Research

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. Back to text

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. Back to text

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

Research Reliability of sentinel node status in predicting axillary lymph node involvement in breast cancer James Kollias, P Grantley Gill, Barry E Chatterton, Vivian E Hall, Melissa A Bochner, Brendon J Coventry and Gelareh Farshid MJA 1999; 171: 461-465 For editorial comment, see Ung & Wetzig Abstract - Introduction - Methods - Results - Discussion - References - Authors' details - - More articles on Oncology Abstract Objectives: To assess the reliability of determining sentinel node status in staging regional lymph nodes in breast cancer. Design and setting: Prospective validation study in a major public teaching hospital, comparing histological sentinel node status with that of remaining axillary nodes. Patients: 117 women who underwent sentinel node biopsy and axillary dissection for primary breast cancer between 1995 and 1998. Main outcome measures: Intraoperative success rate in sentinel node identification; false negative rate; predictive value of negative sentinel node status; overall accuracy of sentinel node status. Results: The sentinel node was identified at operation in 95 patients (81.2%). Tumour involvement of the sentinel node was demonstrated in 29 of 31 women (93.5%; 95% CI, 79%-99%). Sixty-four of the 66 women in whom the sentinel node was negative for tumour showed no further involvement of remaining axillary nodes (standard haematoxylin-eosin histological assessment), giving a predictive value of negative sentinel node status of 97% (95% CI, 89%-100%). The overall accuracy in 95 women in whom sentinel node status was compared with axillary node status was 97.9%. Conclusions: Histopathological examination of the sentinel node is an accurate method of assessing axillary lymph node status in primary breast cancer and is likely to be incorporated into future surgical management of women with primary breast cancer. Introduction Axillary lymph node status is the most important prognostic indicator in early breast cancer, and the detection of nodal metastases is a key factor in recommending adjuvant systemic therapy after surgery.1,2 Surgical removal and histopathological assessment of these nodes remains the only accurate way of determining their involvement with tumour. Axillary dissection also reduces the risk of regional recurrence of breast cancer in the axilla,3 as the risk is inversely related to the number of axillary nodes removed.4However, axillary lymph node dissection is not without morbidity: seroma formation, wound infection, damage to nerves, and reduced shoulder mobility. Of particular importance is lymphoedema, which occurs in 15% and 30% of women.5-8 As a consequence, other, less invasive methods of assessing axillary node status have been investigated (eg, mammography, ultrasound and colour doppler imaging, magnetic resonance imaging [MRI] and positron emission tomography [PET] scanning), but have yet to achieve the accuracy of surgical staging. Axillary node sampling -- removal of a small number of Level 1 nodes (those below the lower border of the pectoralis minor muscle) -- is associated with fewer complications, and has been proposed as an alternative to complete axillary dissection for staging of the axilla.9,10 However, its efficacy has been questioned.11 With the advent of population-based mammographic screening programs, there has been a dramatic decrease in tumour size and lymph node involvement in women diagnosed with early breast cancer.12,13 Thus, an increasing proportion of women will undergo axillary dissection only to find that their lymph glands are free of disease. Ideally, there should be a method of providing accurate assessment of axillary lymph node status without the need for axillary dissection. The sentinel lymph node (the first draining node within a lymph node basin) is the first to receive lymphatic drainage from a tumour site. Selective biopsy of this node allows the detection of metastases in clinically normal nodes with a low false negative rate, and has been used in patients with operable breast cancer by several groups.14-19 Their findings indicate that the status of the sentinel node(s) can accurately predict that of the fully dissected axilla. We report our experience of lymphoscintigraphy, intraoperative sentinel node mapping and sentinel node biopsy in 117 women with primary operable breast cancer. Our aims were: To assess the success rate of lymphoscintigraphy and intraoperative lymph node mapping in identifying the sentinel node; and To assess the accuracy of sentinel node biopsy in staging the axillary nodes. Methods Patients A consecutive series of 117 women treated for primary breast cancer at the Royal Adelaide Hospital Breast Unit between June 1995 and August 1998 entered a prospective evaluation of the technique of sentinel lymph node biopsy in breast cancer. Ethical approval for the study was provided by the Human Ethics Committee of the Royal Adelaide Hospital. All women gave written informed consent to participate in the study. Eligibility criteria were: Operable primary breast cancer (tumour, < 5 cm in diameter), detected clinically and by imaging, and confirmed by cytology, core biopsy or open biopsy; Clinically impalpable axillary lymph nodes; and The usual surgical indications for axillary dissection (ie, invasive, operable cancer). Patients were excluded if their condition did not fulfil these criteria; if they were pregnant or currently breastfeeding; if there was a high clinical suspicion or preoperative verification of axillary nodal involvement; or if they had metastatic breast carcinoma or a preoperative diagnosis of ductal carcinoma-in-situ. The women's ages ranged from 31 to 82 years (median, 60 years). Their clinical characteristics are summarised in Table 1. During the period of study, no eligible women refused entry to the study. Isotope injection technique The radiopharmaceutical used was 99mTc-labelled antimony sulfide colloid ("Lymph-Flo", Royal Adelaide Hospital Radiopharmacy). The colloid underwent filtration through a 0.2-µ sterile filter, ensuring more than 80% of the filtered particles were smaller than 20 nm. A 32-mm, 25-gauge needle was used to inject 40 MBq of tracer to four sites surrounding the palpable margin of the breast lesion. If the lesion was not palpable, ultrasound localisation was performed, and the injection was given in a similar manner under ultrasound guidance. In the initial stages of the study, 0.5 mL of tracer was injected in each of 82 patients. For the remaining 35 women, the injected volume was increased to 4 mL in four divided doses. In these latter women, the injection site was lightly massaged, and they were instructed to move their arms to encourage lymphatic movement. All radioisotope injections were given on the morning of the day of surgery. Lymphoscintigraphy and lymph node mapping After injection, serial anterior and appropriate lateral images were obtained with a large-field-of-view gamma camera (GE XRT, General Electric) at about 15-minute intervals until the initial draining node (or nodes) was visualised (Figure 1). The surface projection of the sentinel node was then marked on the skin with a radioactive marker. Orthogonal projections were made by the established technique of "triangulation"; the marks were joined by a straight line to indicate the base of a right-angled triangle with the node at the apex. Body outline was marked with a radioactive marker, or a transmission image was performed by holding a "flood" source behind the patient. The intraoperative probe (RMD CTC 4 with audible guidance system, Gammasonics, Melbourne) was calibrated in the Nuclear Medicine Department to the counts detected at the skin surface. Surgical technique After completion of lymphoscintigraphy and sentinel node mapping, the patient and hand-held gamma probe were transferred to the operating theatre. In 66 patients, 1-2 mL of 2.5% Patent Blue V dye (Guerbet Laboratories, France; distributed by Fauldings Australia, Adelaide) was injected into the breast parenchyma or subdermal fat overlying the tumour to facilitate intraoperative identification of the sentinel node. Blue dye alone was used in 19 patients before a gamma probe was available. At operation, a 2-cm transverse axillary incision was made in accordance with the planned axillary lymph node dissection, but taking into account the preoperative skin markings indicating the location of the sentinel node at lymphoscintigraphy. An attempt was made to identify the node in vivo before commencement of axillary dissection. The node was identified by its blue colour (if dye was used) and/or by the hand-held gamma probe (in a sterile sheath). The probe enabled detection of individual nodes with radioactivity levels significantly greater than those of the axillary fat (Figure 2). Sometimes more than one sentinel node was identified. If both dye and radioisotope were used for lymphatic mapping, the blue node corresponded to the most radioactive node. Once the sentinel node was removed, its activity was reassessed ex vivo and it was sent for histological examination separately from the main axillary nodal specimen. The axillary fat was then examined with the gamma probe in vivo to exclude any residual activity suggesting further sentinel nodes. The axillary skin incision was then lengthened and a level I and II axillary lymph node dissection was performed. The resected axillary tissue was examined ex vivo using the probe to identify any further radioactive or blue lymph nodes not identified during in-vivo examination. Histopathological examination All specimens were examined by duty histopathologists at the Institute of Medical and Veterinary Science. The histological tumour features were classified according to tumour size and grade,20 and presence or absence of vascular invasion.21 Generally, sentinel nodes were submitted in their entirety for histological evaluation. Those larger than 1.5 cm were sliced before paraffin embedding. Each node was placed in an individual cassette. At least one section of each node was stained with haematoxylin-eosin (H&E) and examined with light microscopy. Immunohistochemical analysis (antikeratin antibody CAM 5.2, Becton Dickinson) was performed in H&E-stained sections suspected of having metastatic tumour deposits. The axillary fat was fixed in formalin and the nodes were later isolated from the fat after clearance in Carnoy's solution. Each node was placed in an individual cassette and larger nodes were sliced before being embedded in paraffin. At least one H&E-stained section of each node was examined. Statistical analysis A false negative sentinel node was defined as an excised sentinel lymph node which contained no microscopically detectable tumour, but which was associated with at least one tumour-positive node in the remaining resected axillary tissue. The false negative rate and the predictive value of negative sentinel node status were calculated together with 95% confidence intervals. The kappa (κ) statistic for paired data was used to assess the level of agreement between sentinel node status and axillary node status.22 A score of -1 indicates perfect disagreement and + 1 indicates perfect agreement. The corresponding z and P values were calculated. Univariate analysis was used to assess clinical and histological factors that predicted intraoperative sentinel node localisation. Fisher's exact and χ2 tests were used for other analyses between groups. Results Lymphoscintigraphy The sentinel node was identified on preoperative lymphoscintigraphy in 74 of 117 women (63.2%). One sentinel node was identified in 52 women, two were identified in 20 women, and in two further women three and four sentinel nodes were identified, respectively. The sentinel node was identified outside the lower axilla in nine patients (Table 2). A significant increase in sentinel node identification at lymphoscintigraphy was noted after the injection of larger isotope volumes into the breast (77% v 57%; χ2 = 4.15; P = 0.04), while rates of intraoperative detection of the sentinel node also increased (91% v 76%; χ2 = 3.4; P = 0.06). Intraoperative sentinel node identification The sentinel node was identified in 95 patients (81.2%) at operation. In 66 women, one sentinel node was identified, two were identified in 20 women, three in eight women, and in one four sentinel nodes were identified. The sentinel node was identified in 35 of the 51 women in whom radioisotope alone was used (68.6%), compared with 18 of 19 women in whom blue dye alone was used (94.7%) and 42 of 47 women in whom both isotope and blue dye were used (89.4%) (χ2 = 9.6; P = 0.008). Of the clinical and histological factors assessed for predicting intraoperative sentinel node identification, only a positive preoperative lymphoscintigram was significant (χ2 = 28.7; P < 0.001) (Table 3). Predictive value of sentinel node(s) In 95 patients in whom the sentinel node was identified, 31 had metastatic tumour involvement of axillary nodes (32.6%). Tumour involvement of the sentinel node was demonstrated in 29 of these 31 women (93.5%; 95% CI, 79%-99%), giving a false negative rate of 6.5%. The sentinel node was the only positive node in 13 of 31 women (41.9%). Of 66 women with a negative sentinel node, 64 had no tumour involvement in the remainder of the axillary nodes (by standard H&E histological assessment), giving a predictive value of negative sentinel node status of 97% (95% CI, 89%-100%). The overall accuracy in 95 patients in whom sentinel node status was compared with axillary node status was 97.9% (κ, 0.95; z = 9.3; P < 0.001) (Table 4). Of the 22 women in whom the sentinel node was not identified at operation, six had nodal metastases on histological examination of the dissected axillary nodes. Discussion The concept of the sentinel lymph node is based on the premise that the first lymph node to receive lymphatic drainage from a tumour site should be the first site of lymphatic spread; that "skip metastases" do not occur; and that the absence of tumour metastases in the sentinel node implies the absence of lymph node metastases in the entire lymphatic basin. This concept was first described in penile carcinoma in 197723 and was later studied in patients with cutaneous melanoma.24 Previous detailed pathological studies of axillary nodes in women with breast cancer have demonstrated a skip metastasis rate of less than 5%.25,26Our results confirm that the status of the sentinel lymph node(s) predicts the overall axillary lymph node status with a high degree of accuracy, and can thus be used to limit the morbidity associated with axillary surgery. More importantly, the predictive value of a tumour-free sentinel node was 97%. As such, women identified with a sentinel node free of metastatic tumour can be reassured that further axillary lymph node involvement is highly unlikely. Other studies of sentinel node biopsy in breast cancer (using blue dye and radioactive isotope techniques) have shown sentinel node status to accurately determine axillary lymph node status in more than 95% of women.14-19 We still need to deal with the problem that 3% of patients exhibited tumour-positive axillary nodes when the biopsied sentinel node was negative. The optimal method of pathological assessment of the sentinel node remains unresolved and was not addressed in our study. This issue was discussed at the Adelaide Workshop on Sentinel Node Biopsy in Breast Cancer27 and is the subject of further studies by one of us (G F). Giuliano et al28 have found that immunohistochemical studies of sentinel nodes showed micrometastases in an additional 11% of women whose sentinel node was tumour negative on light microscopy. However, similar assessment of two women with false negative results in our study did not reveal metastases. The implications of micrometastases detected by sensitive immunohistochemical and polymerase chain reaction (PCR) techniques for multidisciplinary care are unknown. They are currently being investigated in trials in the United States (Merrick Ross, Associate Professor of Surgical Oncology, M D Anderson Hospital, Texas, USA, personal communication). Until the answers to this question are available, a large UK trial (ALMANAC) is assessing sentinel node status by conventional microscopy (R Mansell, Professor of Surgery, Cardiff University, UK, personal communication), as this is the current method on which treatment planning is based. These uncertainties emphasise the need for Australian studies to incorporate detailed protocols for pathology assessment of the sentinel node. The prognostic implications of a false negative sentinel node are uncertain, but should be compared with the considerable physical morbidity associated with axillary dissection in lymph node negative women. There is a definite error rate in routine pathological assessment of axillary dissection specimens which may underestimate metastatic disease by 11%-30%,27,29 while unselective sampling of the axilla fails to remove involved nodes in many women.11 The false negative rate must ultimately be minimised by maximal detection of the sentinel node by scintigraphy, careful operative technique and optimal pathological assessment, which requires an experienced multidisciplinary team. The concomitant intraoperative use of both blue dye and radionuclide methods for lymphatic mapping was particularly useful for sentinel node biopsy. Preoperative lymphoscintigraphy permits identification of the sentinel node and subsequent planning of the site of skin incision. Several radiolabelled colloids are currently in use around the world, but the recent workshop in Adelaide27 identified antimony colloids as having excellent properties for lymphoscintigraphy. This is the only agent available for this purpose in Australia and is able to visualise sentinel nodes in the internal mammary chain as well as in the axillary node group. The blue dye technique facilitated visualisation of the sentinel node at the time of surgery and was supplemented by the use of an intraoperative gamma probe. In all patients in whom both blue dye and radionuclide were used, the blue node corresponded to the "hot" node previously identified on lymphoscintigraphy and identified intraoperatively with the hand-held gamma probe. Furthermore, the identification of a sentinel node at preoperative lymphoscintigraphy was the only factor significantly associated with the intraoperative identification of the sentinel node. Lymphoscintigraphy also demonstrates the number and location of potential sentinel nodes requiring biopsy. The initial rate of preoperative identification of the sentinel node by lymphoscintigraphy in our series was lower than that in published reports. However, this was overcome by increasing the volume of the isotope injection and presumably increasing tissue oncotic pressure, lymphatic uptake and drainage. The importance of isotope volume in achieving successful scintigraphic identification of the sentinel node has also been suggested by others.30 Sentinel lymph node mapping and biopsy are likely to be incorporated into clinical practice, provided they can be successfully performed in most patients, and it can be shown that women with negative sentinel nodes who undergo no further treatment to the axilla are not adversely compromised in terms of disease-free and overall survival. This will be best established by randomised controlled studies comparing sentinel node biopsy with standard axillary surgical management. In addition, these studies should address the implied assumption of lower short and long term morbidity associated with this procedure, the optimal methods of pathological assessment, and allow analysis and comparison with clinicopathological variables in predicting sentinel node status. Studies are currently being undertaken in Europe, the United Kingdom and the United States and it is hoped that Australian women can soon participate in similar trials in Australia. References Carter CL, Allen C, Henson DE. Relation of tumour size, lymph nodes status and survival in 24,740 breast cancer cases. Cancer 1989; 63: 181-187. Fisher ER, Anderson S, Redmond C, Fisher B. Pathologic findings from the National Surgical Adjuvant Breast Project Protocol B-06: 10 year pathological and clinical prognostic discriminants. Cancer 1993; 71: 2507-2514. Fisher D, Woolmark N, Bauer M, et al. The accuracy of clinical nodes staging and of limited axillary dissection as a determinant of histological nodal status in carcinoma of the breast. Surg Gynecol Obstet 1991; 152: 765-772. Axellsson CK, Mouridsen HT, Zedeler K. Axillary dissection of Level I and II lymph nodes is important in breast cancer classification: The Danish Breast Cancer Cooperative Group (DBCG). Eur J Cancer 1992; 28: 1415-1418. Kissin MW, Querci-Della-Rovere G, Easton D, Westbury G. Risk of lymphoedema following the treatment of breast cancer. Br J Surg 1986; 73: 580-584. Aitken RJ, Gayes MN, Rodger A, et al. Arm morbidity within a trial of mastectomy and either node sample with selective radiotherapy or axillary clearance. Br J Surg 1989; 76: 568-571. Larson D, Weinstein M, Goldburg I, et al. Oedema of the arm as a function of the extent of axillary surgery in patients with Stage 1-2 carcinoma of the breast treated with primary radiotherapy. Int J Radiat Oncol Biol Phys 1986; 12: 1575-1582. Liljegren G, Holmburg L. Arm morbidity after sector resection and axillary dissection with or without postoperative radiotherapy in breast cancer. Stage 1: Results from a randomised trial. Uppsala Orebro Breast Cancer Study Group. Eur J Cancer 1997; 33: 193-199. Steel RJC, Forrest APM, Gibson T, et al. The efficacy of lower axillary sampling in obtaining lymph node status in breast cancer: a controlled randomised trial. Br J Surg 1985; 72: 368-369. Dixon JM, Dillon P, Anderson TJ, Chetty U. Axillary node sampling in breast cancer: an assessment of its efficacy. Breast 1998; 7: 206-208. Kissin MW, Thompson PH, Price AB, et al. The inadequacy of axillary sampling in breast cancer. Lancet 1982; 1: 1210-1212. Tabar L, Fagerberg G, Duffy SW, et al. Update of the Swedish two-county program of mammographic screening for breast cancer. Radiol Clin North Am 1992; 30: 187-210. Cady B, Stone MD, Schuler JG, et al. The new era in breast cancer: invasion, size and lymph node involvement dramatically decreased as a result of mammographic screening. Arch Surg 1996; 131: 301-308. Giuliano AE, Kirgan DM, Guenther JM, Morton DL. Lymphatic mapping and sentinel lymphadenectomy in breast cancer. Ann Surg 1994; 220: 391-401. Albertini JJ, Lyman GH, Cox C, et al. Lymphatic mapping and sentinel node biopsy in the patient with breast cancer. JAMA 1996; 276: 1818-1822. Veronesi U, Paganelli G, Galimberti V, et al. Sentinel node biopsy to avoid axillary dissection in breast cancer with clinically negative lymph nodes. Lancet 1997; 349: 1864-1867. Borgstein PJ, Pijpers R, Comans EF, et al. Sentinel lymph node biopsy in breast cancer: guidelines and pitfalls of lymphoscintigraphy and gamma probe detection. J Am Coll Surg 1998; 186: 275-283. Cox CE, Pendas S, Cox JM, et al. Guidelines for sentinel node biopsy and lymphatic mapping of patients with breast cancer. Ann Surg 1998; 227: 645-653. O'Hea BJ, Hill ADK, El-Shirbiny AM, et al. Sentinel lymph node biopsy in breast cancer: initial experience at Memorial Sloan-Kettering Cancer Center. J Am Coll Surg 1998; 186: 423-427. Elston CW, Ellis IO. Pathological prognostic factors in breast cancer. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology 1991; 19: 403-410. Pinder SE, Ellis IO, Galea M, et al. Pathological prognostic factors in breast cancer. Vascular invasion: relationship with recurrence and survival in a large study with long-term follow-up. Histopathology 1994; 24: 41-47. Fliess JL. Statistical methods for rates and proportions. 2nd edition. New York, NY: John Wiley and Sons, 1981. Cabanas RM. An approach for the treatment of penile carcinoma. Cancer 1977; 39: 456-466. Morton DL, Wen D-R, Wong JH, et al. Technical details of intraoperative lymphatic mapping for early stage melanoma. Arch Surg 1992; 127: 392-399. Berg JW. The significance of axillary node levels in the study of breast cancer. Cancer 1955; 8: 776-778. Veronesi U, Rilke F, Luimi A, et al. Distribution of axillary node metastases by level of invasion: an analysis of 539 cases. Cancer 1987; 59: 682-687. Kollias J, Gill PG, Chatterton B, et al. Sentinel node biopsy in breast cancer: recommendations for surgeons, pathologists, nuclear physicians and radiologists in Australia and New Zealand. Aust N Z J Surg 1999. In press. Giuliano AE, Dale PS, Turner RR, et al. Improved axillary staging of breast cancer with sentinel lymphadenectomy. Ann Surg 1995; 222: 387-399. Hainsworth PJ, Tjandra JJ, Stillwell RG, et al. Detection and significance of occult metastases in node negative breast cancer. Br J Surg 1993; 80: 459-463. Krag DN, Ashikaga T, Harlow SH, Weaver DL. Development of sentinel node targeting technique in breast cancer patients. Breast J 1998; 4: 67-74. (Received 22 Apr, accepted 9 Sep, 1999) Authors' details Royal Adelaide Hospital and Women's Health Centre, Adelaide, SA. James Kollias, MB BS, FRACS, Staff Surgeon, Breast-Endocrine and Surgical Oncology Unit. P Grantley Gill, FRACS, MD, Head, Breast-Endocrine and Surgical Oncology Unit; and Associate Professor, University of Adelaide. Barry E Chatterton, MB BS, FRACP, Director, Department of Nuclear Medicine. Vivian E Hall, MB BS, FRACR, Radiologist, Department of Radiology. Melissa A Bochner, MB BS, FRACS, Senior Registrar, Breast-Endocrine and Surgical Oncology Unit. Brendon J Coventry, FRACS, PhD, Senior Surgeon, Breast-Endocrine and Surgical Oncology Unit; and Senior Lecturer, University of Adelaide. Department of Tissue Pathology, Institute of Medical and Veterinary Science, Adelaide, SA. Gelareh Farshid, MB BS, FRCPA, Senior Lecturer, University of Adelaide. Reprints will not be available from the authors. Correspondence: Associate Professor P G Gill, Breast-Endocrine Surgical Oncology Unit, Royal Adelaide Hospital, North Terrace, Adelaide, SA 5000. cbatesbrownswordATmedicine.adelaide.edu.au Back to textBack to textBack to textBack to text 3: Clinical and histological features predicting success in sentinel node identification at operationVariableNo. of womenSentinel node identified (%)χ2 (P)Age (years)< 503330 (91%)2.84> 508465 (77%)(0.09)Tumour site (quadrant)Upper/outer86 69 (80%)0.2Lower/inner31 26 (84%)(0.66)Tumour detectionScreening56 42 (75%)2.7Symptomatic61 53 (87%)(0.1)Previous core biopsyYes1210 (83%)0.04No10585 (79%)(0.84)Previous open biopsyYes11089 (81%)0.1No76 (86%)(0.75)Scintiscan resultPositive74 71 (96%)28.7Negative43 24 (56%)(< 0.001)OperationMastectomy31 24 (77%)1.23Wide local excision5547 (85%)(0.54)Localised wide local excision3124 (77%)Tumour size*< 2cm79 64 (81%)0.03≥ 2cm36 29 (81%)(0.95)Tumour grade*12721 (78%)2.425346 (87%)(0.31)33526 (74%)Lymphatic/vascular invasionNegative101 83 (82%)0.44Positive16 12 (75%)(0.5)Lymph node statusNegative80 64 (80%)0.2Positive37 31 (84%)(0.6) * Excludes two cases of ductal carcinoma-in-situ, diagnosed after excision. 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James Kollias · Barry E Chatterton · Vivian E Hall · Melissa A Bochner · Brendon J Coventry · Gelareh Farshid

Research Iodine deficiency in ambulatory participants at a Sydney teaching hospital: is Australia truly iodine replete? Jenny E Gunton, Graham Hams, Marcelle Fiegert and Aidan McElduff MJA 1999; 171: 467-470 For editorial comment, see Eastman Abstract - Introduction - Methods - Results - Discussion - References - Authors' details - - More articles on Endocrinology Abstract Objective: To assess iodine status in four separate groups -- pregnant women, postpartum women, patients with diabetes mellitus and volunteers. Design and setting: Prospective cross-sectional study at a tertiary referral hospital in Sydney. Participants: 81 pregnant women attending a "high risk" obstetric clinic; 26 of these same women who attended three months postpartum; 135 consecutive patients with diabetes mellitus attending the diabetes clinic for an annual complications screen; and 19 volunteers. There were no exclusion criteria. Methods: Spot urine samples were obtained, and urinary iodine was measured by inductively coupled plasma mass spectrometer. Outcome measures: Iodine status based on urinary iodine concentration categorised as normal (> 100 µg/L), mild deficiency (51-100 µg/L) and moderate to severe deficiency (< 50 µg/L). Results: Moderate to severe iodine deficiency was found in 16 pregnant women (19.8%), five postpartum women (19.2%), 46 patients with diabetes (34.1%) and five volunteers (26.3%). Mild iodine deficiency was found in an additional 24 pregnant women (29.6%), nine postpartum women (34.6%), 51 patients with diabetes (37.8%) and 9 normal volunteers (47.4%). Median urinary iodine concentration was 104 µg/L in pregnant women, 79 µg/L in postpartum women, 65 µg/L in patients with diabetes mellitus and 64 µg/L in volunteers. Conclusions: The high frequency of iodine deficiency found in our participants suggests that dietary sources of iodine in this country may no longer be sufficient. Further population studies are required. Introduction It is currently believed that iodine deficiency does not exist in Australia.1,2 However, iodine status is seldom, if ever, measured in routine clinical care, and iodine deficiency may have significant adverse consequences, particularly during pregnancy (Box 1). Box 2 shows some of the reasons why iodine intake in Australia may be inadequate. The recommended daily intake (RDI) of iodine is 100 µg daily for the general population and 150-200 µg daily for women who are pregnant or breastfeeding6-8,10 (iodine demand increases during pregnancy because of increased renal clearance and fetal iodine transfer). Approximately 90% of iodine is excreted in the urine,1,11 and iodine status is usually assessed by measuring urinary iodine concentration. The accepted minimum adequate level of urinary iodine is 100 µg/L, and levels above this are considered normal.1,6-9,12 Urinary iodine concentrations below 25 µg/L are classified as severe deficiency, and are associated with an increased risk of cretinism; 26-50 µg/L is classified as moderate deficiency, and 51-100 µg/L is regarded as mild iodine deficiency.1,6-9,12 The World Health Organization (WHO) recommends that the median urinary iodine concentration for populations as a whole should be more than 100 µg/L, that less than 20% of the population should have a urinary iodine concentration below 50 µg/L, and that no cretinism occurs.12 Having previously found low levels of free thyroxine in pregnant women,13 and in light of the adverse consequences of iodine deficiency during pregnancy, we initially set out to test the iodine status of a group of pregnant women. We subsequently included other groups to widen our investigation of iodine status. Methods Study participants Our study was conducted at a tertiary referral hospital in Sydney. Participants in the study included women who attended a specialist "high risk" obstetric clinic, patients of both sexes with diabetes who attended the hospital's diabetes clinic, and healthy, non-pregnant volunteers recruited after a presentation about iodine. Participants thus comprised 81 consecutive pregnant women who attended the obstetric clinic between 1 August 1998 and 1 April 1999, 26 of these same women who were reassessed at three months postpartum, 135 consecutive patients who attended the diabetes clinic for an annual complications screen between 1 November 1998 and 1 February 1999, and 19 volunteers recruited between 1 February and 1 July 1999. All participants provided a routine urine sample. There were no exclusion criteria. One of the 81 pregnant women had thyrotoxicosis as a result of Graves' disease -- she particpated before commencing therapy. Twenty-two of the patients attending the diabetes clinic (16.1%) had type 1 diabetes, 103 (76.3%) had type 2 diabetes and 10 (7.5%) had impaired glucose tolerance. One of the patients with diabetes had recently received iodine-containing intravenous contrast medium during a coronary angiogram, and one was taking amiodarone. No other participant was known to have received contrast medium, or to be taking amiodarone or iodine supplements. Urinary iodine measurement Urinary iodine concentrations were determined by means of a Varian UltraMass inductively coupled plasma mass spectrometer with SPS-5 autosampler (Varian Inc., Palo Alto, California, USA). The measurement was calibrated over a range of 0-1000 µg iodine per litre. The lower limit of detection for the assay was 2 µg/L. The reproducibility of the assay as represented by the 100 µg/L calibrator assessed over three months was ± 6 µg/L (± 2 SD). Comparison with the colorimetric/Sandell-Koltkoff reaction method showed a highly significant correlation (P < 0.001; see Box 3). Other authors have also compared the methods and found high correlation.14 In particular, no systematic biases were found at low iodine concentrations. Some investigators use the urinary iodine/creatinine ratio to determine iodine status.1,14 We thus measured urinary creatinine by the Creatinine Jaffa method (Boehringer Mannheim Systems, Mannheim, Germany) and calculated iodine/creatinine ratios (µg iodine/g creatinine) for each participant. The correlation between urinary iodine and iodine/creatinine ratio was high for non-pregnant participants (r = 0.969; P < 0.001) and lower for the pregnant group (r = 0.419; P < 0.001). Twenty-four-hour urinary iodine measurement may be used to assess iodine status,6 but this method can be unreliable because of incorrect or incomplete collection,15 and is less practical than spot samples for population surveys.9,12 To compare this method with our spot sampling, we selected six pregnant women (on the basis of their spot urine concentrations to cover a range of values) who collected 24-hour urine samples for iodine content measurement. The correlation was highly significant (r2 = 0.82), thus confirming that spot urine samples were a reliable way of measuring iodine status. As part of routine care, 70 of the 81 pregnant women and 121 of the 135 patients with diabetes had thyroid function tests. Free thyroxine (FT4) and thyroid-stimulating hormone (TSH) levels were measured by means of an automated chemiluminescence system (Chiron Diagnostics, Scoresby, Vic.). We did not seek ethical approval for this study as it involved no deviation from usual care, except in the case of the 19 volunteers who agreed to provide a urine sample. Statistical analysis We used SPSS for statistical analysis.16 Means are expressed with ± 2 standard deviations, and medians with 95% confidence intervals (CI) are shown where data were not normally distributed. The results of non-parametric variables (including iodine results) were compared by means of the Mann-Whitney Wilcoxon rank sum test. Results Box 4 shows the mean and median ages and the results of spot urinary iodine concentration for the four groups. The three non-pregnant groups had similar urinary iodine concentration results, with a slightly higher median in the postpartum group compared with the group with diabetes. As expected,17-19 the pregnant women had higher urinary iodine concentrations than the other groups as a whole (P = 0.004). The iodine/creatinine ratios also show a high proportion of abnormal results (Box 4). The median iodine concentration in the 26 postpartum women (79 µg/L) who provided repeat urine samples for iodine measurement three months after delivery was considerably lower than that in the 81 pregnant women (104 µg/L). However, this difference was not statistically significant (P = 0.249). The patient with diabetes who had received iodine-containing intravenous contrast medium during a coronary angiogram in the month before the urinary spot test had a urinary iodine concentration of 2170 µg/L. Box 5 shows TSH levels and FT4 levels versus iodine status in pregnant and non-pregnant participants. There was no significant relationship between iodine status and FT4 or TSH levels in either the pregnant group or non-pregnant group. Separate analysis of patients with diabetes and postpartum women did not significantly alter these results. However, there was a weak correlation between FT4 and urinary iodine levels when examined as a continuous variable (Pearson correlation coefficient, 0.26; P = 0.016). Discussion By WHO criteria,12 the median iodine levels in our pregnant participants were only just adequate, while those in postpartum women, patients with diabetes and normal volunteers were inadequate. The slightly higher median iodine level in the postpartum group compared with that in the group with diabetes may have been the result of this concentration not having returned to baseline after pregnancy, although further study is required to document the rate of change post partum. We believe the low values in patients with diabetes was not a problem specific to diabetes, but merely a reflection of low urinary iodine levels in the general population. The similarity between the patients with diabetes and our small group of volunteers supports this view. Our data are consistent with generally low iodine intake. Our findings mirror recent reports from other countries.9,11,20 A United States study showed that the median urinary iodine concentration in 1988-1994 had decreased by more than 50% from that in 1971-1974.9,11 The 1988-1994 results showed 11.7% of the US population to be iodine deficient (a 4.5-fold increase since 1971-1974). The mean urinary iodine concentration in that population was 265 µg/L, and people from higher socioeconomic groups were more likely to be iodine deficient. Our data may also reflect this effect, as, although our patients were attending a public clinic, the hospital catchment area is a relatively high socioeconomic group. Our data suggest that Australia may be experiencing a similar trend to that seen in the US. Iodine deficiency during pregnancy can affect the thyroid glands of both the mother and baby,10,17-19 and may have many adverse health consequences (Box 1). Some, but not all, researchers have found an increase in urinary iodine levels during pregnancy.10,17-19 Smyth et al studied urinary iodine concentration in a group of pregnant women in an area of Ireland with known borderline iodine deficiency.10 In the third trimester, they found a mean urinary iodine concentration of 132 µg/L (standard error of the mean, 6.8), and found that urinary iodine concentration increased during pregnancy. In a more iodine-deficient area, Glinoer et al found that urinary iodine concentration did not increase during pregnancy (median iodine concentration 45 µg/L after 20 weeks' gestation, no mean given).19 So, it is not clear whether the apparently higher levels in our pregnant women were pregnancy related or, in fact, masked iodine deficiency in pregnancy. We found that a considerable percentage of pregnant women (4.9%) were severely iodine deficient, with spot urine results of < 25 µg/L. While this is the threshold below which cretinism may occur, other factors, such as selenium deficiency and the presence of dietary goitrogens, also play a part in determining cretinism,21 and these two factors are not usually seen in Sydney. Therefore, we would not expect to see an increased incidence of cretinism in Sydney on the basis of these results alone. However, more subtle adverse fetal outcomes may occur. Our findings suggest that we should no longer automatically consider Australia an iodine-replete country. We found that iodine deficiency was common among 235 people attending a Sydney teaching hospital and speculate that these data are applicable to the general population, although this will require independent confirmation. The frequency of iodine deficiency in our pregnant population (18.8%) approaches the maximum acceptable level recommended by WHO (20%); this recommendation was exceeded in our group with diabetes (34.1%) and the normal volunteers (26.3%). The postpartum women had a median iodine concentration of 79 µg/L, which is lower than the WHO recommendation of 100 µg/L. This has important public health implications. The weaknesses of this study include the small group of normal volunteers, and perhaps the use of a sample from a teaching hospital rather than the community. The normal volunteers had results which are equivalent to those seen in postpartum women and non-pregnant patients with diabetes. Our subjects were all ambulatory, not inpatients at the time of testing, and generally well. Although 24-hour urinary iodine excretion studies may be the ideal method of assessing iodine status, these are not generally performed in large numbers for a variety of technical and practical reasons. A weak correlation between urinary iodine and free thyroxine was observed for all non-pregnant participants in total, and for the participants with diabetes mellitus. Because of the large number of other factors which influence thyroid function (including pregnancy),13 the relatively loose correlations are an expected finding. Further studies are needed, and these include (i) population surveys in Sydney and elsewhere in Australia; (ii) assessment of thyroid size (eg, by ultrasound) in relation to iodine status; and (iii) detailed assessment of neonates, including thyroid size, neonatal TSH levels, and detailed neurological outcomes. References Hetzel BS. Iodine deficiency disorders. In: Garrow JS, James WPT, editors. Human nutrition and dietetics. Edinburgh: Churchill Livingstone, 1993: 534-555. Mortimer RH. Thyroid disease and pregnancy. Aust N Z J Med 1998; 28: 647-653. Tasmanian Thyroid Advisory Committee. Study in disease surveillance. 1950-1979. Med J Aust 1981; 2: 234-238. Clements FW. Goitre studies. 1. The incidence of endemic goitre in three areas in Australia. Med J Aust 1948; 21: 637-639. Hales I. Studies in diseases of the thyroid gland [MD thesis] Sydney: University of Sydney, 1971. Boyages S. Iodine deficiency disorders. J Clin Endocrinol Metab 1993; 77: 587-591. Clugston GA, Hetzel BS. Iodine. In: Shils ME, Olson JA, Shike M, editors. Modern nutrition in health and disease. 8th ed. Vol. 1. Philadelphia: Lea and Febiger, 1994; 252-263. Delange F. The disorders induced by iodine deficiency. Thyroid 1994; 4: 107-128. Hollowell JG, Staehling NW, Hannon WH, et al. Iodine nutrition in the United States. Trends and public health implications: iodine excretion data from the National Health and Nutrition Examination Surveys I and III (1971-1974 and 1988-1994). J Clin Endocrinol Metab 1998; 83: 3401-3408. Smyth PPA, Hetherton AMT, Smith DF, et al. Maternal iodine status and thyroid volume during pregnancy: correlation with neonatal iodine intake. J Clin Endocrinol Metab 1997; 82: 2840-2843. Dunn JT. What's happening to our iodine? [editorial]. J Clin Endocrinol Metab 1998; 83: 3398-3400. World Health Organization Nutrition Unit. Indicators for assessing iodine deficiency disorders and their control through salt iodization. Document No. WHO/NUT 94.6. Geneva: WHO, 1994: 36. McElduff A. Measurement of free thyroxine levels (fT4) in pregnancy. Aust N Z J Obstet Gynaecol 1999; 39: 158-161. May SL, May WA, Bourdoux PP, et al. Validation of a simple, manual urinary iodine method for estimating the prevalence of iodine-deficiency disorders, and interlaboratory comparison with other methods. Am J Clin Nutr 1997; 65: 1441-1445. McElduff A, Shuter B, Cooper R, et al. Measuring renal function in patients with diabetes mellitus. J Diabetes Complications 1997; 11: 225-229. SPSS [computer program], version 6.0. Chicago, Ill: SPSS Inc, 1996. Silva JE, Silva S. Interrelationships among serum thyroxine, triiodothyronine, reverse triiodothyronine, and thyroid-stimulating hormone in iodine-deficient pregnant women and their offspring: effects of iodine supplementation. J Clin Endocrinol Metab 1981; 52: 671-677. Glinoer D, De Nayer P, Bourdoux et al. Regulation of maternal thyroid during pregnancy. J Clin Endocrinol Metab 1990; 71: 276-287. Glinoer D, Delange F, Laboureur I, et al. Maternal and neonatal thyroid function at birth in an area of marginally low iodine intake. J Clin Endocrinol Metab 1992; 75: 800-805. Valiex P, Zarabska M, Preziosi P, et al. Iodine deficiency in France [letter]. Lancet 1999; 353: 1766-1767. Moreno-Reyes R, Suetens C, Mathieu F, et al. Kashin-Beck osteoarthropathy in rural Tibet in relation to selenium and iodine status. N Engl J Med 1998; 339: 1112-1120. Received 13 Apr, accepted 21 Aug, 1999 Authors' details Royal North Shore Hospital, St Leonards, NSW. Jenny E Gunton, MB BS, Endocrine Fellow, Department of Endocrinology. Graham Hams, MAppSc, Senior Staff Scientist, Pacific Laboratory Medicine Services. Marcelle Fiegert, BEd, MNutri Diet, Dietitian, Department of Nutrition. Aidan McElduff, FRACP, PhD, Senior Staff Specialist in Endocrinology, Department of Endocrinology. Reprints: Dr J E Gunton, C/- Clinic 1, Royal North Shore Hospital, St Leonards, NSW 2065. jennyegAThotmail.com. 1: Iodine deficiency disorders Maternal Goitre Hypothyroidism Decreased fertility Miscarriage Fetal Stillbirth Neonatal Cretinism Increased mortality Goitre Hypothyroidism Back to text 2: The iodine situation in AustraliaIn the past, an increased incidence of goitre and iodine deficiency was documented in certain parts of Australia.3-5 Prevention of iodine deficiency in industrialised countries most commonly relies on iodised salt, iodine in milk, or iodine-supplemented bread.1,6-8 The upper limit of the recommended daily intake of salt (NaCl) is 100 mmol, or 6 g (a heaped teaspoon); 100 mmol of iodised salt per day would provide 175-240 µg of iodine. However, most salt is incorporated into foods before purchase, and the three major Australian manufacturers of processed food we contacted all reported using non-iodised salt only. Non-iodised table salt is readily available, and may be used more frequently than in the past as campaigns to use iodised salt are forgotten. (We reviewed supermarket shelves in our local area, and found that the space allocated for display suggests that more non-iodised than iodised salt is purchased.) In the United States, only 50%-60% of salt currently consumed is iodised.9 Milk products, which used to contain significant concentrations of iodine (up to 300 µg/100 mL) by virtue of iodine-containing solutions used to clean the milk vats, now contain low levels of iodine because volatile cleaning solutions are used (Dairy Farmers Association, Nutrition Panel for Milks, personal communication). While the incidence of iodine deficiency and goitre was decreased by legislation requiring iodine supplementation of bread in 1966,3 this is no longer a requirement (because of concerns about an increased incidence of thyrotoxicosis). Marine fish, shellfish, seaweed and kelp contain high amounts of iodine,1,7 and such ocean seafood, as well as added iodised salt, provide most of the iodine in the Australian diet. However, many people may consume these products rarely, if at all. Back to text Back to text 4: Iodine status resultsGroupPregnant womenPostpartum womenPatients with diabetesVolunteersNumber of participants8126135 19Age (years)Mean (± 2 SD)32.9 ± 9.835.3 ± 11.350.1 ± 35.3*49.5 ± 17.4*Median (95% CI)34 (24-42)35 (25-42)50 (25.7-83.0)49 (45.3-53.8)Spot iodine concentration (µg/L)Median10479‡65† 64(95% CI)(89-129)(44-229)(58-89)(54-75)No. of participants (%) withSevere to moderate deficiency < 50 µg/L16 (19.8%)5 (19.2%)46 (34.1%)5 (26.3%)Mild deficiency 51-100 µg/L24 (29.6%)9 (34.6%)51 (37.8%)9 (47.4%)Normal iodine status > 100 µg/L41 (50.6%)12 (46.1%)38 (28.1%)5 (26.3%)Iodine/creatinine ratio (µg iodine/g creatinine)Median159131114 108(95% CI)(169-232)(106-218)(93-505)(84-209)No. of participants (%) withSevere to moderate deficiency< 50 µg iodine/g creatinine6 (7.4%)2 (7.7%)7 (5.2%)1 (5.3%)Mild deficiency 51-100 µg iodine/g creatinine 22 (27.2%)9 (34.6%) 50 (37.0%)5 (26.3%)Normal iodine status > 100 µg iodine/g creatinine53 (65.4%)15 (57.7%)78 (57.8%)13 (68.4%)* P < 0.001 for comparison with pregnant women. †P < 0.01 for comparison with pregnant women. ‡P < 0.05 for comparison with patients with diabetes. Back to text 5: Levels of thyroid-stimulating hormone and free thyroxine compared with iodine status in pregnant women and patients with diabetesThyroid-stimulating hormone (µIU/mL)Free thyroxine (pmol/L)GroupNo. Mean (± 2 SD)Mean (± 2 SD)Pregnant women70Normal iodine status*411.56 ± 0.8012.9 ± 3.70Mild deficiency†231.67 ± 0.9012.5 ± 3.00Severe to moderate deficiency‡16 1.56 ± 0.7712.1 ± 2.25Patients with diabetes121Normal iodine status*342.1 ± 3.1015.0 ± 2.60Mild deficiency†451.9 ± 1.2015.0 ± 2.60Severe to moderate deficiency‡42 2.6 ± 2.4014.5 ± 2.90 * > 100µg/L. † 51-100 µg/L. ‡ < 50 µg/L. Back to text

Jenny E Gunton · Graham Hams · Marcelle Fiegert · Aidan McElduff

Research End-stage renal disease in Aboriginals in New South Wales: a very different picture to the Northern Territory Alan Cass, Adrian G Gillin and John S Horvath MJA 1999; 171: 407-410 Abstract - Introduction - Methods - Results - Discussion - Acknowledgements - References - Authors' details - - More articles on Aboriginal health Abstract Objectives: To compare the incidence of end-stage renal disease (ESRD) among Aboriginals in New South Wales with the incidence among Aboriginals in the Northern Territory, and to compare the patterns of ESRD among Aboriginals and non-Aboriginals in NSW. Design: Secondary data analysis of information from unpublished and published Australia and New Zealand Dialysis and Transplant Registry reports. Main outcome measures: Average annual incidence of ESRD (persons per million); form of renal replacement therapy; mortality at 31 March 1998; patient and graft survival one and five years after transplant. Results: Each year in NSW, 5-17 new Aboriginal patients are treated for ESRD. There was no increase in the average annual incidence of ESRD among NSW Aboriginals (118 per million in 1988-1989 and 111 per million in 1996-1997), whereas incidence in the NT increased from 255 per million to 800 per million. In NSW, ESRD was attributed to diabetes in 32% of Aboriginal patients, compared with 13% of non-Aboriginal patients (P < 0.001). In NSW, Aboriginal patients were younger and more likely to be female, a pattern similar to that in the NT. The outcome of ESRD treatment is not significantly different between Aboriginals and non-Aboriginals in NSW. Conclusion: There is a different pattern of incidence of ESRD and of outcomes with treatment among Aboriginals in NSW compared with those in the NT. A possible explanation is that the lower incidence in NSW reflects less profound socioeconomic disadvantage and better access to primary and specialist care. Introduction Indigenous Australians experience high morbidity and mortality due to end-stage renal disease (ESRD). In the Northern Territory, the average annual incidence of ESRD for Aboriginals in 1988-1993 was 17.4 times that for non-Aboriginals,1 a disparity made more apparent by age adjustment.2 The number of dialysis treatments in the NT is doubling every two years.3The 30 June 1996 estimate of the Indigenous population (386 049) represented 2.1% of the total Australian population,4 but Aboriginals constitute 5% of the Australian members of the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA).5 Whether the increasing incidence and prevalence of renal disease is occurring in NSW as well as nationally and in the NT has not been well documented. The aims of our study were to document the number of new Aboriginal patients with ESRD in NSW during 1987 to 1998 and compare recent trends in incidence with national and NT data, and to compare for Aboriginal and non-Aboriginal patients in NSW: the patterns of aetiology of ESRD; the demographic characteristics at the time of being entered into ANZDATA; the outcomes for individuals who were notified to the Registry during the period 1987 to 1998; and patient and graft survival for those who received transplants during the period 1987 to 1998. Methods Information was obtained from ANZDATA Annual Reports (12 and 18-21)6-10 and unpublished data from ANZDATA. All nephrology units in Australia and New Zealand that provide dialysis or transplant services submit detailed six-monthly reports to ANZDATA. The reports give information regarding new patients accepted onto treatment programs, deaths that have occurred, and any alteration in treatment for current patients, including changing the mode of dialysis or receiving a transplant. For NSW, the NT and across Australia, we analysed: the number of Aboriginal patients entered into ANZDATA from 1987 to 1998 in NSW, the NT and across Australia; and the average annual incidence of ESRD. For NSW only, we analysed: primary renal disease diagnostic category; mean age; outcome data at 31 March 1998 for people who had been entered into ANZDATA since 1 January 1987. Outcomes were categorised as death, functioning transplant, haemodialysis, continuous ambulatory peritoneal dialysis (CAPD), and loss to follow-up or having moved interstate; causes of death, categorised into cardiac, vascular, infection, social, malignancy and other; patient survival and graft survival for transplants performed between 1 January 1987 to 31 March 1998. The average annual incidence of ESRD was calculated using Australian Bureau of Statistics (ABS) estimates and projections of the Aboriginal and Torres Strait Islander population for the years between actual Census counts. These estimates are based upon current trends in fertility and mortality and take into account an increasing propensity for people to identify themselves as being of Indigenous origin. The definition of "Aboriginality" from both data sources (ANZDATA and ABS) relies upon self-identification. Annual incidence was calculated as an average for each two-year period, as there is marked variability in the number of new patients per year, and small absolute numbers. Statistical analysis of demographic and outcome data was performed using STATA 5.0.11 A t test of means and χ2 test or Fisher's exact test of proportions were performed. Survival analysis was performed at the ANZDATA Registry. Data were provided as actuarial life-table estimates and the log rank test was performed. The data were entered into STATA 5.0 and graphed. Results Incidence Each year in NSW, 5-17 new Aboriginal patients are treated for ESRD (Table 1). The average annual incidence of ESRD among Aboriginals in NSW for the two years 1988-1989 was 118 per million. This remained substantially unchanged at 111 per million in 1996-1997. During the same period the average annual incidence of ESRD in Aboriginals across Australia increased significantly (Table 1); in the NT, the rise in incidence was more marked. The crude incidence for non-Aboriginals in NSW was 78 per million for 1993-1997, a slight rise from the 1980s due to increased acceptance for dialysis of patients over the age of 65 years. Diagnostic categories Diabetes, glomerulonephritis and hypertension are the most common primary renal diseases among Aboriginals with ESRD in NSW (Table 2). Diabetes is listed as the primary renal disease in 32% of Aboriginals, compared with 13% of non-Aboriginals (P < 0.001). Analgesic nephropathy affects a significantly greater proportion of the non-Aboriginal population, mainly among females: 28% in non-Aboriginal females, compared with 10% in Aboriginal females. No definite diagnosis was recorded for 11% of Aboriginals, compared with 5% of non-Aboriginals (P = 0.004). Demographics Significantly more Aboriginal females than males entered the ESRD program in NSW (Table 3), the reverse pattern to non-Aboriginals (P = 0.03). The Aboriginal population was younger at entry to the program and there were significantly fewer people over the age of 65 years (P < 0.001). Outcome, or patient status at 31 March 1998, was not significantly different between the groups (P = 0.59). However, no attempt at age or sex standardisation has been made in this analysis. Causes of death The differences between Aboriginals and non-Aboriginals in NSW in causes of death approach statistical significance (P = 0.07). A significantly larger proportion of Aboriginals died from cardiovascular diseases (P = 0.01). A significantly smaller proportion of deaths were due to social reasons (P = 0.02). Patient and graft survival after transplant Aboriginal patients receiving transplants in NSW during the study period were younger (Figure 1), but experienced lower patient survival and graft survival rates (Figures 2a and 2b), although these differences were not significant (Table 4). Discussion Our data show no evidence of an epidemic of renal failure among Aboriginals in NSW, although the incidence remains higher than among the non-Aboriginal population. Aboriginal patients in NSW with ESRD are on average 10 years younger than non-Aboriginal patients, more likely to be female, and more likely to have diabetes and to die of cardiovascular disease. These features are similar to those reported in the NT.2 However, in NSW, there is no significant difference in outcome between Aboriginal and non-Aboriginal patients who have been entered into the Registry since January 1987, whereas, in the NT, survival is significantly worse in Aboriginal than in non-Aboriginal patients.2 The persistently high rate of withdrawal up to 1997 of NT Aboriginal people from ESRD treatment, about 25%,3 is not present in NSW. Our results show that diabetes, glomerulonephritis and hypertension are the prominent primary causes of ESRD among NSW Aboriginals. The rise in renal failure attributed to diabetes follows a similar pattern to that noted in Aboriginals across Australia.10 The pattern of primary causes of renal disease is consistent between Aboriginal populations in different States.10 Impediments to effective and culturally appropriate service delivery to Aboriginal patients have been postulated as reasons for poor survival and high withdrawal rates from treatment.12 Therapeutic programs have typically removed people from their cultural and social support networks by requiring patients to leave their land, families and communities.13 Unlike in the NT, South Australia and Western Australia, there are few remote, non-urbanised communities in NSW; Aboriginals in NSW reside predominantly in cities and rural towns. The higher proportion of Aboriginal patients with uncertain aetiology of their ESRD is consistent with a lower renal biopsy rate, which may relate to late referral and lack of access to renal specialist services. In NSW, specialist renal services are increasingly being provided where Aboriginals live. The Statistical Local Areas with the highest proportion of Indigenous people are Brewarrina (53.1%), Central Darling (25.3%), Bourke (24.5%) and Walgett (20.4%).14 CAPD training is now occurring in some larger rural centres, and haemodialysis facilities are provided in Bourke and Brewarrina. These initiatives, which significantly reduce the dislocation of patients from their community and remove impediments to the delivery of appropriate ESRD services, may facilitate improved survival. There is a tendency towards lower patient survival and graft survival among NSW Aboriginals compared with non-Aboriginals, despite the Aboriginal graft recipients' being younger. In the NT, graft and patient survival among Aboriginals are significantly worse at one and five years than among non-Aboriginals.2 A significant difference in survival is not evident in the NSW data. The larger 95% confidence intervals in the NSW Aboriginal group are a consequence of fewer transplants being performed: 36 among Aboriginal patients, compared with 1755 among non-Aboriginal patients. These numbers do not provide sufficient power to detect a significant difference between the groups. The pattern of rapidly increasing incidence of ESRD among Aboriginals across Australia, especially in the NT, is not seen in NSW. Spencer et al argue that the increase in the NT is real, not due to ageing of the Aboriginal population or improved ascertainment.2 The reason for this difference in incidence is not clear. It may be due to differences between the populations in apparent predisposition to renal disease or to differences in the prevalence of primary causes and promoters of chronic renal disease. The epidemic of disease in the NT is not only due to an increased prevalence of diabetes. Community screening studies show a prevalence of significant proteinuria in marked excess of the prevalence of diabetes or impaired glucose tolerance.2,15 In the NT, from 1988 to 1993, the average annual incidence of ESRD not attributable to diabetes was 350 per million per year among Aboriginals.1 Lower incidence of ESRD in NSW Aboriginals may reflect less profound socioeconomic disadvantage and readier access to effective primary and specialist care. However, there may be poor ascertainment, particularly in rural areas of NSW. Further study is indicated to analyse this question. Acknowledgements The data reported here have been supplied by the Australia and New Zealand Dialysis and Transplant Registry. The interpretation of these data is the responsibility of the authors and in no way should be seen as an official policy or interpretation of the Australia and New Zealand Dialysis and Transplant Registry. Dr Alan Cass is the recipient of a postgraduate research scholarship from the Centre for Kidney Research, New Children's Hospital, Sydney. We thank Dr Wendy Hoy, who critically reviewed the manuscript, and Dr Zhiqiang Wang, who provided statistical advice. References Hoy WE, Mathews JD, Pugsley DJ. Treatment of end-stage renal disease in the Top End of the Northern Territory: 1978-93. Nephrology 1995; 1: 307-313. Hoy WE, McFarlane R, Pugsley DJ, et al. Markers for cardiovascular and renal morbidity: expectations for an intervention programme in an Australian aboriginal community. Clin Exp Pharmacol Physiol 1996; 23: S33-S37. Spencer JL, Silva DT, Snelling P, Hoy WE. An epidemic of renal failure among Australian Aboriginals. Med J Aust 1998; 168: 537-541. Australian Bureau of Statistics. Experimental estimates of the Aboriginal and Torres Strait Islander population. Canberra: ABS, 1998. (Catalogue No. 3230.0.) Disney AP. Demography and survival of patients receiving treatment for chronic renal failure in Australia and New Zealand: report on dialysis and renal transplantation treatment from the Australia and New Zealand Dialysis and Transplant Registry. Am J Kidney Dis 1995; 25: 165-175. Disney APS, Collins J, Russ GR, et al. ANZDATA Registry Report 1989. Adelaide: Australia and New Zealand Dialysis and Transplant Registry, 1989. Disney APS, Collins J, Russ GR, et al. ANZDATA Registry Report 1995. Adelaide: Australia and New Zealand Dialysis and Transplant Registry, 1995. Disney APS, Collins J, Russ GR, et al. ANZDATA Registry Report 1996. Adelaide: Australia and New Zealand Dialysis and Transplant Registry, 1996. Disney APS, Collins J, Russ GR, et al. ANZDATA Registry Report 1997. Adelaide: Australia and New Zealand Dialysis and Transplant Registry, 1997. Disney APS, Collins J, Russ GR, et al. ANZDATA Registry Report 1998. Adelaide: Australia and New Zealand Dialysis and Transplant Registry, 1998. STATA statistical software [computer program]. Version 5.0. College Station, Texas: Stata Corporation, 1997. Bennett E, Manderson L, Kelly B, Hardie I. Cultural factors in dialysis and renal transplantation among aborigines and Torres Strait Islanders in north Queensland. Aust J Public Health 1995; 19: 610-615. Willis J. Fatal attraction: do high technology treatments for end-stage renal disease benefit aboriginal patients in central Australia? Aust J Public Health 1995; 19: 603-609. Australian Bureau of Statistics. Census of population and housing -- selected social and housing characteristics for statistical local areas, New South Wales and Jervis Bay. Canberra: ABS, 1996. (Catalogue no. 2015.1.) Van Buynder PG. The epidemiology of renal disease in Aboriginal Australians [Master of Public Health thesis]. Sydney: University of Sydney, 1991. (Received 12 Feb, accepted 19 Jul, 1999) Authors' details Menzies School of Health Research, Darwin, NT. Alan Cass, MB BS, FRACP, PhD student. Department of Renal Medicine, Royal Prince Alfred Hospital, Sydney, NSW. Adrian G Gillin, FRACP, PhD, Staff Specialist; John S Horvath, MB BS, FRACP, Professor. Reprints will not be available from the authors. Correspondence: Dr A Cass, Menzies School of Health Research, PO Box 41096, Casuarina, NT 0811. alancassATmenzies.edu.au Back to textBack to textBack to textBack to textBack to textBack to text

Alan Cass · Adrian G Gillin · John S Horvath

Research Is sudden infant death syndrome still more common in very low birthweight infants in the 1990s? Beverley Sowter, Lex W Doyle, Colin J Morley, Anne Altmann and Jane Halliday MJA 1999; 171: 411-413 Abstract - Introduction - Methods - Results - Discussion - References - Authors' details - - More articles on Paediatrics Abstract Objective: To determine the rate of sudden infant death syndrome (SIDS) in very low birthweight children (VLBW) relative to children with low (LBW) and normal birthweights. Design, setting and subjects: Cohort study of consecutive live births in Victoria, 1993-1997 inclusive. Main outcome measures: All sudden unexpected deaths in early childhood over this five-year period; all deaths from SIDS (defined as a sudden unexpected death without a definite pathological explanation); and the proportion of SIDS in live births in three birthweight subgroups (VLBW, 500-1499 g; LBW, 1500-2499 g; and normal birthweight, > 2499 g). Results: There were 316 028 live births (with known birthweight) in Victoria over the five-year period; 224 (0.71 per 1000 live births) died unexpectedly. In 10 of these deaths there was a definite pathological explanation, giving a rate of SIDS of 0.68 per 1000 live births. The rate of SIDS in VLBW children was 2.52 per 1000 live births, lower than the rate reported before the 1990s. The rate of SIDS in VLBW children was not significantly different from the rate in LBW children of 1.98 per 1000 live births (difference per 1000 live births, 0.53; 95% CI, 21.45 to 2.52), but was significantly higher than the rate in normal birthweight children of 0.59 per 1000 live births (difference per 1000 live births, 1.93; 95% CI, 0.06-3.79). Conclusions: The rate of SIDS in VLBW children has fallen in the 1990s, along with the overall fall in the rate of SIDS, but remains higher than that in normal birthweight children. Introduction Most parents learn to live with the fear that their baby may die of sudden infant death syndrome (SIDS). However, the fear of SIDS can be even greater for parents of babies with low birthweight, or those with babies who have been in intensive care or who have had apnoea. Before discharge, many parents attend education sessions on reducing the risks of SIDS and on infant resuscitation. At one of these sessions the parents may ask the difficult question: "Is my baby more likely to die of SIDS because he (or she) was so tiny when born?". Before the 1990s, children with very low birthweight (VLBW, 500-1499 g) were known to have a higher rate of SIDS than those with a normal birthweight (> 2499 g).1-3 With the advent of preventive measures, the overall rate of SIDS in Australia has fallen dramatically in the 1990s (from 1.87 per 1000 live births in 1990 to 0.78 per 1000 live births in 1995).4 However, it is unclear whether the rate of SIDS has also fallen in VLBW children. We aimed to determine the rate of SIDS in the 1990s for VLBW children relative to children of other birthweights (low birthweight [LBW], 1500-2499 g; and normal birthweight, > 2499 g). Methods We studied a cohort of all consecutive live births in Victoria during the five-year period from 1993 to 1997, inclusive, and recorded all sudden deaths in early childhood (divided into the first 28 days [the neonatal period], postneonatal infancy [29-365 days], and early childhood [more than 1 year]). SIDS was defined as a sudden unexpected death without definite pathological features to explain the death. In the SIDS group, some children were considered by the pathologist to have pathological features, but these were insufficient to explain the death. Some had only a minor condition, and in the remainder no pathological features were found. All births with unknown birthweight were excluded. Data sources Data on deaths were obtained from the annual reports of the Consultative Council on Obstetric and Paediatric Mortality and Morbidity,5-9 a government-legislated surveillance body. The Council collects data on all perinatal deaths from 20 weeks' gestation, and all infant and child deaths up to 14 years of age. Death registrations are forwarded directly from the Registry of Births, Deaths and Marriages, and information on all sudden unexpected deaths is supplemented by the Victorian State Coroner. These cases are then all reviewed and classified by an expert pathologist working in the field. Data on births in Victoria were supplied by the Perinatal Data Collection Unit of the Public Health and Development Division of the Department of Human Services. The Unit collects data on all births in Victoria from 20 weeks' gestation under a legislated notification system. Statistical analysis The proportions of deaths from SIDS (and 95% confidence intervals) in each of the birthweight subgroups (VLBW, 500-1499 g; LBW, 1500-2499 g; and normal birthweight, > 2499 g) were calculated,10 and comparisons made between the groups.10 Results Over the five-year period 1993-1997, there were 316 028 live births in Victoria for which birthweight was known. (Birthweight was not known for a total of 90 live births.) Over the same period, there were 224 sudden unexpected deaths with known birthweight, of which 10 (4.5%) had a definite pathological explanation, leaving 214 deaths from SIDS (0.68 per 1000 live births). Of these 214 children with SIDS, 23 (10.7%) died in the neonatal period (including one who died during the primary hospitalisation), 171 (79.9%) died in postneonatal infancy, and 20 (9.3%) died after the age of 1 year. VLBW children made up less than 1% of all live births over this period; the rate of SIDS in VLBW children was 2.52 per 1000 live births (Table). This was not significantly higher than the rate in LBW children of 1.98 per 1000 live births (difference per 1000 live births, 0.53; 95% CI, 21.45 to 2.52), but was significantly higher than the rate in normal birthweight children of 0.59 per 1000 live births (difference per 1000 live births, 1.93; 95% CI, 0.06-3.79). LBW children had a significantly higher rate of SIDS than normal birthweight children (difference per 1000 live births, 1.39; 95% CI, 0.69-2.09). Of the seven deaths in VLBW infants, definite pathological features were found in five, but these were insufficient to explain the death; three of these infants had respiratory disease (pneumonia, bronchiolitis, or tracheobronchitis). Discussion Our study showed no significant difference in the rate of SIDS between VLBW and LBW infants; however, the rate in each of these subgroups was significantly higher than in normal birthweight children. Before recommendations for reducing the risk of SIDS were introduced in 1991, the SIDS rate was higher in VLBW infants compared with those with normal birthweight, for both hospital and regional cohorts. In a VLBW hospital cohort, 1977-1978, the rate of SIDS before 2 years of age was 30.3 per 1000 live births (7/231);1 and in a regional cohort in New Zealand (children born in 1986), the incidence of SIDS in the VLBW group was 13 per 1000 live births, more than three times the rate of 4.0 per 1000 live births for all NZ children born in 1986.2 In a Californian study of 2962 children dying of SIDS between 28 days and 1 year of age in 1978-1982, the overall incidence was found to be 1.5 per 1000 live births. The highest incidence was in the VLBW group (7.5 per 1000 live births), decreasing to 1.3 per 1000 live births for the normal birthweight group.3 Studies have not shown evidence of a fall in the rate of SIDS in VLBW infants just before the recommendations were introduced. For example, in 1985-1991, the rate of SIDS in VLBW infants in the first year of life for singleton births in the United States remained relatively constant (average, 3.66 per 1000 live births) compared with rates for normal birthweight singleton infants (average, 1.07 per 1000 livebirths).11 Studies comparing the period before and after the recommendations have shown a change in rate of SIDS in VLBW children around the beginning of the 1990s. One study cited by l'Hoir et al12 estimated the rate of SIDS in VLBW children in the Netherlands to have decreased from 10 per 1000 in 1983 to 1 per 1000 (presumably live births) in 1995-96, a change in the rate of SIDS over time similar to that comparing our results with rates in the late 1980s. A more recent US report described a smaller reduction in the rate of SIDS in VLBW children before and after the recommendations about sleeping position, and the reduction was similar across birthweight subgroups (between 1991 and 1995 reductions of 37%, 36% and 30% were found for birthweight subgroups 500-1499 g, 1500-2499 g, and > 2499 g, respectively).13 Avoidance of risk factors probably explains the fall in the rate of SIDS in VLBW infants in the 1990s, the same reason that it has fallen for infants overall. The reason SIDS remains more prevalent in VLBW infants compared with normal birthweight infants may relate to the underlying pathological features, which were more common in VLBW infants with SIDS. So, what should we be telling parents when they ask if their tiny baby is more likely to die of SIDS? Firstly, VLBW and LBW children are at increased risk of SIDS. However, 399 out of 400 VLBW children, and 499 out of 500 LBW children, do not die of SIDS. Secondly, parents can help to decrease the risk of SIDS by following the recommendations: putting their baby to sleep supine, not smoking, and not allowing the baby to become overheated or covered over by bedding.4 Thirdly, as most VLBW children who died of SIDS had a definite pathological condition at autopsy, parents should seek medical advice early if the baby appears unwell in any way. Parents often recognise that their baby is unwell, but it is not always easy for them to decide what is a minor illness and when they need to seek medical advice. A scoring system such as "Baby Check" 14 can be used both by parents and general practitioners to help them to determine whether or not a baby is seriously ill. In a recent review of 37 sudden unexpected infant deaths, 3 (8%) scored very highly for serious illness on a retrospective score with Baby Check, suggesting that such a scoring system could have identified serious illness before death and led to appropriate treatment.15 The three VLBW children with significant respiratory disease in our study probably would have shown signs of illness before they died. In conclusion, the rate of SIDS in VLBW children has fallen from over 10 per 1000 live births before the 1990s to 2.5 per 1000 live births at the end of the 1990s, but remains higher than the rate in normal birthweight children. LBW children are also at greater risk of SIDS at the end of the 1990s. References Kitchen WH, Yu VYH, Lissenden JV, Bajuk B. Collaborative study of very-low-birthweight infants: techniques of perinatal care and mortality. Lancet 1982; 1: 1454-1457. Darlow BA, Horwood LJ, Mogridge N, Clemett RS. Prospective study of New Zealand very low birthweight infants: outcome at 7-8 years. J Paediatr Child Health 1997; 33: 47-51. Grether JK, Schulman J. Sudden infant death syndrome and birth weight. J Pediatr 1989; 114: 561-567. Henderson-Smart DJ, Ponsonby AL, Murphy E. Reducing the risk of sudden infant death syndrome: a review of the scientific literature. J Paediatr Child Health 1998; 34: 213-219. The Consultative Council on Obstetric and Paediatric Mortality and Morbidity. Annual Report for the Year 1993, incorporating the 32nd Survey of Perinatal Deaths in Victoria. Melbourne, 1994. The Consultative Council on Obstetric and Paediatric Mortality and Morbidity. Annual Report for the Year 1994, incorporating the 33rd Survey of Perinatal Deaths in Victoria. Melbourne, 1995. The Consultative Council on Obstetric and Paediatric Mortality and Morbidity. Annual Report for the Year 1995, incorporating the 34th Survey of Perinatal Deaths in Victoria. Melbourne, 1996. The Consultative Council on Obstetric and Paediatric Mortality and Morbidity. Annual Report for the Year 1996, incorporating the 35th Survey of Perinatal Deaths in Victoria. Melbourne, 1997. The Consultative Council on Obstetric and Paediatric Mortality and Morbidity. Annual Report for the Year 1997, incorporating the 36th Survey of Perinatal Deaths in Victoria. Melbourne, 1998. Gardner MJ, Altman DG. Statistics with confidence - confidence intervals and statistical guidelines. London: BMJ, 1989. Bigger HR, Silvestri JM, Shott S, Weese-Mayer DE. Influence of increased survival in very low birth weight, low birth weight, and normal birth weight infants on the incidence of sudden infant death syndrome in the United States: 1985-1991. J Pediatr 1998; 133: 73-78. l'Hoir MP, Engelberts AC, van Well GT, et al. Case-control study of current validity of previously described risk factors for SIDS in the Netherlands. Arch Dis Child 1998; 79: 386-393. Malloy MH. Birth weight and gestational age specific sudden infant death syndrome (SIDS) mortality: 1991 vs 1995. Pediatr Res 1999; 45: 249A. Morley CJ, Thornton AJ, Cole TJ, et al. Baby Check: a scoring system to grade the severity of acute systemic illness in babies under 6 months old. Arch Dis Child 1991; 66: 100-105. Cole TJ, Gilbert RE, Fleming PJ, et al. Baby Check and the Avon infant mortality study. Arch Dis Child 1991; 66: 1077-1078. (Received 21 Jun, accepted 6 Sep, 1999) Authors' details Division of Paediatrics, Royal Women's Hospital, Melbourne, VIC. Beverley Sowter, RN, Case Manager. Lex W Doyle, MD, FRACP, Paediatrician; and Associate Professor, Department of Obstetrics and Gynaecology, and Department of Paediatrics, University of Melbourne. Colin J Morley, MD, FRACP, Paediatrician. Consultative Council on Obstetric and Paediatric Mortality and Morbidity, Melbourne, VIC. Anne Altmann, MB BS(Hons), MPH, FAFPHM, Epidemiologist. Victorian Perinatal Data Collection Unit, Melbourne, VIC. Jane Halliday, PhD, Epidemiologist. Reprints will not be available from the authors. Correspondence: Associate Professor L W Doyle, Division of Paediatrics, The Royal Women's Hospital, 132 Grattan Street, Carlton, VIC 3053. l.doyleATobgyn-rwh.unimelb.edu.au Sudden unexpected deaths in early childhood in Victoria, 1993-1997Birthweight subgroup 500-1499 g1500-2499 g> 2499 gTotalLive births278115 630297 617316 028Sudden unexpected deaths (≤ 28 days)07*1623Sudden unexpected deaths (> 28 days)724170201Total sudden unexpected deaths731186224Sudden unexpected deaths explained at autopsy001010Total SIDS731176214Pathological featuresDefinite586174Minor21887107None052833Rate of SIDS (per 1000 livebirths) 2.521.98 0.590.68(95% CI)(1.04-5.19)(1.29-2.68)(0.50-0.68)(0.59-0.77)Data are numbers of infants, unless indicated otherwise. * One infant died while still in hospital after birth. SIDS = Sudden infant death syndrome (sudden unexpected deaths, excluding those explained at autopsy). Back to text

Beverley Sowter · Lex W Doyle · Colin J Morley · Anne Altmann · Jane Halliday

Research A South Australian population survey of the ownership of asthma action plans Richard E Ruffin, David Wilson, Anne Marie Southcott, Brian Smith and Robert J Adams MJA 1999; 171: 348-351 Abstract - Introduction - Methods - Results - Discussion - References - Authors' details - - More articles on Respiratory medicine Abstract Objective: To examine the relationships between ownership of written asthma action plans, asthma morbidity, use of devices, and patients' perceptions of their asthma management. Design and setting: A random population survey (in 1996) of the South Australian population aged 15 years or over, using interviewers to administer a questionnaire. Participants: People who reported that they had current, doctor-diagnosed asthma. Main outcome measures: Prevalence of written asthma action plans; night-time awakenings from asthma; ownership of peak flow meters; and people's perceptions of their asthma management. Results: The ownership of asthma action plans by people with self-reported asthma was 33% and has declined since 1995 (42%; P < 0.001). Fifteen per cent were wakened weekly or more frequently by asthma symptoms. These people were more likely to have a peak flow meter and a written action plan, but less likely to consider they had been provided with enough information about their asthma, to feel comfortable managing their asthma, or to find it easy to see their doctor. Having a written asthma action plan was associated with regular corticosteroid use, understanding asthma, having enough information and owning a peak flow meter. Conclusions: Ownership of asthma action plans in South Australia is suboptimal. Before we develop new strategies to improve asthma outcomes, we must determine whether there is a need to target people with less severe asthma and/or improve the use of guidelines by health professionals. Introduction The Australian and New Zealand Asthma Guidelines, developed in 1989, provide a list of objectives that would be desirable to achieve for every person with asthma,1 and studies of the use of asthma management plans have shown improved health outcomes for people with asthma.2-4 In Australia there is evidence that the promotion of asthma plan guidelines by the Thoracic Society of Australia and New Zealand and the National Asthma Campaign has led to increased uptake of plans.1 In South Australia the prevalence of adults with asthma reporting that they had a written action plan almost doubled between 1992 and 1995.5 However, there is evidence that asthma management is not ideal.6-8In one study in Victoria, 45% of people who died of their asthma had been assessed as having only a history of mild or moderate asthma.6 In another study in Victoria that examined the asthma knowledge of asthma patients, the median score obtained was less than 50%.7The effective implementation of asthma management plans in Australia to date has been seriously questioned by some investigators,8 and Bauman et al have concluded that the treatment and management of asthma is suboptimal.9 Our study aimed to provide representative population information on the ownership of written asthma action plans and the relationship to asthma morbidity and management factors. Methods Survey The data for this study were collected in the 1996 South Australian Health Omnibus Survey,10 a representative survey of people aged 15 years or older (n = 3010; response, 71%) . The survey was a multistage, systematic, clustered area sample of people who live in metropolitan Adelaide and major country centres with a population of over 1000. The survey was selected from a random sample of Australian Bureau of Statistics collector districts. Within each collector's district a random starting point was selected and from this point 10 households were selected using a fixed skip interval. Hotels, motels, hospitals, nursing homes and other institutions were excluded. The person whose birthday was next in each selected household was interviewed in their home by trained health interviewers. There was no replacement for non-respondents. Up to five call-backs were made in an attempt to interview the selected person. The data were weighted by age, sex, and geographic region to the estimated resident population data so that the analysis would be representative of the South Australian population. The part of the survey form dealing with asthma is shown in the Box. A person was classified as having current asthma if they answered yes to the first three questions. Social class was determined by referring to the gradation of occupational prestige given in the Australian Standard Classification of Occupations.11 An asthma action plan was defined as "written instructions of what to do if your asthma is out of control." Data analysis Possession of an asthma management plan and frequency of wakening at night with asthma were used as the two dependent variables for univariate analyses,12 which examined the associations between these variables and reported asthma management, knowledge and attitudes to management. Before conducting multiple logistic regression analyses, the explanatory variables were examined for collinearity or interactions. Stratified analyses were used to check homogeneity of associations across different levels of predictor variables. Smoking status and the information that people with asthma perceive they have for dealing with worsening asthma were found to interact, with an effect of these variables on worsening asthma. An interaction term for the two independent variables was included in the logistic regression analysis for frequency of wakening at night. This interaction term proved significant (P = 0.03), indicating the need to split the model and conduct separate logistic regression analyses of smokers and non-smokers. Therefore, we conducted three logistic regression analyses, using "asthma plan", "waken weekly-non-smokers" and "waken weekly-smokers" as the three response variables. All variables found to be significant at the univariate stage (ie, P = 0.25)13 were entered into each logistic regression. Insignificant variables were progressively omitted until satisfactory models were found that explained possession of an asthma plan and frequency of wakening at night. Results The prevalence of asthma was 11.6% (95% CI, 10.3%-12.9%). Of the 349 survey respondents with asthma, 33% (95% CI, 30.8%-35.2%) had a written asthma action plan and 15.2% (95% CI, 13.7%-15.7%) were awakened by asthma weekly or more frequently. Age, sex, migrant status, education level and socioeconomic status made no significant difference to the rate of possession of an asthma action plan or the rate of wakening with asthma weekly or more frequently. Variables significantly associated with ownership of an asthma action plan at the univariate level are shown in Table 1; those significantly associated with wakening with asthma at night are shown in Table 2. In the multivariate analysis (Table 3), the variables that best described those who had an asthma action plan were: using corticosteroids, understanding the effects of worsening asthma, having a peak flow meter, and believing they have enough information to deal with worsening asthma. The variables that best described non-smokers who waken weekly or more often were: having a peak flow meter, having an asthma action plan, not believing they have enough information to deal with worsening asthma, and not feeling comfortable taking care of their asthma. Only one variable -- not finding it easy or convenient to access their doctor about asthma -- explained wakening weekly or more often for smokers. Discussion The data obtained in this representative population study paint a bleak picture of the effectiveness of asthma management in Australia. As even people with mild asthma can die of the disease,6 every person with asthma may need an action plan. Yet, seven years after the promulgation of Australian guidelines on the implementation of asthma action plans,1 only 33% of people with diagnosed asthma had a written plan. The current level of plan ownership is significantly lower than the 42.1% (P < 0.001) reported 12 months earlier using the same survey methods.5 This may mean that vigilance regarding asthma management is declining. Our study has some limitations. We have no objective data to identify levels of asthma severity and asthma control in the respondents. The validity of the perception questions as repeatable measures has not been verified. Because we focused on ownership of written action plans, our study does not tell us whether patients are making appropriate use of these plans or of verbal instructions. In the multivariate analyses, only use of preventer medication, ownership of a peak flow meter and self-reported understanding of asthma were associated with plan ownership. This association could suggest that the more severe cases have better asthma management. Proof for this requires prospective measures (eg, lung function, medication doses) to assess the two critical factors of asthma severity and asthma control. Such knowledge could inform us of the potential need to target people with less severe asthma. People with asthma with nocturnal symptoms were more likely than those without nocturnal symptoms to report possession of a peak flow meter, and to have asthma action plans, but were less likely to consider they had been provided with enough information about their asthma (non-smokers) or to find it easy to see their doctor (smokers) (Table 2). Thus, although asthmatics with a higher level of morbidity are more likely to receive physical materials to assist in self-care, they continue to have greater unmet needs for general practitioner access and information about asthma self-management. What is the way forward? Randomised studies of the implementation of asthma plans show that good educational and skill objectives can be achieved.2,14-16 However, the complexity of the asthma management problem makes it impossible to provide for every contingency the patient might face in dealing with asthma. Asthma management decisions can be difficult, because the patient, the daily situation, the science base and the disease are constantly changing.2 The objectives of patient asthma management are the development of skills and positive attitudes to problem-solving, accompanied by sufficient knowledge to make sense of changing morbidity and symptoms. A controlled trial evaluation of a brief asthma education program (2.5 to 3 hours group work) demonstrated substantial changes in illness behaviour.2 These programs show that giving the patient the necessary skills cannot be achieved within the normal constraints of general practice. Randomised controlled trials of asthma clinics, where there is an emphasis on self-management, have demonstrated improvements in a range of morbidity and other health-related outcomes in a community-based setting.17 We must identify other ways of training the patient and focus the clinician on that part of the education program that can be managed in general practice. There is evidence that regular review improves asthma outcomes.18 It is pertinent to consider the possibility that inadequate use of guidelines by health professionals may be contributing to the fall in action plan ownership. Ways to improve use of guidelines need to include developments in information technology. Trostle has suggested that the inability of some people to comply with a treatment regimen is an unavoidable byproduct of collisions between the clinical world and other competing worlds of work, family, friends and recreation.19 Often, the process required to inform and empower the patient is more than an educational task. Some of the traditional models of patient education based on health beliefs or compliance frameworks have been seriously questioned.20,21 Patients have to fit their medical problems and medical regimens into the context of their daily lives. In doing so they will vary their compliance with advice and instructions to accommodate the social, psychological, economic and physical influences which are part of their lives.21 We need research that clearly articulates the complexity and variability of how asthma management fits into the context of individual patients' lives. The National Asthma Campaign has provided a guide for health professionals to assist with effective patient communication, which is a starting point for corrective strategies.22 We therefore know what optimal management of asthma is, but its attainment is elusive. Future strategies must be guided by studies defining asthma severity and asthma control, studies identifying factors that influence the use of guidelines by professionals, and studies elucidating the context of asthma management for the individual. References Woolcock A, Rubinfeld AR, Seale P, et al. Asthma management plan, 1989. Med J Aust 1989; 151: 650-653. Yoon R, McKenzie DK, Bauman A, Miles DA. Controlled trial evaluation of an asthma program for adults. Thorax 1993; 48: 1110-1116. Comino EJ, Mitchell CA, Bauman A, et al. Asthma management in eastern Australia. Med J Aust 1996; 164: 403-406. Beasley R, Cushley M, Holgate ST. A self-management plan in the treatment of adult asthma. Thorax 1989; 44: 200-204. Adams R, Ruffin R, Wakefield M, et al. Asthma prevalence, morbidity and management practices in South Australia, 1992-1995. Aust N Z J Med 1997; 27: 672-679. Robertson C, Rubinfeld AR, Bowes G. Deaths from asthma in Victoria: a twelve-month survey. Med J Aust 1990; 152: 511-517. Rubinfeld AR, Dunt DR, McLure BG. Do patients understand asthma? A community survey of asthma knowledge. Med J Aust 1988; 149: 526-530. Bauman A, Young L, Peat JK, et al. Asthma under-recognition and under-treatment in an Australian community. Aust N Z J Med 1992; 22: 36-40. Bauman A, Mitchell CA, Henry RL, et al. Asthma morbidity in Australia: an epidemiological study. Med J Aust 1992; 156: 827-831. Wilson D, Wakefield M, Taylor A. The South Australian Health Omnibus Survey. Health Promotional J Aust 1992; 2: 47-49. Kelley JL, Evans MDR. Using ASCO for socio-economic analysis: assessment and conversion into status and prestige indices. Canberra: Research School of Social Sciences, Australian National University, 1988. SPSS for Windows. Release 8.0 [computer program]. Chicago, IL: SPSS Inc, 1998. Hosmer DW, Lemeshow S. Applied logistic regression. New York: John Wiley, 1989. Wilson-Pessano SR, McNabb WL. The role of patient education in the management of childhood asthma. Prev Med 1985; 14: 670-687. Clark NM, Feldman CH, Evans D, et al. Managing better: children, parents and asthma. Patient Educ Counsell 1986; 8: 27-38. D'Sousa WD, Crane J, Burgess C, et al. Community-based asthma care: trial of a "credit card" asthma self-management plan. Eur Respir J 1994; 7: 1260-1265. Lahdenso A, Haajtela T, Herrala J, et al. Randomised comparison of guided self-management and traditional treatment of asthma over one year. BMJ 1996; 312: 748-752. Asthma management handbook 1998. Melbourne: National Asthma Campaign, 1998. Trostle JA. Medical compliance as an ideology. Soc Sci Med 1988; 18: 1299-1308. Carter WB. Psychology and decision making: modelling health behaviour with multiattribute theory. J Dental Educ 1992, December: 800-807. Morris SL, Schulz RM. Medication compliance: the patients' perspective. Clin Ther 1993; 15: 593-606. Asthma adherence: a guide for health professionals. Melbourne: National Asthma Campaign, 1999. (Received 19 Apr, accepted 26 Aug, 1999) Authors' details The Queen Elizabeth Hospital, Adelaide, SA. Richard E Ruffin, FRACP, MD, Head, Division of Medicine, and Michell Professor of Medicine, University of Adelaide; Anne Marie Southcott, MB BS(Hons), FRACP, Acting Director, Respiratory Medicine; Brian Smith, PhD, FRACP, Director, Clinical Epidemiology and Health Outcomes Unit, and Senior Lecturer, University of Adelaide. Centre for Population Studies in Epidemiology, Department of Human Services, Adelaide, SA. David Wilson, PhD, MPH, Head. Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Robert J Adams, MB BS, FRACP, Research Fellow. Reprints: Professor R E Ruffin, Department of Medicine, University of Adelaide, The Queen Elizabeth Hospital Campus, 28 Woodville Road, Woodville, SA 5011. rruffinATmedicine.adelaide.edu.au Survey questions Have you ever had asthma? Was your asthma confirmed by a doctor? Do you still have asthma? If answer yes to these questions, then: Do you have an asthma action plan (written instructions of what to do if your asthma is out of control)? Do you have a home nebuliser for asthma treatment? Interviewer: if "yes" prompt "have you used it in the last 12 months?" What preventive (not reliever) medicine do you use regularly for your asthma? None - Intal - Becotide - Becloforte Pulmicort - Tilade - Other (specify) Which of the statements shown on this card do you feel are true of your preventer medication? Works by relieving narrowed breathing tubes quickly Needs to be used when you feel unwell Works by slowly reducing inflammation in the breathing tubes Must not have the dose changed Don't know How often do you awaken during the night with asthma? Nightly - Most nights - About twice a week - Weekly - Monthly - Less often than monthly Only at certain times of the year (ie seasonal) Never In the last 12 months have you had any hospital admissions for asthma where you stayed at least one night in hospital? In the last 12 months have you had any days lost from work, school or home duties from asthma? How many days would you estimate? What would you do if you had a bad attack of asthma and six puffs of your reliever (eg, ventolin, respolin) had not helped? Which of these statements shown on this card most closely matches what you would be likely to do? Wait another two hours and take more reliever medication Seek medical advice Take another six puffs of reliever medication and see what happens Call an ambulance Get someone to take you to hospital Do something else (specify) What feelings would you have if you had to get help for a bad attack of asthma? Which of the statements shown on this card most closely match how you would be feeling? You feel that you have failed You would feel embarrassed You do not want to bother others It is the right thing to do You know you will be OK because of past experience Something else (specify) I am now going to read out a number of statements and show you a card for each of them. Could you please tell me which number from 1 to 5 best reflects the way you feel. I am the sort of person who understands all about my asthma Always - Often - Sometimes - Rarely - Never - Don't know/other If I took care of my asthma myself, most of the time, I would . . . Manage well Manage sometimes Not manage at all Don't know/other If I were having a severe attack of asthma I would feel comfortable about going to a doctor or hospital Very comfortable Comfortable Don't mind Uncomfortable Not comfortable at all Don't know/other Going to see a doctor for help with my asthma is Easy and convenient Not easy nor convenient Don't know/other I have information to use (such as "Asthma Action Plan" or other instructions) to deal with worsening asthma. Yes, all I need Some No, none at all Don't know/other Other questions were asked about smoking status, educational level and migrant status. Back to text 1: Variables associated with ownership of an action plan*VariableSubjects (n = 349)%Odds ratioWrong about CS effect10332.01.0Correct about CS effect162†44.41.7 (0.98-2.94) P = 0.04Don't use CS regularly14721.81.0Use CS regularly20241.62.56 (1.54-4.26) P < 0.01No home nebuliser28229.11.0Have home nebuliser6750.72.51 (1.41-4.48) P < 0.01No peak flow meter29626.61.0Have peak flow meter5371.76.99 (3.50-14.14) P <0.01Don't always understand asthma8516.51.0Understand asthma26438.63.19 (1.65-6.27) P < 0.01Not enough information11715.51.0Enough information23255.56.77 (3.98-11.56) P <0.01Feel bad getting help4721.31.0Getting help OK30235.12.26 (1.04-4.90) P = 0.04No hospital admission within 12 months 33432.1 1.0Hospital admission1560.03.17 (1.00-10.32) P = 0.05No days lost from work/school30231.11.0Days lost from work/school4746.81.95 (1.00-3.79) P = 0.05CS = corticosteroids. * Variables tested but not found to be significant were: sex, age, migrant status, educational level, socioeconomic status, weight, access to doctor, uncomfortableness dealing with asthma, perception of dealing with asthma, comfortableness in going to hospital if required, exercise, smoking status, and smoking bans at home. †Only those who regularly used preventive medicine for their asthma (n = 265) were asked about its effects. Back to text 2: Variables associated with the likelihood of wakening with asthma on a weekly basis or more frequently*VariableSubjects (n = 349)%Odds ratioWrong about CS effect1038.71.0Correct about CS effect162†25.83.63(1.60-8.45) P < 0.01No home nebuliser28212.81.0Have home nebuliser6730.81.96 (0.96-3.95) P = 0.04No peak flow meter29612.81.0Have peak flow meter5330.83.02 (1.45-6.27) P < 0.01Not easy to see doctor6033.31.0Easy access to doctor28911.80.27 (0.13-0.53) P < 0.01Uncomfortable taking care of asthma 4836.2 1.0Comfortable taking care30112.30.25 (0.12-0.52) P < 0.01Perception of self-management good 3813.7 1.0Perception poor31129.42.62 (1.09-6.25) P = 0.0 3No days lost from work/school30213.61.0Days lost from work/school4727.72.42 (1.11-5.25) P = 0.02CS = Corticosteroids. * Variables tested but not found to be significant were: sex, age, migrant status, educational level, socioeconomic status, weight, regular use of corticosteroids, not always understanding asthma, not having enough information, feeling bad getting help, comfortableness in going to hospital if required, exercise, smoking status, smoking bans at home, and having an asthma action plan. †Only those who regularly used preventive medicine for their asthma (n = 265) were asked about its effects. Back to text 3: Logistic regression analyses of variables associated with ownership of an asthma management plan and frequency of wakening at night with asthma (n = 349)VariableOdds ratioAsthma planNo peak flow meter1.0Have peak flow meter4.32 (2.91-8.43)Don't always understand asthma 1.0Understand asthma2.01 (1.01-4.02)Not enough information1.0Enough information4.32 (2.11-8.85)Don't use corticosteroid regularly1.0Use corticosteroid regularly2.08 (1.21-3.58)Waken weekly (non-smokers)No peak flow meter1.0Have a peak flow meter7.32 (2.59-20.07)Not enough information1.0Enough information0.12 (0.04-0.39)Uncomfortable taking care of asthma1.0Comfortable taking care0.30 (0.14-0.77)No asthma action plan1.0Asthma action plan2.79 (1.09-7.15)Waken weekly (smokers)Not easy to see doctor1.0Easy to see doctor0.28 (0.10-0.79)All results significant, P < 0.05. Back to text

Richard E Ruffin · David Wilson · Brian Smith · Robert J Adams

Research Erectile dysfunction in the community: a prevalence study Carole B Pinnock, Alan M F Stapleton and Villis R Marshall MJA 1999; 171: 353-357 For editorial comment see Lowy Abstract - Introduction - Methods - Results - Discussion - Acknowledgements - References - Authors' details - - More articles on Urology Abstract Objective: To investigate the prevalence of erectile dysfunction (ED) in the South Australian community, and the influence of demographic and other risk factors. Design: Survey by mailed questionnaire (based on the University of California, Los Angeles prostate cancer index) of a subset (men who agreed to participate) of a probability sample of the South Australian community who completed a multiuser interview survey. Participants and setting: Men over the age of 40 in South Australia. Main outcome measures: Sexual desire, orgasm, ability to have an erection, adequacy (firmness) of erections for intercourse, frequency of erections when wanted, frequency of intercourse, nocturnal or morning erections, and history of prostate surgery; total sexual function score based on these. Results: 612 men (86.7%) agreed to answer the sexual function survey; 427 (69.8%) returned questionnaires. ED was strongly correlated with age in all seven domains of sexual function. Erections inadequate for intercourse affected 3% of 40-49-year-olds, increasing to 64% of 70-79-year-olds. The frequency of intercourse considered normal for age by men 50-69 years was 1-6 times weekly; the disparity between this and reported frequency increased in men over 60 years, as did the difference between sexual desire and potency. A history of vigorous exercise was protective across all ages. High triglyceride levels, blood pressure medication and non-cancer surgery for prostate disease were independent predictors of poor sexual function at older ages. High cholesterol level was an independent predictor of impotence. Conclusions: We found similar or higher levels of ED than in comparable overseas studies. Disparity between potency and desire was greatest, and hence the age group in whom demand for treatment may be highest, in those 60 years and older. Cardiovascular risk factors were predictors of ED in these older men, suggesting that prevention may benefit sexual function. Non-cancer prostate surgery may be a greater contributor to ED than previously realised. Introduction Establishing the prevalence of erectile dysfunction (ED) in the community is difficult,1 but important for understanding the need for services, establishing functional expectations of men as they age and for determining the influence of demographic and preventable risk factors. An understanding of community prevalence of ED is useful when evaluating treatments for prostate disease which carry high risks of ED. Community prevalence has been examined in international, but not Australian, studies.1-4 One Australian study of ED prevalence in a Perth general practice population has been reported in conference proceedings.5 We undertook this study to establish the prevalence of erectile dysfunction among Australian men, and to investigate the influence of risk factors. Methods Questions were included in the spring 1997 Omnibus survey, a multiple-user household interview survey which provides a representative sample of the South Australian population. We have reported the methods of and results from this annual survey previously.6-8 The Omnibus survey included questions about age, educational attainment, marital status, household income, area of residence, blood pressure group (low, normal, borderline, high), cholesterol group (low, normal, high), alcohol intake by frequency (days per week) and volume (standard drinks per day when drinking), doctor's report of high triglyceride levels, body mass index (BMI), whether vigorous exercise was undertaken in the past two weeks, current and previous smoking status, and number of cigarettes per day usually smoked. Also included were questions about the presence of lower urinary tract symptoms (LUTS) such as nocturia, frequency, urgency, and a visit to a doctor for LUTS, as reported previously.6 In addition, men aged 40 years and over were asked if they would be prepared to answer a further, mailed questionnaire on urological issues. This comprised an introductory letter explaining the purpose of the survey,7 questions on sexual function and one on history of prostate surgery. To provide an indication of men's expectations of intercourse frequency across age groups, the first question asked what frequency of intercourse the respondent considered normal for a man of his age. Respondents were then offered the opportunity to return the questionnaire without answering further questions if they considered these too intrusive. Sexual function questions were derived from the UCLA (University of California, Los Angeles) prostate cancer index developed by Litwin et al.9,10 These applied to the previous three months and covered seven domains: (i) sexual desire, (ii) orgasm, (iii) ability to have an erection, (iv) frequency of erections when wanted, (v) frequency of intercourse, (vi) frequency of morning or nocturnal erections, and (vii) firmness of erections. The first six of these had five response options ("nil", "poor", "fair", "good", "very good" for domains i-iii; "never had an erection when I wanted one", "less than half the time when I wanted one", "about half the time I wanted one", "whenever I wanted one" for domain iv; "once or more daily", "1-6 times weekly", "1-3 times monthly", "less than once a month", "not at all" for domain v; "never", "seldom [less than a quarter of the time]", "not often [less than half the time]", "often [more than half the time]", "very often [more than 75% of the time]" for domain vi), while the seventh had four ("no erections at all", "not firm enough for any sexual activity", "firm enough for masturbation and foreplay only", "firm enough for intercourse"). Additional questions involved history of prostate surgery (for cancer and for non-cancerous conditions). Ethical consideration for the study was by Repatriation General Hospital's Research Ethics Committee. Analysis We defined sexual dysfunction as a response of one of the two lowest response categories (eg, "nil" or "poor") in each of the first six domains. Confidence intervals were adjusted for a design effect of 1.1 to allow for clustering.11 Dysfunction in the seventh domain (firmness of erections) was termed "impotence", defined as "usual quality of erections during the past three months not firm enough for intercourse" (corresponds with National Institutes of Health definition)12 -- one of the three lowest response options for this domain. A total erectile function score was derived by adding scores for each of the seven domains. The resulting score out of a possible 34 was expressed as a percentage; a score of 0 indicated worst possible function and 100% indicated best possible function in all domains. The reliability coefficient (Cronbach's alpha) of this seven-item score was 0.940. The association of demographic and cardiovascular risk factors with total sexual function (expressed as a continuous variable) and with impotence (a dichotomous variable) was examined after allowing for the effects of age by means of analysis of variance and logistic regression. For analysis, data were weighted by household size, age, sex and geographic region to benchmarks derived from the resident South Australian population in August 1996. We used SPSS for Windows13 for statistical analysis. Results The numbers and age breakdown of respondents are shown in Box 1. The mean age of respondents was 57.5 years (standard error, 0.58). Of the 745 men aged 40 years and over who responded to the Omnibus survey (representing a response rate of 70.8%), 612 (82.1%) agreed to complete a further, mailed questionnaire on urological issues. These questionnaires were returned by 427 respondents (69.8%), 371 (86.9%) of whom agreed to answer the full questionnaire. Box 1 shows that the age distribution was the same in all of these groups. We weighted further analyses to reflect the age distribution in the South Australian community; marginal totals thus do not correspond to the totals in Box 1. A comparison of respondents who agreed to answer the sexual function questions with those who did not agree to a further survey, did not respond to the mailed form or did not agree to answer the sexual function questions showed no significant differences in age, marital status, blood pressure, cholesterol and triglyceride levels, blood pressure medication or visit to a doctor for LUTS. Men who answered the sexual function questions were more likely to report vigorous exercise in the past two weeks (25.0% v 15.4%; P = 0.001), and more likely to drink alcohol five or more times per week (34.2% v 25.3%; P = 0.026) than those who did not answer these questions. Frequency of intercourse The frequency of intercourse considered by respondents as normal for their age, shown in Box 2(a), and actual reported frequency of intercourse were strongly correlated (Spearman's correlation coefficient, 0.62; P < 0.0001). Most 40-60-year-olds considered that intercourse 1-6 times per week was normal for their age and most reported this frequency of intercourse. In older men, however, a discrepancy emerged: most 70-79-year-olds considered 1-3 times per month to be normal for their age, but most reported an actual frequency of less than once per month. Box 2(b) illustrates this more clearly. In younger age groups, the reported frequency approximated that considered normal for age, but in older age groups it was substantially lower. Similarly, Box 2(c) shows that, while potency exceeds desire in men aged 40-59 years, after age 60 years desire exceeds potency. Prevalence of erectile dysfunction Erectile dysfunction was strongly correlated with age across all seven domains (Box 3). The prevalence of impotence (defined above) increased sharply from 3% in 40-49-year-olds to 42% in 60-69-year-olds and 64% in 70-79-year-olds. Other domains of sexual function, including morning or nocturnal erections, followed this pattern of steep decline in the fifth and sixth decades. Total sexual function scores ranged from 17% to 97%, with a mean of 68.1% (standard error, 1.1); 21% of respondents had a score of 50% or less. The sexual function score was also strongly correlated with age (Pearson's correlation coefficient, 0.63; P < 0.0001). Demographic risk factors Age, income, education, marital status, area of residence, occupation and country of birth were examined for their association with total sexual function and impotence. By far the strongest contributor to total sexual function score was age, and so the contribution of other factors was examined singly after first accounting for the effects of age in analysis of variance models, including first-order interactions (sexual function) and logistic regression (impotence). Where factors or their first-order interactions were significant, a combined model was examined. A summary of these analyses is given in Box 4. Men with lower socioeconomic status (income, education, occupation) tended to have lower sexual function, and this association was seen particularly in older men. In the 70-79 years age group, the total sexual function score varied from 47.1 in the lowest education category to 61.7 in the highest. Sexual function tended to be lower in Australian-born than overseas-born respondents. When tested in a model containing cardiovascular risk factors, this association remained. No demographic factors, apart from age, were significant contributors to impotence. Cardiovascular and other risk factors The cardiovascular risk factors shown in Box 4, as well as presence of LUTS, doctor visit for LUTS and surgery for prostate disease (cancer or non-cancer), were examined for their effects on total sexual function and impotence, as described for demographic factors. A number of factors were significantly (P < 0.05) associated with decreased sexual function after controlling for the effects of age. For total sexual function, these were ever having smoked, taking blood pressure medication and having had surgery for non-cancer prostate disease. A history of vigorous exercise was protective. Risk factors for impotence were high body mass index, high levels of triglycerides and cholesterol, and surgery for non-cancer prostate disease. Again, a history of vigorous exercise was protective. When combined models were constructed with these factors, the number that remained independently significant was reduced (Box 4). For total sexual function, these were vigorous exercise, high triglyceride levels, blood pressure medication, and surgery for non-cancer prostate disease. The combined model for total sexual function explained 55% of the variance. The observed power was low for all non-significant factors. The effects of cardiovascular risk factors were stronger in older age groups. For example, men in their 60s with high triglyceride levels had a total sexual function score of 41% (95% CI, 31%-52%), compared with 64% (95% CI, 59%-70%) for men of the same age who did not have this risk factor. Discussion Few international or Australian studies of the prevalence of sexual dysfunction have surveyed the general community.1 Our study was based on a representative sample of the South Australian community, and employed rigorous methods which have been previously used in other prevalence studies.1,8 The study was undertaken before the recent introduction of the drug oral sildenafil for erectile dysfunction. The subsample who answered questions on sexual function were similar in terms of most demographic and risk factor variables tested, but did report undertaking more vigorous exercise, and more frequent alcohol consumption. They may therefore reflect a more physically active subgroup, and our estimates of erectile dysfunction are likely to be conservative. Relative to other studies with comparable methods and measures of sexual dysfunction, the prevalences we found were similar or higher. For example, a study of frequency of sexual activity reported that 34.7% of married 60-65-year-old people did not have sexual intercourse within the preceding month,14 while we found that 34.3% of 60-69-year-old men reported having intercourse "less than once a month". A survey of 1240 men attending general practices in Perth found a 45% prevalence of "complete ED [erectile dysfunction]" in 70-79-year-old men,5 compared with our finding of impotence in 64.2%, and 64.3% in a study by Diokno et al.15 The frequently quoted Massachusetts Male Aging Study reports a prevalence of complete impotence of 9.6% for a 40-70-year-old population;2 the corresponding figure in our study was 16%. As expected, frequency of intercourse considered normal for age was strongly correlated with the frequency of intercourse reported (Figure 2). Solstad and Hertoft found that, while 40% of interviewed Danish men reported some kind of sexual dysfunction, only 7% considered their problems abnormal for their age,16 implying that men tend to see their own functional level as normal. Nevertheless, in our study, the discrepancy between reported frequency of intercourse and that considered normal for age increased with age. It was greatest in men 70 years and older, suggesting that it is older men who may be most concerned about their sexual function. Consistent with this, potency exceeded desire in younger age groups, but the relationship was reversed in men aged 60 years and over. About one in five men over the age of 50 experience good to very good sexual desire, but nil to poor erectile function; these men may be more likely to seek treatment. If the goal of treatment is to achieve perceived "normal function for this age", this may be a frequency of intercourse of 1-3 times monthly for 70-79-year-olds and weekly in the case of 40-69-year-olds. The effects of demographic risk factors such as income and education were more apparent in older age groups and were consistent with lower sexual function in lower socioeconomic groups. No reason is immediately apparent for the lower sexual function of Australian-born men compared with their overseas-born counterparts. Cardiovascular and medical risk factors reflected a conventional pattern.1,17 Predictors of low total sexual function scores after controlling for age only were smoking, blood pressure medication, high triglyceride levels and non-cancer prostate surgery, while a history of vigorous exercise provided a protective effect. In a combined model, smoking was no longer significant. Predictors of impotence after controlling for age only were high body mass index, high triglyceride levels, high cholesterol level, surgery for non-cancer prostate disease, while vigorous exercise was again protective. In a combined model, only high cholesterol remained significant. However, it is likely that small numbers of respondents limited the power of our study to investigate all these factors simultaneously. Our findings suggest that men experience poor sexual function as a deficit in the same age ranges in which cardiovascular risk factors are major determinants of that function, raising the possibility of prevention. It would be interesting to know whether, for men 60 years and over, improving cardiovascular risk factor profile would also reduce the prevalence of sexual dysfunction. Also of interest is the consistent and independent effect of non-cancer prostate surgery on sexual function. While its effects are small relative to age, it may point to a higher impotence rate than is commonly believed to result from this type of surgery,18 and this warrants further investigation. Acknowledgements We thank Living Health and Quitline for generously sharing their data on cardiovascular risk factors, and the AntiCancer Foundation for funding the prostate cancer questions. We would also like to thank the Behavioural Epidemiology Unit, South Australian Department of Human Services, and Lynne Giles, Flinders University, for assistance with aspects of the statistical analyses. References Bortolotti A, Parazzini F, Colli E, Landoni M. The epidemiology of erectile dysfunction and its risk factors. Int J Androl 1997; 20: 323-334. Feldman HA, Goldstein I, Hatzichristou DG, et al. Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. J Urol 1994; 151: 54-61. Helgason AR, Adolfsson J, Dickman P, et al. Factors associated with waning sexual function among elderly men and prostate cancer patients. J Urol 1997; 158: 155-159. Jonler M, Moon T, Brannan W, et al. The effect of age, ethnicity and geographical location on impotence and quality of life. Br J Urol 1995; 75: 651-655. Chew K, Burio C, Stuckey B, Jamrozik K. Erectile dysfunction in general medical practice. A study in Perth, Australia. Int J Impotence Res 1997; 9 (Suppl 1): S36. Pinnock C, Marshall V. Troublesome urinary symptoms in the community: a prevalence study. Med J Aust 1997; 167: 72-75. Weller D, Pinnock C, Silagy C, et al. Prostate cancer testing in South Australian men: influence of sociodemographic factors, health beliefs and lower urinary tract symptoms. Aust N Z J Public Health 1998; 22: 400-402. Pinnock C, Weller D, Marshall V. Self-reported prevalence of prostate specific antigen (PSA) testing in South Australia: a community study. Med J Aust 1998; 169: 25-28. Litwin MS, Hays RD, Fink A, et al. Quality-of-life outcomes in men treated for localized prostate cancer. JAMA 1995; 273(2): 129-35. [See comments.] Litwin MS, Nied RJ, Dhanani N. Health-related quality of life in men with erectile dysfunction. J General Intern Med 1998; 13: 159-166. Kish L. Estimates of unit variance: design effect. Survey sampling. New York: John Wiley and Sons, 1965: 257-263. NIH Consensus Conference. Impotence. NIH Consensus Development Panel on Impotence. JAMA 1993; 270: 83-88. SPSS for Windows [computer program], version 6.1. Chicago, Ill: SPSS Inc, 1996. Marsiglio W, Donnelly D. Sexual relations in later life: a national study of married persons. J Gerontol 1991; 46(6): S338-S344. Diokno AC, Brown MB, Herzog AR. Sexual function in the elderly. Arch Intern Med 1990; 150: 197-200. Solstad K, Hertoft P. Frequency of sexual problems and sexual dysfunction in middle-aged Danish men. Arch Sexual Behavior 1993; 22: 51-58. Helgason AR, Adolfsson J, Dickman P, et al. Waning sexual function -- the most important disease-specific distress for patients with prostate cancer. Br J Cancer 1996; 73: 1417-1421. Clinical practice guidelines for the management of uncomplicated lower urinary tract symptoms in men. Canberra: National Health and Medical Research Council, 1997. (Received 30 Nov 1998, accepted 28 Jun 1999) Authors' details Repatriation General Hospital, Daw Park, Adelaide, SA. Carole B Pinnock, PhD, Principal Research Scientist, Division of Surgery; Alan M F Stapleton, PhD, FRACS, Director, Urology Unit; Villis R Marshall, MD, FRACS, Head, Division of Surgery, and Head, Department of Surgery, Flinders Medical Centre. Reprints will not be available from the authors. Correspondence: Dr C B Pinnock, Division of Surgery, Repatriation General Hospital, Daws Road, Daw Park, SA 5041. carole.pinnockAThealth.sa.gov.au Back to text Back to text Back to text Back to text

Carole B Pinnock · Villis R Marshall

Editorial Breaking bad news: explaining cancer diagnosis and prognosis Doctors and nurses need training in communicating information about cancer and responding to patients' concerns MJA 1999; 171: 288-289 For related articles see Prince, Lobb et al & Naganathan et al Most patients, if they have cancer, want to be told about it, and they want to know what the likely treatments are, the side effects of treatment and their prognosis.1 A clear understanding of prognosis can be particularly important in conditions such as breast cancer, because patients need prognostic information to make informed decisions about systemic treatment. So, how can this information best be communicated? Based on a literature review and recommendations of a consensus panel of doctors (with input from patients with cancer), Girgis and Sanson-Fisher2 published some useful guidelines on conveying information to patients about serious disease or death. Their guidelines included ensuring privacy and allowing adequate time, assessing patients' understanding, giving information about diagnosis and prognosis simply and honestly, avoiding euphemisms, encouraging patients to express feelings, being empathic, giving a broad but realistic time-frame concerning prognosis, and arranging a review. The crucial question is how well these recommendations are followed in clinical practice, as discussing prognosis should be part of the process of breaking bad news. Audiotape recordings of consultations have shown that doctors break the bad news of a cancer diagnosis to patients in a predictable and routine way regardless of patients' individual information needs.3 Although the doctors gave reassurance that something could be done, few attempted to elicit patients' thoughts and feelings about the symptoms and their cause. They gave the information in a consistent order -- diagnosis, the relevant evidence, the need for further investigations, the treatments being considered and the probable outcome -- with no heed to which issues patients wished to address first. Obvious verbal and non-verbal cues of distress were not acknowledged and patients' immediate concerns were not explored. This consultation structure led patients to believe they were not entitled to talk about their feelings or their major concerns. Consequently, their preoccupation with these feelings and concerns meant that they did not assimilate the information and advice given. On being interviewed at the end of the consultation, patients reported that they were left with important, but undisclosed, concerns and also felt that the information given had been inadequate for their needs. The important article by Lobb and colleagues4 published in this issue of the Journal looks at one aspect of breaking bad news to cancer patients -- explaining prognosis to women with breast cancer. It was clear from the women's answers to a questionnaire and a clinical vignette that many had problems understanding prognostic information in the form it is usually presented. The women also varied considerably in what prognostic information they would like to receive and how they preferred it to be presented. The study's findings showed that not all women will desire or understand standard methods of giving prognostic information. It has been suggested that giving patients the opportunity to talk with nurses after consultations in which they have been told they have cancer, or have been given complex information about cancer prognosis, would result in their disclosing concerns and misunderstandings and these could then be fed back to the treating clinicians.5 However, this solution ignores important evidence that nurses are just as reluctant as doctors to acknowledge patients' distress and elicit their underlying concerns.6 Like doctors, nurses in these situations have been found to adopt behaviours designed to prevent further disclosure.7 These "blocking behaviours" include telling patients that any distress is normal, switching the subject to neutral topics, giving information and advice before patients' concerns have been identified, focusing only on physical aspects of the condition, and using leading, closed and multiple questions.7 Doctors and nurses avoid exploring patients' feelings and concerns because they fear that it will provoke too much emotion, which could be harmful to patients.8 They feel that their training has not equipped them with the necessary skills to explore these issues and respond appropriately.9,10 Feeling that they are not being supported emotionally and practically by colleagues and supervisors has also been linked to a greater use of these "blocking behaviours".6,11 The lack of adequate training of doctors and nurses in communicating information to patients with cancer can have important negative psychological consequences for the patients. The development of clinical anxiety and depression is more likely when patients have unresolved concerns and perceive that they have been given inadequate information.12,13 So, how can these communication deficiencies be remedied? The data collected by Lobb et al4 could be used as a basis for ongoing research to identify how best to structure and describe prognostic information so that concepts such as "median survival" and "relative risk" are made understandable. It would then be possible to develop training programs in communication skills that teach doctors how to elicit patients' preferences for information about prognosis. The use of intradisciplinary10 and multidisciplinary workshops14 has been advocated. While objective evidence of the value of intradisciplinary workshops is awaited, multidisciplinary workshops have proved successful in helping doctors and nurses acquire key communication skills.14 Despite workshops being effective in changing key communication behaviours, it is not certain how much of what is learnt is applied to clinical practice. Two randomised trials are being conducted in the United Kingdom in an effort to determine this. The Cancer Research Campaign (CRC) Psychosocial Oncology Group is studying whether training doctors in small groups enables them to be more effective in communicating with patients and better able to cope with breaking bad news and dealing with patient concerns. The CRC Psychological Medicine Group is assessing whether senior doctors benefit from six sessions of individual feedback on their "bad news" consultations and whether this results in better patient recall and less patient distress in future consultations (as measured by a patient interview and the Hospital Anxiety and Depression Scale), as well as a reduction in the level of burnout in the doctors themselves. Without systematic training, the breaking of bad news and discussions of cancer prognosis are likely to fall short of existing guidelines and patients' needs and expectations. Consultations of this type can be difficult and painful. Yet, for too long, we have expected doctors and nurses to undertake these difficult tasks without the necessary training and support. G Peter Maguire Consultant Psychiatrist; and Director Cancer Research Campaign Psychological Medicine Group, Manchester, UK Meredith C, Symonds P, Webster L, et al. Informational needs of cancer patients in West Scotland: cross sectional survey of patients' views. BMJ 1996; 313: 724-726. Girgis A, Sanson-Fisher RW. Breaking bad news: consensus guidelines for medical practitioners. J Clin Oncol 1995; 13: 2449-2456. Maguire P. Breaking bad news. Cambridge: Cambridge Handbook of Psychology, Health and Medicine, 1998: 273-275. Lobb EA, Butow PN, Kenny DT, Tattersall MHN. Communicating prognosis in early breast cancer: do women understand the language used? Med J Aust 1999; 171: 290-294. Watson M, Denton S, Baum M, Greer S. Counselling breast cancer patients: a specialist nurse service. Counselling Psychol Q 1988; 1(i): 23-31. Wilkinson SM. Factors which influence how nurses communicate with cancer patients. J Adv Nurs 1991; 16: 677-688. Maguire P. Barriers to psychological care of the dying. BMJ 1985; 291: 1711-1713. Maguire P, Faulkner A, Booth K, et al. Helping cancer patients disclose their concerns. Eur J Cancer 1996; 32A: 78-81. Maguire P, Faulkner A. How to improve the counselling skills of doctors and nurses in cancer care. BMJ 1988; 297: 847-849. Fallowfield L, Lipkin M, Hall A. Teaching senior oncologists communication skills: Results from phase 1 of a comprehensive longitudinal programme in the United Kingdom. J Clin Oncol 1998; 16: 1961-1968. Booth K, Maguire P, Butterworth T, Hillier VT. Perceived professional support and the use of blocking behaviours by hospice nurses. J Adv Nurs 1996; 24: 622-527. Parle M, Jones B, Maguire P. Maladaptive coping and affective disorders in cancer patients. Psychol Med 1996; 26: 735-744. Fallowfield LJ, Hall A, Maguire GP, Baum M. Psychological outcomes of different treatment policies in women with early breast cancer outside a clinical trial. BMJ 1990; 301: 575-580. Maguire P, Booth K, Elliott C, Jones B. Helping health professionals involved in cancer care acquire key skills -- the impact of workshops. Eur J Cancer 1996; 32A: 1486-1489.

Research Communicating prognosis in early breast cancer: do women understand the language used? Elizabeth A Lobb, Phyllis N Butow, Dianna T Kenny and Martin H N Tattersall MJA 1999; 171: 290-294 For related articles see Maguire, Prince & Naganathan et al Abstract - Introduction - Methods - Results - Discussion - Acknowledgements - References - Authors' details - - More articles on Oncology Abstract Objectives: To determine the degree to which women with early breast cancer understand the prognostic information communicated by clinicians after breast cancer diagnosis, and their preferences for how this information is presented. Design: Cross-sectional survey conducted within two months of breast cancer diagnosis, using a self-administered written questionnaire. Participants and setting: One hundred women attending five Sydney teaching hospitals and one country hospital, who were diagnosed with early stage breast cancer between January and December 1997. Results: The 100 respondents represented 70% of the 143 women originally approached to participate. Many respondents did not fully understand the language typically used by surgeons and cancer specialists to describe prognosis: 53% could not calculate risk reduction (with adjuvant therapy) relative to absolute risk; 73% did not understand the term "median" survival; and 33% believed a cancer specialist could predict an individual patient's outcome. Women in professional/ paraprofessional occupations understood more prognostic information than non-professional women. There was no agreement on the descriptive equivalent of a "30%" risk, nor the numerical interpretation of a "good" chance of survival. Forty-three per cent of women preferred positively framed messages (eg, "chance of cure"), and 33% negatively framed messages (eg, "chance of relapse"). The information women most wanted was that relating to probability of cure, staging of their cancer, chances of treatment being successful, and 10-year survival figures with and without adjuvant therapy. Conclusions: Our results suggest that misunderstanding is responsible for women's confusion about breast cancer prognosis. Clinicians should use a variety of techniques to communicate prognosis and risk, and need to verify that the information has been understood. Introduction To make informed decisions women with breast cancer must understand what their prognosis is without systemic treatment, and the likely advantages and disadvantages of treatment. While most Australian doctors now tell cancer patients their diagnosis,1 prognosis is less commonly discussed.2 Reticence to provide prognostic information is often based on concerns that the information will be overwhelming, not understood or will destroy hope.3,4 However, it is not clear whether the information itself, or the language used, is the critical feature. Many patients have a poor understanding of their disease and their prognosis,5,6 or have difficulty recalling the information they have been given about their disease.7,8 Similarly, women at risk of developing breast cancer commonly misreport individual and population risk.9 Denial and minimisation of risk are also common psychological reactions to cancer risk notification after screening procedures.10 If it were possible to determine whether patients cannot understand the terminology or mathematics of risk information, or, rather, prefer not to be told or do not absorb the information, clearer directions for best clinical practice in discussing prognosis could be established. Most previous studies on risk communication in cancer have not dealt specifically with issues pertinent to women with breast cancer. In two studies that did, the women surveyed were well down the treatment path and their experience of learning their prognosis was long past.5,11 To our knowledge, there are no reports of women's understanding of specific prognostic information in early breast cancer. We investigated women's understanding of prognostic information and their preferences for the way the information on the risk of their breast cancer recurring after surgery is presented to them. Methods Survey subjects Women were recruited through their treating physician. To ensure input from a range of women, five urban centres attracting referrals from populations with different socioeconomic profiles (Royal Prince Alfred, Royal North Shore, Prince of Wales, St George, and Westmead hospitals, all in Sydney, New South Wales) and one rural centre (Tamworth Hospital, Tamworth, NSW) were approached to participate in the study. Thirteen breast surgeons and 13 medical oncologists from these centres were invited to participate in the study and all agreed. One hundred and forty-three consecutive women newly diagnosed with stage I or II breast cancer at any of the six treatment centres between January and December 1997 were contacted by letter to request their participation. The women received the letter within 2-4 weeks of making their own decisions about adjuvant treatment and within 2 months of their initial diagnosis. (The timing of questionnaire administration was carefully considered to maximise the saliency of the issues while avoiding distressing women making their own treatment decisions.) The letter was followed up by a phone call from the research coordinator, who obtained verbal consent for participation and then sent out the questionnaire by mail. One centre opted to send women a letter signed by their oncologist inviting them to participate in the study. The survey sample included patients of surgeons and medical oncologists in both private and public practice. Women from a non-English-speaking background with insufficient knowledge of English to complete the questionnaire, and women presenting with a second cancer, were excluded. Questionnaire We gathered the data using a self-administered written 17-item questionnaire, designed on the basis of a review of the literature; an analysis of 20 audiotapes of initial oncology consultations with breast cancer patients (collected from two centres -- Royal Prince Alfred Hospital and Westmead Hospital -- during another study undertaken between 1995 and 199712); and expert consultation (a working party set up by the National Breast Cancer Centre). The 20 audiotapes were transcribed and the contents analysed to identify the range of ways in which prognosis was conveyed to patients (eg, absolute and relative risk, cumulative risk, numerical or non-numerical probability, and individual versus population risk). The questionnaire investigated women's understanding of and preferences for these different formats used by doctors for disclosing prognosis and risk information. In addition, a standard hypothetical scenario of adjuvant therapy in early stage breast cancer was included, and women responded to questions applying to that scenario (Box 1). Six of the questions explored women's understanding of different ways in which the risk of breast cancer recurring after surgery could be presented. Two sample questions are shown in Box 2. A "don't know" option was not offered in the items relating to "understanding" in order to force a choice and allow an analysis of common errors in interpretation. The remaining questions focused on the importance of different prognostic information to women's decision making, and on their preferences for presentation of risk - for example: percentages versus numbers (eg, "70%" v. "7 in 10"); numerical versus verbal descriptions of risk (eg, "30%" v. "small"); and positively framed versus negatively framed statements (eg, "70% chance of remaining free of cancer" v. "30% chance of the cancer coming back"). The questionnaire also elicited the women's demographic data and details of their breast cancer diagnosis and treatment (Box 3). Statistical analysis Appropriate sample sizes were calculated using the SAM sample size software package.13 Sample size calculations were based on effect sizes from related studies in patients' level of recall after a variety of interventions. In an Australian study measuring understanding of information presented in an oncology consultation, a sample size of 47 per group was sufficient to detect statistically significant differences of 7% (P < 0.005) in recall between groups. Thus, in a comparison of two patient subgroups (eg, young v. old), a total sample size of 100 would allow us to detect a similar difference in responses in the two groups. A sample size of 100 would also allow detection of a difference of 30% or more (felt to be clinically significant) between subgroups in the proportion of women preferring one presentation of risk versus another, with a power of 0.8 and a significance level of 0.05. A "total understanding" score was calculated by summing correct responses to the six items assessing "understanding". The summary score was normally distributed (K-S Lilliefors .0514). Descriptive statistics were used to identify the percentage of patients understanding and preferring different risk information. Analysis of variance (ANOVA), Student's t tests and χ2 tests of association were used to examine the relationship between demographic variables and outcomes, as appropriate; two-sided tests were used.15 Ethical approval Approval was granted for this study by the Ethics Committee of the University of Sydney, the Central Sydney Area Health Service, the Southern Sydney Area Health Service, and individual hospital ethics committees at Westmead, Royal North Shore and Tamworth hospitals. Results Of the 118 women who agreed to participate in the survey, 100 returned questionnaires (70% of the original 143 women contacted). Demographic data Demographic characteristics of the participants are presented in Box 3. Their mean age was 56 years and most were city dwellers. Just over half had completed the Higher School Certificate, university or some form of tertiary training. The percentage of women with tertiary qualifications was 42% (compared with 37% in the general Australian population16).. Nearly two-thirds worked (or had worked) in professional or paraprofessional occupations, and 22% were working in occupations related to medicine (eg, doctor, nurse, medical receptionist, technician). Questionnaire responses A summary of the women's responses to the questionnaire is given in Box 4. Discussion We have identified some of the problems women with breast cancer experience when trying to interpret prognostic information presented by their doctors. Our results support the hypothesis that it is misunderstanding, not denial, that causes confusion. A considerable number of women in our study did not clearly understand some of the language used to describe the risk of breast cancer recurrence after surgery or how additional treatment might benefit them. Moreover, the response from this group of relatively highly educated women probably represents a "best case" scenario, and, if anything, one might expect understanding to be poorer in the general population of women with breast cancer. These findings have implications for informed consent. Clinicians need to explain what type of prognostic information can be given, and enquire how much of this information women want to hear. They should check very carefully how women have interpreted the information presented to them, and must not assume that, because a woman has already consulted a number of specialists, her prognosis has been conveyed to her and clearly understood. This applies to all patients with breast cancer, but especially those who work in unskilled occupations. It might be argued that our sample was not truly representative, as (i) the women surveyed, having recently been told their diagnosis, may not have been in the best frame of mind to answer the questionnaire clearly and impartially; and (ii) we did not include a similar group of women who had never had breast cancer. Furthermore, patient responses may have been different had the questions concerned personal experience rather than a hypothetical case scenario.5,9,10,19 However, data from Degner et al20 suggest that views expressed by people diagnosed with cancer differ considerably from those of the well population, which underscores the importance of surveying those who have actually been diagnosed with cancer. In addition, we felt that a typical case vignette was the most appropriate tool to control for the influence of individual disease variables and treatment protocols; to reduce the positive bias associated with evaluating one's own treatment team; and to examine all aspects of risk communication in adjuvant therapy. Creative measures to assist women in understanding risk statistics are needed. Bunker et al have recently proposed that a life table constructed from published statistics on national morbidity and mortality may be used to display the likelihood of developing or dying of a disease at any given moment.21 A similar approach could be used to display the likelihood of disease recurrence and premature death after cancer diagnosis. We believe that these and other information aids may contribute to informed patients' involvement in treatment decisions, and a more realistic understanding of prognosis. Acknowledgements We thank Dr Afaf Girgis, Dr Lyn Mann, Ms Kate White, Ms Joan Wilson and Ms Kim Hobbs for their assistance and advice; also the 26 clinicians who participated in this project, and the women who so willingly filled out the questionnaire. The research was funded by the National Health and Medical Research Council National Breast Cancer Centre of Australia. References Charlton RC. Breaking bad news. Med J Aust 1992; 157: 615-621. Butow PN, Kazemi J, Beeney LJ, et al. When the diagnosis is cancer: patient communication experiences and preferences. Cancer 1996; 77: 2630-2637. Oken D. What to tell cancer patients: a study of medical attitudes. JAMA 1961; 175: 1120-1128. Beisecker AE, Helmig I, Graham D, et al. Attitudes of oncologists, oncology nurses and patients from a women's clinic regarding medical decision making with older and younger breast cancer patients. Gerontologist 1994; 34: 505-512. Siminoff LA, Fetting JH, Abeloff MD. Doctor-patient communication about breast cancer adjuvant therapy. J Clin Oncol 1989; 7: 1192-1200. Sheldon JM, Fetting JH, Siminoff LA. Offering the option of randomized clinical trials to cancer patients who overestimate their prognoses with standard therapies. Cancer Invest 1993, 11: 57-62. Dunn SM, Butow PN, Tattersall MHN, et al. General information tapes inhibit recall of the cancer consultation. J Clin Oncol 1993; 11: 2279-2285. Mackillop WJ, Stewart WE, Ginsburg AD, Stewart SS. Cancer patients' perceptions of their disease and its treatment. Br J Cancer 1988; 58: 355-358. Evans DR, Blair V, Greenhalgh R, et al. The impact of genetic counselling on risk perceptions in women with a family history of breast cancer. Br J Cancer 1994; 70: 934-938. Lerman C, Rimer BK, Engstrom PF. Cancer risk notification: psychosocial and ethical implications. J Clin Oncol 1991; 9: 1275-1282. Hughes KK. Decision making by patients with breast cancer: the role of information in treatment decision selection. Oncol Nurs Forum 1993; 20: 623-628. Brown R, Dunn S, Butow P. Meeting patient expectations in the cancer consultation. Ann Oncol 1997; 8: 877-882. Glasziou P. SAM 2.1: a sample size calculator [computer program]. Sydney: NHMRC Clinical Trials Centre, University of Sydney, 1992. Armitage P, Berry G. Statistical methods in medical research. Oxford: Blackwell Scientific, 1994: 397. SPSS Advanced Statistics, TM6.1. Chicago; SPSS Inc, 1994. Australian women's year book. Canberra: Australian Bureau of Statistics, 1997. Degner LF, Kristjanson LJ, Bowman D, et al. Information needs and decisional preferences in women with breast cancer. JAMA 1997; 277: 1485-1492. Bilodeau BA, Degner LF. Informational needs, sources of information, and decisional roles in women with breast cancer. Oncol Nurs Forum 1996; 23: 691-696. Marteau TM. Framing of information: its influence upon decisions of doctors and patients. Br J Soc Psychol 1989; 28: 89-94. Degner LF, Sloan JA. Decision making during serious illness: what role do patients really want to play? J Clin Epidemiol 1992; 45: 941-950. Bunker JP, Houghton J, Baum M. Putting the risk of breast cancer in perspective. BMJ 1998; 317: 1307-1309. (Received 4 Jan, accepted 11 May, 1999) Authors' details University of Sydney, Sydney, NSW. Elizabeth A Lobb, BAdEd, MAppSci, Associate Lecturer, Medical Psychology Unit. Phyllis N Butow, PhD, MPH, Executive Director, Medical Psychology Unit; and Research Co-ordinator, Department of Psychological Medicine, Royal North Shore Hospital. Dianna T Kenny, PhD, MA, Associate Professor of Psychology, Faculty of Health Sciences. Martin H N Tattersall, MD, FRACP, Professor of Cancer Medicine, Department of Medicine. Reprints: Ms E A Lobb, Associate Lecturer, Medical Psychology Unit, Department of Psychological Medicine, University of Sydney, NSW 2006. Email: lizlobbATblackburn.med.usyd.edu.au 1: Hypothetical breast cancer scenario used in the questionnaire Sheila is a 54-year-old woman with breast cancer. Sheila has gone through the menopause. Sheila chose to have her breast cancer (tumour) removed by a lumpectomy, but she also had some of the lymph glands in her armpit removed. Sheila was advised to have radiotherapy after her lumpectomy. Sheila's breast cancer was small, and the lymph nodes under her arm were not affected with cancer. Her tumour contained receptors to oestrogen, suggesting that it may be sensitive to the effects of hormones. Sheila's doctor uses this information to decide if she would benefit from additional treatment. Sheila understands that any additional treatment other than surgery is called "adjuvant" therapy. Adjuvant therapy means giving treatment now after her surgery to try to prevent the cancer returning in the future. Following her breast cancer surgery, Sheila was told of her risk of having her cancer return (her prognosis) if she has no further treatment. This risk can be expressed in different ways. Back to text 2: Examples of questions to assess women's understanding of relative risk reduction Example A: Sheila's doctor told her that 30% of women with a cancer similar to hers will have their cancer come back within 5 years. If Sheila has additional treatment, the risk of her cancer coming back will be reduced by 30%. Tick one only If Sheila has additional treatment this means the risk of her cancer coming back within 5 years is zero. If Sheila has additional treatment this means the risk of her cancer coming back within 5 years is 21%. If Sheila has additional treatment this means the risk of her cancer coming back within 5 years is 30%. Example B: If Sheila's doctor says the median time for her breast cancer to return without further treatment is about 5 years, he/she means: The average time for Sheila's cancer to return is 5 years That 50% of women with breast cancer like Sheila's will have their cancer return within 5 years That the women whose cancer will come back will have it come back within 5 years I don't understand the word "median" Back to text 3: Demographic characteristics of the respondents (n = 100) to a questionnaire about provision of information on breast cancer prognosis*CategoryNumber of participantsAge (mean, 56 years; range, 35-88 years)Postcode City82 Country18Educational level Non-tertiary58 Tertiary42Occupation Professional/paraprofessional63 Non-professional36Marital status Married58 Other41English as first language84Working in medicine-related occupation22Time since diagnosis 1-2 months71 ≥3 months26Treatment for breast cancer Lumpectomy only14 Mastectomy only17 Lumpectomy + R38 Lumpectomy +R + C15 Mastectomy + C15Family member/friend with breast cancer Yes61 No38* Not all categories sum to 100 because of missing data. R = radiotherapy; C = chemotherapy. Back to text 4: Summary of questionnaire responses Understanding of risk Risk concepts tested Absolute risk of relapse: -- 86% of respondents gave a correct response. 30% relative risk reduction, with therapy, of an absolute risk of 30% (sample question A, Box 2): -- 47% gave a correct response; -- 28% thought additional treatment would reduce the risk of relapse to zero; and -- 25% thought the risk would remain at 30%. Median 5-year survival (sample question B, Box 2): -- 27% answered correctly; -- 43% thought it meant "average" survival; -- 10% thought that half the women not having adjuvant therapy would have their breast cancer return within 5 years; and -- 20% did not understand the term "median". Interpretation of a graphical representation of risk: -- 80% of respondents answered correctly. Distinguishing individual risk from population risk: -- 66% gave correct response. -- The remaining women believed that their cancer specialist knew whether or not they would respond to treatment. Association with demographic variables Mean number of correct responses, 3.4 (95% CI, 3.08-3.6); only one woman answered all six questions correctly. Women in professional employment (mean number of correct responses, 3.6 [95% CI, 3.2-4.0]) or paraprofessional employment (mean number of correct responses, 3.4 [95% CI, 3.0-3.8]) understood more prognostic information than women in non-professional employment (mean number of correct responses, 2.5 [95% CI, 1.7-3.4] [F2,87 = 4.24, P = 0.02]). No other variables were found to be associated with understanding of risk (eg, working in a medically related field; having tertiary qualifications; having had surgery, radiotherapy and/or chemotherapy for breast cancer; or time elapsed since consultation in which prognosis was discussed). Interpretation of words versus statistics There was no consistency in respondents' interpretation of "a good chance of remaining free of cancer" in statistical terms, nor agreement on the non-numerical interpretation of "a 30% risk" (17% thought it was a very high or high risk, 34% that it was a medium risk, and 49% that it was a low risk). Preferences for language 44% of respondents preferred "a 70% chance of cure", 13% preferred "a 7 in 10 chance", and the remainder had no preference. 53% of women preferred "a 30% chance of cancer coming back", 38% preferred "a small chance of cancer coming back", and the remainder had no preference. 49% of non-tertiary-educated women versus 24% of tertiary-educated women preferred the descriptive option (a "small" chance) (χ22 = 8.17, P = 0.02). 43% of women preferred the wording "70% chance of cure", 33% preferred "30% chance of the cancer coming back", and 25% had no preference. Preferences for framing of information Reasons given for choosing positively framed prognostic information: "a more positive/optimistic statement" and "encourages determination to manage treatment positively". Reasons given for choosing negatively framed prognostic information: "it emphasises the importance of additional treatment" and "more specific/precise". Importance attributed to prognostic information (Table) Over 90% of respondents regarded information about their chances of being cured, the staging of their cancer, and the chances that the recommended treatment would work as very important to their decision making. Nearly two-thirds of women regarded the 10-year survival rate with adjuvant therapy as very important information, and 45% wanted to know this rate without adjuvant therapy. These percentages are considerably higher than documented in previous studies.17,18 Women's ratings of the importance of different types of prognostic informationPrognostic informationVery importantSomewhat importantNot importantMy chances of being cured94%2%4%What things about my cancer influence my chances of being cured (eg, size of my cancer, whether lymph nodes are involved, etc)92%6%2%The chances that the recommended treatment will work91%7%2%How many women in my situation choosing to have the recommended treatment would be alive in 10 years60%29%11%Statistics about long term outcome of breast cancer50%32%18%How many women not choosing to have the recommended treatment are alive in 10 years45%35%20%The longest anyone in my situation has lived34%19%47%The shortest anyone in my situation has lived30%14%56%The risk of my cancer shortening my life compared with other life events (eg, heart disease, old age)45%23%32%The average time people in my situation have lived44%28%28%Back to text

Elizabeth A Lobb · Phyllis N Butow · Dianna T Kenny

Editorial Diagnosing osteoporosis: the value of quantitative ultrasound Currently, screening by quantitative ultrasound does not appear to be a good deal MJA 1999; 171: 295-296 For related articles see Maguire, Lobb et al & Naganathan et al Towards the end of the 20th century, the problems of diagnosis have not really changed. These remain how to evaluate the risk of disease, and then how to explain risk reduction clearly to patients. What has changed is our ability to predict risk, and to reduce that risk by the powerful public health, pharmacological or surgical interventions now available. What has this to do with osteoporosis, a microarchitectural disorder leading to fragility fracture? Osteoporosis is a classic chronic disorder in which the actual individual risk of clinical disease (in this case future fracture) is often difficult to quantify. The situation is similar for hypertension and hypercholesterolaemia. A few statistics may aid risk evaluation. A risk of 5%-10% or greater over five years of any osteoporotic fracture (arms, legs, pelvis, spine or rib) is generally regarded as requiring intervention. Interventions can reduce fracture risk by about 15%-50%.1,2 To prevent one fracture in such a population, between 20 and 133 patients need to be treated for five years. The risk of osteoporotic fracture depends on age. In women over the age of 65 years, the five-year risk rises dramatically from 5%, and to 20% in women over the age of 90 years.3 The presence of a previous osteoporotic fracture at least doubles the risk of future fracture.4-6 What does bone densitometry have to do with risk evaluation? It is this: when bone density is measured by dual energy x-ray absorptiometry (DEXA), then, for each standard deviation that the result falls below the mean for the individual's age (the Z score), the future risk of fracture doubles. Thus, an individual with a Z score of 22 has a fourfold greater risk of fracture than the average person of the same age. In a 65-year-old, this would give an actual five-year risk of fracture of about 30%. Because the bone density of fracture populations is independent of age, the concept of a standard deviation unit with respect to a fixed, low-risk population -- healthy 20-30-year-olds -- has been introduced (the T score) (see Figure). Significant microarchitectural deterioration (osteoporosis) is defined in bone density terms as a T score of -2.5 or less. Patients with a T score in this range have at least 5.65 times the risk of fracture relative to normal young individuals. However, their absolute five-year risk of fracture is related to the actual population risk at their age; for women aged 65-70 years this is about 18%.2 Factors other than age and bone density contribute to calculation of absolute fracture risk. Particularly important is a previous history of osteoporotic fracture. Currently, bone density risk evaluation by DEXA or quantitative computed tomography is supported by rebates from the Health Insurance Commission (HIC) for patients at high risk based on clinical information. Rebates are for evaluation of individuals who have had an osteoporotic fracture; who have clinical risk factors, such as corticosteroid treatment or premature menopause; or who have had osteoporosis diagnosed on a previous bone density test. The HIC will not fund the first bone density test in unselected individuals, otherwise known as population screening. This is because it is currently considered that bone density testing and the interventions consequent on finding high-risk individuals do not fulfil Australian cost-effectiveness criteria. However, individuals who do not meet current HIC criteria for bone density testing often decide to pay for the test themselves. How should we advise the HIC or the individual patient about the most effective screening for osteoporosis? Based on the epidemiology of fracture in Australia, it could be argued that, as well as the categories of high risk patients already outlined, all women aged 65-75 years should have bone density testing. This is because the population risk of future fracture rises dramatically in this age group. If screening is performed at an earlier age, the benefits are diluted by the small number of patients with detectable osteoporosis and the lack of controlled trial evidence that treatment prevents fracture at these ages when event rates are low. Could ultrasound become a "front end" to DEXA testing? In this issue of the Journal, the article by Naganathan et al7 is a useful contribution to the debate, providing a framework for considering the value of ultrasound screening. Naganathan et al report a simple method for calculating the benefits of testing bone structure by ultrasound compared with the current "gold standard" of DEXA. They achieved this by comparing the pre- and post-test probabilities of DEXA-defined osteoporosis (T score ≤ -2.5 at spine or hip sites) after ultrasound testing. Interestingly, they showed that 37% of their selected population had a normal combined quantitative ultrasound score, and that this finding completely excluded DEXA-defined osteoporosis. However, based on these data, an ultrasound test does not seem to be a good deal either for the individual patient or for the HIC, should it fund screening. The cost of screening 100 patients with ultrasound ($40 each) plus DEXA for those with abnormal ultrasound results ($80 x 63) would be $9040; the cost of screening with DEXA alone would be only $8000. Thus, both patients and the HIC should be advised not to pay for commercial ultrasound testing as a "front end" to DEXA at present. What about the future -- could ultrasound replace DEXA as the "gold standard" for predicting fracture? The answer is yes, possibly. The evidence-based approach would demand large prospective studies showing that ultrasound is better and cheaper than DEXA in predicting fracture, and that patients treated on the basis of ultrasound testing have a reduced risk of fracture compared with those who are not treated. To date, a couple of studies have taken the first steps to show effective fracture prediction in elderly women.8,9 It has taken 20 years to validate DEXA as a clinically useful predictor of patients who should be treated to prevent fracture, so don't hold your breath over ultrasound! Richard L Prince Associate Professor, University Department of Medicine Sir Charles Gairdner Hospital, Perth, WA Reprints: Associate Professor R L Prince, University Department of Medicine, Sir Charles Gairdner Hospital, Nedlands, WA 6009. Eddy DM, Johnston CC, Cummings SR, et al. Osteoporosis: review of the evidence for prevention, diagnosis and treatment and cost-effectiveness analysis. Osteoporos Int 1998; 8 Suppl 4: S7-S80. Cummings SR. Effect of alendronate on risk of fracture in women with low bone density but without vertebral fracture: Results from the Fracture Intervention Trial. JAMA 1998; 280: 2077-2082. Sanders KM, Seeman E, Ugoni AM, et al. The age- and gender-specific rate of fractures in Australia: a population based study. Osteoporos Int 1999. In press. Ross PD, Genant HK, Davis JW, et al. Predicting vertebral fracture incidence from prevalent fractures and bone density among non-black, osteoporotic women. Osteoporos Int 1993; 3: 120-126. Wasnich RD, Davis JW, Ross PD. Spine fracture risk is predicted by non-spine fractures. Osteoporos Int 1994; 4: 1-5. Cummings SR, Nevitt MC, Browner WS, et al. Risk factors for hip fracture in white women. N Engl J Med 1995; 332: 767-773. Naganathan V, March L, Hunter D, et al. Quantitative heel ultrasound as a predictor of osteoporosis. Med J Aust 1999; 171: 297-300. Bauer DC, Gluer CC, Cauley JA, et al. Broadband ultrasound attenuation predicts fractures strongly and independently of densitometry in older women. Arch Intern Med 1997; 157: 629-634. Porter RW, Miller C, Grainger D, Palmer SB. Prediction of hip fracture in elderly women: a prospective study. BMJ 1990; 301: 638-641. Back to text

Richard L Prince

Research Quantitative heel ultrasound as a predictor for osteoporosis Vasi Naganathan, Lyn March, David Hunter, Nick A Pocock, Joanna Markovey and Philip N Sambrook MJA 1999; 171: 297-300 For related articles, see Prince, Maguire & Lobb et al Abstract - Introduction - Methods - Results - Discussion - References - Authors' details - - More articles on Rheumatology Abstract Objective: To determine the diagnostic value of quantitative ultrasound (QUS) to predict bone mineral density (BMD) categories as defined by dual-energy x-ray absorptiometry. Design: Cross-sectional survey. Setting: Rheumatology department of a tertiary care hospital (Royal North Shore Hospital, Sydney, NSW), 1997-1998. Subjects: 326 healthy women aged 45-80 years who had volunteered for a twin study. Our study included both members of non-identical twin pairs but only one randomly selected member of identical twin pairs. Main outcome measures: BMD categories as defined by dual-energy x-ray absorptiometry of lumbar spine and left hip, and QUS of calcaneus; sensitivity, specificity and likelihood ratios (LRs) of QUS parameters to diagnose osteoporosis as defined by BMD. Results: The sensitivity of QUS to diagnose BMD osteoporosis varied between 9% and 47%, depending on the QUS parameter. The specificity of QUS was high (88%-100%). If all QUS parameters were normal, osteoporosis was unlikely (LR, 0-0.2). One QUS parameter, broadband ultrasound attenuation (BUA), was highly predictive of osteoporosis by BMD when in the osteoporotic range (LR, Infinity), but had low sensitivity (9%). QUS results in the osteoporotic range for other parameters and all QUS results in the osteopenic range were less predictive (LR, 1.0-5.2) of osteoporotic BMD. Conclusion: These results suggest that, for most of those tested for osteoporosis by QUS in the community, uncertainty remains about expected BMD. Introduction Quantitative heel ultrasound has recently been introduced in Australian pharmacies as a "screening" tool for osteoporosis. The technology is relatively cheap, radiation-free and portable, but its accuracy in diagnosing osteoporosis is unclear. Bone mineral density (BMD), measured by dual energy x-ray absorptiometry (DEXA), is the best predictor of fracture risk and is currently considered the "gold standard" for diagnosing osteoporosis. Although prospective studies have shown that quantitative ultrasound (QUS) predicts future fracture risk independently of BMD,1,2 most women with abnormal results will proceed to formal BMD measurement to assess the need for therapeutic intervention; women with normal QUS results may be reassured they do not need BMD measurement. It is unclear how many women have unnecessary further investigations or are falsely reassured. When used in this way, QUS has diagnostic value only if it can accurately predict BMD categories as determined by DEXA. Our aim was to examine the role of QUS in predicting BMD diagnostic categories. We determined conventional sensitivity and specificity, as well as likelihood ratios (LRs). These have the advantage of allowing test results to be assessed for several diagnostic categories rather than only at a single cut-off between "normal" and "abnormal".3 Methods Subjects and setting The study was a cross-sectional survey of healthy women aged 45-80 years who had volunteered to take part in a twin study. They were recruited from the Australian Twin Registry and media advertising. Our ultrasound study included both members of each non-identical twin pair and one randomly selected member of each identical twin pair. The study was conducted in the Rheumatology Department of the Royal North Shore Hospital, Sydney, NSW (a tertiary care hospital), in 1997 and 1998. It was approved by the hospital's Human Research Ethics Committee. Assessment Subjects had BMD measurements of their lumbar spine (L1-L4) and left hip (neck of femur and total hip) by DEXA using a Hologic QDR450 instrument (Hologic Inc, Waltham, Mass, USA). The same machine was used on all patients. QUS of the left calcaneus was performed on the same day using a CUBA Mark II ultrasound instrument (McCue Ultrasonics, London, UK). The two most commonly used QUS parameters were measured: broadband ultrasound attenuation (BUA), which is thought to reflect bone mass and architecture, and velocity of sound (VOS), which reflects mass and elasticity of bone.4 Analyses Each BMD and QUS value was converted to a T score (number of standard deviations from the population mean for young, healthy, sex-matched adults). This population mean was estimated from measurements in 50 women aged 20-30 years who also took part in the twin study. T scores were used to categorise BMD values as normal (T > -1) or indicating osteopenia (T, -2.5 to -1) or osteoporosis (T < -2.5), as proposed by a working party of the World Health Organization.5 QUS values were classified in the same way. Although no consensus has been reached on what T-score cut-offs and diagnostic categories to use with QUS, the instrument used commonly in Australian pharmacies uses the WHO criteria and cut-off values. Subjects were classified as having osteoporosis if at least one of the three BMD measurements (lumbar spine, neck of left femur or total left hip) indicated osteoporosis, and as having osteopenia if at least one measurement indicated osteopenia but none indicated osteoporosis. BUA and VOS results were combined as a cQUS category: this was defined as normal if both results were normal, as osteopenic if either indicated osteopenia but neither indicated osteoporosis, and as osteoporotic if either indicated osteoporosis. Some QUS scanners calculate a stiffness parameter (unrelated to mechanical stiffness) from a linear combination of normalised BUA and VOS values. We calculated stiffness in an analogous manner,6 and categorised it as normal, osteopenic or osteoporotic based on T scores in the same way as other QUS values. We calculated the sensitivity and specificity of QUS parameters in predicting BMD-defined osteoporosis and osteopenia. We also calculated the likelihood ratio (LR) for each QUS result (sensitivity/1 - specificity), defined as the ratio of the probability of the particular QUS result (normal, osteopenic or osteoporotic) in women with BMD-defined osteoporosis or osteopenia to the probability of the same result in women with normal BMD.7 As there is no consensus on what QUS cut-off values should be used to diagnose osteoporosis, the statistical analyses were repeated using a range of QUS T-score cut-off values for osteoporosis between -2.5 and -1.0. Results Subjects and osteoporosis There were 326 subjects, with mean age 58.5 years; 255 (78%) were postmenopausal. Of the 326, 47 (14%) had a BMD measurement indicating osteoporosis at one or more of the three sites where BMD was measured, and a further 160 (49%) had a measurement indicating osteopenia. QUS results are compared with BMD results in Box 1. The percentage of women with values in the osteoporotic range varied between QUS parameters (1% for BUA, 17% for VOS and the combined BUA-VOS category, and 14% for stiffness). Sensitivity and specificity of QUS Sensitivity and specificity of QUS for predicting BMD diagnostic categories are shown in Box 2. Sensitivity and specificity varied between QUS parameters. A BUA result in the osteoporotic range (T < -2.5) had very low sensitivity for predicting BMD-defined osteoporosis (9%), but high specificity (100%). In contrast, VOS, cQUS and stiffness results in the osteoporotic range had sensitivities of almost 50%, and specificities that were again high. For predicting either osteoporosis or osteopenia, stiffness had the best combination of sensitivity (77%) and specificity (81%). Positive and negative predictive values are also shown in Box 2. Negative predictive values were high (87%-91%) for QUS as a predictor of BMD-defined osteoporosis versus osteopenia/normal BMD. This indicated that a woman with BMD-defined osteoporosis was unlikely to have a QUS result in the normal-osteopenic range. Likelihood ratios of QUS LRs for different QUS results to predict BMD-defined osteoporosis are summarised in Box 2 and interpreted in Box 3. Normal QUS result: A BUA, VOS, cQUS or stiffness result in the normal range had a low LR (0-0.2) (ie, a normal result significantly lowered the odds or probability of the woman's having BMD-defined osteoporosis). Osteoporotic QUS result: A BUA result in the osteoporotic range had an LR approaching infinity and so was highly predictive of BMD-defined osteoporosis. In contrast, a VOS, cQUS or stiffness result in the osteoporotic range had a much lower LR (4.0-5.2), increasing the odds of BMD-defined osteoporosis, but to a lesser extent than a BUA result in the osteoporotic range. Osteopenic QUS result: QUS results in the osteopenic range were less predictive, as LR ranged from 1.0 to 2.4. Between 37% and 50% of subjects (depending on the QUS parameter) had results in this range (Box 1). LRs for predicting low BMD (ie, osteoporosis or osteopenia; BMD T score < -1) are also shown in Box 2, and followed a similar pattern to LRs for predicting BMD-defined osteoporosis. When QUS T-score cut-off values for osteoporosis were increased from -2.5 to -1.0, sensitivity increased, but at the expense of decreasing specificity and LR (data not shown). For example, a BUA cut-off of -1.0 gave 83% sensitivity, 69% specificity and LR, 2.6. Corresponding values for a VOS cut-off of -1.0 were 96%, 41% and 1.6. Discussion We found that QUS had variable usefulness in predicting BMD categories. Specificity for predicting BMD-defined osteoporosis was high for all QUS parameters (88%-100%), but sensitivity was low and variable (9%-47%). A BUA result in the osteoporotic range was highly predictive of BMD-defined osteoporosis (LR, Infinity), but had low sensitivity (9%). Results in the osteoporotic range for other QUS parameters and in the osteopenic range for all QUS parameters were less predictive of BMD-defined osteoporosis (LRs, 1.0-5.2). In the light of our study, how can we interpret QUS results? If a BUA result is in the osteoporotic range (LR, Infinity), then BMD-defined osteoporosis is almost certain (predictive value, 100%). However, the low sensitivity of BUA (9%) means that many women with osteoporosis would be missed if BUA alone were used. If results are normal for both BUA and VOS (cQUS normal; LR, 0), we can confidently rule out BMD-defined osteoporosis. If LR is 0, then, no matter what the pre-test probability of osteoporosis, the post-test probability will be < 5% (Box 3). All results in the osteopenic range, and VOS and stiffness results in the osteoporotic range, are less predictive of BMD category. Therefore, if QUS were performed on a population similar to ours (14% prevalence of osteoporosis), then (from Box 1) 1% would have a BUA result in the osteoporotic range (likely to have osteoporosis) and 33% would have both BUA and VOS results in the normal range (osteoporosis could fairly confidently be ruled out, with a post-test probability < 5%). However, there would be a degree of uncertainty about the remaining 66%, who would then need a DEXA scan to identify those with osteoporosis. Previous studies of QUS as a predictor of BMD have generally used conventional sensitivity and specificity analyses only, not LRs, and have not used the WHO BMD definitions. For example, two community-based cross-sectional studies on 700 postmenopausal10 and 1000 perimenopausal women,11 respectively, found that there was a 40%-50% overlap in the number of women in the lowest quartile of both DEXA and QUS measurements. Two other studies found QUS parameters to have a sensitivity of 65%-70% for BMD in the lowest quartile.6,12 Only one study other than ours has evaluated QUS in terms of WHO BMD definitions. It found BUA and VOS to have higher sensitivities, of 77% and 69%, respectively, for diagnosing osteoporosis in 100 women aged 60-69 years.13These higher sensitivities may have been due to use of higher BUA and VOS cut-off values. As expected, specificities were lower than in our study. The ultrasound instrument used in this study, the McCue Cuba Mark II, is not identical to the Achilles ultrasound instrument (Lunar, Madison, Wis, USA) used in Australian pharmacies. Nevertheless, a comparison of the two machines found that BUA measurements on a Cuba Mark II instrument were highly correlated with "stiffness" measurements on a Lunar Achilles instrument (r = 0.906; 95% CI, 0.873-0.931).14 Another study compared measurements of 30 women between the Cuba Mark II used in our study and an Achilles, finding an r value of 0.8.15 Therefore, it is unlikely that the Achilles instrument would be a significantly better predictor of BMD than our Cuba Mark II. There is no consensus on what cut-off values to use with QUS to diagnose osteoporosis. We found that changing the cut-off could achieve higher sensitivity, but only by accepting higher rates of false positives (lower specificity) and less discriminating LRs. Although there is enough evidence to support the use of QUS as an independent predictor of fracture risk,1,2 our study shows that QUS should not been seen as a substitute for BMD measurement. The results of our study suggest that, when women in the community are "screened" for osteoporosis using QUS, a few women will be confidently identified with BMD-defined osteoporosis. Another small group will be able to be reassured that they are unlikely to have osteoporosis. However, for the great majority, the presence or absence of osteoporosis will remain uncertain. References Hans D, Dargent MP, Schott AM, et al. Ultrasonographic heel measurements to predict hip fracture in elderly women: the EPIDOS prospective study. Lancet 1996; 348 (9026): 511-514. Bauer DC, Gluer CC, Cauley JA, et al. Broadband ultrasound attenuation predicts fractures strongly and independently of densitometry in older women. A prospective study. Study of Osteoporotic Fractures Research Group. Arch Intern Med 1997; 157: 629-634. Sackett DL, Haynes BR, Guyatt GH, et al. Clinical epidemiology. A basic science for clinical medicine. 2nd ed. Boston: Little, Brown and Company, 1991. Gluer CC, Wu CY, Jergas M, et al. Three quantitative ultrasound parameters reflect bone structure. Calcif Tissue Int 1994; 55: 46-52. World Health Organization Study Group. Assessment of fracture risk and its application to screening for prostmenopausal osteoporosis. World Health Organ Tech Rep Ser 1994; 843: 1-129. Herd RJ, Blake GM, Miller CG, et al. The ultrasonic assessment of osteopenia as defined by dual X-ray absorptiometry. Br J Radiol 1994; 67: 631-635. Fletcher RH, Fletcher SW, Wagner EH. Clinical epidemiology: the essentials. 3rd ed. Baltimore: Williams & Wilkins, 1988: 65. Fagan TJ. Normogram for Bayes theorem [letter]. N Engl J Med 1975: 293; 257. Australian National Consensus Conference 1996. The prevention and management of osteoporosis. Consensus statement. Med J Aust 1997; 167 Suppl: S1-S15. van Daele Burger H, Algra D, et al. Age-associated changes in ultrasound measurements of the calcaneus in men and women: the Rotterdam Study. J Bone Miner Res 1994; 9: 1751-1757. Massie A, Reid DM, Porter RW. Screening for osteoporosis: comparison between dual energy X-ray absorptiometry and broadband ultrasound attenuation in 1000 perimenopausal women. Osteoporos Int 1993; 3: 107-110. Young H, Howey S, Purdie DW. Broadband ultrasound attenuation compared with dual-energy X-ray absorptiometry in screening for postmenopausal low bone density. Osteoporos Int 1993; 3: 160-164. Langton CM, Ballard PA, Bennett DK, Purdie DW. A comparison of the sensitivity and specificity of calcaneal ultrasound measurements with clinical criteria for bone densitometry (DEXA) referral. Clin Rheumatol 1997; 16: 117-118. Greenspan SL, Bouxsein ML, Melton ME, et al. Precision and discriminatory ability of calcaneal bone assessment technologies. J Bone Miner Res 1997; 12: 1303-1313. Harris ND, Griffiths MR, Nguyen TV, et al. Quantitative ultrasound of the heel: a comparison of Lunar and McCue instruments [abstract]. Proceedings of the Australian and New Zealand Bone and Mineral Society 7th Annual Scientific Meeting. 1997. 29 Sept-1 Oct; Canberra, ACT: 62. (Received 24 Dec 1998, accepted 9 Jul 1999) Authors' details Department of Rheumatology, Royal North Shore Hospital, Sydney, NSW. Vasi Naganathan, FRACP, Research Scholar; Lyn March, FRACP, FAFPHM, Staff Specialist; David Hunter, MB BS, Advanced Physician Trainee in Rheumatology; Joanna Markovey, MSc, Research Bone Densitometry Technician; Philip N Sambrook, FRACP, MD, Head of Department. Department of Nuclear Medicine, St Vincent's Hospital, Sydney, NSW. Nick A Pocock, FRACP, MD, Senior Staff Specialist. Reprints will not be available from the authors. Correspondence: Dr V Naganathan, Department of Rheumatology, Royal North Shore Hospital, St Leonards, NSW 2065. Email: vasinATmed.usyd.edu.au 1: Association between quantitative heel ultrasound (QUS) results and bone mineral density* in 326 women aged 45-80 yearsBone mineral densityQUS resultNormal (n = 119)Osteopenia (n = 160)Osteoporosis (n = 47)Total (n = 326)Broadband ultrasound (BUA) Normal103918202 (62%) Osteopenia166935120(37%) Osteoporosis0044 (1%)Velocity of sound (VOS) Normal81332116 (36%) Osteopenia369623155 (47%) Osteoporosis2312255 (17%)Combined category (cQUS) Normal79280107 (33%) Osteopenia3810125164 (50%) Osteoporosis2312255 (17%)Stiffness Normal96444144 (44%) Osteopenia209421135 (41%) Osteoporosis3222247 (14%) * Measured by dual energy x-ray absorptiometry. Combined result for broadband ultrasound and velocity of sound: normal if both normal; osteopenic if either osteopenic and neither osteoporotic; and osteoporotic if either osteoporotic. Back to text 2: Use of ultrasound parameters to predict osteoporosis or osteopenia defined by dual energy x-ray absorptiometry (DEXA) measurement of bone mineral densityPredictive valuesLikelihood ratio for ultrasound measurement (95% confidence interval)Sensitivity SpecificityPositiveNegativeNormalOsteopeniaOsteoporosisTo predict osteoporosisBroadband ultrasound (BUA)9%100%100%87%0.2 (0.11-0.38)2.4 (1.9-3.1)InfinityVelocity of sound (VOS)46%88%40%91%0.1 (0.03-0.4)1.0 (0.7-1.4)4.0 (2.6-6.2)Combined category* (cQUS)47%88%40%91%0(1.1 (0.8-1.5)4.0 (2.6-6.2)Stiffness47%91%46%91%0.2 (0.08-0.5)1.1 (0.8-1.6)5.2 (3.2-8.4)To predict osteoporosis or osteopeniaBroadband ultrasound (BUA)52%87%87%51%0.6 (0.5-0.7)3.7 (2.3-6.0)InfinityVelocity of sound (VOS)83%68%82%70%0.25 (0.18-0.35)1.9 (1.4-2.6)15.0 (3.7-60.5)Combined category* (cQUS)86%66%82%74%0.20 (0.14-0.29)1.9 (1.4-2.5)15.2 (3.8-61.3)Stiffness77%81%87%67%0.3 (0.2-0.4)3.3 (2.2-5.0)8.4 (2.7-26.5) DEXA = dual energy x-ray absorptiometry. * Combined broadband ultrasound attenuation and velocity of sound category. Back to text 3: Interpretation of likelihood ratios The likelihood ratio (LR) indicates how much a test result raises or lowers the probability of an individual's having "disease". It can be used to determine post-test probability of a disease from the estimated pre-test probability using a normogram (Figure). Thus, if an early postmenopausal woman (aged 60-64 years) had a pre-test probability of osteoporosis of 15%,9 then, from the normogram, a cQUS result in the osteoporot ic range (LR, 4.0) would increase her probability to 40%. If she had a very high pre-test probability of osteoporosis, for example 50%, because of multiple risk factors (eg, including family history of osteoporosis and recent wrist fracture after a fall), then a cQUS result in the osteoporotic range would increase her probability to 80%. A BUA result in the osteoporotic range (LR, Infinity) would make BMD-defined osteoporosis highly likely, no matter what the pre-test risk. However, a cQUS result in the normal range (LR, 0) would make BMD-defined osteoporosis unlikely. QUS results in the osteopenic range, with LRs closer to unity (LR, 1.0-2.4), would make BMD category far less certain. Normogram for applying likelihood ratios, adapted from Fagan.8 Lines show post-test probabilities when LR = 4.0 and pre-test probabilities are 15% and 50%, respectively. Back to text

Vasi Naganathan · Lyn March · David Hunter · Nick A Pocock · Joanna Markovey · Philip N Sambrook

Research Hypertension in pregnancy: maternal and fetal outcomes according to laboratory and clinical features Mark A Brown and Megan L Buddle MJA 1996; 165: 360-365 Abstract - Introduction - Methods - Results - Discussion - Acknowledgements - References - Authors' details - - More articles on Sexual health Abstract Objectives: To determine the predictive value of clinical and laboratory parameters for maternal and fetal complications in pregnant women with hypertension. Design: Prospective data collection. Setting: Two primary referral hospitals in the southern suburbs of Sydney between March 1987 and July 1994. Subjects: 1183 pregnant women with hypertension managed conjointly by a physician and obstetrician. Intervention: Uniform management protocol, plus antihypertensive medications if systolic blood pressure was persistently ≥ 160 mmHg and/or diastolic blood pressure ≥ 90 mmHg. Main outcome measures: Maternal and fetal complications, as defined by the Australasian Society for the Study of Hypertension in Pregnancy Consensus Statement. Results: Of 825 women with pre-eclampsia (502 mild; 323 severe), univariate analysis showed that hyperuricaemia, proteinuria and severe hypertension were significantly associated with a higher rate of maternal and fetal complications. In multivariate analyses without confounders, only primiparity, low serum albumin levels and absence of diabetes were significantly associated with severe pre-eclampsia. Severe pre-eclampsia, high haemoglobin levels and low platelet count were associated with higher rates of small-for-gestational-age babies, but only low serum albumin levels were associated with increased perinatal mortality rates. Low birthweight was associated with severe hypertension and severe pre-eclampsia. Conclusions: Simple clinical and laboratory parameters are useful predictors for maternal and fetal outcomes in pregnancies complicated by hypertension. Introduction Hypertensive disorders in pregnancy are common and their incidence appears to be increasing.1 These disorders comprise hypertension de novo in pregnancy (variably called pre-eclampsia, gestational or transient hypertension), and chronic forms of hypertension (essential and secondary hypertension), and have multiple modes of clinical presentations. With the current emphasis on outpatient management of pregnant women with non-proteinuric hypertension,2 clinicians require readily available clinical and laboratory parameters as indicators of the likely outcome of pregnancies complicated by hypertension. Such information is often difficult to obtain because of the selective nature of cases and complications reported by high-risk tertiary-care obstetric units, and is confounded by the varying treatments given to pregnant women before referral.3,4 Our study examined prospectively the maternal and fetal outcomes in women with hypertension in pregnancy, and the associated clinical and laboratory features. In particular, we sought to determine whether complications were greater if the woman had hyperuricaemia, severe hypertension and/or proteinuria, was nulliparous, or presented with hypertension early in the pregnancy. We also sought to determine which clinical and laboratory features were associated with severe pre-eclampsia. Methods The study group consisted of all pregnant women with hypertension who were referred by their obstetrician to one physician (M A B) at primary referral hospitals (St George or Hurstville community hospitals) in Sydney between March 1987 and July 1994. Indications for referral were: Hypertension failing to settle after overnight rest in hospital, or repeated measurement in a day-only unit; The presence of proteinuria or other abnormal urinalysis, abnormal biochemistry (serum electrolytes and creatinine levels, liver function tests) or thrombocytopenia; Recurrent admissions for hypertension; or A suspected secondary cause for hypertension. The definitions, classifications and complications of hypertension in pregnancy used in our study were those of the Australasian Society for the Study of Hypertension in Pregnancy (ASSHP) (Boxes 1 and 2).5 The maternal biochemical and haematological data used in our analysis were those recorded immediately before delivery. Complications were those having occurred by the time of discharge from hospital or by the postpartum check-up (after three months). Each patient's management was overseen by one physician (M A B) in conjunction with the patient's obstetrician. A standardised management protocol was followed by all staff during the course of this study (Box 3). Statistical analysis All data were stored in a database program (iBANK) and analysed using Minitab statistical package6 and BMDP statistical software.7For initial bivariate analyses, the frequency of adverse events within groups was tested by χ2 analysis and, where significant, by 2 x 2 contingency tables. Biochemical and haematological indices and birthweights were compared using Student's t tests, and significance assessed using Hochberg's method for interpreting multiple comparisons. The maternal-outcome variable was severity of pre-eclampsia. Logistic regression analysis was used to analyse the following variables as predictors of severe pre-eclampsia: parity; gestation at presentation; age; plasma uric acid level; serum albumin, haemoglobin and haematocrit levels; and diabetes. Proteinuria, platelet count and serum creatinine levels were not analysed because abnormalities of these form part of the diagnosis of severe pre-eclampsia. Fetal-outcome variables were birthweight, small-for-gestational-age (SGA) and perinatal mortality (PNM). Each of the following variables was analysed as a predictor of poor fetal outcome: maternal complications, age, parity, diabetes, gestation at presentation and laboratory data. Multiple regression analysis was used for birthweight and logistic regression analysis for SGA and PNM. For regressions, backward elimination was used until all remaining predictors were statistically significant (P < 0.05). Results Clinical details From March 1987 to July 1994, 1183 pregnant women with hypertension fulfilled the criteria for referral to a physician (M A B) and were entered into the study, representing 6.7% of all confinements at the two hospitals. During this period, 2121 women were documented in hospital records as having hypertension in pregnancy, representing 12% of all confinements. There were 825 women (70%) with pre-eclampsia (mild, 502; severe, 323), 82 (7%) with superimposed pre-eclampsia, 223 (19%) with essential hypertension, and 53 (4%) with secondary hypertension (predominantly renal disease). Oral antihypertensive medications were given to 563 women (48%), additional parenteral antihypertensives were required by 281 (24%), and 339 (29%) received no antihypertensive medications. Thirteen women (1%) received "prophylactic" low-dose aspirin. Five women (0.4%) required dialysis during or after pregnancy and four women (0.3%) had convulsions. Seventy-three women (6%) had pre-existing or gestational diabetes mellitus. Of the 1242 babies born to the women in the study, there were 15 perinatal deaths (12 per 1000 hypertensive pregnancies). There was one maternal death (0.08%) in a 29-year-old woman who presented at 29 weeks' gestation with severe pre-eclampsia and who delivered immediately and died unexpectedly the next day. Despite autopsy, the cause of death was not established. Predictors of outcomes in women with pre-eclampsia Univariate analysis Hyperuricaemia was significantly associated with higher rates of all maternal complications and SGA babies and babies with lower average birthweights than normal plasma uric acid levels (Box 4). Severe hypertension was significantly associated with higher maternal complication rates and earlier gestation at delivery than mild hypertension (Box 4). This group of women had babies of a lower average birthweight, a higher proportion of SGA babies and a higher perinatal mortality rate. Proteinuria was significantly associated with similar maternal and fetal complication rates as severe hypertension, and the proportion of SGA babies was similar to non-proteinuric hypertension (Box 4). Parity did not affect maternal complication rates, except for a higher prevalence of severe hypertension and liver disease in nulliparae (Box 5). Early gestation at presentation with hypertension (at or before 32 weeks' gestation) was significantly associated with a higher prevalence of proteinuria than later presentation (Box 5). Multivariate analysis Severe pre-eclampsia was associated with low serum albumin (odds ratio [OR], 0.93; 95% confidence interval [CI], 0.90-0.97; P = 0.0001), primiparity (OR, 0.51; 95% CI, 0.33-0.79; P = 0.002) and the absence of diabetes (OR, 0.21; 95% CI, 0.05-0.93; P = 0.04). SGA was associated with severe pre-eclampsia (OR, 2.5; 95% CI, 1.6-3.9; P = 0.0001), high maternal haemoglobin levels (OR, 3.7; 95% CI, 1.1-12.8; P = 0.04) and low platelet counts (OR, 1.4; 95% CI, 1.1-1.8; P = 0.02). Birthweight was positively associated with gestation at presentation (regression coefficient [β], 41; standard error [SE], 5; P < 0.0001) and serum albumin levels (β, 28; SE, 5; P < 0.0001) and inversely associated with severe hypertension (β, 2193; SE, 69; P < 0.005) and severe pre-eclampsia (β, 2311; SE, 60; P < 0.0001). Perinatal mortality was associated only with low serum albumin levels (OR, 0.88; 95% CI, 0.82-0.95; P < 0.0003), but there were too few perinatal deaths to support a useful formal analysis. Outcomes in women with all forms of hypertension in pregnancy Box 6 shows the maternal and fetal outcomes in women with the different forms of hypertension in pregnancy. Maternal and fetal outcomes were better for women with essential hypertension than for the other groups. Twenty-seven per cent (or 10% if proteinuria was included in the diagnosis) of women with essential hypertension developed superimposed pre-eclampsia. Women with superimposed pre-eclampsia delivered their babies earlier, had babies with lower average birthweights, significantly more SGA babies and significantly higher rates of all maternal complications than women with essential hypertension alone. Women with secondary (predominantly renal) hypertension had similar maternal and fetal outcomes to women with superimposed pre-eclampsia (data available from author). Discussion In our prospective study, there was uniform management of all women with hypertensive disorders in pregnancy. As the database excluded very mild cases of hypertension in pregnancy, an inherent bias exists, but our study provides a general estimate of fetal and maternal outcomes for women with hypertension managed in primary referral hospitals. During the study period, 12% of all confinements were complicated by hypertension, which is either similar to or higher than previous reports.8-11 Hjertberg et al. noted a 5% incidence of hypertension in pregnancy, of whom 83% had hypertension de novo in pregnancy.12 In our study, 70% of women had pre-eclampsia (hypertension de novo in pregnancy), 19% had essential hypertension alone, 7% had superimposed pre-eclampsia, and 4% had a renal or other secondary cause. These results are similar to those from a smaller study in a tertiary referral unit.13 When analysed separately, hyperuricaemia, proteinuria and severe hypertension were associated with higher rates of all maternal and fetal complications, while parity was associated with severe hypertension and liver disease. Presentation before 32 weeks' gestation impacted negatively on fetal outcome. We have reported previously on the adverse impact of proteinuria on maternal and fetal outcomes.14 Hyperuricaemia is an established marker of severe pre-eclampsia, correlating histologically with the severity of renal lesions,15 and clinically with adverse fetal outcomes.16 We found that hyperuricaemia, when considered alone, was associated with higher maternal complication rates and fetal growth retardation, but, with multivariate analysis, was not a significant predictor of adverse maternal or fetal outcomes. Hyperuricaemia remains a useful marker of pre-eclampsia, but women with normal serum uric acid levels and pre-eclampsia may still develop complications. Severe hypertension was confirmed by multivariate analysis to be associated with low birthweight babies, and, in univariate analysis, with a higher incidence of all fetal complications and a higher incidence of SGA babies. Therefore, the more severe the hypertension, the more the likelihood of fetal as well as maternal complications. Pre-eclampsia has long been considered a disorder of primigravidae.17 However, it is clear that pre-eclampsia does occur in second or subsequent pregnancies (particularly following a change of partner); in our study, approximately two-fifths of the women with pre-eclampsia were parous women. Parous women had a lower incidence of severe hypertension and liver disease when compared with nulliparae, but there were no other differences in outcomes between these groups. Therefore, equal risk to the fetus should be assumed in both groups of women once hypertension has developed in the second half of pregnancy. The gestation at presentation in pre-eclampsia influences fetal outcome because of the likelihood of early delivery, but we are unaware of any prospective studies that relate gestation at presentation to maternal complication rates. Apart from proteinuria, maternal complication rates for women presenting before 33 weeks' gestation in our study were similar to those who presented later. Two retrospective studies have reported a higher incidence of maternal complications in women with pre-eclampsia of early onset.18,19 Our patients presenting early with pre-eclampsia had milder disease than that reported by Sibai et al.20 As expected, the earlier the gestation with pre-eclampsia the lower the birthweight (because gestation did not proceed as far as those presenting later), but the likelihood of having an SGA baby was not increased. Although maternal diabetes was associated with a lower risk of severe pre-eclampsia, only 6% of our study population had diabetes. Therefore, it should not be assumed that diabetes protects pregnant women against severe pre-eclampsia. The consistent relationship between low serum albumin levels and adverse maternal and fetal outcomes was independent of proteinuria and implies that hepatic albumin synthesis is altered in severe pre-eclampsia. The association between high maternal haemoglobin levels and SGA babies presumably reflects a reduced plasma volume and haemoconcentration, which is associated with poor fetal growth.21 In conclusion, for women with pre-eclampsia, the traditional clinical markers of proteinuria, parity and severe hypertension remain useful clinical indices of maternal risk, while severe pre-eclampsia, severe hypertension, elevated haemoglobin and low serum albumin levels portend increased fetal risk. Acknowledgements We wish to thank the obstetricians of St George and Hurstville community hospitals, Professor J A Whitworth, Ms Jodie Wilkinson and Dr M Jones (Intstat Australia Pty Ltd). References Crawford JS. Epidemic pre-eclampsia. Lancet 1987; 1: 329-330. Tuffnell DJ, Lilford RJ, Buchan PC, et al. Randomised controlled trial of day care for hypertension in pregnancy. Lancet 1992; 339: 224-227. Horvath JS, Korda A, Child A, et al. Hypertension in pregnancy. A study of 142 women presenting before 32 weeks' gestation. Med J Aust 1985; 143: 19-21. Clarke M, Mason ES, Macvicar J, Clayton DG. Evaluating perinatal mortality rates: effects of referral and case mix. BMJ 1993; 306: 824-827. Australasian Society for the Study of Hypertension in Pregnancy. Consensus Statement on Management of Hypertension in Pregnancy: Executive Summary. Med J Aust 1993; 158: 700-702. Minitab [computer program], version 9.1. Pennsylvania State College: Minitab Inc, 1993. BMDP [computer program]. Berkeley, Calif: University of California, 1990. Martikainen AM, Heinonen KM, Saarikoski SV. The effect of hypertension in pregnancy on fetal and neonatal condition. Int J Gynaecol Obstet 1989; 30: 213-220. Andrews WW, Cox SM, Sherman ML, Leveno KJ. Maternal and perinatal effects of hypertension at term. J Reprod Med 1992; 37: 73-76. Safflas AF, Oldson DR, Franks AL, et al. Epidemiology of pre-eclampsia and eclampsia in the United States, 1979-1986. Am J Obstet Gynecol 1990; 163: 460-465. Pietrantoni M, O'Brien WF. The current impact of the hypertensive disorders of pregnancy. Clin Exp Hypertens 1994; 16: 479-492. Hjertberg R, Bellrage P, Hanson U. Conservative treatment of mild and moderate hypertension in pregnancy. Acta Obstet Gynecol Scand 1992; 71: 439-446. Horvath JS, Phippard A, Henderson-Smart D, et al. High risk hypertensive pregnancies: maternal and foetal outcome. Clin Exp Hypertens Pregnancy 1983; B2: 21-28. Brown MA, Buddle ML. The importance of non proteinuric hypertension in pregnancy. Hypertens Pregnancy 1995; 14: 57-65. Pollak VE, Nettles JB. The kidney in toxemia of pregnancy: a clinical and pathologic study based on renal biopsies. Medicine (Baltimore) 1960; 39: 469-526. Redman CWG, Beilin LJ, Bonnar J, Wilkinson PH. Plasma urate measurements in predicting fetal death in hypertensive pregnancy. Lancet 1976; 2: 1370-1373. Chesley LC. Diagnosis of pre-eclampsia. Obstet Gynecol 1985; 65: 423-425. Sibai BM, Taslimi M, Abdella TN, et al. Maternal and perinatal outcome of conservative management of severe pre-eclampsia in midtrimester. Am J Obstet Gynecol 1985; 152: 32-37. Railton A, Allen DG. Management and outcome of pregnancy complicated by severe pre-eclampsia of early onset. S Afr Med J 1987; 72: 608-610. Sibai BM, Mercer BM, Schiff E, Friedman SA. Aggressive versus expectant management of severe pre-eclampsia at 28 to 32 weeks' gestation: a randomized controlled trial. Am J Obstet Gynecol 1994; 171: 818-822. Brown MA, Zammit VC, Mitar DM. Extracellular fluid volumes in pregnancy-induced hypertension. J Hypertens 1992; 10: 821-829. (Received 9 Oct 1995, accepted 13 May 1996) Authors' details Departments of Medicine, Renal Medicine and Obstetrics, St George and Hurstville community hospitals, University of NSW. Mark A Brown, MB BS, FRACP, MD, Associate Professor of Medicine; Megan L Buddle, SRN, Hypertension Unit Registered Nurse. No reprints will be available. Correspondence: Associate Professor M A Brown, Department of Renal Medicine, St George Hospital, Kogarah, NSW 2217. E-mail: "nest::brown"ATdodo.ssahs.unsw.edu.au 1: ASSHP classifications and definitions of hypertension in pregnancy Hypertension: A sitting systolic blood pressure (BP) ≥ 140 mmHg and/or diastolic BP (phase IV Korotkoff sound) ≥ 90 mmHg, or a rise in systolic BP of ≥ 25 mmHg and/or diastolic BP ≥ 15 mmHg from first-trimester BP (two readings taken six hours apart). Proteinuria: ≥ 300 mg/day (24-hour urine collection) or persistently (over two or more days) ≥ 2+ protein (1 g/L) on urinalysis (dipstick testing). As urinalysis was performed daily, non-proteinuric hypertension that progressed to proteinuric hypertension was always detected. Hyperuricaemia: Plasma uric acid level > 0.35 mmol/L. Pre-eclampsia: The development of hypertension after 20 weeks' gestation in a woman with no known history of hypertension or renal disease and whose blood pressure (BP) was normal in the first half of the pregnancy and returned to normal after delivery: (i) mild pre-eclampsia: hypertension only; (ii) severe pre-eclampsia: hypertension and evidence of maternal organ dysfunction (see Maternal complications, Box 2). Essential hypertension: Hypertension in the first half of pregnancy (often occurring before pregnancy) without a demonstrable secondary cause, or the appearance of hypertension in the second half of pregnancy in a woman whose BP failed to return to normal within three months after delivery. Superimposed pre-eclampsia: The development of proteinuria and/or hyperuricaemia in the second half of pregnancy in a woman with essential hypertension. Secondary hypertension: To exclude a secondary cause of hypertension, all women had serum potassium levels measured and had urinalysis, microscopy and a clinical examination; urinary catecholamines and renal ultrasound were performed in selected cases. Within this group, superimposed pre-eclampsia was not diagnosed as a separate entity as it was too difficult to ascertain whether changes (e.g., increasing proteinuria) reflected superimposed pre-eclampsia or progression of the underlying (usually renal) disease. ASSHP = Australasian Society for the Study of Hypertension in Pregnancy.5 Back to text 2: ASSHP complications of hypertension in pregnancyMaternal complications:(i)Severe hypertension: Blood pressure (BP) ≥ 170 mmHg systolic and/or ≥ 110 mmHg diastolic;(ii)Proteinuria (Box 1);(iii)Haematological abnormalities: haemolysis (haemoglobin < 110g/L, with reticulocytosis, fragments) or thrombocytopenia (< 150 x 109/L platelets);(iv)Renal impairment: serum creatinine level ≥ 0.10 mmol/L;(v)Liver disease: elevated serum aspartate aminotransferase level > 40 IU/L, with or without severe epigastric pain;(vi)Neurological disturbances: visual scotoma; severe headaches with hyperreflexia; hyperreflexia with sustained clonus (> 3 beats). Fetal complications:(i)Small-for-gestational-age (SGA): birthweight below the 10th centile for gestation, corrected for sex;(ii)Perinatal mortality (PNM): stillbirths and neonatal deaths per 1000 hypertensive pregnancies. ASSHP = Australasian Society for the Study of Hypertension in Pregnancy.5Back to text 3: Management protocol during pregnancy Maternal complications: Blood pressure (BP) measurements six times per day; Fetal cardiotocograph recordings on alternate days (or more often if clinically indicated); Daily urinalysis; Biochemistry and haematological testing at least twice weekly; Bedrest if there is evidence of intrauterine fetal growth retardation, or maternal neurological features or severe hypertension. Antihypertensive therapy: Oral antihypertensive therapy (single agent or combinations) of oxprenolol, hydralazine, methyldopa, prazosin or nifedipine was instituted if the systolic BP was persistently > 160 mmHg or diastolic BP persistently > 90 mmHg after overnight bedrest in hospital. Parenteral antihypertensive therapy (sublingual nifedipine or intravenous hydralazine) was given for severe hypertension (Box 2). Convulsion prophylaxis (intravenous phenytoin followed by oral phenytoin) was used for women with neurological disturbances (Box 2). Indications for delivery. Delivery (by induction) was scheduled after 38 weeks' gestation if the BP remained stable and the cervix was favourable. Indications for delivery before 38 weeks' gestation were:5 Fetal compromise: premorbid (cardiotocographic) tracing of fetal heart rate or failure of fetal growth (assessed by doppler ultrasound). Inability to control maternal BP; Persistent neurological disturbances (see Box 2); Progressively rising liver enzyme or serum creatinine levels, or worsening thrombocytopenia. Women whose pregnancies could not be prolonged beyond 30 weeks' (and occasionally 32 weeks') gestation were sometimes transferred before delivery to a tertiary referral unit with neonatal intensive care facilities. Outcomes of this group were included in our analysis. Back to textFor box 4 click here 5: Maternal and fetal outcomes in women with pre-eclampsia (mild and severe) according to parity and gestation at presentation (see text for definitions). Data are percentages or means (standard deviation). Gestation at presentationNulliparae ParousP ≤ 32 wks> 32 wks Pn508317129696Age (years)27 (5)30 (5) < 0.0001*29 (5)28 (5)0.30Nulliparae (%)10000.0001*57630.20Gestation at presentation (weeks)36 (4)35 (6)0.00927 (7)37 (2)< 0.0001*Gestation at delivery (weeks)38 (3)38 (2) 0.8935 (4)38 (2)< 0.0001*Hyperuricaemia (%)61540.0456590.53Maternal complicationsSevere hypertension24%15%0.001*29%19%0.008Thrombocytopenia11%8%0.1011%10%0.75Proteinuria21%16%0.0931%17%0.003*Renal insufficiency8%5%0.089%7%0.27Liver disease12%6%0.005*15%9%0.04Neurological13%10%0.4116%11%0.09Laboratory dataPlasma creatinine (mmol/L).07 (.04).07 (.02).18.08 (.08)0.07 (.02) 0.51Plasma uric acid (mmol/L).40 (.20).37 (.04) .01.38 (.09)0.39 (0.17)0.66Plasma albumin (g/L)33 (5)34 (5) .3431 (8)34 (4)0.002*Haemoglobin (g/L)119 (23)122 (16) .03117 (37)121 (15)0.20Haematocrit (%)35.1 (5.5)35.9 (5.6) .1033.7 (8.7)35.7 (4.7)0.02Platelets (x 109/L)223 (82)232 (82) .11206 (95)230 (79)0.009*Fetal complicationsSGA (%)17210.1724180.10PNM (per 1000)1730.06544< 0.0001*Birthweight (g)2984 (701)2985 (694) 0.982312 (960)3105 (561)< 0.0001* * Statistically significant . SGA = small-for-gestational-age. PNM = perinatal mortality. Back to text 6: Maternal and fetal outcomes in women with different forms of hypertension in pregnancy (ASSHP classifications). Data are percentages or means (standard deviation). Pre-eclampsiaEssential hypertension Superimposed pre-eclampsiaP*n82523382Age (years)28 (5)30 (530 (5)> 0.0001†Nulliparae (%)6237560.290.002†Gestation at presentation (weeks)35 (5)26 (10)28 (10) < 0.0001†0.17Gestation at delivery (weeks)38 (3)38 (2)36 (1)0.0007†< 0.0001†Hyperuricaemia (%)581683< 0.0001†0.0001†Maternal complicationsSevere hypertension21%13%38%0.0005†< 0.0001†Thrombocytopenia10%1%16%0.11< 0.0001†Proteinuria19%035%0.0005†< 0.0001†Renal insufficiency7%09%0.62< 0.0001†Liver disease10%1%11%0.79< 0.0001†Neurological12%3%20%0.06< 0.0001†Laboratory dataPlasma creatinine (mmol/L)0.07 (0.04)0.06 (0.02)0.07 (0.02)0.78< 0.0001†Plasma uric acid (mmol/L)0.39 (0.16)0.32 (0.25)0.46 (0.35)0.090.002†Plasma albumin (g/L)33 (5)35 (6)33 (5)0.810.04Haemoglobin (g/L)120 (20)119 (14) 117 (17)0.140.52Haematocrit (%)35.4 (5.5)35.1 (4.0) 34.7 (5.4)0.290.64Platelets (x 109/L)226 (82)256 (68) 235 (78)0.360.03Fetal complicationsSGA (%)199280.20< 0.0001†PNM (per 1000)129120.930.80Birthweight (g)2984 (701)3260 (652) 2795 (935)0.080.0001†* Significance of difference between outcomes for women with pre-eclampsia and superimposed pre-eclampsia (and for women with essential hypertension and superimposed pre-eclampsia). †Statistically significant. SGA = small-for-gestational-age. PNM = perinatal mortality. ASSHP = Australasian Society for the Study of Hypertension in Pregnancy.5 Back to text

Mark A Brown · Megan L Buddle

Research Evaluation of the PAPNET system in a general pathology service Annabelle Farnsworth, Fay M Chambers and Colin S Goldschmidt MJA 1996; 165: 429-431 Abstract - Introduction - Methods - Results - Discussion - References - Disclaimer of conflict of interest - Authors' details - - More articles on Obstetrics & gynaecology and women's health Abstract Objective: To compare the results of an automated rescreening device (PAPNET) with manual screening of Papanicolaou (Pap) smears. Design: All normal or technically unsatisfactory smears and a random sample of abnormal smears on manual screening were submitted for PAPNET rescreening. Setting: Large general pathology laboratory in Sydney between January and September 1995. Results: Of 54 658 PAP smears classified on manual screening as normal, 266 were reclassified as abnormal after PAPNET screening (32 atypical squamous cells of uncertain significance, 217 low-grade squamous intraepithelial lesions and 17 high-grade intraepithelial lesions). Of the random sample of 1022 smears classified on manual screening as abnormal, all high-grade intraepithelial lesions (122 smears) and squamous cell carcinomas (2 smears) were also detected by PAPNET, and 112 were reclassified as normal by PAPNET (14 atypical squamous cells of uncertain significance and 98 low-grade squamous intraepithelial lesions). Histological follow-up confirmed 15 of the 17 smears classified as high-grade intraepithelial lesions on PAPNET screening and detected a further seven that had been classified by PAPNET as either atypical squamous cells of uncertain significance or low-grade squamous intraepithelial lesions. Conclusions: When used as a quality-control measure in a general pathology laboratory, the PAPNET automated screening system detects higher numbers of abnormal PAP smears than manual screening. Introduction Papanicolaou (Pap)-smear examination has been shown to lower mortality and morbidity from cervical cancer,1 but the screening test itself is imperfect. False negative results (when a smear is reported as normal but has been taken from a woman with a high-grade lesion in her cervix) have been reported to be between 10%-20%.2The failure of Pap smears to detect some high-grade abnormalities is the result of either sampling or laboratory error.2 Sampling error occurs when the person taking the smear fails to collect the abnormal cervical cells because of either poor technique or the small size or localised nature of the lesion.3 Laboratory error is usually caused by the screening cytologist failing to detect the abnormal cells on the slide. Screening of Pap smears is a labour-intensive task requiring a high degree of skill and concentration. Even in laboratories using well-recognised quality control measures and staffed by highly trained cytologists, many high-grade abnormalities remain undetected by routine manual screening. These may also be missed on a manual rescreen.3 PAPNET is an automated interactive system for analysis of Pap smears which has been shown to detect abnormalities that were repeatedly missed on manual screening.4,5 We introduced the PAPNET system into our laboratory in January 1995 as a quality-control measure for rescreening of all negative (normal) smears. Here, we compare the detection of abnormalities by PAPNET with those detected by manual screening in our laboratory, and report on the histological follow-up of the PAPNET cytopredictions and the work practices of cytologists using this system. Methods Our laboratory is a large general practice in Sydney with a referral base covering metropolitan and country areas of New South Wales. During the period of our survey (23 January to 30 September 1995), all Pap smears were screened manually using routine methods. Quality assurance measures used in the study (e.g., rescreening and follow-up of abnormal smears) were routine procedures used in our laboratory. All smears considered "normal" (negative) and "technically unsatisfactory" on routine manual screening, together with a random sample of smears considered "abnormal" on routine screening during the same period, were submitted for PAPNET analysis. Smears were considered technically unsatisfactory when a confident report could not be given because of scanty material, or obscuring of cellular detail by blood, inflammation, cellular degeneration or air drying. The abnormal smears were randomly selected from the recent file of atypical smears. The PAPNET rescreening was undertaken blind to the results of manual screening. (See Box 1 for a description of the PAPNET technology.) Interim reports were generated for smears considered normal and technically unsatisfactory, and, after the slide review was completed in the laboratory, a final report was issued incorporating the PAPNET findings. Reporting terminology was based on the Bethesda system of reporting cervical/vaginal cytological diagnoses.6 A record was kept of the number of cases each cytologist was able to review per day with PAPNET. The number of slides that required manual rechecking and complete rescreening was also recorded. This involved the cytologists using the light microscope to recheck individual abnormal cells that were tagged on the PAPNET monitor. If these cells were considered to be significantly atypical, the whole slide was rescreened. If any degree of abnormality was found after rescreening, the slide was submitted to the cytopathologist for checking. To test the specificity of PAPNET, histological follow-up was performed for all patients who had an additional lesion predicted by PAPNET and were recommended to have colposcopy for this lesion. As follow-up of cytological predictions can take many months, the process was expedited and, where possible, histology results are given. In some cases, follow-up was still pending or the referring doctor had decided to follow-up by repeated observation and Pap smears. These are designated as "follow-up to come". In some cases, follow-up was unavailable; the referring doctor had been unable to contact the patient, the patient had moved or had decided to proceed no further with management. These cases are designated as "lost to follow-up". Results During the 10-month period of this survey, 60 317 Pap smears were submitted to the laboratory for examination. These smears are categorised in Box 2 (cytopredictions). The results fall within suggested National Cervical Screening Programme standards for reporting categories of technically satisfactory smears. PAPNET screening was performed on 54 658 smears classified on manual screening as negative (or within normal limits) and 1819 smears classified as technically unsatisfactory. Of the 3840 smears classified on manual screening as abnormal, 1022 smears (27%) were randomly selected and submitted for PAPNET screening: 807 low-grade squamous intraepithelial lesions, 122 high-grade squamous intraepithelial lesions, 91 atypical squamous cells of uncertain significance, and two cases of squamous cell carcinoma. Manual screening compared to PAPNET screening Of the smears classified as negative on manual screening, 266 were reclassified as abnormal after PAPNET rescreening, including 17 reported as high-grade squamous intraepithelial lesions (Box 3). This represents a 7% increase in abnormal smears after PAPNET rescreening. All of the 122 smears reported as high-grade squamous intraepithelial lesions and both squamous cell carcinomas detected on manual screening were also detected by PAPNET (Box 3). Fourteen (15%) of the 91 smears reported as atypical squamous cells of uncertain significance and 98 (12%) of the 807 reported as low-grade squamous intraepithelial lesions were reclassified as negative on PAPNET rescreening (Box 3). Histological follow-up of PAPNET cytopredictions Histology confirmed an abnormality in 28% of smears reported as atypical squamous cells of uncertain significance and 61% reported as low-grade squamous intraepithelial lesions (Box 4). Of the 17 smears reported as high-grade squamous intraepithelial lesions on PAPNET rescreening, 15 (88%) were confirmed on histology (Box 4). Three of the 32 cases reported as atypical squamous cells of uncertain significance and four of the 31 reported as low-grade squamous intraepithelial lesions (where colposcopy was recommended) were also shown to have a high-grade lesion on histological biopsy. In total, there were an extra 22 histologically confirmed high-grade lesions not detected on manual screening, of which 15 were detected by PAPNET. Cytologists' work practices In our laboratory, cytologists manually screened between 25 and 50 slides (mean, 42; standard deviation [SD], 6) per day. The large SD reflected the range of experience among the laboratory's cytologists, who alternate between gynaecological and non-gynaecological cytology. PAPNET rescreening was included in this rotation. After training, cytologists performing PAPNET rescreening were able to screen between 100 and 160 slides (mean, 126; SD, 15) per day. This included loading and unloading the tapes, viewing and assessing the images on the PAPNET screen, documentation and generating patient reports. The number of cases submitted for limited rechecking varied between 10%-90%, depending on the cytologist. The number requiring complete rescreening by a senior cytologist varied between 0 to 10 per cytologist per day and averaged five per day. The number of cases submitted to a cytopathologist by each cytologist averaged one per day. Discussion Pap smears remain the highest-volume pathology test that is not automated. Attempts have been made to automate this complex process for nearly 40 years, but it is only recently that advances in the development of automated systems have occurred which offer practical advantages in a laboratory. Although the detection rate of abnormalities on manual screening was well within normal standards in our study, PAPNET rescreening was able to detect an increased number of abnormal Pap smears. This increase was not associated with a loss of specificity, as often occurs with increased detection by manual screening.3 Many studies have shown the ability of PAPNET rescreening to detect a significant number of abnormal Pap smears when compared with manual screening, but these have been predominantly smaller studies using archived material.8,9 Our study was undertaken as part of the routine workflow in a laboratory processing a large number of smears and is the first Australian study to compare the two screening systems. The reported increase in detection of abnormalities in other studies has been as high as 16%,10 and the company which developed PAPNET (Neuromedical Systems Inc., New York, USA) claims increases of up to 30%. The increase in our study was much smaller (7%), with most detected abnormalities being low-grade lesions. However, we believe this increase was worthwhile given the reasonably high rate of detection on manual screening and the large volume of routine smears processed. Boon et al. reported the results of a large series of smears that were not double-screened, but had been either manually screened or PAPNET screened. Higher detection rates of abnormalities were found in the PAPNET group. Our study is the first report of a large series in which all negative smears were screened both manually and by PAPNET. Our study showed that the PAPNET system could be feasibly integrated into a routine working laboratory situation. It was a valuable educational and quality assurance tool. Cytologists found it easy to use and were able to review slides at three to four times their manual-screening rate. From our experience, cytologists did not become complacent in their manual screening, but rather became more cautious knowing that all the negative smears would be examined by a computerised device. The additional work for cytopathologists and senior cytologists was not great. PAPNET is only one of a number of automated cytology systems currently available as an additional test for routine Pap-smear screening. We did not undertake a comparison of other automated systems or their cost-effectiveness. Further studies on the cost-effectiveness of PAPNET testing and its efficacy for use in public health screening programs are needed. It may be that automated testing technology will replace current screening methods in the future. Disclaimer of conflict of interest This work was conducted independently. Neither Douglass Hanly Moir Pathology nor any of the individual authors has any financial or other association with the suppliers of the PAPNET service, Neuromedical Systems Inc. References Mitchell HS, Giles GG. Cancer diagnosis after a report of negative cervical cytology. Med J Aust 1996; 164: 270-273. Koss LG. The Papanicolaou test for cervical cancer detection. A triumph and a tragedy. JAMA 1989; 261: 737-743. Boscha MC, Rietveld-Scheffers PEM, Boon ME. Characteristics of false negative smears tested in the normal screening situation. Acta Cytol 1992; 36: 711-716. Koss LG, Hin E, Schreiber K, et al. Evaluation of the PAPNET cytologic screening system for quality control of cervical smears. Am J Clin Pathol 1994; 101: 220-229. Boon M, Kok CP. Neural network processing can provide means to catch errors that slip through human screening of Pap smears. Diagn Cytopathol 1993; 9: 411-416. The Bethesda system of reporting cervical/vaginal cytologic diagnoses: revised after the second National Cancer Institute Workshop, April 29-30, 1991. Acta Cytol 1993; 37: 115-124. Royal College of Pathologists of Australasia. Performance Standards for Australian Laboratories Reporting Cervical Cytology. Sydney: RCPA Quality Assurance Programs, 1995. Rosenthal DL, Acosta D, Peters RK. Computer-assisted re-screening of clinically important false negative cervical smears using the PAPNET testing system. Acta Cytol 1996; 40: 120-126. Sherman ME, Mango LJ, Kelly D, et al. PAPNET analysis of reportedly negative smears preceding the diagnosis of a high grade squamous intraepithelial lesion or carcinoma. Mod Pathol 1994; 7: 578-581. Elgert PA, Suhrland MJ, Re E, et al. Prospective quality control of cervical smears using the PAPNET system [abstract No. 5]. In: Abstracts of the Scientific Session of the 42nd Annual Scientific Meeting of the American Society of Cytology; 1994 Nov 1-6; Chicago. Acta Cytol 1994; 38: 793-805. Boon ME, Kok LP, Beck S. Histologic validation of neural network assisted cervical screening: comparison with the conventional procedure. Cell Vision 1995; 2: 23-27. (Received 10 Jan, accepted 14 Aug 1996) Authors' details Douglass Hanly Moir Pathology, 95 Epping Road, North Ryde, NSW. Annabelle Farnsworth, MB BS, FRCPA, Cytopathologist. Fay M Chambers, MB BS, FRCPA, Cytopathologist. Colin S Goldschmidt, MB BCh, FRCPA, Cytopathologist. Reprints: Dr A Farnsworth, Douglass Hanly Moir Pathology, 95 Epping Road, North Ryde 2113. Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/> We appreciate your comments. 1: The PAPNET system. PAPNET consists of a scanning apparatus and a review station.4 In Australia, the cervical slides are sent to Hong Kong for the initial scanning. The scanning apparatus includes an automated microscope with an attached video camera which transmits images to a primary classifier. Selected images are then passed into a neural net computing unit which chooses the 128 highest-ranking images for storage on an optical disk or digital tape, which is sent back to Australia for display at the review station. The review station is located in the cytology laboratory where manual screening takes place. The 128 recorded images are displayed in panels on a high-resolution colour monitor and are reviewed by a cytologist. If an abnormality is suspected, the original slide is manually checked and, if necessary, manually rescreened. Back to text 2: Categories of Pap smears on manual screening (23 January to 30 September 1995). CytopredictionNumber of smearsNegative*54 658 (90.6%)Low-grade squamous intraepithelial lesions 2974 (4.9%)High-grade squamous intraepithelial lesions 432 (0.7%)Atypical squamous cells of uncertain significance434 (0.7%)Technically unsatisfactory1819 (3%)Total60 317 (100%)* Cellular appearance was within normal limits. Back to text 3: PAPNET rescreening of PAP smears classified as normal and abnormal on manual screening. CytopredictionNormal smears: manual screeningPAPNET rescreeningAbnormal smears: manual screeningPAPNET rescreeningNegative*54 65854 359--112Atypical squamous cells of uncertain significance--329177Low-grade squamous intraepithelial lesions--217807709High-grade squamous intraepithelial lesions--17122122Squamous cell carcinoma--022Technically unsatisfactory18191852---- * Cellular appearance was within normal limits. The 112 negative smears on PAPNET screening had been classified on manual screening as atypical squamous cells of uncertain significance (14 smears) and low-grade squamous intraepithelial lesions (98 smears). Back to text 4: Histological follow-up of PAPNET cytopredictions. Histological follow-up PAPNET-detected abnormalitiesNegative/inflammation*Low-grade squamous intraepithelial lesionsHigh-grade squamous intraepithelial lesionsFollow-up to comeLost to follow-upTotalAtypical squamous cells of unknown significance66371032Low-grade squamous intraepithelial lesions21544631High-grade squamous intraepithelial lesions 01150117 *Cellular appearance was within normal limits. Back to text

Annabelle Farnsworth · Fay M Chambers · Colin S Goldschmidt

Research Urinary urge incontinence: randomised crossover trials of penthienate versus placebo and propantheline Graham M Coombes and Richard J Millard MJA 1996; 165: 473-476 Abstract - Introduction - Methods - Results - Discussion - Acknowledgements - References - Authors' details - - More articles on Obstetrics & gynaecology and women's health Abstract Objective: To compare the efficacy of penthienate with that of propantheline and placebo for treatment of primary idiopathic detrusor instability. Design: Two prospective, randomised, crossover trials (double-blind for penthienate versus placebo and non-blinded for penthienate versus propantheline). Setting: Urology Clinic of Prince Henry Hospital, Sydney, NSW (an outpatient clinic of a tertiary referral hospital), in 1993-1994. Participants: Neurologically intact patients with urodynamically proven detrusor instability, urgency and urge incontinence, but no stress incontinence (20 participated in the penthienate/placebo trial and 23 in the penthienate/propantheline trial). Outcome measures: Cystometrography results before and after treatment; frequency and volumes of urine voided in weeks 1 and 4 of treatment; and patient scores for degree of continence, side effects, efficacy and acceptability of treatment. Interventions: Penthienate (5 mg), propantheline (15 mg) or placebo (all three times a day) for 4 weeks. Results: Penthienate produced significantly greater improvements than placebo in frequency (daytime, P = 0.002; and night-time, P = 0.02), incontinence scores (P = 0.002) and amplitude of unstable detrusor contractions, when present (P = 0.01), and significantly increased diurnal and nocturnal bladder capacity, both on cystometrography (P = 0.003) and by voiding-diary records (P < 0.001). It also increased residual urine volume over the baseline level, but not significantly. Side effects, especially dry mouth, were common with penthienate, and one patient developed urinary retention. Penthienate was significantly better than propantheline in improving cystometric capacity (P = 0.03), and reducing the amplitude of unstable detrusor contractions (P = 0.01), and was perceived as more effective by patients for frequency, nocturia and incontinence. Conclusions: Penthienate (5 mg three times a day) was objectively and subjectively significantly better than both placebo and propantheline (15 mg three times a day) for treatment of primary idiopathic detrusor instability. Introduction Detrusor instability is a common urologic problem, causing symptoms of urgency, frequency and urge incontinence. It is defined by the International Continence Society as the presence of detrusor contractions with pressure greater than 15 centimetres of water during the filling phase of cystometrography while the patient is trying to inhibit micturition.1 Although detrusor instability may result from neuropathy (e.g., after spinal injury and in multiple sclerosis, where it is best termed detrusor hyperreflexia), in most patients it is primary and idiopathic.2Many treatments have been used, including bladder training, biofeedback, anticholinergics, analgesics, muscle relaxants, tricyclic antidepressants and acupuncture.2-7 More invasive, surgical procedures, such as subtrigonal phenol injections, neuromodulation and bladder augmentation, are less commonly required. Success rates are variable, and depend partly on the cause of the instability, but are usually no higher than 70%.8,9 The anticholinergic propantheline bromide is used worldwide for detrusor instability and, along with oxybutynin, is among the most often studied anticholinergic agents. However, penthienate bromide, which was originally marketed in Australia for gastrointestinal spasm, has been in clinical use for detrusor instability at Prince Henry Hospital, Sydney, NSW, and, in our clinical experience, may be more effective than propantheline. It is a quaternary ammonium antimuscarinic that inhibits parasympathetic, postganglionic bladder smooth muscle receptors, has a short half-life and is optimally absorbed from the gastrointestinal tract on an empty stomach. However, its comparative efficacy has not been established. We therefore undertook randomised trials of penthienate versus placebo and penthienate versus propantheline in primary idiopathic detrusor instability. Methods Approval for the trials was given by the Eastern Sydney Area Health Service Ethics Committee. The trials were independent of drug company participation or sponsorship, apart from the manufacture and supply of placebo and penthienate tablets (for the first trial). Penthienate versus placebo The first trial was a prospective, randomised, double-blind crossover trial of penthienate versus placebo. Participants were 20 neurologically intact patients recruited from the outpatient Urology Clinic and Urodynamic Service of Prince Henry Hospital, Sydney, NSW. Inclusion criteria. These were: Age over 18 years; Presence of symptomatic urgency or urge incontinence; Detrusor instability (shown on medium-fill, room-temperature, videourodynamic studies); No history of neurologic disease, narrow-angle glaucoma or severe cardiac disease (American Heart Association Grade 3 or 4); No stress incontinence, bladder-outlet obstruction, significant postvoid residual urine (residuum greater than 10% of voided volume), current urinary tract infection or interstitial cystitis; No current gastrointestinal obstruction; No allergy or sensitivity to anticholinergic agents; Not pregnant; and Patient gave informed consent to active and placebo treatment. First phase. The trial began with a one-week run-in period in which patients kept charts of frequency and volume of urine voided. Informed consent was then obtained and patients were randomised in a double-blind fashion to placebo or penthienate. Codes were generated from randomisation tables in blocks of ten, and provided in sealed envelopes by the Pharmacy Department; neither patients nor investigators knew the code until after collection of all follow-up data. Patients received either placebo or penthienate (5 mg three times a day before meals) for four weeks. Dosage reduction was ethically necessary if the patient developed blurred vision, severe constipation, or excessive mouth dryness that interfered with nutrition. Placebo and penthienate tablets were made to the same size, shape and colour specifications by the manufacturer and stored in the refrigerator. Assessment. All patients were asked to keep records of frequency and volume of urine voided for two 72-hour periods in the first and fourth weeks of treatment. A visual analogue score for continence was also kept (from 1 [nil leakage], to 5 [wet all the time]) and episodes of incontinence were noted. Apart from keeping voiding diaries at the set times, patients were taught no formal bladder- training techniques. In the final (fourth) week of treatment, patients attended the outpatient clinic for assessment. History was taken and time/volume charts collected. Medium-fill room-temperature saline-filling cystometrography was performed by the urology registrar, and residual urine volume, flow rate, cystometric capacity and incidence and amplitude of any unstable detrusor contractions were recorded. Urodynamic methods, definitions and units conformed to the standards recommended by the International Continence Society.1In addition, patients scored side effects, efficacy of treatment and willingness to have that treatment in the future on a scale of 1-100. Second phase. After a five-day washout period, patients crossed to the other arm of the trial. As it was not considered ethical to subject patients to a further urodynamic study during this period (to prove stable disease course), treatment-period interaction could not be totally excluded. Again, treatment was for four weeks, with the same assessment as previously. Penthienate versus propantheline The second trial was an unblinded, prospective, randomised crossover trial of penthienate and propantheline in 23 patients with detrusor instability. Inclusion criteria, run-in period and randomisation were the same as those in the first trial, except that neither patients nor observers were blinded to the treatment. Patients received either penthienate (5 mg three times a day) or propantheline (15 mg three times a day) for four weeks. There was no placebo arm. All patients were then assessed as outpatients, with the same outcome measures as those in the first trial. After a five-day drug washout period, patients crossed over to receive the other medication for a further four weeks before reassessment. Statistical analyses Analysis of paired data was by the Wilcoxon matched-pairs signed-rank test. Unpaired group data were analysed with the Mann-Whitney U test. Results Penthienate versus placebo Patients comprised 16 women and four men, with median age 63.5 years (range, 36-85). Urological baseline characteristics are shown in Box 1. There were no significant differences in baseline data between those patients receiving placebo first and those receiving penthienate first. To investigate the possibility of a carryover effect of penthienate in patients who received placebo second, the data were analysed initially in groups according to which drug had been given first. In the placebo arm of the trial there were no significant differences in cystometric capacity, residual postvoid volume, amplitude of unstable detrusor contractions, flow rate, frequency, nocturia or subjective incontinence scores between patients who took placebo first and those who took it second. Thus, five days was adequate for washout of penthienate. Thereafter, data were analysed without regard to which drug was taken first. Continence and urodynamic characteristics after penthienate and placebo treatment are shown in Box 1. After penthienate treatment, there were increases over the baseline in daytime voiding interval, mean voided volume (daytime and night-time) and cystometric capacity, and decreases in night-time frequency and subjective incontinence score. Values for all these parameters were significantly "better" after penthienate than after placebo. The decrease in median incontinence score with penthienate was dramatic, from a baseline of 5 ("wet all the time") to 1 ("nil leakage"), compared with 4 for placebo. Ten of 20 patients taking penthienate became dry (incontinence score of 1, 50% cure rate), compared with only two patients taking placebo. The same 10 patients taking penthienate were also completely stable (detrusor pressure < 15 cm H2O) to a capacity of 500 mL on cystometrography. Among the other 10, the median amplitude of unstable detrusor contractions was reduced from 40 to 27 cm H2O. However, with placebo only four patients (20%) tested stable and the other 16 had unstable detrusor contractions, with a median pressure of 30 cm H2O. The difference between the penthienate and placebo groups in detrusor pressures in those patients who remained unstable was significant (P = 0.05). Residual urine volume increased from the baseline level in the penthienate group and decreased in the placebo group, but neither change was significant. However, the resulting difference between penthienate and placebo residual volumes was significant (P = 0.02). Urine flow rate increased significantly in both the penthienate and placebo group over the baseline level (P = 0.01), but did not differ significantly between the two groups. The increase in flow rate appeared to be related to the increase in voided volume, as there was no change in percentile performance on the Haylen Liverpool flow nomogram.10 Side effects of treatment were common with penthienate (Box 2). All patients mentioned a dry mouth, and in one elderly patient this led to difficulty swallowing, which necessitated reducing the penthienate dose. Although 11 of 20 patients taking placebo also mentioned mouth dryness, the scores for degree were significantly less than for penthienate. A patient taking penthienate complained of diarrhoea, but there was no evidence of faecal impaction to suggest spurious diarrhoea caused by decreased gastrointestinal motility. Another patient taking penthienate in the second phase of the trial developed chronic urinary retention (with a residual postvoid volume of 550 mL). This patient's results were excluded from the analysis. Patients' subjective impressions of treatment are also shown in Box 2. There was a significant preference for penthienate compared with placebo in both perceived efficacy and willingness for retreatment (P = 0.002). Penthienate was considered beneficial by 17 (85%), but placebo by only five (25%). Two patients preferred placebo to penthienate; their cystometric capacities and filling pressures on testing differed little between penthienate and placebo, but their voiding diaries showed greater daytime and night-time voided volumes during the penthienate arm. Penthienate versus propantheline Patients comprised 18 women and five men, with median age 63 years (range, 34-85). Propantheline was given first to 12 patients and penthienate to 11. Baseline characteristics are compared with those after propantheline and penthienate treatment in Box 3. Both penthienate and propantheline significantly increased daytime voiding interval, cystometric capacity and flow rate over baseline figures. However, the improvements in cystometric capacity were significantly greater with penthienate than with propantheline. Furthermore, penthienate, but not propantheline, significantly increased voided volume (both daytime and night-time) and decreased night-time frequency and the incidence of incontinence (by patient score). Consequently, daytime voided volume and incontinence score were significantly "better" for penthienate than for propantheline. The difference in incontinence score was dramatic -- 1.5 after penthienate (where 1 = "nil leakage"), but 5 ("wet all the time") after propantheline. Stable cystometrograms were seen in 13 of the 23 patients (56%) after penthienate, but in only 10 (43%) after propantheline. In the patients with residual unstable detrusor contractions, the amplitude of these contractions decreased with penthienate but increased with propantheline, which led to a significant difference between the two treatments (P = 0.01). Although residual urine volume increased over the baseline value with penthienate, the change was not significant. Similarly, although detrusor compliance (detrusor pressure at a given bladder volume, which measures bladder-wall stiffness) increased after penthienate but decreased after propantheline, none of the changes were significant and did not lead to significant differences between the two drug treatments. Side effects and subjective response to treatment are shown in Box 4. Mouth dryness was significantly worse with penthienate, but patients believed that it had significantly greater efficacy and were more willing to repeat penthienate treatment. Discussion Our trials showed a significantly greater response to penthienate than to placebo or propantheline treatment, both objectively and subjectively, in primary idiopathic detrusor instability. For drug therapy to be useful in this condition, it needs to be more effective than placebo, which can produce significant improvement11 (up to 43%, or as high as that of some active drug therapies).12 In addition, results should be at least as good as those that can be achieved with non-invasive therapies such as bladder training, without intolerable side effects. The Urology Clinic at Prince Henry Hospital has previously shown that bladder training and/or biofeedback gives up to 74% cure or improvement in symptoms of detrusor instability.5 In this study, we found that after penthienate there were objective improvements in bladder capacity, stability and amplitude of unstable detrusor contractions and 50%-56% of patients became objectively dry. There were also improvements in subjective criteria for continence after penthienate, with 85% feeling subjectively cured or improved. These subjective criteria were included to assess clinical worth from the patients' perspective, as statistical significance may not necessarily equate with clinical significance.4There have been no previous comparative trials of the relative efficacy of penthienate and propantheline for detrusor instability. We found that, in the doses studied (manufacturer's recommended starting doses), both produced some urodynamic and symptomatic improvements, but that penthienate was significantly better than propantheline in improving cystometric capacity and reducing the amplitude of unstable detrusor contractions, and was perceived as more effective by patients for frequency, nocturia and incontinence. Most recent studies on propantheline in detrusor instability have compared it with another anticholinergic, oxybutynin, which has been found to produce response rates of up to 60% and a median increase in cystometric capacity of 104 mL;13 it was more effective than propantheline in some studies,12,14 but not others.15 Similarly as for penthienate, the price of its therapeutic effect was a higher residual urine volume and higher rate of side effects.12 However, as we found for penthienate, the anticholinergic side effects were generally tolerable and, if the treatment was discontinued, short-lived. Nevertheless, in detrusor hyperreflexia caused by multiple sclerosis oxybutynin and propantheline treatment had to be discontinued because of side effects in 22% and 27% of patients, respectively.15 We conclude that penthienate bromide has a significant place in the management of detrusor overactivity. It has been our practice to use penthienate as first-line drug treatment in those patients with idiopathic detrusor instability not responsive to conservative measures such as bladder training and biofeedback. Unfortunately, it is currently unavailable in Australia as it is no longer manufactured locally. The side effects of anticholinergic treatment are well recognised and occurred with both penthienate and propantheline. With appropriate modifications of dosage (e.g., in the elderly, who are more likely to have side effects, and in those with neurogenic bladders and detrusor hyperreflexia caused by multiple sclerosis, who are more sensitive to penthienate), most patients can tolerate these side effects and still benefit from therapy. Treatment should start with the lowest therapeutic dose and be monitored closely to maximise patient compliance if long term use is considered. Acknowledgements Winthrop Laboratories manufactured and supplied the penthienate (Monodral) and placebo tablets for the first crossover trial. We thank Dorothy Wheeler, RN, and Marilynne Berg, RN, of the Urology Training Unit, Prince Henry Hospital, for their help in the follow-up studies. References Abrams P, Blaivas JG, Stanton SL, Andersen JT. The standardisation of terminology of lower urinary tract function. Scand J Urol Nephrol 1988; Suppl 114: 5-19. Tapp AJS, Cardozo LD, Versi E, Cooper D. The treatment of detrusor instability in controlled study postmenopausal women with oxybutynin chloride: a double blind placebo. Br J Obstet Gynaecol 1990; 97: 521-526. Blaivas JG, Labib KB, Michalik SK, Zayed AAH. Cystometric response to propantheline in detrusor hyperreflexia: therapeutic implications. J Urol 1980; 124: 259. Wein AJ. Pharmacologic treatment of incontinence. J Am Geriatr Soc 1990; 38: 317-328. Millard RJ, Oldenburg BF. The symptomatic, urodynamic and psychodynamic results of bladder re-education programs. J Urol 1983; 53: 565-566. Chang PL. Urodynamic studies in acupuncture for women with frequency, urgency and dysuria. J Urol 1988; 140: 563-566. Burgio KL, Engel BT. Biofeedback-assisted behavioural training for elderly men and women. J Am Geriatr Soc 1990; 38: 338-340. Koldewijn EL, Rijkhoff NJM, van Kerrebroeck PE, et al. Selective stimulation of sacral nerves for bladder control: a computer model. Neurourol Urodyn 1992; 11: 328-330. Mundy AR. Detrusor instability. Br J Urol 1988; 62: 393-397. Haylen BT, Ashby D, Sutherst JR, et al. Maximum and average urine flow rates in normal male and female populations -- the Liverpool nomograms. Br J Urol 1989; 64: 30-38. Benson H, Epstein MD. The placebo effect. JAMA 1975; 232: 1225. Thuroff JW, Bunke B, Ebner A, et al. Randomized, double blind, multicenter trial on treatment of frequency, urgency and incontinence related to detrusor hyperactivity: oxybutynin versus propantheline versus placebo. J Urol 1991; 145: 813-817. Moore KH, Hay DM, Imrie AE, et al. Oxybutynin Hydrochloride (3 mg) in the treatment of women with idiopathic detrusor instability. Br J Urol 1990; 66: 479-485. Gajewski JB, Awad SA. Oxybutynin versus propantheline in patients with multiple sclerosis and detrusor hyperreflexia. J Urol 1986; 135: 966-968. Holmes DM, Montz FJ, Stanton SL. Oxybutynin versus propantheline in the management of detrusor instability. A patient-regulated variable dose trial. Br J Obstet Gynaecol 1989; 96: 607-612. (Received 22 Jun, accepted 20 Jul 1996) Authors' details Department of Urology, Prince Henry Hospital, Sydney, NSW. Graham M Coombes, FRACS, Urology Registrar. Currently, Royal North Shore Hospital, Sydney, NSW; Richard J Millard, FRACS, FRCS, Associate Professor of Urology, University of NSW, Sydney, NSW. Reprints: Dr G M Coombes, 74 Osborne Road, Lane Cove, NSW 2066. 1: Continence and urodynamic characteristics before and after treatment with penthienate and placebo (median and range)*Baseline (n = 20)Penthienate (n = 19)†Placebo (n = 19)†P‡Daytime voiding interval (hours)2 (1-5)3 (2-6)2 (1-4)0.002Night-time frequency (times)2.5 (1-6)1 (0-5)2 (0-4)0.02Mean daytime voided volume (mL)200 (75-400)270 (125-400)168 (50-300)0.0002Mean night-time voided volume (mL)250 (50-650)300 (195-740)275 (50-700)0.02Incontinence score§5 (2-5)1 (1-5)4 (1-5)0.002Urodynamic testingCystometric capacity (mL)283 (150-450)500 (225-600)400 (200-500)0.003Amplitude of unstable detrusor contractions (cm H2O)¶40 (16-80)27 (16-40)30 (20-45)0.05Residual postvoid volume (mL)30 (0-160)40 (0-150)15 (5-50)0.02Flow rate (mL/s)14 (6-25)17 (10-30)20 (15-45)0.68Number of patients With stable cystometrogram**0104NA"Dry" (incontinence score of 1)0102NANA=not assessed. *Unless otherwise stated. †One patient was excluded because of chronic urinary retention. ‡ For difference between penthienate and placebo. § On analogue scale, with range 1 ("nil leakage") to 5 ("wet all the time"). ¶ n = 10 for penthienate and n = 16 for placebo, after exclusion of subjects with stable cystometrogram. ** Detrusor pressure < 15 cm H2O on filling cystometrography to a capacity of 500 mL. Back to text2: Side effects and subjective patient impressions of penthienate and placebo PenthienatePlaceboDry mouthNumber of patients20 (100%)11 (55%)Mean score (range)*65 (25-95)25 (0-80)Nasal dryness2 (10%)0Constipation/lower abdominal pain1 (5%)0Upper abdominal pain1 (5%)0Blurred vision1 (5%)0Chronic urinary retention1 (5%)0Mean subjective efficacy (range)*80 (10-95)23 (0-95)Number of patients Improved17 (85%)5 (25%) Willing to repeat treatment12 (60%)5 (25%)* Subjective score on scale of 0-100. Patient had diagnosed hiatus hernia, but no documented peptic ulcer or reflux oesophagitis. Back to text3: Continence and urodynamic characteristics before and after treatment with penthienate and propantheline (median and range)*Baseline (n = 23)Penthienate (n = 23)Propantheline (n = 23)P †Daytime voiding interval (hours)2 (1-5)3 (2-6)3 (2-4)0.53Night-time frequency (times)2 (1-6)1 (0-5)2 (1-6)0.07Mean daytime voided volume (mL)200 (75-400)260 (125-400)200 (125-450)0.001Mean night-time voided volume (mL)250 (50-650)300 (195-740)325 (230-550)0.17Incontinence score‡5 (2-5)1.5 (1-5)5 (1-5)0.001Urodynamic testingCystometric capacity (mL)280 (150-450)500 (225-600)470 (275-550)0.03Amplitude of unstable detrusor contractions (cm H2O)40 (15-80)27 (16-40)50 (20-75)0.01Residual postvoid volume (mL)25 (0-160)37 (0-150)17.5 (0-100)0.1Flow rate (mL/s)15 (6-29)20 (10-50)20 (15-35)0.48Compliance (mL/cmH2O)70 (12-210)100 (23-600)55 (14-166)0.08Number with stable cystometrogram§01310NANA=not assessed. * Unless otherwise stated. † For difference between penthienate and propantheline. ‡ On analogue scale, with range 1 ("nil leakage") to 5 ("wet all the time"). § Detrusor pressure < 15 cm H2O on filling cystometrography to a capacity of 500 mL. Back to text 4: Side effects and subjective patient impressions of penthienate and propanthelinePenthienate PropanthelineP*Mean score for subjective efficacy† (range)83 (10-95)38 (5-90)0.002Mean score for mouth dryness† (range)73 (25-45)55 (30-90)0.05Mean score for constipation† (range)5 (0-50)7 (0-75)0.73Number of patients "dry" (incontinence score, 1)1310 NANumber of patients improved1913NANumber of patients willing to repeat treatment1211 NANA=not assessed. * By Wilcoxon matched-pairs signed-rank test. † Subjective score on scale of 0-100. Back to text

Graham M Coombes · Richard J Millard

Research Outcomes after hip or knee replacement surgery for osteoarthritis A prospective cohort study comparing patients' quality of life before and after surgery with age-related population norms Lyn M March, Marita J Cross, Helen Lapsley, Alan J M Brnabic Katherine L Tribe, Clarissa J M Bachmeier, Brett G Courtenay and Peter M Brooks* MJA 1999; 171: 235-238 For editorial comment, see Williamson Abstract - Introduction - Methods - Results - Discussion - Acknowledgements - References - Authors' details - - More articles on Orthopaedic surgery Abstract Objective: To compare the health-related quality of life of people with osteoarthritis before and after primary total hip and knee replacement surgery with that of the general Australian population. Design: A prospective cohort study. Setting: Three Sydney hospitals, public and private. Participants: Patients with osteoarthritis undergoing primary total hip (n = 59) and knee (n = 92) joint replacement surgery. Main outcome measure: Medical Outcomes Study Short Form (SF-36) scores before and 12 months after joint replacement surgery (compared with population norms). Results: Patients in each age group showed a significant improvement in health-related quality of life after joint replacement surgery in most scales of the SF-36, particularly physical function, role physical and bodily pain. SF-36 scores for the 42 hip-replacement patients aged 55-74 years improved to equal or exceed the population norm on all scales. SF-36 scores of the 52 knee replacement patients aged 55-74 years improved, but physical function and bodily pain scores remained significantly worse than the population norm. SF-36 scores for both hip (n = 17) and knee (n = 40) replacement patients aged 75 years and over improved significantly, becoming similar to population norms for this age group. Conclusions: Total hip or knee replacement for osteoarthritis significantly improves patient health and well-being at 12 months after surgery. Age alone should not be a barrier to surgery. Introduction Osteoarthritis is one of the leading causes of pain and disability in the Australian population.1,2 Total joint replacement is the most common treatment for advanced osteoarthritis of the hip or knee, with the primary goal of the procedure being to improve the patient's quality of life.3In Australia, in the financial year 1997/98, Medicare benefits of $13 500 000 were paid for 17 000 hip and knee replacements. This number represents only some of the total surgery performed, as the number of operations on Veterans' Affairs patients and on public patients in public hospitals are not available. Despite joint replacement surgery being one of the most common operations performed in this country, very limited Australian outcomes data have been published.4 The Medical Outcomes Study Short-Form 36 (SF-36) has been used extensively to assess the effect on quality of life of several procedures, including total joint replacement,5,6 and it has been suggested that it should be the focus of preoperative and postoperative outcome evaluation for total hip arthroplasty.7 As a generic measure of health-related quality of life with standardised scoring, it enables comparisons between diseases, treatments and published population norms. It measures health on eight 100-point scales: physical function, role physical (ie, role limitations due to physical problems), bodily pain, general health, vitality, social function, role emotional (ie, role limitations due to emotional problems), and mental health. It is one of the most widely used health-related quality-of-life instruments and has been shown to be reliable and valid. Studies in the US have shown that the SF-36 detects a significant improvement in health-related quality of life in patients undergoing total hip or knee replacement when preoperative scores are compared with postoperative scores.8-11 The SF-36 also demonstrates a difference in outcome between total hip and total knee replacement patients,8,10 with patients undergoing total hip replacement achieving significantly better outcomes than the knee replacement patients. We aimed to compare the health-related quality of life (as measured by the SF-36) of people with osteoarthritis undergoing primary total hip and knee replacement surgery with that of the normal Australian population.2 Putting changes in the health-related quality of life of these patients in the context of population norms for the same age group gives us a meaningful measure of the effectiveness of this surgery. It also provides information in a way that allows comparisons with other diseases and treatments, assisting rational choices to be made about the use of the limited healthcare dollar. Methods The information on the patients undergoing total joint replacement collected for this analysis was part of a long-term follow-up of patients in a cohort study aiming to assess the costs of arthritis and the effectiveness of its treatment. The cohort includes patients from both public and private hospitals and surgeons operating in both sectors are involved. Patients with osteoarthritis booked for primary total hip or knee replacement surgery at three Sydney hospitals (St Vincent's public and private hospitals and the Centre for Bone and Joint Diseases, North Ryde) between March 1994 and December 1995 were approached to participate in the study. Recruitment was through regular contact with the orthopaedic surgeons and their practice staff. Baseline information was collected from patients through a series of questionnaires, including the SF-36. Questionnaires were administered between one week and three months before surgery. After surgery, patients completed the SF-36 questionnaire at the end of each three months for their first postoperative year. Most questionnaires were self-administered, with less than 10% requiring face-to-face interview. This is consistent with the Australian Bureau of Statistics methodology for collecting general population data.2 Annual follow-up of these patients by mail is continuing. This article presents SF-36 information from patients at baseline and 12 months after surgery. Ethics committee and Medical Board approval was obtained from the St Vincent's campus of the University of New South Wales Medical School, the Centre for Bone and Joint Diseases and the Royal North Shore Hospital. All patients in the study gave written informed consent. Analysis Mean scores for each of the SF-36 dimensions were calculated for patients in the age groups 55-64, 65-74 and 75 years and over. Scores for men and women were combined, as, apart from older males undergoing joint replacement having lower preoperative scores for role emotional, there was no significant difference in scores between the sexes. Scores for each dimension were transformed according to the SF-36 user's guide12 to a scale of 0-100 (100 = best possible score). We used one-sample t tests to compare the transformed scores with general population norms derived by the Australian Bureau of Statistics from the 1995 National Health Survey. The t test was chosen on the assumption that the population value was the real value (given that published standard errors were so low) and that we were observing the variance of the study data from the population value. A P value of 0.05 was considered to be significant and no adjustment was made for multiple comparisons. SF-36 on the web More information about the SF-36 health survey can be found on the SF-36 website: http://www.sf-36.com An online demonstration of the SF-36 survey (score yourself and read an explanation of the result in comparison with US population norms) is available at: http://www.qmetric.com/demo/sf-36v1.shtml Results Two-thirds of the eligible patients were recruited (226 of 343). Reasons for exclusion included being unable to be contacted before surgery (50% of those who did not participate in the study), being non-English-speaking (10%) and refusal or inability to complete the questionnaires (40%). Eligible patients who did not participate in the study did not differ significantly from the cohort in terms of age, sex or type of joint replacement (ie, hip or knee) (data not shown). At the time of analysis, we had complete information for 151 patients at 12 months' follow-up (59 with hip replacement and 92 knee replacement; 52% female; median age, 72 years). An additional 75 patients (60% female; median age, 74 years) had incomplete follow-up information. Their last recorded SF-36 scores showed no significant differences from scores at the same stage of follow-up among those with complete information (data not shown). Patients' SF-36 scores before and 12 months after surgery are shown in the Figure, in comparison with scores for the general population. Knee replacements 55-64 years age group: Eight patients undergoing knee replacement were recruited. Six of these patients reported having other illnesses, most commonly cardiovascular disease (reported by five patients). At 12 months' follow-up, these eight patients showed improvement from baseline according to mean SF-36 scores for physical function, role physical, bodily pain and vitality, but these scores remained significantly lower than the population norms. The power to detect the observed difference to be statistically significant at the 5% level ranged from 83% to 100% for these four comparisons. Their scores on the other four scales (general health, social function, role emotional, mental health) remained lower than population norms, but this difference was not statistically significant (power to detect a significant difference ranged from 7% to 55%). 65-74 years age group: Twenty-eight of the 44 patients (64%) reported having a comorbid illness, with the most commonly reported again being cardiovascular disease (61% of those with comorbidity). Mean SF-36 scores improved significantly on all scales except general health. The mean general health score was significantly higher than the population norm at 12 months' follow-up, but had been higher to begin with at baseline. Mean physical function, role physical and bodily pain scores remained significantly lower than the population norms at 12 months' follow-up. The power to detect these differences ranged from 85% to 99%. Mean vitality, social function, role emotional and mental health scores improved from baseline to be similar to population norms. The power to detect the significance of these differences ranged from 8% to 36%. 75 years and over: Thirty-two of the 40 patients (80%) reported suffering from another illness, most commonly cardiovascular disease (60% of those with comorbidities). Mean SF-36 scores improved significantly on most scales (particularly role physical, physical function and bodily pain), but not on general health and mental health, which were fairly high before surgery. The mean general health score was significantly higher than the population norm at 12 months' follow-up; the other scores improved to population levels. Given the small difference seen between patient and population scores, large numbers would be required to show statistically significant differences (power ranged from 7% to 33%). Hip replacements 55-64 years age group: Comorbidities were reported by 5 of the 14 patients (36%). All five had cardiovascular disease among other comorbidities. Mean scores for vitality and social function improved to become significantly higher than the population norms (power to detect significant difference, 90% and 96%, respectively), while the other scores improved to be similar to the population norms, with particular improvement in physical function, role physical and bodily pain. 65-74 years age group: Thirteen of the 28 patients reported suffering from a comorbid illness, most commonly cardiovascular disease (46% of patients with comorbidities). Mean SF-36 scores improved on all scales except general health, which had a baseline value above the population norm. Mean scores for general health and mental health were significantly higher than the population norms at 12 months' follow-up (power to detect difference, 85% and 75%, respectively) and the other scores improved to be similar to the population norms (power to detect difference ranged from 7% to 58%). The improvement from baseline was particularly evident in role physical, physical function and bodily pain scores. 75 years and over: Comorbidities were reported by 12 of the 17 patients (71%), most commonly cardiovascular disease (reported by 58% of those with comorbidities). Mean SF-36 scores improved on all scales except general health and mental health. At 12 months' follow-up, mean scores on none of the scales were significantly different from the population norms, possibly due to the small numbers in this group (power to detect a difference less than 30% for most scales). Again, there was improvement to population norms in role physical, physical function and bodily pain. Discussion We found that knee or hip replacement surgery significantly improved the health-related quality of life of patients with osteoarthritis. Before surgery, the patients had poor SF-36 scores for bodily pain, physical function and role physical, a clear reflection of the impact of chronic osteoarthritis on health-related quality of life. After surgery, the biggest improvements were in these scores. Improvement in these physical dimensions of health is likely to lead to improvements in social function, mental health and vitality. We found no improvement in general health despite gains in the other scales. This has been shown in other studies,11 and has been suggested to be due to the patients' previous medical history and pre-existing and general health-related conditions. In our study it was apparent that the general health of patients was already higher at baseline than the population norm, suggesting that relatively healthy patients are being selected for total joint replacement. A US study that compared patients undergoing total hip replacement with age-matched and sex-matched population norms found that age and sex made important differences in SF-36 scores.9 Men younger than 65 years had scores lower than the norms in the physical scales, but were comparable in the mental scales, and women scored lower than the norm in all scales. No sex differences were found in our study, but similar age differences were observed, particularly for patients undergoing total knee replacement, among whom the youngest age group had the poorest outcome relative to the age-matched population. We hypothesise that this may be related to the higher population norms for this age group, unrealistic expectations for outcomes among patients, and the presence of existing comorbidities in younger patients requiring knee replacement. One implication of these findings is that older age should not be a barrier to joint replacement surgery, as the outcome is likely to be relatively successful for older patients. Potential limitations that need to be considered when interpreting these results include the non-randomised cohort design, the power of the analysis given the small sample size of the subgroups, and the overall response rate. However, the inclusion of several groups of surgeons operating at different sites and across the public and private sectors contributed significantly to the generalisability of the results. This study showed the improvement of SF-36 scores of patients undergoing total hip or knee replacement up to and in some cases beyond population norms. Whether these statistically significant differences are clinically important remains to be seen. Longer follow-up is required to determine whether the dramatic improvement from baseline is maintained. Nonetheless, at one year follow-up, it would appear that total knee or hip joint replacements are successful at restoring health and well-being, and that older age alone should not be a barrier to surgery. Acknowledgements This study was funded by grants from the National Health and Medical Research Council. We are grateful to the secretarial staff of the orthopaedic surgeons for their assistance with recruitment to this study and to the patients who have been so cooperative. References Australian Bureau of Statistics. Disability and handicap, Australia 1988. Canberra: ABS, 1996 (Catalogue No. 4120.0). Australian Bureau of Statistics National Health Survey: SF-36 population norms, Australia, 1995. Canberra: ABS, 1997 (Catalogue No. 4399.0). Bombardier C, Melfi CA, Paul J, et al. Comparison of a generic and a disease-specific measure of pain and physical function after knee replacement surgery. Med Care 1995; 33 Suppl 4: AS131-AS144. Van Essen GJ, Chipchase LS, O'Connor D, Krishnan J. Primary total knee replacement: short-term outcomes in an Australian population. J Quality Clin Practice 1998; 18: 135-142. Bayley KB, London MR, Grunkemeier GL, Lansky DJ, Measuring the success of treatment in patient terms. Med Care 1995; 33 Suppl 4: AS226-AS235. Stucki G, Liang MH, Phillips C, Katz JN. The Short-Form 36 is preferable to the SIP as a generic health status measure in patients undergoing elective total hip arthroplasty. Arthritis Care Res 1995; 8: 174-181. Ritter MA, Albohm MJ, Overview: maintaining outcomes for total hip arthroplasty. The past, present and future. Clin Orthop 1997; 344: 81-87. Hozack J, Rothman RH, Albert TJ, et al. Relationship of total hip arthroplasty outcomes to other orthopaedic procedures. Clinical Orthop 1997; 344: 88-93. Lieberman JR, Dorey F, Shekelle P, et al. Outcome after total hip arthroplasty. Comparison of a traditional disease-specific and a quality of life measurement of outcome. J Arthroplasty 1997; 12: 639-645. Kiebzak GM, Vain PA, Gregory AM, et al. SF-36 general health status survey to determine patient satisfaction at short-term follow-up after total hip and knee arthroplasty. J Southern Orthop Assoc 1997; 6: 169-172. Ritter MA, Albohm MJ, Keating EM, et al. Comparative outcomes of total joint arthroplasty. J Arthroplasty 1995; 10: 737-741. Medical Outcomes Trust. How to score the SF-36 health survey. Boston: The Trust, 1994. (Received 16 Oct 1998, accepted 12 Jun 1999) Authors' details University of Sydney, Department of Rheumatology, Royal North Shore Hospital, Sydney, NSW. Lyn M March, MB BS, PhD, FRACP, FAFPHM, Associate Professor. Department of Medicine, University of New South Wales, Sydney, NSW. Marita J Cross, BSc(Hons), Research Assistant; Katherine L Tribe, BSc(Hons), Research Assistant; Clarissa J M Bachmeier, MD, MMed(ClinEpidem), Research Fellow. School of Health Services Management, University of New South Wales. Helen Lapsley, BA, MEc, Senior Lecturer. Northern Sydney Public Health Unit, Hornsby Ku-ring-gai Hospital, Sydney, NSW. Alan J M Brnabic, MSc, Statistician. Department of Orthopaedics, St Vincent's Hospital, Sydney, NSW. Brett G Courtenay, MB BS, FRACS, Orthopaedic Surgeon. Faculty of Health Sciences, University of Queensland, Brisbane, Qld. Peter M Brooks, MB BS, FRACP, FAFPHM, Executive Dean. No reprints will be available from the authors. Correspondence: Associate Professor L M March, Department of Rheumatology, Royal North Shore Hospital, St Leonards, NSW 2065. Email: lmarcATdoh.health.nsw.gov.au Click in figure for a larger version Back to text

Lyn M March · Marita J Cross · Helen Lapsley · Katherine L Tribe · Brett G Courtenay · Peter M Brooks

Research Impact of written information on knowledge and preferences for cardiopulmonary resuscitation Ian H Kerridge, Sallie-Anne Pearson, Isobel E Rolfe, Michael Lowe and John R McPhee MJA 1999; 171: 239-242 Abstract - Introduction - Methods - Results - Discussion - Acknowledgements - References - Authors' details - - More articles on Ethics Abstract Aim: To investigate knowledge about and attitudes to cardiopulmonary resuscitation (CPR), and to determine whether written information about CPR alters knowledge and choices made. Design: Questionnaire-based survey before and immediately after provision of written information describing CPR and its risks and benefits. Subjects and setting: All health professionals (803) and competent inpatients (260) in a tertiary care hospital (John Hunter Hospital, Newcastle, New South Wales, Australia) in June 1994. Main outcome measures: CPR knowledge scores and choice scores (number of hypothetical clinical scenarios in which CPR would be chosen) before and after provision of information about CPR. Results: Response rates were 64% (health professionals) and 58% (patients). Patients had limited awareness of procedures involved in CPR, while both patients and health professionals overestimated its success rates. Mean knowledge scores increased after provision of information: for patients, from 6.4 out of 18 (95% confidence interval [CI], 6.0-6.9) to 10.4 (95% CI, 9.9-11.1); and for health professionals, from 11.9 (95% CI, 11.7-12.1) to 13.9 (95% CI, 13.7-14.2). In contrast, mean choice scores decreased after provision of information: for patients, from 5.3 out of 12 (95% CI, 4.7-5.7) to 4.4 (95% CI, 3.9-4.8); and for health professionals, from 4.1 (95% CI, 3.9-4.2) to 3.5 (95% CI, 3.3-3.7). Conclusion: Our results imply that people understand and use prognostic information to make decisions about CPR. To make autonomous judgements, patients and health professionals need better education on CPR outcomes. Introduction While cardiopulmonary resuscitation (CPR) can be lifesaving, success rates (survival to discharge) are less than 5% in some types of patients, particularly those with chronic illness or multiple comorbidities.1 Among those who survive, quality of life is often poor and life expectancy often short.2 In the mid-1970s, growing concern about inappropriate application of CPR and increased awareness of patient rights led to the development of "do-not-resuscitate" (DNR) orders.3 Health professionals are now increasingly encouraged to discuss DNR decisions with patients and their families.4 However, for decision-making about CPR to be appropriate, patients and their surrogates must have some understanding of the likelihood of surviving CPR and the possible adverse effects. Previous research has found that 50%-80% of patients claimed awareness of CPR, but their knowledge was very limited and derived mainly from television dramas. Most patients believed erroneously that CPR is generally successful,5,6 and both patients and health professionals were found to overestimate its success by up to 300%.7 We aimed to investigate knowledge of and attitudes to CPR among hospital inpatients and health professionals and to determine whether written information about CPR alters knowledge and preference for CPR. We have previously reported the opinions of patients and health professionals on the process of decision-making about CPR.8 Methods Subjects and setting The study was conducted at the John Hunter Hospital, Newcastle, New South Wales (a 530-bed tertiary care hospital), over a four-day period in June 1994. Subjects comprised all health professionals working in the hospital (doctors, nurses and allied health professionals) and all eligible (competent) inpatients, as described previously.8 Informed consent was obtained by trained interviewers, and a Mini Mental State Examination (MMSE) performed on patients. Those with MMSE scores < 24 were excluded. A questionnaire for self-completion was administered before and immediately after provision of written information about CPR. Questionnaire The questionnaire asked about: sociodemographic characteristics; sources of information on CPR (respondents could nominate as many as applied from a list of 11); whether each of 10 procedures is part of CPR (possible answers: yes, no or don't know); how successful CPR is in eight clinical scenarios, using a five-point scale: rarely (< 5%), seldom (5%-30%), sometimes (31%-60%), mostly (61%-90%) or almost always (> 91%); and whether respondents would like CPR performed on themselves in 12 specific clinical scenarios (possible answers: yes or no). On completing the questionnaire, respondents were given a one-page information sheet that explained various aspects of CPR, including its definition, procedures that may or may not be considered part of CPR, risks and benefits, success rates, and prognostic indicators (good prognosis: after acute myocardial infarction; poor prognosis: cancer, severe infection, organ failure). Respondents were then asked to repeat the questions on knowledge and choices. Statistical analyses Data were analysed with SPSS version 6.0 for Windows.9 Sociodemographic characteristics of patients and health professionals were compared using continuity-corrected χ2 analyses. All other analyses were performed for patients and health professionals separately. Knowledge of CPR was scored by allocating a point for each correct response. We assessed the relationship between this score and sociodemographic characteristics by standard multiple linear regression, with knowledge score as the dependent variable. For this analysis, we converted the discrete sociodemographic variable (health professional background) into a set of dichotomous independent variables using dummy variable coding (ie, doctors versus all other health professionals, and nurses versus all other health professionals). Significance of change in knowledge scores after provision of information was examined by one-way repeated-measures analysis-of-variance (ANOVA). As answers to some of the knowledge questions may be contentious (whether CPR involves intravenous drugs, intubation and defibrillation), analyses were repeated using scores with these questions omitted. Composite "choice scores" about CPR were calculated by allocating a point for each condition in which the subject would choose to have CPR. The relationship between choice score, sociodemographic characteristics and knowledge score after provision of information was assessed by standard multiple linear regression, with choice score as the dependent variable and knowledge score and sociodemographic factors as independent variables. Significance of change in choice scores after provision of information was examined by ANOVA. Ethical approval The study was approved by the Hunter Area Health Service Research Ethics Committee and the University of Newcastle Human Research Ethics Committee. Results Subjects Of the 803 questionnaires delivered to health professionals, 511 (64%) were returned (148 from doctors, 312 from nurses and 51 from allied health professionals). Of the 443 adult patients in the hospital during the study, 183 were excluded (because of dementia, neurological impairment or delirium [110], incompetence as assessed by MMSE [35], visual or language problems [24], psychiatric illness [9], or as they were undergoing procedures [5]); 153 (58%) of the remaining 260 completed the questionnaire. Sociodemographic characteristics of respondents are shown in Box 1. Knowledge about CPR Sources of information about CPR most commonly identified by health professionals were first aid or in-service courses (33% of responses); school, college or university (27%); and other health professionals (17%). Sources most commonly identified by patients were television (28% of responses), books or magazines (15%), first aid classes (15%), and school (10%). Knowledge before provision of information is shown in Box 2. Patients' knowledge scores were low (mean, 6.4 out of 18; 95% confidence interval [CI], 6.0-6.9), mainly because of lack of awareness of success rates of CPR, with 90% overestimating success for the "all patients" category. Health professionals' knowledge scores were higher than patients' (mean, 11.9; 95% CI, 11.7-12.1), but health professionals also overestimated success of CPR, with 65% overestimating success for "all patients". ANOVA showed that knowledge scores improved significantly after provision of written information for both patients and health professionals (patients: mean, 10.4; 95% CI, 9.9-11.1; health professionals: mean, 13.9; 95% CI, 13.7-14.2). The only sociodemographic characteristics that significantly predicted knowledge scores before provision of information were age (for patients) and professional background (for health professionals): younger patients achieved higher scores than older patients, while doctors and nurses achieved higher scores than allied health professionals. Repeat analysis of the data after omission of contentious questions did not affect the relationship between sociodemographic variables and knowledge scores or the change in knowledge scores after provision of information. Choices about CPR Percentages of patients and health professionals who chose CPR are shown in Box 3. Percentages varied between clinical scenarios, but decreased after provision of information for almost all. ANOVA showed that choice scores also decreased significantly for both patients and health professionals. Mean choice scores decreased for patients from 5.3 out of 12 (95% CI, 4.7-5.7) to 4.4 (95% CI, 3.9-4.8), and for health professionals, from 4.1 (95% CI, 3.9-4.2) to 3.5 (95% CI, 3.3-3.7). CPR was chosen for more scenarios by patients who were younger or had lower knowledge scores and by health professionals who were younger, male, tertiary educated or had better self-reported health status. Discussion We found that patients in an Australian teaching hospital had poor knowledge of CPR, and that both they and, to a lesser extent, hospital staff had unrealistic expectations about its success rates. We also found that provision of written information about CPR risks, benefits and success rates had a clear impact on whether patients and health professionals reported wanting CPR performed on themselves in hypothetical clinical scenarios, decreasing their preference for CPR. Other studies have also found that patients are unaware of the procedures involved in CPR and, along with their relatives, generally overestimate success rates.10 This is not surprising, as television, books and magazines are often their most common sources of information. In addition, community education tends to be positive about CPR, often failing to describe its real success rates. Several previous studies have investigated the relationship between choices about CPR and estimated probability of survival.5,11 They found, similarly to us, that many patients change their minds about wanting CPR when they learn the true probability of survival. Furthermore, formal processes of information disclosure, including discussion of the likely outcome of resuscitation in specific clinical situations, has been shown to modify preferences for CPR.12 In our study, the change in preference followed provision of a one-page information sheet. It is possible that a more optimal form of education (eg, repeated explanations tailored to the individual, with time for reflection and questions) would have produced a greater change in preferences. Perceived morbidity after CPR also strongly influences many people's choices. A survey of 200 medical inpatients found that choice of CPR or DNR status was strongly influenced by anticipated outcome; 90% of patients desired CPR if they were to be restored to their normal health, 30% if the likely outcome after recovery was dependence, 15% if it was perceived as "hopeless", and 6% if it was coma.13 Other studies from the United States14 and United Kingdom15 have found that senile dementia, more than any other condition, is associated with a preference for DNR status. We found similarly that patients and health professionals would be unlikely to opt for CPR in the presence of brain injury or severe dementia. Nevertheless, as found by others,6,10 some patients continued to opt for CPR even if they were likely to have a serious disability, such as coma or terminal illness. We also found, in common with others overseas, that health professionals vastly overestimate the success rates of CPR. These rates (3%-30% in general hospitals) have not changed significantly in the past 30 years.1,16 However, they are well below the rates perceived by physicians and nurses, who are responsible for making decisions about resuscitation status and informing patients and their surrogates.17,18 There are several limitations to our study. Subjects included hospitalised patients with acute illness, and the findings may not be generalisable to other patient populations. The study instrument was a self-report questionnaire using hypothetical clinical scenarios; answers may not accurately reflect what individuals would choose in reality. However, the study has strengths; it assessed both knowledge of and attitudes to CPR in variable clinical contexts and included a formal assessment of competence (the MMSE). The study also used trained interviewers rather than clinicians to distribute questionnaires and so was less likely to introduce bias and perhaps more likely to elicit patients' true preferences. As factors such as likelihood of survival and functional status after resuscitation may contribute to patients' wishes for CPR, it is ethically and clinically desirable that patients be provided with this information. Furthermore, the High Court of Australia has reaffirmed that patients must be given adequate information when making decisions concerning their healthcare.19,20 It is also essential that health professionals who advise patients are aware of the real success rates of CPR. Otherwise, they have failed to meet the standards required both for ethical medical care and by law.21 Respect for autonomy demands that the views of patients or their surrogates should be sought in decision-making about CPR. Our study implies that patients understand and use prognostic information in their decision-making. For truly autonomous judgements, patients and health professionals clearly need better education on risks and benefits of CPR. Acknowledgements We would like to thank the interviewers and patients and staff of the John Hunter Hospital for their generous participation in this study. References Robinson GR, Hess D. Post-discharge survival and functional status following in-hospital cardiopulmonary resuscitation. Chest 1994; 105: 991-994. Landry FJ, Parker JM, Phillips YY. Outcome of cardiopulmonary resuscitation in the intensive care setting. Arch Intern Med 1992; 152: 2305-2308. Rabkin MT, Gillerman JD, Rice NR. Orders not to resuscitate. N Engl J Med 1976; 295: 364-366. Decisions relating to cardiopulmonary resuscitation. A statement from the British Medical Association and the Royal College of Nursing in association with the Resuscitation Council (UK). London: BMA, 1993. Miller DL, Jahnigen DW, Gorbien MJ, Simbarti L. Cardiopulmonary resuscitation: how useful? Attitudes and knowledge of an elderly population. Arch Intern Med 1992; 152: 578-582. Schonwefter RS, Walker RM, Kramer DR, Robinson BE. Resuscitation decision-making in the elderly: the value of outcome data. J Gen Intern Med 1993; 8: 295-300. Potter JM, Stewart D, Duncan G. Living wills: would sick people change their minds? Postgrad Med J 1994; 70: 818-820. Kerridge IH, Pearson SA, Rolfe IE, Lowe M. Decision making in CPR: attitudes of hospital patients and health care professionals. Med J Aust 1998; 169: 128-131. SPSS. Statistical package for the social sciences. Version 6.0 for Windows. Chicago, Ill: SPSS Inc, 1990. Schmerling RH, Bedell SE, Lilienfeld A, Delbanco TL. Discussing cardiopulmonary resuscitation: a study of elderly outpatients. J Gen lntern Med 1988; 3: 317-321. Murphy DJ, Burrows MD, Santilli S, et al. The influence of the probability of survival on patients' preferences regarding cardiopulmonary resuscitation. N Engl J Med 1994; 330: 545-549. Schonwetter RS, Teasdale TA, Taffet G, et al. Educating the elderly: cardiopulmonary resuscitation decisions before and after intervention. J Am Geriatr Soc 1991; 39: 372-377. Frankl D, Oye RK, Bellamy PE. Attitudes of hospitalised patients toward life support: a survey of 200 medical inpatients. Am J Med 1989; 6: 645-648. Ebell MH, Doukas DJ, Smith MA. The do-not-resuscitate order: a comparison of physician and patient preferences and decision-making. Am J Med 1991; 91: 255-260. Robertson GS. Resuscitation and senility: a study of patients' opinions. J Med Ethics 1993; 19: 104-107. Bedell SE, Delbanco TL, Cook EF, Epstein FH. Survival after cardiopulmonary resuscitation. Crit Care Med 1983; 309: 569-576. Miller DL, Gorbien MJ, Simbarti LA, Jahnigen DW. Factors influencing physicians in recommending in-hospital cardiopulmonary resuscitation. Arch Intern Med 1993; 153: 1999-2003. Wagg A, Kinirons M, Stewart K. Cardiopulmonary resuscitation: doctors and nurses expect too much. J R Coll Physicians Lond 1995; 29: 20-24. Rogers v Whitaker (1992) 175 CLR 479. Chappel v Hart [1998] HCA 55. Wyong Shire Council v Shirf (1980) 146 CLR 40. (Received 13 Jan, accepted 7 Jul, 1999) Authors' details Faculty of Medicine and Health Sciences, University of Newcastle, Newcastle, NSW. Ian H Kerridge, MPhil, Lecturer in Clinical Ethics; Sallie-Anne Pearson, PhD, Research Academic; Isobel E Rolfe, MMedEd, Senior Lecturer in Medical Education; Michael Lowe, FRACP, Tutor in Clinical Ethics; John R McPhee, BCom(Hons) (Legal Studies), Consultant in Health Law. Reprints will not be available from the authors. Correspondence: Dr I H Kerridge, Clinical Unit in Ethics and Health Law, Locked Bag 1, Hunter Region Mail Centre, Newcastle, NSW 2310. Email: ikerridgATmail.newcastle.edu.au 1: Sociodemographic characteristics of patients and health professionals surveyed about cardiopulmonary resuscitationPatients (n =153)Healthcare professionals (n =511)PAge > 35 years*90 (59%)235 (46%) 0.007Female98 (65%)373 (73%)< 0.001Marital status† Married/de facto97 (64%)328 (64%) Single/divorced/widowed55 (36%)183 (36%) 0.99Education† Secondary or less117 (77%)72 (14%) Tertiary35 (23%)438 (86%) < 0.001Religion† Religious‡127 (84%)401 (79%) Not religious25 (16%)109 (21%) 0.18Ethnic background† Australian/British144 (95%)463 (91%) Other7 (5%)45 (9%) 0.09Self-reported health status Good68 (45%)493 (97%) Fair/poor/very poor84 (55%)17 (3%)< 0.001CI = confidence interval. * Median split. †Data were missing for some respondents. ‡Any belief system: Christian, Jewish, Islamic, Hindu or Buddhist. Back to text 2: Percentages of 153 patients and 511 health professionals who replied correctly to questions about cardiopulmonary resuscitation (CPR) before provision of written information% Correct (95% confidence interval)QuestionCorrect responsePatientsHealthcare professionalsWhat is involved in CPR?Chest compression (external cardiac massage)Yes*84% (77%-90%)100%Kidney machine (dialysis)No62% (54%-70%)99% (98%-100%)Intravenous drugsYes*25% (18%-33%)84% (80%-87%)Mouth-to-mouth (artificial respiration) Yes86% (80%-91%)99% (98%-100%)Feeding tube into the nose (nasogastric tube)No48% (40%-56%)96% (94%-98%)AntibioticsNo56% (48%-64%)98% (93%-97%)Tube into the throat to assist breathing (intubation)Yes*35% (27%-43%)85% (82%-88%)External electric shock to the heart (defibrillation)Yes*60% (51%-68%)91% (88%-93%)SurgeryNo48% (40%-56%)98% (96%-99%)Breathing machine (ventilator)No27% (20%-35%)57% (53%-61%)How successful is CPR?All patients5%-30%1% (0-4%)26% (22%-30%)Nursing home patients< 5%8% (4%-13%)62% (58%-66%)Patients who have had recent heart attack31%-60%40% (32%-48%)40% (36%-44%)Patients with widespread cancer< 5%42% (34%-50%)61% (57%-65%)Patients with severe infections (eg, pneumonia)< 5%17% (11%-24%)28% (24%-32%)Patients with kidney failure< 5%25% (18%-33%) 39% (35%-43%)Patients under 60 years5%-30%5% (2%-10%)22% (18%-26%)Patients over 70 years5%-30%15% (10%-22%)34% (30%-38%)* As these answers are contentious, analyses were performed using both responses. 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Ian H Kerridge · Sallie-Anne Pearson · Isobel E Rolfe · Michael Lowe · John R McPhee

Research Investigation of a cluster of leukaemia in the Illawarra region of New South Wales, 1989-1996 Victoria J Westley-Wise, Bernard W Stewart, Irene Kreis, Paolo F Ricci, Anthony Hogan, Chris Darling, Steve Corbett, John Kaldor, Neill H Stacey, and Pauline Warburton MJA 1999; 171: 178-183 For editorial comment, see Cartwright Abstract - Introduction - Methods - Results - Discussion - Conclusions - Follow-up - Acknowledgements - References - Authors' details - - More articles on Haematology Abstract Objectives: To investigate a cluster of leukaemia among young people and assess the plausibility of a disease-exposure relationship. Design: Descriptive analysis of population-based leukaemia incidence data, review of evidence related to the causation of leukaemia, assessment of environmental exposures to known leukaemogens, and resulting risks of leukaemia. Setting: Illawarra region of New South Wales, Australia, focusing on suburbs between the Port Kembla industrial complex and Lake Illawarra (the Warrawong area). Main outcome measures: Standardised incidence ratios (SIRs) for leukaemia; current measured and past estimated ambient air benzene concentrations; and expected leukaemia cases attributable to estimates of ambient air benzene concentrations. Results: In 1989-1996, 12 leukaemia cases among Warrawong residents aged less than 50 years were observed, more than the 3.49 cases expected from the rate in the rest of the Illawarra region (SIR, 343.8; 99% CI, 141.6-691.7). These people lived in suburbs immediately to the south-southwest of a coke byproducts plant (a major industrial source of benzene, one of the few known leukaemogens). The greatest excess was among 15-24-year-olds (SIR, 1085.6; 99% CI, 234.1-3072.4). In 1996, ambient air concentrations of benzene averaged less than 1 part per billion (ppb). Since 1970, ambient air concentrations of benzene were estimated to have averaged up to 3 ppb, about one-thousandth of the level at which leukaemia risk has been identified in occupational epidemiological studies. Using the risk assessment model developed by the US Environmental Protection Agency, we estimate that past benzene levels in the Warrawong area could have resulted in 0.4 additional cases of leukaemia in 1989-1996. Conclusions: The excess occurrence of leukaemia in the Warrawong area in 1989-1996 is highly unusual. Current environmental benzene exposure and the reconstructed past environmental benzene exposure level are too low to explain the large excess of leukaemia. The cause of the cluster is uncertain. Introduction In July 1996 the Illawarra Public Health Unit (located in the Wollongong/Port Kembla region, New South Wales) was notified that four former students of a local high school had been diagnosed with leukaemia since 1989. Preliminary investigations established that a cluster of at least 11 people aged less than 40 years who had lived in suburbs near the school had been diagnosed with leukaemia since 1989. On the basis of New South Wales cancer registration data, only about 2 to 3 cases would have been expected. Established causes of leukaemia include occupational benzene exposure, ionising radiation, chemotherapeutic agents, and some inherited and congenital conditions.1-5 Coke byproduct plants are a recognised source of occupational, and potentially of environmental, benzene exposures.1,6,7 The people in the cluster lived in suburbs adjacent to the Port Kembla industrial complex, which includes coke ovens and an associated byproducts plant. We report the investigation of the Illawarra region leukaemia cluster and discuss the plausibility of a disease-exposure relationship. Methods Our investigation followed published guidelines for cancer cluster investigations.8-10 The main components were evaluations of: the pattern of leukaemia incidence in the Illawarra region, with specific attention to residential areas near the Port Kembla industrial complex; environmental exposure to known and putative leukaemogens; and the plausibility of a disease-exposure relationship (whether past environmental exposures to known leukaemogens could explain the excess leukaemia occurrence). The NSW Cancer Council Ethics Committee approved the study. Case finding and investigation Active and passive case-finding methods were used to identify all people resident in the Illawarra region (Wollongong, Shellharbour and Kiama Local Government Areas) aged less than 50 years who had been diagnosed with leukaemia in 1989-1996. The cut-off at age 50 years was chosen as the index cases were young and the age interval 40-50 years represents a natural change in leukaemia occurrence, when the leukaemia risk begins to rise steeply. We actively identified cases from bone marrow aspirate reports, hospital discharge and day-only admission data, and discussions with clinicians in Sydney and Wollongong, community members and organisations. The population-based New South Wales Central Cancer Registry provided the passive case-finding data. For each leukaemia case, we sought to review the medical record and interview the patient and/or a relative to obtain or confirm information about dates of birth and diagnosis, leukaemia cell-type, genetic and medical risk factors, residential and school histories, and personal and/or parental occupational histories. Occurrence evaluation Leukaemia incidence was analysed in eight areas within the Illawarra region with a similar population size (about 20 000-30 000 in 1986), including the area close to the Port Kembla industrial complex (Area 1) (Figure 1). Leukaemia incidence rates in the whole Illawarra region, and each of the eight areas within it, were compared with rates in a reference population by calculating standardised incidence ratios (SIRs) as a means of indirect age standardisation.11 The reference population used was "Urban NSW" (Sydney, Wentworth, Central Coast, Hunter and Illawarra administrative health areas). The calculation of rates was based on place of residence at diagnosis. Using Central Cancer Registry data, we calculated leukaemia SIRs for males and females and for people aged less than 50 years for four five-year periods which had Census years as their mid-points: 1974-1978, 1979-1983, 1984-1988 and 1989-1993. The SIR is the ratio of the number of cancer cases in a study population to the number of cases expected according to the age-specific rate in the reference population (multiplied by 100). For the Illawarra region, leukaemia rates could be calculated to 1996. Thus, for 1989-1996, leukaemia SIRs were calculated for each of the Illawarra areas. In Area 1, they were also classified by age group and cell-type (according to ICD-9),12 using the rest of the Illawarra region as the reference population. Australian Bureau of Statistics (ABS) census data for 30 June 1976, 1981, 1986 and 1991 were used for urban NSW reference populations.13 For the Illawarra region, the ABS provided population data by postcode. Exact Poisson confidence intervals (CI) around the SIRs were estimated.14 CIs were set at 99%, rather than 95%, to reduce the possibility of identifying a chance excess of cancer as statistically significant. SIRs and CIs were calculated with SAS for Windows version 6.11. NSW Central Cancer Registry data and urban NSW population data were accessed from NSW Health's Health Outcomes Information and Statistical Toolbox, a repository of health-related databases for New South Wales. Environmental monitoring and historical exposure reconstruction We undertook an extensive review of the literature on risk factors for and causes of leukaemia, and on carcinogenic effects of occupational and environmental exposures. The environmental assessment focused on exposure to known leukaemogens from the 1970s to 1996. It involved interviewing representatives from industry, government agencies, local residents and workers; inspecting relevant sites; reviewing government, industry and press reports; and collecting and reviewing information on environmental and occupational exposure for residents and workers. The NSW Environment Protection Authority (EPA) and BHP Steel began daily ambient air benzene monitoring in September 1996 in the residential areas nearest the plant (Figure 2). Monitoring was also conducted at three control sites. The EPA used the standard protocol developed by the US Environmental Protection Agency (US EPA) for assessing toxic organic compounds in ambient air.15 BHP used personal samplers, adapted to a stationary role, which collected organic vapours onto an active adsorbent medium by drawing air through the sampler. Both the EPA and BHP analysed the samples with gas chromatography at laboratories registered with the National Association of Testing Authorities. We estimated environmental benzene exposure from the main local sources before September 1996. Using methods developed by the US EPA,16 we estimated levels of emissions from the coke production facilities for each year since 1970 (based on levels in 1996, adjusted for changes in plant equipment and processes and changes in coke and benzene production). Information related to benzene emissions from motor vehicles and other petroleum sources, including Roads and Traffic Authority data on local traffic volumes, was used to provide an upper estimate of the extent to which emissions from these other major local sources may have differed in previous years relative to 1996. Risk estimation The US EPA's benzene risk assessment model of dose-response17 was used to estimate the number of excess leukaemia cases expected in Area 1 between 1989-1996. It was assumed that the Area 1 population had breathed ambient air (70 kg person breathing 20 m3 of air daily) with benzene concentrations equivalent to the estimated maximum annual average concentration since 1970 for the maximally exposed site, continuously over a lifetime (24 hours per day for 70 years). Results Case finding and investigation The same cases were identified by both active and passive case-finding methods. We identified 44 Illawarra residents aged less than 50 years who were diagnosed with leukaemia in 1989-1996. These included 12 people resident in Area 1 at diagnosis, and a 13th person who had moved out of Area 1 a few months before diagnosis (Table 1). None of these 13 people from Area 1 were found to have genetic or medical risk factors for leukaemia. Nor had they ever worked in the production of coke or its byproducts. Six were diagnosed with acute lymphoblastic leukaemia (ALL), four with chronic myeloid leukaemia (CML), and three with acute myeloid leukaemia (AML). Immunophenotypic features and leukaemic classifications revealed no unusual patterns. Six people have died. Of the nine people from Area 1 aged 20 years or less, seven had lived there all their lives, and two for about 11 years. Four attended the same high school in the late 1980s, with three being in the same school year; these three people had leukaemia of different cell-types. Occurrence evaluation For the four five-year periods between 1974-1993, leukaemia incidence in the Illawarra region, and each of its areas, was not significantly different to that throughout urban New South Wales.18 The incidence of total cancers and other specific cancers (including lymphoma and multiple myeloma) was also not significantly higher in Area 1.18However, leukaemia incidence among Area 1 residents aged less than 50 years in 1989-1996 was more than three times higher than in the rest of the Illawarra region (12 cases observed, versus 3.49 expected; SIR, 344; P = 0.0003) (Table 2). The SIR was more than 200 for all leukaemia cell-types, and was significantly increased for ALL (Table 3). The greatest excess of leukaemia was among teenagers and young adults. Among 15-24-year-olds, five cases were observed, versus 0.46 expected (SIR, 1086; 99% CI, 234.1-3072; P = 0.0001). Environmental monitoring and reconstruction of historical exposure The Port Kembla industrial complex contains heavy industries such as copper smelting, sulphuric acid and superphosphate manufacture, petroleum depots, and Australia's largest steelworks, which includes coke ovens and their byproducts plant. In spring and summer, the predominant wind direction is from the northeast; hence, the residential area where the people with leukaemia lived received the greatest exposure from industrial emissions in the region. Benzene was the only known leukaemogen for which local environmental exposures may have been relevant. While ionising radiation is also an established leukaemogen, and there is evidence that exposure to occupational ethylene oxide or 1,3-butadiene can cause leukaemia,3-5 no specific local environmental sources of these agents were identified. At the byproducts plant, coke oven gases are distilled into a benzene- toluene-xylene commercial product (which is 80% benzene), while past practices (until 1977) separated them. The closest residences are more than 1 km from the plant, with all but two Area 1 cases residing 1-3 km from the plant. The other major benzene sources in Area 1 are motor vehicles and petroleum storage tanks. Both EPA and BHP monitoring found that ambient air benzene concentrations in Area 1 averaged less than one part per billion (ppb) in 1996 (Table 4), typical of urban sites in Sydney.19 Analysis of benzene, toluene and xylene ratios in the EPA's samples indicated that about 50% of the benzene was from petroleum. Annual average ambient air benzene concentrations at the most exposed site within Area 1, since 1970, are estimated to have been up to about 3 ppb. Roads and Traffic Authority data showed that traffic volumes in Area 1 have not changed appreciably since the 1970s.20 Local petroleum storage tanks had a greater storage capacity in previous years, which may have been associated with higher emissions.20 Risk estimation The estimated maximum annual average ambient air benzene concentration in Area 1 of 3 ppb is only about one-thousandth of concentrations at which leukaemia risk has been detected in occupational studies.1 The World Health Organization (WHO) has concluded that occupational exposure to an average of 1 part per million (1 ppm, ie 1000 ppb) over a working lifetime has been associated with no statistical increase in leukaemia deaths.1Using the US EPA benzene risk assessment model,17 if a population of 17 500 people (the number of people in Area 1 aged less than 50 years in 1991) had all breathed air with an average benzene concentration of 3 ppb over a lifetime, at the most 0.2 excess leukaemia deaths (or 0.4 cases) would have been expected in 1989-1996. Discussion This investigation into the reported cluster found a highly significant excess leukaemia occurrence in the Warrawong area, particularly among teenagers, in 1989-1996. Estimated past environmental benzene levels are too low to explain this excess. Cluster studies Cancer cluster studies have rarely provided insights into aetiology.3,8-10,21,22 Studies of very rare diseases with well-defined, high exposures are the most likely to yield conclusive results.22 However, these circumstances, in the context of geographic (spatial or spatiotemporal) clusters, are uncommon.10,22 Disease clusters occur continually in any population, and as such represent "expectedly unexpected" events.9,22Drawing boundaries tightly around people observed in clusters inadvertently identifies and overestimates disease excesses.21,22 However, in this study, the geographic, age and time criteria setting the boundaries were not defined or varied to influence the magnitude of the observed excess. Area 1 was a natural geographic grouping of postcodes bounded by industrial zones, Lake Illawarra and the Pacific Ocean. It included suburbs and a postcode area in which no cases were resident. The age range 0-49 years was broad given that the reported cluster was among teenagers. On the other hand, the most recent period analysed (1989-1996) was preceded by a period in which few leukaemia cases were diagnosed.18 Possible leukaemogens Several known leukaemia causes and risk factors were excluded as explanations for the cluster: ionising radiation, ethylene oxide, 1,3-butadiene, and genetic and medical risk factors. For other agents considered, such as dioxins, pesticides, and heavy metals, evidence is lacking of a causal relationship between these agents and leukaemia, despite numerous studies conducted worldwide.5 Although benzene is structurally related to carcinogenic polycyclic hydrocarbons, these agents are generally associated with lung and some other cancers, but not leukaemia.23 Similarly, the influence of genetic polymorphisms, specifically within the cytochrome P450 family, has been associated with lung cancer rather than leukaemia.24Viruses have been causally associated with the rare hairy cell leukaemia and adult T-cell leukaemia.4,5 They have also been suspected to cause leukaemia in childhood and adolescence, but there is still little convincing evidence that they play an important role.4,5,25 Several studies have associated parental smoking with childhood leukaemia.3,26 While many other parental occupational and/or personal exposures (including pesticides, benzene, solvents, petroleum products, and spray paints) have also been implicated in childhood leukaemia, most relevant studies have used poor exposure measures, with inconsistent results.2,3 To our knowledge no leukaemia "clusters" have been reported and investigated in close proximity to industrial facilities similar to those in the Warrawong area. Occupational exposure during steel and coke production has been causally associated with an increased risk of lung and certain other cancers, but not leukaemia.23,27-29 Benzene Benzene was the only known human leukaemogen to which people in Area 1 had potentially significant environmental exposures. Despite the inevitable focus on the steelworks and coke byproducts plant as a benzene source, petrol exhaust and tobacco smoke (the primary source of benzene for smokers, and relevant to non-smokers through passive smoking) are the most significant sources in urbanised populations.1 Food and water are not major sources of benzene exposure,30 and the possibility of contamination of the water supply in Area 1 with benzene from local sources was examined and excluded.20While other haematological malignancies have been associated with occupational benzene exposure,31-36 the evidence has been considered strongest for AML,1 which affected only three people in this cluster. However, a recent review concluded that the few available studies of leukaemia cell-types do not indicate larger or more consistent elevations in risk for AML than for other cell-types.36 Study strengths and limitations Studies of geographic cancer clusters must typically deal with poor information about environmental exposures.22 In this study we had to rely on estimates of past environmental benzene exposure, but several factors suggest that the emission estimates for the coke production facilities are accurate. An independent audit of the emissions estimates concluded that the underlying assumptions were robust and that the emissions inventory was calculated as accurately as possible without an onsite testing program.37 The estimated past annual average ambient air benzene concentration in the maximally exposed part of the Warrawong area, 3 ppb, was similar to concentrations measured38-40 and modelled41 at similar distances from byproducts plants overseas. Measured occupational benzene exposures for Port Kembla byproducts plant workers between 1979 and 199642 were similar to occupational monitoring results for byproducts plant workers from the United States43 and Britain in the 1980s.29,44Using the US EPA benzene risk assessment model,17 even if we assume that average ambient air benzene concentration in Area 1 was 30 ppb (rather than the estimated 3 ppb), this level of exposure would still only explain up to four excess leukaemia cases. Given that the observed leukaemia excess was primarily among young people, the default assumption of 70 kg adults used in our risk estimate is also likely to have slightly overestimated the risk, and hence the number of expected cases. Consistent with public health principles, the US EPA benzene risk assessment model, which uses data from studies of US rubber and chemical workers,36,45,46 is itself based on assumptions that would exaggerate rather than minimise risk, including a linear relationship between exposure to genotoxic carcinogens and leukaemia risk. However, results from some animal studies suggest that a non-linear response may be more biologically plausible.47,48 If this applies to benzene-induced human leukaemia, application of the US EPA model may considerably overestimate risks in the low exposure range. More plausible are biologically based multistage stochastic models for chemical carcinogenesis, which account for cellular birth, death, initiation, promotion and other biological processes, each stage being linked by a stochastic transition probability that accounts for exposure (or dose).47,48 Such models are likely to produce lower estimates of leukaemia risk for low levels of environmental exposure. However, large uncertainties are inherent in any conversion of risk estimates from animal studies or occupational studies to risk estimates for benzene exposure in the general community. Many people -- children, people of reproductive age, those with other risk factors -- may have susceptibilities to leukaemia quite different from those of the male workers studied in occupational studies. Animal and human studies have begun to clarify the potential risk associated with relatively high transient and/or intermittent benzene exposure49 versus cumulative exposure, but the relationship is still poorly understood for low dose extrapolations. In addition, people in the community are exposed to a variety of agents, which may have as yet unidentified additive and possibly synergistic effects. Conclusions On current knowledge, the recent ambient air benzene concentrations in the Warrawong area represent a negligible leukaemia risk, and the estimated past benzene concentrations are too low to explain the large excess of leukaemia cases that occurred in 1989-1996. However, factors such as variation in susceptibilities of individuals and population groups such as children, the possible effects of intermittent and high transient benzene exposures, and interactions between different agents, mean that we cannot exclude a causal association between leukaemia occurrence among young people in the Warrawong area and chemical exposures. Follow-up A feasibility study is being undertaken to examine the potential for relating disease to chemical exposures through a case-control study. Broadly, chemical exposures of interest are personal exposures (environmental and individual, to benzene and industrial emissions in general) and parental exposures (focusing on those with prior evidence of an association with leukaemia). In addition, routine surveillance of leukaemia and lymphoma is continuing, as is ambient air monitoring for benzene and other hazardous pollutants in the Warrawong area. Acknowledgements We gratefully acknowledge the assistance given by the individuals with leukaemia and their relatives, and other community members who participated in the investigation's Community Reference Group. We give special thanks to members of the Illawarra Leukaemia Investigation Steering Committee for their commitment and contributions: Giovanna Crocco and David Gilmour (Community Reference Group), Richard Willison and Trevor Dunn (Illawarra Public Health Unit), Joe Woodward and Craig Lamberton (NSW Environmental Protection Authority), Ron Hales (Wollongong City Council), and Christine Ewan (University of Wollongong). Many individuals and organisations assisted in and supported the study, but we would particularly like to thank the following organisations: NSW Health; Illawarra Area Health Service; New South Wales Cancer Council; BHP Port Kembla; NSW Environmental Protection Authority; and the University of Wollongong. We also thank John Marthick (University of Wollongong) and Paddy Ranasinghe (Illawarra Public Health Unit) for preparing the maps. References World Health Organization. Benzene (Environmental Health Criteria No. 150). Geneva: International Programme on Chemical Safety, 1993. Ross JA, Davies SM, Potter JD, Robison LL. Epidemiology of childhood leukaemia, with a focus on infants. Epidemiol Rev 1994; 16: 243-272. Cartwright RA, Staines A. Acute leukaemias. Clin Haematol 1992; 5: 1-26. Finch SC, Linet MS. Chronic leukaemias. Clin Haematol 1992; 5: 27-56. Tomatis L, editor. Cancer: causes, occurrence and control (IARC Scientific Publications No. 100). Lyon: International Agency for Research on Cancer, 1990. Fishbein L, O'Neill IK, editors. Benzene and alkylated benzenes. Environmental carcinogens: methods of analysis and exposure measurement, vol. 10 (IARC Scientific Publications No. 85). Lyon: International Agency for Research on Cancer, 1988. 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Some industrial chemicals and dyestuffs (IARC monographs on the evaluation of the carcinogenic risk of chemicals to humans, vol. 29). Lyon: IARC, 1982. United States Environment Protection Agency. Benzene emissions from coke byproduct recovery plants -- background information for proposed standards (EPA-450/3-83-016a). Research Triangle Park, NC: Office of Air Quality Planning and Standards, 1984. BHP Flat Products Division. Report to the Illawarra Area Health Service. Port Kembla: BHP Flat Products Division, 1997. Runion HE, Scott LM. Benzene exposure in the United States, 1978-1983: an overview. Am J Indust Med 1985; 7: 385-393. Drummond L, Luck R, Afacan AS, Wilson HK. Biological monitoring of workers exposed to benzene in the coke oven industry. Br J Indust Med 1988; 45: 256-261. Rinsky RA, Young RJ, Smith AB. Leukemia in benzene workers. Am J Indust Med 1981; 2: 217-245. Ott MG, Townsend DT, Fishbeck WA, Langner RA. Mortality among workers occupationally exposed to benzene. Arch Environ Health 1978; 33: 3-10. Cox LA Jr, Ricci PF. Reassessing benzene cancer risks using internal doses. Risk Analysis 1992; 12: 401-409. Cox LA Jr, Ricci PF. Dose-response non-linearities for benzene revisited: A reply to C Crump. Risk Analysis 1993; 14: 485-486. (Received 2 July 1998, accepted 18 May 1999) Authors' details Illawarra Public Health Unit, Illawarra Area Health Service, Wollongong, NSW. Victoria J Westley-Wise, MPH, FAFPHM, Director; Anthony Hogan, MSc(Hons), PhD, Public Health Officer. Children's Cancer Research Institute, Sydney Children's Hospital, Sydney, NSW. Bernard W Stewart, PhD, FRACI, Research Director; now Head of Cancer Control Program, South Eastern Sydney Area Health Service. University of Wollongong, Wollongong, NSW. Irene Kreis, PhD, FAFPHM, Senior Lecturer; Paolo F Ricci, MSc, PhD, Professorial Fellow. BHP Steel Flat Products Division, Wollongong, NSW. Chris Darling, MSc(Occup Med), FAFOM, Occupational Health Advisor. NSW Health Department, Sydney, NSW. Steve Corbett, MPH, FAFPHM, Manager. National Centre for HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, NSW. John Kaldor, PhD, Deputy Director, and Professor of Epidemiology. University of Sydney, Sydney, NSW. Neill H Stacey, BSc(Hons), PhD, Associate Professor. Illawarra Regional Hospital, Illawarra Area Health Service, Wollongong, NSW. Pauline Warburton, MB BS, FRACP, Director. Reprints: Dr V J Westley-Wise, Illawarra Public Health Unit, PO Box 66, Keiraville, NSW 2500. Email: vwestATdoh.health.nsw.gov.au Figure 1 (above): Map of the Illawarra region, showing areas used for comparing leukamia incidence. Back to textFigure 2 (below): Map of the Warrawong area (central portion of area 1), showing the location of the four ambient air monitoring stations. Back to textBack to textBack to textBack to textBack to text

Victoria J Westley-Wise · Bernard W Stewart · Irene Kreis · Paolo F Ricci · Anthony Hogan · Chris Darling · Steve Corbett · John Kaldor · Neill H Stacey · Pauline Warburton