diary of the frequency of hot flushes and night sweats for four weeks before the commencement of treatment and for the entire 12 weeks of the study period. The secondary end-points of the study were the effect of treatment on each of the four domains of the Menopause Specific Quality of Life (MENQOL) Questionnaire and on urinary phytoestrogen excretion. The MENQOL Questionnaire is a validated instrument that tests physical, vasomotor, psychosexual and sexual domains of quality of life.8 It can differentiate between women according to quality of life, as well as measure changes in quality of life. A minimum score of zero corresponds to no symptoms and a maximum score of seven corresponds to extremely bothersome symptoms. The smallest clinically relevant change is a difference in one point within the domains, representing a 15% change. As dietary history is a poor guide to phytoestrogen ingestion, a potential confounding factor, we also measured urinary phytoestrogen excretion in women participating in the trial. Total urinary daidzein and genistein excretion was measured in 24-hour urine samples at baseline and at Week 12.9 Subjects were asked not to modify their dietary pattern for the study period. Sample size and statistical analysis The sample size was calculated based on the primary end-point of change in hot flushes and night sweats. A clinically relevant effect of treatment is considered to be at least a 40% reduction in vasomotor events.10-12 Anticipating a 30% placebo response, for power of 80% and a significance level of 5%, a sample size of 28 subjects in each treatment group was required. This sample size was also adequate to determine a clinically relevant change of score of one point in the MENQOL domains.8Statistical analysis was performed using Statview.13 For each participant the percentage change from baseline in the frequency of hot flushes and night sweats for each of the 12 weeks of the study period, and the absolute difference in scores between Week 12 and baseline for each domain of the MENQOL Questionnaire, were calculated. Repeated analysis of variance was used to analyse the effects of treatment within and between groups over the study period for these outcomes. The Wilcoxon two-sample test was used to analyse the effect of treatment on the excretion of the phytoestrogen metabolites daidzein and genistein. Additional analysis was undertaken to determine the effect of baseline characteristics (age, BMI, duration of amenorrhoea, and previous use of HRT or natural therapies for relief of vasomotor symptoms) on the average percentage change in vasomotor symptoms and on the difference in scores for each domain of the MENQOL Questionnaire. This was performed using analysis of covariance. Continuous variables were categorised into two groups based on the median value (age: < 55 years and ≥ 55 years; BMI: ≤ 25 kg/m2 and > 25 kg/m2; duration of amenorrhoea: < 4 years and ≥4 years). Results Study population Of the 78 subjects who were randomised, 28 in the active group and 27 in the placebo group completed the study (Box 2). Baseline characteristics of those who withdrew and those who completed the study were similar, except for the previous use of natural therapies for menopausal symptoms, which was more frequent in those who withdrew. Most withdrawals were owing to taste intolerance and occurred within the first week after randomisation. There were no significant differences in baseline characteristics between the placebo and CMH treatment groups (Box 3). Effect of intervention on vasomotor symptoms The frequency of vasomotor symptoms was reduced in both CMH and placebo groups (CMH: - 15.0%; 95% CI, - 31.1% to + 1.2%; placebo: - 31.4%; 95% CI, - 41.5% to - 21.2%). The difference between the two groups was not significant (+16.4%; 95% CI, + 35.2% to - 2.4%; P = 0.09). A progressive decline in the frequency of vasomotor symptoms with treatment duration was seen in both groups (CMH, P = 0.001; placebo, P = 0.006). The difference between the two groups was not significant (P = 0.26). Effect of intervention on MENQOL Questionnaire scores A reduction in score was seen in all four domains of the questionnaire with both CMH and placebo. This was significant only for the physical (- 1.14; 95% CI, - 1.78 to - 0.50), vasomotor (- 0.57; 95% CI, - 0.89 to - 0.24) and sexual (- 0.69; 95% CI, - 1.10 to - 0.28) domains in the CMH group, and the physical (- 0.74; 95% CI, - 1.41 to - 0.07) domain in the placebo group. However, the difference between the two treatment groups was not significant for any of the four domains. Effect of baseline characteristics on treatment effect The effects of baseline characteristics are shown in Box 4. Women with more than four years of amenorrhoea had a significantly greater response to placebo than to CMH (Box 4). A significantly greater reduction in score was seen with CMH compared with placebo in the vasomotor domain of the MENQOL Questionnaire for the baseline characteristics of age < 55 years, BMI ≤ 25 kg/m2, and previous non-users of natural therapies (Box 4). There was a significant difference in treatment effect between those who had and those who had not previously used natural therapies for the physical, vasomotor and sexual domain scores. A significant difference in treatment effect was also seen for the two age categories and for the two BMI categories for the vasomotor domain score. Phytoestrogen measurements No significant change was seen in daidzein or genistein excretion with either CMH or placebo, and there was no difference between the two treatment groups. Adverse events The frequency of reported adverse events did not differ between the two groups. Abdominal bloating was reported by three women treated with placebo and one with CMH; two women with CMH reported lower abdominal pain and loose stools. Fifteen women (placebo, 9; CMH, 6) reported headache, joint pain or dizziness. Discussion In our study of extracts of CMH administered as granules reconstituted to a beverage, there was no significant or clinically relevant difference in the frequency of vasomotor symptoms between placebo and CMH therapy. Furthermore, there was no significant or clinically relevant difference in the scores for the four domains of the MENQOL Questionnaire. This study was adequately powered to distinguish at least a 40% reduction in the frequency of vasomotor symptoms, as well as a clinically meaningful reduction in the MENQOL domain scores with treatment. The effect of CMH compared with placebo on the frequency of vasomotor symptoms was not modified by age, BMI, duration of amenorrhoea, previous use of HRT or natural therapies. However, the scores for the physical, vasomotor and sexual domains were modified by previous use of natural therapies: women who had no prior use of natural therapies for their menopausal symptoms responded to therapy, whereas prior users did not. The vasomotor domain was also modified by age and BMI. It is of interest that prior users of natural therapies showed a clinically relevant greater response to placebo than CMH for the physical, vasomotor and sexual domains. That baseline characteristics, particularly prior natural therapy use, significantly modified the response to treatment in this study is an important observation of relevance to future studies of natural therapies. That our findings differ from reports of studies conducted in China4,5 is most likely owing to differences in study design. The Chinese studies have not been placebo-controlled, have employed raw herbs, and have allowed for modification of herbal constituents during the studies according to individual responses.4,5 The preparation of medicinal tea from raw herbs is very time consuming, and was deemed a major obstacle to compliance in a non-Asian study population. The granules used in this study were supplied by a company that routinely prepares herbs in this manner for medicinal purposes in China, and there is no evidence to indicate that the granules do not retain the therapeutic properties of the original herbs. In summary, our study of the effects of CMH versus placebo on vasomotor events and menopausal symptoms in non-Asian Australian women found no overall benefit of the CMH. The modifying effects of prior use of natural therapies is an important positive finding that deserves further investigation and confirmation. Acknowledgements The study was supported by a research grant from the Australasian Menopause Society. Cathay Herbal, Sydney, kindly donated the study preparations. We thank Dr Tikky Wattanapenpaiboon of Monash University for assistance in the evaluation of the food frequency questionnaire, and Associate Professor Flavia Cicuttini of Monash University for valuable input to this study. Dr James C G Doery of Monash Medical Centre offered guidance in testing the study herbal preparations for heavy metal contamination. We also thank all the participants. References Dennerstein L, Smith AM, Morse C, et al. Menopausal symptoms in Australian women. Med J Aust 1993; 159: 232-236. Abraham S, Perz J, Clarkson R, Llewellyn-Jones D. Australian women's perception of hormone replacement therapy over 10 years. Maturitas 1995; 21: 91-95. Waldman TN. Menopause: when hormone replacement therapy is not an option. Part 1 [review]. Women's Health 1998; 7: 559-565. Yao SA. Review on the research and development of Chinese medicine in menopausal syndrome (in Chinese). J Tradit Chin Med 1994; 35: 112-114. Li CJ. Menopausal symptoms. In: Dai DY, editor. Current application and research of Chinese medicine and pharmacology: gynecology. Shanghai: Shanghai University of Traditional Chinese Medicine Publishing House, 1995; 174-182. Wahlqvist M, Kouris-Blazos A, Hsu-Hage B, et al. Food habits and health status of Anglo-Celtic Australians. A questionnaire on food frequency. Melbourne: Monash University. Microsoft Excel 95 [computer program]. Redmond: Microsoft Corporation, 1995. Hilditch JR, Lewis J, Peter A, et al. A menopause specific quality of life questionnaire: development and psychometric properties. Maturitas 1996: 24; 161-175. Dalais FS, Rice GE, Wahlqvist ML, et al. Effects of dietary phytoestrogens in postmenopausal women. Climacteric 1998; 1: 124-129. Murkies AL, Lombard C, Strauss BJ, et al. Dietary flour supplementation decreases postmenopausal hot flushes: effect of soy and wheat. Maturitas 1995; 21: 189-195. Poller L, Thomson JM, Coope J. A double-blind cross-over study of piperazine oestrone sulphate and placebo with coagulation studies. Br J Obstet Gynaecol 1980; 87: 718-725. Hailes JD, Nelson BJ, Schneider M, et al. Conjugated equine oestrogen versus placebo in the management of menopausal symptoms. Med J Aust 1981; 2: 341-342. Statview [computer program]. Abacus Concepts Inc, Berkeley, CA, 1995. (Received 28 Aug, accepted 1 Oct, 2000) Authors' details The Jean Hailes Foundation, Melbourne, VIC. Susan R Davis, FRACP, PhD, Associate Professor and Director of Research; Run Q Chen, MA, Master's Student; Henry G Burger, AO, FRACP, FAA, Consultant Endocrinologist. Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC. Esther M Briganti, MB BS, FRACP, Senior Lecturer; Michael Bailey, MSc, Statistical Consultant. International Health and Development Unit, Monash University, Clayton, VIC. Fabien S Dalais, PhD, Senior Research Officer. Reprints will not be available from the authors. Correspondence: Associate Professor S R Davis, The Jean Hailes Foundation, 173 Carinish Road, Clayton, VIC 3168. suedavisATnetlink.com.au Make a comment 1: The defined formula of the Chinese medicinal herbs Pharmaceutical name Chinese name Dose* Rehmannia glutinosa Cornus officinalis Dioscorea opposita Alisma orientalis Paeonia suffruticosa Poria cocos Citrus reticulata Lycium chinensis Albizzia julibrissin Zizyphus jujuba Eclipta prostrata Ligustrum lucidum Shu Di Huang Shan Zhu Yu Shan Yao Ze Xie Dan Pi Fu Shen Chen Pi Di Gu Pi He Huan Pi Suan Zao Ren Han Lian Cao Nu Zhen Zi 15 10 12 8 8 12 5 20 15 10 15 10 *Dose in grams of dried herb per day. Back to text 2: Flow diagram of participation in the study CMH = Chinese medical herbs. HRT = hormone replacement therapy. Back to text 3: Baseline characteristics of study participants Baseline characteristics Placebo Chinese medicinal herbs P Number Age (years)* Body mass index (kg/m2)* Duration of amenorrhoea (years)* Previous use of hormone replacement therapy Previous use of natural therapies Frequency of hot flushes or night sweats, per week* MENQOL domains Physical domain* Vasomotor domain* Psychosexual domain* Sexual domain* 27 54.1 (52.6, 55.5) 26.1 (24.3, 27.9) 4.6 (3.0, 6.2) 44.4% 37.0% 46.6 (35.4, 57.8) 5.6 (4.9, 6.2) 4.0 (3.3, 4.8) 3.9 (3.3, 4.6) 3.4 (2.5, 4.3) 28 56.3 (54.3, 58.3) 25.7 (23.9, 27.5) 5.8 (3.9, 7.7) 53.6% 35.7% 46.2 (38.75, 53.7) 5.5 (5.2, 6.5) 3.8 (3.1, 4.5) 3.6 (3.0, 4.2) 3.3 (2.4, 4.3) 0.07 0.75 0.34 0.50 0.92 0.94 0.57 0.67 0.45 0.95 *Values are mean (95% confidence limits). Back to text 4: Effect of Chinese medicinal herbs (CMH) compared with placebo on frequency of vasomotor symptoms and MENQOL domain scores, by baseline characteristics* Mean reduction in MENQOL domain score (95% confidence limits) Mean reduction in vasomotor symptoms (95% confidence limits) Physical Vasomotor Psychosexual Sexual Age +8.1% (-16.5%, +32.8%) -0.74 (-1.91, +0.42) -0.94 (-1.74, -0.14) -0.22 (-1.00, +0.57) -0.72 (-2.82, +1.38) ≥55 years +17.9% (-10.7%, +46.5%) -0.36 (-1.76, +1.03) +0.51 (-0.56, +1.58) +0.10 (-0.77, +0.96) -0.14 (-1.30, +1.03) Body mass index ≤25 kg/m2 +7.1% (-21.4%, +35.5%) -1.16 (-2.57, +0.25) -0.85 (-1.61, -0.08) -0.17 (-1.01, +0.68) -1.00 (-2.66, +0.65) >25 kg/m2 +26.2% (-0.48%, +52.9%) +0.28 (-0.92, +1.48) +0.42 (-0.73, +1.58) +0.13 (-0.68, +0.95) +0.18 (-1.46, +1.82) Amenorrhoea < 4 years +4.8% (-24.6%, +34.2%) -0.28 (-1.72, +1.17) -0.31 (-1.67, +1.06) +0.18 (-0.81, +1.16) +0.52 (-1.59, +2.62) ≥4 years +26.8% (+3.8%, +49.9%) -0.49 (-1.70, +0.72) -0.09 (-0.61, +0.42) -0.08 (-0.70, +0.54) -0.96 (-2.08, +0.16) Previous use of hormone replacement therapy No +12.1% (-14.4%, +38.6%) -0.69 (-2.02, +0.65) -0.24 (-1.47, +1.00) +0.03 (-0.74, +0.80) +0.17 (-1.74, +1.40) Yes +22.4% (-6.3%, +51.2%) -0.05 (-1.37, +1.27) -0.16 (-0.75, +0.43) +0.02 (-0.90, +0.95) -0.59 (-2.43, +1.26) Previous use of natural therapies for symptoms of menopause No +11.1% (-11.2%, +33.3%) -1.16 (-2.35, +0.02) -1.09 (-1.68, -0.49) -0.33 (-1.07, +0.41) -1.19 (-2.75, +0.37) Yes +26.1% (-10.0%, +62.3%) +0.93 (-0.38, +2.24) +1.30 (-0.06, +2.67) +0.63 (-0.29, +1.56) +1.15 (-0.33, +2.64) *Values are the percentage or point difference between CMH and placebo (CMH effect minus placebo effect). As vasomotor symptoms and all domain scores improved for both treatment groups, a negative value indicates a greater effect from CMH and a positive value indicates a greater effect from placebo. For shaded values, 95% confidence limits do not include 0. For boxed values, there is a significant difference in treatment effect between the two categories (P Back to text

Susan R Davis · Esther M Briganti · Run Q Chen · Fabien S Dalais · Michael Bailey · Henry G Burger

Research Use of fake tanning lotions in the South Australian population Kerri R Beckmann, Barbara A Kirke, Kieran A McCaul and David M Roder MJA 2001; 174: 75-78 Abstract - Methods - Results - Discussion - Conclusions - References - Authors' Details - - More articles on Public and environmental health Abstract Objective: To explore the relationship between the use of fake tanning lotions and repeated sunburn among South Australian adults, with a view to informing the Anti-Cancer Foundation of South Australia's (ACFSA) policy on fake tanning products. Study design: Population survey. Participants: 2005 South Australians aged 18 years or older, selected randomly from the electronic White Pages. Main outcome measures: Self-reported use of fake tanning lotions in the past 12 months; frequency of sunburn over summer; and various sun-protective behaviours. Results: 2005 of the 2536 eligible participants (79%) were surveyed by telephone. Fake tan use was most prevalent among women (15.9%), people aged 18-24 years (15.4%), and people with household incomes above $40 000 per year (11.9%). Fake tan users were more likely than non-users to use sunscreens (81.3% v 56.5%; P < 0.001), but less likely to take other precautions such as wearing hats (40.9% v 51.0%; P = 0.04) and protective clothing (22.3% v 34.1%; P = 0.005). They were also more likely to report having been burnt more than once over summer (26.2% v 16.5%; P = 0.025). Multivariate analysis indicates a statistically significant association between fake tan use and repeated sunburn (odds ratio, 2.07; 95% confidence interval, 1.17-3.69), which was independent of age, sex, skin type and sun-protection practices. Conclusion: Users of fake tanning products may be at greater risk of repeated sunburn. The ACFSA sees no justification at this stage for altering its present policy position of not actively promoting the use of fake tanning lotions as a means of reducing sunburn. Anticancer organisations in Australia have been conducting programs aimed at reducing Australia's high rate of skin cancer for over two decades.1 The main objective of these programs is to encourage people to reduce their exposure to solar ultraviolet radiation, the major contributing factor to the development of skin cancer.2In Australia public awareness about the dangers of overexposure to the sun is generally high. In spite of this, a suntan is still desired by some sectors of the community -- in particular, young, fashion-conscious people.3,4 Skin cancer prevention programs have attempted to change attitudes that value tanned skin as attractive and healthy with such messages as "there is no such thing as a safe tan" and "a tan is a sign of skin damage". Last year, Chapman challenged anticancer organisations to consider the role that fake tanning lotions might play in reducing sun exposure, suggesting that they should be assessed as a potential harm-reduction strategy.5 The Anti-Cancer Foundation of South Australia (ACFSA) has, for a number of years, provided information on fake tanning lotions. While not actively encouraging their use, the information suggests that, for those desiring a tan, using fake tanning lotions is preferable to exposure to artificial or solar ultraviolet radiation. In October 1999, the ACFSA included a question on the use of fake tanning lotions in a Health Monitor Survey along with questions on skin type, experience of sunburn and frequency of wearing hats, cover-up clothing, applying sunscreen and seeking shade. This article reports the findings of that survey and discusses them in relation to the position taken by the ACFSA regarding fake tanning lotions. Methods Questions relating to sun exposure and ultraviolet radiation protective behaviours, including one relating to the use of fake tanning lotions, were asked of a random sample of South Australians, by computer-assisted telephone interviewing. These questions (Box 1) were part of a larger health-related survey organised and conducted by the Department of Human Services, South Australia, in October 1999. Except for the question relating to fake tan use, these questions have been used routinely in monitoring sun-protection behaviours in South Australia and were originally validated as written questions in a national Secondary School Children's Survey conducted triennially since 1990.6 The question on fake tan use is a slightly modified version of a question asked in Victorian surveys in 1993 and 1995.7,8Ethical approval for the survey that incorporated the questions used in this study was obtained through the Department of Human Services, with legal authorisation under section 64d of the South Australian Health Commission Act (1976). A sample of 3400 residences from rural and metropolitan areas within South Australia was drawn from the electronic White Pages. One adult from each household (the person whose birthday was the most recent) was invited to participate. Two thousand and five interviews were conducted from the 2536 households that could be contacted after six callback attempts, giving a participation rate of 79.1%. All data were weighted by age, sex and region, and on the probability of selection within the household. The population profile for weighting was obtained from the Australian Bureau of Statistics' estimated population for South Australia, 1997. Geographical region was defined as either metropolitan or country region. Both descriptive analysis of the survey data and logistic regression modelling were undertaken using STATA version 6,9 as this software allows calculation of robust estimates of standard error using methods devised by Huber10 and White.11 Consequently, variance estimates are adjusted for the data weighting. The relationship between fake tan use and reported sunburn over summer was examined using logistic regression modelling, allowing adjustment for age, sex, skin type and sun-protective behaviours. We first constructed a model containing known risk factors for sunburn and then added fake tan use to this model to establish if this improved the fit of the model. "Having been burnt two or more times during the previous summer" was the dependent (outcome) variable. For each of the sun protective behaviour questions, respondents were coded as regular users if they indicated that they "usually, almost always, or always" took such precautions when out in the sun for an hour or more, and were coded as irregular users if they indicated that they "never, rarely or sometimes" took these measures. Results Based on results from this survey, the estimated prevalence of fake tanning lotion use during the past 12 months among South Australians aged 18 years or more was 8.7% (95% confidence interval [CI], 7.3%-10.5%). The prevalence of fake tan use among various subgroups of the population is shown in Box 2. The use of fake tanning lotions is most common among younger people, particularly women, with the peak prevalence being 28% among young women aged 18-24 years. Fake tan use is also more common among those who report that their skin burns before tanning, compared with those whose skin just tans or just burns. Fake tan use also appears to be related to household income, with those with relatively high household incomes (above $40 000 per year) more likely to use fake tanning lotions. Individuals who had used fake tanning lotions in the past year were more likely to report regularly using sunscreen with a sun protection factor (SPF) of 15+ or higher when in the sun than non-users (81% v 57%; P < 0.001). However, they were less likely to report regularly wearing hats (41% v 51%; P = 0.04) or protective clothing (22% v 34%; P = 0.005). They reported seeking shade at levels similar to those who had not used fake tanning lotions (80% v 76%, P = 0.4). Those who had used fake tanning lotions were also more likely to report having been burnt two or more times during the previous summer (26% v 17%; P = 0.025) (Box 3). Factors such as age, skin type, sex and regular sun-protective behaviours are likely to confound the association between fake tan use and risk of burning. Results of logistic regression modelling, which takes into account the effects of these potential confounders, indicate an increased risk among fake tan users of having been sunburnt more than once (odds ratio [OR], 2.07; 95% CI, 1.17-3.69), as shown in Box 4. As the use of fake tanning lotions was much more prevalent among women than men, we also undertook regression analyses for women and men separately. No association between fake tan use and sunburn was found among men (OR, 0.90; 95% CI, 0.14-5.97). This was most probably owing to the fact that only 12 men reported using fake tanning lotions. There was, however, a strong association between using fake tanning lotions and repeated sunburn among women (OR, 2.47; 95% CI, 1.38-4.42). Discussion While the overall prevalence of fake tan use among adult South Australians is low (8.7%; 95% CI, 7.3%-10.5%), the use of fake tanning lotions is fairly common in younger women, with more than one in four women aged 18-24 years reporting having used fake tanning lotions in the past year. These findings are consistent with the reported prevalence of use in Victoria.7,8Respondents who reported using fake tanning lotions were more likely to report regularly using SPF 15+ or higher sunscreen when out in the sun during summer, but were less likely to report wearing hats or protective clothing. Fake tan users were more likely to report being sunburnt two or more times over the past summer. When other known risk factors were taken into account, fake tan users had twice the risk of repeated sunburn over summer compared with non-users. The only previously reported findings in relation to the association between fake tan use and sunburn are from two surveys conducted in Victoria, one in 19937 and one in 1995.8 The first of these surveys found a higher prevalence of sunburn among fake tan users (66% v 46%), while the latter survey found no difference (39% v 40%). The inconsistency of these two reports may have been owing to the relatively small sample size of each survey (n < 700). Owing to the limited nature of the questions in this survey, we were unable to determine whether fake tanning lotions were used just at the start of the season to give a tanned look before a sun-induced tan could be achieved, or throughout the summer as a substitute for sunbathing. Given the timing of the survey (ie, spring), there may be some inaccuracy in people's recall of sunburn in the previous summer. However, it seems unlikely to us that one group would have been more or less likely to under-report having been sunburnt, so any recall effect would have been equivalent in both groups. Another limitation in relation to the timing and cross-sectional nature of the survey is the inability to establish a temporal relationship. In some cases, sunburn may have preceded the use of fake tanning lotions. We can not conclude that fake tan use contributes directly to an increased risk of sunburn. We can only suggest that the behaviours of fake tan use and sun exposure may be linked. A further limitation of this study is that we did not ask about the reason for or frequency of use. We do not know whether there are differences in the risk of sunburn among those who use fake tanning lotions only on special occasions (eg, theatrical performances) compared with those who use such products regularly to maintain a tanned appearance. This lack of detail does not negate the finding that, as a whole, those who use fake tanning lotions are at greater risk of sunburn. Regardless of when and why people use fake tanning lotions, the results of this survey do not offer any evidence that use of fake tanning lotions, as currently practised, protects against sunburn. However, since this is an observational study, we can not rule out the possibility that the use of fake tanning lotions may actually offer some protection. It is conceivable that, had users not been applying fake tanning lotions, sunburn levels could have been even higher in this group. Further clarification of this issue would require a longitudinal (experimental) study design. Our results suggest that, rather than reducing their sun exposure, fake tan users are more likely to be exposing their skin to damaging levels of ultraviolet radiation than non-users. The evidence also suggests that, in general, fake tan users take fewer precautions to protect their skin from the sun. While fake tan users are more likely to report using sunscreens, they appear to rely on sunscreens alone for sun protection rather than using multiple strategies, as recommended by the Anti-Cancer Foundation. Some fake tan users may believe that the tanned effect provided by fake tanning lotions offers protection against the sun. Further confusion may arise in cases where their chosen brand of tanning lotion contains sunscreen. An inspection of fake tanning lotions currently available in South Australia showed that most brands do not include a sunscreen, and many state on the label that the fake tan does not provide protection against solar ultraviolet radiation. Some brands also include the advice to use a regular SPF 30+ sunscreen when going into the sun. However, a few brands of fake tanning lotions do contain sunscreen, varying in their sun protection factor from 4 to 15. One commonly available product with an SPF 4 rating states on its label, "UV Protection: Protects you in the sun, providing 4 times your natural sunburn protection". While technically correct, the protection would apply only to the period immediately after application and not for the time that the tan remains visible on the skin. Such claims are obviously very misleading. Anticancer organisations advise that sunscreens need to be reapplied regularly, ideally two-hourly, to maintain adequate protection. If such advice was followed when using a fake tanning lotion containing a sunscreen, the colour of the tan would deepen with each application. Also, it may take up to four hours for the tan colour to fully develop. Most products recommend removal of dry or flaky skin before applying the fake tanning lotion. The need to do this and the effect of repeated applications on tan colour are likely to preclude regular reapplication of fake tanning lotions, thereby increasing the likelihood of users risking sunburn if they rely on the protection offered by one application. In our view, including a sunscreen in a fake tanning lotion offers no obvious benefit. On the contrary, it has the potential to generate a false sense of protection which may lead to sunburn in fake tan users. Conclusions In response to the discussion posed by Chapman5 in relation to the use of fake tanning lotions as a "harm minimisation" approach, the ACFSA was prompted to review its policy in relation to the promotion and sale of fake tanning lotions. The results of this study do not point to a reduced risk of harmful sun exposure among fake tan users. Rather, they suggest an elevated risk of sunburn. In the light of these findings, the ACFSA sees no justification for altering its current position on the use of fake tanning lotions. The use of fake tanners is not actively promoted by the ACFSA. However, where there is a strong desire for a tan, people are advised that the use of fake tanning lotions is a better alternative than sunbathing or using a solarium. They are also advised that a fake tan does not provide protection against the sun and are warned about the limited protection offered by products that contain a sunscreen. More in-depth investigation of why and when fake tanning lotions are used, and the extent to which fake tan users believe they are protected from the harmful effects of the sun while using such products, is needed to inform education strategies and guide any policy change by organisations such as the ACFSA. The potential of the labelling of fake tan products containing sunscreens to be misleading needs to be brought to the attention of the relevant authorities. References Gray N. Report of the Chairman of the Education Committee. Australian Cancer Society Annual Report, 1979. Sydney: ACS, 1979: 9. Armstrong BK. Stratospheric ozone and health. Int J Epidemiol 1994; 23: 873-885. Arthey S, Clarke V. Suntanning and Sun protection: A review of the psychological literature. Soc Sci Med 1995; 40 (2): 265-274. Clarke V, Williams T, Arthey S. Skin type and optimistic bias in relation to the sun protection and suntanning behaviors of young adults. J Behav Med 1997; 20: 207-222. Chapman S. Faking it: should cancer control agencies promote fake tanning lotions? Med J Aust 1999; 170: 603-604. Broadstock M, Borland R, Hill D. Knowledge, attitudes and reported behaviours relevant to sun protection and suntanning in adolescents. Psychol Health 1996; 11: 527-539. Purchase M, Borland R. Public reaction to the 1992/93 SunSmart campaign: results from a representative survey of Victorians. SunSmart Evaluation Studies 3. Melbourne: Anti-Cancer Council of Victoria, 1994: 93. Dixon H, Cappiello M, Borland R. Reaction to the 1994/95 SunSmart campaign: results from a representative household survey of Victorians. SunSmart Evaluation Studies 5. Melbourne: Anti-Cancer Council of Victoria, 1997: 64. Stata version 6 [computer program]. College Station, TX: Stata Corporation, 1999. Huber PJ. The behavior of maximum likelihood estimates under non-standard conditions. Proceedings of the Fifth Berkeley Symposium on Mathematical Statistics and Probability 1967; 1: 221-233. White H. A heteroskedasticity-consistent covariance matrix estimator and direct test for heteroskedasticity. Econometrica 1980; 48: 817-830. (Received 21 Mar, accepted 31 Jul, 2000) Authors' Details Anti-Cancer Foundation of South Australia, Adelaide, SA. Kerri R Beckmann, BSc(Hons), MPH, Program Evaluation Officer; Barbara A Kirke, DipN, MPHC, Skin Cancer Prevention Project Officer. Collaborative Research Centre for Asthma, University Department of Medicine, Sir Charles Gairdner Hospital, Perth, WA. Kieran A McCaul, BSc, MPH, Biostatistician. Epidemiology Branch, South Australian Department of Human Services, Adelaide, SA. David M Roder, AM, MPH, DDSc, Director. Reprints will not be available from the authors. Correspondence: Ms K R Beckmann, Anti-Cancer Foundation of South Australia, PO Box 929, Unley, SA 5061. kbeckmannATcancersa.org.au Make a comment Back to text Back to text Back to text 4: Factors associated with being burnt more than once over summer All respondents Women only Adjusted Adjusted odds ratio 95% CI P odds ratio 95% CI P Fake tan use Non-users Users 1.00 2.07 - 1.17-3.69 0.013 2.47 1.38-4.42 0.002 Sex Female Male 1.00 2.99 - 2.09-4.29 - - - Age (group years) 65+ 18-24 25-34 35-44 45-54 55-64 1.00 13.70 5.83 4.72 2.46 1.27 - 7.00-26.78 3.19-10.65 2.66-8.38 1.34-4.53 0.61-2.66 0.004 0.529 15.46 4.40 5.12 3.56 0.40 5.34-44.77 1.71-11.34 2.04-12.86 1.37-9.23 0.09-1.65 0.002 0.001 0.009 0.203 Skin type Just tan Burn then tan Just burn 1.00 2.07 2.47 - 1.20-3.56 1.47-4.16 0.009 0.001 1.86 2.12 0.69-5.01 0.83-5.39 0.222 0.117 Sunscreen use Irregular Regular 1.00 1.03 - 0.72-1.48 0.876 0.82 0.44-1.49 0.509 Hat wearing Irregular Regular 1.00 0.69 0.48-0.98 0.038 0.91 0.52-1.59 0.746 Protective clothing Irregular Regular 1.00 0.63 - | 0.44-0.91 0.014 0.95 0.56-1.61 0.856 Shade seeking Irregular Regular 1.00 0.91 - 0.62-1.32 0.604 0.55 0.30-1.01 0.056 *Logistic regression modelling using forced entry of all variables. Separate models for all respondents and women only. Back to text

Kerri R Beckmann · Barbara A Kirke · Kieran A McCaul · David M Roder

The Research Enterprise Australian medical patents granted in the United States in 1984-1999 Eugen Mattes and Michael C Stacey MJA 2001; 174: 83-87 Abstract - Methods - Results - Discussion - Acknowledgements - References - Authors' details - - More articles on Law Abstract Objective: To describe all medical patents granted in the United States to Australian-resident inventors between 1984 and 1999. Data sources: All patent data originated from the US Patent and Trademark Office. Data for 1984-1994 were compiled by CHI Research Inc, and data for 1995-1999 were obtained from the Community of Science website. Main outcome measures: Number of medical patents granted in the US to Australian-resident inventors; assignees (owners) of these medical patents; proportion of these medical patents related to biotechnology. Results: From 1984 to 1999, 7835 utility patents were granted in the US to Australian-resident inventors. Of these, 1308 patents (17%) were identified as medical patents; 489 (37%) of these were biotechnology patents. Medical patents account for an increasing proportion of all US patents granted to Australian inventors, increasing from 10% in 1984 to 25% in 1999. Biotechnology accounted for an increasing proportion of medical patents, rising from 10% to 55% between 1984 and 1999. More than half the medical patents are owned by commercial interests, and 33% by only 14 organisations, six of which are universities and their affiliated institutions. Conclusion: Only a few organisations account for most of the patenting of medical technology. The inventors and their organisations listed on medical patents could be canvassed when developing government policy and targeted for support in commercialising their medical technology. Interest in harnessing the economic value of medical technology conceived and created in Australia has been growing.1-3 This is reflected in the creation of Cooperative Research Centres (CRCs). Since 1991, 67 CRCs have been created, of which 10 have a medical focus.4 Despite these initiatives, medical inventors, unlike sports stars, are virtually unrecognised by the Australian public and scientific community. Where do our new technologies in medicine come from -- industry, universities, or the lone inventor? We chose to study all patents for inventions (utility patents) granted in the United States to Australian residents. These patents are economically more significant than patents granted in Australia, as the increased cost and effort of patenting in another country is thought to filter out trivial inventions.5 Because of the importance of the US market, the US is also the first country where multinational corporations submit their patent applications outside the patent's country of origin.6 Thus, Australian patents in the US are arguably the most important subset of Australian patents in other countries.7 Our aim was to describe Australian medical patents and to compare them with non-medical patents. Methods This is a descriptive study of patents granted in the US from 1984 to 1999 to inventors resident in Australia. Utility patents were examined, with design and plant patents excluded. Sources of data All patent data originated from the US Patent and Trademark Office. US patents listing one or more Australian-resident inventors for 1984-1994 were compiled by Computer Horizons Incorporated (CHI) Research Inc8 of the US and, for 1995-1999, were updated from the Community of Science website.9 Our electronic patent database contained the following information for each patent: year of patent being granted; US patent registration number; title of patent; all listed inventors and assignees and their country of residence; and number of citations of scientific literature. When required for classifying patents, the patent abstracts or full patents were examined on the Internet (using the US patent registration number) at either the US Patent and Trademark Office Web Patent Database Centre,10 or the Delphion (formerly IBM) Intellectual Property Network.11 Categorisation of medical patents As there are no published guidelines for selecting medical patents, we defined a medical patent as any technology used for: managing patients and their illnesses, such as drugs, diagnostic tests, surgical instruments, and rehabilitation devices (dental technologies were excluded); preventing illness, such as sunscreen lotion; or medical research, such as laboratory instruments. Generic technologies used in other fields, such as information technology, were excluded. Patents were classified as medical, possibly medical or non-medical after reading the title and the name of the assignees (owners). For all patents labelled as possibly medical, we read the abstract, and if necessary the complete patent, to properly classify the patent. Medical patents related to biotechnology12 were identified separately, and included devices, processes, DNA sequences, transgenic animals and manufacturing processes in the medical industry. Biotechnology patents related to other industries, such as agriculture, mining and food processing, were excluded. Describing inventors and assignees The inventors and assignees on patents were sorted alphabetically in Microsoft Excel,13 and any errors or differences in spelling were corrected. The median number of inventors and assignees per patent was calculated as a measure of collaboration. The assignees on each patent were categorised as a business, university, government, research institute, CRC, non-government organisation, technology transfer office, or individual. Categorising was usually straightforward using the name of the assignee, but, if there was uncertainty, a search was made on the Internet using the search engine Dogpile.14 Data analysis The data were stored, tabulated and graphed in Microsoft Excel,13 and statistical analysis was conducted using SPSS for Windows.15 The χ2 test or Fisher's exact test was used to compare independent proportions. The Mann-Whitney U test was used to compare medians. Ethical issues All the information in this study, including the names of inventors and companies, is publicly available on numerous patent bibliographic databases. Results From 1984 to 1999, 7835 utility patents were granted in the US to Australian-resident inventors. From examination of the title and assignee names of these patents, 9% (673/7835) were classified as medical and 35% (2767/7835) as possibly medical. The abstracts of all patents classified as possibly medical were examined, and 11% (869/7835) required the full patent to be read. In total, 1308 (17%) Australian patents in the US were classified as medical. Of these, 489 (37%) were biotechnology patents. Trends in medical patenting The annual number of patents granted in the US to Australian-resident inventors in 1984-1999 more than doubled, rising from 310 to 800 (Box 1). During this 16-year period, the proportion of medical patents rose from 10% (30/310) to 25% (202/800). Biotechnology accounted for an increasing proportion of medical patents, rising from 10% (3/30) to 55% (112/202) over the same period. Comparison of medical and non-medical patents In terms of inventors, medical patents were: more likely to have multiple inventors listed, with a median of two inventors per medical patent versus one per non-medical patent (P < 0.001, Box 2); and twice as likely to be part of an international collaboration, with co-inventors who are residents of other countries in 21% (275/1308) of medical and 10% (649/6527) of non-medical patents (P < 0.001, Box 3). Most US patents listing Australian inventors have either an Australian inventor or assignee owning the patent (68% for medical and 81% for non-medical patents) (Box 3). The technology most likely to arise from another country is that owned by an assignee in another country and listing an inventor from another country. Thus, 15% of medical and 7% of non-medical patents in our study may have originated outside Australia (Box 3). Patents are either assigned, usually to an organisation, or unassigned (thus owned by the inventor). We found 82% of medical patents were assigned, compared with 69% of non-medical patents (P < 0.001, Box 2). For assigned patents, both medical and non-medical patents usually have one assignee (Box 2). For these assigned patents, there were three large differences, with medical patents being (Box 4): less likely to be owned by a business; four times more likely to be owned by a university; and 40 times more likely to be owned by a research institute. Both medical and non-medical patents are increasingly owned by business and universities, with fewer being unassigned. From 1984 to 1999, patents assigned to business increased from 49% to 63%; patents assigned to universities increased from 2% to 7%; and unassigned patents decreased from 36% to 20% of all patents. Medical patents were three times as likely as non-medical patents to quote from published scientific articles. Sixty per cent (785/1308) of medical patents cited one or more scientific publications, compared with only 23% (1475/6527) of non-medical patents (P < 0.001). Characteristics of medical patents Most of the 1785 medical inventors are not prolific, with 67% (1200/1785) listed only once in 1984-1999. About 18% (318/1785) of medical inventors are listed on three or more medical patents. However, the 17 most prolific medical inventors (Box 5) were responsible for 13% (169/1308) of Australian medical patents. Eleven of these prolific inventors are clustered around four different technologies: electromedical devices (cardiac pacemakers and cochlear ear implants), biosensors, ribozymes, and the relaxin gene. Just 14 organisations own 33% (438/1308) of medical patents; six of these organisations are Australian universities and their affiliated institutions (Box 6). Surprisingly, 20% (264/1308) of medical patents were owned by just five organisations: the University of Melbourne, Telectronics, the Commonwealth Scientific and Industrial Research Organisation (CSIRO), Biotech Australia, and the University of New South Wales. The three most common types of medical technologies are cardiac pacemakers (7%), syringes or parenteral drug delivery technology (4%), and cochlear ear implants (3%). Discussion Principal findings We believe that this is the first published report that has examined Australian medical patents in detail. Australia, like all countries of the Organisation for Economic Co-operation and Development (OECD), has shown a strong rise in the number of US patents granted per capita since the 1960s.5,16 However, Australia is still ranked a low 16 of 20 OECD countries,7 with only a modest increase in the proportion of utility patents granted to Australian inventors in the US during 1984-1999 (from 0.46% [309/67200] to 0.52% [800/153492]16). As expected, Australia's comparative technological advantage is found mainly in mining and agriculture. This is similar to other resource-abundant OECD countries like Canada, Finland and Norway.5,7 However, our study, along with others,7,17 indicates a shift in Australia to patenting in higher technologies. Our study suggests that medical technology, especially medical biotechnology, is an increasingly important part of Australia's intellectual property portfolio. This may explain why Australia appears to be developing a technological advantage in biotechnology and pharmaceuticals.17 To place this trend in a global perspective, our study would need to be repeated for other, especially OECD, countries. There is a dip in the total number of US patents granted to Australian inventors from 1990 to 1993 (Box 1), possibly reflecting the economic recession at the time. Interestingly, the trend in medical and medical biotechnology patents did not show this decrease, suggesting that development of such technology may be more resistant to downturns in the economy. Another feature was the 51% jump in the number of US patents granted to Australian inventors from 1997 to 1998 -- possibly a flow-on from the 54% increase in the number of patent applications filed by Australians in the US between 1994 and 199818 (noting that it usually takes two years from lodging a patent application until it is granted19). This trend coincides with increased research and development spending in Australia, particularly by business (which unfortunately declined in 1996-97).20 However, these changes may also reflect increased processing of patent applications by the US Patent and Trademark Office7 -- the overall number of utility patents issued jumping 32% from 111 983 in 1997 to 147 520 in 1998.16 Our study lends support to recent findings of the importance of university-based research in underpinning high-technology patents and industries.1,21 Universities and their affiliated institutions: make up more than a third of the most prolific patenting organisations; own an increasing proportion of US patents granted to Australian inventors; and are the source of 97% of the scientific articles cited in Australian medical patents.17 These findings could be the result of Australian governments actively encouraging universities to fund and commercialise research and develop links to industry. The CRCs were part of such initiatives, but the fact that only eight patents are owned by CRCs suggests that they are not very productive in commercialising research. However, this is difficult to judge, as the patents may be assigned to commercial or university partners. Our data also support the emerging ideas on the importance of clusters of co-located industries and universities where collaboration and competition act as constant spurs to innovation, such as is seen in Silicon Valley in California.21 In Australia, such clusters appear to be growing in Melbourne and Sydney for industries in biotechnology and electromedical devices. This is demonstrated by examining the prolific inventors and their assignees, indicating varied links between industry and publicly funded institutions. Strengths and weaknesses of the study Possible weaknesses in our study relate to three areas of potential misclassification in our patent data. Classification of country of origin: We classified patents as Australian if any inventor was an Australian resident. This may result in the inclusion of technology originating in another country but which had an Australian inventor working on it (estimated to be about 15% for medical and 7% for non-medical patents). Definition of medical patents: Given the absence of any published guidelines, it could be debated whether certain technologies are really "medical" (such as those related to optometry and sunscreen lotions) and whether dental technologies should have been excluded. Classification of assignees as "business": Assignees with a business-type suffix (ie, "Pty Ltd", "Ltd", "Corp", "Inc", "NV", "AG" and "GMBH"), unless detected through searches on the Internet as belonging to another category such as a technology transfer organisation, would have been misclassified as a business. It is difficult to predict whether the first two potential biases could alter our conclusions. The third may lead to an overestimation of the number of patents owned by business. When identifying the country of origin of a patent, the main convention is to use the residency of the inventor16,17 rather than assignees, partly because a large proportion of patents are unassigned (29% in our study). Like other technology or innovation indicators, patent statistics have advantages and disadvantages.22,23 Our study treats all patents as being of equal importance; however, a patent's commercial value can vary enormously.23,24 Furthermore, patent data do not capture all new technology, as some may not be patentable, and patenting can vary with economic conditions and with the strategic concerns of companies.23,24 For example, patenting as a means of protecting intellectual property is very important for the pharmaceutical industry but of little relevance to the rubber industry.24 In addition, the difficulty when describing patents owned by business is that many are granted under the names of subsidiaries and divisions that are different from the names of parent companies. Some companies even actively hide emerging technologies under different company names, so-called "submarine" patents.5,25 Possible mechanisms and implications for policymakers Australia has a substantial and growing trade deficit in high-technology goods,21 making it more imperative to capture more of the economic value of Australian medical patents. But how? First, the more prolific medical inventors and their organisations could be canvassed when developing government policy which may impact on the commercialisation of medical technology. Such surveys could also identify emerging technologies, which may be the basis of new industries, enabling government to take an anticipatory stance on industry policy. Second, the medical inventors and assignees could be actively targeted with assistance in developing their medical technology. To foster the growing culture of enterprise and innovation within academia,4 it may be worth considering a reward for the prolific inventors and assignees. Such rewards may encourage other inventors and promote inventors as role models for other scientists. Acknowledgements We are grateful to Associate Professors Sam Garrett-Jones and Tim Turpin from the Centre for Research Policy at the University of Wollongong for providing the database of Australian patents in the US for 1984-1994, and to Ms Christine Porter, Manager of the European and Commonwealth Office, Community of Science, for providing free access to the US patents on their website. We would like to thank Dr Dora Marinova from ISTP at Murdoch University and Professor Jane Marceau, Pro Vice Chancellor (Research) at the University of Western Sydney Macarthur, for their valuable advice. Eugen Mattes was the recipient of an Eva K A Nelson Medical Research Scholarship from the University of Western Australia from 1995 to 1998 and an advanced academic registrar funded by the Royal Australian College of General Practitioners in 1999 and the Registrar Scholarship and Research Fund of the College in 2000. We also want to acknowledge the support of Professor Max Kamien and the Department of General Practice, University of Western Australia. We would also like to thank the reviewers for their helpful comments. References Wills PJ (Chairman). Health and Medical Research Strategic Review. The virtuous cycle: working together for health and medical research. Canberra: Department of Health and Aged Care, 1999. The National Innovation Summit. <http://www.isr. gov.au/industry/summit/index.html> Accessed 24 February 2000. Biotechnology Australia. Developing Australia's biotechnology future. Discussion Paper. Canberra: Commonwealth of Australia, 1999. Mercer D, Stocker J (Steering Committee). Review of greater commercialisation and self funding in the Cooperative Research Centres Programme. Canberra: Department of Industry, Science and Tourism, 1998. Patel P, Pavitt K. Australia's technological capabilities: an analysis using US patenting statistics. Brighton: Science Policy Research Unit, University of Sussex, 1995. Bertin G, Wyatt S. Multinationals and industrial property: the control of the world's technology. Hemel Hempstead, Hertfordshire, England: Harvester-Wheatsheaf, 1988. Department of Industry, Science and Technology (DIST). Australian business innovation: a strategic analysis. Report No. 5. Canberra: AGPS, 1996. CHI Research Inc. <http://www.chiresearch.com/> Accessed 7 February 2000. Community of Science. US patents. <http://patents.cos.com/> Accessed 10 July 2000. US Patent and Trademark Office. USPTO Web Patent Database. <http://www.uspto.gov/patft/index.html> Accessed 7 February 2000. Intellectual Property Network. <http://www. delphion.com/home> Accessed 7 December 2000. National Science and Technology Council. Biotechnology for the 21st Century: New Horizons. Washington: USGPO, 1995. Available at <http://www.nal.usda.gov/bic/bio21>. Microsoft Excel 97 SR-2 [computer program]. Cambridge, Massachusetts: Microsoft, 1997. Dogpile. <http://www.dogpile.com/> Accessed 7 February 2000. SPSS for Windows [computer program]. Version 8.0. Chicago, Illinois: SPSS Inc, 1997. Patent counts by country/state and year. Utility patents. January 1, 1963 - December 31, 1999. Technology Assessment and Forecast (TAF) Program, Office for Patent and Trademark Information, US Patent and Trademark Office. <http://www.uspto.gov/web/offices/ac/ido/oeip/taf/ cst_utl.pdf> Accessed 10 July 2000. Narin F, Albert M, Kroll P, Hicks D. Inventing our future: the link between Australian patenting and basic science. <http://www.arc.gov.au/ publications/arc_pubs/00_02.pdf> Accessed 30 October 2000. Number of utility patent applications filed in the United States, by country of origin, calendar years 1965 to present. Technology Assessment and Forecast (TAF) Program, Office for Patent and Trademark Information, US Patent and Trademark Office. <http://www.uspto.gov/web/offices/ac/ido/oeip/taf/ appl_yr.pdf> Accessed 30 October 2000. Trilateral Statistical Report 1997. US Patent and Trademark Office. <http://www.uspto.gov/web/offices/ dcom/olia/trilat/tsr97/> Accessed 10 July 2000. Science and Technology Policy Branch of the Department of Industry, Science and Resources. Australian science and technology at a glance 2000. <http://www.isr.gov.au/science/analysis/glance2000/> Accessed 30 October 2000. Marceau J, Manley K, Sicklen D. The high road or the low road? Alternatives for Australia's future. Sydney: Australian Business Foundation; 1997. Patel K, Pavitt K. Paterns of technological activity: their measurement and interpretation. In: Stoneman P, editor. Handbook of the economics of innovations and technical change. Oxford: Blackwell, 1995; 14-51. Industry Analysis Branch of the Department of Industry, Science and Resources. Measuring the knowledge-based economy. How does Australia compare? Canberra: Commonwealth of Australia, 1999. Geroski P. Markets for technology: knowledge, innovation and appropriability. In: Stoneman P, editor. Handbook of the economics of innovation and technical change. Oxford: Blackwell, 1995; 90-131. Garrett-Jones S, Aylward D. Measuring linkages between basic scientific research and Australian industrial technologies using patent data. Wollongong: Centre for Research Policy, University of Wollongong, 1995. (Received 14 Jul, accepted 2 Nov, 2000) Authors' details University of Western Australia, Perth, WA. Eugen Mattes, MB BS, MPH, Advanced Academic Registrar, Department of General Practice, and PhD Scholar, Department of Surgery, Fremantle Hospital; Michael C Stacey, DS, FRACS, Associate Professor, Department of Surgery. Reprints will not be available from the authors. Correspondence: Dr E Mattes, Visiting Research Fellow, TVW Institute for Child Health Research, Division of Population Sciences, 100 Roberts Road, Subiaco, WA 6008. emattesATcyllene.uwa.edu.au Make a comment 1: Number of utility patents granted in the United States to Australian-resident inventors from 1984 to 1999 Back to text 2: The number of medical and non-medical patents granted in the United States to Australian-resident inventors between 1984 and 1999, and numbers of inventors and assignees (owners) Medical Non-medical Total Patents 1308 6527 7835 Inventors Number listed Number of individuals Inventors/patent (median)* 3270 1785 2 11127 7092§ 1 14397 8744¶ Assigned patents† 1068 (82%) 4533 (69%) 5601 Assignees Number listed Number of individual assignees‡ Assignees/assigned patent (median)* 1192 448 1 4909 2309 1 6101 2701¶ * The medians were significantly different (Mann-Whitney U test; P < 0.003). For assignees this is unlikely to be of practical significance. † Medical and non-medical groups are significantly different (Pearson χ2, P < 0.001). ‡After correcting errors or differences in spelling (16% of medical and 9% of non-medical assignees were either misspelt or spelt differently). § Calculated using ratio from medical patents: there were 1785 individual medical inventors after correcting the spelling of the initial list of 1878 individuals. So, for non-medical inventors, it was estimated that there were 7092=7461 x (1785/1878) individuals, assuming a similar 5% difference in spelling of the 7461 non-medical inventors listed initially. ¶Not equal to the sum of inventors or assignees on medical and non-medical patents, as 133 inventors and 56 assignees are on both types of patents. Back to text 3: The location of inventors and assignees for United States patents listing Australian inventors for 1984-1999 Location of inventors Location of assignees Medical Non-medical Australia Unassigned patents* Australia Australia and other countries Other countries* Subtotal 226 (17%) 660 (50%) 8 (1%) 139 (11%) 1035 (79%) 1942 (30%) 3357 (51%) 74 (1%) 505 (8%) 5878 (90%) Australia and other countries (international collaboration) Unassigned patents Australia* Australia and other countries* Other countries* Subtotal 14 (1%) 48 (4%) 22 (2%) 191 (15%) 275 (21%) 52 (1%) 114 (2%) 40 (1%) 443 (7%) 649 (10%) Total 1308 (100%) 6527 (100%) Global Pearson χ2 is significant (P <0.001.). * Significant difference between medical and non-medical patents (P <0.001). Back to text 4: Classifications of assignees listed on the 1068 medical and 4533 non-medical assigned US patents listing Australian-resident inventors for 1984-1999 Assignee Medical patents Non-medical patents Business* University* Research institute* Government* CSIRO Individual* Technology transfer organisation Non government organisation† Cooperative research centre Total 700 (59%) 206 (17%) 97 (8%) 70 (6%) 60 (5%) 30 (2.5%) 22 (1.8%) 6 (0.5%) 1 (0.1%) 1192 (100%) 3913 (80%) 181 (4%) 8 (0.2%) 195 (4%) 272 (6%) 257 (5%) 69 (1%) 7 (0.1%) 7 (0.1%) 4909 (100%) Global Pearson χ2 is significant (P <0.001). Pairwise comparisons were done using Pearson χ2, except where Fisher's exact test was needed when an expected count was less than 5. *Significant difference between medical and non-medical patents (P <0.004). †Significant difference between medical and non-medical patents (P=0.027). CSIRO=Commonwealth Scientific and Industrial Research Organisation. Back to text 5: The 17 most prolific Australian medical inventors listed on 10 or more Australian medical patents in the US for 1984-1999, grouped by technology Main technology Inventor Number of patents Main assignees Method for constructing proteins and other molecules Simpson R 18 Ludwig Institute for Cancer Research, US Cardiac pacemakers and cochlear ear implants Money D Kuzma J Daly C Milijasevic Z 15 12 10 10 Telectronics Pty Ltd, NSW, and Cochlear Pty Ltd, NSW Biosensors Cornell B Braach-Maksvytis V Raguse B 14 13 10 Australian Membrane and Biotechnology Research Institute, NSW Ribozymes - gene shears Jennings P Cameron F 14 (1) 11 Gene Shears Pty Ltd, NSW and ACT Vitamin B12 as carrier for oral drugs Russell-Jones G 14 (1) Biotech Australia Pty Ltd, NSW Intraocular lenses Barrett G 13 Alcon Laboratories Inc, and Chiron, US, and Oversby Pty Ltd, WA Relaxin gene Tregear G Niall H 13 (1) 10 (1) Howard Florey Institute, VIC Syringe or drug infusion devices Whisson M 12 Eastland Technology Australia Pty Ltd, WA Matrix metalloprotease inhibitors Grobelny D 10 Glycomed Inc, US, and Narhex Ltd, Hong Kong Contact lenses Meijs G 10 (6) CIBA Vision Group, US Back to text 6: The most prolific assignees listed on 15 or more Australian medical patents in the United States for 1984-1999 Assignee Medical Non-medical Total University of Melbourne and affiliated institutions 76 28 104 Telectronics NV or Telectronics Pty Ltd or Telectronics Pacing Systems Inc 75 0 75 CSIRO 60 272 332 Biotech Australia Pty Ltd 28 3 31 University of New South Wales and affiliated institutions 25 51 76 Australian National University and Anutech Pty Ltd 23 30 53 University of Sydney 22 26 48 Monash University and affiliated institutions 21 8 29 AMRAD Corp Ltd 21 3 24 Ludwig Institute for Cancer Research* 21 0 21 University of Queensland and Queensland Institute of Medical Research (QIMR) Council 20 18 38 Cochlear Pty Ltd 16 0 16 Commonwealth of Australia 15 87 102 Gene Shears Pty Ltd 15 0 15 Total 438 526 964 *16 of the 21 patents originated from the Melbourne branch (Dr C Thumwood, Scientific Administrator, Ludwig Institute for Cancer Research, personal communication). Back to text

Eugen Mattes · Michael C Stacey

The Research Enterprise General practice research in Australia, 1980-1999 Alison M Ward, Derrick G Lopez and Max Kamien MJA 2000; 173: 608-611 For editorial comment, see Van Der Weyden Abstract - Methods - Results - Summary and conclusions - Acknowledgements - References - Authors' details - - More articles on General practice and primary care Abstract There has been a nearly fivefold increase in the amount of Australian general practice research published in 1990-1999 compared with the previous decade. The university departments of general practice and other university departments have been responsible for most of the research. GPs were involved in at least 60% of all of the research reviewed. Half of the research was found to be clinically pertinent to the front-line GP. The National Health Priority areas, introduced in 1994, were poorly represented, but it is probably too soon for this research to be published. There has also been little research on rural general practice. This review provides a starting point for classifying general practice and primary healthcare research in the future. In Australia, the general practice research effort, begun by a few enthusiastic general practitioners (GPs) in the early 1970s, now extends to academic programs involving GPs and social scientists with an interest in general practice. The inception of academic departments of general practice resulted in a gradual professionalisation and an increase in research.1In 1991-92 the research effort received an extra boost through the General Practice Evaluation Program (GPEP) of the Commonwealth Department of Health, which aimed to develop data on the dynamics of general practice in Australia and to improve standards and quality assurance. In April this year, the Department announced a new funding initiative -- a national strategy for Primary Health Care Research, Evaluation and Development.2 In the light of these developments, we reviewed and analysed Australian general practice research published in the past 20 years to provide a baseline for future research initiatives. Methods Data sources We conducted literature searches in March and April 2000 to identify all Australian articles relating to general practice research published since 1980. Letters and editorials were excluded. The search strategies, search terms and outcomes are shown in Box 1. Study selection We restricted the review to the two decades 1980-1989 and 1990-1999; and We used a similar definition of general practice research to that used by Starfield for primary care research; that is, even if the problem being examined is a problem seen in general practice, it is not necessarily general practice research unless the context of the research is general practice.3We identified general practice research published in the past two decades by scanning the abstracts of the 2242 articles retrieved by our search (those articles without abstracts [about 28%] were viewed in full). Scanning identified 663 general practice research articles. The remainder were discussion papers, or not general practice research. Classification categories We classified each article and the research reported according to nine variables: Country of publication; Journal; Affiliation of authors: Determining affiliation was complicated by the name changes of departments of general practice. We compiled lists of department names and of academic GPs to help identify who was doing the research. Type of research: Searches of the Australian and overseas literature failed to find a comprehensive classification system for type of general practice research.3,4-6 We extended the classification categories used by the National Information Service (NIS) for the GPEP grants, giving 13 categories of general practice research. Research methodology: The research methods used were difficult to classify.7,8 The usual method categories for public health research do not include some methods used in general practice. We used the public health categories (see Box 6) as a starting point and expanded on these. International Classification of Primary Care (ICPC);9 National Health Priority areas; 10,11 Rural health; Other areas of concern (eg, Aboriginal or Torres Strait Islanders; aged or adolescent populations). Data analysis One of us (A M W) coded all articles and trained a research officer to check the coding. A test-retest reliability check on 41 articles showed an average reliability across the classification variables of 92% (98% for affiliation, 83% for type of research, 83% for methodology, 95% for ICPC category, 98% for National Health Priority areas, 98% for areas of concern, 90% for rural research). The classified data were analysed using SPSS.12 Results Number and location of publications (Boxes 2 and 3) Publications of Australian general practice research increased markedly in the second decade, with 82% published since 1990. As expected, most were published in Australia, but the proportion published overseas has increased from 17.1% in 1980-1989 to 31.7% in 1990-1999, with a marked increase in publications in England in the second decade. Over half of the research has been published in two journals -- Australian Family Physician (31%) and The Medical Journal of Australia (21%). The proportion published in Australian Family Physician almost halved in the second decade, with publications increasing across a range of other journals. Authors and affiliation (Box 4) The States with two or more universities with departments of general practice produced most research, with the amount from New South Wales (37%) being more than double that from any other State. Victoria was second with 18%, followed by Queensland (12%) and South Australia (12%). Universities were responsible for 58% of the research, with hospitals accounting for 12% and the Royal Australian College of General Practitioners (RACGP) 7%. The "other" category included health departments, and the Divisions of General Practice (the latter published less than 1%). The number of articles without a recorded affiliation decreased over the decades (the "institution" field was added to MEDLINE in 1988), but, as many of the early articles had no abstracts and were viewed in full, we were often able to identify the first author's affiliation. The contribution made by GPs to research not conducted in general practice academic departments was assessed by searching for GPs among the co-authors; 39% of the research in other academic departments had GPs as co-authors. We also found that 36% of the research conducted in hospitals and other organisations (eg, health departments) had GPs as co-authors. Overall, GPs were involved as authors in at least 64% of all research in general practice. This has implications for discussions about research conducted by GPs as opposed to research conducted on GPs. Type of research (Box 5) Twenty-seven per cent of research was in the category "GP behaviour, views and opinions". This includes screening, health prevention and promotion, prescribing, counselling and many other general practice activities. The number of GP behaviour studies increased in the second decade. Next most common was studies into education and training -- both undergraduate and postgraduate training. The "encounter" category included studies such as the Australian Morbidity and Treatment Survey (AMTS), clinical epidemiology studies, clinical presentation studies and Health Insurance Commission (HIC) data analyses. Very little research was found in workforce, finance or evidence-based medicine. The "other" category included studies evaluating national health promotion campaigns, and studies that could not be classified elsewhere. Methodologies used (Box 6) Two-thirds of the research was observational, nearly a quarter involved some form of intervention, and little qualitative research was published. There was an increase in both interventional and observational studies over the decades. Forty-one per cent of the studies were purely descriptive, many of these being surveys of GPs' views. Only 5% were randomised controlled trials. Many of the evaluation studies were evaluations of educational or training programs for GPs. Research topics (Box 7) ICPC categories: The psychological category was the most frequently studied (13%); over a quarter of these studies were on smoking behaviour. Most of the "female genital" studies were cervical or breast screening studies and 62% of the "respiratory" studies were on asthma. In over half of the studies, no specific ICPC category applied; 22% of these were education and training studies. However, at least half the research topics focused on a clinical area, indicating their pertinence for practising GPs. The main differences between the two decades were increases in cervical, breast and skin cancer studies, and in respiratory studies. National Health Priority (NHP) areas: Nearly two-thirds of the research did not focus on NHP areas. Research into cancer control accounted for 15%, and the proportion doubled over the two decades, followed by mental health (10%). Studies on asthma, cardiovascular disease and diabetes combined accounted for less than 10% of all the research. Other areas of concern: Only 5% of studies dealt with Aboriginal and Torres Strait Islanders, and aged or adolescent populations. Rural research: We found very little research on rural populations. The amount of rural research has remained constant (16%) over these two decades. The bulk is conducted by academic departments (56%), followed by hospitals (14%) and the RACGP (6%). Summary and conclusions This is the first rigorous review of general practice research in Australia. It has demonstrated a marked increase in the amount of research conducted in the past decade. The university departments of general practice have been responsible for most of the research, and GPs were involved in at least 60% of all of the publications reviewed. Half of all the research was found to be clinically pertinent to the front-line GP. The National Health Priority areas were poorly covered in the reviewed articles, but, as these were only formulated in 1994, there has been insufficient time to conduct the research and get it published. There has also been little research in rural general practice; most was conducted by university departments, although not always the general practice departments. The paucity of research on rural populations may be due partly to the fact that many rural studies were not focused specifically on general practice and not listed under "Family practice" in MEDLINE. In addition, the Australian Journal of Rural Health was not indexed in MEDLINE until 1995, which may account for the small number of general practice publications identified in this journal. The limitations of our review are that only one database was searched (MEDLINE) and several journals relevant to general practice research (eg, Education for General Practice) are not indexed in MEDLINE. By checking the curricula vitae of three prominent researchers in Australian general practice, we know that we missed some publications. This is because of inconsistencies in department names in the institution field and omission of the terms "family practice" or "physicians, family" in the medical subject headings (MeSH) field. We encountered difficulties in developing a comprehensive classification system for type of general practice research. We wanted the codes to be useful to both policy makers and providers, but the final categories were still broad. We will continue to refine this coding system in the future. This review did not examine quality of the research, an area which has presented problems for previous researchers.8 However, the proportion of randomised controlled trials was small, mirroring the findings of a review of general practice research in the United Kingdom in the mid-1990s.5 The 11 university departments of general practice in Australia are relatively small, with an average of three full-time equivalent core academic positions each. Most staff have large teaching loads and little time to pursue research activities. The marked increase in research being conducted by these departments over the last decade shows a commitment to research, despite the problems of finding time and adequately trained staff. To further encourage a research culture in general practice in Australia, the General Practice Strategy Review made several recommendations in 1998, including strengthening the research environment in academic departments of general practice, developing and supporting multidisciplinary career pathways in general practice research, and involving consumers and Divisions of General Practice.13 The success of the recently announced national strategy for Primary Health Care Research, Evaluation and Development1 in implementing the recommendations of the General Practice Strategy Review will, in part, be demonstrated by an increase in the quality, quantity and relevance of general practice research in Australia over the next decade. This overview of general practice research takes stock of where we are now and provides a starting point for classifying general practice and primary healthcare research in the future. Acknowledgements We would like to thank Sandra Pullman, of the University of Western Australia medical library, for performing the literature searches. References Lawson KA, Chew M, Van Der Weyden MB. The rise and rise of academic general practice in Australia. Med J Aust 1999; 171: 643-648. General Practice Branch, Department of Health and Aged Care. General practice in Australia: 2000. Canberra: The Department, May 2000: p 377. Starfield B. A framework for primary care research. J Fam Pract 1996; 42: 181-185. Silagy CA, Schattner P, Baxter RG. Current status of general practice research in Australia. Med J Aust 1992; 157: 108-113. Thomas T, Fahey T, Somerset M. The content and methodology of research papers published in three United Kingdom primary care journals. Br J Gen Pract 1998; 48: 1229-1232. Jones R. Primary care research: ends and means. Fam Pract 2000; 17: 1-4. Dawson-Saunders B, Trapp RG. Basic and clinical biostatistics. Connecticut: Appleton & Lange, 1990. Meijman FJ, de Melker RA. The extent of inter- and intrareviewer agreement on the classification and assessment of designs of single-practice research. Fam Pract 1995; 12: 93-97. Lamberts H, Wood M, editors. International classification of primary care. New York: Oxford University Press; 1989. National Health Priorities. In: Wood T, editor. Australia's health 1998. The sixth biennial health report of the Australian Institute of Health and Welfare. Canberra: Australian Institute of Health and Welfare, 1998: 75. Better Health Outcomes for Australians. Canberra: AGPS; 1994. SPSS [computer program], version 8.0. Chicago, Ill: SPSS Inc, 1997. General Practice Strategy Review Group. General practice, changing the future through partnerships. Department of Health and Family Services. Canberra: The Department, 1998. (Received 27 Sep, accepted 9 Nov, 2000) Authors' details Department of General Practice, University of Western Australia, Perth, WA. Alison M Ward, BPsych, PhD, Senior Research Fellow. Derrick G Lopez, BSc, MMedSci, Research Officer. Max Kamien, MD, FRACGP, FRACP, Professor and Head of Department. Reprints: Dr A M Ward, Department of General Practice, University of Western Australia, 328 Stirling Highway, Claremont, WA 6010. alison.wardATuwa.edu.au Make a comment 1: Australian general practice research -- main search strategies, search terms and outcomes MEDLINE (via Ovid Technologies) 1. General practice research by Australian researchers The terms (physicians, family or family practice) in the medical subject headings (MeSH) field combined with the terms (australia$) or (tasmania or queensland or victoria$ or ACT or northern territory or new south wales or NSW) in the institution field; and 2. Research conducted by GPs regardless of the topic The terms (australia$) or (tasmania or queensland or victoria$ or ACT or northern territory or new south wales or NSW) in the institution field combined with the names of all the academic departments of general practice ((family or general) and (physician$ or practi$)) in the institution field. Outcome 881 articles 3. General practice research published in Australia whether or not by GPs The terms (physicians, family or family practice) in the text field combined with (australia$) in the country-of-publication field. Outcome 834 articles 4. Research from departments possibly missed because of name changes The terms (australia$ or tasmania or queensland or victoria$ or ACT or northern territory or new south wales or NSW) in the institution field combined with ((community or primary) and (health or medicine or practice)) in the institution field. Outcome 480 articles 5. Additional searches, including using additional department names in the institution field; and the names of all heads of departments of general practice, and all professors of general practice in the author field. Outcome 47 articles Australasian Medical Index (AMI) (publications not catalogued in MEDLINE) Using the terms (family practice or physicians, family) in the MeSH field, we identified a further 991 possible articles. Many of these were in non-refereed journals, were duplicates of the MEDLINE articles or were only marginally relevant to general practice research. Because their short truncated titles and abstracts made it impossible to classify the type of research being reported they were not included. We estimate this meant possibly another 100-200 references were missed. Total 2242 articles $ = wild card (ie, search finds all words beginning with the letters before the $ sign). Back to text 2: Country of publication -- number (%) of publications Country 1980-1989 (n = 117) 1990-1999 ( n = 546) Australia England United States Europe (excluding England) Canada Unknown 97 (82.9%) 16 (13.7%) 3 (2.6%) 1 (0.9%) 0 0 373 (68.3%) 126 (23.1%) 35 (6.4%) 9 (1.6%) 1(1.6%) 2 (0.4%) Back to text 3: Top five journals publishing Australian general practice research -- number (%) of publications Journal 1980-1989 Journal 1990-1999 Aust Fam Physician Med J Aust Fam Pract Aust N Z J Psychiatry Community Health Stud* 59 (50.4%) 30 (25.6%) 9 (7.7%) 4 (3.4%) 2 (1.7%) Aust Fam Physician Med J Aust Aust N Z J Public Health* Fam Pract Aust J Rural Health † 145 (26.6%) 112 (20.5%) 44 (8.1%) 36 (6.6%) 21 (3.8%) * Community Health Stud became Aust N Z J Public Health in 1996. †Not indexed in MEDLINE until 1995. Back to text 4: Affiliation of first author -- number (%) of publications Afiliation 1980-1989 (n = 117) 1990-1999 (n = 546) University department of general practice Other university departments Other (eg, health department) Hospital RACGP Unknown 35 (29.9%) 17 (14.5%) 19 (16.2%) 12 (10.3%) 6 (5.1%) 28 (23.9%) 205 (37.5%) 131 (24.0%) 89 (16.3%) 65 (11.9%) 38 (7.0%) 18 (3.3%) Back to text 5: Type of research -- number (%) of publications Type of research 1980-1989 (n = 117) 1990-1999 (n = 546) Encounter and clinical epidemiology studies GP behaviour, views, opinions Education and training Patient behaviour, views, opinions, compliance GP and patient behaviour Workforce Organisation of general practice Health services interface Research methodology Finance Ethical/legal/professional Evidence-based medicine Other 28 (23.9%) 27 (23.1%) 15 (12.8%) 15 (12.8%) 10 (8.5%) 7 (6.0%) 5 (4.3%) 4 (3.4%) 2 (1.7%) 1 (0.9%) 0 0 2 (2.6%) 66 (12.1%) 153 (2.80%) 81 (14.8%) 34 (6.2%) 62 (11.4%) 14 (2.6%) 31 (5.7%) 51 (9.3%) 20 (3.7%) 7 (1.3%) 5 (0.9%) 3 (0.5%) 19 (3.5%) Back to text 6: Methodology used -- number (%) of publications Methodology 1980-1989 (n = 117) 1990-1999 (n = 546) Intervention Evaluation of a service Randomised controlled trial Other controlled trial 15 (12.8%) 3 (2.6%) 1 (0.9%) 102 (18.7%) 28 (5.1%) 6 (1.1%) Observation Descriptive without analytical component Cross-sectional quantitative or qualitative Observational over time Cohort 46 (39.3%) 19 (16.2%) 1 (0.9%) 1 (0.9%) 224 (41.0%) 112 (20.5%) 26 (4.8%) 9 (1.6%) Reviews Systematic review Meta-analysis alone 2 (1.7%) 0 11 (0.2%) 1 (0.2%) Other None of the above 29 (24.8%) 27 (4.9%) Back to text 7: International Classification of Primary Care categories -- number (%) of publications* ICPC category 1980-1989 (n = 117) 1990-1999 (n = 546) Psychological Female genital (pap smears, mammogram) Respiratory Pregnancy, child bearing, family planning Skin Circulatory Endocrine, metabolic, nutritional Digestive General and unspecified Male gential (eg, prostate screening) No ICPC category applied 20 (17.1%) 3 (2.6%) 1 (0.9%) 5 (4.3%) 1 (0.9%) 5 (4.3%) 4 (3.4%) 2 (1.7%) 3 (2.6%) 1 (0.9%) 69 (59.0%) 65 (11.9%) 37 (6.8%) 36 (6.6%) 20 (3.7%) 22 (4.0%) 17 (3.1%) 16 (2.9%) 12 (2.2%) 8 (1.5%) 8 (1.5%) 282 (51.6%) * Categories with fewer than 1% of articles (musculoskeletal; neurological; social problems; blood-forming organs; immune mechanisms; eye; urological; ear; hearing) are not listed. 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Alison M Ward · Derrick G Lopez · Max Kamien

The Research Enterprise Exploring the unknown: the challenges of a career in biomedical research Gordon L Ada Gordon Ada reminisces on his career as a researcher and a facilitator MJA 2000; 173: 612-615 Getting started - Walter and Eliza Hall Institute, Melbourne - John Curtain School of Medical Research, Canberra - World Health Organization, Geneva - Retirement projects - The take-home message? - References - Authors' details - - More articles on Immunology and allergy The attractions of a career in research are many, but first among these is the opportunity to be involved in important discoveries, either personally or though close association with other researchers. Experimenting first with viruses and then in immunology at the Walter and Eliza Hall Institute (1948-1968) was a great start. Later, by becoming head of a world-class microbiology department at the John Curtin School of Medical Research at the Australian National University, I was able to establish an environment that spawned important discoveries in medical science. Getting started I had a happy childhood. I was the fourth in a family of six children -- three boys and three girls. My father studied electrical engineering at Sydney University and later became a senior executive with the New South Wales Railways, but my mother had to leave school early when her mother died. When I entered Sydney University in 1940, my aim was to study biochemistry, having received a fascinating book the previous Christmas -- The science of life, by H G Wells, Julian S Huxley and G P Wells. My years at university might not have been so enjoyable if Jack Still had not returned to Sydney University in 1941 from Gowland Hopkins' Biochemistry Department at Cambridge. He enthused us with stories about the exciting research being done there. My first research position at the Commonwealth Serum Laboratories (CSL) (1944-1946), studying ways of stabilising human serum and avoiding denaturation, convinced me of the need for new techniques to isolate and study individual proteins. I applied for leave from CSL to work at the National Institute of Medical Research in London, where moving-boundary electrophoresis and ultracentrifugation were being used for this purpose. This request, although supported by the Director of CSL, Frederick G Morgan, was refused at a higher level, so I resigned, travelled to England, and worked unpaid at the Institute with Arthur S McFarlane, Head of the Biophysics Department. After a few months, McFarlane recommended my paid appointment to the research staff. Walter and Eliza Hall Institute, Melbourne In the early 1940s, Macfarlane Burnet, Director of the Walter and Eliza Hall Institute (WEHI), on a visit to Harvard University to give the Dunham Lectures, saw the need for his institute to gain these new techniques for studying proteins. He obtained a government grant of £20 000 to establish the technologies (including, later, electron microscopy) at the WEHI. As there was no expertise in Australia, Burnet invited me to join the staff at the WEHI and, with the senior biochemist, Henry Holden, to set up moving-boundary electrophoresis and ultracentrifugation. I arrived back in Australia in August 1948. Fortunately, Holden did much of the establishing and I was able to spend most of my time on research. I became a virologist, working mainly with influenza and later Murray Valley encephalitis viruses, studying their composition and biological properties. I crystallised the Vibrio cholerae neuraminidase. In 1957, after publication of his clonal selection theory,1 Burnet decided to phase out virology in favour of immunology at the Institute. In 1962, I decided to make the switch and, after much reading, began studying immune responses, in particular the fate of tiny amounts of antigen (using the highly immunogenic Salmonella flagella and flagellin labelled with radioactive iodine) to establish the nature and location of cells which bind antigen. Because of my general ignorance of this field, I asked Gus Nossal, then the Deputy Director (Immunology) at the Institute, to help me get started. He kindly agreed, but, when the first autoradiographs showing localisation of antigen over rat primary lymphoid follicles (Box 1) were so striking, Gus decided to collaborate full-time. When presented at a meeting in the United States, our findings ranked a column in the New York Times. The next six years studying the fate and role of antigen during primary and secondary immune responses were like a taste of researcher's heaven, and Gus was a great colleague. We studied the role of antibody in antigen localisation and demonstrated the absence of antigen in antibody-forming cells. Burnet later wrote: What I can be certain about however, is the immense importance of the work on the cellular localisation of antigen led by Ada and Nossal in the 1962-5 period.2 All these findings, together with studies on the influence of antigen structure on immunogenicity with a new PhD student, Chris Parish, were published individually and then finally woven into a monograph.3 John Curtain School of Medical Research, Canberra Despite the attractions of working at WEHI, an invitation to head a department with an international reputation in virology was too exciting to refuse, and in 1968 I succeeded Frank Fenner as Head of the Department of Microbiology at the John Curtin School of Medical Research. Although much was known about the humoral response to viral infections, knowledge about cell-mediated immune responses was almost non-existent. I reasoned that research projects combining both virological and immunological approaches, supported by basic research in both these fields, would surely lead to some exciting findings. This turned out to be the case. For example: In 1972 Chris Parish was the first to show the inverse relationship between antibody and cell-mediated immune responses, which led others to describe two classes of helper T cells. Bruce Stillman's studies on adenovirus in 1978 started him on the road to becoming Director of the renowned Cold Spring Harbor Laboratories in New York State. Robert Blanden was to lay the foundations for a major finding. Our department was acknowledged as a world leader in poxvirus research,4 and Blanden was studying the immune response to ectromelia, a poxvirus pathogenic for mice. In the next few years, using technology for assaying the newly discovered cytotoxic T cells gleaned from overseas meetings, Blanden, in late 1972, became the first to show that cytotoxic T cells would kill cells infected with ectromelia virus. But how did these cells recognise virus-infected cells? Early indications were that major histocompatibility (MHC) antigens were involved in some way, so some inbred mouse strains (members of the same strain having identical MHC antigen specificities) were imported to facilitate further studies. Peter Doherty came to the department as a postdoctoral fellow in 1972, and started work on lymphocytic choriomeningitis (LCM) virus infections of mice. In early 1973, Rolf Zinkernagel, a Swiss medical graduate, worked for a while with Blanden to learn about assaying cytotoxic T cell activity. I then asked Doherty and Zinkernagel to share the same laboratory, as they clearly had similar research interests. In some very elegant experiments, they found that cytotoxic T cells formed during an LCM viral infection would only lyse infected target cells if effector and target cells shared at least some MHC antigen specificities (ie, the T cell lytic activity was "MHC restricted"). They suggested that the cytotoxic T cell receptor recognised at the infected cell surface some virus-induced alteration of the MHC molecule, possibly caused by complexing with a viral antigen.5 They proposed the fundamental concept -- that a central function of MHC antigens on cells was to signal changes in "self", to what they now called "altered self", to the immune system.6 Once identified, such a cell would be lysed. This finding stimulated much research both in the department and elsewhere, and studies investigating the details of MHC restriction of T cell responses became a leading immunological topic internationally. Needless to say, Zinkernagel was awarded a PhD scholarship and graduated in record time. Both he and Doherty left to work overseas in the mid-1970s. Subsequently, analysis of crystals of MHC molecules, isolated from the surface of infected cells by US researchers, showed a viral peptide occupying a cleft in the MHC molecule so that parts of each were recognised by the cytotoxic lymphocyte receptor (Box 2). The award of the 1996 Nobel Prize in Physiology or Medicine to Rolf Zinkernagel and Peter Doherty (Box 3) recognised the importance of their original discovery, as it was the first description of the molecular mechanism used by vertebrates for the control and clearance of most intracellular infectious agents, especially viruses. World Health Organization, Geneva For 20 years, from 1971, I became associated with different World Health Organization programs, concerned mostly with the development and use of vaccines (Box 4). I was the first Chairman of the Programme for Vaccine Development (1984-1989), which is now a much larger WHO program with Gus Nossal as Chairman. These experiences focused my own research towards defining the roles of different components of the immune response to viral infections. Retirement projects As I approached retirement (December 1987), I was invited to do a six-month consultancy at WHO (to plan for a major review of studies on developing a vaccine to control pregnancy in women), to spend my retirement at Johns Hopkins School of Hygiene and Public Health in Baltimore, and to give the plenary lecture on The prospects for HIV vaccines at the Fourth International AIDS Congress in Stockholm in May 1988. I had never worked with HIV, but the Swedes apparently wanted an "independent" opinion. Stockholm By 1986, HIV RNA had been largely sequenced, and there was great optimism that a vaccine could be developed quickly. However, in the next two years, several disturbing findings were made, especially the very great sequence variation of the envelope antigen in different HIV isolates. There are three desirable properties of an infectious agent which can facilitate vaccine development (Box 5). At the Stockholm lecture,7 I listed seven reasons why it would be very difficult to develop an HIV vaccine based primarily on strong infectivity-neutralising antibody formation (Box 5). I then drew on recent research by two of my colleagues, David Boyle and Ian Ramshaw, at the John Curtin School of Medical Research. They had shown that DNA, coding for antigens of other infectious agents and of cytokines, could be inserted into the DNA of a poxvirus, such as vaccinia virus. Vaccination with this "chimeric" virus could protect against infection by the agent which was the source of the inserted DNA. I therefore suggested that, because the internal antigens of HIV (which are the source of many T cell epitopes) showed considerably less variation, a vaccine might be developed based on vaccinia virus containing the genes coding for the internal HIV antigens, gag and pol, as well as for the cytokine, interferon gamma.7 In mice, such a construct generated a strong cytotoxic T cell response; in man, this might be sufficient to better control, if not clear, an HIV infection. The 8000-strong audience was largely stunned by my assessment of the situation, although none subsequently disputed it. However, major vaccine manufacturers ignored it, determined to make an antibody-inducing subunit vaccine based on the HIV envelope antigen, a strategy driven by the success of the hepatitis B viral vaccine which contains the surface antigen of that virus. Baltimore and Washington On arrival in Baltimore in July 1988, I was warmly welcomed, made Associate Director of a new Center for AIDS Research and later became Director. In Washington, I was asked to participate in meetings and activities of the Division of AIDS (DAIDS) of the National Institute of Allergy and Infectious Disease. In 1991, after three years in the United States, my wife and I decided to return to Australia, but I was invited to continue the relationship with DAIDS and to join a new HIV Vaccine Working Group. The crunch came in 1995, when the Director of the US National Institute of Allergy and Infectious Disease refused to support a Phase III clinical trial of the then leading HIV candidate vaccine, based on the envelope antigen. Many reasons were given, but two critical ones were: Antibody from volunteers immunised with this candidate vaccine did not prevent infection by newly isolated HIV field strains; and The vaccine did not induce cytotoxic T cell formation in the volunteers. This was a major turning point in international HIV vaccine research. The National Institute of Allergy and Infectious Disease completely revamped its HIV vaccine development program, and my hectic travel schedule to and from the United States came to an end. My last task for the Working Group was to review the evidence supporting a role for cytotoxic T cells in controlling HIV infections.8 Return to Canberra In 1991, I was appointed Visiting Fellow in the (now) Division of Immunology and Cell Biology at the John Curtin School and Chairman of the HIV Vaccine Working Group, one of the committees of the National Centre in HIV Epidemiology and Clinical Research in Sydney. Ian Ramshaw had recently shown that a vaccination schedule involving priming with plasmids containing DNA coding for selected antigens, followed by boosting with chimeric fowlpox virus coding for the same antigens, gave a greatly enhanced immune response in mice. Stephen Kent (now at the University of Melbourne) and Ramshaw and their colleagues showed that Macaca nemestrina monkeys immunised in this way developed a strong cytotoxic T cell response and rapidly cleared a subsequent HIV infection.9 Any antibody induced was irrelevant. Supporting findings for this approach were later reported from the United States. Now Australia was set to develop an HIV vaccine initiative based on this vaccination technology. At a meeting of the HIV Vaccine Working Group, David Cooper, Head of the National Centre in HIV Epidemiology and Clinical Research, was elected to head an Australian HIV Vaccine Consortium. In June this year, out of 20 international applications received, the National Institute of Allergy and Infectious Disease awarded four contracts, three to US groups and the fourth to the Australian consortium ($27 million over five years) to carry out clinical trials of their vaccine formulation. It is anticipated that a strong immune capability based on cytotoxic T lymphocyte activity will greatly reduce viral titres. Thus, those infected by HIV will live longer and be much less likely to infect others. If this vaccination technology can be shown to generate strong cytotoxic lymphocyte responses in humans, it heralds a new approach to controlling other difficult infectious diseases, such as malaria, trachoma and pelvic inflammatory disease, and even pandemic influenza. The take-home message? From a career path in biochemistry, I switched to virology, then to immunology and became an enthusiastic supporter for the application of immunisation technology, not only for the more difficult infectious diseases but also for non-communicable diseases. Young researchers should jump at the chance to switch fields when exciting opportunities arise. Acknowledgement: I wish to acknowledge with gratitude the great support of my wife, Jean Ada, during my career. References Burnet FH. A modification of Jerne's theory of antibody production using the concept of clonal selection. Aust J Sci 1957: 20; 67-69. Macfarlane Burnet I. Walter and Eliza Hall Institute, 1915-65. Melbourne: Melbourne University Press, 1971. Nossal GJV, Ada GL. Antigens, lymphoid cells and the immune response. New York: Academic Press, 1971. Fenner F. Nature, nuture and my experience with smallpox eradication. Med J Aust 1999; 171: 638-641. Zinkernagel RM, Doherty PC. Restriction of in vitro cell-mediated cytotoxicity in lymphocytic choriomeningitis within a syngeneic or semi-allogeneic system. Nature 1974; 248: 701-702. Doherty PC, Zinkernagel RM. A biological role for the major histocompatibility antigens. Lancet 1975; 1: 1406-1409. Ada GL. Prospects for HIV vaccines. J Acquir Immune Defic Syndr 1988; 1: 295-303. Ada GL, McElrath MJ. Perspectives. HIV type-1 vaccine-induced cytotoxic T cell responses: potential role in vaccine efficacy. AIDS Res Hum Retoviruses 1997; 13: 243-248. Kent SJ, Zhao A, Best SJ, et al. Enhanced T-cell immunogenicity and protective efficacy of a human immunodeficiency virus type 1 vaccine regimen consisting of consecutive priming with DNA and boosting with recombinant fowlpox virus. J Virol 1998; 72: 10180-10188. Authors' details John Curtin School of Medical Research, Australian National University, Canberra, ACT. Gordon L Ada, AO, DSc, FAA, Emeritus Professor, and Visiting Fellow in the Division of Immunology and Cell Biology. Correspondence: Professor G L Ada, John Curtin School of Medical Research, P O Box 334, Canberra, ACT 2601. Make a comment 1: Antigen in the immune response Autoradiograph showing localisation of antigen over primary lymphoid follicles of rat popliteal lymph nodes, after footpad injection of Salmonella flagellin labelled with radioactive iodine. Back to text 2: The function of major histocompatibility antigens Schematic diagram of the cytotoxic T lymphocyte receptor recognition of the complex between the major histocompatibility antigen molecule and a nonapeptide derived from an infectious agent protein expressed on the surface of the infected cell. Back to text 3: At the 1996 Nobel Prize awards Evening banquet after the awarding of Nobel Prizes, Stockholm, December 1996. From left to right: Gordon Ada, Peter Doherty and Frank Fenner at the display of Nobel Prize medals and citations (photograph courtesy of Peter Pockley). Back to text 4: Involvement with World Health Organization programs 1971-1973 Member, Fellowship Selection Committee 1973-1976 Member, then Chairman (1975-1976), Scientific Council, International Agency for Research on Cancer, Lyons, France 1978-1984 Member, Scientific and Technical Advisory Committee, Tropical Diseases Research 1981-1984 Member, Global Advisory Committee on Medical (Health) Research 1984-1989 Chairman, Scientific Advisory Group of Experts, Programme for Vaccine Development. Member and later Consultant (1988), Vaccination Committee, Human Reproduction Programme 1985-1988 Member, Regional (Western Pacific) Advisory Committee on Health Research 1987-1989 Member, Research and Development Group, Expanded Programme on Immunization Back to text 5: Factors for and against the development of an effective vaccine Factors favouring the development of an effective vaccine Only one or a few strains of the infective agent exist; little or preferably no antigenic variation within a strain. Infective agent causes an acute infection; host completely recovers from a sublethal dose of the agent; agent does not persist. Agent is moderately (rather than highly) infectious. Factors militating against development of an effective vaccine (all these factors apply to HIV) Great antigenic variation; antigenic drift. Integration of viral DNA/cDNA into the host cell genome. Infection may be transmitted by cells which are latently infected. Immune enhancement: antibody can enhance infection of macrophages/monocytes if these cells are susceptible to infection. Agent infects cells in immunoprivileged sites in the host. Crucial cells of the immune system are infected, and either destroyed or their function is impaired. Failure to produce protective antibody and/or persisting cell-mediated immunity responses. Back to text

Gordon L Ada

The Research Enterprise John Kerr and apoptosis Michael G E O'Rourke and Kay A O Ellem MJA 2000; 173: 616-617 On 14 March 2000, John Foxton Ross Kerr, Emeritus Professor of Pathology at the University of Queensland, received the Paul Ehrlich and Ludwig Darmstaedter Prize for his description of apoptosis, a form of cell death. The prize, which he shared with Boston biologist Robert Horvitz, is considered to be one of the most prestigious European awards in science, second only to the Nobel Prize. John Kerr's discovery, initially called "shrinkage necrosis" but which he later renamed "apoptosis", came about in the late 1960s, when his attention was caught by a curious form of liver cell death during his studies of acute liver injury in rats. The findings of this seminal study were first published in 1965.1 Subsequently, Kerr and his co-authors (including Jeffrey Searle) described the unique morphological changes of this type of cell death, compared with those of necrosis, in a series of articles published during the 1970s and 1980s.2-4 These studies extended the range of pathological and physiological states in which apoptosis is known to occur. Further studies with other collaborators (who later included Alastair Currie and Andrew Wyllie)5 led to an increase in the understanding of the role of apoptosis in embryogenesis, spermatogenesis, cancer growth, and tissue remodelling during healing or functional regression. At first thought to be somewhat arcane as a topic, the literature on apoptosis initially grew slowly. However, recognition of the significance of this "protected" form of cell death on immune function and regulation was followed by an explosion of related publications in immunology. Biochemists now recite a mantra of enzymes involved in apoptosis, and chant a list of factors capable of modulating or regulating its expression. It has become de rigueur to adorn seminars and lectures with charts of the increasingly complex interactions which occur between signalling pathways as they are traversed by the informing reactions (which either trigger or defuse the suicidal steps leading to apoptotic cell death). The astonishing total number of publications on apoptosis is now over 35 539, including some of the world's leading scientific journals, such as Nature6-8 and Science.9-11 Apoptosis is now a growth industry, the clinical implications of which can be applied to chemotherapy, the endocrine treatment of cancer, autoimmune disease and neurodegenerative disease. This body of evidence is a tribute to the catalytic influence that John Kerr's insights have had in so many disparate disciplines and areas of biological study. These insights revealed the importance of this process as a universal microphenomenon in the macroevents of tissue and organismal function, and in disease. References Kerr JF. A histochemical study of hypertrophy and ischaemic injury of rat liver with special reference to changes in lysosomes. J Path Bact 1965; 90: 419-435. Kerr JF, Cooksley WG, Searle J, et al. The nature of piecemeal necrosis in chronic active hepatitis. Lancet 1979; 20: 827-828. Searle J, Lawson TA, Abbott PJ, et al. An electron-microscope study of the mode of cell death induced by cancer-chemotherapeutic agents in populations of proliferating normal and neoplastic cells. J Pathol 1975; 116: 129-138. Weedon D, Searle J, Kerr JF. Apoptosis. Its nature and implications for dermatopathology. Am J Dermatopathol 1979; 2: 133-144. Kerr JF, Wyllie AH, Currie AR. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 1972; 26: 239-257. Wallach D. Apoptosis: Placing death under control. Nature 1977; 388: 123-126. Hengartner MO. Apoptosis: death cycle and Swiss army knives. Nature 1998; 391: 441-442. Martinou JC. Apoptosis: key to the mitochondrial gate. Nature 1999: 399; 411-412. Barinaga M. Apoptosis: forging a path to cell death. Science 1996; 273: 735-737. Barinaga M. Apoptosis: death by dozens of cuts. Science 1998; 280: 32-34. Brenner C, Kroener G. Apoptosis: Mitochondria -- the death cell integrators. Science 2000; 289: 1150-1151. Cotran R, Kumar V, Collins T, editors. Pathological basis of disease. 6th ed. Philadelphia: W. B Saunders, 1997: 18-24. Kerr JF, Winterford CM, Harmon BV. Apoptosis. Its significance in cancer and cancer therapy. Cancer 1994; 73: 2013-2026. Walker NI, Harmon BV, Gobe GC, et al. Patterns of cell death. Methods Achiev Exp Pathol 1988; 13: 18-32. Sandford N, Searle JW, Kerr JF. Sucessive waves of apoptosis in the rat prostate after repeated withdrawal of testosterone stimulation. Pathology 1984; 16: 406-410. Soubrane C, Mouawad R, Antoine EC, et al. A comparative study of Fas and Fas-ligand expression during melanoma progression. Br J Dermatol 2000; 143: 307-312. Andrane F, Casciola-Rosen L, Rosen A. Apoptosis in systemic lupus erthymatosus. Clinical implications. Rheum Dis Clin North Am 2000; 26: 215-227. Make a comment John Kerr (right) with Roland Koch, Prime Minister of Hesse, Germany, and Honorary Chairman of the Board of Trustees of the Paul Ehrlich Foundation, at a dinner for award recipients. 1: Other awards and lectures recognising John Kerr's achievements Keynote opening addresses at the Cold Spring Harbor, New York, Symposia, 1990. Opening lecture, The cell and molecular biology of apoptosis, at the Queensland Institute of Medical Research Cell and Molecular Biology Symposium, 1992. Opening lecture at the conference Apoptosis in AIDS, Paris, 1993. 12th Mildford D. Schultz Lecture, Harvard Medical School, Boston, 1993. Bancroft Medal (Queensland AMA), 1993. John Earnshaw Memorial Lecture, International Melanoma Conference, Brisbane, 1994. Fred W Stewart Award, Memorial Sloane-Kettering Cancer Center, New York, for contribution to cancer research, 1995. Doctor of Science honoris causa, University of Queensland, 1998. Fellowship of the Australian Academy of Science, 1998. Back to text 2: Apoptosis: programmed cell death The term "apoptosis" is derived from the Greek for "falling off" and describes a distinct form of cell death whereby cells die in a tightly regulated and morphologically uniform fashion.12 Morphologically, there is condensation of the nucleus and cytoplasm, membrane blebbing, and the formation of discrete, packaged apoptotic bodies which are phagocytosed by nearby cells, without provoking an inflammatory reaction.13 In contrast to necrosis, a degenerative process in which cells swell and lyse after irreversible tissue injury, apoptosis appears to be an active process14 which is subject to genetic regulation. Apoptosis can be triggered either from within the cell, or from outside the cell (mediated by binding of surface membrane receptors to "death activators" such as Fas-ligand and tumour necrosis factor). Electron micrograph showing apoptosis occurring spontaneously in cell culture. Note the discrete, membrane-enclosed nuclear fragments, with characteristic segregation of uniformly compacted chromatin, the crowding of well preserved cytoplasmic organelles and the marked convolution of the cellular surface, which is a prelude to conversion of the cell into a number of membrane-bound fragments or apoptotic bodies. N = nucleus, O = organelles. Apoptosis may occur in several different physiological, adaptive and pathological settings. For example, apoptosis acts as a homoeostatic mechanism for controlling cell populations, and in hormone-dependent tissue involution such as endometrial breakdown during menstruation, prostatic atrophy after castration,15 and cessation of lactation after weaning.12 Localised apoptosis plays a role in embryonic development, such as formation of interdigital clefts and involution of phylogenetic vestiges.5 In malignant tumours, apoptosis may occur spontaneously, or may increase in response to cytotoxic chemotherapy or irradiation.13 Impaired regulation of apoptosis is known to be associated with the development of various types of cancer,16 and with the pathogenesis of some autoimmune diseases such as systemic lupus erythematosus.17 Back to text

Research Recent trends in the use of antidepressant drugs in Australia, 1990-1998 Peter McManus, Andrea Mant, Philip B Mitchell William S Montgomery, John Marley and Merran E Auland MJA 2000; 173: 458-461 For editorial comment, see Parker Abstract - Introduction - Methods - Results - Discussion - Acknowlegdements - References - Authors' details - - - More articles on General practice and primary care Abstract Objective: To determine the pattern of use of antidepressant drugs in the Australian community, 1990-1998, and to compare this with those of other developed countries. Design: Retrospective analyses of prescription and sales data, together with information about patient encounters for depression (from an ongoing survey of service provision by general practitioners) and population-based prevalence estimates for affective disorders (from community health surveys). Main outcome measures: National and international consumption of antidepressants, expressed in defined daily doses (DDDs) per 1000 population per day. Changes in both the frequency of general practice patient encounters for depression and population-based prevalence estimates for affective disorders. Results: Dispensing of antidepressant prescriptions through community pharmacies in Australia increased from an estimated 12.4 DDDs/1000 population per day in 1990 (5.1 million prescriptions) to 35.7 DDDs/1000 population/day in 1998 (8.2 million prescriptions). There has been a rapid market uptake of the selective serotonin reuptake inhibitors (SSRIs), accompanied by a decrease of only 25% in the use of tricyclic antidepressants (TCAs). In 1998, the level of antidepressant use in Australia was similar to that of the United States, while the rate of increase in use between 1993 and 1998 was second only to that of Sweden. In Australia, depression has risen from the tenth most common problem managed in general practice in 1990-91 to the fourth in 1998-99, and the number of people reporting depression in the National Health Surveys (1995 v 1989-90) has almost doubled. Of the prescriptions dispensed in 1998 for antidepressant drugs subsidised by the Pharmaceutical Benefits Scheme, 85% were written by general practitioners, and 11.2% by psychiatrists. Conclusions: As in most developed countries, antidepressant use increased between 1990 and 1998. The rapid market uptake of the new antidepressants, particularly SSRIs, is likely to have been driven by increased awareness of depression, together with availability and promotion of new therapies. Introduction The World Health Organization report on the global burden of disease placed major depression fourth among the leading causes of disease burden in the developing world in 1990, and predicted that it would rise to second by the year 2020.1 In parallel with the increasing awareness of depression as an important health issue, the past decade has seen an increase in the pharmacotherapy options for managing depression with the arrival of several new classes of antidepressants. To review trends in antidepressant use in Australia, the Drug Utilisation Sub-Committee (DUSC) of the Pharmaceutical Benefits Advisory Committee, Department of Health and Aged Care, convened a working group in 1998. The working group, which comprised representatives from the DUSC and from the Australian Pharmaceutical Manufacturers Association (APMA), reviewed Australian and international data on antidepressant sales and dispensing. The aim was to determine patterns of antidepressant use in Australia between 1990 and 1998 and to compare Australian patterns with those in similar developed countries. To assist in interpretation of Australian drug use trends, the group reviewed changes in both the frequency of general practice patient encounters for depression and in population-based prevalence estimates for affective disorders. Methods Prescription and sales data Prescription dispensing data were obtained from the database maintained by the DUSC that monitors the dispensing of prescription medicines through community pharmacies in Australia.2 No data on public hospital use are included in this database. The measurement units used are either prescription volumes or the number of defined daily doses (DDDs) per 1000 population per day. The DDD is based on the assumed average daily dose of the drug when used for its main indication by adults. It is the unit approved by the World Health Organization (WHO) for drug use studies, and allows for comparisons independent of differences in price, preparation and quantity per prescription.3 Within the data on dispensing of antidepressant drugs subsidised by the Pharmaceutical Benefits Scheme (PBS), it is also possible to determine the major specialty of the prescribing doctor. Data on total sales of antidepressants from wholesalers to retail and hospital pharmacies for all countries, except Sweden, were obtained from IMS Health Incorporated. IMS Health is the leading international provider of information on drug usage to the pharmaceutical and healthcare industries.4 Data were retrieved as kilograms of active ingredient and then converted to DDDs per 1000 population per day. Excluded were the use of lithium, Hypericum (St John's wort) or tryptophan, and combinations involving these drugs or their active constituents. Utilisation data for Sweden, where separate local arrangements apply, were supplied by the Swedish Association of the Pharmaceutical Industry (LIF). The 1999 WHO defined daily doses (DDDs) were used in calculations. Drugs unique to particular markets that did not have DDDs available were provisionally assigned values using standard references and information provided by drug information centres in the countries involved.5 Prescriber surveys Information related to general practice patient encounters for depression was obtained from the General Practice Statistics and Classification Unit of the Family Medicine Research Centre (FMRC), University of Sydney, which is conducting an ongoing survey of service provision by general practitioners (GPs).6 This involves 1000 randomly selected, active, recognised GPs per year, each recording details of 100 consecutive consultations on structured encounter forms. Rolling recruitment ensures that the recording weeks are distributed evenly over the year and that there is constant change in participants. These data can be compared with the findings of an earlier FMRC study of morbidity and treatment in general practice that used simpler but compatible methods.7 Information on prescribing by specialists is not included in these GP surveys. Community health surveys The 1995 National Health Survey was a household survey conducted by the Australian Bureau of Statistics to obtain national benchmark information on a range of health-related issues and to enable the monitoring of trends in health over time.8 A previous health survey, collecting broadly comparable data, was conducted in 1989-90.9The 1997 National Survey of Mental Health and Wellbeing of Adults was also conducted by the Australian Bureau of Statistics and used a representative sample of people aged 18 years or over living in private dwellings.10 The survey was interview-based with a diagnostic component administered through a modified version of the WHO Composite International Diagnostic Interview (CIDI). The CIDI translates the criteria of the Diagnostic and statistical manual of mental disorders, 4th edition (DSM-IV),11 and the International classification of diseases, 10th edition (ICD-10),12 into sets of questions that can be readily answered by the general adult population. Specific combinations of symptoms may indicate a specific mental disorder. Results Antidepressant use in Australia The dispensing of prescriptions for antidepressants through community pharmacies in Australia increased from an estimated 12.4 DDDs/1000 population per day in 1990 (5.1 million prescriptions) to 35.7 DDDs/1000 population per day in 1998 (8.2 million prescriptions). Trends in the use of the selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), moclobemide, venlafaxine and nefazodone between 1990 and 1998 are shown in Box 1. The market uptake of the SSRIs has been rapid and accompanied by a decrease of only 25% in the use of the TCAs. Other new agents included moclobemide (a reversible monoamine oxidase type A inhibitor), nefazodone (a 5-HT2 antagonist) and venlafaxine (a serotonin-noradrenaline reuptake inhibitor). The 10 most commonly dispensed antidepressants in Australia in 1998 were, in descending order, sertraline, dothiepin, paroxetine, amitriptyline, fluoxetine, doxepin, moclobemide, imipramine, venlafaxine and citalopram. Of these, only the four tricyclic antidepressants were on the market in 1990, with dothiepin alone maintaining or improving its position over this period. Of the PBS-subsidised prescriptions dispensed for antidepressants in 1998, 85% were written by GPs, while 11.2% were written by psychiatrists. International comparisons We compared retail and hospital sales of antidepressants in Australia and seven major developed countries for the years 1993 and 1998 (Box 2). In 1998, sales of antidepressants in Australia (34.2 DDDs/1000 population per day) were similar to those of the United States (34.2 DDDs/1000 population per day), less than in Sweden (37.1 DDDs/1000 population per day) and France (36 DDDs/1000 population per day) and higher than in Canada (30.8 DDDs/1000 population per day) and the United Kingdom (30.4 DDDs/1000 population per day). Germany and Italy had considerably lower usage levels (12 and 9.9 DDDs/1000 population per day, respectively). The rate of increase in Australia between 1993 and 1998 was second only to that of Sweden. For these same countries in 1998, Box 3 shows the percentage split (based on DDDs/1000 population per day) of the antidepressant market by drug class. There was considerable variability in the percentage that TCAs represented of overall antidepressant use, from a low level of 11% in Sweden through to a high of 67% in Germany. Australia, Canada and France had a similar profile, with TCAs representing about 20% of antidepressant use. Venlafaxine was marketed in all eight of the countries surveyed and ranged between 1.5% and 5.2% of the total use. Mianserin had a low level of use in most countries, except for France and Italy, where it represented about 4% of antidepressant use. It was not available in North America. Similarly, moclobemide had a low level of use in most countries, except in Australia, where it represented 12% of the antidepressant market. Prescriber surveys Surveys conducted in 1990-91 and 1998-99 by the Family Medicine Research Centre have shown the increasing prominence of depression as a problem managed in general practice.6,7 In 1998-99, depression ranked as the fourth most common general practice problem, compared with the tenth in 1990-91. The rate of patient encounters involving depression per 100 encounters has increased from 2.1 in 1990-91 to 3.5 in 1998-99. In 1998-99, compared with 1990-91, antidepressants were more likely to be prescribed per every 100 encounters for depression (58.4 prescriptions [95% CI, 56.1-60.8] v 52.3 prescriptions [95% CI, 49.2-55.5]). Comparisons with age and sex demographics for total general practice encounters (women, 58.7%) suggest that female patients were over-represented at encounters for depression. The most frequent patient age group in encounters at which a tricyclic antidepressant was prescribed was 45-64 years (38%), whereas for encounters at which SSRIs were prescribed it was 25-44 years (43%). Sex distribution was similar for both drug groups, with about a third of the patients being men. Depression was the most common problem for which TCAs and SSRIs were prescribed in 1998-99, although the proportion of TCAs prescribed for depression (48.8% [95% CI, 44.3%-53.3%]) was lower than that of SSRIs (81.9% [95% CI, 79.7%- 84.1%]). Other specific problems managed with TCAs were sleep disturbance (7%), anxiety (5%) and back complaints (4.5%). For the SSRIs, these were anxiety (5.8%) and phobia/compulsive disorder (1.7%). When used for depressive disorders, TCAs had a prescribed daily dose consistently lower than the WHO DDD. The prescribed daily doses and DDDs for the most commonly dispensed TCAs were amitriptyline (mean, 59 mg; median, 50 mg; DDD, 75 mg), doxepin (mean, 61 mg; median, 50 mg; DDD, 100 mg) and dothiepin (mean, 85 mg; median, 75 mg; DDD, 150 mg). The prescribed daily doses for the most commonly dispensed SSRIs were much closer to the DDD: fluoxetine (mean, 24 mg; median, 20 mg; DDD, 20 mg), paroxetine (mean, 23 mg; median, 20 mg; DDD, 20 mg) and sertraline (mean, 72 mg; median, 50 mg; DDD, 50 mg). Community health surveys The 1997 National Mental Health and Wellbeing Profile of Adults identified a 5.8% prevalence of affective disorders (depression, 5.1%; dysthymia, 1.1%) during the 12 months before the survey among people aged 18 years or over.10 Women were more likely than men to have experienced affective disorders (7.4% compared with 4.2%). Although based on self-reports, household surveys conducted by the Australian Bureau of Statistics in 1989-90 and 1995 identified marked changes in the number of people reporting current or previous depression. In the 1995 National Health Survey, 8.1 persons per 1000 population reported depression as a long term condition, compared with 2.8 persons per 1000 in the 1989-90 survey. For depression as a recent illness, 11.4 per 1000 population reported this in 1995, compared with 5.8 per 1000 in 1989-90.8,9 Discussion The past decade has seen a remarkable change in the number of people recognised with and managed for depression, in the range of drug therapy options available, and in the volume of antidepressants prescribed. Previously, depression had been reported as under-recognised and undertreated.13-15Prominent among the likely reasons for this change are increased community awareness of depression as an important health issue, and attempts, most notably through government and community campaigns, to reduce the stigma of mental illness and the gaps in professional expertise inhibiting adequate recognition and treatment of depression.16,17 Coincident with these campaigns, important treatment recommendations were released in the United Kingdom in 1992 (the Royal College of General Practitioners and the Royal College of Psychiatrists) and, in the United States, in 1993 (Agency for Health Care Policy and Research).13,18 In Australia, the Psychotropic drug guidelines19 are the endorsed national standard, and the National Health and Medical Research Council has published clinical practice guidelines for managing depression in young people.20,21 The 1995 Australian National Health Survey showed that the number of people reporting depression as a recent and/or long term condition had nearly doubled compared with the earlier survey conducted in 1989-90. Such a change in the true underlying prevalence of disease is unlikely over a relatively short period of time, and the increase is far more likely to reflect a greater awareness of depression, with patients being more comfortable about coming forward for help and doctors, particularly in general practice, being more willing to provide it. This increased awareness of depression by doctors and patients, together with the availability and promotion of new drug therapy options (between 1990 and 1998, five SSRIs have been approved for PBS subsidy together with moclobemide, venlafaxine and nefazodone), accounts for the rise from the tenth to the fourth most common problem managed in general practice between 1990-91 and 1998-99. In 1998-99, encounters for depression were also more likely to generate a prescription for an antidepressant. This change is reflected in drug utilisation statistics. The market uptake of the SSRIs has been rapid and, remarkably, accompanied by only a relatively small decrease in the use of the TCAs. As a result, the overall antidepressant market has expanded greatly, with utilisation (as defined by DDDs/1000 population per day) being nearly three times greater in 1998 than in 1990. Prescription rates, however, have risen only 60% over that time, as the newer antidepressants are more likely to be dosed closer to the DDD than the older tricyclic antidepressants. TCAs are prescribed for sleep disturbance in a small proportion (7%) of patients, which is not the case for SSRIs. Most developed countries have seen similar trends, with sales in Australia consistent with US sales and slightly higher than those in the UK. The percentage that the SSRIs represented of total antidepressant use in Australia in 1998 was similar to that in the United Kingdom. The considerably lower levels of antidepressant use in Germany are probably related to Germany's strong tradition of use of complementary medicines (substantial use of Hypericum preparations [St John's wort] were not included in the comparisons); and the lower levels in Italy may be because, in 1994-98, SSRIs were not reimbursed by the national health system in Italy, but were fully paid for by the patient (Dr Alberto Vaccheri, Associate Professor, Department of Pharmacology, University of Bologna, personal communication, June 1999). Although there are interesting differences between countries, the rapid uptake of the new antidepressants is likely to have been driven by increased awareness, together with the availability and promotion of new therapies. The drug utilisation patterns, supported by evidence from population and general practice surveys, showed that there has been growth in the actual market rather than just redistribution within the market. Public health benefits of this major change in drug use (eg, reductions in suicide rates) are anticipated in the long term, but measuring population-level outcomes from changes will not be easy. Acknowledgements Other members of the Antidepressants Working Group who helped prepare these data were the Australian Pharmaceutical Manufacturers Association and the pharmaceutical industry (Susan Alexander, Mark Bradley, Michelle Burke, Liz Campbell, Victoria Croker, Marnie Firipis, Deborah Monk, Michael Ortiz, Ruth Stokes, Nick Williams). Drug Utilisation Sub-Committee secretariat (John Dudley). General Practice Statistics and Classification Unit, Family Medicine Research Centre, University of Sydney (Helena Britt and Geoff Sayer, who conducted the analyses of the depression data from BEACH). Disclosure: Philip B Mitchell has been a member of scientific advisory boards for Eli Lilly, SmithKline Beecham and Wyeth. References Murray CJ, Lopez AD. The global burden of disease: summary. Cambridge, Mass: Harvard School of Public Health, Harvard University Press (on behalf of the World Health Organization and the World Bank), 1996. Edmonds DJ, Dumbrell DM, Primrose JG, et al. Development of an Australian drug utilisation database: a report from the Drug Utilization Sub-Committee of the Pharmaceutical Benefits Advisory Committee. PharmacoEconom 1993; 3: 427-432. World Health Organization Collaborating Centre for Drug Statistics Methodology. Guidelines for ATC classification and DDD assignment. 2nd edition. Oslo, Norway: WHO, 1998. Hurley SF, McNeil JJ, Berbatis CG. Sources of Australian pharmacoepidemiology data. Commun Health Stud 1988; 12(1): 82-96. World Health Organization Collaborating Centre for Drug Statistics Methodology. ATC Index with DDDs, 1999. Oslo, Norway: WHO, 1998. Britt H, Sayer GP, Miller GC, et al. BEACH (Bettering the Evaluation And Care of Health): a study of general practice activity, six-month interim report. AIHW Catalogue No. GEP 1. Canberra: Australian Institute of Health and Welfare (General Practice series no.1). Bridges-Webb C, Britt H, Miles D, et al. Morbidity and treatment in general practice in Australia 1990-1991 [Errata in Med J Aust 1993; 158: 72, 652]. Med J Aust 1992; 157 (Suppl Oct 19): S1-S56. Australian Bureau of Statistics. 1995 National Health Survey: use of medications, Australia. Canberra: ABS, 1995. (Catalogue No. 4377.0.) Australian Bureau of Statistics. 1989-90 National Health Survey: summary of results, Australia. Canberra: ABS, 1991. (Catalogue No. 4364.0.) Australian Bureau of Statistics. 1997 Mental Health and Wellbeing: profile of adults. Canberra: ABS, 1997. (Catalogue No. 4326.0.) American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 4th edition (DSM-IV). Washington, DC: APA, 1994. World Health Organization. International classification of diseases, 10th edition (ICD-10). Geneva: World Health Organization, 1993. Paykel ES, Priest RG. Recognition and management of depression in general practice: a consensus statement. BMJ 1992; 305: 1198-1202. Hirschfeld RMA, Keller MB, Pamico S, et al. The National Depressive and Manic-Depressive Association consensus statement on the undertreatment of depression. JAMA 1997; 277: 333-340. Kendrick T. Prescribing antidepressants in general practice: watchful waiting for minor depression, full dose treatment for major depression. BMJ 1996; 313: 829-830. Paykel ES, Tylee A, Wright A, et al. The Defeat Depression Campaign: psychiatry in the public arena. Am J Psychiatry 1997; 154 (6 Suppl): 59-65. The National Mental Health Strategy. Community Awareness Program: a review. Canberra: Commonwealth Department of Health and Aged Care, November 1998. US Department of Health and Human Services. Agency for Health Care Policy and Research (AHCPR). Depression in primary care: Vol 11. Treatment of major depression. Rockville, Md: AHCPR, 1993. Psychotropic drug guidelines. 4th edition. Melbourne: Therapeutic Guidelines, 2000. National Health and Medical Research Council. Depression in young people. A guide for general practitioners. Canberra: NHMRC, 1997. National Health and Medical Research Council. Depression in young people. A guide for mental health professionals. Canberra: NHMRC, 1997. (Received 5 May, accepted 31 Aug, 2000) Authors' details Drug Utilisation Sub-Committee, Department of Health and Aged Care, Canberra, ACT. Peter McManus, MMedSc, BPharm, Secretary. South Eastern Sydney Area Health Service, Sydney, NSW. Andrea Mant, MD, FRACGP, MA, Area Adviser, Quality Use of Medicines; and Associate Professor, School of Community Medicine, University of New South Wales, Sydney, NSW. School of Psychiatry, University of New South Wales, NSW. Philip B Mitchell, MD, FRANZCP, FRCPsych, Professor; and Administrative Director, Mood Disorders Unit, Prince of Wales Hospital, Sydney, NSW. Health Economics and Outcomes Research, Eli Lilly Australia Pty Ltd, Sydney, NSW. William S Montgomery, BPharm, DipHospPharm, GradCertHealthEcon, Health Outcomes Research Manager. Department of General Practice, University of Adelaide, Adelaide, SA. John Marley, MD, MB ChB, Professor. Health Economics and Pricing Department, SmithKline Beecham (Australia) Pty Ltd, Melbourne, VIC. Merran E Auland, PhD, Health Economist. No reprints will be avaliable from the authors. Correspondence: Mr P McManus, Secretary, Drug Utilisation Sub-Committee, Mail Drop Point 83, Department of Health and Aged Care, GPO Box 9848, Canberra, ACT 2601. peter.mcmanusAThealth.gov.au Make a comment Back to text Back to text Percentage split of antideprssant sales (based on defined daily doses per 1000 population per day) by drug class in 1998 (data for all countries, except Sweden, from IMS Health; Swedish data from the Swedish Association of the Pharmaceutical Industry). SSRI = selective serotonin reuptake inhibitor. TCA = tricyclic antidepressant. Back to text

Peter McManus · Andrea Mant · Philip B Mitchell · William S Montgomery · John Marley · Merran E Auland

Research Diabetes-related lower-limb amputations in Australia Craig B Payne MJA 2000; 173: 352-354 For editorial comment, see Colman & Beischer; see also Campbell et al. Abstract - Methods - Results - Discussion - Acknowledgements - References - Authors' details - - More articles on Endocrinology Abstract Objective: To identify the prevalence of diabetes-related lower-limb amputations and its regional variations in Australia. Design and setting: Cross-sectional analysis of a hospital morbidity dataset in Australia. Methods: Analysis of the National Hospital Morbidity Database of all hospital separations for the ICD codes 84.10-84.19 (lower-limb amputations) and 250.0-250.9 (diabetes and its complications) for the financial years 1995-96 to 1997-98. Main outcome measure: Number of lower-limb amputations in people with diabetes mellitus in Australia, and in each State and Territory. Results: 7887 diabetes-related lower-limb amputations were reported during the study period, with a mean ± SD of 2629 ± 47 per year. The prevalence in Australia was 13.97 per 100 000 total population, and varied from 11.34 per 100 000 in the Australian Capital Territory to 20.68 per 100 000 in South Australia. Conclusion: Diabetes-related lower-limb amputation poses a substantial personal and public health cost in Australia. The loss of a limb is a frequent complication of diabetes mellitus, most commonly the result of diabetic foot problems such as ulcers and infection. The risk of amputation of the lower limb is increased up to 15-fold in people with diabetes. Contributory factors include the loss of sensation from the sensory neuropathy; deformity and gait abnormalities from the motor neuropathy; abnormal blood flow regulation from the autonomic neuropathy; ischaemia from the macrovascular disease; limited joint mobility from the increased glycolation of collagen; poor glycaemic control; and increased risk of infection. It is usually some trigger or traumatic event superimposed on these risk factors that causes a lesion such as ulceration or infection which starts a pathway leading to amputation.2,3 Inadequate and inappropriate self-care is also a major factor. The National Diabetic Foot Disease Management Program, as part of the National Diabetes Strategy and Implementation Plan,4 has called for a 50% reduction in lower-limb amputations by the year 2005. Data on diabetes-related lower-limb amputations in Australia are lacking.4 The aim of my study was to identify the prevalence of diabetes-related lower-limb amputations in Australia, as well as variations among States and Territories. Methods Approval for the study was given by the Faculty of Health Sciences Human Ethics Committee at La Trobe University (Victoria). The dataset for my analysis was obtained from the Australian Institute of Health and Welfare (AIHW) for the financial years 1995-96, 1996-97 and 1997-98. The AIHW obtained permission from the relevant State and Territory agencies to release the information, which did not include any personal identifying data. Information was obtained from the National Hospital Morbidity Database (compiled by the AIHW) on all separations from public and private hospitals in Australia for the International Classification of Disease (ICD)5 procedure codes 84.10 to 84.19 (amputations of the lower extremity) and diagnosis codes 250.0 to 250.9 (indicating diabetes and its complications) as the principal or secondary diagnoses. Information was also obtained on sex, age, ethnicity, duration of hospital stay, and State or Territory of residence of each patient who had an amputation. A spreadsheet was used to determine the number of amputations in each region and the duration of hospital stay. The data for each State and Territory were age- and sex-standardised6 to the estimated Australian population as at 30 June 1998.7 This information was then used to determine the rate for each State and Territory. Results A total of 7887 diabetes-related lower-limb amputations (68.2% in men) were recorded as occurring in the three-year period, with an annual mean of 2629 ± 47 (SD) (Box 1). Most occurred in the 65-79 years age groups (Box 2). The age- and sex-standardised prevalence of lower-limb amputation varied among the States and Territories (Box 3), from 11.34 per 100 000 total population in the Australian Capital Territory to 20.68 per 100 000 total population in South Australia. The duration of hospital stay (Box 3) also varied among the States and Territories. The shortest mean hospital stay was 20.0 (95% CI, 17.4-22.6) days in South Australia and the longest was 40.2 (95% CI, 23.1-57.3) in the Northern Territory. It was not possible to analyse the ethnicity data, as two States/Territories would not agree to the release of this information. Discussion The 2629 diabetes-related lower-limb amputations in Australia per year represent a significant personal burden on people with diabetes and on the healthcare system. The loss of a limb is a personal tragedy for those with diabetes,8 and is associated with a deterioration of functional status and residential status,9 with a significant number requiring long term care.10 People with diabetes who have a lower-limb amputation have a higher mortality rate,1,11 especially perioperative mortality.12 Half the people with an amputation will require an amputation of the remaining limb within five years.13,14 This morbidity results in high medical and rehabilitation costs: about 10% of diabetes-related healthcare costs are associated with lower-limb amputations.15The sex differences in lower-limb amputation rates of about 2:1 for men to women reported here are consistent with previous reports,20 and may be related to the levels of adherence to advice, the amount of social support, psychological factors such as denial, or a higher prevalence of the physiological risk factors for amputation such as macrovascular disease.21 Ethnicity is a well-recognised risk factor for lower-limb amputation,22,23 but was not analysed in this project as two of the States/Territories would not release this information. The duration of hospital stay has been identified as one of the main determinants of cost associated with a lower-limb amputation.17 The mean number of bed-days reported here (24.7 days) is less than the mean in the Netherlands15 (42 days) and more than that in the United States16 (15.9 days). There was a large variation among the Australian States and Territories in the mean hospital stay; South Australia has the highest prevalence of lower-limb amputation, but the shortest mean stay. Regional variations have been reported previously in New Zealand for hospital admissions for diabetic foot complications.18 Such regional variations are most likely to be due to variations in clinical practice and access to services.19 A number of shortcomings are inherent in the type of dataset analysed here. Of primary concern is the accuracy of the recording of data. Diabetes has been reported as being under-recorded on discharge records,24,25 so the numbers reported here are most likely an underestimate. There is also concern that the dataset does not distinguish the number of multiple amputations in the same individual; this will bias the population towards the characteristics of these individuals. A number of modifiable risk factors for diabetes-related lower-limb amputation have been identified,26-28 including the lowering of blood pressure, improving glycaemic control and reducing or eliminating smoking. With proper foot care, patient education and provision of appropriate services, such as regular podiatric care, a reduction in the number of amputations can be achieved.4 A number of studies have shown the value of multidisciplinary teams in reducing amputations by up to 50%.29-32 A reduction of this magnitude has the potential to save up to $24 million (based on the assumption that the direct cost of diabetes-related lower-limb amputations in Australia is $48 million per year4). However, a significant proportion of this potential saving will need to be directed to programs to prevent the amputations. Acknowledgements Funding for this project was provided by the Australasian Podiatric and Education Foundation. References Nelson R, Gohdes DM, Everhart JE, et al. Lower extremity amputations in NIDDM: 12 year follow up study in Pima Indians. Diabetes Care 1998; 11: 8-16. Payne CB, Scott RS, Moir C. Trigger events for acute admission to hospital for diabetic foot disease. Australas J Podiatric Med 1998; 32: 57-64. Pecoraro RE, Reiber GE, Burgess EM. Pathways to diabetic amputation -- basis for prevention. Diabetes Care 1990; 13: 513-521. Colagiuri S, Colagiuri R, Ward J. National Diabetes Strategy and Implementation Plan. Canberra: Diabetes Australia, 1998. The International classification of diseases. 9th Revision. Clinical modification. Commission on Professional and Hospital Activities. Michigan, 1990. Beaglehole R, Bonita R, Kjellstrom T. Basic epidemiology. Geneva: World Health Organization, 1993. Australian Bureau of Statistics. Australian demographic statistics. Canberra: ABS, 1999. (Catalogue no. 3101.0.) Fitzpatrick MC. The psychologic assessment and psychosocial recovery of the patient with an amputation. Clin Orthop 1999; 381: 98-107. Frykberg RG, Arora S, Pomposelli FB, LoGerfo F. Functional outcome in elderly following lower extremity amputation. J Foot Ankle Surg 1998; 37: 181-185. Lavery LA, van Houtum WH, Armstrong DG. Institutionalisation following diabetes related lower extremity amputation. Am J Med 1997; 103: 383-388. Faris I, Duncan H, Young C. Factors affecting the outcome of diabetic patients with foot ulcers or gangrene. J Cardiovasc Surg 1988; 29: 736-740. Ebskov LB. Relative mortality in lower limb amputees with diabetes mellitus. Prosthet Orthot Int 1996; 20: 147-152. Silbert S. Amputation of the lower extremity in diabetes mellitus. Diabetes 1952; 1: 297-299. Ebskov LB. Diabetic amputation and long-term survival. Int J Rehab Res 1998; 21: 403-408 Van Houtum WH, Lavery LA, Harkless LB. The costs of diabetes-related lower extremity amputations in the Netherlands. Diabetic Med 1995; 12: 777-781. Ashry HR, Lavery LA, Armstrong DG, et al. Cost of diabetes related amputations in minorities. J Foot Ankle Surg 1998; 37: 186-190. Solomon C, van Rij A, Barnett R, et al. Amputations in the surgical budget. N Z Med J 1994; 107: 78-80. Payne CB, Scott RS, Moir C. Hospital discharges for diabetic foot disease in New Zealand 1980-1993. Diabetes Res Clin Pract 1998; 39: 69-74. Sanders D, Coulter A, McPherson K. Variations in hospital admission rates: a review of the literature. London: King Edward's Hospital Fund, 1989. Armstrong DG, Lavery LA, van Houtum WH, Harkless LB. The impact of gender on amputation. J Foot Ankle Surg 1997; 36: 66-69. Vogt MT, Wolfson SK, Kuller LH. Lower extremity arterial disease and the aging process -- a review. J Clin Epidemiol 1992; 45: 529-542. Lavery LA, Ashry HR, van Houtum W, et al. Variation in the incidence and proportion of diabetes related amputations in minorities. Diabetes Care 1996; 19: 48-51. Simmons D, Scott D, Kenealy T, Scragg R. Foot care among diabetic patients in South Auckland. N Z Med J 1995; 108: 106-108. Williams DRR, Fuller JH, Stevens LK. Validity of routinely collected hospital admissions data on diabetes. Diabetic Med 1998; 6: 320-324. Phillips DE, Mann JI. Diabetes -- inpatient utilisation, costs and data validity. Dunedin 1985-9. N Z Med J 1992; 105: 313-315. Moss SE, Klein R, Klein BEK. The prevalence and incidence of lower extremity amputation in a diabetic population. Arch Intern Med 1992; 152: 610-616. Lehto S, Ronnemaa T, Pyorala K, Laakso M. Risk factors predicting lower extremity amputations in patients with NIDDM. Diabetes Care 1996; 19: 607-611. Hamalainen H, Ronnemaa T, Halonen JP, Toikka T. Factors predicting lower extremity amputations in patients with type 1 or type 2 diabetes mellitus: a population based 7 year follow-up study. J Intern Med 1999; 246: 97-103. Edmonds ME, Blundell MP, Morris ME, et al. Improved survival of the diabetic foot -- the role of a specialised foot clinic. QJM 1986; 60: 763-771. Malone LM, Snyder M, Anderson G, et al. Prevention of amputation. Am J Surg 1989; 158: 520-523. Ebskov LB. Epidemiology of lower extremity amputation in Denmark. Int Orthop 1991; 15: 285-288. Larson J, Apelqvist J, Agardh CD, Stenstrom A. Decreasing incidence of major amputation in diabetic patients -- a consequence of a multidisciplinary foot care team approach. Diabetic Med 1995; 12: 770-777. (Received 25 Nov 1999, accepted 20 Jul 2000) Authors' details Faculty of Health Sciences, La Trobe University, Melbourne, VIC. Craig B Payne, DipPod(NZ), MPH, Lecturer, Department of Podiatry. Reprints: Dr C B Payne, Department of Podiatry, School of Human Biosciences, Faculty of Health Sciences, La Trobe University, Bundoora, VIC 3083. c.payneATlatrobe.edu.au Make a comment 1: Number of diabetes-related lower-limb amputations in Australia Men Women Total1995-96 1996-97 1997-98 1729 1849 1804 851 824 830 2580 2673 2634 Mean ±SD 1795 ±61 834 ±14 2629 ±47 Total 5382 (68%) 2505 (32%) 7887 Back to text Click in box for larger versionBack to text 3: Age- and sex-standardised prevalence and duration of hospital stay for lower-limb amputations in Australia for 1995-1998 Mean ±SD lower extremity amputations per year Rate (95% CI) per 100000 total population New South Wales Victoria Queensland South Australia Western Australia Tasmania Northern Territory Australian Capital Territory Australia 801 ±13 695 ±12 468 ±8 308 ±6 219 ±4 67 ±2 36 ±1 35 ±1 2629 ±47 12.59 (9.54-15.78) 14.87 (11.6-18.17) 13.48 (10.56-16.45) 20.68 (17.18-24.18) 11.89 (8.90-14.88) 14.21 (12.63-16.17) 18.86 (15.53-22.19) 11.34 (8.34-13.56) 13.97 (11.98-15.87) Duration of hospital stay Mean (95% CI) bed days Median (range) bed days New South Wales Victoria Queensland South Australia Western Australia Tasmania Northern Territory Australian Capital Territory Australia 24 (23-26) 22 (21-23) 30 (28-33) 20 (17-23) 26 (22-29) 27 (19-35) 40 (23-57) 33 (18-47) 25 (24-26) 18 (1-210) 16 (1-183) 21 (1-283) 13.5 (1-176) 18 (1-183) 21 (1-197) 24 (1-224) 24 (1-223) 17 (1-283) Back to text

Craig B Payne

Research Rates of in-hospital arrests, deaths and intensive care admissions: the effect of a medical emergency team Peter J Bristow, Ken M Hillman, Tien Chey, Kathy Daffurn, Theresa C Jacques, Sandra L Norman, Gillian F Bishop and E Grant Simmons MJA 2000; 173: 236-240 Abstract - Methods - Results - Discussion - Conclusion - Acknowledgements Authors' details - - More articles on Emergency medicine Abstract Objectives: To evaluate the effectiveness of a medical emergency team (MET) in reducing the rates of selected adverse events. Design: Cohort comparison study after casemix adjustment. Patients and setting: All adult (≥ 14 years) patients admitted to three Australian public hospitals from 8 July to 31 December 1996. Intervention studied: At Hospital 1, a medical emergency team (MET) could be called for abnormal physiological parameters or staff concern. Hospitals 2 and 3 had conventional cardiac arrest teams. Main outcome measures: Casemix-adjusted rates of cardiac arrest, unanticipated admission to intensive care unit (ICU), death, and the subgroup of deaths where there was no pre-existing "do not resuscitate" (DNR) order documented. Results: There were 1510 adverse events identified among 50 942 admissions. The rate of unanticipated ICU admissions was less at the intervention hospital in total (casemix-adjusted odds ratios: Hospital 1, 1.00; Hospital 2, 1.59 [95% CI, 1.24-2.04]; Hospital 3, 1.73 [95% CI, 1.37-2.16]). There was no significant difference in the rates of cardiac arrest or total deaths between the three hospitals. However, one of the hospitals with a conventional cardiac arrest team had a higher death rate among patients without a DNR order. Conclusions: The MET hospital had fewer unanticipated ICU/HDU admissions, with no increase in in-hospital arrest rate or total death rate. The non-DNR deaths were lower compared with one of the other hospitals; however, we did not adjust for DNR practices. We suggest that the MET concept is worthy of further study. Certain in-hospital deaths may be preventable.1-3 Nearly 85% of hospital inpatients who suffer a cardiorespiratory arrest have documented observations of deterioration in the eight hours before the arrest.4,5 Recent studies have demonstrated suboptimal care of hospitalised patients before their admission to the intensive care unit (ICU), and that these patients have a higher mortality.6-8 The authors of these studies urge earlier intervention. One approach to providing an early response to at-risk inpatients throughout the hospital is the medical emergency team (MET),9,10 which replaces the conventional cardiac arrest team. The MET responds to specific clinical criteria (such as bradycardia, tachycardia, hypotension and threatened airway) in order to prevent further deterioration. Others have advocated similar approaches to reduce unexpected hospital deaths and morbidity.11,12 In our study, selected outcomes in a hospital with a MET were compared with outcomes in two hospitals with conventional cardiac arrest teams. These outcomes were rates of cardiorespiratory arrest, unanticipated admission to the ICU or high dependency unit (HDU), death, and deaths where there was no prexisting "do not resuscitate" (DNR) order. Methods This study was a prospective cohort comparison of three hospitals, testing whether an early intervention team, the MET, was associated with fewer adverse events among inpatients, after adjusting for casemix differences. The study was approved by the ethics committees of each participating hospital and the University of New South Wales. Setting The hospitals were similarly sized Australian public hospitals, with bed capacities in the range 380-530. At Hospital 1, the cardiac arrest team was replaced by a MET, which any staff member could call for immediate assistance. Staff could summon the MET if concerned about a patient's condition or if the patient's vital signs exceeded certain levels (Box 1).10 An education program explained the MET's role to all new staff. However, calling the MET when criteria were met was not compulsory. The MET consisted of the ICU registrar and senior nurse, and medical registrar. At Hospitals 2 and 3, the arrest team was paged by nursing or medical staff for cardiorespiratory arrest. The arrest team consisted of the ICU registrar, medical registrar, and ICU or coronary care nurse. Data collection We identified all cardiorespiratory arrest calls, deaths, and ICU/HDU admissions at the three hospitals among patients 14 years and over in hospital during the period from 8 July to 31 December 1996. These were designated "events". Soon after an event, the patient's medical record was reviewed for demographic information. In addition, for cardiac arrests and deaths, documentation of a DNR order before arrest or death was recorded. Each ICU/HDU admission was classified as to whether the patient was admitted to ICU/HDU for the same reason he or she was admitted to hospital. If not, the ICU/HDU admission was defined as unanticipated. For example, a patient admitted to ICU with respiratory distress after a cholecystectomy would be unanticipated. Data were collected by three critical care nurses (one at each hospital) trained in the use of a specifically designed form, which was piloted for two weeks before data collection. The nurses were familiar with the medical record at the three hospitals. Where the information contained in the history was unclear, the attending staff were asked for clarification. Data were entered into a database.13 Data cleaning was performed and any anomalies checked by reference to the datasheet or medical record. Data were then exported to SAS14 for analysis. Outcome measures The primary endpoints were the casemix-adjusted rates of ICU/HDU unanticipated admission, cardiac arrest, death, and deaths without a prior DNR order. These were called "total event rates". For any patient, one event could result in additional events (eg, cardiac arrest followed by unanticipated ICU admission and then death). The "index event" was defined as the event the data collectors considered the first in a series of events. The casemix-adjusted rates of index events were compared between the three hospitals as secondary endpoints. To ensure that any decline in the rate of unanticipated admissions was not caused by excess anticipated admissions, the casemix-adjusted rate of all ICU/HDU admissions was calculated as a control measure. Casemix adjustment Demographic and diagnostic data on the patient population (aged ≥ 14 years) admitted to the hospitals for the period were obtained. The study data were merged by medical record number and date of admission with the complete inpatient statistical data to create a dataset with 50 942 records. This enabled us to identify the admissions for which an event occurred and analyse the data at the patient level. Using simple and multiple logistic regression, we modelled the probability of an event occurring during hospitalisation, adjusted for patient demographics and diagnostic characteristics. Models were derived independently for each total event and for each index event. Parameters were added to the model in a stepwise fashion. To prevent overparameterising the models (where minor, non-significant differences cumulatively hide true differences), when C (equivalent to the area under the receiver operator characteristics curve) reached 0.85 no further parameters were added to the model. This always occurred with fewer than six parameters used. Demographic and casemix independent variables that were tested for use in the models are detailed in Box 2. The models developed used groups of diagnostic categories based on ICD-9-CM codes using the principal diagnosis and the stay diagnosis only.15 The ICD-9-CM code groupings used are available from the principal author (PJB). The performance of the models was assessed by Hosmer-Lemeshow goodness-of-fit tests.16 The risk of an event occurring in a hospital compared with the MET hospital was presented as an adjusted odds ratio with 95% confidence intervals. A level of significance of 5% was used in all statistical tests. Results Hospital demographics Characteristics of all patients (aged ≥ 14 years) admitted to the three hospitals during the study period are shown in Box 3. Hospital 2 had fewer admissions than the other hospitals. Hospital 1 had a higher proportion of male patients admitted, and a lower proportion of admissions from the emergency department (ED). This hospital also had a younger patient population, which is reflected in differences in casemix: Hospital 1 had lower proportions of patients with stroke, severe acute heart disease, gastrointestinal disease, and musculoskeletal and connective tissue diseases, but higher proportions with severe trauma and follow-up care without acute diagnosis (eg, dialysis). The rates of DNR orders in dying patients were 77% in Hospital 1, and 64% and 70% in Hospitals 2 and 3, respectively (P = 0.006). Prevalence and characteristics of events A total of 1510 adverse events (unanticipated ICU/HDU admissions, arrest calls, and deaths) were recorded during the study period for the three hospitals. There were 1100 index events. The prevalence and characteristics of events are summarised in Box 4 for total event rates and Box 5 for index rates. There was a significantly reduced rate of unanticipated ICU/HDU admissions at the MET intervention hospital after casemix adjustment (for both the total event rate and the index rate). After adjustment, Hospital 2 had 49 (95% CI, 20-87) more unanticipated ICU/HDU admissions over a six-month period, and Hospital 3 had 92 (95% CI, 47-146) more, compared with Hospital 1. The rate of all ICU/HDU admissions was lower at Hospital 1 than at one control hospital, and trended to lower than at the other. There was no statistically significant difference in cardiac arrest rate or death rate after casemix adjustment. The casemix-adjusted death rate in patients where there was no documentation found of a DNR order was significantly higher at Hospital 2, translating to 27 (95% CI, 7-53) extra non-DNR deaths. Model performance Box 6 presents an example of the odds ratios after addition of the most significant variables in the multiple logistic regression models derived from the data for the total arrest data. It shows the C statistic as each variable was added to the cardiac arrest model. In the cardiac arrest models, the variables that were adjusted for were emergency admissions, age over 74, heart disease, lung disease and infectious disease as diagnoses. In the total death models, the terms adjusted for were emergency admissions, age over 74, single day stay emergency admissions, and cancer and infectious disease. The same demographic variables were used in the index death model, although in the total non-DNR death model both age ≥ 75 and age 65-74 were used in the model. In the unanticipated ICU/HDU models, the variables adjusted for were single day admission, emergency admission, and cancer and gastrointestinal disease diagnoses. The total unanticipated ICU/HDU model also included the variables stroke and infectious disease as diagnoses. All models satisfied the Hosmer- Lemeshow test.16 Discussion Rationale for our methods In this study, we attempted to determine if the MET system was associated with a reduced rate of adverse events among inpatients. To do this, we compared the rates of adverse events between three hospitals after casemix adjustment.17-19 This method was chosen as we decided that randomisation at the patient level was impractical. A random pattern of response to calls would probably have dissuaded staff caring for patients from calling the MET. Randomisation by ward would have risked contamination bias and engendered problems of casemix, as wards differ in the nature of their patients. Historical comparison at Hospital 1 between a period before and a period after introduction of the MET team was impractical, as the team had been trialled and evolved for six years before the study. The models we used appear to adequately fit the data, according to the Hosmer-Lemeshow goodness-of-fit tests, and with good model performance measured by C statistics. However, multiple methods of casemix adjustment are possible, and these may give divergent results. This is a limitation of casemix adjustment methodology.20 To avoid concealing real differences by excessive modelling, parameters were added stepwise by multivariate analysis until the models reasonably represented the data. The terms which appeared in the final models were usually those that could be expected to influence the outcomes. Thus, advanced age and emergency admissions were factors in the death and cardiac arrest models. The cardiac arrest models also included the terms for heart disease, lung and infectious disease. Infectious disease was an unexpected variable and was also significant in the total death model. Other differences (such as levels of hospital funding, ICU/HDU capacity, the number and seniority of medical and nursing staff, and the level of out-of-hours cover) may also have contributed to the results. However, to adjust for these would have been more difficult than for the variables studied, which relate directly to the patients at risk and are easily and reliably obtained. Explanation of findings After casemix adjustment, we found reduced rates of both total and index unanticipated ICU/HDU admissions at the MET intervention hospital. There were no differences in the rates of cardiac arrests or deaths. However, at one hospital without the MET, there was a higher rate of non-DNR deaths, the subset of deaths most likely potentially preventable by a MET. The reduction in unanticipated ICU/HDU admissions that was seen in the MET intervention hospital could result from many factors. One possible explanation is that the MET was effective and able to intervene on the wards and prevent further deterioration. Another possible reason may relate to differences in referral practices: perhaps the presence of MET backup engendered a feeling that ICU/HDU referral was not needed. Misclassification of ICU/HDU admissions as anticipated rather than unanticipated was excluded as an explanation of the difference by the finding that the rate of all ICU/HDU admissions was lower at the intervention hospital than one control hospital and trended to lower at the other. The lack of efficacy of the MET to prevent cardiorespiratory arrest and modify death rate may be related to lack of sensitivity of calling criteria, or because pathophysiological processes (eg, shock) become irreversible. Another possible explanation for the lack of effect of the MET on event rates is underutilisation. Based on a previous study,21 up to 706 MET calls could have been expected, and yet only 150 were made. Frequent education is probably also required to ensure the appropriate calling of a MET.22 No special efforts regarding staff education in the study period were made. The clinical staff of the hospital were unaware of the study, to negate any possible Hawthorne effect.23 Finally, organisational changes such as introduction of a MET are difficult to implement in hospitals.24,25 Our results probably reflect the effectiveness of the implementation of the MET system as much as the concept of early intervention. Future directions Our study cannot answer definitively if the MET was the cause of the benefit we observed; it does show that the MET concept is worthy of further study. The study could be likened to a Phase II trial of a drug comparing three hospitals at one point in time. Further studies of the MET system's efficacy are needed, such as a before-after comparison in several hospitals, or a comparison of a larger sample size of intervention and control hospitals. Such studies should be repeated some time after the intervention. Is the benefit observed useful and worth pursuing? If it is possible to reduce unanticipated ICU admissions without increased mortality this may result in cost saving. It has been estimated that the US spends about 1% of its gross national product on intensive care facilities.26 However, any savings in intensive care would be offset by the cost of establishing and maintaining a MET. The MET may also have unexpected costs and benefits on processes such as staff satisfaction with care provided. Again, these need to be quantified. Conclusion In this study, we found that fewer patients were unexpectedly admitted to ICU or HDU at a hospital with the MET system, and this hospital had fewer non-DNR deaths than one of the other hospitals. There was no significant change in the casemix-adjusted rate of arrests or total deaths. This may be an advantage of an early response team, which could have important implications for patient care in hospitals. We believe that the MET concept should be studied further in a larger sample of institutions. Acknowledgements Funding for the study was provided by a Commonwealth Department of Health and Family Services Research and Development Grant (HS338). Associate Professor Robert Gibberd assisted with the statistical analysis. References Brennan TA, Leape LL, Laird N, et al. Incidence of adverse events and negligence in hospitalised patients: results of the Harvard Medical Practice Study I. N Engl J Med 1991; 324: 370-376. Leape LL, Brennan TA, Laird N, et al. Nature of adverse events in hospitalised patients: results of the Harvard Medical Practice Study II. N Engl J Med 1991; 324: 377-384. Wilson R McL, Runciman WB, Gibberd RW, et al. The Quality in Australian Health Care Study. Med J Aust 1995; 163: 458-471. Schein RMH, Hazday N, Pena M, et al. Clinical antecedents to inhospital cardiopulmonary arrest. Chest 1990; 98: 1388-1392. Franklin C, Mathew J. Developing strategies to prevent inhospital cardiac arrest: analyzing responses of physicians and nurses in the hours before the event. Crit Care Med 1994; 22: 246-247. Lundberg JS, Perl TM, Wiblen T, et al. Septic shock: an analysis of outcomes for patients with onset on hospital wards versus intensive care units. Crit Care Med 1998; 26: 1020-1024. Goldhill DR, Sumner A. Outcome of intensive care patients in a group of British intensive care units. Crit Care Med 1998; 26: 1337-1345. McQuillan P, Pilkington S, Allan A, et al. Confidential inquiry into quality of care before admission to intensive care. BMJ 1998; 316: 1853-1858. Lee A, Bishop G, Hillman KM, Daffurn K. The medical emergency team. Anaesth Intensive Care 1995; 23: 183-186. Hourihan F, Bishop G, Hillman KM, et al. The medical emergency team: a new strategy to identify and intervene in high risk patients. Clin Intensive Care 1995; 6: 269-272. Frank ED. A shock team in a general hospital. Anesth Analg 1967; 46: 740-745. Goldhill DR. Introducing the postoperative care team [editorial]. BMJ 1997; 314: 389. Microsoft Access [computer program]. Version 2.0. Redmond, Wa: Microsoft, 1994. SAS for Windows [computer program]. Version 6.12. Cary, NC: SAS Institute Inc, 1997. Stremple JF, Bross DS, Davis CL, McDonald GO. Comparison of postoperative mortality and morbidity in VA and nonfederal hospitals. J Surg Res 1994; 56: 405-416. Hosmer DW, Lemeshow S. Applied logistic regression. New York: John Wiley and Sons, 1989. Iezzoni LI. The risks of risk adjustment. JAMA 1997; 278: 1600-1607. Dubois RW, Rogers WH, Moxley JH, et al. Hospital inpatient mortality. Is it a predictor of quality? N Engl J Med 1987; 317: 1674-1680. Green J, Passman LJ, Wintfield N. Analyzing hospital mortality. The consequences of diversity in patient mix. JAMA 1991; 265: 1849-1853. Iezzoni LI, Shwartz M, Ash A, et al. Severity measurement methods and judging hospital death rates for pneumonia. Med Care 1996; 34: 11-28. Hillman KM, Bishop G, Lee A, et al. Identifying the general ward patient at high risk of cardiac arrest. Clin Int Care 1996; 7: 242-243. Daffurn KD, Lee A, Hillman KM, et al. Do nurses know when to summon emergency assistance? Intensive Crit Care Nurs 1994; 10: 115-120. Grufferman S. Complexity and the Hawthorne effect in community trials [editorial]. Epidemiology 1999; 10: 209-210. Garside P. Organisational context for quality: lessons from the fields of organisational development and change management. Qual Health Care 1998; 7 Suppl: S8-15. Koeck C. Time for organisational development in healthcare organisations [editorial]. BMJ 1998; 317: 1267-1268. Cerra FB. Healthcare reform: the role of coordinated critical care. Crit Care Med 1993; 21: 457-464. (Received 15 Feb, accepted 10 Jul, 2000) Authors' details Liverpool Hospital, Sydney, NSW. Peter J Bristow, MB BS, FRACP, Staff Specialist, Department of Intensive Care; Ken M Hillman, MB BS, FFICANZCA, Professor, University of New South Wales Clinical School; Kathy Daffurn, RN, MAppSc, Co-Director, Division of Critical Care; Sandra L Norman, MN, BAppSc, Clinical Nurse Specialist, Department of Intensive Care; Gillian F Bishop, MB ChB, FFICANZCA, Director, Department of Intensive Care; Tien Chey, BSc, MAppStat, Statistician, Epidemiology Unit. Department of Intensive Care, St George Hospital, Sydney, NSW. Theresa C Jacques, MB BS, FFICANZCA, Director. Department of Intensive Care, Illawarra Regional Hospital, Wollongong, NSW. E Grant Simmons, MB BS, FFICANZCA, Director. Reprints will not be available from the authors. Correspondence: Dr P J Bristow, Intensive Care Offices, Alfred Hospital, Commercial Road, Prahran, VIC 3181. p.bristowATalfred.org.au Make a comment 1: Criteria for calling the medical emergency team10 Cardiorespiratory arrest Threatened airway Respiratory rate ≤5 breaths per minute ≥36 breaths per minute Pulse rate ≤40 beats per minute ≥140 beats per minute Systolic blood pressure ≤90mmHg Repeated or prolonged seizures Fall in Glasgow Coma Score >2 points Concern about patient status not detailed above Back to text 2: Variables available for calculation of the various models Sex (binary) Seven age categories (14-24, 25-34, 35-44, 45-54, 55-64, 65-74, ≥75) Same-day admission (binary) (ie, admission and discharge occurred on the same calendar day) Referral from emergency department (binary) Australian born (binary) Casemix categories (16 indicator variables, available from author) Hospital (three indicator variables) Back to text 3: Characteristics of admissions at the three study hospitals from 8 July to 31 December 1996 Hospital* Characteristic 1 2 3 Test of Independence† Number of admissions 18338 13059 19545 Male admissions 44.9% 42.9% 42.8% χ2=21.06‡ (2 df) Same-day admissions 47.7% 47.0% 46.7% χ2=4.35 (2 df) Admission via emergency department 29.6% 36.0% 35.1% χ2=186.53‡ (2 df) Australian born Country of birth not stated 49.3% 6.8% 67.2% 0.5% 50.2% 23.2% Not tested Age distribution 14-24 25-34 35-44 45-54 55-64 65-74 ≥75 9.7% 14.9% 14.3% 12.4% 18.1% 20.5% 10.0% 8.6% 15.2% 9.6% 9.8% 18.5% 22.2% 16.0% 7.8% 13.1% 11.1% 10.4% 14.4% 22.1% 21.1% χ2=1146‡ (12 df) Diagnostic category 1. Cancer 2. Stroke 3. Severe acute heart disease 4. Metabolic and electrolyte disorders 5. Pulmonary disease 6. Ophthalmologic disease 7. Low risk heart disease 8. Gastrointestinal disease 9. Urologic disease 10. Musculoskeletal, connective tissue disease 11. Infectious diseases 12. Symptoms and ill-defined conditions 13. Severe trauma 14. Follow-up care without acute diagnosis 15. Pregnancy, childbirth, puerperium 16. Others 4.4% 1.4% 2.6% 1.3% 3.3% 2.0% 3.5% 6.4% 1.9% 1.8% 1.0% 3.2% 2.9% 34.0% 10.8% 19.5% 4.1% 1.8% 3.0% 1.6% 2.9% 1.2% 2.9% 8.9% 1.7% 3.4% 0.7% 3.0% 2.1% 30.1% 14.1% 18.5% 5.3% 1.6% 3.2% 1.1% 4.2% 0.5% 4.6% 10.2% 1.9% 3.2% 1.0% 6.7% 1.8% 23.4% 11.0% 20.5% χ2=1562‡ (50 df) *Hospital 1 had the medical emergency team. †Test for any difference between the three hospitals. ‡P Back to text 4: Comparisons of total event rates by hospitals Event n Crude rates/10000 Unadjusted ORs Adjusted ORs* Cardiac arrest Hospital 1 Hospital 2 Hospital 3 69 66 99 38 51 51 1.00 1.34 (0.96-1.89) 1.35 (0.99-1.83) 1.00 1.14 (0.81-1.61) 1.00 (0.73-1.37) Death Hospital 1 Hospital 2 Hospital 3 243 240 295 133 184 151 1.00 1.39 (1.16-1.67) 1.14 (0.96-1.35) 1.00 1.08 (0.89-1.30) 0.83 (0.70-1.00) Non-DNR death Hospital 1 Hospital 2 Hospital 3 55 86 88 30 66 45 1.00 2.20 (1.57-3.09) 1.50 (1.07-2.11) 1.00 1.68 (1.19-2.36) 0.94 (0.67-1.33) Unanticipated ICU/HDU admission Hospital 1 Hospital 2 Hospital 3 118 146 234 64 112 120 1.00 1.73 (1.36-2.21) 1.86 (1.49-2.32) 1.00 1.59 (1.24-2.04) 1.73 (1.37-2.16) *Odds ratios (ORs) adjusted for patient characteristics and diagnostic categories. Hospital 1 (which has the medical emergency team) is the reference for the ORs. For shaded ORs, 95% CIs do not cross 1.0. DNR="do not resuscitate" order documented. ICU=intensive care unit. HDU=high dependency unit. Back to text 5: Comparisons of index event rates by hospitals Event n Crude rates/10000 Unadjusted ORs Adjusted ORs* Cardiac arrest Hospital 1 Hospital 2 Hospital 3 60 63 84 33 48 43 1.00 1.48 (1.04-2.10) 1.31 (0.94-1.83) 1.00 1.24 (0.87-1.78) 0.96 (0.69-1.35) Death Hospital 1 Hospital 2 Hospital 3 119 139 191 65 106 98 1.00 1.65 (1.29-2.11) 1.51 (1.20-1.90) 1.00 1.24 (0.97-1.60) 1.05 (0.82-1.33) Unanticipated ICU/HDU admission Hospital 1 Hospital 2 Hospital 3 82 140 222 45 107 114 1.00 2.41 (1.83-3.17) 2.56 (1.98-3.30) 1.00 2.17 (1.65-2.87) 2.35 (1.82-3.04) *Odds ratios (ORs) adjusted for patient characteristics and diagnostic categories. Hospital 1 (which has the medical emergency team) is the reference for the ORs. For shaded ORs, 95% CIs do not cross 1.0. ICU=intensive care unit. HDU=high dependency unit. Back to text 6: An example of how the odds ratios and C statistic changed as variables were added stepwise to the model for total cardiac arrests Odds ratio* (95% CI) Hospital 2 Hospital 3 C statistic Crude odds ratio Admission via emergency department Age ≥75 years Severe acute heart disease Low risk heart disease Infectious disease Pulmonary disease 1.34 (0.96-1.89) 1.16 (0.83-1.63) 1.06 (0.75-1.49) 1.06 (0.75-1.49) 1.07 (0.76-1.50) 1.09 (0.77-1.53) 1.14 (0.81-1.61) 1.35 (0.99-1.83) 1.19 (0.87-1.62) 0.98 (0.72-1.34) 0.99 (0.72-1.35) 0.99 (0.72-1.35) 1.00 (0.73-1.37) 1.00 (0.73-1.37) 0.533 0.755 0.798 0.809 0.826 0.833 0.850 *Hospital 1 is the reference for the odds ratios. Back to text

Peter J Bristow · Ken M Hillman · Tien Chey · Kathy Daffurn · Theresa C Jacques · Sandra L Norman · Gillian F Bishop

Research Characteristics and outcomes of older patients presenting to the emergency department after a fall: a retrospective analysis Anthony J Bell, Janet K Talbot-Stern and Annemarie Hennessy MJA 2000; 173: 179-182 For editorial comment, see Close & Glucksman Abstract - Methods - Results - Discussion - References - Authors' details - - More articles on Emergency medicine Abstract Objectives: To study older patients presenting to the emergency department after a fall -- factors associated with the fall, injuries sustained and outcome. Design: A retrospective analysis using the Emergency Department Information System (EDIS), the Trauma Registry and the patient information database (CCIS), in addition to the patient's emergency and inpatient medical records. Setting: Emergency department of a major inner city teaching hospital, 1 June - 30 November 1997. Patients: All patients over 65 years presenting to the emergency department (ED) after a fall, for whom complete medical records were available. Results: Of 803 patients over 65 years presenting to the ED after a fall, complete records were available for 733 (91.3%) (283 men and 450 women). Extrinsic (accidental) causes were implicated in more than a third of falls (313 patients [42.7%]). A high proportion of the patients were living at home (520; 70.9%) and walking unaided (389; 53.1%). Although absolute numbers of women increased with age, men were as likely as women to present after a fall. Many patients had fallen before -- 39% of the men (111/283) and 24% of the women (110/450). In 78 patients (10.6%), alcohol misuse may have been a direct cause of the fall. The overall injury rate was 70.5% (517/733 patients), the most common injury being an isolated fracture (269/517 patients; 52.0%). In all, 419 patients (57.2%) were admitted to hospital, 48% (200/419) with a fracture and 52% (219/419) for investigation of the medical cause of the fall. The median length of hospital stay was 6 days (mean, 10.4 days; range, 1-129 days); 35% (146/419) of patients were in hospital for more than 10 days. Conclusion: Older patients presenting to the ED after a fall had high injury rates, high admission rates and often prolonged hospitalisation. About a third had fallen before. Patients at risk can be identified in the ED and referred to falls prevention programs. Census data for 1996 show that 12.1% of Australians are aged 65 years or over.1 This proportion is expected to double in the next 40 years,2 with major implications for healthcare costs. Alone, the cost of falls in patients over 70 years in Australia was estimated to be $398 million in 1989.3In the United States, trauma causes a considerable proportion of presentations (and subsequent hospital admissions) of older patients. Falls account for most of these presentations.4 The annual incidence of all falls increases from 25% at age 70 years to 35% after the age of 75; the risk increases with age and is higher among those living in long-stay institutions.5 Up to 10%-15% of falls result in serious injury, of which at least half are fractures. Even falls not resulting in injury may have serious psychological consequences.5,6 The "postfall anxiety syndrome"7 and fear of falling leads to decreased activity,8 and ultimately an increased risk of future falls.9 Patients have reported continued disability two months after a fall.10 No Australian report has been published specifically about patients in this age group presenting to the emergency department (ED) after falls, although previous studies have looked at older people presenting to the ED.11,12 Our aim was therefore to focus on patients over 65 years who presented to our ED as a result of a fall. Several features were of interest: why the patients fell; what, if any, injuries were sustained; what proportion of patients required admission to hospital; and what morbidity and mortality resulted from the fall. Methods Royal Prince Alfred Hospital is a 700-bed tertiary referral centre with 60 000 admissions and 45 000 ED attendances per year. A retrospective review of attendances for the six-month period June - November 1997 was undertaken. All older patients who had fallen were eligible for the study. Patient data Data were obtained from the sources below and thereafter patients remained anonymous. EDIS: Patients eligible for the study were identified by a search of the EDIS (Emergency Department Information System) for "falls" in the age group chosen. EDIS is a computerised database in the ED with demographic information, presenting complaint, diagnosis and disposition for each patient. Medical records: A predetermined dataset was recorded from the medical record for each patient presenting to the ED. This included medical record number, age, sex, type of residence (home, hostel or nursing home), prefall mobility, nature of fall, alcohol misuse, recurrent fall, referral status, triage category, injury score, specific area of the body injured, fracture, admission, specialty, length of stay, mortality, and discharge disposition. Prefall mobility was further defined as unaided versus aided (use of a stick, frame, crutches, assistance by another person) versus unknown. Trauma Registry: Additional data were obtained from the hospital's Trauma Registry. An Injury Severity Score (ISS) is calculated for patients requiring admission after trauma. ISS is the sum of the squares of the highest Abbreviated Injury Scores (an anatomical system classifying injuries by body region on a scale of 1 [minor] to 6 [serious]) for the three most seriously injured body regions. ISS ranges from 1 (minor injury) to 75 (severe injury).13 CCIS: For patients transferred to an affiliated geriatric and rehabilitation hospital, the patient information database (CCIS [Central Sydney Area Health Service Clinical Information System]) was accessed for the length of stay. None of the patients in our study were transferred to non-affiliated geriatric and rehabilitation hospitals. Population data: The Australian Bureau of Statistics supplied population data for the hospital's catchment area.14 Definitions Fall: "Inadvertently coming to rest on the ground or other lower level with or without loss of consciousness."15 Extrinsic (accidental) causes: Environmental factors (eg, rugs, steps, uneven floors). Falls as a result of external trauma, such as motor vehicle accidents and violence, were excluded. Intrinsic (non-accidental) causes: Syncope, dizziness or vertigo, postural drop, central nervous system lesion (haemorrhage or infarct), drop attack, and balance or gait disturbance. Alcohol misuse: A history of alcohol misuse related temporally to the event, a record of alcohol on the breath, or a statement in the ED record about the patient's being intoxicated. Statistical analysis We used Minitab Statistical Software16 for statistical analysis and performed χ2 tests. Analysis was based on age group or sex and compared with a number of variables: presentation as a result of a fall, nature of the fall, outcome of a fracture, and admission status. A multivariate analysis was performed on four aspects of the falls considered to be related to place of residence or mobility: extrinsic cause, recurrent falls, fracture/no fracture and admission. Odds ratios (95% CI) were calculated for each of these groups. Multivariate analysis was also used to calculate odds ratios (95% CI) for whether alcohol use contributed to selected outcomes: admission (yes/no), extrinsic or recurrent falls versus other falls, and age under or over 80 years. Results Patient characteristics Of a total of 22 782 patients presenting to the ED during the six-month study period, 4489 (19.7%) were patients older than 65 years and 803 (17.8%) of these patients presented as a direct consequence of a fall. Of these patients, 733 (91.3%) had medical records available for review at the time of analysis and complete for the purposes of the dataset. Age and sex: The average age was 78.6 years (range, 65-101 years) and the median age was 79 years: 263 patients were aged 65-74 years, 279 were 75-84 years and 191 were 85 years or older. Increasing age of the patients was associated with presenting to the ED as a result of a fall (χ2 test for trend, P < 0.001) (Box 1). There were 283 men and 450 women. However, the number of men and women presenting to the ED after a fall reflected the age and sex distribution within the catchment population (Box 2). Thus, men were as likely as women to present as a result of a fall. Residence: At the time of the fall, 83% (211/253) of the 65-74 year olds, 74% (200/269) of the 75-84 year olds and 57% (109/191) of those over 85 years were living in their own homes. Thus, the proportion of those living in either a hostel or a nursing home increased with advancing age. In 20 patients residence could not be classified. Previous falls: 39% of the men (111/283) and 24% of the women (110/450) had fallen before. Mobility: Patients were classified according to mobility: walking aided or unaided. As expected, as the patients aged the use of a walking aid increased. Cause of fall Extrinsic or intrinsic: Overall, extrinsic causes for the fall accounted for 42.7% of patients presenting to the ED. In the age group 65-74 years extrinsic causes accounted for 49.4% of falls, which is more than expected when compared with the proportion in the older age groups (39.0% and 38.7%, respectively). Intrinsic causes were more likely with advancing age (χ2 test; P = 0.018) and accounted for 50.5% (95% CI, 45%-57%), 60.9% (95% CI, 55%-67%) and 64.2% (95% CI, 54%-68%) of falls in the respective age groups. The breakdown of all causes for falls presenting to the ED is shown in Box 3. Despite extensive review of the medical records we were unable to classify 23% of falls as either extrinsic or intrinsic. Alcohol misuse: This was documented in 78 patients (10.6%): 18% of the 65-74 year olds, 10% of the 75-84 year olds, and was not a factor in those over 85 years (χ2 test; P = 0.001). Sixty-five (83%) of these patients were living in their own homes. Multivariate analysis for alcohol misuse at the time of fall showed it to be significantly associated with an increased risk of both accidental and recurrent falls (Box 4). Outcomes Injury: 517 (70.5%) patients sustained an injury as a result of the fall: 73.3% (379/517) had an ISS of 4 or less (a score of 9 correlated with a femoral fracture); 13 patients had scores between 15 and 25, with all of these patients (except one with spinal cord compression) sustaining intracranial injury. The most common injuries were fractures (36.7%), soft tissue injuries (16%), lacerations and skin tears (14.5%). Fracture: 269 patients (36.7%) sustained a fracture: 36% (98/269) of which were neck-of-femur fractures, 16% fractured wrists, 12% fractured humeral neck and 5% pelvic fractures. The breakdown of fractures in each group is shown in Box 5. Women sustained both neck-of-femur and all fractures more frequently than men (χ2 test; P < 0.001): 64% (63/98) of femoral-neck fractures and 73% (125/171) of all other fractures (95% CI, 66%-80%). Interestingly, in women, the proportion of fractured neck of femur to all fractures was 33.5% (63/188) (95% CI, 27%-40%), whereas in men it was 43% (35/81) (95% CI, 32%-54%). Fracture rate overall was not found to be related to advancing age in either sex. Admission: The total number of patients admitted to hospital was 419, or 57.2% of all older patients with falls (representing 38% of all older patients admitted during the study period). Sixty-three per cent of those 85 years or older were admitted, compared with 60% of the 75-84 year olds and 50% of the 65-74 year olds (χ2 test; P = 0.009). Of the 269 patients with fractures, 200 (74%) were admitted. There was no statistically significant difference in the fracture admission rate across the age groups (χ2 test; P = 0.53). Of the 200 patients admitted, in 49% the cause of the fracture was intrinsic. Patients admitted to hospital after a fall had a mean length of stay of 10.4 days (95% CI, 10.2-10.6) and a median stay of 6 days (range, 1-129 days). Hospitalisation for more than 10 days was necessary in 35% (146/419) of patients. Deaths: Thirty-two patients died in hospital, representing 4.4% of all patients presenting to the ED after a fall: half of those who died were over 85 years of age and half were from nursing homes. In those who died, the cause of the fall was intrinsic rather than extrinsic (27/32), and the most common injury was a fracture of the neck of the femur (10/32). Data analysis: Multivariate analysis of place of residence or mobility and extrinsic cause, recurrent falls, fracture/no fracture and admission showed no significant interaction. Discussion We found that older patients presenting to the ED after a fall had a high injury rate (71%), high admission rates (57%) and often prolonged hospitalisation (> 10 days in about a third of those admitted). Our study complements others performed in Australia and elsewhere on older patients who fall, particularly those who present to an ED.11,12Some studies have found that women in the community fall more frequently than men,17 and others, as we did, found no difference.18 Institutionalised patients have been reported to have higher fall rates than patients living at home,17,19 but most of our patients lived at home and walked unaided. Falls may be caused by an environmental hazard alone or a simple syncopal event, or there may be a complex interaction of environment, physical illness, and type of activity. Changes in vision, vestibular function and proprioception affect physical stability, and musculoskeletal changes affect gait. Postural hypotension from dehydration, drug effects or autonomic dysfunction may be involved. Additionally, acute illness such as respiratory tract infection, arrhythmias, carotid sinus hypersensitivity,20 cardiac failure and neurological problems (eg, Parkinson's disease) may increase the risk of falling. All these intrinsic factors may be compounded by environmental hazards.5,6,17 We found gait disturbance, syncope, central nervous system lesion, postural hypotension and dizziness to be the most common intrinsic causes, and these were statistically more likely to be the underlying reason for a fall as age increased. The proportion of patients with falls in association with alcohol misuse contrasts with the findings of Adams et al.21 They surveyed older patients over an eight-week period for alcohol use, and found a negative relationship between alcohol use and falls. A high proportion of our patients with alcohol misuse lived at home, with perhaps easy access to alcohol. These patients had a greater risk of extrinsic and recurrent falls, a potential relationship that warrants further study. A UK study found that most falls in the community do not result in serious injury.17 We found that patients presenting to the ED after a fall have a high rate of injuries, consistent with previous reports,17,22 but the rate was significantly higher than that found by Tinetti et al.23 We found women to be statistically more likely to suffer a fracture than men. Grisso et al,10 in an older inner-city population in the United States, found that women generally had higher rates of fall injury than men. In addition, they found that injury rates increased with advancing age, a finding that we could not confirm. There were fewer hip fractures in older men than older women in our study, confirming previous findings.24 This is probably related to the higher prevalence of osteoporosis in women. Previous reports have shown that older men with hip fracture have higher mortality rates than age-matched women.23 The high admission rate in our study, which increased in older patients, is only slightly higher than that found by Richardson,11 but this was in patients over 75 years, in whom a higher admission rate is expected. A UK study found admission was needed in only 34% of patients.22 Admission rates for patients with a fracture did not vary significantly across our three age groups, nor were they different according to place of residence or prefall mobility. Length of hospital stay similarly did not depend on place of residence or prefall mobility, differing from the Richardson study, in which a significant relationship was found between accommodation status and outcome at 90 days.11 US studies report that 75% of deaths after a fall occur in patients over 65 years.6 We found that the single most important factor associated with death was hip fracture, a finding similar to that in previous studies.7,11 Modification of the environment and dealing with intrinsic problems such as drug side effects and gait dysfunction can reduce falls,25-27 prevent hospitalisation26 and shorten length of stay.15 If 95% of problems can be identified from the history and physical examination alone, as suggested by Rubenstein et al,15 the emergency physician is well able to identify those patients at risk of further falls. Intrinsic causes can be treated and the patient's general practitioner or specific falls prevention programs can then proceed to modify the risk of recurrence. References Australian Bureau of Statistics. Australia in brief (Census data, 1996). Canberra: ABS, 1998. <www.abs.gov.au> Davis JA. Older Australia: a positive view of ageing. Sydney: Harcourt Brace, 1994. Smith RD, Widiatmoko D. The cost-effectiveness of home assessment and modification to reduce falls in the elderly. Aust N Z J Public Health 1998; 22: 436-440. Spaite DW, Criss EA, Valenzuela TD, et al. Geriatric injury: an analysis of prehospital demographics, mechanisms and patterns. Ann Emerg Med 1990; 19: 1418-1421. Tinetti ME, Speechley M. Prevention of falls among the elderly. N Engl J Med 1989; 320: 1055-1059. Nelson RC, Murlidhar AA. Falls in the elderly. Emerg Med Clin North Am 1990; 8: 309-324. Rubenstein LZ, Josephson KR, Robbins AS. Falls in the nursing home. Ann Intern Med 1994; 121: 442-451. Nevitt MC, Cummings SR, Kidd S, Black D. Risk factors for recurrent nonsyncopal falls: a prospective study. JAMA 1989; 261: 2663-2668. Gostynski M, Ajdacic-Gross V, Gutzwiler F, Michel JP. Epidemiological analysis of accidental falls by the elderly in Zurich and Geneva. Schweiz Med Wochenschr 1999; 129: 270-275. Grisso JA, Schwarz DF, Wishner AR, et al. Injuries in an elderly inner city population. J Am Geriatr Soc 1990; 38: 1326-1331. Richardson DB. Elderly patients in the emergency department: a prospective study of characteristics and outcome. Med J Aust 1992; 157: 234-239. Stathers GM, Delpech V, Raftos JR. Factors influencing the presentation and care of elderly people in the Emergency Department. Med J Aust 1992; 156: 197-200. Baker SP, O'Neill B, Haddon W. The Injury Severity Score. J Trauma 1974; 14: 187. Needs Assessment and Health Outcomes Unit. A demographic profile of the Central Sydney Area Health Service from the 1996 Census. Sydney: Central Sydney Area Health Service, March 1998. Rubenstein LZ, Robbins AS, Josephson KR, Schulman BL. The value of assessing falls in an elderly population: a randomised clinical trial. Ann Intern Med 1990, 113: 308-316. Minitab Statistical Software [computer program], version 12. State College, Pa: Minitab Inc, 1998. Blake AJ. Falls in the elderly. Br J Hosp Med 1992; 47: 268-272. Campbell AJ, Borrie MJ, Spears GF, et al. Circumstances and consequences of falls experienced by a community population 70 years and over in a prospective trial. Age Ageing 1990; 19: 136-141. Cummings SR, Nevitt MC. Falls [editorial]. N Engl J Med 1993; 331: 872-873. Ward CR, McIntosh S, Kenny RA. Carotid sinus hyersensitivity -- a modifiable risk factor for fractured neck of femur. Age Ageing 1999; 28: 127-133. Adams WL, Magruder-Habib K, Trued S, Broome HL. Alcohol abuse in elderly Emergency Department patients. J Am Geriatr Soc 1992; 40: 1236-1240. Davies AJ, Kenny RA. Falls presenting to the Accident and Emergency Department: types of presentation and risk factor profile. Age Ageing 1996; 25: 362-366. Tinetti ME, Speechley M, Ginter SF. Risk factors for falls among elderly persons living in the community. N Engl J Med 1988; 319: 1701-1707. Diamond TH, Thornley SW, Sekel R, Smerdely P. Hip fracture in elderly men: prognostic factors and outcomes. Med J Aust 1997; 167: 412-414. Province MA, Hadley EC, Hornbrook MC, Lipsitz LA. The effects of exercise on falls in elderly patients: a preplanned meta-analysis of the FICSIT trials. JAMA 1995; 273: 1341-1347. Close J, Ellis M, Hooper R, Glucksman E. Prevention of falls in the elderly trial (PROFET): a randomised controlled trial. Lancet 1999; 353: 93-97. Tinetti ME, Baker DI, McAvay G, Claus EB. A multifactorial intervention to reduce the risk of falling among elderly people living in the community. N Engl J Med 1994; 331: 821-827. (Received 10 Aug 1999, accepted 29 May 2000) Authors' details Department of Emergency Medicine, Royal Prince Alfred Hospital, Sydney, NSW. Anthony J Bell, MB BS, Emergency Medicine Registrar. Janet K Talbot-Stern, MD, FACEM, FACEP, Director, Emergency Department; and Clinical Senior Lecturer, Department of Surgery, University of Sydney. Department of Medicine, University of Sydney, Sydney, NSW. Annemarie Hennessy, MB BS, PhD, Senior Lecturer. Reprints will not be available from the authors. Correspondence: Dr A J Bell, Department of Emergency Medicine, Royal Prince Alfred Hospital, Missenden Road, Camperdown, NSW 2050. Make a comment 1: Patients presenting to the emergency department, by age group, June - November, 1997 65-74 years (n=2060) 75-84 years (n=1672) ≥85 years (n=757) Total (n=4489) Presentation after a fall Other presentations 295 (14.3%) 1765 317 (19.0%) 1355 191 (25.2%) 566 803 (17.9%) 3686 χ2 test for age trend (P<0.001). Back to text 2: Age and sex distribution of patients presenting to the emergency department after a fall compared with the catchment population 65-74 years 75-84 years ≥85 years Men Presentation after a fall Proportion of catchment population 124/263 (47%) 15415/32185 (47.9%) 107/279 (38%) 7251/18448 (39.3%) 52/191 (27%) 1650/6038 (27.3%) Women Presentation after a fall Proportion of catchment population 139/263 (53%) 15770/32185 (49.0%) 172/279 (62%) 11187/18448 (60.6%) 139/191 (73%) 4388/6038 (72.7%) Back to text Back to text 4: Multivariate analysis (logistic regression) of alcohol misuse and selected variables in older patients presenting to the emergency department after a fall Variable Alcohol misuse odds ratio (95% CI) Age at presentation 5.5 (2.8-10.6) Extrinsic cause of fall 1.72 (1.05-2.83) Recurrent falls 2.24 (1.35-3.72) Back to text 5: Fractures in older patients presenting to the emergency department after a fall, by age group (years) Fracture 65-74 (n=263) 74-85 (n=279) >85 (n=191) Total (n=733) Neck of femur 28 (11%) 37 (13%) 33 (17%) 98 (13.4%) Other 74 (28%) 59 (21%) 38 (20%) 171 (23.3%) No fracture 161 (61%) 183 (66%) 120 (63%) 464 (63.3%) Back to text

Anthony J Bell · Janet K Talbot-Stern · Annemarie Hennessy

Research Moderate alcohol intake is associated with survival in the elderly: the Dubbo Study Leon A Simons, John McCallum, Yechiel Friedlander, Michael Ortiz and Judith Simons MJA 2000; 173: 121-124 For editorial comment, see Stockwell Abstract - Methods - Results - Discussion - Acknowledgements - References - Authors' details - - More articles on Cardiology and cardiac surgery Abstract Objective: To examine the relationship between alcohol intake and survival in elderly people. Design and setting: A prospective study over 116 months of non-institutionalised subjects living in Dubbo, a rural town (population, 34 000) in New South Wales. Participants: 1235 men and 1570 women aged 60 years and over who were first examined in 1988-89. Main outcome measures: All-causes mortality; gross cost of alcohol per life-year gained. Results: Death occurred in 450 men and 392 women. Intake of alcohol was generally moderate (ie, less than 14 drinks/week). Any intake of alcohol was associated with reduced mortality in men up to 75 years and in women over 64 years. In a proportional hazards model, the hazard ratio for mortality in men taking any alcohol was 0.63 (95% CI, 0.47-0.84) and in women was 0.75 (95% CI, 0.60-0.94). Cardiovascular deaths in men were reduced from 20/100 (95% CI, 14-26) to 11/100 (95% CI, 9-13) and in women from 16/100 (95% CI, 13-19) to 8/100 (95% CI, 6-10). The reduction in mortality occurred in men and women taking only 1-7 drinks/week -- hazard ratios, 0.68 (95% CI, 0.49-0.94) and 0.78 (95% CI, 0.61-0.99), respectively, with a similar protective effect from intake of beer or other forms of alcohol. After almost 10 years' follow-up, men taking any alcohol lived on average 7.6 months longer, and women on average 2.7 months longer, compared with non-drinkers. The gross cost for alcohol per life-year gained if consuming 1-7 drinks/week was $5700 in men, and $19 000 in women. Conclusions: Moderate alcohol intake in the elderly appears to be associated with significantly longer survival in men 60-74 years and in all elderly women. The consumption of moderate amounts of alcohol, compared with abstention or with heavy alcohol intake, appears to be associated with reduced all-causes mortality in middle-aged subjects.1-3 This effect may be partially mediated through a reduced risk of coronary heart disease (CHD)4 and stroke.5 Some studies attribute the protection to a specific effect of wine;6,7 other studies attribute it to any type of alcohol.8In elderly people, some of this benefit from moderate alcohol intake may be negated by mortality from other causes.9 In a prospective study of men and women aged 65 years and over in the United States (Established Populations for Epidemiologic Studies of the Elderly), alcohol intake under 21 drinks/week was associated with a 30%-40% lower all-causes mortality in two cohorts, but with no influence in a third cohort.10 In Australian men and women aged 60 years and over with 77 months' follow-up, the intake of 1-7 drinks/week was associated with a 22%-25% reduction in all-causes mortality, although this reduction did not achieve statistical significance.11 We have examined the relationship between alcohol intake and survival in this Australian cohort during a more extended follow-up of 116 months. We present the results and include an economic analysis of moderate alcohol intake. Methods Dubbo Study The Dubbo Study is an ongoing prospective examination of cardiovascular and other diseases in an elderly Australian cohort first examined in 1988-89. All non-institutionalised residents of Dubbo, New South Wales, born before 1930 were eligible; participation rate was 73% (1235 men and 1570 women). Methods and measures have already been described in detail.12,13 The baseline examinations comprised demographic, psychosocial and standard cardiovascular risk assessments, including examination of fasting blood samples. Alcohol usage Questions on alcohol usage were those asked in the National Heart Foundation Risk Factor Prevalence Study,14 and yielded an approximation of usual alcohol intake coded as zero, 1-7, 8-14, 15-28 and more than 28 drinks/week (referring to a standard drink containing 10 g of alcohol). Specific intakes of beer, wine and spirits were not separately sought, but subjects were asked whether they normally drank beer or not, allowing a separation of drinking behaviour into beer and "other". Survival analysis Outcomes from August 1988 to 31 December 1998 were included in the analysis, a median 116 months' follow-up. Hospitalisation and death records were monitored continuously, and postal surveys were conducted every two years to confirm vital status. The survey in 1997 successfully traced more than 98% of surviving participants. Records were coded according to the International classification of diseases, ninth revision, clinical modification (ICD-9-CM). The independent contribution of any risk factor to mortality was examined in a Cox proportional hazards model. Point estimates and 95% CIs for the relative hazard of death were calculated from the regression coefficients (presented as hazard ratio, a measure of relative risk). The models included categories of alcohol intake as described above, and, where relevant, a categorical term describing whether a subject normally drank beer or "other" (ie, wine/spirits). The proportional hazards model assumes constant relative hazard over the length of follow-up. This assumption was confirmed for each model by a plot of log-minus-log survival, demonstrating parallel curves over all categories of alcohol intake. Statistical analyses were conducted using SPSS for Windows NT.15 Economic analysis A weighted alcohol acquisition cost per week using the midpoint of the intake ranges was calculated for each alcohol intake stratum and for each sex using 1999 Dubbo club prices. Individuals were assumed to remain in their initial consumption strata over the whole time period. Survival curve data from the Cox model were used to calculate total expenditure on alcohol, as well as survival benefit for each stratum of intake. An incremental analysis (difference in cost/difference in benefit) was conducted using the no-alcohol-consumption stratum as the reference. This yielded an estimate of the gross cost per life-year gained. Although the study collects hospitalisation records, hospitalisation costs were not available and a net cost per life-year gained could not be estimated. Ethical approval The study was approved by the institutional ethics committees at St Vincent's Hospital, Sydney, the University of New South Wales and the Australian National University. All participants gave informed, written consent. Results Pattern of alcohol intake The pattern of alcohol intake and its clinical associations have been fully documented in an earlier report.11 The pattern of alcohol intake, by quantity and type, is shown in Box 1. On a day when alcohol was consumed, 40% of all men and 45% of all women took one or two drinks, 23% and 7% took three or four drinks, and 15% and 1%, respectively, took five or more drinks. All-causes mortality Death occurred in 450 men (36%) and 392 women (25%). Consumption of more than 14 drinks/week was uncommon. Hence, where relevant, the use of alcohol has been grouped into zero use and any use. Alcohol intake: Age-specific all-causes mortality by alcohol intake is presented in Box 2. Alcohol use in men appeared to be associated with reduced mortality up to age 74 years, but not beyond. In women, its use was associated with reduced mortality in all groups older than 64 years. Predictors of all-causes mortality: The independent contribution of alcohol to all-causes mortality was explored in men 60-74 years and in all women in proportional hazards models which adjusted for the presence of major demographic, psychosocial and cardiovascular variables at study entry. The significant predictors of all-causes mortality are summarised in Box 3. (Alcohol intake was not a significant predictor of mortality in men aged more than 74 years.) Any alcohol intake was significantly associated with reduced all-causes mortality in both sexes. Quantity or type of alcohol intake: The relationship between quantity or type of alcohol intake and all-causes mortality in the proportional hazards model is presented in Box 3. The risk of mortality was significantly reduced at all levels of alcohol intake, except in women taking 15-28 drinks/week (representing only 3% of women in the study). A similar degree of reduction in all-causes mortality was observed at all levels of alcohol intake. The protection observed was broadly similar in those using beer versus wine/spirits, although this only reached statistical significance for beer consumption. Pattern of alcohol intake: In a subsequent model, the quantity of alcohol consumed per week was replaced by a variable denoting the usual number of drinks taken on a given day, a measure of the pattern of drinking. Using zero intake as the reference group, the hazard ratio in men with a consumption of one or two drinks on a given day was 0.64 (95% CI, 0.46-0.89), with three or four drinks 0.68 (95% CI, 0.47-0.98), and with five or more drinks 0.69 (95% CI, 0.45-1.06). The corresponding hazard ratios in women were 0.74 (95% CI, 0.59-0.93), 0.68 (95% CI, 0.38-1.22) and 1.38 (95% CI, 0.58-3.29) (there were only 17 women in this group). Hazard curves: The hazard curves calculated from the proportional hazards models in men and women are presented in Box 4. By the end of almost 10 years' follow-up, men taking any alcohol lived on average 7.6 months longer, and women on average 2.7 months longer, than their counterparts taking no alcohol. Specific causes of death: Cardiovascular death (ie, CHD and stroke) was reduced from 20/100 (95% CI, 14-26) in non-drinkers to 11/100 (95% CI, 9-13) in men taking any alcohol. The corresponding reduction in cardiovascular death in women was from 16/100 (95% CI, 13-19) to 8/100 (95% CI, 6-10). Deaths attributed to any cancer were unchanged in men (6/100 [95% CI, 3-9] versus 7/100 [95% CI, 5-9]) and in women (4/100 [95% CI, 2-6] versus 5/100 [95% CI, 3-7]). Gross cost for alcohol per life-year gained From the number of life-years added to survival for each quantity of intake, we have estimated the gross cost for alcohol per life-year gained. In men 60-74 years and in women 60 years and over taking 1-28 drinks/week, the respective costs were $13 000 and $31 000 per life-year gained. Since much of the benefit from alcohol intake was observed at a moderate intake of only 1-7 drinks/week, the respective costs at this intake were $5700 and $19 000 per life-year gained. Discussion In this well-defined, community-based sample of rural elderly Australians, alcohol intake could be described as moderate rather than heavy.11 Our results confirm that any intake of alcohol is associated with significantly reduced all-causes mortality in men 60-74 years and in all elderly women, consistent with our previous report at 77 months' follow-up.11 Statistical significance has now been reached due to the greater number of deaths and increased statistical power. Absolute death rates in men were substantially higher than in women, especially in the "young old". This would account for the greater average survival advantage shown in Box 4 (7.6 months versus 2.7 months). Equivalent reductions in mortality occurred at 1-7 drinks/week and at higher intakes. In men there was no evidence of a differential effect between 1-2 drinks on a given day and an intake of five or more drinks on a given day. Not all studies have documented an association between all-causes mortality and alcohol intake.16,17 The reduction in CHD and stroke mortality associated with alcohol use we observed is consistent with findings of previous reports,8,18,19 as well as those of recent reports in large middle-aged cohorts from the United States.4,5,20 These data are gradually causing health authorities to reconsider public policy on moderate alcohol intake, say 1-7 drinks/week, in the prevention of future morbidity and mortality.21 Studies in younger populations indicate a "U"- or "J"-shaped relationship between alcohol intake and all-causes mortality.2 This has not been a general finding in the elderly, possibly because these cohorts contain an excess of "healthy survivors".10 It is surprising that we could find no relationship between alcohol intake and mortality in men aged over 74 years, but it is plausible that very elderly men lose the benefit of alcohol intake because they become subject to competing causes of mortality.9 There is a potential for misclassification of alcohol intake between zero and low intake because of under-reporting. This would diminish any apparent relative benefit of alcohol intake on all-causes mortality. Hence, our statistically significant findings may represent a minimum estimate of the benefit of moderate alcohol intake. We have demonstrated essentially a "threshold effect" between alcohol intake and all-causes mortality in either sex. Protection does not improve greatly as alcohol intake increases further (Box 3). Thus, under-reporting would then have less impact on our findings. This threshold effect is important, particularly if we were to move to a public health position of suggesting that abstainers should begin to imbibe! The economic findings take no account of any changes in healthcare costs arising downstream through the benefits or otherwise of alcohol intake. What we regard as an acceptable cost per life-year gained is arbitrary, but it is informative to compare our calculated costs with, for example, recently published gross costs for the use of simvastatin in patients with established CHD, with survival increased by around 20%.22 Assuming such patients receive lifetime therapy with simvastatin from their mid-50s, the gross cost per life-year gained in the UK population would be £5100 (or about $13 000). Although one is comparing unrelated "therapy", moderate alcohol intake, at least in older men, may turn out to be a popular and cost-effective means of improving survival which does not require government subsidy! The relative merits of wine versus other forms of alcohol consumption remain controversial. Data from France6 and Denmark7 highlight specific benefits of wine, and this has generated a new research effort to identify which components of wine, apart from alcohol, may be the most beneficial. Antioxidants are among the most prominent suggestions.23 Others consider that alcohol in any form gives protection against cardiovascular disease,8 largely through its effect in raising high density lipoprotein (HDL) cholesterol levels.11 In Dubbo, the quantity of alcohol intake was highly correlated with HDL cholesterol (r = 0.32, P < 0.001 and r = 0.23, P < 0.001 in men and women, respectively). Other suggested mechanisms for cardiovascular protection include favourable effects of alcohol on thrombotic and fibrinolytic pathways, reduced insulin resistance and improved endothelial function through increased nitric oxide production.5 Alcohol may also influence survival in ways which currently defy measurement: regular alcohol intake may reflect a special lifestyle integrated with less tangible factors.21 Although excess alcohol intake is undoubtedly toxic to the central nervous system, recent studies suggest that a moderate intake may reduce the risk of dementia. In a study of elderly French people 65 years and over, appropriately from Bordeaux, the rate of hospitalisation for dementia in non-drinkers over three years was 4.9/100, but only 3.9/100 in those taking any alcohol (with a more striking effect on the risk of Alzheimer's disease).24 During 116 months' follow-up in the Dubbo population, the respective rates of hospitalisation for dementia were 4.3/100 and 2.5/100 (P < 0.01). It is premature to promote the use of alcohol for prevention of dementia, but the 21st century may witness a completely new role for alcohol in health. Acknowledgements The Dubbo Study is supported in part by grants from the National Health and Medical Research Council of Australia, Astra Pharmaceuticals Pty Ltd, Amrad Pharmaceuticals Pty Ltd, Bristol-Myers Squibb Australia Pty Ltd, Merck Sharp & Dohme Australia Pty Ltd, Parke Davis Pty Ltd and Pfizer Pty Ltd. We acknowledge the dedication of the Dubbo Nurse-Manager Kerrie Pearson, the assistance of Gina Brinsmead in economic analysis and Helen Adams in preparation of the manuscript. References Klatsky AL, Armstrong MA, Friedman DD. Alcohol and mortality. Ann Intern Med 1992; 117: 646-654. Holman CDJ, English DR, Milne E, Winter MG. Meta-analysis of alcohol and all-cause mortality: a validation of NHMRC recommendations. Med J Aust 1996; 164: 141-145. Thun MJ, Peto R, Lopez AD, et al. Alcohol consumption and mortality among middle-aged and elderly US adults. N Engl J Med 1997; 337: 1705-1714. Albert CM, Manson JE, Cook NR, et al. Moderate alcohol consumption and the risk of sudden cardiac death among US male physicians. Circulation 1999; 100: 944-950. Berger K, Ajani UA, Kase CS, et al. Light-to-moderate alcohol consumption and the risk of stroke among US male physicians. N Engl J Med 1999; 341: 1557-1564. Renaud S, Geuguen R, Siest G, Salamon R. Wine, beer, and mortality in middle-aged men from Eastern France. Arch Intern Med 1999; 159: 1865-1870. Gronbaek M, Deis A, Sorensen TIA, et al. Mortality associated with moderate intakes of wine, beer or spirits. BMJ 1995; 310: 1165-1169. Rimm EB, Klatsky A, Grobbee D, Stampfer MJ. Review of moderate alcohol consumption and reduced risk of coronary heart disease: is the effect due to beer, wine or spirits? BMJ 1996; 312: 731-735. Van de Water HA, Boshuizen HC. The impact of substitute morbidity and mortality on public health policies. Leiden: TNO Prevention and Health, Division of Public Health and Prevention, 1995. Scherr PA, LaCroix AZ, Wallace RB, et al. Light to moderate alcohol consumption and mortality in the elderly. J Am Geriatr Soc 1992; 40: 651-657. Simons LA, Friedlander Y, McCallum J, Simons J. Alcohol intake and survival in the elderly: a 77 month follow-up in the Dubbo Study. Aust N Z J Med 1996; 26: 662-670. Simons LA, McCallum J, Friedlander Y, et al. Dubbo Study of the elderly: sociological and cardiovascular risk factors at entry. Aust N Z J Med 1991; 21: 701-709. Simons LA, McCallum J, Friedlander Y, Simons J. Predictors of mortality in the prospective Dubbo Study of Australian elderly. Aust N Z J Med 1996; 26: 40-48. Risk Factor Prevalence Study Management Committee. Risk Factor Prevalence Study: Survey No 3 1989. Canberra: National Heart Foundation Australia and Australian Institute of Health, 1990. SPSS for Windows NT [computer program], version 9.0. Chicago, Ill: SPSS Inc, 1999. Leino EV, Romelsjo A, Shoemaker C, et al. Alcohol consumption and mortality. II. Studies of male populations. Addiction 1998; 93: 205-218. Hart CL, Smith GD, Hole DJ, Hawthorne VM. Alcohol consumption and mortality from all causes, coronary heart disease, and stroke: results from a prospective cohort study of Scottish men with 21 years follow up. BMJ 1999; 318: 1725-1729. Hennekens CH, Willett W, Rosner B, et al. Effects of beer, wine and liquor in coronary deaths. JAMA 1979; 242: 1973-1974. Stampfer MJ, Colditz GA, Willett WC, et al. A prospective study of moderate alcohol consumption and the risk of coronary disease and stroke in women. N Engl J Med 1988; 319: 267-273. Sacco RL, Elkind M, Boden-Albala B, et al. The protective effect of moderate alcohol consumption on ischemic stroke. JAMA 1999; 281: 53-60. Hommel M, Jaillard A. Alcohol for stroke prevention? N Engl J Med 1999; 341: 1605-1606. Pickin DM, McCabe CJ, Ramsay LE, et al. Cost effectiveness of HMG-CoA reductase inhibitor (statin) treatment related to the risk of coronary heart disease and cost of treatment. Heart 1999; 82: 325-332. Frankel EN, Kanner J, Germann JB, et al. Inhibition of oxidation of human low-density lipoprotein by phenolic substances in red wine. Lancet 1993; 341: 454-457. Orgogozo J-M, Dartigues J-F, Lafont S, et al. Wine consumption and dementia in the elderly: a prospective community study in the Bordeaux area. Rev Neurol (Paris) 1997; 153: 185-192. (Received 23 Dec 1999, accepted 10 Apr 2000) Authors' details University of New South Wales Lipid Research Department, St Vincent's Hospital, Sydney, NSW. Leon A Simons, MD, FRACP, Associate Professor of Medicine; Judith Simons, MACS, Analyst-Programmer. Faculty of Health, University of Western Sydney MacArthur, Sydney, NSW. John McCallum, DPhil, Professor and Dean. Department of Social Medicine, Hebrew University - Hadassah Hospital, Jerusalem, Israel. Yechiel Friedlander, PhD, Associate Professor in Epidemiology. Pfizer Pty Ltd, Sydney, NSW. Michael Ortiz, PhD, Health Outcomes Manager. Reprints will not be available from the authors. Correspondence: Professor L A Simons, Lipid Research Department, St Vincent's Hospital, Darlinghurst, NSW 2010. l.simonsATnotes.med.unsw.edu.au Make a comment Back to text 2: Age-specific all-causes mortality rate and alcohol intake during 116 months' follow-up of subjects 60 years and over. Data are mortality rates per 100 subjects (95% CI and number of subjects in each group in parentheses) Men Women Zero alcohol Any alcohol Zero alcohol Any alcohol 60-64 y 65-69 y 70-74 y 75-79 y 80+ y All ages 26 (17-35) (88) 37 (24-50) (54) 57 (45-69) (65) 51 (35-67) (37) 83 (68-98) (23) 44 (38-50) (267) 17 (13-21) (326) 26 (21-31) (266) 41 (34-48) (184) 64 (55-73)(120) 83 (74-92) (63) 34 (31-37) (959) 9 (5-13) (193) 22 (16-28) (172) 31 (24-38) (154) 45 (36-54) (121) 72 (63-81) (104) 31 (28-34) (744) 10 (7-13) (288) 14 (9-19) (191) 11 (6-16) (166) 36 (27-45) (107) 54 (42-66) (68) 20 (17-23) (820) Back to text 3: Proportional hazards model of all-causes mortality and alcohol intake in elderly subjects Hazard ratio (95% CI) Men 60-74 years Women 60+ years Significant predictors of all-causes mortality Any alcohol intake Age (/year) Current smoker Ex-smoker Prior stroke Blood pressure medication Diabetes Atrial fibrillation Poor expiratory flow 0.63 (0.47-0.84) 1.07 (1.04-1.11) 2.81 (1.90-4.16) 1.76 (1.26-2.46) 1.58 (1.03-2.42) 1.54 (1.16-2.06) 1.99 (1.38-2.87) -- 1.53 (1.09-2.17) 0.75 (0.60-0.94) 1.08 (1.06-1.10) 1.74 (1.22-2.49) -- -- -- 2.06 (1.46-2.92) 2.77 (1.65-4.64) 2.00 (1.43-2.79) Relationship of quantity or type of alcohol to all-causes mortality Drinks/week Nil 1-7 8-14 15-28 >28 1.00 0.68 (0.49-0.94) 0.58 (0.39-0.85) 0.62 (0.40-0.95) 0.56 (0.33-0.96) 1.00 0.78(0.61-0.99) 0.66 (0.45-0.97) 0.67 (0.29-1.55) Alcohol type Nil Beer Wine/spirits 1.00 0.62 (0.46-0.84) 0.70 (0.44-1.12) 1.00 0.64 (0.47-0.86) 0.85 (0.66-1.11) The reference category for alcohol usage was zero intake. Other variables in the models were body mass index, family history of coronary heart disease (CHD), prevalent CHD, blood pressure, lipid levels, self-rated health, and physical disability. Poor expiratory flow refers to peak expiratory flow tertile I. Back to text Back to text

Leon A Simons · John McCallum · Yechiel Friedlander · Michael Ortiz · Judith Simons

Research A randomised crossover trial of chemotherapy in the home: patient preferences and cost analysis Danny Rischin, Michelle A White, Jane P Matthews, Guy C Toner, Kathryn Watty, Anthony J Sulkowski, Jan L Clarke and Lois Buchanan MJA 2000; 173: 125-127 Abstract - Methods - Results - Discussion - References - Authors' details - - More articles on Oncology Abstract Objectives: To determine patient preferences and cost differences between home-based and hospital-based chemotherapy. Design: Randomised crossover trial. Setting: A tertiary cancer hospital in Melbourne, Victoria. Participants: 20 patients who required chemotherapy suitable for administration at home. Interventions: Patients were assigned at random to receive their first chemotherapy treatment in either the home or the hospital and the second treatment in the alternative setting. Main outcome measures: Patient preference, costs. Results: There was universal agreement by the 20 patients in the randomised trial that home-based chemotherapy was the preferred option (P < 0.0001). No problems were nominated by the patients as being associated with home-based chemotherapy. Home-based treatment was estimated to result in an increased cost of $83 (P = 0.0002) for each chemotherapy treatment compared with hospital-based treatment. Reported advantages for chemotherapy in the home included the elimination of travel, reduction in treatment-associated anxiety, reduction in the burden on carers and family, and the ability to continue other duties. There were no significant complications associated with administration of chemotherapy in the home. Conclusions: Patients prefer home-based chemotherapy to hospital-based treatment. The future of chemotherapy-in-the-home programs in Australia will depend on whether patient preferences are deemed to offset any potential increase in costs. Patients with cancer who require treatment with chemotherapy will experience major changes in lifestyle and overall well-being. Some intravenous chemotherapy regimens require frequent visits to hospital to receive treatment. This may be time-consuming and inconvenient for a patient, and may also disrupt the lives of other family members and carers. The concept of home-based therapy is not new,1-3 but there have been few reports on chemotherapy-in-the-home programs, and these have had a different emphasis from our study (eg, costs [in a US paediatric population];4 costs and safety [in a retrospective review of an Australian adult population]5). We performed a randomised crossover trial, the aim of which was to compare (i) patient preference for hospital-based versus home-based chemotherapy; and (ii) the cost of therapy administered in hospital versus that in the home. Methods Patient eligibility Patients were considered eligible if they met the following criteria: they were to receive chemotherapy that was suitable to be given at home; their first two treatments were planned to be identical; they had not received chemotherapy in the preceding 12 months; they lived in an area that was geographically suitable for treatment at home; and they were aged 18 years or over. Patients gave written informed consent and the study was approved by the ethics committee of the Peter MacCallum Cancer Institute. Study design At enrolment, patients were randomly assigned to receive their first chemotherapy treatment in hospital and the second at home, or their first treatment at home and the second in hospital. They were assigned according to a computer-generated randomisation chart, using an allocation scheme based on a biased coin design.6Chemotherapy treatment refers to the first two administrations of chemotherapy. Following completion of the first two treatments, patients filled out a questionnaire regarding the two different locations of therapy. Questions focused on (i) patients' preference for where to receive their remaining chemotherapy after completing their two study treatments; and (ii) any perceived difficulties or advantages of treatment in hospital or in the home. Chemotherapy nurse specialists who also worked in the chemotherapy day ward at the hospital administered all home chemotherapy treatments. Patients were reviewed by a doctor before each chemotherapy cycle. Cost assessment Cost comparisons for hospital-based versus home-based therapy were made specifically from the perspective of the treating hospital, not the patient or society in general. Costs were estimated using Transition software (Eclipsys Transition Systems, Boston, MA), which distributes direct and indirect costs for an entire financial year between patient episodes on the basis of the services received. It was decided to compare only those components of the cost for which there could be a genuine difference to the hospital attributable to the site of delivery of the chemotherapy. Thus, costs related to patient records, allied health, medical staff and pharmacy were excluded. All overheads associated with the chemotherapy-in-the-home program, including vehicle costs and travelling time, were apportioned by Transition to nursing costs on the basis of time spent with each patient. Similarly, hospital overheads were apportioned on the basis of nursing times. The cost of providing a single meal was included in the hospital costs. Statistical methods A target sample size of 20 eligible patients with identical chemotherapy for their first two treatments was chosen, to provide 84% power to test the null hypothesis that no one setting is preferred versus the alternative hypothesis that at least 85% of patients prefer one setting over the other, using a two-sided test of significance at a significance level of 0.05. To determine if significantly more patients preferred treatment at home rather than in hospital, or vice versa, the proportion of patients preferring to have their third treatment in the same location as their first treatment was compared between the two randomisation arms using Fisher's exact test for 2 x 2 contingency tables. This test is valid even if there are "period" effects -- that is, if patients tolerate their second chemotherapy treatment better than their first, or vice versa.7 Standard methods for a 2 x 2 crossover trial7 were used to compare costs of chemotherapy in hospital with costs in the home, and costs between the first and second chemotherapy given ("period" effects), after ensuring there were no significant carryover effects. (Carryover effects were tested by comparing the sum of the costs in the home and hospital for patients in the "hospital first" arm with patients in the "home first" arm.) Statistical significance and 95% confidence intervals (CIs) were estimated from the means and standard errors assuming a Student's t-distribution. Two-sided P-values have been given throughout. All statistical tests were carried out using Stat Xact 4 (CYTEL Software Corporation, Cambridge, MA, 1998) and Microsoft Excel (Microsoft Corporation, Redmond, WA, 1996) software. Results Patient selection and profile The trial accrued the target 20 patients, out of a total of 64 registered on the chemotherapy-in-the-home program, between February 1996 and March 1997 (see Box 1). Patient demographics are shown in Box 2. Patient preferences When asked where they would have preferred to receive their first two treatments if they had had their time again, 70% of patients expressed a preference for having both treatments at home, while none said they would have preferred to have both treatments in hospital (Box 3). Patients were then asked to nominate their preferred site for the remaining treatments (the primary endpoint of the trial). All 20 patients (100%; 95% CI, 83%-100%) preferred to have their remaining therapy given at home (P < 0.0001). None of the patients in the trial reported concerns with chemotherapy being given in their home; however, four (20%) reported concerns with treatment in hospital, relating to transport difficulties and waiting times. Eighteen (90%) of the patients felt there were advantages with treatment in the home. The reasons given included convenience; avoidance of travel and parking problems (particularly not having to travel while feeling unwell); reduction in treatment-associated anxiety; not burdening their carers and family; and being able to continue other duties, such as caring for their dependants. Only one patient felt there were specific advantages to chemotherapy in the hospital. This patient felt it was good to see other people who were worse off. No major complications of chemotherapy administration (eg, hypersensitivity reactions or extravasation) were reported. Costing Overall, chemotherapy in the home was associated with an estimated average increased cost of $83 (95% CI, $46-$120; P = 0.0002) relative to the cost of chemotherapy in the hospital. The average cost of the first treatment was estimated to be $57 more than the cost of the second (95% CI, $20-$94; P = 0.0044). There was no carryover effect (P = 0.16). Discussion This study has demonstrated that patients have an overwhelming preference for home-based therapy. Clearly, home-based therapy is not possible, or indeed appropriate, for all patients. Patients living outside designated geographical areas or having special needs that can be met in the hospital setting (eg, need for an interpreter) would be more easily treated at the hospital.8 Complex or prolonged chemotherapy regimens or those associated with a risk of an immediate serious complication are more appropriately administered in the hospital day ward setting. Nevertheless, many commonly administered chemotherapy regimens are suitable for administration in the home, and this study clearly demonstrates that, given the choice, patients prefer to have such treatments at home. While in our study the cost of home-based treatment was on average $83 higher than the cost of hospital-based therapy, this estimate did not include costs to the patient (such as travelling costs, lost time for the patient or carers, and childcare costs). These could all have made the hospital episode more costly relative to the home episode. Furthermore, given that the cost per visit for any chemotherapy-in-the-home program is dependent on the throughput of patients and the geographical spread of the patients, an increase in the frequency of home visits or a more limited geographical spread of patients might further reduce the difference between home and hospital costs. Unlike some other hospital-in-the-home programs, chemotherapy in the home does not necessarily result in cost savings to the administering hospital, as treatment in the hospital does not require overnight admission. The future of chemotherapy-in-the-home programs in Australia will depend on how governments, hospital administrators, oncologists and nurses balance the overwhelming patient preference for treatment at home with any potential increase in costs. References Grayson ML, Silvers J, Turnidge J. Home intravenous antibiotic therapy. A safe and cost effective alternative to inpatient care. Med J Aust 1995; 162: 249-253. Koopman MMW, Prandoni P, Piovella F, et al. Treatment of venous thrombosis with intravenous unfractionated heparin administered in the hospital as compared with subcutaneous low molecular weight heparin administered at home. N Engl J Med 1996; 334: 682-687. Bielory L, Long GC. Home health care costs: intravenous immunoglobulin home infusion therapy. Ann Allergy Asthma Immunol 1995; 74(3): 265-268. Close P, Burkey E, Kazak A, et al. A prospective, controlled evaluation of home chemotherapy for children with cancer. Pediatrics 1995; 95: 896-900. Lowenthal RM, Piaszczyk A, Arthur GE, et al. Home chemotherapy for cancer patients: cost analysis and safety. Med J Aust 1996; 165: 184-187. Wei LJ, Lachin JM. Properties of the urn randomization in clinical trials. Control Clin Trials 1988; 9: 345-364. Jones B, Kenward MG. Design and analysis of cross-over trials. London: Chapman and Hall Ltd, 1989. Zalcberg JR, Siderov J, Petty M. Outpatient chemotherapy: there's no place like home - sometimes. Med J Aust 1996; 165: 182. (Received 11 Oct 1999, accepted 24 May, 2000) Authors' details Peter MacCallum Cancer Institute, Melbourne, VIC. Danny Rischin, MB BS(Hons), FRACP, Consultant Medical Oncologist, Division of Haematology and Medical Oncology; Michelle A White, MB BS(Hons), FRACP, Clinical Fellow, Division of Haematology and Medical Oncology; Jane P Matthews, BSc(Hons), PhD, AStat, Director, Statistical Centre; Guy C Toner, MD, BS, FRACP, Head of Medical Oncology, Division of Haematology and Medical Oncology; Kathryn Watty, RN, RM, Clinical Nurse Consultant, Division of Nursing; Anthony J Sulkowski, RN, BEd, Clinical Nurse Consultant, Division of Nursing; Jan L Clarke, RN, Clinical Nurse Consultant, Division of Nursing; Lois Buchanan, RN, RM, Clinical Nurse Consultant, Division of Nursing. Reprints will not be available from the authors. Correspondence: Dr D Rischin, Division of Hematology and Medical Oncology, Peter MacCallum Cancer Institute, Locked Bag 1, A'Beckett Street, Melbourne, VIC 8006. drischinATpetermac.unimelb.edu.au Make a comment Click in box for larger version Back to text 2: Patient demographics, by randomisation arm (first chemotherapy treatment given at hospital vs first treatment at home). Values are number of patients unless otherwise stated Hospital first Home first Total (%) Sex Male Female 1 8 4 7 25% 75% Age Median (years) Range (years) 40-49 50-59 60-69 70 61 47-71 0 2 1 5 1 59 26-69 1 4 1 5 0 -- -- 5% 30% 10% 50% 5% Diagnosis Breast cancer Colon cancer Non-Hodgkin's lymphoma Pancreatic cancer 5 3 0 1 5 5 1 0 50% 40% 5% 5% Chemotherapy CMF(P)* 5-FU† ± folinic acid or levamisole CHOP‡ 5 4 0 5 5 1 50% 45% 5% Support at home Spouse/parent Parent Son/daughter Other Not specified 4 1 3 0 1 7 0 1 3 0 55% 5% 20% 15% 5% * Cyclophosphamide, methotrexate, 5-fluorouracil ±prednisolone. † 5-Fluorouracil. ‡Cyclophosphamide, doxorubicin, vincristine and prednisolone. Back to text 3: Preferred location for chemotherapy treatments, by randomisation arm (first chemotherapy treatment given at hospital vs first treatment at home). Values are number of patients Hospital first Home first Total (%) For first 2 treatments Both at home First at home, second at hospital No preference First at hospital, second at home Both at hospital 7 0 1 1 0 7 2 1 1 0 14 (70%) 2 (10%) 2 (10%) 2 (10%) 0 For subsequent treatments Home Hospital 9 0 11 0 20 (100%) 0 Back to text

Danny Rischin · Michelle A White · Jane P Matthews · Guy C Toner · Kathryn Watty · Anthony J Sulkowski · Jan L Clarke · Lois Buchanan

Research Early discharge and postnatal depression: a prospective cohort study Jane F Thompson, Christine L Roberts, Marian J Currie and David A Ellwood MJA 2000; 172: 532-536 For editorial comment see Lumley Abstract - Methods - Results - Discussion - Acknowledgements - References - Authors' Details - - More articles on Psychiatry Abstract Objectives: To determine whether women discharged from hospital ≤ 72 hours after childbirth (early discharge) were at greater risk of developing symptoms of postnatal depression during the following six months than those discharged later (late discharge), their reasons for early discharge and their level of postnatal support. Design and setting: Population-based, prospective cohort study with questionnaires at Day 4, and at 8, 16 and 24 weeks postpartum, conducted at all birth sites in the Australian Capital Territory (ACT). Participants: Women resident in the ACT giving birth to a live baby from March to October 1997. Main outcome measure: A score > 12 on the Edinburgh Postnatal Depression Scale (EPDS). Results: 1295 (70%) women consented to participate; 1193 (92%) were retained in the study to 24 weeks and, of these, 1182 returned all four questionnaires. Of the 1266 women for whom length-of-stay data were available, 467 (37%) were discharged early and 799 (63%) were discharged late. There were no significant differences between the proportion of women discharged early who ever scored > 12 on the EPDS during the six postpartum months and those discharged late (17% v. 20%), even after controlling for other risk factors (adjusted OR, 0.67; 95% CI, 0.44-1.01). Of women discharged early, 93% had at least one postnatal visit at home from a midwife and 81% were "very satisfied" with the care provided. Most women (96%) reported they had someone to help in practical ways. Conclusions: Women discharged early after childbirth do not have an increased risk of developing symptoms of postnatal depression during the following six months. In Australia, and internationally, the length of time spent in hospital following childbirth has been steadily decreasing since the early 1980s. This has prompted concern about the consequences of early discharge for both mothers and babies.1,2 Postnatal depression (PND) is a common disorder with long-term consequences for both mother and infant.3,4 It has been associated with psychosocial and obstetric factors3,5-7 and possibly dissatisfaction with length of stay.8,9 The association with early discharge is not clear. A small randomised controlled trial of early discharge from Sweden10 reported no difference in depression, while in a similar Canadian study women discharged early were less likely to be depressed.11 In observational studies, women discharged early have been reported to be either equally8,9,12,13 or less likely14,15 to be depressed. A recent Australian study reported an increased risk of PND in women discharged early.16 However, this study made no detailed assessment of support available to women, a factor that may be critical to emotional wellbeing of new mothers.17Here, we aimed to investigate whether early discharge following childbirth was associated with an increased risk of PND, why women elect early discharge, and to examine the social support available to women after discharge from hospital. Methods Participants This population-based, prospective cohort study included women resident in the ACT, planning to reside there for at least six months, aged ≥ 16 years, who gave birth to a live baby between March and October 1997 in any of the ACT's two public hospitals (one included a birth centre), two private hospitals, or at home. Women were excluded if their baby was admitted to the neonatal intensive care unit or adopted, if critically ill themselves, unable to give informed consent or complete the questionnaires for other reasons, or participating in another study. Participants were compared with all women who gave birth in the ACT during 1997 using data from the ACT Maternal and Perinatal Data Collection.18 Procedure The study was approved by the ACT Department of Health & Community Care Research Ethics Committee, and the ethics committees of participating hospitals. Postnatal ward or domiciliary midwives gave information sheets to women in the first few days after giving birth. Participants gave written informed consent when completing the first questionnaire as close to Day 4 as possible. They were then mailed questionnaires at eight, 16, and 24 weeks postpartum. Questionnaires The first questionnaire covered sociodemographic characteristics of mother and partner, a nine-item personality scale identifying "vulnerable" and "resilient" personality dimensions;16 a maternity "blues" questionnaire;19 a subset of four items from the Medical Outcomes Study Social Support Scale;20 questions about availability of and satisfaction with practical support, emotional support from partner, and a single summary question assessing global satisfaction with partner scored on a five-point Likert scale. Three questions asked about the nature of women's past relationship with their parents in relation to warmth/care, overprotection/controlling and independent decision making, with responses on a four-point scale. Questions were also included about the mother's history of depression (at any time as well as during or after a pregnancy) and whether the infant was breastfed. In the second questionnaire, women were asked to indicate whether any of a list of 30 possible reasons for their actual length of stay applied to them and whether they thought their length of stay was too long, about right or too short. The third questionnaire included questions about the number of and satisfaction with domiciliary visits. Satisfaction was measured by quality of care, accessibility and convenience,21 and a single summary question assessing overall satisfaction with care. Postnatal depression Postnatal depression was assessed at eight, 16 and 24 weeks using the 10-item Edinburgh Postnatal Depression Scale (EPDS), a self-report measure of depression developed for use in the postpartum period.22-24 Women scoring above 12 are likely to be suffering from a depressive illness. Length of stay For comparability with previous Australian research,16 and in keeping with ACT definitions, early discharge was defined as discharge up to 72 hours after giving birth, and late discharge as more than 72 hours after giving birth. Power of study A sample size of 944 is sufficient to detect with 95% confidence and 80% power an increase in prevalence of PND in the early discharge group at eight, 16 or 24 weeks from 7% to 14%,16 assuming 30% are discharged early and an overall attrition rate of 25%. To allow for variations in these assumptions, we set a target sample size of 1200 women. Statistical analyses The prevalences of EPDS scores greater than 12 were compared between women discharged early and late by means of contingency tables and unconditional logistic regression. We used logistic regression to assess the effect of previously identified risk factors on the association between early discharge and high EPDS scores. Six separate models were fitted for women ever scoring > 12 during the six postpartum months; for those who scored > 12 at eight weeks, 16 weeks or 24 weeks; and for women who scored > 12 on either two occasions or all three occasions. Results are expressed as crude and adjusted odds ratios (OR) with 95% confidence intervals. Results Study population Of 1961 ACT residents asked to participate in the study, 105 were ineligible and 1295 (70%) of the remainder agreed to participate. After 24 weeks, 1193 (92%) remained in the study. Of the 1295 who agreed to participate, 869 (67%) gave birth in a public hospital, 411 (32%) in a private hospital, and 15 (1%) at home, of whom six were transferred to hospital. Compared with all women who gave birth in 1997, participants were slightly older, more likely to be married or in a defacto relationship, to have given birth in a private hospital, and to have been discharged late (Box 1). The 102 (8%) who were lost to follow-up differed from those who remained in that they were significantly (P ≤ 0.001) more likely to be aged < 25 years (32% v. 12%), unmarried (14% v. 4%), born in a non-English-speaking country (19% v. 9%), and public patients (74% v. 56%). They were not significantly more likely to be in the early discharge group (46% v. 36%), but were significantly (P ≤ 0.001) less likely to be in paid employment in the previous 12 months (56% v. 74%), to have a paid position to resume after maternity leave (43% v. 63%) and to have been educated beyond Year 11 (60% v. 82%). They did not differ with respect to the following factors known to be associated with PND: vulnerable personality, level of social support, past history of depression, dissatisfaction with relationship with partner, or dissatisfaction with past relationship with mother. Length of stay After excluding the nine women who gave birth at home and were not transferred to hospital, and the 20 with missing data, there were length-of-stay data for 1266 (98%) women, 467 (37%) with early and 799 (63%) with late discharge. The early discharge group was significantly (P ≤ 0.001) more likely to be aged < 25 years (21% v. 10%), public patients (80% v. 44%) or to have delivered in a public hospital (94% v. 52%), multiparous (61% v. 54%), and to have given birth at > 39 weeks' gestation (85% v. 75%). Women discharged early were also significantly (P ≤ 0.001) more likely to have had a spontaneous onset of labour (74% v. 55%), an unassisted vaginal birth (90% v. 56%) and to formula-feed their infant from birth (10% v. 5%). They were significantly (P ≤ 0.001) less likely to have been in paid employment in the past 12 months (68% v. 76%), to have a paid position to resume (55% v. 66%) and to have been educated beyond Year 11 (74% v. 84%). They were significantly (P ≤ 0.001) less likely to rate their length of stay as "about right" than women discharged late (72% v. 82%), and more likely to rate their length of stay as "too short" (23% v. 8%). There were no statistically significant differences in vulnerable personality (17% v. 16%), level of social support (median score, 7 for both groups), past history of depression (29% v. 29%), maternity blues score (median score, 4 v. 5), dissatisfaction with partner (8% v. 6%), and past relationship with mother (not warm/caring, 6% v. 5%; overprotective/controlling, 52% v. 52%; did not encourage independent decision-making, 20% v. 21%). Postnatal depression Of the 1252 (97%) women with complete data at eight weeks postpartum, 129 (10%) scored > 12 on the EPDS. At 16 weeks, 91 of 1219 (8%) and at 24 weeks 90 of 1187 (8%) scored > 12. The cumulative incidence of an EPDS score > 12 over the six months of follow-up was 224/1295 (17%). Among women with complete data, 37/1172 (3%) had EPDS scores > 12 on two occasions and 23/1172 (2%) on all three occasions. Length of stay and postnatal depression Women discharged early were not more likely to ever score > 12 on the EPDS during the six months of follow-up than women discharged late: 72/429 (17%) compared with 150/751 (20%). The association between length of postnatal stay and PND symptoms remained statistically non-significant after adjusting for other risk factors (Box 2). This finding was robust for other outcome measures (Box 3). For all outcomes there was a consistent trend towards a reduced risk of PND symptoms for women discharged early. Reasons for choosing early discharge Reasons were given by 447 women (96%). The most common reason was a preference to be at home with their partner or family (74%). Other reasons were feeling confident with their baby and preferring to be at home (73%); so the father could be more involved in baby care (47%); being unhappy in hospital and unable to sleep or rest (41%); greater privacy (41%); to rest or recover after the birth (40%); not liking hospitals (34%); to establish breastfeeding (33%); and to have time to focus on the baby (32%). Of the women discharged early, 15% said they did not feel they had a choice about length of stay, and 14% felt under pressure from midwives to leave early. Women discharged early who felt they had no choice about length of stay were not significantly more likely to ever score > 12 on the EPDS (17% v. 17%), and neither were those who felt pressured to leave early (21% v. 16%; P = 0.4). Early discharge and postnatal support All women discharged within three days were eligible for home visits from midwives. Data were available on the number and nature of these visits for 432 women discharged early (93%). Of these, 404 (94%) had at least one visit, and 176 (41%) were visited up to Day 7. The maximum number of visits in the first seven days was 12, and 107 women (27%) were visited at least once after seven days. Eighty-eight per cent of the women thought the number of visits was "just right", while 8% thought it "not enough" and 4% "too many". Overall, 81% of these women said they were "very satisfied" with the care provided at home, 15% "satisfied in some ways but not in others" and 4% "very dissatisfied". Some women discharged after 72 hours were also eligible for and received home visits. The participating public hospitals' policy was for home visiting to be available up to Day 3, but sometimes this extended beyond 72 hours depending on the time of birth. Home visits were also available in cases of special need, and community-based maternal and child health nurses and midwives also offer some home visiting. Of the women discharged late, 364 (47%) received at least one visit at home from a midwife. In addition to support provided by health professionals, 96% of women discharged early reported that they had someone to help in practical ways in the first eight weeks postpartum. For 92% this was a partner, and for 47% their mother. Other family members (22%), friends (20%) and mothers-in-law (19%) were the next most common sources of help. The help received was satisfactory for 90% of the respondents; however, 23% said that they would like to know more people who could be asked for help. There were no statistically significant differences between women discharged early or late in availability of and satisfaction with practical help. Discussion The postnatal stay has become shorter without being properly evaluated in randomised controlled trials (RCTs). As shorter stays have become standard practice, the window of opportunity for conducting an appropriate RCT may have been lost.25 The best alternatives are prospective studies with heterogeneous samples of sufficient size to detect clinically significant effects of short postnatal stays. We found that women resident in the ACT electing short postnatal stays were not at increased risk for developing symptoms of PND. Our finding is consistent with those from two Victorian surveys,8,13 but differs from that of a study in Sydney which found a significantly increased risk of PND during the first six months in mothers discharged within three days.16 There are several possible explanations for the discrepant results between this study and our own, including differences in the outcome measures, population characteristics, postnatal support and reasons for early discharge. The same assessment tool to identify possible cases was used in the Victorian,8,13 Sydney16 and ACT studies, but in the Sydney study a psychiatric interview was added to confirm the diagnosis of PND. The use of a psychiatric examination is unlikely to explain differences in the results, as high scores on the EPDS coincide closely with diagnoses of PND. A validation study in Australian women found the EPDS to be highly sensitive (100%) and specific (96%), with a positive predictive value of 70%.22 Differences in the characteristics of women discharged early may also contribute to the different outcomes observed. In both the Sydney and the ACT studies, women discharged early were more likely to be multiparous, to have a lower level of education and to formula feed their infants in the first week than women discharged late. However, the women discharged early in the Sydney study16 were more likely than those in our study to report a poor relationship with parents and to have a history of depression; these associations were controlled for in the statistical analyses in the Sydney study and so cannot fully explain their different findings. Low levels of social support have been identified as a risk factor for PND,5 and another possible explanation for the differences in findings is that the two populations differed in the extent, nature of and satisfaction with postnatal support provided to women through early discharge programs and non-professional contacts. The authors of the Sydney study reported that only half of the women who elected early discharge participated in an early discharge program with domiciliary midwifery care.26 In our study, 94% of the women discharged early had had at least one visit from a midwife at home and the level of satisfaction with this care was high. Also, only 4% of women discharged early said they had no one to provide practical support at home. An overwhelming majority reported that their partners assisted them and most were satisfied with the level of help. Early discharge was introduced partly to offer more choices in care in a climate of increasing consumer participation in decisions. However, economic imperatives to increase patient throughput may lead to increasing pressure on women to leave hospital earlier than they would otherwise choose. The Sydney study26 did not report reasons for early discharge. Reasons given by women for leaving ACT hospitals early were generally positive, although 15% felt they did not have a choice and 14% felt pressured to leave (not mutually exclusive reasons). Several things should be considered when interpreting the results of our study. Firstly, as the Sydney study found double the rate of PND after early discharge,16 we formed our null hypothesis (that early discharge makes no difference) in the expectation that it would be disproved. Instead, we found no evidence of a significant difference in the rate of PND; in fact, early discharge tended to a protective effect (but this was not statistically significant). Our study does not prove that there is not an increased rate of PND for early discharge. However, in this population, it is unlikely that the true risk for early discharge was double that for late discharge. Secondly, although only 70% of women approached participated in the study, the characteristics of women who did participate were similar in important respects to those of the source population. However, our findings may not be generalisable to populations with differing PND risk factors or early discharge programs. Lastly, the women in our study selected their length of postnatal stay. Although we have controlled for known determinants, confounding by unknown determinants for PND cannot be excluded. We found that women who selected early discharge from hospital after childbirth and received midwifery support at home, and who were well supported by other family members, were not more likely to experience depressive symptoms in the first six months after childbirth. Very few women in this study were discharged early without home support, so it was not possible to determine whether early discharge without support was associated with an increased risk of PND symptoms. It may be important to ensure that all women discharged early after childbirth, in particular those lacking other sources of support, receive additional help from the healthcare system. What constitutes adequate postnatal support could be examined by RCTs comparing different patterns of home visiting. Acknowledgements This work was supported by a project grant from The Canberra Hospital Private Practice Fund. Additional funding was provided by The Canberra Hospital Auxiliary, the Nurses' Board of the ACT, and the ACT Department of Health & Community Care. The assistance of the midwives in recruiting women for this study is gratefully acknowledged. Robyn Attewell provided statistical advice. We are especially grateful to the women of the ACT who so generously gave their time to complete this study. References Buist AE. Counting the costs of early discharge after childbirth [editorial]. Med J Aust 1997; 167: 236-237. Braveman P, Egerter S, Pearl M, et al. Problems associated with early discharge of newborn infants. Early discharge of newborns and mothers: a critical review of the literature [review]. Pediatrics 1995; 96: 716-726. Boyce PM, Stubbs JM. The importance of postnatal depression. Med J Aust 1994; 161: 471-472. Murray L, Cooper P. Effects of postnatal depression on infant development. Arch Dis Childhood 1997; 77: 99-101. O'Hara MW, Swain AM. Rates and risk of postpartum depression -- a meta-analysis. Int Rev Psychiatry 1996; 8: 37-54. Boyce PM, Todd AL. Increased risk of postnatal depression after emergency caesarean section. Med J Aust 1992; 157: 172-174. Warner R, Appleby L, Whitton A, Faragher B. Demographic and obstetric risk factors for postnatal psychiatric morbidity. Br J Psychiatry 1996; 168: 607-611. Astbury J, Brown S, Lumley J, Small R. Birth events, birth experiences and social differences in postnatal depression. Aust J Public Health 1994; 18: 176-184. Dowswell T, Piercy J, Hirst J, et al. Short postnatal hospital stay: implications for women and service providers. J Public Health Med 1997; 19: 132-136. Waldenström U. Early and late discharge after hospital birth: fatigue and emotional reactions in the postpartum period. J Psychosomatic Obstet Gynaecol 1988; 8: 127-135. Carty EM, Bradley CF. A randomized, controlled evaluation of early postpartum hospital discharge. Birth 1990; 17: 199-204. Beck CT, Reynolds MA, Rutowski P. Maternity blues and postpartum depression. J Obstet Gynecol Neonatal Nurs 1992; 21: 287-293. Brown S, Lumley J, Small R. Early obstetric discharge: does it make a difference to health outcomes? Paediatr Perinat Epidemiol 1998; 12: 49-71. Burnell J, McCarthy M, Chamberlain GVP, et al. Patient preference and postnatal hospital stay. J Obstet Gynaecol 1982; 3: 43-47. James ML, Hudson CN, Gebski VJ, et al. An evaluation of planned early postnatal transfer home with nursing support. Med J Aust 1987; 147: 434-438. Hickey AR, Boyce PM, Ellwood D, Morris-Yates AD. Early discharge and risk for postnatal depression. Med J Aust 1997; 167: 244-247. Barclay KM, Chamberlain ME, Homer CS, Barclay LM. Early discharge and risk for postnatal depression [letter]. Med J Aust 1998; 168: 419-420. Bourne M. Maternal and perinatal status, ACT, 1997 tables. Canberra: Clinical Epidemiology and Health Outcomes Centre, ACT Department of Health & Community Care, 1999. Kennerley H, Gath D. Maternity blues. 1. Detection and measurement by questionnaire. Br J Psychiatry 1989; 155: 356-362. Sherbourne CD, Stewart AL. The MOS social support survey. Soc Sci Med 1991; 32: 705-714. Kenney P, Cameron S, King M, et al. Evaluation of obstetric early discharge: client satisfaction. Centre for Health Economics Research & Evaluation. Discussion Paper Series No 10. 1992. Boyce P, Stubbs J, Todd A. The Edinburgh postnatal depression scale: validation for an Australian sample. Aust N Z J Psychiatry 1993; 27: 472-476. Cox JL, Holden JM, Sagovsky R. Detection of postnatal depression: development of the 10-item Edinburgh Postnatal Depression Scale. Br J Psychiatry 1987; 150: 782-786. Murray L, Carothers AD. The validation of the Edinburgh Postnatal Depression Scale on a community sample. Br J Psychiatry 1990; 157: 288-290. Thompson JF, Roberts CL, Ellwood DA. Early discharge after childbirth: Too late for a randomised trial? Birth 1999; 26: 192-195. Hickey AR, Boyce PM, Morris-Yates AD, Ellwood DA. Early discharge and risk for postnatal depression [letter]. Med J Aust 1998; 168: 420. (Received 7 Oct 1999, accepted 3 Apr 2000) Authors' Details The Canberra Hospital, Garran, ACT. Jane F Thompson, MSc, PhD, Senior Research Officer, Women's & Children's Health. Marian J Currie, BapplSc, GDPH, Midwife, Maternity and Gynaecology Outpatients and Fetal Medicine Unit. David A Ellwood, FRANZCOG, Dphil, Professor of Obstetrics and Gynaecology, The Canberra Clinical School. New South Wales Centre for Perinatal Health Services Research, Departments of Obstetrics and Gynaecology and Public Health and Community Medicine, School of Population Health Services Research, University of Sydney, NSW. Christine L Roberts, MB BS, MHP, Senior Lecturer. Reprints: Dr J F Thompson, Women's and Childrens Health, The Canberra Hospital, PO Box 11, Woden, ACT 2606. jane.thompsonATact.gov.au ©MJA 2000

Jane F Thompson · Christine L Roberts · Marian J Currie · David A Ellwood

Abstract Objectives: To compare rates of mortality from coronary heart disease (CHD) between populations living within and outside Australian capital city statistical divisions. Design and setting: Descriptive epidemiological study based on data for all residents of Australia aged 30-69 years who died between 1986 and 1996 in all States and Territories of Australia. Main outcome measures: Standardised mortality rates from all causes and coronary heart disease as coded by the Australian Bureau of Statistics, and estimated excess deaths in populations living outside capital city statistical divisions. Results: Between 1986 and 1996, mortality from CHD declined by 46% in men and 51% in women, and accounted for 61% of the decline in mortality from all causes in men and 48% in women. More deaths than expected from acute myocardial infarction resulted in mortality rates from CHD up to 30% higher in men and 21% higher in women living outside the capital city statistical divisions, and accounted for an overall estimated excess of 3835 deaths from CHD in men (32% of excess deaths from all causes), and 1385 deaths from CHD in women (27% of excess deaths from all causes) over the 11-year study period. Conclusions: Although there were impressive declines in coronary mortality in all Australian States and Territories from 1986 to 1996, populations living outside capital cities continue to have higher death rates from CHD. These differences in mortality rates indicate a need for further research into factors which may influence mortality rates for CHD in rural and remote areas, and immediate measures to ensure optimal treatment of coronary risk factors and acute coronary events in such populations. Coronary heart disease (CHD) remains the largest single cause of death in Australia.1 Although there has been a steady decline in the death rate associated with CHD over the past 30 years, rates of decline have not been equal throughout Australia.2,3 A study of coronary mortality in Tasmania showed higher rates of mortality outside the capital city region.4 We examined official data for Australian men and women aged 30-69 years between 1986 and 1996 for evidence of differences in rates of death from CHD between capital city and regional populations. Methods The Australian Bureau of Statistics (ABS) collects and disseminates social, demographic and economic statistics for 66 Statistical Divisions based on an Australian Standard Geographical Classification (ASGC).5 The boundaries of capital city statistical divisions are determined by the anticipated development of the city for a period of at least 20 years, and delimit an area that is stable for general statistical purposes. Statistical divisions outside a capital city are relatively homogeneous regions characterised by identifiable social and economic links between the inhabitants and between the economic units within the region, under the unifying influence of one or more major towns or cities. We obtained ABS estimates of the size of the Australian population aged 30-69 years, and its distribution between capital city and other statistical divisions for the years 1986 and 1996. We also obtained ABS data for mortality from all causes, and from CHD, acute myocardial infarction (AMI) and subacute and chronic myocardial ischaemia for men and women aged 30-69 years living within and outside capital city statistical divisions for each year from 1986 to 1996. We excluded deaths at 70 or more years because certification of the cause of death in older people may be unreliable.6 We defined mortality from CHD as deaths with an underlying cause classified under rubrics 410, 411, 413 and 414 of the International classification of diseases, ninth revision (ICD-9-CM),7 with mortality from AMI classified under ICD-9-CM rubric 410, and mortality from subacute and chronic myocardial ischaemia classified under rubrics 411, 413, 414. Statistical methods Annual age-standardised rates for mortality from all causes, CHD, AMI and subacute and chronic myocardial ischaemia were calculated as follows: The number of deaths in each age group (30-39, 40-49, 50-59 and 60-69 years), coded to each cause of death category, were summed. Age-specific rates were calculated and then standardised with weightings obtained from Segi's "world population" (World Health Organization standard population).8 The normal approximation for the distribution was used to calculate 95% confidence intervals. For each State and the Northern Territory, we calculated expected numbers of deaths in each age group for populations living outside capital city statistical divisions by applying age-specific mortality rates from populations living within the capital city statistical division. Differences between the actual (observed) number of deaths and the expected number of deaths were then summed across 10-year age strata to give total expected numbers of deaths. Excess deaths were calculated as the difference between the sum of the observed and the sum of the expected number of deaths for all States and the Northern Territory. The population of the Australian Capital Territory living outside the Canberra Statistical Division was less than 0.1% of the total population of the ACT and was not included in the calculation. Results Population size and distribution Unpublished regional population data from the ABS estimated that, in 1986, there were 7 174 246 Australians aged 30-69 years, 64.4% of whom lived in capital city statistical divisions. The sex distribution in capital cities was 49.9% men and 50.1% women, compared with 51.0% men and 49.0% women outside capital cities. By 1996, the estimated population of Australians aged 30-69 years had increased to 8 793 107, 63.5% of whom lived in capital city statistical divisions. The sex distribution in capital cities was 49.8% men and 50.2% women, compared with 50.7% men and 49.3% women outside capital cities. Trends in mortality rates among men Between 1986 and 1996, mortality from all causes in all 30-69-year-old Australian men declined by 23%; this decline within capital city statistical divisions was 25%, compared with 21% among men living outside capital city statistical divisions (Box 1). Mortality from all causes in populations outside the capital cities remained higher than in capital city populations, with the difference increasing from 12% in 1986 to 18% in 1996. Between 1986 and 1996, mortality from CHD in Australian men aged 30-69 years declined by 46% and accounted for 61% of the decline in all-cause mortality. Mortality among men living within capital city statistical divisions declined by 49%, compared with 41% among men living outside capital city statistical divisions (Box 1). Mortality from CHD in populations outside the capital cities remained higher than in capital city populations, with the difference increasing from 13% in 1986 to 30% in 1996. Mortality from AMI among men living within capital city statistical divisions declined by 62%, compared with 50% among men living outside capital city statistical divisions (Box 1). Mortality from AMI in men living outside the capital cities remained higher than in capital city populations, with the difference increasing from 24% in 1986 to 63% in 1996. Excess mortality outside capital city statistical divisions Box 2 shows that, among men, CHD accounts for 32% of the excess deaths from all causes from 1986 to 1996 occurring outside the capital city statistical divisions. Among those deaths coded as CHD, observed deaths from AMI exceeded expected deaths by 5487. The number of excess deaths from CHD is smaller than that from AMI, as there was a higher rate of death from subacute and chronic myocardial ischaemia in capital city populations. Observed deaths from AMI among men aged 30-39 years living outside capital city statistical divisions exceeded expected deaths by 79%; corresponding figures for the remaining age groups were 72% (40-49 years), 51% (50-59 years), and 25% (60-69 years). Trends in mortality rates among women Between 1986 and 1996, mortality from all causes in all 30-69-year-old Australian women declined by 21%; this decline within capital city statistical divisions was 24%, compared with 18% among women living outside capital city statistical divisions (Box 1). Mortality from all causes in populations outside the capital cities remained higher than in capital city populations, with the difference increasing from 6% in 1986 to 15% in 1996. Between 1986 and 1996, mortality from CHD in Australian women aged 30-69 years declined by 51% and accounted for 48% of the decline in all-cause mortality. Mortality among women living within capital city statistical divisions declined by 54%, compared with 50% among women living outside capital city statistical divisions (Box 1). Mortality from CHD in populations outside the capital cities remained higher than in capital city populations, with the difference increasing from 13% in 1986 to 21% in 1996. Mortality from AMI among women living within capital city statistical divisions declined by 59%, compared with 54% among women living outside capital city statistical divisions (Box 1). Mortality from AMI in women living outside the capital cities remained higher than in capital city populations, with the difference increasing from 24% in 1986 to 38% in 1996. Excess mortality outside capital city statistical divisions Box 2 shows that, among women, CHD accounts for 27% of the excess mortality from all causes occurring outside the capital city statistical divisions. Observed deaths from AMI exceeded expected deaths by 1479. Observed deaths from AMI among women aged 30-39 years living outside capital city statistical divisions exceeded expected deaths by 108%; corresponding figures for the remaining age groups were 75% (40-49 years), 44% (50-59 years), and 20% (60-69 years). Overall mortality Box 3 shows that death rates from CHD outside capital cities are consistently higher than within capital cities in all Australian States and the Northern Territory, the only exception being mortality from CHD among women in the Northern Territory in 1986. Discussion The contribution of reduced CHD mortality to the overall decline in all-cause mortality in Australia from 1986 to 1996 was 61% for men and 48% for women. However, our findings show that CHD mortality rates were higher outside capital cities, and that discrepancies increased from 1986 to 1996 and were largest in younger age groups. It is likely that the differences we found in CHD mortality are real, as they are matched by parallel trends in all-cause mortality rates, and at least two studies have confirmed the validity of deaths coded by the ABS to CHD.9,10 While a study based on 1979 data questioned the validity of subcategories of CHD such as rubric 410 (AMI),11 we found consistently higher death rates from AMI in populations outside capital cities in all Australian States and the Northern Territory (data not shown), despite variations in medical certification requirements between States. The apparent higher rates of mortality in capital city populations from subacute and chronic CHD may be the result of a coding anomaly or of deaths occurring in large population centres after patients were moved there for the management of their subacute or chronic CHD. Our study was limited to documenting the difference in CHD mortality between capital cities and other areas. Clearly, an understanding of the factors associated with higher CHD mortality outside capital cities has implications for prevention and improved treatment of CHD. This would require detailed examination of population characteristics to determine which populations outside capital cities, including subpopulations such as Indigenous people, are most at risk of higher mortality. It is also necessary to consider factors such as differences in socioeconomic status, in risk factors for CHD, and in access to medical care. Previous reports showed that the decline in mortality from CHD in NSW was slower in lower income populations, many of which were in rural or regional areas.12,13 Also, sudden cardiac death in Tasmanian men was found to occur twice as frequently in unemployed men compared with employed men.14 While the association between populations with lower socioeconomic status and higher risk for CHD is recognised, the actual factors that influence this association have not been well delineated. Risk factors for CHD clearly have an influence on mortality. Much of the decline in mortality from CHD in Finland from 1972 to 1992 can be explained by changes in the three main coronary risk factors: serum cholesterol level, blood pressure and smoking.15 In Australia, the National Heart Foundation (NHF) Risk Factor Prevalence Surveys found significant declines between 1980 and 1989 in the prevalence of hypertension and cigarette smoking, but no overall favourable trend in lipid levels.16 However, these surveys are limited to capital cities, and it is not known whether regional areas of Australia have seen the same trends in risk factor prevalence. In 1992, a major risk factor prevalence survey based on the 1989 NHF Risk Factor Prevalence Survey was undertaken in two rural regions of Tasmania. The prevalence of major coronary risk factors was consistent with the high rate of mortality from CHD among men in North-West Tasmania, but did not explain variation in rates of mortality in women across the three regions of Tasmania.17 Differences in mortality from CHD may be the result of differential incidences of CHD or differences in case-fatality rates. A detailed study of sudden cardiac death among previously asymptomatic men found that the higher rate of deaths in the two rural regions of Tasmania occurred mostly among men for whom symptomatic CHD could have been diagnosed, implying a higher case-fatality rate for CHD.14 This finding was supported by higher rates of coronary deaths occurring after hospitalisation in the two rural regions of Tasmania from 1986 to 1989,4 and in Newcastle in 1984.18 A higher case-fatality rate may result from differences in risk of death from factors such as previous infarction, delays in reaching medical care, or differences in medical care.19 While the relative geographic isolation of most populations outside the capital cities may be expected to result in delays in reaching secondary and tertiary medical centres, the findings of the MONICA study did not support changes in time to medical care (including ambulance staff) having a significant effect on deaths before hospitalisation in major population centres.18 A significant decline in case fatality after hospitalisation did, however, make an important contribution to the overall decline in coronary deaths in the MONICA centres of Auckland (New Zealand), Newcastle (Australia) and Perth (Australia) from 1984 to1993. Medical management of acute coronary events has changed substantially over the past 20 years. The use of aspirin, thrombolytic therapy and coronary angioplasty as first-line treatments for AMI has resulted in reductions in mortality of up to 43%.20,21 The use of thrombolytic therapy in the MONICA centres increased from being rare in the early 1980s, to being used in approximately 50% of hospitalised patients with non-fatal definite myocardial infarction or coronary death by the early 1990s.22,23 The benefits of such treatments are dependent on them being given soon after the event,24 and it is not clear whether populations living at any distance from secondary or tertiary medical centres experience delays in access to new treatment methods for symptomatic CHD. In southern Tasmania between 1992 and 1996, 849 doses of streptokinase and tissue plasminogen activator were administered for AMI. No thrombolytic therapy was administered outside the capital city of Hobart (Royal Hobart Hospital Pharmacy Supplies Report), despite 15% of the population of the Southern Region living outside the capital city and having mortality rates approximately 40% higher than the capital city population. In conclusion, although there have been impressive declines in mortality from CHD in all Australian States and Territories over the past 30 years, the 35% of the Australian population living outside the capital cities continue to have higher coronary mortality. Our results indicate the need for increased research into factors which may influence mortality rates for CHD in rural and remote areas. Acknowledgements This study was supported by funding from Roche Products Pty Ltd and the Tasmanian branch of the AMA, and by assistance in-kind from the Hobart City Council and Australian Hospital Care Ltd. We are grateful to Chris Sweeney from the Australian Bureau of Statistics and to the Pharmacy Department of the Royal Hobart Hospital. References Tonkin AM, Bennett S. Cardiovascular disease at the turn of the century. Med J Aust 1999; 170: 408-409. Gibberd RW, Dobson AJ, Florey C du Ve, Leeder SR. Differences and comparative declines in ischaemic heart disease mortality among sub-populations of Australia 1969-1978. Int J Epidemiol 1984; 13: 25-31. Sexton PT, Woodward DR, Gilbert N, Jamrozik K. Interstate differences in trends in coronary mortality and risk factors in Australia. Med J Aust 1990; 152: 531-534. Sexton PT, Jamrozik K, Walsh J, et al. Regional variation in coronary mortality within Tasmania. Med J Aust 1992; 157: 449-451. Australian Bureau of Statistics. Australian Standard Geographical Classification. Canberra: ABS, 1998. Christie D. Mortality from cardiovascular disease. Med J Aust 1974; 1: 390-393. National Coding Centre, Faculty of Health Sciences, University of Sydney. Australian version of the international classification of diseases. 9th revision, clinical modification (ICD-9-CM). 2nd ed. Vol.1: Tabular list of diseases. Sydney: NCC, University of Sydney, July 1996. Doll R. Comparison between registers, age-standardised rates. IARC Sci Publ 1976; 3: 453-459. Martin CA, Hobbs MST, Armstrong BK. Estimation of myocardial infarction mortality from routinely collected data in Western Australia. J Chron Dis 1987; 40: 661-669. Sexton PT, Jamrozik K, Walsh J. Death certification and coding for ischaemic heart disease in Tasmania. Aust N Z J Med 1992; 22: 114-118. Dobson AJ, Gibberd RW, Leeder SR. Death certification and coding for ischaemic heart disease in Australia. Am J Epidemiol 1983; 117: 397-405. Burnley IH. Inequalities in the transition of ischaemic heart disease mortality in New South Wales, Australia. Soc Sci Med 1998; 47: 1209-1222. Taylor R, Chey T, Bauman A, Webster I. Socio-economic, migrant and geographic differentials in coronary heart disease occurrence in New South Wales. Aust N Z J Public Health 1999; 23: 20-26. Sexton PT, Jamrozik K, Walsh J. Sudden unexpected cardiac death among Tasmanian men. Med J Aust 1993; 159: 467-470. Vartiainen E, Puska P, Pekkanen J, et al. Changes in risk factors explain changes in mortality from ischaemic heart disease in Finland. BMJ 1994; 309: 23-27. Bennett SA, Magnus P. Trends in cardiovascular risk factors in Australia. Results from the National Heart Foundation's Risk Factor Prevalence Study, 1980-1989. Med J Aust 1994; 161: 519-527. Thomson A, Rundle S, Singh BB, et al. Regional differences in cardiovascular risk factor prevalence in Tasmania: are they consistent with the increased cardiovascular mortality. Aust N Z J Med 1995; 25: 290-296. Beaglehole R, Stewart AW, Jackson R, et al. Declining rates of coronary heart disease in New Zealand and Australia, 1983-1993. Am J Epidemiol 1997; 145: 707-713. Beaglehole R. Medical management and the decline in mortality from coronary heart disease. BMJ 1986; 292: 33-35. Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico (GISSI). Effectiveness of intravenous thrombolytic treatment in acute myocardial infarction. Lancet 1986; 1: 397-402. Second International Study of Infarct Survival Collaborative Group. Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17 187 cases of suspected acute myocardial infarction: ISIS-2. Lancet 1988; 2: 349-360. Doggen CJM, van der Palen J, Beaglehole R. Trends in medical management of acute myocardial infarction. N Z Med J 1993; 106: 278-281. Dobson AJ, Jamrozik KD, Hobbs MST, et al. Medical care and case fatality from myocardial infarction and coronary death in Newcastle and Perth. Aust N Z J Med 1993; 23: 12-18. Bett JHN. LATE assessment of thrombolytic efficacy with alteplase (rt-PA) six-24 hours after onset of acute myocardial infarction. Aust N Z J Med 1993; 23: 745-748. (Received 23 Sep 1999, accepted 31 Jan 2000) Authors' details The Hobart Private Hospital, Hobart, TAS. Peter T Sexton, PhD, FAFPHM, Director of Medical Services; Tiina-Liisa H Sexton, BCom, CA, Research Assistant. Reprints: Dr P T Sexton, The Hobart Private Hospital, Cnr Argyle and Collins Streets, Hobart, TAS 7000. 1: Comparison of mortality rates between populations aged 30-69 years living within and outside capital cities in Australia Back to text 2: Estimated excess deaths from all causes, CHD and AMI among men and women living outside capital city statistical divisions from 1986 to 1996 Age group (years) 30-3940-4950-5960-69Total Men Mortality from all causes Observed deaths8599126982622760856108380 Expected deaths736310718216195672596425 Excess deaths123619804608413111955 Mortality from CHD (ICD-9-CM 410, 411, 413, 414) Observed deaths682270372391824128865 Expected deaths493209959021653625030 Excess deaths189604 133717053835 Mortality from AMI (ICD-9-CM 410) Observed deaths470197253341328721063 Expected deaths263114435411062815576 Excess deaths207828 179326595487 Women Mortality from all causes Observed deaths38877021138633146756238 Expected deaths32025998119722991851090 Excess deaths6851023189115495148 Mortality from CHD (ICD-9-CM 410, 411, 413, 414) Observed deaths143537 187869379495 Expected deaths91381 150361358110 Excess deaths52156 3758021385 Mortality from AMI (ICD-9-CM 410) Observed deaths102391 140050736966 Expected deaths49223 97242435487 Excess deaths53168 4288301479 CHD=coronary heart disease. AMI=acute myocardial infarction Back to text 3: Mortality within and outside capital city statistical divisions by Australian States and Territories Men Age-standardised mortality rate per 100000 (95% CI) % changeEstimated excess 1986 1996 per yeardeaths from CHD All causesCHDAll causesCHDfrom CHD1986-1996 New South Wales Capital722 (702-741)223 (212-234)511 (496-527)106 (99-113)-4.8 Balance761 (736-786)232 (218-246)601 (581-622)143 (133-153)-3.51506 Victoria Capital658 (638-678)199 (188-210)487 (470-503)97 (90-105)-4.7 Balance755 (722-789)242 (223-261)583 (556-611)131 (118-144)-4.21015 Queensland Capital691 (657-724)226 (207-245)549 (523-575)122 (109-134)-4.2 Balance754 (723-785)227 (210-245)585 (562-609)136 (125-147)-3.6444 South Australia Capital653 (619-687)213 (194-232)528 (499-557)125 (110-139)-3.8 Balance707 (650-764)234 (201-267)633 (583-683)160 (135-186)-2.9291 Western Australia Capital638 (603-673)183 (164-202)498 (471-525)102 (89-114)-4.0 Balance779 (716-841)249 (214-285)594 (546-642)121 (100-143)-4.7203 Tasmania Capital605 (526-684)141 (103-179)595 (520-669)102 (71-133)-2.5 Balance758 (685-831)276 (232-320)619 (558-680)144 (115-174)-4.3243 Northern Territory Capital640 (463-817)115 (46-185)716 (569-863)97 (36-158)-1.4 Balance1443 (1206-1679)233 (138-329)1030 (862-1199)132 (73-191)-3.9133 Australian Capital Territory 598 (521-675)205 (159-251)428 (372-484) 111 (82-140)-4.2 All of Australia Capital679 (668-690)209 (203-215)510 (501-519)107 (103-111)-4.4 Balance763 (747-778)237 (228-245)602 (590-614)139 (133-145)-3.83835 Women Age-standardised mortality rate per 100000 (95% CI) % changeEstimated excess 1986 1996 per yeardeaths from CHD All causesCHDAll causesCHDfrom CHD1986-1996 New South Wales Capital391 (377-405)82 (76-88)284 (273-296)32 (28-36)-5.5 Balance420 (401-439)89 (80-97)335 (319-350)45 (39-51)-4.5564 Victoria Capital360 (346-375)65 (59-72)274 (262-286)31 (27-35)-4.8 Balance361 (338-384)68 (58-77)307 (287-327)35 (28-41)-4.4277 Queensland Capital371 (347-395)67 (57-78)308 (288-328)39 (32-46)-3.8 Balance378 (355-400)75 (65-85)299 (282-316)36 (30-42)-4.7171 South Australia Capital347 (323-371)69 (58-79)285 (264-306)31 (24-38)-5.0 Balance291 (317-400)83 (64-103)339 (301-377)39 (26-52)-4.8143 Western Australia Capital349 (324-374)59 (49-70)275 (255-295)37 (30-45)-3.4 Balance386 (339-433)78 (296-372)334 (57-99)36 (24-49)-4.9105 Tasmania Capital424 (360-488)68 (42-93)365 (308-422)49 (28-70)22.5 Balance421 (367-475)87 (62-111)385 (336-434)54 (36-72)-3.462 Northern Territory Capital434 (271-597)46 (-10-103)392 (261-523)41 (-3-86)-1.0 Balance911 (702-1120)37 (-6-81)762 (593-932)88 (28-148)+12.563 Australian Capital Territory 380 (319-440)56 (32-80)267 (223-311)41 (23-59)-2.4 All of Australia Capital372 (363-380)71 (68-75)284 (278-291)33 (31-36)-4.9 Balance396 (384-407)80 (75-85)326 (317-335)40 (37-44)24.51385 CHD=coronary heart disease. Capital=within capital city statistical divisions. Balance=outside capital city statistical divisions. Back to Text

Peter T Sexton · Tiina-Liisa H Sexton

Research Prevention of perinatal group B streptococcal disease: screening practice in public hospitals in Victoria Mary Connellan and Euan M Wallace MJA 2000; 172: 317-320 For editorial comment, see Oats Abstract - Introduction - Methods - Results - Discussion - Acknowledgements - References - Authors' details - - More articles on Infectious diseases and parasitology Abstract Objectives: To survey clinical protocols for prevention of early-onset group B streptococcal disease (EOGBSD) of the newborn in public maternity hospitals. Design: Postal questionnaire with telephone follow-up when required. Setting: All hospitals that undertook deliveries in public patients in the State of Victoria, November 1997 to January 1998. Results: The survey was sent to 84 hospitals: 71 responded and 64 met the criteria and provided usable data (76% response rate). These 64 represented 42 784 births (68% of births in Victoria in 1996). Most hospitals (62; 97%) undertook actions that would identify and treat pregnant women at risk of EOGBSD. 48 (75%) performed bacteriological screening for maternal GBS carriage, but only 20 of these had a unified protocol. Screening was mostly by low vaginal swab (15 hospitals) and before 30 weeks' gestation (12 hospitals). Low vaginal swab plus anal swab was used in only one hospital. Bacteriological screening was significantly more common in metropolitan hospitals than in rural hospitals (100% versus 67%; P = 0.007, Fisher's exact test). Targeting of prophylaxis by recognised risk factors was reported by 59 (92%) hospitals, 45 of which also undertook screening. There was considerable variation in the specific risk factors used. Conclusions: While there was clearly widespread awareness of EOGBSD in Victorian public hospitals, prevention programs varied considerably. The development of consensus practice guidelines might improve EOGBSD prevention, reducing morbidity, mortality and costs. Introduction Since the 1970s, group B streptococci (GBS) have been recognised as a major cause of neonatal systemic infection in the first week of life -- so called early-onset group B streptococcal disease (EOGBSD). The reported incidence of this condition varies between 1 and 4 per 1000 livebirths.1 Infants acquire the infection by vertical transmission from an asymptomatic mother during delivery.2 Clinical disease manifests at birth or within 24-48 hours as pneumonia, septicaemia or, less commonly, meningitis.1In Australia, the prevalence of GBS vaginal carriage has been estimated at 12%-15%,3-5 and about 1%-2% of infants born to women carrying GBS develop EOGBSD, with about 6% of cases being fatal.2,5-7The risks of EOGBSD and death are particularly high in preterm infants.2 However, antibiotic prophylaxis given to "at risk" women during labour has been shown to significantly reduce the incidence of EOGBSD, and is an important and worthwhile public health measure.2,7-9 While the value of prophylactic antibiotic intervention in at-risk women is now widely agreed, the best means of targeting these women is perhaps less clear. Comprehensive reviews of the available evidence have been published both in Australia1,5,10 and overseas.2,11-13 There are two broad approaches to targeting prophylaxis -- identification of GBS carriers by bacteriological screening or treating by clinical risk factors. No trials have compared the efficacy of the two approaches. It is therefore perhaps not surprising that, anecdotally, GBS intervention practices differ greatly between public hospitals across the State of Victoria. However, no objective data are available to assess the extent of these differences and the appropriateness of current practice. We surveyed all public maternity hospitals in Victoria to explore what GBS intervention programs were in place and, in particular, to assess whether practice was in line with currently available evidence. Methods The Victorian Perinatal Data Collection Unit, Melbourne, provided contact details of all maternity hospitals in Victoria and identified those that undertook deliveries in public patients. Between November 1997 and January 1998, a six-page survey form containing 18 questions was sent to the Delivery Suite Nursing Unit Manager, or equivalent, in each of these hospitals. The survey was multiple-choice format with some free-text fields. Non-respondents were sent a second copy of the survey form two months later and were telephoned if necessary. Data on deliveries in 1996 were supplied by the Victorian Perinatal Data Collection Unit. Statistical analyses were performed using Statview 4.1.14 Significance was taken as P < 0.05. Results Of the 84 hospitals surveyed, 71 responded and 64 met the criteria and provided usable data, giving a final response rate of 76% (three respondents delivered only private patients, one cared for postnatal women only, and three did not provide GBS screening information). The 64 hospitals that provided usable data accounted for 42 784 births in 1996 (68% of all births and 93% of all births to public patients in Victoria) and comprised 16 hospitals in metropolitan Melbourne and 48 rural hospitals. Of the 64 hospitals, 62 (97%) reported undertaking procedures that would identify and treat at least some women with a baby at risk of EOGBSD; 48 hospitals (75%) undertook routine antenatal screening for maternal GBS carriage, including 45 which also offered antibiotic prophylaxis on the basis of risk factors. Another 14 hospitals (22%) used the latter approach alone. Screening for GBS The hospitals which undertook routine antenatal bacteriological screening accounted for 97% of all deliveries in the 64 responding hospitals. They comprised all 16 metropolitan hospitals and 32 of the 48 rural hospitals, a significant difference in proportions between metropolitan and rural hospitals (P = 0.007, Fisher's exact test). Of the 48 hospitals that undertook screening, 20 had a unified hospital screening protocol, with the remainder using individual-doctor protocols. The 20 with a unified protocol comprised nine of the 16 metropolitan hospitals and 11 of the 32 rural hospitals (P = 0.22, Fisher's exact test). Characteristics of the screening protocols among these 20 hospitals are shown in Box 1. Most protocols (65%) were less than five years old, and 40% were less than two years old. The most common approach to bacteriological screening was to perform a low vaginal swab only (15 of 20 hospitals), or, less commonly, a high vaginal swab only (four hospitals). Only one hospital performed a low vaginal swab combined with an anal swab. All but one hospital screened only once in the pregnancy, either before 30 weeks' gestation (12 hospitals) or between 30 and 34 weeks' gestation (seven). The hospital that screened more than once did not specify gestations. All hospitals that performed bacteriological screening administered intrapartum antibiotics to all women who were GBS-positive. Screening of private patients Bacteriological screening was offered to private patients by some or all obstetricians at 37 of the 64 hospitals. This was a smaller proportion of hospitals than offered screening to public patients, although the difference did not reach significance (P = 0.06, Fisher's exact test). In only 18 of these 37 hospitals did all obstetricians offer screening to their private patients. In 13 hospitals, none offered screening to private patients, and in 14 the respondent did not know if it was offered. Risk-factor-targeted prophylaxis Targeting of prophylaxis by recognised clinical risk factors was reported by 59 of the 64 hospitals (92%). Criteria used are shown in Box 2. Antibiotics were reported to be given most commonly for clinical signs of intrapartum infection (51 hospitals) and pre-labour rupture of the membranes (43 hospitals), although the time from membrane rupture to starting antibiotic administration varied considerably. Only 10 hospitals administered antibiotics to women admitted in preterm labour below a specified gestation. All were metropolitan hospitals that also performed routine bacteriological screening. Only four hospitals (6%) administered antibiotics on the basis of all five recognised criteria. Two of these also undertook screening. With regard to the antibiotic used as chemoprophylaxis, 14 of the 20 hospitals with a unified protocol used penicillin, four amoxycillin and two ampicillin. The 14 hospitals using penicillin all had different treatment regimens. Of the hospitals that lacked a unified protocol, only four reported the antibiotic regimen used -- penicillin in three and amoxycillin in one. Discussion To our knowledge, this is the first survey of GBS screening practices in pregnancy to be reported in Australia. It reveals that prenatal screening and prophylaxis for GBS infection were widely practised in public hospitals in Victoria. However, the specific strategies varied considerably, and, while this variation is understandable (given the lack of robust comparative data for the various possible approaches2,10,12,15), it translated into a less than ideal approach in many centres. Current evidence suggests that the optimum approach to reduce EOGBSD is to offer intrapartum chemoprophylaxis, using penicillin (or erythromycin in women allergic to penicillin) to at-risk mother-infant pairs. These at-risk pairs are identified by bacteriological screening, involving a low vaginal and anal swab performed at 36-38 weeks' gestation and/or by clinical risk factors (Box 3).2,10 In our survey, most hospitals reported targeting prophylaxis through bacteriological screening. However, the varied approaches to this screening revealed that current practice may not be as effective as possible. In addition, while most hospitals undertook screening, only 20 had a unified protocol, while the remaining 28 reported that protocols differed between doctors. This, together with the variable practice for private patients, suggests that it may be useful to develop more uniform Australian guidelines. Indeed, that only two hospitals (3% of respondents) reported a current protocol that would be expected to maximally prevent EOGBSD (targeting prophylaxis by bacteriological screening and by all risk factors shown in Box 3) suggests that the introduction of uniform practice guidelines would be worthwhile. The most common differences between the reported screening protocols and an approach expected to minimise EOGBSD were the maternal sites sampled and the timing of screening. GBS carriage within individuals is not constant. Consequently, bacteriological swabs taken at 28 weeks' gestation have only a 50%-70% positive predictive value for carriage at delivery, while about 5%-10% of women who are GBS-positive at delivery are negative at 28 weeks.3,13,16 Therefore, the closer to delivery that bacteriological screening is undertaken, the greater its utility, both as sensitivity and specificity are increased,2,10,16 and as the costs of screening are saved for the 5% of pregnant women who deliver preterm (and should receive prophylaxis irrespective of the screening result.2,11). Thus, bacteriological screening is probably best undertaken at 36-38 weeks' rather than at less than 30 weeks' gestation, the most popular time in our survey. Nevertheless, despite these theoretical considerations, a significant reduction in the incidence of EOGBSD was recently reported by King George V Hospital, Sydney, where screening is performed at 28 weeks' gestation.17 This result emphasises that bacteriological screening at 28 weeks' gestation is preferable to no screening at all. Detection of GBS is increased by 5%-25% if an anal swab is collected in addition to a vaginal swab.16,18,19 Only one hospital in our survey reported collecting both swabs; most took only a low vaginal swab. It has been suggested that Australian women would find collection of anal swabs unacceptable,20 but no objective evidence has been presented for this. Furthermore, most United States centres surveyed by the Centers for Disease Control took anal swabs,21 suggesting that the practice may be more acceptable than is assumed. It would certainly be worthwhile asking Australian women, and reappraising the method of screening most appropriate for our population. Collection of high vaginal swabs, reported by four hospitals in our survey, is inappropriate for GBS screening. The most cost-effective approach to preventing EOGBSD is to offer antibiotic prophylaxis to women with identified risk factors, without bacteriological screening.15 This approach has been recommended by some Australian groups (Professor James King, Mater Perinatal Epidemiology Unit, Mater Misericordiae Mothers' Hospital, Brisbane, Qld, personal communication). Most hospitals surveyed (92%) offered prophylaxis on the basis of risk factors, but only four (6%) used all recognised risk factors appropriately (Box 3). As the relative risk of EOGBSD is significantly greater in preterm neonates than in babies born at term,7 any EOGBSD prevention program should ideally include intrapartum prophylaxis for any woman labouring before 37 weeks' gestation, irrespective of whether she was screened earlier in pregnancy or of the result of that screening.2,11 It was disappointing that only a minority of the hospitals surveyed had such a policy, particularly as infection per se is a major recognised cause of preterm labour. That no rural hospital had such a policy may reflect that these hospitals transfer such women for level 3 neonatal care, and that preparation for transfer focuses more on tocolytic therapy and corticosteroid prophylaxis. If so, then an educational campaign to encourage early antibiotic treatment instituted at the referring hospital might be worthwhile. We were also surprised that only a few hospitals offered antibiotic prophylaxis to women who had had a previous baby with EOGBSD. Neonatal EOGBSD is a devastating infection, and, in our experience, parents who have had an infected child usually seek interventions to prevent infection in a future delivery. That most clinicians and hospitals do not routinely offer prophylaxis in this situation suggests a lack of awareness that this history is an important risk factor. Similarly, the variable responses to the other accepted risk factors suggest that a significant proportion of health providers are either unaware of the epidemiology of EOGBSD or do not perceive EOGBSD as an important clinical problem. Our survey of Victorian public hospitals showed that, while most are clearly aware of EOGBSD, only a minority currently have a strategy that maximises prevention of EOGBSD and represents most cost-effective practice. However, very minor changes in practice would be expected to improve EOGBSD prevention and significantly reduce costs,15 for both screening and treatment. Accordingly, our data support the case for a comprehensive, statewide, or possibly national, education program, and for the development and introduction of uniform consensus practice guidelines. Acknowledgements The authors would like to thank the participating hospitals as well as Dr Jane Halliday and Ms Sofia Mercer, from the Victorian Perinatal Data Collection Unit. EMW was partly funded by a Charles and Sylvia Viertel Clinical Investigator Fellowship. Disclosure: We are not aware of any conflict of interest arising from performing or reporting this work. References Vigneswaran R, O'Loughlin JA, McDonald HM. Group B streptococcus and pregnancy. Aust N Z J Obstet Gynaecol 1995; 35: 117-119. Prevention of perinatal group B streptococcal disease: a public health perspective. Centers for Disease Control and Prevention. MMWR Morb Mortal Wkly Rep 1996; 45 (RR-7): 1-24. McDonald H, Vigneswaran R, O'Loughlin JA. Group B streptococcal colonization and preterm labour. Aust N Z J Obstet Gynaecol 1989; 29: 291-293. Australasian Study Group for Neonatal Infections. Early-onset group B streptococcal infections in Aboriginal and non-Aboriginal infants. Med J Aust 1995; 163: 302-306. Jefferey HE, McIntosh ED. Antepartum screening and non-selective intrapartum chemoprophylaxis for group B streptococcus. Aust N Z J Obstet Gynaecol 1994; 34: 14-19. Garland SM, Fleigner JR. Group B streptococcus (GBS) and neonatal infections: the case for intrapartum chemoprophylaxis. Aust N Z J Obstet Gynaecol 1991; 31: 119-122. Zangwill KM, Schuchat A, Wenger JD. Group G streptococcal disease in the United States, 1990: report from a multistate active surveillance system. Morb Mortal Wkly Rep CDC Surveill Summ 1992; 41: 25-32. Smaill F. Intrapartum antibiotics for Group B streptococcal colonisation (Cochrane review). The Cochrane Library, 1999: 3. Oxford: Update Software. Schrag SJ, Zywicki S, Farley MM, et al. Group B streptococcal disease in the era of intrapartum antibiotic prophylaxis. N Engl J Med 2000; 342: 15-20. Gilbert GL, Isaacs D, Burgess MA, et al. Prevention of neonatal group B streptococcal sepsis: is routine antenatal screening appropriate. Aust N Z J Obstet Gynaecol 1995; 35: 120-126. Schuchat A. Group B streptococcus. Lancet 1999; 353: 51-56. Rouse DJ, Goldenberg RL, Cliver SP, et al. Strategies for the prevention of early-onset neonatal group B streptococcal sepsis: a decision analysis. Obstet Gynecol 1994; 83: 483-494. Regan JA, Klebanoff MA, Nugent RP, et al, VIP Study Group. Colonization with group B streptococci in pregnancy and adverse outcome. Am J Obstet Gynecol 1996; 174: 1354-1360. Statview 4.1. Berkeley, CA: Abacus, 1994. Garland SM, Kelly N. Early-onset group B streptococcal sepsis: economics of various prevention strategies. Med J Aust 1995; 162: 413-417. Boyer KM, Gadzala CA, Kelly PD, et al. Selective intrapartum chemoprophylaxis of neonatal group B streptococcal early-onset disease. II. Predictive value of prenatal cultures. J Infect Dis 1983; 148: 802-809. Jefferey HE, Lahra MM. Eight-year outcome of universal screening and intrapartum antibiotics for maternal group B streptococcal carriers. Pediatrics 1998; 101: E2. Badri MS, Zawaneh S, Cruz AC, et al. Rectal colonisation with group B streptococcus: relation to vaginal colonisation of pregnant women. J Infect Dis 1977; 135: 308-312. Dillon HC, Gray E, Pass MA, Gray BM. Anorectal and vaginal carriage of group B streptococci during pregnancy. J Infect Dis 1982; 145: 794-799. Prevention of neonatal group B streptococcal sepsis: is routine antenatal screening appropriate? [editorial comment]. Aust N Z J Obstet Gynaecol 1995; 35: 120. Adoption of hospital policies for prevention of perinatal group B streptococcal disease -- United States, 1997. MMWR Morb Mortal Wkly Rep 1998; 47: 665-670. (Received 10 Nov 1999, accepted 14 Feb 2000) Authors' details Monash Medical Centre, Melbourne, VIC. Mary Connellan, RM, MPH, Midwife, Women's Health Program, Southern Healthcare Network; Euan M Wallace, MD, FRACOG, Senior Lecturer, Department of Obstetrics and Gynaecology, Monash University. Reprints: Dr E M Wallace, Department of Obstetrics and Gynaecology, Monash University, Monash Medical Centre, 246 Clayton Road, Clayton, VIC 3168. euan.wallaceATmed.monash.edu.au Make a comment 1: Characteristics of screening for group B streptococcus in 20 hospitals with a unified screening protocol Number of hospitalsYears since screening protocol introduced < 28 (40%) 2-55 (25%) > 5-91 (5%) > 92 (10%) Not known4 (20%) Form of screening Low vaginal swab only15 (75%) High vaginal swab only4 (20%) Low vaginal swab and anal swab1 (5%) Frequency per pregnancy Once only19 (95%) More than once1 (5%)Timing < 30 weeks' gestation12 (60%) 30-34 weeks' gestation7 (35%) Unknown1 (5%)**The hospital that screened more than once did not specify gestations. Back to text 2: Criteria for intrapartum administration of antibiotics in 64 hospitals in Victoria CriteriaNumber of hospitals usingClinical signs of intrapartum infection51 (80%)Pre-labour rupture of membranes43 (67%) < 6h4 (6%) 6-12h0 > 12-18h10 (16%) > 18-24h4 (6%) > 24h21 (33%) Doctor-dependent4 (6%)Previous GBS-affected baby30 (47%)GBS-positive vaginal swab in previous pregnancy22 (34%)Preterm labour10 (16%) Gestation < 37 weeks7 (11%) Gestation < 34 weeks2 (3%) Gestation < 32 weeks1 (2%)GBS=Group B streptococcus. Back to text 3: Key risk factors for early-onset neonatal group B streptococcal disease (EOGBSD) Preterm delivery (< 37 weeks' gestation) Prolonged rupture of membranes (> 18h) Previous infant with EOGBSD GBS bacteriuria during pregnancy Intrapartum maternal pyrexia Back to text

Mary Connellan · Euan M Wallace

Abstract Objective: To describe the epidemiological pattern of newly diagnosed HIV infection and AIDS among Indigenous Australians. Design and setting: National surveillance for newly diagnosed HIV infection and AIDS in Australia. Information on Indigenous status was sought at HIV/AIDS notification in all State/Territory health jurisdictions, except the Australian Capital Territory, and Victoria before June 1998. Main outcome measures: Number of people with newly diagnosed HIV per year and population rate of HIV diagnosis; demographic characteristics of people with HIV and AIDS diagnoses by Indigenous status. Results: From 1992 to 1998, 127 Indigenous Australians were newly diagnosed with HIV infection and 55 were diagnosed with AIDS. The population rate of HIV diagnosis among Indigenous Australians (5.23/100 000 per year) was similar to that among non-Indigenous Australians (5.51/100 000 per year). The annual number of HIV diagnoses among Indigenous people was relatively stable, but among non-Indigenous people it declined steadily over time. A higher proportion of Indigenous people diagnosed with HIV were women (26.8% v 8.9%; P < 0.001). Although male homosexual contact was the predominant source of exposure for both Indigenous (46.7%) and non-Indigenous (75.0%) people with HIV infection, exposure by heterosexual contact (36.7% v 15.3%; P < 0.001) was reported more frequently among Indigenous people. Conclusion: Although HIV incidence was similar among Indigenous and non-Indigenous Australians, the lack of a recent decline in incidence and the higher proportion of Indigenous people exposed to HIV by heterosexual contact indicate the need to intensify interventions to prevent HIV transmission among Indigenous people. Introduction The epidemic of HIV transmission peaked in Australia in the mid 1980s, and there was a subsequent peak in AIDS incidence of nearly 1000 cases in 1994.1 The estimated number of people diagnosed with HIV infection in Australia to the end of 1998 was 16 714, with an estimated 11 800 living with HIV infection. Although the peaks of both the HIV and AIDS epidemics in Australia have passed, HIV infection continues to be transmitted, predominantly through male homosexual contact, at an estimated level of 450 cases per year.1 Despite evidence of a relatively well-controlled HIV epidemic in Australia, evaluation of the Third National HIV/AIDS Strategy noted an increase in the reported number of Indigenous Australians diagnosed with HIV infection in the early 1990s.1 Furthermore, high rates of other sexually transmissible infections in some Indigenous communities indicate the potential for HIV transmission.1 To define the pattern of HIV infection among Indigenous Australians, and to assess time trends in new diagnoses of HIV infection and AIDS, we examined national HIV and AIDS notification data by Indigenous status for the years 1992-1998. National Health and Medical Research Council guidelines on ethical matters in Aboriginal and Torres Strait Islander health research were followed.2 Methods National surveillance procedures Surveillance procedures for newly diagnosed HIV infection and AIDS have been described previously.3,4 Briefly, newly diagnosed HIV infection and AIDS are notifiable conditions in each State or Territory health jurisdiction in Australia. Information sought at national notification of newly diagnosed HIV infection includes the State or Territory of diagnosis, postcode of residence, namecode (based on the first two letters of the family name and the first two letters of the first given name), sex, date of birth, Indigenous status, date of HIV diagnosis, CD4 cell count at HIV diagnosis, evidence of newly acquired HIV infection, and patient-reported source of exposure to HIV. Information sought at AIDS notifications also includes the date of AIDS diagnosis, AIDS-defining illnesses, and use of antiretroviral therapy before AIDS diagnosis. People with newly diagnosed HIV infection with evidence of newly acquired HIV infection (ie, a negative or indeterminate HIV antibody test result or a diagnosis of HIV seroconversion illness within 12 months of HIV diagnosis) were defined as having "newly acquired HIV infection". People with AIDS were classified as having "late HIV diagnosis" if HIV infection was newly diagnosed within three months of AIDS diagnosis. Indigenous status From 1985, information on Indigenous status, obtained through self-identification as Aboriginal or Torres Strait Islander, was routinely sought at notification of HIV infection and AIDS for people newly diagnosed in the Northern Territory, Queensland, South Australia, Tasmania and Western Australia. In New South Wales, Indigenous status has been sought for newly diagnosed cases of HIV infection and AIDS since 1992. Indigenous status was not available for people with HIV infection or AIDS diagnosed in the Australian Capital Territory, or from Victoria before June 1998. Information on Indigenous status has been sought nationally from 1995; available information on Indigenous status for cases diagnosed before 1995 was obtained retrospectively through State or Territory health authorities. Exposure category HIV exposure was classified as male homosexual contact, male homosexual contact plus injecting drug use, injecting drug use, heterosexual contact only, haemophilia/coagulation disorder, receipt of blood or tissue, mother with or at risk for HIV infection, and other or undetermined exposure. Statistical analysis A χ2 or Fisher's exact test and odds ratios were used to test for differences between Indigenous and non-Indigenous cases with respect to demographic characteristics (sex, residence), newly acquired HIV 1infection, late HIV diagnosis, HIV exposure category, and individual AIDS-defining illnesses. Residence was divided into "metropolitan" and "non-metropolitan" on the basis of postcode. "Metropolitan" was defined as capital city (including Canberra), and "non-metropolitan" was defined as other than capital city. In the analyses, cases without information on Indigenous status were grouped with non-Indigenous cases. The population-based rate of HIV diagnosis was calculated by Indigenous status and year (for States and Territories other than Victoria and the ACT) using Australian Bureau of Statistics (ABS) census data for 1996.5 Results Information on Indigenous status was available for 91% of people with newly diagnosed HIV infection. For the period 1992-1998, 5313 cases of newly diagnosed HIV infection were notified to the national HIV surveillance centre, of which 127 (2.4%) were Indigenous cases. For the same period, 3638 AIDS cases were notified, of which 55 (1.5%) were Indigenous cases. The annual number of HIV diagnoses among Indigenous people was relatively stable over this period (Box 1). In contrast, the annual number of HIV diagnoses among non-Indigenous people gradually declined over the years 1992-1998. During this period, the annual HIV diagnosis rate per 100 000 population among Indigenous people (diagnosed in States and Territories other than Victoria and the ACT) (5.23) was similar to that among non-Indigenous people (5.51) (Box 1). A higher proportion of Indigenous people with HIV were female (26.8% v 8.9%; P < 0.001) (Box 2). The median age at HIV diagnosis (30 years v 33 years; P < 0.001) and AIDS diagnosis (32 v 37 years; P < 0.001) was lower among Indigenous cases. The pattern of exposure to HIV reported by Indigenous people was different from that reported by non-Indigenous people both for newly diagnosed HIV infection and AIDS (Box 2). Although male homosexual contact was the predominant source of exposure to HIV for both Indigenous (46.7%) and non-Indigenous (75.0%) people, a history of heterosexual contact only was reported more frequently by Indigenous people (36.7% v 15.3%; P < 0.001). The proportion of Indigenous and non-Indigenous people with AIDS with "late HIV diagnosis" was similar (23.6% and 18.3%; P = 0.42), as was the proportion reporting antiretroviral therapy before AIDS diagnosis (56.4% and 62.2%; P = 0.5). No difference between Indigenous and non-Indigenous cases was observed in the median CD4 cell count at diagnosis of HIV and of AIDS. The spectrum of AIDS-defining illnesses for Indigenous and non-Indigenous people with AIDS is shown in Box 3. Cryptococcal disease (odds ratio [OR], 3.3; 95% CI, 1.4-7.6; P = 0.004), oesophageal candidiasis (OR, 1.8; 95% CI, 0.95-3.38; P = 0.05), and atypical mycobacterium (OR 8.3; 95% CI, 2.4- 25.42; P = 0.002) were more frequent among Indigenous AIDS cases, whereas Kaposi's sarcoma was less frequent (OR, 0.12; 95% CI, 0.01-0.80; P = 0.01). Among people with HIV, there were more Indigenous than non-Indigenous cases in non-metropolitan locations (36% v 16%) (P < 0.01). Similarly, among people with AIDS, there were more Indigenous than non-Indigenous cases in non-metropolitan locations (37% v 19%) (P = 0.002). Discussion The HIV epidemic among Indigenous Australians has been relatively limited to date, with an overall rate of HIV diagnosis comparable with that for non-Indigenous Australians over the years 1992-1998. However, there have been contrasting trends in these rates, with a declining rate of HIV diagnosis among the non-Indigenous population, but a relatively stable rate among Indigenous people. Features that distinguish the Indigenous from the non-Indigenous HIV epidemic are a higher proportion of women affected, a higher proportion with heterosexual exposure to HIV, a younger age at HIV and AIDS diagnosis, and a higher proportion of people with HIV in rural areas. The low proportion of people with "late HIV diagnosis" among both Indigenous and non-Indigenous AIDS cases would suggest that a large pool of undiagnosed HIV infection is not present in Australia. The very low HIV prevalence among prison entrants in all States and Territories, including those where Indigenous Australians constitute a large proportion of prison inmates, is further confirmation that HIV prevalence among Indigenous Australians remains low.6 Our findings also extend those of an earlier study that showed comparable rates of HIV infection in both the Indigenous and the non-Indigenous population in Queensland.7 In interpreting our findings, several limitations to the study methods need to be considered. Firstly, the lack of a uniform reporting system for Indigenous status in all States and Territories may result in under-reporting in some jurisdictions. However, there is evidence that in recent years Indigenous status has been more completely reported, with 91% of HIV notifications in those States/Territories other than the ACT and Victoria currently reporting Indigenous status.1 Secondly, reporting of Indigenous status was based on "self-identification", which may either not be reported correctly by the patient, or not requested by the clinician. If identifying as Indigenous is more likely in a census setting than in clinical practice, our rates of Indigenous HIV diagnosis may be underestimates. Thirdly, reported rates of HIV and AIDS diagnoses are dependent on the level and extent of HIV testing. Poor access to and uptake of confidential testing by some Indigenous people, and fear of possible stigmatisation arising from positive test results, may influence the extent of HIV testing among Indigenous people. The explanation for the apparently limited HIV epidemic among Indigenous Australians is almost certainly multifaceted. The drop in HIV transmission from the mid 1980s has meant that the extent of the Australian HIV epidemic has been limited compared with many other countries.1 Behaviour change among homosexual men was largely responsible for the initial reduction in HIV transmission from the mid 1980s,1 with other measures such as the widespread introduction of harm minimisation programs for injecting drug users,8 and high condom use and low rates of sexually transmissible infections among most sex workers9 contributing to the ongoing relatively low level of HIV transmission. The absence of substantial levels of HIV infection among injecting drug users and female sex workers1 may have limited the spread of HIV into the heterosexual population. Despite the fact that the proportion of HIV diagnoses attributed to heterosexual contact has increased in recent years, homosexual contact remains the exposure category for about 85% of new HIV diagnoses.1 Australia's Indigenous people are not a homogeneous group. There are many hundreds of language groups and a wide diversity of cultural, social, economic and geographical settings within and between Indigenous Australian communities. Most Indigenous Australians suffer a higher burden of illness and die at a younger age than non-Indigenous Australians for almost every type of disease or condition for which information is available.10 Indigenous Australians are more likely to have lower annual incomes, are less likely to have qualifications beyond secondary school,11 and are 15 times more likely to be imprisoned than non-Indigenous Australians.11 These factors, combined with the remote locations in which many Indigenous Australians live and the resulting poor access to health services, contribute to their vulnerability to sexually transmissible infections.12 Associations in other industrialised countries between socioeconomic disadvantage and HIV transmission from heterosexual exposure and injecting drug use13 highlight the need to provide HIV prevention services which reach all sectors of society. The higher proportion of Indigenous people with HIV in rural areas should alert policymakers to the need for access to culturally appropriate health services in these locations. Likewise, the higher proportion of Indigenous people with HIV infection who are women, who report heterosexual exposure only and who inject drugs shows a need for broadly focused HIV prevention programs. This demographic pattern, the relatively stable level of HIV diagnoses in Indigenous people, and the continuing high rates of other sexually transmissible infections among some Indigenous communities,1 highlight the need to strengthen both sexual health and harm-minimisation strategies for Indigenous Australians. Following the recommendations of the Evaluation of the Third National HIV/AIDS Strategy, several measures have been implemented in an attempt to reduce the higher rates of sexually transmissible infections among Indigenous Australians and the associated risk of HIV infection. These include the establishment of an Indigenous Australians' Sexual Health Working Party and the subsequent implementation of the National Indigenous Australians' Sexual Health Strategy 1996-97 to 1998-99, which proposed a comprehensive approach to HIV prevention through a range of strategies considering treatment and care, partnership agreements and a properly resourced workforce.14 In particular, the Strategy emphasises the need for access to primary care services for communities without adequate facilities for diagnosing and treating sexually transmissible infections and the provision of information on reducing the risk of acquisition. Strategies aimed at the underlying causes of low socioeconomic status, low levels of education and low levels of employment must also be employed in order to reduce the risk of transmission of HIV and other sexually transmissible infections in Indigenous Australians. Acknowledgements The National Centre in HIV Epidemiology and Clinical Research (NCHECR) is funded by the Commonwealth Department of Health and Aged Care. We would like to acknowledge the valuable input and feedback received from the National Australian Indigenous Sexual Health Working Party during the drafting of this article. We also thank Ms Yueming Li for statistical analyses, Ms Patty Correll (NCHECR) for her assistance in extracting data, and Ms Suzanne Blogg (National Centre for Epidemiology and Population Health [NCEPH]) for her guidance and assistance. We thank the doctors who reported cases of newly diagnosed HIV infection and AIDS under national surveillance procedures, and the National HIV Surveillance Committee for their collaboration. The National HIV Surveillance Committee comprises Ms Irene Passaris (ACT), Mr Robert Menzies (NSW), Dr Jan Savage (NT), Dr Hugo Ree (QLD), Ms Therese Davey (SA), Mr Neil Cremasco (TAS), Ms Cathy Keenan (VIC), Dr Gary Dowse (WA), Professor John Kaldor (NCHECR), and Ms Ann McDonald (NCHECR). References Commonwealth Department of Human Services and Health. Valuing the past -- investing in the future. Evaluation of the National HIV/AIDS Strategy 1993-94 to 1995-96. Canberra: AIDS/Communicable Diseases Branch, CDHSH, 1995. National Health and medical Research Council. Guidelines on ethical matters in Aboriginal and Torres Strait Islander health research. Canberra: NHMRC, 1991. McDonald AM, Crofts N, Blumer CE, et al. The pattern of diagnosed HIV infection in Australia, 1984-1992. AIDS 1994; 8: 513-519. Kaldor J, McDonald AM, Blumer CE, et al. The acquired immunodeficiency syndrome in Australia: incidence 1982-1992. Med J Aust 1993; 158: 10-17. Australian Bureau of Statistics. Population distribution, Indigenous Australians. Canberra: ABS 1997. (Catalogue No. 4705.0.) McDonald AM, Ryan J, Brown PR, et al. HIV prevalence at reception into Australian prisons, 1991-1997. Med J Aust 1999; 171: 18-21. Neilson G, Hill PS. Human immunodeficiency virus notifications for Aborigines and Torres Strait Islanders in Queensland. Med J Aust 1993; 158: 155-157. MacDonald M, Wodak A, Ali R, et al. HIV prevalence and risk behaviour in needle exchange attenders: a national study. Med J Aust 1997; 166: 237-240. O'Connor CC, Berry G, Rohrsheim R, et al. Sexual health and use of condoms among local and international sex workers in Sydney. Genitourin Med 1996; 72(1): 4-51. Australian Bureau of Statistics. The health and welfare of Australia's Aboriginal and Torres Strait Islander peoples, 1997. Canberra: ABS, 1997. (Catalogue No. 4704.0.) Office of the Aboriginal and Torres Strait Islander Social Justice Commissioner. Indigenous deaths in custody 1989 to 1996. Sydney: Human Rights and Equal Opportunity Commission, October 1996. Fairley CK, Bowden FJ, Gay NJ, et al. Sexually transmitted diseases in disadvantaged Australian communities. JAMA 1997; 278: 117-118. Centers for Disease Control and Prevention. HIV/AIDS Surveillance Report 1998; 10 (No. 2): 1-43. ANCARD Working Party on Indigenous Australians' Sexual Health, Commonwealth Department of Health and Family Services. The National Indigenous Australians' Sexual Health Strategy, 1996-1997 to 1998-1999. Canberra: CDHFS, 1997. Authors' details National Centre in HIV Epidemiology and Clinical Research, Sydney, NSW. Jillian A Guthrie, BA, MAE (Indigenous Health) also at National Centre for Epidemiology and Population Health, Australian National University, Canberra, ACT. Gregory J Dore, FRACP, MPH, Lecturer. Ann M McDonald, MPH, Coordinator, National HIV/AIDS Surveillance. John M Kaldor, PhD, Professor; and Head, Epidemiology Unit. Reprints will not be available from the authors. Correspondence: Professor J M Kaldor, National Centre in HIV Epidemiology and Clinical Research, Level 2, 376 Victoria Street, Darlinghurst, NSW 2010. jkaldorATnchecr.unsw.edu.au 2: Newly diagnosed HIV infection and AIDS, 1992-1998, by Indigenous status and selected characteristicsHIV diagnoses IndigenousNon-IndigenousP Odds ratio (95% CI)Total casesn=127n=5186Males93 (73.2%)4726 (91.1%)<0.0010.27 (0.17-0.41)Median age (years)3033Median CD4 cell count4844000.10Newly acquired HIV*24 (18.9%) 930 (17.9%)0.79Late HIV diagnosis?---HIV exposure categoryn=120?n=4507?Male homosexual contact56 (46.7%)3382 (75.0%) <0.0010.29 (0.20-0.43)Male homosexual contact and injecting drug use 12 (10.0%)191 (4.2%)0.0022.51 (1.29-4.78)Injecting drug use6 (5.0%)176 (3.9%)0.3Heterosexual contact only44 (36.7%)689 (15.3%)<0.0013.21 (2.16-4.77)Receipt of blood/tissue0 (0.0)34 (0.8%)0.4Mother-to-child transmission2 (1.7%)35 (0.8%)0.2Other/Undetermined7679 AIDS diagnoses IndigenousNon-IndigenousPOdds ratio (95% CI)Total casesn=55n=3583Males43 (78.2%)3411 (95.2%)<0.0010.18 (0.09-0.37)Median age (years)3237<0.001Median CD4 cell count90600.71Newly acquired HIV*---Late HIV diagnosis?13 (23.6%)675 (18.8%)0.42HIV exposure catergoryn=52?n=3405?Male homosexual contact26 (50.0%)2783 (81.7%)<0.0010.22 (0.12-0.38)Male homosexual contact and injecting drug use7 (13.5%)167 (4.9%)0.0162.95 (1.20-6.93)Injecting drug use1 (1.9%)127 (3.7%)0.4Heterosexual contact only17 (32.7%)238 (7.0%)<0.0016.28 (3.33-11.75)Receipt of blood/tissues0 (0.0)76 (2.2)0.3Mother-to-child transmission1 (1.9%)15 (0.4%)0.2Other/Undetermined3178 *A negative or indeterminate HIV antibody test result or a diagnosis of HIV seroconversion illness within 12 months of HIV diagnosis. ?HIV infection newly diagnosed within three months of AIDS diagnosis. ?The "other/undetermined" category was excluded from the calculation of the percentage of cases attributed to each HIV exposure category.

Jillian A Guthrie · Gregory J Dore · Ann M McDonald · John M Kaldor

Research Complementary therapies: have they become accepted in general practice? Marie V Pirotta, Marc M Cohen, Vicki Kotsirilos and Stephen J Farish MJA 2000; 172: 105-109 For related articles see Lewith and Newell Abstract - Methods - Results - Discussion - Acknowledgements - Disclosure - Authors' details - - More articles on complementary medicine Abstract Objectives: To describe Victorian general practitioners' attitudes towards and use of a range of complementary therapies. Design: A self-administered postal survey sent to a random sample of 800 general practitioners (GPs) in Victoria in July 1997. Participants: 488 GPs (response rate, 64%). Main outcome measures: GPs' knowledge; opinions about harmfulness and effectiveness; appropriateness for GPs to practise; perceived patient demand; need for undergraduate education; referral rates to complementary practitioners; and training in and practice of each therapy. Results: Acupuncture, hypnosis and meditation are well accepted by the surveyed GPs, as over 80% have referred patients to practitioners of these therapies and nearly half have considered using them. General practitioners have trained in various therapies -- meditation (34%), acupuncture (23%), vitamin and mineral therapy (23%), hypnosis (20%), herbal medicine (12%), chiropractic (8%), naturopathy (6%), homoeopathy (5%), spiritual healing (5%), osteopathy (4%), aromatherapy (4%), and reflexology (2%). A quarter to a third were interested in training in chiropractic, herbal medicine, naturopathy and vitamin and mineral therapy. General practitioners appear to underestimate their patients' use of complementary therapies. Conclusions: There is evidence in Australia of widespread acceptance of acupuncture, meditation, hypnosis and chiropractic by GPs and lesser acceptance of the other therapies. These findings generate an urgent need for evidence of these therapies' effectiveness. The past decade has seen a dramatic increase in the reported use of non-orthodox or complementary therapies by the public.1-4 In one year in Australia, almost half of a representative sample had used at least one non-medically prescribed complementary remedy and at least one in five had attended a non-medically trained complementary therapist.1 Further, Australians consume as much non-traditional medicine, vitamin and mineral supplements as prescription drugs.5There is evidence that the increasing public use of complementary medicine is paralleled by acceptance among family doctors. In one region of the United Kingdom in one week, 25% of general practitioners (GPs) referred patients for complementary therapies,6 while in Canada half7 to two-thirds8 of family doctors had at some time referred patients to alternative practitioners; these studies did not explore reasons for such referral. However, patient pressure is an acknowledged factor in medical referrals,9 so willingness of family doctors to refer their patients for these therapies may not be a good measure of their acceptance of them. Interest by GPs in training in and practising complementary therapies may give a better indication. In New Zealand, 54% of GPs were interested in further training in non-orthodox therapies,10 while in Israel 88% wanted training and 16% had trained.11 Estimates of practice of complementary therapies by GPs vary from around 16% in Canada8 and the UK,6,12 to 30% in New Zealand,10,13 47% in Holland (mainly homoeopathy)14 and up to 85% in Germany (mainly herbal medicine).15 Despite this degree of interest in and use of complementary therapies by family doctors, in the United States it has been estimated that 70% of people who attend non-medically trained complementary therapists do not inform their family doctor.3 The corresponding situation in Australia is largely unknown. At least 15% of Australian GPs practise acupuncture,16 the only non-orthodox therapy that attracts specific funding from Medicare. In this study, we describe Victorian GPs' attitudes towards and use of a range of complementary therapies. Methods We obtained a random sample of 800 Victorian GPs who had each seen at least 1500 patients in 1996 from the Health Insurance Commission, which administers the national health insurance scheme (Medicare). We designed an 11-page survey to investigate various aspects of GPs' interactions with the following complementary therapies: acupuncture, aromatherapy, chiropractic, herbal medicine, homoeopathy, hypnosis, meditation, naturopathy, osteopathy, reflexology, spiritual healing (eg, Reiki) and vitamin and mineral therapy. We developed the survey from the existing literature17 and by using a focus group of local GPs. After pilot testing, the survey was mailed to the 800 GPs with a reply paid envelope in July 1997. Non-responders were sent a reminder postcard and then a follow-up survey if necessary. Doctors who had left their clinic leaving no forwarding address, taken extended leave, were seriously ill, or had moved overseas, retired or died were excluded. The study received ethical approval from both the University of Melbourne and Monash University. The statistical analysis was performed using SAS.18 Responses were analysed to search for groupings of common levels of use/acceptance. (In all instances, for these data the 95% confidence intervals for percentages never exceed ± 4.5%.) Qualitative data from space left for comments were coded and classified by themes. Results Thirty-six GPs were excluded according to the exclusion criteria, leaving 764 GPs. Questionnaires were returned by 488, giving a response rate of 64%. The sample was representative of Australian GPs19,20 in terms of sex, age distribution, metropolitan or rural practice location and number of patients seen per week up to 199; doctors seeing more than 200 patients per week, however, were underrepresented. There was no significant difference in age or sex between responders and non-responders. Knowledge of complementary therapies At least 80% of GPs reported that they knew something of acupuncture, hypnosis, meditation and chiropractic; about half knew something of herbal medicine, naturopathy and vitamin and mineral therapy; while 60%-70% had only heard of osteopathy, homoeopathy, spiritual healing, reflexology and aromatherapy. Opinions on the harmfulness and effectiveness of complementary therapies Most GPs agreed that the well-known therapies (acupuncture, meditation, hypnosis and chiropractic) were moderately to highly effective (see Box 1); three-quarters also agreed that chiropractic was occasionally harmful. When given the opportunity to write comments, many doctors expressed concern that complementary therapies could be harmful if a diagnosis is delayed or missed or if a proven (orthodox) therapy is neglected. Complementary therapies were considered to have a strong placebo effect. Some respondents commented that, while some therapies were effective in certain conditions, one could not generalise and effectiveness may depend upon the training and competence of the therapist. General practitioners frequently differentiated between medical and non-medical practitioners and expressed greater confidence in medically trained colleagues who practised these therapies. Opinions on the appropriateness of GPs to practise complementary therapies and eligibility for Medicare subsidy Box 2 shows responses to the question of whether it is appropriate for general practitioners to practise these therapies. Although chiropractic was considered occasionally harmful by 75% of general practitioners surveyed, 55% considered it appropriate for trained GPs to practise. Doctors who agreed that it was appropriate to practise a therapy were asked whether GPs should be eligible for Medicare funding when practising these therapies. Nearly all GPs agreed that acupuncture should be funded. There was also strong support for specific funding for GPs practising hypnosis (91%), meditation (77%) and chiropractic (69%). Even the relatively unknown therapies had support from approximately a quarter of GPs for specific Medicare funding. Teaching in undergraduate curricula Most respondents (93%) agreed that there should be some education on complementary therapies in core medical undergraduate curricula. However, doctors were evenly divided over a five-point scale about the importance of this education for students. Patient demand Fifty-nine per cent of GPs reported that patient demand for complementary therapies was increasing, 29% reported demand was static, and 10% were unsure. A third of doctors estimated that less than 10% of their patients used complementary therapies and another third thought that 11%-30% did. Nearly half of the GPs reported that less than 5% of their patients had asked them about complementary therapies in the past month. Referrals for complementary therapies Box 3 summarises GPs' responses on referrals to complementary therapists, from how they would respond if a patient suggested consulting a complementary therapist to how often they themselves refer patients to these therapists. The question did not specify whether the therapists were medically trained. Most GPs (93%) had referred at least once and 82% had referred at least a few times a year for a complementary therapy. Just under half of the sample referred at least a few times per year for the best-known therapies -- acupuncture, meditation, hypnosis and chiropractic. While approximately two-thirds of the general practitioners would encourage a patient who suggested consulting a practitioner of acupuncture, meditation or hypnosis, only 29% would do so for chiropractic. In the remaining therapies, GPs were twice as likely to have actually referred a patient for these therapies than to endorse a patient's suggestion to consult a practitioner. Training and use of complementary therapies Box 4 shows that half of the GPs expressed an interest in training in acupuncture, meditation and hypnosis and a quarter to a third in chiropractic, herbal medicine, naturopathy and vitamin and mineral therapy. Nearly 20% of GPs practised one of the therapies, 8% used two therapies, 6% three, and 3% of general practitioners practised between 4 and 11 of these complementary therapies. For most of the complementary therapies, 80% or more of the GPs who trained in them practised them to some degree; exceptions were meditation (50%), hypnosis (56%), herbal medicine (62%) and vitamin and mineral therapy (64%). The practice of some complementary therapies, notably homoeopathy, vitamin and mineral therapy, naturopathy and herbal medicine, represented more than half of the clinical work for a small number of Victorian GPs. Discussion Our survey provides the first comprehensive description of the use of complementary therapies by GPs in Victoria. As the large sample is, in nearly all characteristics, similar to Australian GPs as a whole, our findings about GP attitudes and use of complementary therapies are likely to reflect the situation across the country. Nearly 20% of GPs had used acupuncture, meditation or hypnosis, and almost half had considered practising these therapies. Over 80% of GPs had referred patients to practitioners of these therapies. A quarter to a third were interested in training in chiropractic, herbal medicine, naturopathy and vitamin and mineral therapy. Further, around 5% of doctors use therapies, such as osteopathy, homoeopathy, aromatherapy and spiritual healing, which are relatively unknown to most of their colleagues. It is interesting to speculate on the discrepancy between the number of GPs who trained in meditation, hypnosis, herbal medicine and vitamin and mineral therapy and the number who actually practise these therapies (Box 4). Possible reasons may include GP or patient dissatisfaction with outcomes, poor acceptance by patients, lack of financial reward, or difficulty accommodating more time-consuming therapies in a busy clinic. The GPs we surveyed estimated a lower use of complementary therapies by their patients than indicated by population-based research. This may be because the portion of the population who do not attend GPs for their primary health care may attend complementary therapists, and because those who do attend GPs may be less likely to use complementary therapies. The interpretation of our findings is limited by several possible sources of bias. We have no information on non-responders, and the 64% who did respond may have been more likely to participate because they had particularly strong positive or negative views. The effects of self-report and recall bias are also unknown. Further, we did not define the therapies listed in the questionnaire and GPs may have different interpretations of the terms used, particularly vitamin and mineral therapy. Reviewing studies of various designs shows that Victorian doctors have similar levels of interest in training in, and of referral of patients for, complementary therapies as their colleagues in other Western countries, with the exceptions of Holland and Germany.6-8,10,12-15 However, the popularity of therapies varies. For example, the most popular therapy practised in Victoria was acupuncture, with 23% of respondents having trained, whereas only 8% of GPs in Canada8 and 4% in the UK12 had had acupuncture training. By contrast, homoeopathy, which has an established role in Europe,4 was the most popular complementary therapy practised by British GPs,6,12 but one of the least popular therapies in Victoria. Complementary therapies may well have something to offer, but it is of concern that therapies of unproven effectiveness are apparently being accepted in mainstream general practice. Many editorials, while acknowledging that randomised controlled trial evidence is lacking for many aspects of orthodox Western medical practice, have called for quality trials in complementary therapies.21,22 The Cochrane Library is coordinating a search for randomised controlled trials of complementary therapies and is undertaking systematic reviews of therapies for specific conditions.23 Meanwhile, other reviews have found some evidence of efficacy, for example St John's wort in treating mild to moderate depression,24 acupuncture for antiemesis,25 and also an overall greater than placebo effect for homoeopathy in a meta-analysis of trials for various conditions.26 There are diverse reasons for the lack of evidence for complementary therapies. Many therapies have not been challenged before because of their long history, "natural" origins or patients' or doctors' anecdotal reports of success. In this era of evidence-based medicine, there are difficulties applying the gold standard of randomised controlled trials to therapies which are based on different and varied paradigms of health and illness. Funding for trials in "natural" therapies is also lacking. Freely available herbs cannot be patented, so there is little incentive for research, particularly if the public is buying them regardless of evidence. Lewith et al suggest that lack of structure to enhance research in complementary therapies is a barrier in Britain.27 Our experience would suggest a similar situation in Victoria. Our findings show that general practitioners are actively using complementary therapies. Therefore, whatever the profession's attitude towards these therapies, well-designed trials, disseminated and accessible results and education are urgently needed to inform GPs' decision-making. Further research is also required into why GPs decide to practise these therapies and why they are less likely to endorse a patient's suggestion to consult a complementary therapist than to refer themselves. The problems of compliance with and interactions between orthodox and complementary therapies are also areas where much research is needed. As our findings support those of Eisenberg et al3 that GPs may not communicate sufficiently with their patients and are not aware of their widespread use of complementary therapies, the issues of communication between doctors and complementary therapists, as well as between doctors and their patients, also need to be addressed. Conclusions Acupuncture, meditation, hypnosis and, possibly, chiropractic may be considered to be well-accepted therapies in Victorian general practice, while herbal medicine, naturopathy, vitamin and mineral therapy, osteopathy and homoeopathy are accepted by a sizable minority of doctors. Doctors underestimate their patients' use of these therapies, which may contribute to compliance and medication interaction problems. There is an urgent need for well-designed trials to search for evidence of the effectiveness of these non-orthodox therapies, to inform doctors' and patients' use of them. Acknowledgements We thank Dr Jane Gunn and Dr Ngaire Kerse for advice, and Eleni Sita and Sue Vallance for assistance with data collection. Dr I Brighthope, Blackmores Ltd, Aveda, Nutrition Care Pharmaceuticals and the Australian Integrative Medicine Association contributed funding for this research. Disclosure Those who funded this trial had no input into its design, analysis, conclusions, writing of the manuscript or the decision to submit it for publication. References MacLennan A, Wilson D, Taylor A. Prevalence and cost of alternative medicine in Australia. Lancet 1996; 347: 569-573. Lloyd P, Lupton D, Wiesner D, Hasleton S. Choosing alternative therapy: an exploratory study of sociodemographic characteristics and motives of patients resident in Sydney. Aust J Public Health 1993; 17: 135-144. Eisenberg D, Davis R, Ettner S, et al. Trends in alternative medicine use in the United States, 1990-1997: results of a follow-up national survey. JAMA 1998; 280: 1569-1575. Fisher P, Ward A. Complementary medicine in Europe. BMJ 1994; 309: 107-111. Australian Bureau of Statistics. Australian social trends 1998. Canberra: ABS, 1998. (Catalogue No. 4102.0). White A, Resch K, Ernst E. Complementary medicine: use and attitudes among general practitioners. Fam Pract 1997; 14: 302-306. Verhoef M, Sutherland L. Alternative medicine and general practitioners. Can Fam Physician 1995; 41: 1005-1011. Goldszmidt M, Levitt C, Duarte-Franco E, Kaczorowski J. Complementary health care services: a survey of general practitioners' views. Can Med Assoc J 1995; 153: 29-35. De Marco P, Dain C, Lockwood T, Roland M. How valuable is feedback of information on hospital referral patterns? BMJ 1993; 307: 1465-1466. Hadley C. Complementary medicine and the general practitioner: a survey of general practitioners in the Wellington area. N Z J Med 1988; 101: 766-768. Schachter L, Weingarten M, Kahan E. Attitudes of family physicians to nonconventional therapies. Arch Fam Med 1993; 2: 1268-1270. Perkin M, Pearcy R, Fraser J. A comparison of the attitudes shown by general practitioners, hospital doctors and medical students towards alternative medicine. J R Soc Med 1994; 87: 523-525. Marshall R, Gee R, Israel M, et al. The use of alternative therapies by Auckland general practitioners. N Z J Med 1990; 103: 213-215. Visser G, Peters L. Alternative medicine and general practitioners in the Netherlands: towards acceptance and integration. Fam Pract 1990; 7: 227-232. Himmel W, Schulte M, Kochen M. Complementary medicine: are patients' expectations being met by their general practitioners? Br J Gen Pract 1993; 43: 232-235. Easthope G, Beilby J, Gill G, Tranter B. Acupuncture in Australian general practice: practitioner characteristics. Med J Aust 1998; 169: 197-200. Hopper I, Cohen M. Complementary medicine and the medical profession: a survey of medical students attitudes. Altern Ther Health Med 1998; 3(4): 68-73. SAS [computer program], version 6.12. Cary, NC: SAS Institute Inc, 1996. Australian Institute of Health and Welfare. Medical labour force 1995. Canberra: AIHW 1997. Commonwealth Department of Health and Family Services. General practice in Australia: 1996. Canberra: AGPS, 1996. Hensley M, Gibson P. Promoting evidence-based alternative medicine. Med J Aust 1998; 169: 573-574. Kerr D. In search of truth. J R Coll Physicians Lond 1996; 30: 405. The Cochrane Library Complementary Medicine Field. Oxford: Update Software, 1998. Linde K, Ramirez G, Mulrow C, et al. St John's wort for depression -- an overview and meta-analysis of the randomised clinical trials. BMJ 1996; 313: 253-258. Vickers A. Can acupuncture have specific effects on health? A systematic review of acupuncture antiemesis trials. J R Soc Med 1996; 89: 303-311. Linde K, Clausius N, Ramirez G, et al. Are the clinical effects of homoeopathy placebo effects? A meta-analysis of placebo-controlled trials. Lancet 1997; 350: 834-843. Lewith G, Kenyon J, Lewis P. Complementary medicine: an integrative approach. New York: Oxford University Press. 1996. (Received 13 May, accepted 5 Oct,1999) Authors' details Department of General Practice and Public Health, University of Melbourne, Carlton, VIC. Marie V Pirotta, MMed, FRACGP, Senior Lecturer. Stephen J Farish, BSc(Hons), MEd, Biostatistician and Senior Lecturer. Complementary Medicine Research Unit, Monash University, Melbourne, VIC. Marc M Cohen, PhD, MB BS(Hons), Senior Lecturer. Clayton, VIC. Vicki Kotsirilos, MB BS, General Practitioner. Reprints will not be available from the authors. Correspondence: Dr M V Pirotta, Department of General Practice and Public Health, University of Melbourne, 200 Berkeley Street, Carlton, VIC 3053. m.pirottaATgpph.unimelb.edu.au Make a comment 1: Attitudes among the 488 general practitioners on the harmfulness and effectiveness of complementary therapies* Harmful Effective FrequentlyOccasionallySeldomHighlyModeratelySeldomAcupuncture1 (0)76 (16%)395 (82%)93 (21%)294 (67%)41 (9%)Chiropractic32 (7%)362 (75%)82 (17%)48 (11%)306 (70%)61 (14%)Hypnosis1 (0) 141 (29%)305 (63%) 77 (18%)260 (60%)61 (14%)Meditation0 10 (2%)436 (90%)124 (29%)230 (53%)41 (10%)Osteopathy12 (3%)180 (37%)141 (29%)31 (7%)138 (32%)114 (26%)Herbal medicine20 (4%)262 (54%)144 (30%)14 (3%)128 (30%)199 (46%)Naturopathy16 (3%)200 (42%)165 (34%)19 (4%)125 (29%)191 (44%)Vitamin and mineral therapy11 (2%)214 (45%)182 (38%)22 (5%)94 (22%)224 (52%)Spiritual healing (Reiki)8 (2%)57 (12%)199 (41%)12 (3%)83 (19%)123 (28%)Homoeopathy13 (3%)143 (30%)188 (39%)10 (2%)72 (17%)217 (50%)Aromatherapy3 (1%)22 (5%)313 (65%)5 (1%)67 (16%)215 (50%)Reflexology12 (3%)47 (10%)198 (41%)4 (1%)31 (7%)207 (48%)*Many GPs offered no opinion, resulting in some missing values. Back to text 2: Opinions among general practitioners about the appropriateness of GPs to practise and charge Medicare for complementary therapies Appropriate for trained GPs to practise Should be eligible for Medicare rebates*Acupuncture97% (419/434)91% (384/422)Hypnosis92% (396/430)91% (364/399)Meditation80% (342/428)77% (282/367)Chiropractic55% (238/432)69% (207/301)Vitamin and mineral therapy44% (184/423)54% (137/254)Herbal medicine43% (183/427)53% (138/263)Naturopathy28% (117/424)42% (93/224)Osteopathy27% (113/423)44% (94/216)Homoeopathy23% (98/424)36% (77/213)Spiritual healing (Reiki)18% (74/422)27% (50/189)Aromatherapy17% (73/428)24% (47/197)Reflexology11% (48/426)22% (38/174)*Follow-on question answered only if the therapy was considered appropriate to practise. Back to text 3: Referral of patients for complementary therapies among general practitioners Those who ever referred patients Frequency of referrals Encourage a patient's suggestion to attend% (No.)RarelyFew times a yearAt least monthlyAt least weeklyMeditation74% (374/470)80% (379/476)31% (118)40% (153)20% (76)9% (32)Acupuncture71% (332/470)90% (424/473)24% (100)47% (199)19% (82)10% (43)Hypnosis62% (292/470)82% (386/473)44% (168)46% (179)10% (37)1% (2)Chiropractic29% (137/470)69% (326/476)37% (122)41% (135)17% (54)5% (15)Vitamin and mineral therapy17% (79/469)33% (157/472)57% (90)30% (47)8% (12)5% (8)Osteopathy16% (75/467)30% (141/476)55% (78)30% (42)11% (15)4% (6)Spiritual healing (Reiki)14% (66/469)20% (93/476)74% (69)20% (19)4% (4)1% (1)Naturopathy13% (62/470)30% (141/474)56% (79)26% (37)13% (18)5% (7)Herbal medicine12% (56/469)29% (138/474)63% (87)24% (33)9% (13)4% (5)Homoeopathy9% (43/470)20% (91/473)73% (66)18% (16)8% (7)2% (2)Aromatherapy9% (42/471)18% (83/475)70% (58)23% (19)6% (5)1% (1)Reflexology7% (22/470)10% (48/476)77% (37)17% (8)6% (3)0 Back to text 4: Training in and practice of complementary therapies among general practitioners Those who practise the therapy % Who practise Interest in trainingHave trained*No.5%6%-24%25%-50%>50%Meditation59% (283/477)34% (151/441)7567% (50)27% (20)5% (4)1% (1)Hypnosis52% (246/478)20% (89/442)5078% (39)20% (10)02% (1)Acupuncture49% (235/477)23% (102/441)9958% (59)34% (33)4% (4)3% (3)Herbal medicine36% (169/474)12% (53/438)3361% (20)27% (9)3% (1)9% (3)Vitamin and mineral therapy34% (160/470)23% (98/434)6346% (29)38% (24)3% (2)13% (8)Naturopathy25% (117/476)6% (26/439)2556% (14)24% (6)8% (2)12% (3)Chiropractic24% (112/475)8% (34/437)2976% (22)21% (6)3% (1)0Aromatherapy17% (83/477)4% (19/438)1883% (15)16% (3)00Homoeopathy16% (75/477)5% (23/440)2167% (14)19% (4)014% (3)Osteopathy13% (61/475)4% (17/437)†22†68% (15)18% (4)9% (2)5% (1)Spiritual healing (Reiki)12% (57/473)5% (21/439)1771% (12)24% (4)06% (1)Reflexology7% (33/475)2% (9/438)†12†100% (12)000*Includes self-taught. †These figures, which show that more doctors use osteopathy and reflexology than have actually trained in it, reflect inconsistencies in individual responses. 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Marie V Pirotta · Marc M Cohen · Vicki Kotsirilos · Stephen J Farish

Abstract Objective: To assess Australian radiation and medical oncologists' self-reported knowledge about and attitudes towards a range of non-traditional therapies used by people with cancer. Design: Postal survey during May and June 1997 of all 265 radiation and medical oncologists practising in Australia. Participants: 161 oncologists returned surveys (61% response rate). Main outcome measures: Oncologists' own level of knowledge, and, for each known therapy, their perceptions of its likely harm or benefit in patients being treated curatively and palliatively, and of the prevalence of use among their patients. Results: Oncologists reported knowing most about acupuncture, antioxidant therapy and meditation and least about cellular therapy, magnetotherapy and psychic surgery. The therapies most likely to be considered helpful were meditation, acupuncture and hypnotherapy. Those most likely to be considered harmful were coffee enemas, psychic surgery, Iscador therapy and diet therapies. Perceptions of patients' use of most therapies varied widely, with herbal therapies, antioxidant therapy and meditation considered the most commonly used. Conclusions: These results indicate self-identified gaps in oncologists' knowledge about non-traditional therapies their patients may use; they suggest a need to consider including education about these therapies in oncologists' training. Introduction Recent studies have confirmed the popularity of non-traditional therapies among Australian cancer patients: 22%-52% of medical oncology patients,1,2 40% of those being treated palliatively3 and 46% of children with cancer4 report using at least one non-traditional therapy. Many of the most popular non-traditional therapies are psychosocial (eg, relaxation, meditation and visual imagery) and are unlikely to pose threats to patients' health.1-4 However, other popular therapies include dietary therapies, antioxidants, high dose vitamins and herbal therapies,1-4 many of which are poorly evaluated and could pose physical threats to patients, either directly, or by interfering with traditional therapies. Despite the lack of scientific evidence, 25%-73% of patients using non-traditional therapies expect them to cure their cancer or to prolong their lives,1-4 and 74%-86% expect them to assist their traditional therapies.2 Despite fairly high reported levels of satisfaction and perceived benefit with non-traditional therapies,1,2 17% of patients in one study reported negative side effects,4 10%-36% of patients reported no perceived benefit or feeling worse,1,2 and around 20% reported they would not take the therapy again or recommend it to other patients.2 Even if not harmful, many non-traditional therapies are expensive,1,2 and only 64% of patients felt the non-traditional therapies provided value for money.1 Recent guidelines highlight the need for oncologists to be aware of non-traditional therapies being used or considered by their patients, and to encourage patients to discuss them.5 This would require oncologists having at least a basic understanding of these therapies. We were able to identify only two relevant studies in this area -- a quantitative survey of 106 Italian oncologists6 and a qualitative study of 18 Canadian oncologists.7 They found limited knowledge about non-traditional therapies,6,7 relatively positive attitudes towards psychological therapies,6,7 more negative attitudes towards more invasive therapies,7 negative attitudes towards non-traditional therapy practitioners6 and more positive attitudes towards the use of non-traditional therapies by palliative patients.7 As there is a lack of data in this field, we explored Australian medical and radiation oncologists' knowledge of and attitudes to non-traditional therapies, and their perceptions of the frequency with which their patients used them. Given the increased tolerance among overseas oncologists of palliative patients using non-traditional therapies,7 we assessed attitudes to palliative and curative patients separately. We use the term "non-traditional therapies" to describe all therapies other than surgery, radiotherapy, chemotherapy and hormone therapy. Methods In May and June 1997, 273 questionnaires about 19 non-traditional therapies covering a wide range of psychosocial and physical therapies commonly discussed in the literature and media were mailed to all oncologists who practise in Australia. Non-responders received a written reminder after four weeks and a telephone reminder after six weeks. Ethical approval for this study was granted by the University of Newcastle's Human Research Ethics Committee. Sample identification We identified all medical and radiation oncologists practising in Australia through the Clinical Oncological Society of Australasia (COSA) and the Royal Australasian College of Radiologists' (RACR) Faculty of Radiation Oncology. The list of all the individuals registered with the Medical and Radiation Oncology Groups of COSA in late April 1997 comprised 155 Australian-based medical oncologists and 62 radiation oncologists. As the Medical Oncology Group of Australia advised they were aware of only 165 practising Australian-based medical oncologists, we considered the COSA list comprehensive for medical oncologists. However, the RACR advised they had 123 members currently practising in Australia, and, in line with its policy of not releasing members' contact details, they agreed to mail surveys to any of their members not on the COSA list -- an additional 56 radiation oncologists. The final sample of 273 thus comprised 155 medical and 118 radiation oncologists. The survey We designed a brief survey whereby oncologists rated, on a four-point scale ("none/never heard of it", "very little", "some" or "lots"), their own levels of knowledge about each of 19 non-traditional therapies; we provided no additional information about these therapies. Oncologists were also asked to rate each therapy they knew (also on a four-point scale: "very", "fairly", "neither" or "don't know"), according to how harmful or helpful they considered it for patients being treated palliatively and curatively. Finally, they were asked to estimate the proportion of their palliative and curative patients they believed were using, or had used, each known therapy. Copies of the survey may be obtained from the authors. Statistical analysis We report descriptive statistics on oncologists' knowledge and attitudes, including 95% confidence intervals around the proportion of oncologists knowing "lots" about each therapy. All analyses were conducted with the SAS statistical package;10 95% confidence intervals were calculated using Microsft Excel,11 based on the standard binomial approximation formula.12Results Of the 273 oncologists identified, four medical and two radiation oncologists were no longer practising and two radiation oncologists received surveys through both the COSA and RACR lists, leaving 265 eligible oncologists. Completed surveys were returned by 161 (61%) -- 60 radiation oncologists, 64 medical oncologists and 37 who could not be classified because they had destroyed the identifying number that allowed us to make this differentiation. Knowledge about non-traditional therapies Box 1 shows that meditation, relaxation and visual imagery were the therapies that most oncologists (about a quarter) reported knowing a lot about. Approximately a fifth of the oncologists surveyed also reported knowing a lot about antioxidant therapy and microwave, or Tronado, therapy. The least-known therapies were cellular therapy, magnetotherapy and psychic surgery. Perceptions of each therapy's potential harmfulness or helpfulness Box 2 shows that oncologists tended to consider the psychosocial therapies helpful for patients being treated both palliatively and curatively. Acupuncture was also considered helpful, especially for palliative patients. Many therapies were considered more likely to help palliative patients and, conversely, more harmful for curative patients. Not surprisingly, the less familiar, more physical or invasive therapies dominated those considered likely to be harmful. Perceptions of their patients' use of each therapy Box 3 compares the median proportion of their curative and palliative patients that oncologists believed were using or had used each non-traditional therapy with levels of use reported by Australian cancer patients.1-4 The oncologists showed a consistent trend to estimate higher use among palliative patients. The oncologists' estimates were within the ranges reported by Australian cancer patients for acupuncture, antioxidants, faith healing, hypnotherapy, iridology and meditation, relaxation and visual imagery. However, the oncologists overestimated patients' use of aromatherapy, coffee enemas, herbal therapies, naturopathy, homoeopathy, magnetotherapy and shark cartilage therapy. No patient data were available to compare cellular, mistletoe, microwave and ozone therapies or psychic surgery, and estimates for diet therapy were difficult to compare because of variation in the definitions used. Discussion As in the overseas studies,6,7 we found that oncologists identified gaps in their knowledge about many non-traditional therapies. It is interesting to note, however, that the therapies most patients reported using (meditation, relaxation and visual imagery and antioxidants) were also the therapies that most oncologists -- although still only up to a quarter -- reported knowing a lot about. Also consistent with the overseas studies,6,7 psychosocial therapies were viewed positively, and non-traditional therapies were considered more likely to be potentially helpful to patients being treated palliatively and potentially harmful to those being treated curatively. The more positive attitudes towards psychosocial therapies may reflect oncologists' awareness of some evidence of proven benefits from these therapies.8,9 Although our respondents tended to accurately estimate their patients' use of more commonly used non-traditional therapies, they tended to overestimate patients' use of more radical therapies, especially those with higher media profiles, such as coffee enemas and shark cartilage therapy. While the oncologists' and patients' estimates come from different surveys of different populations collected at different points in time, making some degree of variation inevitable, such variation is unlikely to explain the reasonably large differences for many of the lesser-used therapies. The trend for oncologists to estimate higher use of non-traditional therapies among palliative than curative patients is consistent with Australian and international data suggesting that patients with more advanced cancers are more likely to use non-traditional therapies.2,13-15 Our study has some other limitations. Firstly, for brevity, we sought no demographic information, thus prohibiting any assessment of the respondents' representativeness of Australian oncologists. However, as we targeted all Australian oncologists, and received responses from over 60% of the population, covering the full range of responses, we are confident that our data provide the first quantitative, reasonably representative overview of Australian oncologists' knowledge of and attitudes to non-traditional therapies. Secondly, we used self-report rather than an objective assessment of oncologists' actual knowledge about non-traditional therapies. As the oncologists are unlikely to have deliberately underestimated their knowledge levels, these estimates of how much they know should probably be interpreted as best-case scenarios. Also, we provided no definitions of "helpful" or "harmful", leaving individual oncologists to decide what constituted a harm or a help. This was done intentionally, as patients seek a range of benefits from non-traditional therapies, including physical, psychosocial and spiritual ones. Finally, while our results represent the first quantitative data on oncologists' knowledge and attitudes in this area, they cannot be generalised to other clinicians who treat people with cancer, such as surgeons, haematologists and general practitioners. Sceptics may question the need for oncologists to increase their knowledge about non-traditional therapies when the benefit of most remains unproven. However, without some basic knowledge of what is involved in each therapy, and of any demonstrated benefits or adverse reactions, oncologists may be unable to give adequate advice to patients. As outlined in the National Health and Medical Research Council guidelines, overly heavy-handed and dismissive attitudes are less likely to succeed in discouraging patients from using potentially harmful non-traditional therapies than more rational and considered discussions.5 Conclusions Research is needed to facilitate the production of evidence-based information summaries for oncologists in the area of non-traditional therapies, to compare oncologists' perceptions of use with their own patients' reported use of such therapies, and to establish the knowledge and attitudes of other clinicians treating cancer patients. Acknowledgements This research was funded by the NSW Cancer Council's Cancer Education Research Program. The views expressed are not necessarily those of the Cancer Council, which had no direct role in the design and/or analyses of this study or in the decision about publication of the results. We gratefully acknowledge the assistance of the Clinical Oncological Society of Australasia and the Royal Australasian College of Radiologists' (RACR) Faculty of Radiation Oncology for their assistance with identifying eligible oncologists, and the oncologists who completed the surveys. References Begbie SD, Kerestes ZL, Bell DR. Patterns of alternative medicine use by cancer patients. Med J Aust 1996; 165: 545-548. Miller M, Boyer MJ, Butow PN, et al. The use of unproven methods of treatment by cancer patients: frequency, expectations and cost. Supportive Care Cancer 1998; 6: 337-347. Yates PM, Beadle G, Clavarino A, et al. Patients with terminal cancer who use alternative therapies: their beliefs and practices. Sociol Health Illness 1993; 15: 199-216. Sawyer MG, Gannoni AF, Toogood IR, et al. The use of alternative therapies by children with cancer. Med J Aust 1994; 160: 320-322. National Health and Medical Research Council. Clinical practice guidelines: the management of early breast cancer. Sydney: The Stone Press; 1995. Crocetti E, Crotti N, Montella M, Musso M. Complementary medicine and oncologists' attitudes: A survey in Italy. Tumori 1996; 82: 539-542. Bourgeault IL. Physicians attitudes toward patients' use of alternative cancer therapies. Can Med Assoc J 1996; 155: 1679-1685. Meyer TJ, Mark MM. Effects of psychosocial interventions with adult cancer patients: a meta-analysis of randomized experiments. Health Psychol 1995; 14: 101-108. Devine EC, Westlake SK. The effects of psychoeducational care provided to adults with cancer: meta-analysis of 116 studies. Oncol Nurs Forum 1995; 22: 1369-1381. SAS [computer program], version 6.12. Cary, NC: SAS Institute Inc, 1998. Microsoft Excel [computer program], version 97. Seattle: Microsoft Corporation, 1997. Dobson AJ. Calculating sample size. Trans Menzies Found 1984; 7: 75-79. Risberg T, Lund E, Wist E. Use of non-proven therapies. Differences in attitudes between Norwegian patients with non-malignant disease and patients suffering from cancer. Acta Oncologica 1995; 34: 893-898. Sollner W, Zingg-Schir M, Rumpold G, Fritsch P. Attitude toward alternative therapy, compliance with standard treatment, and need for emotional support in patients with melanoma. Arch Dermatol 1997; 133: 316-321. Risberg T, Lund E, Wist E, et al. The use of non-proven therapy among patients treated in Norwegian oncological departments. A cross-sectional national multicentre study. Eur J Cancer 1995; 31A: 1785-1789. (Received 5 Jul, accepted 5 Nov, 1999) Authors' details NSW Cancer Council Cancer Education Research Program (CERP). Sallie Newell, PhD Research Academic (also Conjoint Lecturer, Discipline of Behavioural Science in Medicine, Faculty of Medicine and Health Sciences, University of Newcastle; currently Epidemiologist (Health Promotion Evaluation, Northern Rivers Institute for Health and Research, Lismore, NSW). Rob W Sanson-Fisher, PhD, Director (also Professor, Discipline of Behavioural Science in Medicine, Faculty of Medicine and Health Sciences, University of Newcastle; currently Dean of Faculty). Reprints will not be available from the authors. Correspondence: The Secretary, NSW Cancer Council Cancer Education Research Program, Locked Bag 10, Wallsend, NSW 2287. cherylmATmail.newcastle.edu.au Make a comment Back to text 2: Percentage of the 161 oncologists believing non-traditional therapies about which they reported at least some knowledge ("very little" or more) to be helpful or harmful Curative patients Palliative patients TherapyNo. reporting some knowledge of therapy*HelpfulHarmfulHelpfulHarmfulAcupuncture16025%1% 58%1%Antioxidants/high-dose vitamin C1605% 30%5%23%Aromatherapy1569%2% 21%1%Cellular therapy57029% 026%Coffee enemas1511%71% 1%70%Diet therapy (Gerson/macrobiotic)1422% 49%4%48%Faith healing/spiritualism15212%24% 23%15%Herbal therapies/naturopathy1598% 22%13%15%Homoeopathy1504%12% 8%6%Hypnotherapy15631%4% 46%3%Immune-enhancing therapy1313%27% 5%22%Iridology144 1%15%1%8%Iscador/mistletoe therapy1032%55% 2%45%Magnetotherapy695%8% 8%6%Meditation/relaxation/visual imagery15969% 3%82%2%Microwave/Tronado therapy1207%45% 7%37%Ozone therapy961%46% 2%37%Psychic surgery872%57% 2%56%Shark cartilage therapy1501%23% 1%17% *The remaining response options were "neither helpful nor harmful" and "don't know" - the balance of the oncologists with some knowledge of the therapy selected one of these options. Back to text 3: Perceptions among the 161 oncologists of their patients' use of non-traditional therapies compared with that reported by Australian cancer patients Oncologists' perceptions TherapyNo. reporting some knowledge of therapyMedian curative patientsMedian palliative patientsAcupuncture1606%10%Antioxidants/high-dose vitamin C16015%20%Aromatherapy1565%10%Cellular therapy573%3%Coffee enemas1513%5%Diet therapy (Gerson/macrobiotic)*14210%10%Faith healing/spiritualism1525%10%Herbal therapies/naturopathy15920%25%Homoeopathy15010%15%Hypnotherapy1565%5%Immune-enhancing therapy1315%8%Iridology1443%5%Iscador/mistletoe therapy1032%3%Magnetotherapy692%3%Meditation/relaxation/visual imagery15920%20%Microwave/Tronado therapy1201%1%Ozone therapy963%5%Psychic surgery871%1%Shark cartilage therapy1505%10% Reported use Therapy% Paediatric patients (n=48)4% Palliative patients (n=151)3% Medical oncology patients (n=319) 1% Medical oncology patients (n=156)2Acupuncture- 7%3%5%Antioxidants/high-dose vitamin C8%24%12%12%-16%Aromatherapy- --0.5%Cellular therapy----Coffee enemas---1%Diet therapy (Gerson/macrobiotic)*8%18%13%30%(diet therapy)(special foods)(diet therapy)(changed diet) 0.5% (Gerson)Faith healing/spiritualism6%9%7%3%Herbal therapies/naturopathy8%3%-8%6%5%-10%Homoeopathy2% 5%3%2%Hypnotherapy15%--3%Immune-enhancing therapy-3%4% -Iridology- --3%Iscador/mistletoe therapy----Magnetotherapy--- 0.5%Meditation/relaxtion/visual imagery4%-17%19%10%-13%12%-28%Microwave/Tornado therapy----Ozone therapy----Psychic surgery----Shark cartlilage therapy---4% *As diet therapies included those ranging from basic dietary changes through to very restricted diets (eg, Gerson diet), the actual wording used in each of the studies is included. 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Sallie Newell · Rob W Sanson-Fisher

Research Hepatitis C virus antibody prevalence among injecting drug users at selected needle and syringe programs in Australia, 1995-1997 Margaret A MacDonald, Alex D Wodak, Kate A Dolan, Ingrid van Beek, Philip H Cunningham, and John M Kaldor, for the Collaboration of Australian NSPs* MJA 2000; 172: 57-61 For editorial comment see Watson Abstract - Introduction - Method - Results - Discussion - Acknowledgements - References - Authors' details - - More articles on Infectious diseases and parasitology Abstract Objectives: To describe point prevalence of HCV antibody and relevant risk behaviour among people who inject drugs and who attended selected needle and syringe programs throughout Australia in 1995, 1996 and 1997. Design and setting: Repeated cross-sectional surveys of one week's duration were carried out in 21, 20 and 23 needle and syringe program sites throughout Australia in 1995, 1996 and 1997, respectively. Participants: All clients attending participating sites during the designated survey week were asked to complete a self-administered questionnaire and provide a finger-prick blood sample for HCV antibody testing. Main outcome measures: Prevalence of HCV antibody. Results:Survey response was 41% (n = 979) in 1995, 51% (n = 1463) in 1996 and 48% (n = 1699) in 1997. HCV prevalence declined significantly from 63% in 1995 to 51% in 1996 and 50% in 1997 (P < 0.001). Among respondents who reported injecting for less than three years, prevalence declined from 22% in 1995 to 13% in 1996 and 1997 (P < 0.001). Reported use of needles and syringes after someone else in the previous month declined from 31% in 1995 and 28% in 1996 to 15% in 1997 (P < 0.001). Conclusions: Despite an apparent decline in HCV prevalence, carriage rates of HCV antibody remain high. Introduction Hepatitis C virus (HCV) infection is predominantly spread through blood contact.1 In most First World countries, most prevalent and incident cases of HCV infection involve people who have, at some time, illicitly injected drugs. In such people, transmission is believed to occur predominantly through sharing of injecting equipment.2 HCV infection is a public health concern because of its serious complications, such as cirrhosis of the liver and hepatocellular carcinoma,3 as well as its high prevalence, long latent period and high probability of long-term carriage and infectiousness. Australia adopted a harm reduction approach as part of its national drug strategy in 1985.4 An extensive network of needle and syringe programs (NSPs) has been established in Australia; in the financial year 1994-95, around 700 NSPs distributed six million syringes nationally and an additional four million were distributed through pharmacies.5 Early and vigorous implementation of harm reduction measures, such as methadone maintenance, peer-based education and NSPs, has successfully maintained low seroprevalence of HIV infection among people who inject drugs in Australia.6 In contrast, prevalence and incidence of HCV infection among this population remain high.2,7 To assess the impact of prevention activities on HIV and HCV infection, a monitoring system was established at selected NSPs throughout Australia.6 Cross-sectional surveys at NSPs among people who inject drugs offer a practical and repeatable mechanism for recruiting large samples of injecting drug users. This provides a basis for systematic monitoring of HCV and HIV infection, and of injecting behaviours associated with transmission of these viruses. We report the results of the first three years of national HCV monitoring among NSP attenders in Australia. Methods The survey methods have been described in detail previously.6 Briefly, trained staff at participating NSPs asked all clients attending during one-week periods in March 1995, June 1996 and October 1997 to complete a brief, self-administered questionnaire and provide a finger-prick blood sample. Participating NSP sites were selected for number of attendances and coverage of all Australian States and Territories (see Box 1). Those selected in 1995 distributed approximately 40% of the syringes distributed nationally through NSPs. There was some change in sites over the three years because the number of NSPs increased, but a core group of 16 sites was maintained. Sex and age group were recorded for all clients who attended participating sites during the survey week. As some clients attended more than once, a record was kept as to whether the attendance was the first for that week to measure survey response rate. Participants completed a brief questionnaire on basic demographic characteristics and injecting and sexual behaviour. Capillary blood was collected on blotting paper by finger prick with single-use lancets. Venous blood was not obtained, as few NSPs had appropriate facilities for collecting and storing large amounts of blood. Specimens were tested for HCV antibody by a modified third-generation enzyme immunoassay (Abbott HCV 3.0, Chicago, USA). A modified cutoff value for optical density was calculated to capture more than 95% of the seronegative population. Specimens were considered positive for HCV antibody if the optical density to cutoff ratio was greater than or equal to one on initial and subsequent testing. In 1998, as a quality control measure, 60 samples were randomly selected from each year's survey and retested for HCV antibody as described. Retest results were 100% concordant for the 1995 and 1997 surveys but only 88% for 1996. Subsequently, all available stored 1996 samples (83%) were retested. Ethical approval for this study was obtained from relevant ethics committees associated with the investigators and with participating sites. Statstical analysis Data were analysed with the Stata computer package.8 We assessed change in demographic, behavioural or serological variables using the χ2 test for categorical variables and the Kruskal-Wallis or Mann-Whitney tests for discrete variables. To control for changes in sample characteristics between surveys, we assessed change in HCV prevalence from 1995 to 1997 for all participants, and, for participants who reported only one or two years of drug injection, by multivariate logistic regression analysis. We also used multivariate logistic regression analysis, restricted to sites that participated in all surveys, to assess change in HCV prevalence. Associations between HCV prevalence and participants' characteristics were evaluated by the χ2 test and χ2 test for linear trend. To control for intralaboratory variation with HCV antibody tests, we calculated HCV prevalence for 1996 participants using retested results where available. In addition, for participants with insufficient stored sera for retesting, the original estimates of HCV prevalence were adjusted for each category of variables used in the analysis, by the overall difference between original and retest test results. Associations between HCV prevalence and participants' characteristics in 1997 were also assessed using multivariate logistic regression. Factors significantly associated with HCV infection on univariate analysis (with an inclusion criterion of P ≤ 0.05) or factors that were considered a priori to be predictors of HCV risk were included in the logistic regression model. Results Characteristics of respondents As shown in Box 1, 979 clients in 1995, 1463 in 1996 and 1699 in 1997 completed a questionnaire and provided a blood sample suitable for HCV antibody testing, giving overall response rates of 41%, 51% and 48%, respectively. There was a higher response rate among clients aged less than 25 years compared with those aged 25 years or more in 1996 (56% v. 49%), but no difference in 1995 and 1997. There was a higher response rate among females than males in 1995 (46% v. 39%) and 1997 (63% v. 39%). The age ranges for respondents in the three years were 14-54 years in 1995, 13-53 years in 1996 and 15-58 years in 1997. The median age of respondents was significantly higher in 1995 than in 1996 (29 years v. 28 years; P = 0.009) and 1997 (29 years v. 27 years; P < 0.001). Median age at commencement of injecting drug use was 18 years in the three surveys. Consequently, the median number of years that respondents had injected drugs was significantly higher in 1995 than in 1996 (10 years v. 8 years; P = 0.001) and 1997 (10 years v. 7 years; P < 0.001). Similar proportions of males (65%, 67% and 66%), respondents reporting being heterosexual (79%, 78% and 79%), and those reporting having been imprisoned in the past year (15%, 13% and 14%) participated in the 1995, 1996 and 1997 surveys. Almost a third of respondents in each year reported no contact with health services such as counselling, detoxification or methadone maintenance treatment. The proportion of respondents on methadone treatment, however, was significantly lower in 1997 (33%) than in 1995 (40%; P = 0.001) or 1996 (36%; P = 0.02). More respondents reported that heroin was the last drug they injected in 1996 and 1997 than in 1995 (53% and 56% v. 44%) and fewer reported last injecting amphetamines (19% and 18% v. 21%) and methadone (12% and 11% v. 19%; P < 0.001). Daily or more frequent injection increased from 41% of respondents in 1995 and 1996 to 51% in 1997 (P = <0.001). Syringe use after someone else Reported use of a needle and syringe after someone else in the preceding month declined significantly from 1995 and 1996 to 1997 (31%, 28%, and 15%, respectively; P < 0.001). This practice was significantly more common among females than males in 1995 and 1997 (35% v. 28% and 17% v. 14%; P = 0.04). In 1997, respondents aged less than 25 years were more likely than older respondents to report syringe use after someone else in the past month (19% v. 12%; P = 0.001). HCV antibody prevalence Box 2 shows that HCV antibody prevalence was significantly lower in 1996 and 1997 than in 1995 (51% and 50% v. 63%; P < 0.001). This difference remained significant after adjustment for differences in sample characteristics between surveys (adjusted odds ratio, 0.5; 95% CI, 0.4-0.7). Sex, age, duration of drug injecting, last drug injected, frequency of drug injection and health service contact were included in the model. A similar pattern was found when analysis was restricted to the 16 sites that participated in all three surveys (63% in 1995 v. 50% in 1996 and 51% in 1997; P < 0.001) and when respondents who reported participation in more than one survey were excluded from the analysis (63% v. 49% and 47%; P < 0.001). HCV antibody prevalence was also significantly lower in 1996 and 1997 (13%) than in 1995 (22%) among respondents who reported less than three years of drug injection (P = 0.03). This difference also remained significant after adjustment for sex, age, last drug injected, frequency of drug injection and health service contact (adjusted odds ratio, 0.4; 95% CI, 0.2-0.7). HCV antibody prevalence was lower in 1996 and 1997 than in 1995 among respondents aged less than 25 years, regardless of whether the last drug injected was heroin (trend test, P = 0.03) or amphetamine (trend test, P = 0.002; Box 3a). Box 3b shows that, when respondents were grouped according to the year they started injecting, HCV antibody prevalence was higher among those reporting most recent injection of methadone or heroin than among those reporting most recent injection of amphetamine. HCV antibody prevalence was also significantly higher among respondents from New South Wales and Victoria than those from Queensland, and remained higher when the analysis was restricted to respondents reporting heroin as the last drug injected and stratified according to the year drug injection started (Box 3c). Multivariate logistic regression analysis showed that other factors significantly associated with presence of HCV antibody in 1997 included being female, having been imprisoned in the past year, having a history of methadone treatment, being aged 25 years or more, having injected drugs for more than five years, and daily or more frequent injection (see Box 2). Discussion Our findings indicate that HCV antibody prevalence, although high, is declining, particularly among participants new to injecting. While all cases of HCV infection among respondents who reported having injected for only one or two years cannot be classified as new infections, it is highly likely that the vast majority reflect recent transmission. Variation in the populations surveyed in the three years of the study cannot be excluded as an explanation for our observations. Respondents in 1997 were younger and newer to injecting than in 1995. Nonetheless, the decline in HCV antibody prevalence remained statistically significant when multivariate logistic regression analysis was used to control for differences in demographic characteristics, when analysis was restricted to respondents who reported less than three years of drug injection, and when analysis was restricted to sites that participated in all three surveys. It is also conceivable that HCV infection status influenced participation in the survey. For example, people infected with HCV might be more likely to participate than those not infected because of the services provided by NSPs or because they have an interest in blood-borne infections by virtue of having one. Alternatively, people with HCV infection might be reluctant to provide a blood sample in a non-clinical setting because of concerns about inadvertent spread of infection. It is not possible to determine whether people with HCV infection were more or less likely than those without infection to participate in the surveys. If such bias occurred it is unlikely that the direction changed from 1995 to 1996 and 1997. However, the extent to which the magnitude of such bias may have changed over the three surveys is not known. Comparison of our data with those of other Australian studies reporting HCV antibody prevalence according to type of drug injected and duration of injecting supports our observation that HCV antibody prevalence is declining among people who inject drugs. Among opiate injectors who had been injecting for less than three years, HCV antibody prevalence was 70% in the late 1980s9 and almost 50% in the early 1990s,10 compared with 20% in our study. Declining HCV antibody prevalence has also been reported from other cities that implemented HIV prevention measures in the mid-1980s, namely Geneva11 and Glasgow.12 We also found that the proportion of respondents who reported using a syringe after someone else was significantly lower in 1997 than in 1995 and 1996. There has been a marked decline in reported sharing of syringes in Australia since 1984, when more than 90% of respondents reported having done so in the month before interview.13 Of concern was the higher rate of sharing reported among respondents aged less than 25 years than among older respondents in 1997. Younger injecting drug users are probably more recent initiates to injecting; this is a subpopulation previously identified as being at extremely high risk of acquiring HCV infection.14 An extremely high incidence of HCV infection has also been reported recently among young people with a history of drug injecting in Sydney.7 It is difficult to explain the marked geographic variation in HCV antibody prevalence detected in our study. The sample recruited from Queensland was significantly different from other States and Territories with regard to known correlates of HCV infection such as duration of injecting and type of drug injected. Nonetheless, significantly lower prevalence persisted among respondents from Queensland compared with those from New South Wales and Victoria when the sample was stratified according to these factors. Despite our finding of declining HCV antibody prevalence among people who inject drugs in Australia, and even though an epidemic of HIV infection has so far been prevented, the prevalence and incidence of HCV infection in this group remain high.2,7 Percutaneous transmission is more efficient for HCV than for HIV infection.1 More importantly, the carriage rate of HCV among injecting drug users was already considerably higher than that for HIV when harm reduction policies were first introduced.9 It is likely that occasional instances of shared injection equipment and other blood contact during injection have been sufficient to maintain high levels of HCV transmission without an increase in HIV transmission. It can not be assumed that the results of our surveys are generalisable to all people who inject drugs in Australia. However, NSP clients represent a heterogeneous population of injecting drug users who are readily accessible for targeted prevention initiatives. Prevention efforts encompassing education, drug treatment and needle exchange need to be enhanced to improve consistency and coverage so that transmission of HCV infection is reduced further and the current low prevalence of HIV infection is sustained. * The Collaboration of Australian NSPs: ACT Drug Referral and Information Centre (Maureen Cane); AIDS Council of Central Australia (Sue Fielding); Australian IV League (Judith Byrne); Biala Alcohol & Drug Services (Margaret Holtham); Centre for Immunology, St Vincent's Hospital Sydney (Phillip Cunningham & Claire Temby); Clovelly Park, Norlunga, SAVIVE and Salisbury NSP, Adelaide; Drug Intervention Services Cabramatta (Sue Heard & Lisa Maher); GAIN (Richard Beckman & Diane Flint); Gold Coast Hospital (Dr Lynn Hawken); HIV and Sexual Health Services Cairns (Chris Barron & Mark Mills); Kirketon Road Centre & K2 (Dr Ingrid van Beek & Damian Hull); Macfarlane Burnet Centre for Medical Research (Dr Nick Crofts); Melbourne Inner Needle Exchange (Craig Mercer); Northern Rivers Health Service (Wendy Evans); Northern Territory AIDS Council (Charles Roberts); Resource & Education Program (IDU): Redfern & Canterbury (Julie Dixon & Anna Miraglia); St George NSP (Richard Sulovsky); St Kilda NSP (Simon Kroes); Sexual Health Services, Toowoomba (Bill Rutkin); SHARPS Melbourne (Sean Swift & Melissa Virtue); South Australian Drug and Alcohol Services Council (Dr Robert Ali & Bob Braithwaite); Tasmanian Council on AIDS and Related Diseases (Melinda Tonks); Tasmanian Users Health Support League (Stuart Williams); Wentworth NSP (Elizabeth O'Neil & Andy Hart); West Australian AIDS Council Inc. (Katrina Roberts & Samantha Nicholson); Western Australia Substance Users' Assoc. Inc. (Tamara Speed); Western Region AIDS and Hepatitis Prevention (Sandra Fox); Western Sydney AIDS Prevention Services: Harris Park & Blacktown (Anton Evers). Acknowledgements We acknowledge the contribution of survey participants, needle and syringe program staff and site coordinators who facilitated the surveys. We also thank Dr Greg Dore for his comments on earlier drafts. Surveys were funded by the Commonwealth Department of Health and Aged Care. The National Centre in HIV Epidemiology and Clinical Research is supported by the Commonwealth Department of Health and Aged Care through the Australian National Council on AIDS and Related Diseases and its Research Advisory Committee. References MacDonald M, Crofts N, Kaldor J. Transmission of hepatitis C virus: rates, routes and cofactors. Epidemiol Rev 1996; 18: 137-148. 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. Seeff LB. Natural history of hepatitis C. Hepatol 1997; 3 Suppl: 21S-28S. Blewett N. National Campaign against drug abuse: Assumptions, arguments, and aspiration. Canberra: AGPS, 1987. (NCADA Monograph No. 1.) Wodak A, Lurie P. A tale of two countries: Attempts to control HIV among injecting drug users in Australia and the United States. J Drug Issues 1996; 27: 117-134. MacDonald M, Wodak A, Ali R, et al, on behalf of the Collaboration of Australian Needle Exchanges. HIV prevalence and risk behaviour in needle exchange attenders: a national study. Med J Aust 1997; 166: 237-240. van Beek I, Dwyer R, Dore GJ, et al. Infection with HIV and hepatitis C among injecting drug users in a prevention setting: retrospective cohort study. BMJ 1998; 317: 433-437. Stata Statistics/Data Analysis [computer program]. Version 5.0. Texas: Stata Corporation, 1997. Bell J, Batey RG, Farrell GC, et al. Hepatitis C virus in intravenous drug users. Med J Aust 1990; 153: 217-273. Crofts N, Hopper JL, Milner R, et al. Blood-borne virus infections among Australian injecting drug users: Implications for spread of HIV. European J Epidemiol 1994; 10: 687-694. Broers B, Junet C, Bourquin M, et al. Prevalence and incidence rate of HIV, hepatitis B and C among drug users on methadone maintenance treatment in Geneva between 1988 and 1995. AIDS 1998; 12: 2509-2066. Goldberg D, Cameron S, McMenamin J. Hepatitis C antibody prevalence among injecting drug users in Glasgow has fallen but remains high. Commun Dis Public Health 1998; 1: 95-97. Crofts N, Webb-Pullman J, Dolan K. An analysis of trends over time in social and behavioural factors related to the transmission of HIV among injecting drug users and prison inmates. Evaluation of the National HIV/AIDS Strategy 1993-94 to 1995-96. Technical Appendix 4. Canberra: AGPS, 1996. Garfein RS, Vlahov D, Galai N, et al. Viral infections in short-term injection drug users: the prevalence of hepatitis C, hepatitis B, human immunodeficiency, and human t-lymphotropic viruses. Am J Public Health 1996; 86: 655-661. (Received 1 Jun, accepted 16 Sep, 1999) Authors' details National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, NSW. Margaret A MacDonald, BSocSci, DipEpidemiol, Senior Research Assistant. John M Kaldor, PhD, Deputy Director. Alcohol and Drug Services, St Vincent's Hospital, Sydney, NSW. Alex D Wodak, FRACP, FAFPHM, Director. National Drug and Alcohol Research Centre, University of New South Wales, Sydney, NSW. Kate A Dolan, PhD, Senior Lecturer. Kirketon Road Centre, Sydney, NSW. Ingrid van Beek, MBA, FAFPHM, Director. Centre for Immunology, St Vincent's Hospital, Sydney, NSW. Philip H Cunningham, BAppSc, Senior Hospital Scientist. Reprints: Ms M A MacDonald, National Centre in HIV Epidemiology and Clinical Research, Level 2, 376 Victoria Street, Darlinghurst, NSW 2010. mmacdATnchecr.unsw.edu.au Make a comment Back to text 2: Hepatitis C virus antibody prevalence according to demographic and injecting characteristics (1995-1997), and multivariate logistic regression analysis (1997) 1995 1996 1997 CharacteristicNo. tested% with HCVNo. tested% with HCVNo. tested% with HCVAdjusted odds ratio (95% CI)Total979631463 51169950-Sex Male63963981 49‡111947*1 Female32764467 56574552 (1.5-2.7*)Imprisonment in previous year No82160*122448*145947*1 Yes14678190 71234702.3 (1.6-3.5*)Health service contact NSP only30032*483 17*53220*1 Detoxification, counselling12552 18338276351.4 (0.9-2.2) Past methadone maintenance15779 2657132570 3 (1.9-4.6*) Current methadone maintenance39584524 77563743.8 (2.5-5.8*) 1995 1996 1997 CharacteristicNo. tested% with HCVNo. tested% with HCVNo. tested% with HCVAdjusted odds ratio (95% CI)Age at survey (years) <206528*138 18*18419*1 20-2422639363 22440231.1 (0.6-1.9) 25-2919863308 50368471.9 (1.0-3.4‡) 30-3423775282 68290642 (1.0-3.8‡) 35+246 8436381414 845.7 (2.9-11.0*)Years of drug use <3131 22*24013*308 13*1 3-5165 3528521345 261.3 (0.8-2.1) 6-1020962309 51362442 (1.2-3.3†) >104568658081642 837.5 (4.4-13.0*)Last drug injected Amphetamine20635*274 22*31218*1 Heroin43167780 54951542.3 (1.4-3.7*) Combined drugs8572126 63104591.7 (0.8-3.5) Methadone18987169 82180783 (1.5-5.9†) Other6546109 45142462.1 (1.1-4.1‡) 1995 1996 1997 CharacteristicNo. tested% with HCVNo. tested% with HCVNo. tested% with HCVAdjusted odds ratio (95% CI)Frequency of drug injecting Less than daily50761†745 49†70741*1 Daily or more39968609 56867582 (1.5-2.7*) Not in last month704798 4111845-Syringe use after someone else in the last month No624 62†96850*1284491 Yes27971382 58220531.3 (0.9-2.0)State or Territory Queensland30940*490 33*47929*1 Victoria11853191 48436512.4 (1.6-3.5*) New South Wales41284497 71523702.2 (1.4-3.3*) Other14059285 50261461.6 (1.0-2.6‡)NSP=needle and syringe program. *P<0.001; †P<0.01 and >0.001; ‡P<0.05 and >0.01. Back to text 3: HCV antibody prevalence in relation to age, injecting habits and State or Territory. Back to text Back to text Back to text

Margaret A MacDonald · Alex D Wodak · Kate A Dolan · Philip H Cunningham

The Research Enterprise Funding Australia's basic biomedical research of 1993 and 1994 The meshing of two databases of scientific publications -- the Wellcome Trust's Research Outputs Database, and the Research Evaluation and Policy Project's database of Australian publications -- allows a detailed analysis of the funding agencies providing external (as opposed to intramural) support for Australia's basic biomedical research. This analysis shows the success Australian researchers are having in attracting funding from overseas, and the high citation rates achieved by publications with external funding. Linda Butler MJA 1999; 171: 629-633 Introduction - Characteristics of basic biomedical research funding - Comparison of funded and unfunded publications - The impact of funded research - Conclusions - References - Authors' details - - More articles on Economics

Linda Butler

The Centenary Institute of Cancer Medicine and Cell Biology The institute with the long name, short history, and tall goalposts Antony Basten Introduction - The first decade: - The second decade: - The future: the next decade - References - Authors' details - - More articles on Immunology and allergy Introduction As the joint centenaries of the University of Sydney's Medical School and its campus teaching hospital, Royal Prince Alfred Hospital (RPAH), crept closer in the early 1980s, a small group of clinical academics from medical, surgical, and obstetric specialties could be seen huddled together in corridors. What were they meeting about? asked their colleagues, exuding, as always, the paranoia and suspicion so common in academia. The answer soon became clear. Having trained and then exported, to other States and overseas, some of Australia's most talented researchers and clinical department heads, the time was ripe for the medical school and the hospital to reverse the New South Wales brain drain. The proposed mechanism was to be the creation on campus of a centre of excellence in medical research, akin to the successful Victorian institutes (the Walter and Eliza Hall, Baker and Howard Florey institutes) and the Garvan Institute in Sydney. The first decade: 1981-1989 The idea of a centre of excellence in medical research was warmly endorsed, not just by the university and hospital, but by the then Federal Liberal Government and the New South Wales State Labor Government, which jointly funded a feasibility study for construction of a research building, to accommodate 300 staff, adjacent to the medical school and hospital campus. In recognition of the need for a single major centre specialising in all aspects of cancer research and cell biology, the proposed institute received the name it still bears under an Act of the NSW Parliament: the Centenary Institute of Cancer Medicine and Cell Biology.1 Although failing to fit on any conference registration form, the name was intended to cover "all bases" -- in particular, to embody the concept that, to understand the abnormalities responsible for disease, the biology of normal cells must be studied first. In 1984, an Australian Science and Technology Council (ASTEC) Working Party2 reviewed the proposal and concluded that it was far too ambitious. The Working Party's verdict was that it was better to start small and build up slowly around a competitive research group. As a result, the wind was taken out of the Centenary Institute's sails and the project was becalmed for four long years. In retrospect, it is clear that this delay worked to the Institute's disadvantage in the long term. Instead of being established before the value of the specialised research centre was fully appreciated in NSW, its creation as a functional entity coincided with the rush to institute status by multiple groups on our own campus and elsewhere, leading ultimately to the current situation, with too many "institutes" competing for limited resources. In 1989, I was invited to be the inaugural Director of the Centenary Institute. At the time, as head of the Clinical Immunology Research Centre, one of the original 10 Commonwealth Centres of Excellence, I was trying to juggle exciting new research based on transgenic technology with the task of advising the Federal Government on medical and scientific aspects of HIV/AIDS. Little did I suspect, back then, that I would be jumping out of the frying pan into the fire. The second decade: 1989-1999 Early days The challenge in 1989 was to create an independent institute at a time of dwindling resources, both in the tertiary education sector and in the healthcare system. The Clinical Immunology Research Centre, operating from its crowded quarters in the 1880 building shared with other hospital and university staff, became the core unit of the Institute. We were faced with three formidable tasks. The first was to cope with the loss of our Centre of Excellence grant from the Australian Research Council, as funding for medical research centres was now deemed to be the responsibility of the National Health and Medical Research Council (NHMRC). Despite negotiating an increase in our NHMRC program grant, we were faced with an immediate loss of around $250 000 in research funding -- not the most auspicious start for a new institute. The second task was to appoint a new Board and Chairperson. A vigorous search, itself an experience for a naive academic like me, enabled us to secure the former Chairman of the Stock Exchange, Jim Bain, to chair the new Board. Under his stewardship, the Institute was steered through the next three difficult years and the Board established a Foundation, chaired by Tim Besley (Chairman of the Commonwealth Bank). The "Kick a Goal for Life" fundraising campaign, the brainchild of Ken Cowley (Chief Executive of News Ltd), a Foundation Trustee, gave us, for the first time, a public profile and much-needed funds. The campaign was launched to coincide with the final of the Commonwealth Bank Cup, awarded to the winners of the schoolboy rugby league competition. Alas, the number of on-field brawls reached such a pitch that the Commonwealth Bank promptly withdrew its support and our initial foray into the community came to an abrupt halt! The third vital task in 1989 was to obtain funding for a new building. Two further feasibility studies and six years later, four and a half floors of the Institute's new six-storey research facility were completed and fitted out at a cost of $17.24 million. This was funded largely from Federal and State capital works grants, with additional assistance from the NSW State Cancer Council and our two parent organisations, the University of Sydney and the Central Sydney Area Health Service. The Institute building is strategically located in the grounds of RPAH, adjacent to the university medical school, and was officially opened by the Prime Minister in 1997. The new team As the new edifice took shape, it was time to begin assembling a team of researchers with the skills to create a "critical mass" in immunology. My group, with its interest in self-tolerance in the B cell lineage, and that of Warwick Britton, head of a research program in mycobacterial infection, were already in place. Jon Sedgwick, well known for his work on autoimmunity in the central nervous system, was the first recruit from overseas. Described by the late Alan Williams of Oxford University as the best "postdoc" he had ever had, Jon was instrumental in grafting "knockout" (gene ablation) technology onto the Institute's existing expertise in transgenesis. Jon was followed by four other immunologists. Barbara Fazekas de St Groth, who, as a medical undergraduate, had done a BSc(Med) under my supervision a decade earlier, was the first. Returning to Sydney from postdoctoral study with Mark Davis at Stanford Medical School, Barbara is now recognised internationally for her work on tolerance and autoimmunity in T cell receptor transgenic models. Together with Patrick Bertolino, who joined us from Lyons in France two years ago, they make a formidable CD4+/CD8+ T cell team. Roland Scollay, known at the time as one of Australia's two leading exponents on thymus biology, was recruited from the Walter and Eliza Hall Institute, along with Phil Hodgkin from the John Curtin School of Medical Research in Canberra. Phil's recent studies on immune regulation and the relationship between division number and lymphocyte behaviour are among the most original contributions to immunology in the past five years. The final member of the quintet was Alan Baxter, who joined us from Cambridge (UK). Alan is rapidly acquiring an excellent international reputation in the field of insulin-dependent diabetes and the genetics of autoimmune diseases, including systemic lupus erythematosus and autoimmune gastritis (see Box). Achievements: the upside During the past decade, the staff has risen from 20 to 95; two NHMRC program grants have been held by research group heads; and the Institute, by virtue of its independent status, has brought to the campus more than $30 million in capital works and infrastructure funds, in addition to over $20 million in peer-reviewed grants. We were particularly delighted that Nobel laureate and immunologist, Peter Doherty, saw fit on the occasion of the official opening of the new building in 1997 to designate us as "Australia's major immunology research centre". A significant amount of the credit for these achievements must go to the Board and to Ken Tribe, its Chairman from 1994 to 1999. Ken brought to the Institute a wealth of knowledge and experience and gave us stable governance during this crucial period in our development. At the same time the work of the research staff has been underpinned by a dedicated research support and management team who have become past masters at maintaining an effective enterprise on the very shortest of shoestrings. Their loyalty and strength of purpose have been most gratifying to me personally. It has also been encouraging to work closely with the other four established independent institutes in NSW (the Garvan, Children's Medical Research, Prince of Wales Medical Research and Heart Research institutes) when negotiating with government and other bodies over issues such as infrastructure funding. The downside If one is honest there is inevitably a downside to any enterprise during its formative years and this has certainly applied to the Centenary Institute. Due to the delay already alluded to in "getting out of the blocks", the Institute has found itself competing for a dwindling pool of resources in the era of what cynics describe as the "epidemic of institutes". Some of them strive to be "independent" like us, while others are "motels" for existing academic and clinical staff or simply single departments renamed for the purpose of raising their profile and respectability. The end-result has been ongoing confusion among funding bodies, government, and even the community at large about who is most deserving of support. The consequence for the well intentioned Director and staff of the Centenary Institute was that when the new building opened they faced a hostile reception on campus, particularly from colleagues who were short of funds and research space. They saw our hard-earned new building as the answer to their prayers, while failing to appreciate our statutory charter and independent status. If only the building had not resembled a casino! Like all of the fledgling independent research centres which have emerged during the recent "epidemic", the Centenary Institute has had to deal with three major issues: inadequate infrastructure, limited funds for developing new groups of merit, and insufficient job security (not to mention salaries) for our full-time career scientists. Perhaps of greatest concern is the fact that the days when one can offer "fame and poverty" to the very best researchers, as Fiona Stanley so aptly put it, are dwindling fast.3 This was driven home to me when two of our most senior group heads were lured to the United States by the offer, not just of much higher salaries, but of far better resources. "If only I did not have to write so many grants for such pathetic amounts of money I would actually have time to do some research", Jon Sedgwick said to me before his departure. The future: the next decade Medical research in Australia Do institutes, independent or otherwise, have a future, or are they likely to acquire the same mortality rate as the biotechnology companies of yesteryear? I believe that some institutes like ours must survive and flourish if Australian medicine is to retain its place at the international table. We have clearly moved into the era of specialisation, in which it is quite acceptable to be recognised as a superb teacher or clinician or researcher, but what is no longer feasible is to be good at every aspect of medicine. The role of institutes, with their critical mass of full-time research staff, is to serve as a focus for collaborative research on the campuses of teaching hospitals and universities with which they are usually affiliated. It is timely that the Wills Review4 has just been published, coinciding as it does with the Federal Government's most welcome commitment to doubling NHMRC funding over the next five to six years. Not only does the Review promote competitive research by extending the concept of partnerships to both Government itself and industry, but it contains a series of innovative recipes which acknowledge the value of the independent institute as a research entity in Australia and of the full-time career scientist. Its implementation is therefore eagerly awaited, particularly by the 30-odd members of the Association of Australian Medical Research Institutes, which between them employ over 2500 research staff. In response to the Wills Review, the challenge for all of us in the medical research community is to secure sufficient ongoing funds to ensure that its recommendations bear fruit. In the case of an institute like ours, this means adding to the existing infrastructural support from the NSW State Government and the Central Sydney Area Health Service by raising funds in the non-Government sector, including from industry and the corporate and wider communities. While creating a public profile and exploiting research are anathema to the purists of the research world, the reality is that the rest of society expects to know about us if they are going to provide the financial support we urgently need. Medical research at the Centenary Institute Having commissioned a new building and recruited high-quality staff, the Institute is now poised to complete the final stage of its 10-year strategic plan. The goal is to create a second critical mass of career researchers in molecular and cellular oncology. A major step forward occurred earlier this year when a $6 million funding package was approved by the Prime Minister. The package is designed to support a strategic alliance with the Sydney Cancer Centre, whereby the Institute would develop a basic cancer research program in the remaining one and a half floors of our building to dovetail with translational and clinical research studies at the Sydney Cancer Centre, located on the adjacent RPAH campus. The first move towards this collaboration has now been made, with the conjoint appointment of John Rasko, a haematologist, who has returned to his old alma mater from the Fred Hutchinson Cancer Research Center in Seattle to head up the Institute's gene therapy laboratory (see Box). The combination of our brand of cellular immunology (traditionally one of Australia's strongest disciplines) with molecular biology targeted at cancer is designed to give the Institute a discrete niche in the postgenomic era now upon us. Edward Jenner as the role model On reading an article recently about the famous country general practitioner, Edward Jenner,5 I rapidly perceived that he was the ideal role model for the institute director of the future. Jenner, famous for his discovery of smallpox vaccination, had other admirable but lesser-known attributes, including an entrepreneurial flair for raising funds, a fascination with diverse areas of science, and proficiency as a poet and musician. When the veracity of his findings on smallpox was being disputed by the inevitable envious colleagues in the United Kingdom and the United States, he raised funds from the public to extend his work (in the absence of any NHMRC equivalent). Later in his life he demanded and received special grants, the first of no less than £10 000, from the government of the day in Great Britain to compensate for the expenses incurred by his research and to set up free vaccination clinics for the public. In 1789 he was elected to the Royal Society, not for his work on vaccination, but rather for his authoritative studies on the habits of the cuckoo nestling. He also found time to classify the botanical specimens brought back by Joseph Banks from James Cook's second voyage to Australia. Despite working full-time on his research, Jenner managed to raise funds and remain a civilised human being. How wonderful it would be for those of us who are institute directors to aspire to just one or two of his many attributes. References Centenary Institute of Cancer Medicine and Cell Biology Act 1985 (NSW). Australian Science and Technology Council. Annual Report 1983-1984. Appendix C. Canberra: AGPS, 1984: 30-36. Stanley FJ. The TVW Telethon Institute for Child Health Research: the birth and growth of a research institute. Med J Aust 1998; 169: 630-633. Wills PJ (Chairman). Health and Medical Strategic Review. The virtuous cycle: working together for health and medical research. Canberra: Department of Health and Aged Care, 1999. Friedman M, Friedland GW. Edward Jenner and vaccination. In: Medicine's 10 greatest discoveries. New Haven: Yale University Press, 1998: 65-93. Authors' details Centenary Institute of Cancer Medicine and Cell Biology, Sydney, NSW. Antony Basten, AO, FAA, FTSE, Executive Director. Reprints: Professor A Basten, Centenary Institute of Cancer Medicine and Cell Biology, Locked Bag 6, Newtown, NSW 2042. a.bastenATcentenary.usyd.edu.au Prime Minister John Howard (center) with Professor Peter Doherty (right) and Professor Antony Basten (left) at the offical opening of the Institute's new building in 1997. The original headquarters of the Centenary Institute located in multipurpose building 94 at the Royal Prince Alfred Hospital. The new Institute building commissioned in 1994. The Centenary Institute of Cancer Medicine and Cell Biology at a glance YearCorporate milestonesResearch milestones 1985Established under an Act of the NSW Parliament as an independent institute with its own Board of Governors and affiliated with the University of Sydney and RPAH 1989Became a functional entity with appointment of Professor Tony Basten as Director and Mr Jim Bain as Chairman of the Board Staff of 20. Director's Clinical Immunology Research Centre became core unit of Institute, comprising his B cell Biology Group and Mycobacterial Research Group (Associate Professor Warwick Britton, University of Sydney) 1991Creation of Foundation with Mr Tim Besley (Chairman), Mr Ken Cowley and Mr Tony Berg as trustees Became a Member Institute of AMRAD Immunopathology Group (Dr Jon Sedgwick, Wellcome Trust SRF)† NHMRC Program Grant to Director renewed 1992Devolved from management of University Appointment of General Manager (Denyse Bartimote) Capital works funding of $17.24 million obtained for new building T cell Biology Group (Dr Barbara Fazekas de St Groth, Wellcome Trust SRF) Thymus Biology Group (Dr Roland Scollay, NHMRC SPRF)† 1994Mr Ken Tribe appointed Chairman of the Board 1995Four and a half floors of new six-storey building commissionedImmune Regulation Group (Dr Phil Hodgkin, Medical Foundation SRF) Liver Immunobiology Group (Professor Geoff McCaughan, RPAH) 1997New building officially opened by Prime Minister New research and development infrastructure funding scheme introduced by State Health Department, providing Institute with $800000 per annumAutoimmunity Research Group (Dr Alan Baxter, NHMRC R Douglas Wright Research Fellow) 1998NHMRC Program Grant in diabetes (Alan Baxter co-chief investigator) 1999$6 million package announced by Prime Minister for joint cancer research program with Sydney Cancer Centre, RPAH Mr Malcolm Noad appointed Chairman of the Board Total staff of 95 Gene Therapy Research Group (Dr John Rasko) Total funding brought to the campus by the Institute was in excess of $50 million *For further details on research programs refer to web site <http://www.centenary.usyd.edu.au> †Left Institute to take up position in United States NHMRC = National Health and Medical Research Council. RPAH = Royal Prince Alfred Hospital. SPRF = Senior Principal Research Fellow. SRF = Senior Research Fellow.

Antony Basten

The Research Enterprise Nature, nurture and my experience with smallpox eradication A career influenced by chance events Frank Fenner MJA 1999; 171: 638-641 Introduction - Family and education - Infectious diseases - Myxomatosis - The Intensified Smallpox Eradication Programme - References - Career outline - Why smallpox could be eradicated - Remaining problems with smallpox - Subsequent eradication programs - Authors' details - - More articles on Infectious diseases and parasitology

Frank Fenner