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Prevalence of hepatitis G virus in Queensland blood donors Len D Moaven, Catherine A Hyland, Ian F Young, D Scott Bowden, Rhonda McCaw, Leigh Mison and Stephen A Locarnini MJA 1996; 165: 369 Subsequently cited in Moaven L. Should we be screening blood donors for hepatitis G virus? The case for screening. MJA 1998; 169: 373-374 and Wong et al. Should we be screening blood donors for hepatitis G virus? The case against screening. MJA 1998; 169: 375-377 Readers may print a single copy for personal use. No further reproduction or distribution of the articles in whole or in part should proceed without the permission of the publisher. For copyright permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au/>". Abstract - Introduction - Methods - Blood donors - Serological and biochemical testing - Reverse transcription PCR testing - Results - Discussion - Box - References - Authors' details - - ©MJA1996 Abstract Objective: To determine the prevalence of hepatitis G virus (HGV) carriage in Queensland blood donors. Design: Cross-sectional survey with retrospective longitudinal study of HGV-positive donors. Setting: Brisbane Red Cross Blood Bank, 1995. Subjects: 100 consecutive blood donors attending the Blood Bank on two days in October 1995 and 20 blood donors with a raised plasma alanine aminotransferase (ALT) level on their last donation. Outcome measures: Presence of HGV RNA by reverse transcription polymerase chain reaction (RT-PCR) in currently donated blood and in blood samples archived for up to 34 months. RT-PCR used two different reverse transcription methods and three different specific sets of primers and probes. Results: Five of the 120 blood donors were positive for HGV RNA by all RT-PCR methods (four of the 100 with normal ALT levels [4%] and one of the 20 with raised ALT levels [5%]). Retrospective testing of archived samples showed that four of these five had been persistently HGV RNA-positive for at least two years, while the fifth had been HGV RNA-negative on two donations before becoming HGV RNA-positive. No risk factors were identified for this donor. Conclusions: A relatively large number of Queensland blood donors (4%) are persistently HGV RNA-positive. MJA 1996; 165: 369-371 Introduction S ince the introduction of improved diagnostic assays for hepatitis C virus 1 and increased screening of blood donors, 2 the incidence of post-transfusion hepatitis has been reduced to low levels. However, there are still cases of post-transfusion hepatitis where an aetiological agent is not identified. 3 While searching for novel agents that may be associated with post-transfusion hepatitis, two independent groups recently discovered an RNA virus that causes acute and chronic infection in man. 4,5 The two isolates, designated hepatitis G virus (HGV) and GB virus C, respectively, belong to the same species, 6 and findings for one seem applicable to the other. Currently, the only reliable method for determining the prevalence of infection with these viruses is specific reverse transcription polymerase chain reaction (RT-PCR) assay to detect viral RNA. A serological assay to detect carriers of HGV is unlikely to be available in the immediate future, and much of the epidemiology of HGV will rely on RT-PCR-based assays. From the available RT-PCR data, it appears that HGV is transmitted parenterally, with increased prevalence in injecting drug users and patients who have received multiple transfusions. 4,7,8 HGV has a high prevalence in developed countries, with about 1.5% of volunteer blood donors from the United States and Europe being positive for HGV RNA. 4,8 It is not known whether these positive donors are transiently infected or chronic carriers of HGV. We examined the prevalence of HGV in Queensland blood donors. As most donors had plasma stored from previous donations, we were also able to collect unique longitudinal data. Methods Blood donors Consecutive blood donors at the Brisbane Red Cross Blood Bank over two days in October 1995 were asked to participate. The first 100 to sign a consent form agreeing to be tested for HGV were studied (compliance was 100%). These donors all had normal plasma alanine aminotransferase (ALT) levels. Blood was also collected over a three-month period from 20 donors with a raised ALT level on their most recent donation. Six of the 20 had raised ALT levels on two or more previous donations. All donors had signed the donor declaration form indicating they did not fall into an "at risk" group. All testing was performed with the approval of the Queensland Red Cross Blood Transfusion Service Ethics Committee. Serological and biochemical testing All donors were tested for antibodies to hepatitis C virus (HCV), HIV 1, HIV 2 and human T-cell lymphotropic virus (HTLV) and for hepatitis B surface antigen (HBsAg) (Abbott Diagnostics, Chicago, Illinois, USA). They were also screened with a syphilis antibody assay, Sysmic RPR (Diagast, Lille, France). Plasma ALT levels were measured by a microtitre tray assay. 9 Samples positive for HGV RNA were also tested for hepatitis B core specific antibody (Abbott Diagnostics). Reverse transcription PCR testing For RT-PCR testing, the recommendations of Kwok and Higuchi 10 were followed to prevent sample contamination. Blood samples were collected in acid-citrate-dextrose and plasma was stored at 2 70 o C within two hours of collection. RNA was subsequently extracted from these plasma samples with a guanidine thiocyanate and phenol-chloroform extraction procedure. 11 RT-PCR was performed with random hexamers and two sets of PCR primers from the 5 9 untranslated region and the region encoding the non-structural protein 5a of the HGV genome. These primers are part of an HGV primer and capture probe set commercially available from Boehringer Mannheim (Germany). In addition, RT-PCR was performed with primers from the region encoding the protein 5b, as described previously. 12 If a plasma sample was positive for HGV RNA, a separate aliquot of plasma was retrieved from frozen storage and RNA was extracted and tested with all three primer sets. Samples positive for HGV RNA were also tested for HCV RNA (Amplicor, Roche Diagnostic Systems, Branchberg, New Jersey, USA). Donors positive for HGV RNA were tested retrospectively by recovering archived frozen plasma samples from previous donations. These samples had been frozen within two hours of collection and stored at 2 30 o C. As controls, archived plasma samples were also recovered from donors negative for HGV RNA. Archived samples were coded and tested blind. In addition, four of the five donors found to be positive for HGV RNA returned subsequently to donate blood and were retested for HGV RNA. These retrospective and prospective samples were tested with the NS5b primers alone. Results Five of the 120 blood donors were HGV-positive by RT-PCR with all three of the primer sets. These positive donors comprised four of the 100 with normal ALT levels (4%; 95% confidence interval [CI], 1%-10%) and one of the 20 with raised ALT levels (5%; 95% CI, 0.1%-25%). This donor had not had raised ALT levels previously. The remaining 115 donors were negative by all three primer sets. Repeat PCR testing of a separate aliquot of each HGV-positive sample revealed complete concordance of results. The five HGV-positive donors were negative for hepatitis B core-specific antibody and HCV RNA. All donors were negative for antibodies to HCV, HIV 1, HIV 2 and HTLV, for HBsAg and for syphilis RPR antibody. Plasma samples from 22 previous donations given by the five HGV-positive donors were also tested for HGV RNA (see Box). Four donors were HGV-positive for all previous donations ( n = 18), made up to 22-34 months previously. The fifth, a 38-year-old man, was HGV-positive from August 1994, but two previous donations (May 1994 and November 1993) were HGV-negative. His ALT level was normal on each occasion and no risk factor or illness could be identified for this donor despite specific questioning about the period May 1994 to August 1994. Potential risk factors were noted for three of the other HGV carriers (see Box). All HGV-positive donors were well. Four returned for further testing, including the donor who appeared to acquire HGV infection in 1994; they remained HGV-positive on all occasions (up to six months after initial tests). The control archived plasma samples were tested blindly and found to be HGV-negative. Discussion This is the first study to describe the prevalence of HGV in an Australian blood donor population and to provide longitudinal data on a cohort of HGV-infected donors. Five of 120 blood donors (4.2%) were HGV-positive, a higher prevalence than seen in other developed countries. 4,8 All five appeared to be chronic carriers of HGV (assuming infection does not resolve after HGV carriage for longer than a year). It has yet to be determined why this infection is so prevalent in a group normally assumed to be at low risk for exposure to blood-borne viruses. Mother-to-baby (and early horizontal) transmission may account for the pattern of distribution (analogously to HBV in developing countries). 12 One donor had grown up in a developing country and another had potential risk factors (e.g., tattooing). Even so, one of the donors appeared to acquire HGV infection recently, without evident risk factors. This suggests that there are multiple modes of transmission. We found that only one of the HGV-positive donors had a raised ALT level, and on only one occasion. Although HGV infection is associated with an early and mild rise in results of liver function tests in some recipients of HGV-infected blood, 4 this is not unusual in acute viral infections. There is currently little evidence that HGV commonly causes chronic liver disease, but this does not preclude association with another disease. Indeed, we would argue that it is unlikely that a positive-strand RNA virus could cause chronic infection and not be associated with a disease syndrome. It is worth noting that with such a high prevalence of HGV in the general population the demonstration of a disease association will have to be particularly rigorous. The strategy we developed for HGV testing is time consuming and expensive, but, without a reliable serological or alternative virological marker, nucleic acid amplification by PCR remains the method of choice. An alternative to our PCR strategy could be use of a single reliable primer set, with automation of RNA extraction and RT-PCR. Blood donations may have to be tested for HGV RNA when suitable assays become available for mass screening, especially if evidence emerges that it causes significant disease. A National Health and Medical Research Council working party on novel viral hepatides has been set up in collaboration with the Red Cross Blood Transfusion Service to determine the significance of HGV in blood donations. In the meantime, it is important that recipients of donated blood continue to be advised of the potential complications of heterologous blood transfusion and, specifically, that they may acquire HGV infection. 2 However, currently the clinical significance of HGV infection is unclear and further clinical and epidemiological studies are needed on this new and emerging virus. References Aach RD, Stevens CE, Hollinger B, et al. Hepatitis C virus infection in post-transfusion hepatitis: an analysis with first and second generation assays. N Engl J Med 1991; 325: 1325-1329. Sloand EM, Pitt E, Klein HG. Safety of the blood supply. JAMA 1995; 274: 1368-1373. Alter HJ. Transfusion transmitted hepatitis C and non-A, non-B, non-C. Vox Sang 1994; 67: 19-24. Linnen J, Wages J, Zhen-Yong ZK, et al. Molecular cloning and disease association of hepatitis G virus: a transfusion-transmissible agent. Science 1996; 271: 505-508. Simons JN, Leary TP, Dawson JG, et al. Isolation of novel virus-like sequences associated with human hepatitis. Nat Med 1995; 1: 564-569. Zuckerman AJ. Alphabet of hepatitis viruses [editorial]. Lancet 1996; 347: 558-559. Bowden DS, Moaven LD, Locarnini SA. New hepatitis viruses: are there enough letters in the alphabet? Med J Aust 1996; 164: 87-89. Dawson GJ, Schlauder GG, Coleman P, et al. Prevalence and clinical significance of GBV-C [abstract]. Proceedings of the Ninth Triennial International Symposium on Viral Hepatitis and Liver Disease; 1996 April 21-25; Rome (Italy). Rome: CpA (Viale delle Medaglie d'Oro, 342100136), 33: 116. Hyland CA, Douglas R, Mazzocchi R, Young IF. Surrogate testing for non-A, non-B hepatitis in Queensland, Australia, an ALT microtitre tray method for screening blood donors. Pathology 1988; 20: 271-274. Kwok S, Higuchi R. Avoiding false positives with PCR. Nature 1989; 339: 237-238. Chemczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate phenol-chloroform extraction. Anal Biochem 1987; 167: 156-159. Moaven LD, Tennakoon PS, Bowden DS, Locarnini SA. Mother-to-baby transmission of hepatitis G virus. Med J Aust 1996; 165: 84-85. (Received 15 May, accepted 9 Aug 1996) Authors details Victorian Infectious Diseases Reference Laboratory, Fairfield Hospital, Melbourne, VIC. Len D Moaven, FRCPA, Senior Registrar in Virology; D Scott Bowden, PhD, Senior Scientist (Molecular Virology); Rhonda McCaw, BSc, Scientist (Molecular Virology); Stephen A Locarnini, PhD, MRC(Path), Director. Red Cross Blood Transfusion Service, Brisbane, QLD. Catherine A Hyland, PhD, Scientist-in-Charge (Viral Serology); Ian F Young, FRCPA, Director; Leigh Mison, BSc, Scientist. Reprints: Dr S A Locarnini, Victorian Infectious Diseases Reference Laboratory, Fairfield Hospital, PO Box 65, Fairfield, VIC 3078. E-mail: stephenL AT hna.ffh.vic.gov.au <URL: http://www.mja.com.au/> © 1997 Medical Journal of Australia. We appreciate your comments.

Len D Moaven · Catherine A Hyland · Ian F Young · Rhonda McCaw · Leigh Mison · Stephen A Locarnini

An outbreak of Japanese encephalitis in the Torres Strait, Australia, 1995 Jeffrey N Hanna, Scott A Ritchie, Debra A Phillips, Jack Shield, M Clare Bailey, John S Mackenzie, Michael Poidinger, Bradley J McCall and Phillip J Mills MJA 1996; 165: 256-260 Readers may print a single copy for personal use. No further reproduction or distribution of the articles in whole or in part should proceed without the permission of the publisher. For copyright permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au/>". Abstract - Introduction - Methods - Results - Discussion - Acknowledgements - References - Authors' details - Register to be notified of new articles by email - - ©MJA1996 Abstract Objectives: To determine the distribution of virus infection during an outbreak of Japanese encephalitis (JE) in the Torres Strait, and to describe the environmental factors facilitating the outbreak. Design: Human and porcine serological surveys for JE virus activity throughout the Torres Strait, and mosquito and household surveys on the island of Badu. Setting: The island of Badu (where the clinical cases occurred) and the other islands of the Torres Strait, Australia, during April-May 1995. Results: The serological surveys identified recent JE virus infection among residents or domestic pigs on at least nine outer Torres Strait islands. A JE virus, confirmed by nucleotide sequencing, was isolated from two asymptomatic Badu residents. Virus isolations and mosquito surveys implicated Culex annulirostris as the major vector involved in the outbreak. There was prolific Cx. annulirostris breeding in a variety of water bodies close to and within the Badu community. Over half (53%) of the households kept pigs in pens, and many (63%) of the pigpens were situated near standing water; in 56% of these "wet" pigpens Cx. annulirostris was breeding. Conclusions: There was evidence of widespread JE virus activity throughout the outer islands of the Torres Strait. We suggest that migratory birds and/or wind-blown mosquitoes could have imported the virus into the Torres Strait from a focus of viral activity, possibly in Papua New Guinea, thereby initiating the outbreak. A combination of environmental factors, with large numbers of domestic pigs in close proximity to human dwellings and mosquito breeding sites, undoubtedly facilitated the outbreak on Badu. MJA 1996; 165: 256-260 Introduction Over a two-week period in March-April 1995, three cases of Japanese encephalitis (JE) occurred among residents of the island of Badu in the Torres Strait, Australia 1 ( Box 1). Although JE is widespread throughout Asia, 3 the Torres Strait outbreak is the first time that it has been recognised in Australia. J E is caused by a mosquito-borne flavivirus, and results in an acute illness characterised by headache, fever, convulsions, depressed level of consciousness and coma. It has a high case-fatality rate and there is a high prevalence of neurological sequelae in those who survive the acute illness. However, infection with the JE virus does not invariably cause disease; there is a high ratio of asymptomatic to symptomatic infections. 3 The JE virus is maintained in a natural cycle involving water birds such as egrets and herons. Pigs are very efficient amplifying hosts for the virus and therefore almost always contribute to outbreaks of JE in human populations. However, humans and other large verte brates, such as horses, are not efficient amplifying hosts, and are therefore "dead-end" hosts for the JE virus. 3 The outbreak was assumed to have been caused by a mosquito-borne virus, and Murray Valley encephalitis (MVE) virus (the major cause of arboviral encephalitis in Australia) was first suspected. Although the current status of flavivirus infections in the Torres Strait is uncertain, MVE and other Australian flaviviruses (Alfuy, dengue, Kokobera, Kunjin, Stratford and Sepik viruses) have been reported from either Cape York or Papua New Guinea (PNG). 4 Once laboratory findings confirmed the outbreak as JE, further investigations were undertaken. Methods Serological survey In April 1995, a serological survey was undertaken among residents of Badu. A non-random convenience sample was used. Human sera were screened for the presence of (i) flavivirus IgG and IgM by enzyme-linked immunosorbent assay (ELISA) 5 and haemagglutination inhibition assay, 6 and (ii) antibodies to JE, MVE and Kunjin viruses by plaque reduction neutralisation assay. 7 Sera testing positive for flavivirus IgM by ELISA were fractionated by ultracentrifugation over a sucrose gradient. IgM fractions were then tested for haemagglutination-inhibiting antibodies against JE, MVE and Kunjin viruses. 8 A diagnosis of a recent JE virus infection was made if there was a fourfold or greater rise in haemagglutination-inhibiting antibody titres in paired sera tested in parallel, or if JE virus IgM antibody and JE neutralising antibody were detected in serum at significantly higher titres than antibody to MVE and Kunjin viruses. Blood samples for serological studies were also collected from domestic animals, in particular pigs, on Badu. The animal sera were screened for the presence of total (i.e., IgM and IgG) antibody to JE, MVE and Kunjin viruses by haemagglutination inhibition assay. A portion of the sera positive for total JE antibody by haemagglutination inhibition assay was then tested by plaque reduction neutralisation assay. The presence of neutralising antibody at significantly higher titres to JE virus than to MVE and Kunjin viruses was considered evidence of exposure of an animal to JE virus. Isolation of virus Virus isolations were attempted from human sera obtained from residents of Badu: 100 m L of serum was inoculated onto confluent monolayers of C6/36 ( Aedes albopictus ) cells. 9 Viral growth was monitored by testing the culture super natant for haemagglutinating ability. Box 2 details the method used for identification of virus isolates. Mosquito survey Because the outbreak was initially suspected to be MVE, mosquito surveillance focused on the primary vector of MVE in Australia, Culex annulirostris . 4 Commencing on 7 April, larval and adult mosquito surveys were conducted within a 1-km radius of the centre of the Badu community. Mosquito larvae were sampled with a 350 mL dipper and adult mosquitoes were trapped with Centers for Disease Control light traps -- eight, each baited with 1 kg of dry ice (carbon dioxide) and 1-octen-3-ol (octenol; release rate 10 mg/h), 16 were run overnight at locations throughout the community on four occasions throughout April 1995. Household survey In May 1995, environmental health staff undertook a house-to-house survey to interview one adult resident of each household on Badu about household characteristics that may have contributed to the outbreak of JE. These included the presence of backyard pigs and horses and the state of repair of waste disposal (drainage and sewerage) systems. Survey of other communities To determine the extent of recent JE infection, blood was taken from convenience samples of people residing on 12 other outer islands, three inner islands and seven Cape York communities. Blood was also taken from pigs from eight other outer islands, three inner islands and two Cape York communities. Results Serological survey Two hundred and fifteen Badu residents were tested for JE infection: 35 people had serological evidence of recent JE infection (Box 3), and 21 of these had a fourfold or greater rise in JE-specific antibody titres in paired sera. All 11 pigs from Badu (tested by plaque reduction neutralisation assay) showed serological evidence of JE infection (Box 3). Most of the horses (7/10) and dogs (10/16) tested also showed serological evidence of JE infection, but not one of six chickens was positive. Isolation of virus JE virus was isolated from the sera of two Badu residents, both of whom remained asymptomatic. Nucleotide sequences obtained by reverse transcriptase-polymerase chain reaction (RT-PCR) amplification showed that the two viruses (designated FU and NO) were definitely strains of JE, with a 90% nucleotide homology with other strains of JE virus but with less than 70% homology with other flaviviruses. Both Badu isolates were very closely related, with 99% homology with each other. Detailed sequence comparison of the prM region of the viruses with that of other JE virus isolates showed that the Badu viruses were most closely related (92% homology) to other viruses of genotype III, 12,13 especially WTP-70/22 (from Malaysia) and B1065 (from southern Thailand) (Figure 1). The nucleotide sequences of JE-FU and JE-NO have been deposited in GenBank (the international computerised depository of genomic-sequence information), with accession numbers L43565 ( prM ) and L48968 ( NS5 ) for JE-FU, and L43566 ( prM ) and L48967 ( NS5 ) for JE-NO. Mosquito survey Numerous water bodies contained large numbers of Cx. annulirostris larvae. There were extensive swampy areas close to the community, and those contaminated by horse faeces had high larval densities ( >= 10 larvae/dip). A waterhole on the inland side of the community contained a large amount of grass clippings, rubbish and horse faeces; high larval densities were found along the margins. Many of the concrete-lined drains running through the community were overgrown with vegetation and contained mosquito-infested accumulations of water. High densities were also found in some of the defective household waste disposal systems (see below), and in pools in horse hoofprints. A total of 22 190 adult mosquitoes were trapped in the Badu community in April. Aedes kochi , Aedes culiciformis and Cx. annulirostris comprised 99% of the collection, with means of 364, 243 and 127 adult mosquitoes per trap, respectively. While the largest collections of Cx. annulirostris (up to 607 per trap) were taken from swampy areas near the community, collections of more than 100 per trap were taken within the community and close to houses. Eight JE viruses were isolated from 2871 Cx. annulirostris mosquitoes collected at Badu, but not from any other species (S A Ritchie, D A Phillips and A K Broom, unpublished data). Six of the isolates were from mosquitoes collected from within the community. Household survey An adult resident from 97 of the 102 houses in the community was interviewed for the household survey. Fifty-one (53%) of the households kept pigs; 35 (69%) of the pigpens were within 50 metres of the house. There were 179 domestic pigs in the community, an average of 3.5 (range, 1-11) per pig-rearing household. On inspection, 32 (63%) of the pigpens were situated either over or surrounded by standing water, and in 18 (56%) of these "wet" pigpens Cx. annulirostris was breeding. The householders of 15 (15%) of the houses owned a total of 18 horses; they were all kept in paddocks within 500 metres of the houses. The interviewees reported that 62 (64%) of the 97 houses had defective waste disposal systems: 49 of these houses had either waste water or raw sewage overflowing from septic tanks either into the house or into the yard, with 10% of the defective septic tanks containing Culex larvae. Survey of other communities A total of 1242 human serum samples were collected from the other communities. Twenty people from three other outer islands had serological evidence of recent JE virus infection. There was no evidence of JE infection in those tested from the inner islands or from the Cape York communities (Box 3). There was no evidence of any prior infection (i.e., only IgG JE antibodies) in any individual. Of the 182 pig sera collected from the other communities, 121 (66%) were tested by plaque reduction neutralisation assay. There was serological evidence of JE infection in pigs from all eight other outer islands, but no evidence of infection in pigs from the inner islands and Cape York Peninsula (Box 3). Discussion The human serological survey indicated that people from four outer islands had been recently infected with the JE virus. The porcine serological survey found evidence of JE activity in pigs from another five outer islands. Therefore, the two surveys indicated widespread, and presumably recent, JE virus activity in at least nine of the outer Torres Strait islands. There was no evidence of either human or porcine infection in the communities surveyed on the inner islands or on Cape York. The lack of evidence of prior infection in those tested suggests that the 1995 outbreak was the first incursion of the JE virus into the Torres Strait. Nucleotide sequencing studies clearly defined the virus strains isolated from the two people from Badu (and presumably the virus that infected people and pigs throughout the outer Torres Strait islands) as JE virus, and that the isolates were distinct from, but related to, virus strains that were circulating in southern Thailand, Malaysia and Indonesia between 1968 and 1983. 12 The virus differed, however, from a newly recognised genotype known to be circulating in Indonesia in 1980-1981. A strain (JKT-6468, Figure 1) of this latter genotype has been isolated from culicine mosquitoes collected from Flores, east of Bali, and is therefore the closest known isolate to Australia. 13 JE virus has not been isolated or reported as causing human disease in either PNG or Irian Jaya. Although no evidence of JE virus has been demonstrated conclusively in a number of serological surveys, there was possible JE seropositivity in a few single-serum specimens collected in 1956-1957 in the Western Province of PNG. 17 More recently, antibody to JE virus was detected by competitive ELISA in at least 23% of human sera collected in the Western Province in 1989 (R A Hall and J S Mackenzie, unpublished data), and 49% of porcine sera collected in the Western Province in 1995 were positive for neutralising antibody to JE virus (J Shield and R A Lunt, unpublished data). Thus, it seems possible that JE virus has become enzootic in parts of southwestern PNG. The northwestern islands (Boigu, Dauan and Saibai), because of their closeness to PNG, receive Papuan visitors virtually every day, raising the question of whether a viraemic visitor could have brought the JE virus across from PNG to the Torres Strait. However, humans, as "dead-end" hosts of the JE virus, have a low level of JE viraemia of short duration. 3 On the other hand, a viraemic pig imported from PNG, being a very efficient amplifying host, might have initiated the Torres Strait outbreak. However, the Australian Quarantine Act 1908 (Cwlth) prohibits the movement of live animals from PNG to the Torres Strait. The ban is actively enforced and respected; since the appointment of the first indigenous Quarantine Officers in 1982 they have not had occasion to seize even one illegally imported pig (P Stephen, Australian Quarantine and Inspection Service, personal communication). Therefore, we believe it most unlikely that an imported pig initiated the outbreak. Over 100 species of bird migrate annually between Australia and New Guinea, usually in a predictable seasonal pattern. 18 A further 63 species cross the Torres Strait at irregular intervals; these include numerous aquatic species, including wading birds. 18 The rufous night heron ( Nycticorax caledonicus ), for example, is a common nomad found throughout the Torres Strait; 18 it is closely related to the black-crowned night heron ( N. nycticorax ), a principal bird species implicated in the natural JE virus bird-mosquito cycle in Asia. 19 Experimental JE virus infection of the rufous night heron produces levels of viraemia that are quite adequate to infect the most efficient JE vector in Asia ( Culex tritaeniorhynchus ). 20 From December to April the prevailing wind in the region is from the northwest, raising the possibility that the dispersal of "wind-blown" mosquitoes could have carried the JE virus from New Guinea to the Torres Strait. Indeed, it has been reported that female Cx. annulirostris mosquitoes "can disperse at least 12 km and probably further"; 21 the northernmost outer islands are all less than 10 km from the PNG coastline (Box 1). We therefore suggest that two natural phenomena -- viraemic migratory birds and/or infectious wind-blown mosquitoes -- are plausible mechanisms for the importation of the JE virus from New Guinea to the Torres Strait, thereby initiating the outbreak. Cx. annulirostris was undoubtedly the major vector at Badu, and presumably at the other outer islands. Multiple JE virus isolations were made from Cx. annulirostris but not from any other mosquito species. The very small (fewer than one adult mosquito per trap) collections of Culex quinquefasciatus and Culex bitaeniorhynchus (both recognised as being either "marginal" or "occasional" vectors of the JE virus in Asia) 3 indicate that these species were of no importance in this outbreak. Cx. annulirostris was breeding in abundance in a variety of sites close to the community. However, the natural surface waters were extensive, and produced the most mosquitoes. The waterhole with run-off watercourses passing through the community meant that there was extensive mosquito breeding close to the $omestic pigs and to the people. The close proximity of the blocked drains to many of the houses also made them a significant risk. Defective waste disposal systems may also have contributed to the outbreak. The most striking combination of environmental factors contributing to the outbreak was the large number of domestic pigs adjacent to human dwellings and prolific mosquito breeding sites (Figure 2). The density of pigs, the abundance of the vector species and the human population density are all critical factors in determining the risk of human infection. 3,22 Horses, although "dead-end" hosts for the JE virus, 3 nevertheless contributed to the outbreak by providing numerous hoofprint breeding sites, nutrient (i.e., faeces) to the larvae and bloodmeals for female mosquitoes. 23 We need to determine the likelihood of future incursions of the JE virus into the Torres Strait. At the same time there is a clear need not only to reduce the mosquito breeding potential but also to improve the environmental conditions on the islands. Meanwhile, an inactivated JE vaccine has been offered to the inhabitants of the outer islands to confer protection while these risk assessment studies and risk reduction interventions are being implemented. 24 Acknowledgements Many people assisted with the investigation of the outbreak. We thank the staff of the Community Health Centers throughout the Torres Strait, Torres Strait Public Health Program, Tropical Public Health Unit, Australian Quarantine and Inspection Service, Queensland Department of Primary Industries, Laboratory of Microbiology and Pathology and the Australian Animal Health Laboratory. We are particularly grateful to Dr Ted Tsai (Division of Vector-Borne Viral Diseases, Centres for Disease Control and Prevention, USA) for his expert advice and support. References Hanna J, Ritchie S, Loewenthal M, et al. Probable Japanese encephalitis acquired in the Torres Strait. Commun Dis Intell 1995; 19: 206-208. The Torres Strait Health Workshop Working Party. Torres Strait Health Strategy. Thursday Island: Torres Strait Health Council, 1993. Vaughn DW, Hoke CH Jr. The epidemiology of Japanese encephalitis: prospects for prevention. Epidemiol Rev 1992; 14: 197-221. Mackenzie JS, Lindsay MD, Coelen RJ, et al. 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Identification of mosquito-borne flavivirus sequences using universal primers and reverse-transcriptase-polymerase chain reaction. Res Virol 1994; 145: 93-104. Sellner LN, Coelen RJ, Mackenzie JS. A one-tube, one manipulation RT-PCR reaction for detection of Ross River virus. J Virol Methods 1992; 40: 255-264. Chen W-R, Tesh RB, Rico-Hesse R. Genetic variation of Japanese encephalitis virus in nature. J Gen Virol 1990; 71: 2915-2922. Chen W-R, Rico-Hesse R, Tesh RB. A new genotype of Japanese encephalitis virus from Indonesia. Am J Trop Med Hyg 1992; 47: 61-69. Ni H, Barrett ADT. Nucleotide and deduced amino acid sequence of the structural protein genes of Japanese encephalitis viruses from different geographical locations. J Gen Virol 1995; 76: 401-407. Sumiyoshi H, Mori C, Fuke I, et al. Complete nucleotide sequence of the Japanese encephalitis virus genome RNA. Virology 1987; 161: 497-510. Ritchie SA, Kline DL. Comparison of CDC and EVS light traps baited with carbon dioxide and octenol for trapping mosquitoes in Brisbane, Queensland (Diptera: Culicidae). J Aust Entomol Soc 1995; 34: 215-218. Anderson SG, Price AVG, Nanadai-Koia, Slater K. Murray Valley encephalitis in Papua and New Guinea: II. Serological survey, 1956-1957. Med J Aust 1960; 2: 410-413. Draffan RDW, Garnett ST, Malone GJ. Birds of the Torres Strait: an annotated list and biogeographical analysis. The Emu 1983; 83: 207-234. Buescher EL, Scherer WF, McClure HE, et al. Ecologic studies of Japanese encephalitis virus in Japan. IV. Avian infection. Am J Trop Med Hyg 1959; 8: 678-688. Boyle DB, Dickerman RW, Marshall ID. Primary viraemia responses of herons to experimental infection with Murray Valley encephalitis, Kunjin and Japanese encephalitis viruses. Aust J Exp Biol Med Sci 1983; 61: 655-664. Bryan JH, O'Donnell MS, Berry G, Carvan T. Dispersal of adult female Culex annulirostris in Griffith, New South Wales, Australia: a further study. J Am Mosq Control Assoc 1992; 8: 398-403. Gingrich JB, Nisalak A, Latendresse JR, et al. Japanese encephalitis virus in Bangkok: factors influencing vector infections in three suburban communities. J Med Entomol 1992; 29: 436-444. Kay BH, Boreham PFL, Fanning ID. Host-feeding patterns of Culex annulirostris and other mosquitoes (Diptera: Culicidae) at Charleville, southwestern Queensland, Australia. J Med Entomol 1985; 22: 529-535. Hanna J, Barnett D, Ewald D. Vaccination against Japanese encephalitis in the Torres Strait. Commun Dis Intell 1996; 20: 188-190. (Received 9 Feb, accepted 27 May 1996) o Authors' details Tropical Public Health Unit, Queensland Health, Cairns, QLD. Jeffrey N Hanna, MPH, FAFPHM, Public Health Physician. Scott A Ritchie, PhD, Medical Entomologist. World Health Organization Collaborating Centre for Arbovirus Reference and Research, Laboratory of Microbiology and Pathology, Queensland Health, Brisbane, QLD. Debra A Phillips, BSc, MASM, Supervising Scientist. Queensland Department of Primary Industries, Cairns, QLD. Jack Shield, BVSc, Veterinary Officer. Torres Strait Public Health Program, Queensland Health, Thursday Island, QLD. M Clare Bailey, MAIEH, Environmental Health Officer. Department of Microbiology, The University of Queensland, Brisbane, QLD. John S Mackenzie, PhD, FASM, Professor of Microbiology. Michael Poidinger, PhD, Research Officer (NHMRC). Southern Zone Public Health Unit, Queensland Health, Upper Mount Gravatt, QLD. Bradley J McCall, MPH, FAFPHM, Public Health Physician. Queensland Health, Thursday Island, QLD. Phillip J Mills, Executive Officer, Torres Sector. Reprints: Dr J Hanna, Tropical Public Health Unit, Queensland Health, PO Box 1103, Cairns, QLD 4870. Email: troppubATcitec.qld.gov.au - Register to be notified of new articles by email - - To top of article - ©MJA1996 < URL: http://www.mja.com.au/> © 1996 Medical Journal of Australia.

Jeffery H Hanna · Scott A Ritchie · Debra A Phillip · Jack Shield · John S Mackenzie · Michael Poidinger · Bradley J McCall · Phillip J Mills

Error rates in Australian chemical pathology laboratories Mounira Khoury, Leslie Burnett and Mark A Mackay MJA 1996; 165: 128-130 For editorial comment, see Bryant Readers may print a single copy for personal use. No further reproduction or distribution of the articles in whole or in part should proceed without the permission of the publisher. For copyright permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au/>". Abstract - Introduction - Methods - Measurement criteria - Participants - Survey - Statistical analysis - Results - Participation - Transcription errors - Analytical performance - Combined error rates - Discussion - Acknowledgements - References - Authors' details Register to be notified of new articles by email - - ©MJA1996 Abstract Objective: To measure transcription and analytical errors made by Australian chemical pathology laboratories. Design: Retrospective data collection covering the period 1 November 1993 to 1 April 1994. Setting and participants: Fourteen pathology laboratories in five Australian States (seven in the public sector, and seven in the private sector). Main outcome measures: Error rates in transcribing information from request forms to computer record systems, and laboratory performance on chemical analysis. Results: Pathology laboratories had a transcription-error rate of up to 39% and an error rate of up to 26% for analytical results. The worst-performing laboratory had errors (of patient identification or results of analysis) in 46% of requests. The three best-performing laboratories achieved 85% error-free reporting, with one achieving 95%. Conclusions: Error rates in Australian pathology laboratories vary widely, but may be as high as 46% for all specimens in some laboratories. The types of errors reported were under the control of the laboratory, and would affect the accuracy of reported pathology test results, with potential adverse outcomes for patient care and inefficient use of health-care resources. There is a need to establish broader quality assurance programs and performance requirements to reduce these types of error. MJA 1996; 165: 128-130 Introduction T he Quality in Australian Health Care Study 1 described an unacceptable rate of preventable adverse events involving patients which occur in Australian hospitals. Errors introduced into the process of requesting pathology tests can adversely affect patient management and will detract from quality of care and services. 2 At best, a sample may need to be collected again to repeat the analysis, inconveniencing the patient, delaying treatment and increasing the cost. At worst, a doctor may act on incorrect results and the patient may be treated inappropriately. In its most common diagnostic setting, the process of requesting pathology tests seems simple: the doctor writes a request, the pathology laboratory interprets the request, transcribes information from the request form to its computer system, performs the analysis, and the pathologist produces a printed report for return to the doctor. This process assumes that the patient has been correctly identified, an appropriate specimen has been obtained, analysis has been correctly performed, and the results of analysis have been communicated to the original requesting practitioner. We recently examined the accuracy of one part of the process of obtaining pathology test results in a hospital environment and found that the address of the referring doctor had been incorrectly recorded on 3% of all printed reports issued, delaying or preventing delivery of the final pathology report. 3 If this rate of error were typical for the many other steps of the requesting process for pathology tests, then the total error rate in obtaining results would be extremely high. To address this question, we surveyed clinical pathology laboratories from both public and private sectors of five Australian States to determine whether error rates in pathology are as widespread and as clinically significant as our earlier study suggested. Methods Measurement criteria We identified potential indicators using national Quality Award criteria for benchmarking indicators, 4 focusing on factors affecting medical outcomes which arose from the pathology laboratory. In this paper, we report on transcription errors and analytical performance in chemical pathology quality assurance programs. Details of these criteria and how they were measured are shown in Box 1. We did not examine how laboratories functioned to deliver these outcomes. Participants We approached 18 large National Association of Testing Authorities-registered laboratories, well recognised in the industry, representing both public and private sectors, in five Australian States (Queensland, New South Wales, Victoria, Tasmania and South Australia). Survey Survey forms, which included detailed instructions and operational defini tions of the information required, were completed by the laboratories between 1 May and 31 July 1994. One hundred hand-written pathology request forms dated between 1 November 1993 and 1 April 1994 were randomly selected by the participating laboratories. We excluded request forms which also contained requests for blood transfusion or tissue pathology because some laboratories adopt more stringent identification criteria for these types of specimens. Laboratories scored the number of transcription errors (defined as any instances where the data on individual request forms were not identical to the data entered into the laboratory's computer system 5 ). Chemical pathology quality assurance (QA) data were from one cycle of analysis within the QA program (there are two or three cycles annually, depending on the program) during 1993 and 1994. Laboratories scored the total number of QA samples analysed, and the proportion of results of these analyses that lay outside the allowable limits of error of the QA program. All data, as well as a summary of the relative performance of all other participants (each assigned a number so that they were not identifiable), were returned to each laboratory for validation before final analysis. Statistical analysis Data analysis was based on the binomial distribution. 5 Calculation of combined error rates was based on the product of constituent error-free components, with the standard deviation calculated from the sum of variances of individual component errors. Results Participation Fourteen laboratories (seven public and seven private, numbered 1-14 to preserve anonymity) completed the entire benchmarking study; all five States were represented. Transcription errors Box 2 shows our findings for particular types of transcription errors. Most laboratories lay within a tight distribution clustered around median error rates of 1% to 3%. For each transcription error listed, a single outlier -- a different laboratory in each case -- performed particularly badly. The Figure shows that, while two laboratories were able to achieve overall transcription-error rates of less than 3%, four had error rates more than two standard deviations above the mean error rate (13%) of participating laboratories ( P < 0.05). The laboratory with the poorest performance reported a transcription-error rate of 39%. Analytical performance Laboratories recorded errors outside the allowable limits of error in up to 26% of analytical results. As shown in the Figure, four laboratories reported unacceptable performance more than two standard deviations above the mean rate (11.4%) of participating laboratories ( P < 0.05). Combined error rates By matching the transcription-error rate with analytical performance, we were able to measure the proportion of all pathology requests that would have been free of either type of error (Figure). Three laboratories showed superior performance compared with peers, achieving 85% error-free reporting, with one achieving 95% error-free reporting (a total error rate of less than 5%). These three laboratories represented both the public and private sectors, were all from different States, and each used a different computer system and clinical chemistry analyser. The two laboratories which showed the poorest performance reported transcription errors or unacceptable ana lytical performance in more than a third of all requests. They were both hospital laboratories from the same State. Their high total error rates were particularly influenced by transcription errors. Discussion This pilot survey of laboratory performance is the first of its kind to have been done in Australia. Previous studies have reported particular types of laboratory errors (e.g., patient ward location or address) in 0.08% 6 to 3% 3,6,7 of requests. We have confirmed that median error rates for individual types of errors in routine pathology requests are of the order of 3% 3 (see Box 2), and overall error rates can be as high as 46%. While some of the laboratories operated with few or no errors, eight of the fourteen reported significantly inferior performance (Figure). Further, our findings indicate that some laboratories may be making transcription errors in up to 39% of all request forms, and can have error rates of 9% in patient identification data and 17% in data such as sex and date-of-birth. Such error rates should be a cause of clinical concern. Risk management in pathology laboratories recognises the relationship between proper identification of specimens and the prevention of adverse patient-care-related incidents. 2 Our study was not designed to trace particular errors to final clinical outcomes, or to distinguish between errors on the basis of severity. However, it would be surprising if transcription-error rates of the magnitude we encountered did not contribute to adverse clinical outcomes. Are the errors caused by the requesting doctor, or by the laboratory? Several laboratories used direct electronic capture of patient data from a database, which should minimise errors in patient identification data arising from illegible handwriting. These laboratories did not have lower rates of transcription error for patient identification data than those relying solely on handwritten pathology requests. Indeed, the two laboratories with the highest overall rates of transcription error both obtained their patient identification data from a central database. This leads us to conclude that poor handwriting by the requesting doctor was not the major factor in high rates of transcription errors. Errors in pathological tests come at a considerable cost to the community. Expenditure on pathology investigations in Australia amounts to some $1.4 billion -- approximately 4% of total health services expenditure (Australian Association of Pathology Practices, personal communication). Incorrect tests being performed in up to 15% of cases wastes medical resources. Requesting doctors being incorrectly identified on up to 17% of requests will result in laboratories incurring unnecessary delivery costs and doctors incurring additional costs, as they will need to obtain duplicate copies of reports not delivered, and will request repeat testing for results unable to be located. We believe that most of these errors could have been prevented by the laboratories. The three best-performing laboratories in our study used different equipment and computer systems, and operated in both public and private sector environments. We therefore suggest that superior overall performance can be achieved by controlling error rates at each step in the process, and that this can be done in diverse ways. All recognised medical testing laboratories within Australia are required to be accredited, and to participate in QA programs for analytical quality. However, there are no minimum standards of performance which laboratories are required to maintain within these QA programs. There are also no Australian QA programs which monitor non-analytical aspects of pathology laboratories, such as transcription errors. We recommend that QA programs should be introduced for a range of clinically important areas of laboratory performance, such as request transcription accuracy, transport and analysis times for key analytes (e.g., potassium), rapid reporting of critical patient data, and client satisfaction, in addition to existing programs for analytical quality. We also recommend that summaries of actual and achievable performance in these QA programs be published. Without laboratory participation and satisfactory performance in such programs, doctors cannot be confident that test results are correct. Indeed, they cannot even be confident that the result was obtained for the correct patient. Lower error rates in pathology tests should lead to improved patient outcomes and less wastage of health resources. Acknowledgements We thank the staff of the participating laboratories for their assistance with this study. We are grateful to Elizabeth Benson, Jon Currie, Jeremy Chapman, Doug Chesher and Ruth Pojer for their critical comments on the manuscript. References Wilson RM, Runciman WB, Gibberd RW, et al. The Quality in Australian Health Care Study. Med J Aust 1995; 163: 458-471. Lord JT. Risk management in pathology and laboratory medicine. Arch Pathol Lab Med 1990; 114: 1164-1167. Banning J, Brown J, Hooper L, et al. Reduction of errors in laboratory test reports using continuous quality improvement (CQI) techniques. Clin Lab Management Rev 1993; 7: 424-437. Australian Quality Awards Foundation. Assessment criteria and application guidelines. Sydney: Australian Quality Council, 1994. Grant EL, Leavenworth RS. Statistical quality control. 6th ed. Singapore: McGraw-Hill. 1988. Burnett L, Banning J. Reduction of errors in laboratory test reports: comparison of continuous quality improvement techniques with laboratory information system techniques. In: Parkany M, editor. Quality assurance and TQM for analytical laboratories. Cambridge, UK: The Royal Society of Chemistry, 1995: 97-101. Chambers AM, Elder J, O'Reilly DStJ. Blunder-rate in a clinical biochemistry service. Ann Clin Biochem 1986; 23: 470-473. (Received 20 Nov 1995, accepted 22 May 1996) Authors' details Faculty of Clinical Chemistry, School of Life Sciences, University of Technology (Gore Hill Campus), Sydney, NSW. Mounira Khoury, MSc(Clin Biochem), Graduate Student. Institute of Clinical Pathology and Medical Research, Westmead Hospital, Sydney, NSW. Leslie Burnett, PhD, FRCPA, Director of Clinical Chemistry. Mark A Mackay, MSc, Hospital Scientist and Quality Facilitator. Reprints: Associate Professor Leslie Burnett, Assistant Director, Institute of Clinical Pathology and Medical Research, Westmead Hospital, Westmead, NSW 2145. < URL: http://www.mja.com.au/> © 1996 Medical Journal of Australia.

Mounira Khoury · Leslie Burnett · Mark A Mackay

Flexible sigmoidoscopy screening for colorectal cancer in average-risk subjects: a community-based pilot project John K Olynyk, Sina Aquilia, David R Fletcher and Jim A Dickinson ©MJA1996; 165: 74-76. This article has been cited in Sladden MJ, Ward JE. Australian general practitioners' views and use of colorectal cancer screening tests. MJA 1999; 170: 110-113 Readers may print a single copy for personal use. No further reproduction or distribution of the articles in whole or in part should proceed without the permission of the publisher. For copyright permission, contact the Australasian Medical Publishing Company Abstract - Introduction - Methods - Subjects - Data management - Acceptability survey - Results - Subject recruitment - Screening results - Reasons for non-compliance with screening - Discussion - Acknowledgements - References - Author's Details - Register to be notified of new articles by email - - To top of article - ©MJA; 1996 Abstract Objective: To test a pilot screening program for colorectal cancer. Design: Subjects, chosen at random and recruited by mail, were examined by flexible sigmoidoscopy. Participants and setting: Normal-risk, asymptomatic men and women aged 55-59 years recruited from the community, July to December, 1995. Main outcome measures: Number of polyps detected and cancers diagnosed, and compliance with screening. Results: Letters of invitation were sent to 3500 subjects; of these, 2881 were eligible for inclusion in the study and 342 (12%) consented to participate. A further 3.5% of non-compliant subjects attended the screening program after a telephone survey assessing reasons for non-attendance. Common reasons for non-attendance were a lack of interest (30%) or a lack of time, mainly due to work commitments (28%). A third of subjects had polyps and 46% of these were adenomas. Three subjects were found to have adenocarcinoma: in two the cancer was confined to a polyp and treated with polypectomy, and one subject underwent anterior resection (overall prevalence of cancer, 0.9%). The median depth of insertion achieved with flexible sigmoidoscopy was 55 cm (range, 25-100 cm). Median pain level (on a scale of 0 = no pain to 10 = worst pain imaginable) was 2 (range, 0-8.5), and 99% of the subjects would have the test again if required. Conclusions: Flexible sigmoidoscopy was well tolerated and had an acceptable detection rate of adenomatous polyps and early cancer. Subject compliance emerged as a major issue which requires further evaluation to maximise participation in future programs. MJA 1996; 165: 74-76 Introduction C olorectal cancer is the commonest cancer affecting both sexes and isnow the second-commonest cause of cancer-related death in both men and women. 1 Several studies have shown that screening asymptomatic populations may reduce mortality from colon cancer by up to 30%, 2-4 and recently the World Health Organization recommended screening of asymptomatic subjects beginning at age 50. 5 However, in Australia there are no uniformly agreed methods for screening asymptomatic subjects for colorectal cancer. 6 Factors such as screening efficacy, cost, subject compliance and strategies employed to evaluate positive results all influence the choice of screening test. Faecal occult blood testing for colo rectal cancer is relatively cheap, but is limited by a high rate of false positive results and poor sensitivity. 7-9 A recent report also suggests that up to half the mortality reduction observed with faecal occult blood screening may be due to chance selection for colonoscopy. 10 Flexible sigmoidoscopy has been proposed as an alternative screening test. It is more expensive but would prevent more cancer deaths than faecal occult blood testing alone. 8,11 Apart from determining the best screening methods, rates of compliance with screening programs range widely (8%-80%). 8,12 These issues, together with implications for health service resource allocation, have prompted recommendations for pilot programs to determine the efficacy of screening and compliance rates before more generalised screening is introduced. 6,8,13 The Western Australian Department of Health provided funds for such a pilot project at Fremantle Hospital. Thus, we were able to conduct a pilot community-based flexible sigmoid oscopy screening program, between July and December 1995, for colorectal cancer in normal-risk asymptomatic individuals, and in this setting determine (i) yield of screening, and (ii) subject compliance with screening and factors which influence compliance. Methods A flexible sigmoidoscopy facility dedicated to colorectal cancer screening was established at Fremantle Hospital. All procedures were performed on an outpatient basis after informed written consent. No sedation was used. After administration of a phosphate enema, procedures were performed either by a qualified gastroenterologist, or a general practitioner who was undergoing supervised training in flexible sigmoidoscopy. An Olympus TI100 colonoscope (Olympus Optical, Japan) was used, allowing insertion up to 100 cm. Biopsies were taken from polyps seen during the procedure. Subjects with biopsy-proven adenomas were advised to have a follow-up colonoscopy. A computer-generated report was issued to all subjects after the procedure, with instructions to return to their general practitioner for ongoing care. The study was approved by the Ethics Committee of Fremantle Hospital. Subjects We recruited male and female subjects aged 55 to 59 years of age using a computerised database derived from the Western Australian Electoral Commission. Letters were sent to 3500 randomly selected subjects inviting their participation. Exclusion criteria (apart from age less than 55 or greater than 59 years) were: symptoms of recent alteration in bowel habit, constipation, diarrhoea, or passage of blood with bowel motions; previous history of colonic polyps or colorectal cancer; and family history of colorectal cancer. A telephone survey of 200 subjects who did not respond to the initial letter showed that the reason for non-attendance in 14% of these subjects was that they met the exclusion criteria. Data management All data were recorded on a customised database from which reports were generated. We recorded basic demographic data, presence or absence of exclusion criteria, operator information, date of procedure, adequacy of bowel preparation, insertion depth, polyp data (number, size, pedunculated or sessile, biopsy report and date), and follow-up advice. Acceptability survey After the procedure, 77 consecutive subjects filled in a brief questionnaire, which included a standard 10-cm linear analogue pain scale. They marked a 10-cm line (labelled "0 = no pain" and "10 = worst pain imaginable") at a point which corresponded to their level of pain. Results Subject recruitment One hundred and fifty letters were returned, indicating that the subject was no longer resident at the mailing address. As 14% of non-attending subjects were found by the telephone survey to meet exclusion criteria, we estimate there were 2881 eligible subjects. Of those, 342 (12%) consented to participate in the study. There were 200 men and 142 women participants; 95% were born in Australia. Screening results Findings at flexible sigmoidoscopy are summarised in Box 1. The median depth of insertion achieved was 55 cm (range, 25-100 cm; 70% of subjects had at least 50 cm of bowel examined by flexible sigmoidoscopy. Thirty-five subjects (10%) were incompletely prepared with one enema and required a repeat bowel preparation before the procedure. Thirty-five per cent of subjects had polyps -- 46% of these polyps were adenomas, the remainder being hyperplastic or metaplastic polyps. The median adenoma size was 4 mm (range, 1-60 mm). Nineteen of the adenomatous polyps (5.6%) were at least 1 cm in size. One subject with a 6-cm sessile villous adenoma underwent anterior resection. Three subjects were found to have adenocarcinoma -- in two the cancer was confined to a polyp and treated with polypectomy, while the third required anterior resection for a cancer detected at follow-up colonoscopy. The overall prevalence of cancer in this group of subjects was 0.9%. The median pain score attributed to the procedure was 2 (range, 0-8.5). Seventy-six (99%) of these subjects would have the test again if required. Most subjects found the procedure interesting (they were able to watch on a video screen) and worthwhile. Reasons for non-compliance with screening The commonest reasons given for non-compliance were a lack of interest (30%) or a lack of time, mainly due to work commitments (28%) (Box 2). Interestingly, 16% of subjects who did not attend stated that they had either discussed the issue of bowel cancer screening to their satisfaction with their local general practitioner or had been screened for bowel cancer. Seventeen (8%) of the 200 subjects who did not attend as a result of the initial mail-out indicated that they would like to participate as a direct result of the telephone interview and were offered appointments; seven (3.5%) of these subjects have since attended for screening. Discussion The cancers detected by flexible sigmoidoscopy in our study were early cancers, but our three cases represent a detection rate of 8.8 cancers per 1000 asymptomatic subjects aged 55-59. Western Australian data for this age group predict an annual incidence of about 1 per 1000. 1 Our yield of polyps at least 1 cm in size (5.6%) is consistent with the previously reported prevalence of polyps in persons aged 55-59 14 and in asymptomatic Australian men of mean age 66 (3.8%). 15 However, the depth of insertion and number of polyps found in our study are both greater than those reported in several recent studies of flexible sigmoidoscopy: their average depth of insertion ranged from 30 to 50 cm 16-19 and polyp yield ranged from 1% to 4%. 18,19 There is little doubt that population response to screening will be a major determinant of the utility of flexible sigmoidoscopy as a screening tool for colo rectal cancer. The reasons given for non-compliance are similar to those reported for non-attendance in faecal occult blood screening programs. 20 Although the initial response in the pilot program was 12%, the survey of non-compliant subjects demonstrated a significant opportunity for improvement. An additional 3.5% of subjects could immediately be given an appointment at the time of the telephone survey of non-compliant subjects, bringing the compliance rate to 15.5%. Of the remaining reasons determined for non-compliance, most could be addressed by better education of subjects, and rescheduling of screening times to suit the work practices of potential candidates. It remains to be seen how much this would actually improve screening rates. Sixteen per cent of non-compliant subjects reported that they had either been screened for colorectal cancer or had discussed the issue to their satisfaction with their local general practitioner. This may reflect the growing public and general practitioner awareness of colon cancer screening; this has recently been reported from South Australia. 21 There is no doubt that the highest possible compliance should be aimed for, but in a society where currently only 41% of subjects with rectal bleeding seek medical attention 22 it would seem that much education needs to occur to facilitate this process. We have reported the first Australian pilot study of flexible sigmoidoscopy screening of asymptomatic subjects aged 55-59 years in which a high yield of adenomatous polyps and early cancers was found. The procedure was well tolerated. Subject compliance emerged as a major issue which requires further evaluation in order to maximise participation in future programs. This study strongly supports a more broad-scale evaluation of flexible sigmoidoscopy screening of asymptomatic subjects for colorectal cancer and polyps. Acknowledgements We wish to thank Dr Digby Cullen, Mr Graham Cullingford and the Gastroenterology Departments of Fremantle Hospital, Sir Charles Gairdner Hospital and Royal Perth Hospital; Dr Andrew Penman, formerly Chief Health Officer of the Health Department of Western Australia, and the Fremantle Division of General Practice, for their support of this study. References Dobson SK, Penman AG, and 82 others. Clinical health goals and targets for Western Australia, Vol. 2. First report of the Western Australian Task Force on State Health Goals and Targets. Perth: Health Department of Western Australia, July 1994. Mandel JS, Bond JH, Church TH, et al. Reducing mortality from colorectal cancer by screening for faecal occult blood. N Engl J Med 1993; 328: 1365-1371. Selby JV, Friedman GD, Quesenberry CP Jr, et al. A case-control study of screening sigmoidoscopy and mortality from colorectal cancer. N Engl J Med 1992; 326: 653-657 . Newcomb PA, Norfleet RG, Storer BE, et al. Screening sigmoidoscopy and colorectal cancer mortality. J Natl Cancer Inst 1992; 84: 1572-1575. Winawer SJ, St John DJ, Bond JH, et al. Prevention of colorectal cancer: guidelines based on new data. Bull World Health Organ 1995; 73: 7-10. Goulston K, St John J, Bokey L, et al. Guidelines for early detection, screening and surveillance for colo rectal cancer. 2nd edition. Sydney: Australian Gastroenterology Institute and Gastroenterological Society of Australia, 1994. Austoker J. Screening for colorectal cancer. BMJ 1994; 309: 382-386. Lieberman D. Screening/early detection model for colorectal cancer. Cancer 1994; 74: 2023-2027. Solomon MJ, McLeod RS and Canadian task force on periodic health examination. Can Med Assoc J 1994; 150: 1961-1970. Lang CA, Ransohoff DF. Faecal occult blood screening for colorectal cancer: is mortality reduced by chance selection for screening colonoscopy? JAMA 1994; 271: 1011-1013. Lieberman DA. Cost-effectiveness model for colon cancer screening. Gastroenterology 1995; 109: 1781-1790. Blalock SJ, De-Vellis BM, Sandler RS. Participation in faecal occult blood screening: a critical review. Prev Med 1987; 16: 9-18. St John J. Screening for colorectal cancer: "On your marks. . ." Med J Aust 1994; 160: 596-597. Arminski TC, McLean DW. Incidence and distribution of adenomatous polyps of the colon and rectum based on 1000 autopsy examinations. Dis Col Rectum 1964; 7: 249-261. Chapuis PH, Goulston KJ, Dent OF, Tait AD. Predictive value of rectal bleeding in screening for rectal and sigmoid polyps. BMJ 1985; 290: 1546-1548. Krevsky B, Fisher RS. Yield of rescreening for colonic polyps using flexible sigmoidoscopy. Am J Gastroenterol 1994; 89: 1165-1168. Maule WF. Screening for colorectal cancer by nurse endoscopists. N Engl J Med 1994; 330: 183-187. Renneker M, Saner H. Low-cost flexible sigmoid oscopy screening: a community demonstration and education project. J Cancer Educ 1995; 10: 25-30. Sakamoto MS, Hara JH, Schlumpberger JM. Screening flexible sigmoidoscopy in a low-risk, highly screened population. J Fam Pract 1994; 38: 245-248. Lindholm E, Berglund B, Haglind E, et al. Factors associated with participation in screening for colorectal cancer with faecal occult blood testing. Scand J Gastroenterol 1995; 30: 171-176. Weller D, Hiller J, Beilby J, et al. Screening for colorectal cancer: knowledge, attitudes and practices o f South Australian GPs. Med J Aust 1994; 160: 620-624. Crossland A, Jones R. Rectal bleeding: prevalence and consultation behaviour. BMJ 1995; 311: 486-488. (Received 6 Feb, accepted 22 Apr 1996) For editorial comment, see Solomon, page 68; see also Macrae, page 102. Authors' details University Department of Medicine and Department of Gastroenterology, Fremantle Hospital, Fremantle, WA. John K Olynyk , FRACP, MD, Senior Lecturer and Head of Department of Gastroenterology. Sina Aquilia , BA(Psych), Research Assistant. University Department of Surgery and Department of Gastroenterology, Fremantle Hospital, Fremantle, WA. David R Fletcher , FRACS, MD, Professor of Surgery, Head of Department of Surgery. University Department of General Practice, Fremantle Hospital, Fremantle, WA. Jim A Dickinson , FRACGP, PhD, Professor of General Practice. Reprints: Dr J Olynyk, University Department of Medicine, Fremantle Hospital, PO Box 480, Fremantle, WA 6160. E-mail: jolynyk AT uniwa.uwa.edu.au < URL: http://www.mja.com.au/> © 1996 Medical Journal of Australia.

John K Olynyk · Sina Aquilia · David R Fletcher · Jim A Dickinson

Prevalence of latex allergy in a dental school Constance H Katelaris, Richard P Widmer and Ross M Lazarus Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au/>". Abstract - Introduction - Methods - Results - Discussion - Acknowledgements - References - Authors' details - ©MJA1997 Abstract Objective: To determine the prevalence of latex allergy in dental workers. Design: Questionnaire survey of staff of a dental school. Setting: The Westmead Dental School, a large dental facility in western Sydney. Participants: 230 staff members of the Westmead Dental School (consisting of general and specialist dentists, chairside assistants and registered nurses, laboratory technicians, dental therapists and hygienists) received questionnaires. Main outcome measures: The prevalence of latex allergy, defined by prompt onset of hand urticaria with or without generalised symptoms, and the prevalence of hand dermatitis and other glove-related symptoms. Also, the relationship between latex allergy and associated atopic status. Results: 177 staff (77%) responded by the set collection date; 33% reported symptoms related to wearing gloves and 22% satisfied the criteria for glove dermatitis. Sixteen respondents (9%) reported characteristics suggestive of latex- glove allergy. Conclusions: Confirmation of the 9% prevalence of latex allergy among dental workers will require further studies incorporating an objective measure of IgE-mediated hypersensitivity. MJA 1996; 164: 711-714 Introduction Adverse reactions to rubber products have been recognised for many years, and irritant reactions and cell-mediated hypersensitivity reactions such as contact dermatitis are well described. The latter are thought to be caused by one or more low-molecular-weight chemical compounds added in the rubber-making process.1 It is now recognised that latex allergy is a particular problem for certain "at risk" groups, including health care workers, patients with spina bifida or other spinal cord abnormalities and patients who have had multiple operations. In addition, atopic individuals are more likely to develop IgE antibodies to latex protein with increased exposure.2 The clinical manifestations of type I hypersensitivity reactions to latex protein are wide ranging, from contact urticaria to life-threatening anaphylaxis and death. There is now little doubt that at least some episodes of intraoperative anaphylaxis have occurred because the patient has been sensitised by latex and reacts after mucosal contact with the operating staff's gloves. This has led to some institutions providing latex-free operating suites. No studies of latex allergy in Australia have been published. In this study, we examined the prevalence of latex glove-associated symptoms in the staff of a dental institution. Dental workers are an excellent group for studying the question of latex glove-related symptoms as they may wear gloves for 8-10 hours daily, 4-5 days a week, giving them a much greater degree of exposure to latex than most other health care workers. Methods All 230 staff of the Westmead Dental School, a large dental facility in western Sydney, New South Wales, were surveyed by anonymous questionnaire distributed during Feburary 1995, with a three-week collection time allocated. Personnel surveyed included general and specialist dentists, chairside assistants, dental technicians and dental hygienists. Questionnaire details The questionnaire was divided into four sections. Section A dealt with dental practice and contained questions on demographic characteristics, including age, gender, job description and years in present occupation. Section B sought information about glove use and working habits, including the number of patients seen per day, duration that each pair of gloves was worn, information about hand washing and glove changing and the type of gloves worn. Section C sought information about symptoms or problems on contact with surgical gloves. Respondents who acknowledged glove-related problems then answered detailed questions about symptoms, the time course of symptom development, non-hand-related symptoms such as rhinoconjunctivitis, asthma, angioedema, hypotension, symptoms on contact with other dipped-rubber products such as balloons, domestic gloves and condoms, and specific interventions sought by the respondent because of the symptoms. Section D was directed at all respondents and dealt with history of other allergies, including other contact dermatitis, food allergies (with specific foods listed), animal and drug allergies. Also included were questions for eliciting a history of asthma, allergic rhinitis and eczema, both directly, by symptoms, and by requesting information about medications used. Definitions Glove dermatitis: Report of the presence of two or more symptoms of itching, redness and rash (excluding hives) which had been present long term. Latex hypersensitivity: Report of the prompt onset (within 30 minutes of wearing gloves) of hand urticaria with or without the occurrence of allergic rhinoconjunctivitis, lower respiratory tract symptoms such as cough, wheeze or chest tightness, generalised cutaneous itch or urticaria, or upper-airway oedema, hypotension, dizziness or collapse. Atopy: Present if the respondent gave positive answers to any two or more questions on a history of asthma, allergic rhinitis or atopic dermatitis. Statistical analysis All statistical analysis was performed using the SAS package.3 Fisher's exact test was used to test for marginal association in all two-way tables. For other contingency tables, the chi-squared statistic was used to test for marginal association unless otherwise specified. The distribution of demographic characteristics of the staff of the Dental School was used to estimate response rates in order to test for sampling (volunteer) bias. Ethical approval Ethics approval was obtained from the Westmead Hospital Human Research Ethics Committee. Results Completed questionnaires were received from 177 of the 230 staff (77%) by the closing date. Table 1 (below) shows the distribution of non-response from the population, sampled by age group, by sex and by job category. Not all respondents answered all the demographic questions and the response rates are slightly underestimated because 2.3% of age, 8.5% of sex and 14.1% of job category data were missing. It was not possible to compare non-respondents with respondents as the questionnaires contained no personal identifying data. Year of graduation was the question most frequently not answered (32 of 177 questionnaires [18%]). Almost all of the youngest staff responded, whereas among older individuals response rates were as low as 32% for age 51 or 60. As three cells of this Table had expected counts of less than five, we used Fisher's exact test, which showed a significant association (P < 0.00001) between non-response and age group. Men were significantly more likely to respond than women (chi-squared = 26.1; P < 0.00001). The job categories with the highest non-response rates were the small group of registered nurses (58.3%) and the general dentists (43.9%). Evidence that response rate was associated with job category was weak (chi-squared = 11.1; P = 0.05), and this question was not answered by a substantial proportion of respondents. Two-thirds of the study group spent more than half their working day wearing gloves. Symptoms attributed to glove use were reported by one-third of subjects, with itch and redness being the commonest symptoms reported. Table 2 (above) compares selected demographic and allergic characteristics of the 39 subjects (22%) who satisfied the criteria for glove dermatitis with the 16 subjects (9%) fulfilling the criteria set for latex hypersensitivity. Other symptomatic and allergic characteristics of the 16 dental workers with latex hypersensitivity are compared with those of the rest of the respondents in Table 3 (below). Almost all of the individuals reporting latex-allergic symptoms also met the criteria for glove dermatitis. Nineteen per cent of the latex-allergic group reported food allergy, although none reported symptoms with foods such as avocado, banana, nuts or soy products, foods which have been described previously as cross-reacting with latex protein. Fisher's exact test was used to test the hypothesis that atopic diathesis was associated with latex hypersensitivity and glove dermatitis. Atopy was associated with both latex hypersensitivity (P = 0.014) and with glove dermatitis (P = 0.006). Subjects who reported experiencing symptoms of either glove dermatitis or latex-allergic symptoms were asked to indicate any action they had taken; of those with glove dermatitis 59% had never sought professional help and one-third of the latex hypersensitivity group had not sought medical attention. Discussion Our findings indicate a significant occupational health problem among dental personnel wearing latex gloves. In our study, 33% of those surveyed reported some symptoms with glove use; 22% met criteria for glove dermatitis and 9% for latex allergy. The distribution of non-response rates by demographic characteristics shown in Table 1 indicates that the volunteer sample was not fully representative of the study population. In particular, female staff, older staff, general dentists and registered nurses were less likely to respond. As a result of these sampling biases, our findings may not be fully generalisable to dental workers. For example, if staff experiencing symptoms were more likely to volunteer for the survey, then our rates will be overestimates of true prevalences. Our results should be interpreted with caution, and future surveys should aim to obtain more representative samples. Relying on questionnaire data alone to determine hypersensitivity reactions has obvious shortcomings. Contact urticaria with glove use may be caused by non-IgE-mediated mechanisms, so our findings may overestimate the prevalence of latex allergy. However, the occurrence of symptoms in other organ systems soon after gloves are used is highly suggestive of an IgE-mediated allergic reaction. Confirmation of this prevalence rate will require some objective measure of IgE-mediated hypersensitivity such as skin testing with appropriate extracts, or in-vitro assay of specific IgE antibodies to the latex allergens. Our prevalence rate of 9% for latex allergy among dental personnel is comparable with, although lower than, rates reported elsewhere. In a similar questionnaire survey without objective testing, Berky et al.4 reported "symptoms of an allergic nature" in 13.7% of 1043 United States Army dental officers. However, this figure included those reporting delayed symptoms as well as those reporting localised contact urticaria or generalised urticarial reactions. Furthermore, a third of those reporting symptoms were unable to be classified as having either contact dermatitis or latex allergy from their questionnaire responses. Only 25% of those reporting latex allergy in the Berky study had consulted a physician. Rankin et al.5 also conducted a questionnaire survey in a large dental facility in the US, obtaining a 15% prevalence of adverse reactions to latex gloves (Table 4). A number of studies4-6 have confirmed a relationship between atopy and latex allergy (Table 4). We also found a significant association when atopy was defined by our criteria (reported presence of any two of asthma, allergic rhinitis or atopic dermatitis). Walsh et al.7 examined factors influencing the wearing of protective gloves in general dental practice in Brisbane. Of 201 dentists who replied to a survey, 84.6% (170) reported that they routinely used gloves in their practice, compared with 13.9% (28) who reported that they did not. Reasons given for not wearing gloves included reduced sensation, reduced movement, low infection risk, skin reaction, patient acceptance and cost. Our results imply that there is a high rate of glove-related symptoms, particularly of glove dermatitis, in this dental workforce. This indicates a need to educate this occupational group about proper hand care as repeated washing, scrubbing and numerous glove changes contribute to hand irritation. Latex allergy has many implications for health care workers which extend beyond the occupational setting. Most reports of life-threatening anaphylactic reactions during surgery and other procedures have involved sensitised health care workers.8 These individuals need to know the risk they run when they themselves are patients. Mucosal contact with latex appears to be a far more potent trigger for anaphylactic reactions than cutaneous contact. People with latex allergy must be given anaesthesia and surgery in a totally latex-free environment. Atopic individuals appear to be especially at risk for sensitisation to the latex protein. Adequate counselling about occupational exposure and advice about methods of minimising the risk need to be considered in view of this and other studies. Latex gloves from different sources vary in the amount of latex protein detectable on the surface.9 Presumably, those with less cause less sensitisation and should be preferred in a workplace where glove use is mandatory. Acknowledgements We would like to thank Maggie Melink for valuable assistance and the staff of the Westmead Dental School for their cooperation. References Toner JS. Rubber. In: Fisher AA, editor. Contact dermatitis. 3rd ed. Philadelphia, Pa: Lea & Febiger, 1986: 603-643. Slater JE. Rubber anaphylaxis. N Engl J Med 1989; 320: 1126-1130. PC SAS [computer program], version 6.04. Cary, NC: SAS Institute Inc, 1991. Berky ZT, Luciano J, James WD. Latex glove allergy. A survey of the US Army Dental Corps. JAMA 1992; 268: 2695-2697. Rankin KV, Jones DL, Rees TD. Latex glove reactions found in a dental school. J Am Dent Assoc 1993; 124: 67-71. Turjanmaa K. Incidence of immediate allergy to latex gloves in hospital personnel. Contact Derm 1987; 17: 270-275. Walsh LJ, Lange P, Savage MW. Factors influencing the wearing of protective gloves in general dental practice. Quintessence Int 1995; 26: 203-209. Leynadier S, Pecquet C, Dry J. Anaphylaxis to latex during surgery. Anesthesia 1989; 44: 547-550. Yunginger JW, Jones RT, Fransway AS, et al. Extractable latex allergens and proteins in disposable medical gloves and other rubber products. J Allergy Clin Immunol 1994; 93: 836-842. (Received 19 Sep 1995, accepted 6 Apr 1996) Authors' details Department of Immunology, Westmead Hospital, Sydney, NSW. Constance H Katelaris, PhD, FRACP, Senior Consultant. Department of Paediatric Dentistry, Westmead Dental School, Sydney, NSW. Richard P Widmer, MDSc, FRACDS, Associate Professor. Department of Public Health and Community Medicine, University of Sydney, Sydney, NSW. Ross M Lazarus, MB BS, FAFPHM, Lecturer. Reprints: Dr C H Katelaris, Department of Immunology, Westmead Hospital, Westmead, NSW 2145. ©MJA 1997 <URL: http://www.mja.com.au/> © 1997 Medical Journal of Australia.

Age-specific HIV incidence among homosexually active men in Australia Matthew G Law, Philip S Rosenberg, Ann McDonald and John M Kaldor MJA 1996; 164: 715-718. This article has been published in the Medical Journal of Australia. Readers may print a single copy for personal use. No further reproduction or distribution of the articles in whole or in part should proceed without the permission of the publisher. For copyright permission, contact the Australasian Medical Publishing Company Abstract - Introduction - Methods - Results - Discussion - Acknowledgements - References - Author's Details - Table - Figure 1 - Figure 2 Register to be notified of new articles by email - To Current Issues list - ©MJA1996 Abstract Objective: To estimate age at HIV infection among homosexually active men in Australia. Design: Age-specific back-projection estimates of HIV incidence. Methods: Monthly counts of AIDS among homosexually active men diagnosed by 30 June 1994 and reported by 31 March 1995 were obtained from the National AIDS Registry and were adjusted for reporting delays. The progression rate to AIDS was estimated from a large cohort study of HIV-infected homosexual men, with adjustment for the effect of age at HIV infection and the effect of antiretroviral and prophylactic treatments. Results: The median age at HIV infection was estimated to have decreased from 31 years of age between 1982 and 1984 to between 23 and 27 years in the periods 1987 to 1989 and 1990 to 1994. Despite the trend to a younger median age at HIV infection during the current epidemic, HIV incidence was estimated to have declined in all age groups from a peak in the mid-1980s. This decline was more pronounced in the older age groups, with more modest reductions in age groups under 30 years. Conclusion: Most HIV infections among homosexually active men since 1987 appear to have occurred in men aged under 30 years. This has implications for education programs aimed at preventing HIV infection among homosexually active men. MJA 1996; 164: 715-718 Introduction A rapid increase in HIV incidence in Australia in the early 1980s (with a peak of around 3300 cases per year in the mid-1980s, followed by a rapid decline) was reported by both the National Working Group on HIV Projections in 19921 and the Evaluation of the National HIV/AIDS Strategy in 1996.2Cumulative HIV incidence to the end of 1993 was estimated to be between 13 000 to 19 000 cases, with a preferred estimate of 15 200 cases. The estimated annual incidences of HIV infection from 1981 to 1993 for homosexually active men, for heterosexual women, and for women and heterosexual men who were intravenous drug users, are shown in the Box.3 About 85% of both AIDS cases and diagnosed HIV infections in Australia have been in men who have had homosexual contact.4 Over the period of the current AIDS epidemic, it could be expected that a new generation of homosexual men has become sexually active and at risk of HIV infection. An important question, therefore, is whether and how HIV incidence among younger homosexually active men has changed over time. The method of back-projection has become the preferred method for estimating past HIV incidence, and for projecting future AIDS incidence, in most developed countries.5-7 Here, using an extension of the back-projection method,8 we estimate the age at HIV infection among homosexually active men in Australia. Methods Our analyses were based on AIDS cases diagnosed by 30 June 1994 and reported to the National AIDS Registry (NAR) at the National Centre in HIV Epidemiology and Clinical Research by 31 March 1995 in men with a history of homosexual contact, including those who were intravenous drug users. These AIDS incidence data were adjusted for the reporting delay between the time of diagnosis to the time of entry of the case on the NAR.9 All estimates of HIV incidence were adjusted for underreporting of AIDS cases to the NAR, which is currently estimated to be about 10%.3 Age-specific HIV incidence was estimated using the back-projection method suggested by Rosenberg,8 in which the rate of progression to AIDS is assumed to be associated with age.10 To reflect the uncertainty in the rate of progression to AIDS, particularly beyond 10 years following HIV infection, we used two different progression-rate distributions derived from a large-cohort study of HIV-infected homosexual men.11 A faster progression-rate distribution was based on a median "time-to-AIDS" of nine years for people aged 30 at diagnosis of HIV infection, and the rate of progression to AIDS was taken to increase by 1.042 for each year the age at HIV infection was above 30, and to decrease by 1/1.042 for each year the age was below 30. A slower progression rate was based on a median "time-to-AIDS" of 9.8 years and an age-effect of 1.037. As the effect of age on modifying the progression rate to AIDS is uncertain and the assumption of an age-effect would lower the back-projection estimate of median age at HIV infection, we also analysed the progression rates with the age-effects at both zero and half of the above values. The extended definition of AIDS adopted in Australia in January 1988 was assumed to result in a 10% increase in the rate of progression to AIDS.12 The effect of antiretroviral and prophylactic treatments on the progression rate was incorporated into the analysis by assuming that 20% of HIV-infected people were first diagnosed as HIV positive at diagnosis of AIDS and so would not have received treatment before the diagnosis of AIDS,13 and that zidovudine became available in Australia from mid-1987 and was accepted and tolerated by up to 90% of people with diagnosed HIV infection. The effect of treatment was assumed to be a modest 20% reduction in the rate of progression to AIDS and to gradually diminish during ex- tended use, consistent with randomised clinical trials of zidovudine.14-16 We also did further analyses assuming a stronger treatment effect which corresponded to a 50% reduction in the progression rate. Back-projections were conducted for five time periods (early 1977 to mid-1981, mid-1981 to mid-1984, mid-1984 to mid-1986, mid-1986 to mid-1989 and mid-1989 to mid-1994) and for five age groups (17 to 20, 21 to 24, 25 to 29, 30 to 39 and 40 to 59 years). To allow direct comparison of estimates of HIV incidence in different age groups and time periods, estimates of HIV incidence in a given age group and time period were standardised by dividing the estimated total number of new HIV infections by the product of the number of age-years and calendar-years. Results There were 4661 cases of AIDS diagnosed by 30 June 1994 and reported to the NAR by 31 March 1995 among homosexually active men. After adjusting for reporting delays, analyses were based on 4769 cases of AIDS. We did not analyse other exposure categories as there were too few AIDS cases in these categories. The patterns of HIV incidence were similar for both the faster and the slower progression-rate distributions, with a rapid increase in the annual number of HIV infections in the early 1980s to a peak of between 2600 and 3100 per year in the mid-1980s, followed by a steep decline. The faster progression rate gave a smaller estimate of the cumulative HIV incidence to 30 June 1994 than the slower progression rate: 11 800 HIV infections, compared with 14 700, respectively. Both the pattern of HIV incidence and the cumulative HIV incidence estimated by the age-specific analysis are consistent with the non-age-specific back-projections for homosexually active men shown in the Box. The median age at HIV infection was similar for both the faster and slower progression-rate distributions (Figures 1a and 1b). As the epidemic developed, there was a decline in the median age at HIV infection, from 31 years in 1982 to 1984, to 23 and 25 years for both the faster and slower progression-rate distributions, respectively, in 1987 to 1989, and to 25 and 27 years in 1990 to 1994. The age-effect of zero on the progression rate to AIDS gave similar results, showing a decline in median age at HIV infection from 34 and 33 years for both the faster and slower progression-rate distributions, respectively, in 1982 to 1984, to 24 and 26 years, respectively, in 1987 to 1989, and to 27 and 28 years, respectively, in 1990 to 1994. Analyses which assumed half the age-effect also gave similar results. Figure 1: Estimated median age at HIV infection by calendar year (a) faster progression-rate distribution, (b) slower progression-rate ditribution (see text) Although the median age at HIV infection has declined during the epidemic, HIV incidence has declined in all age groups from a peak in the mid-1980s (Figures 2a and 2b). However, this decline has been more pronounced in the older age groups; most HIV infections in recent years appear to have been in men under 30 years. HIV incidence was similar in the age groups 21 to 24, 25 to 29 and 30 to 35 years in 1982 to 1984, but by 1990 to 1994 HIV incidence was substantially higher in the 21 to 24 years age group. Figure 2: Estimated HIV incidence by age group at HIV infection and by calendar year (a) faster progression-rate distribution, (b) slower progression-rate ditribution (see text) Sensitivity analyses which assumed a stronger treatment effect (a 50% reduction in the progression rate to AIDS) gave similar results and are not shown. Discussion The decrease in the estimated median age at HIV infection among homosexually active men, as shown by our age-specific back-projection analysis, has previously been reported using similar methods in the United States,17 and has also been observed in open cohorts of homosexual men attending genitourinary medicine clinics in London between 1988 and 1994.18 Since 1991, another Australian source of information about new HIV infections has been reported cases to the NAR of newly acquired HIV infection. Diagnosed HIV infections are considered to be newly acquired if the person had a negative HIV test within a year of their positive HIV test or if a HIV seroconversion illness was diagnosed. About 200 newly acquired HIV infections are reported each year,4 and the median age of these people has been around 30 to 31 years since 1991 (more than the median age of between 25 and 27 years estimated by the age-specific back-projection analyses in our study). However, HIV incidence since 1991 has been estimated to be around 500 cases per year,3 so only about 40% of these cases are diagnosed each year as newly acquired. It is possible that this 40% is a biased sample of all new HIV infections and, in particular, slightly older than new HIV infections which are not diagnosed as newly acquired. Back-projection analyses are based on assumptions that are subject to uncertainty, in particular the assumed progression-rate distributions. The available Australian data were part of a large- cohort study of HIV-infected homosexual men,11 and indicate that the overall progression rate in homosexually active men in Australia is broadly consistent with both the faster and slower progression-rate distributions that were assumed in the age-specific back-projections. Other major sources of uncertainty are in the modifying effect of age at HIV infection and the effect of antiretroviral and prophylactic treatments on the progression rate to AIDS. The general trend of decreasing age at HIV infection was, however, a robust feature of sensitivity analyses which investigated these uncertainties, suggesting that this trend is at least qualitatively correct. Examining the history of the HIV epidemic among homosexually active men in Australia lends further support for a decreasing age at HIV infection. When the HIV epidemic began in Australia around 1980, homosexually active men of all ages were at risk of infection. As the epidemic progressed, new homosexual men were at risk of HIV infection as they became sexually active, generally at a younger age. Thus, the age distribution of homosexually active men at risk of HIV infection (and hence of those already infected) would be expected to have decreased as the epidemic progressed. The estimates of HIV incidence were standardised for the number of calendar-years and age-years in each time period and age group. This allows direct comparison of HIV incidence if the number of homosexually active men can be assumed to be constant across different age groups over the time period of the epidemic. Based on the 1991 census,19 the resident male population in Australia was fairly uniformly distributed across the age range 15 to 44 years (at about 140 000 men per age-year) but there were fewer men in older age groups. In the age range 17 to 39 years, however, direct comparison of the standardised estimates of HIV incidence appears valid, provided that the proportion of homosexual men is constant over the age range. One feature of our analyses which requires cautious interpretation is the apparent small increase in HIV infection in some age groups between 1987 to 1989 and 1990 to 1994. As few people infected with HIV in the most recent period would be expected to have progressed to AIDS, these figures are uncertain. The most appropriate interpretation is that the number of new HIV infections has been reasonably stable in all age groups between 1987 and 1994. In conclusion, age-specific back-projections suggest that the median age at HIV infection among homosexually active men has decreased over the period 1982 to 1994, and that most HIV infections in more recent years have occurred in men aged under 30. These results suggest that education programs aimed at preventing HIV infections in homosexually active men should be targeted towards younger age groups, in particular homosexually active men in their early twenties. Register to be notified of new articles by email - To Current Issues list - ©MJA1996 Acknowledgements The National Centre in HIV Epidemiology and Clinical Research is funded by the Australian National Council on AIDS through the Commonwealth AIDS Research Grants Committee. The authors thank the National HIV Surveillance Committee and the doctors who reported AIDS cases under national surveillance procedures. References National Working Group on HIV Projections. Estimates and projections of the HIV epidemic in Australia, 1981-1994. Internal technical report 1. Sydney: National Centre in HIV Epidemiology and Clinical Research, April 1992. Valuing the past . . . investing in the future. Evaluation of the National HIV/AIDS Strategy 1993-94 to 1995-96. Canberra: Commonwealth Department of Human Services and Health, 1995. National Centre in HIV Epidemiology and Clinical Research. Estimates and projections of the HIV epidemic in Australia, 1981-1997. In: Technical appendix no. 1: An epidemiological assessment of the HIV epidemic in Australia. Evaluation of the National HIV/AIDS Strategy 1993-94 to 1995-96. Canberra: Commonwealth Department of Human Services and Health, 1996. National Centre in HIV Epidemiology and Clinical Research. Australian HIV Surveillance Report, Vol. 12, No. 1. Sydney: National Centre in HIV Epidemiology and Clinical Research, 1996. Brookmeyer R, Gail MH. A method for obtaining short-term projections and lower bounds on the size of the AIDS epidemic. J Am Stat Soc 1988; 3: 301-308. Taylor JM. Models for the HIV infections and AIDS epidemic in the United States. Stat Med 1989; 8: 45-58. Becker NG, Watson LF, Carlin JB. A method of non-parametric back-projection and its application to AIDS data. Stat Med 1991; 10: 1527-1542. Rosenberg PS. Backcalculation models of age-specific HIV incidence rates. Stat Med 1994; 13: 1975-1990. Brookmeyer R, Liao J. The analysis of delays in disease reporting: methods and results for the acquired immunodeficiency syndrome. Am J Epidemiol 1990; 132: 355-365. Rosenberg PS, Goedert JJ, Biggar RJ, for the multicenter Hemophilia Cohort Study and the International Registry of Seroconverters. Effect of age-at-seroconversion on the natural AIDS incubation distribution. AIDS 1994; 8: 803-810. Biggar RJ and the International Registry of Seroconverters. AIDS incubation in 1891 HIV seroconverters from different exposure groups. AIDS 1990; 4: 1059-1066. Selik RM, Buelher JW, Karon JM, et al. Impact of the 1987 revision of the case definition of Acquired Immune Deficiency Syndrome in the United States. J AIDS 1990; 3: 73-82. Kaldor JM, French MAK. When do patients present with HIV infection? Med J Aust 1993; 158: 37-38. Volberding PA, Lagakos SW, Koch MA, et al. Zidovudine in asymptomatic human immunodeficiency virus infection: A controlled trial in persons with fewer than 500 CD4-positive cells per cubic millimeter. N Engl J Med 1990; 322: 941-949. Cooper DA, Gatell JM, Kroon S, et al. Zidovudine in persons with asymptomatic HIV infection and CD4+ cell counts greater than 400 per cubic millimeter. N Engl J Med 1993; 329: 297-303. Concorde Coordinating Commitee. Concorde: MRC/ANRS randomised double-blind controlled trial of immediate and deferred zidovudine in symptom-free HIV infection. Lancet 1994; 343: 871-881. Rosenberg PS, Biggar RJ, Goedert JJ. Declining age at HIV infection in the United States [letter]. N Engl J Med 1994; 330: 789-790. Miller E, Waight PA, Tedder RS, et al. Incidence of HIV infection in homosexual men in London, 1988-94. BMJ 1995; 311: 545. Australian Bureau of Statistics. Australia in profile. Canberra: ABS, 1993. (Catalogue No. 2821.0.) (Received 13 Nov 1995, accepted 2 April 1996) Authors' details National Centre in HIV Epidemiology and Clinical Research, The University of New South Wales, Sydney, NSW. Matthew G Law, MSc, Statistician. Ann McDonald, MPH, Senior Research Assistant. John M Kaldor, PhD, Professor of Epidemiology. National Cancer Institute, Rockville, USA. Philip S Rosenberg, PhD, Biostatistician. No reprints will be available. Correspondence: Mr M G Law, National Centre in HIV Epidemiology and Clinical Research, The University of New South Wales, 376 Victoria Street, NSW 2010. E-mail: mlaw@nchecr.unsw.edu.au Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/> © 1996 Medical Journal of Australia.

Matthew G Law · Philip S Rosenberg · Ann McDonald · John M Kaldor

Limited adverse occurrence screening: using medical record review to reduce hospital adverse patient events Alan M Wolff Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au/>". Abstract - Introduction - Methods - Results - Discussion - Acknowledgements - References - Authors' details - - ©MJA1997 Abstract Objectives: To determine whether continuous detection of adverse patient occurrences followed by analysis and medical intervention can alter the rate of adverse occurrences. Design and participants: 15 912 patients discharged from one hospital were reviewed in two stages. Medical records were screened retrospectively by medical records staff for one or more of eight general patient outcome criteria. Those that screened positive for the criteria were reviewed by one of four doctors. If an adverse occurrence was confirmed, further analysis and recommendations for action to prevent its recurrence were made at meetings of the four doctors, and forwarded to a committee of visiting medical officers who decided on the appropriate course of action. Setting: A rural base hospital in Horsham, Victoria, between July 1991 and June 1994. Main outcome measures: The rate and severity of adverse patient occurrences in each year. Results: 1465 records were screened positive for one or more criteria, and an adverse patient occurrence was confirmed in 155. 88 cases were determined to be minor or not preventable and further action (mostly by changes to hospital policies) was recommended for the remaining 67. Over the three years, the number of adverse occurrences fell from 69 (1.35% of all patient discharges in the first year) to 33 (0.58% of all patient discharges in the third year) ( P < 0.0001) and there was no significant change in severity. Conclusions: The rate of adverse patient occurrences can be significantly reduced by their continuous detection using retrospective screening in conjunction with review, analysis and action to prevent recurrences. MJA 1996; 164: 458-461 Introduction The objective of medical quality assurance programs is to improve the quality of care provided to patients. However, "quality medical care" has proved difficult to define, leading some programs to attempt to detect "disquality", or events that should not happen under optimal conditions.1 Quality, then, may be defined as the absence or lowering of the rate of adverse patient events or occurrences. Many preventable adverse patient events occur in hospitals. The Quality in Australian Health Care Study, which reviewed over 14 000 patient admissions in 28 hospitals in New South Wales and South Australia, found 16.6% involved an adverse event; half of these were assessed as highly preventable.2 The Harvard Medical Practice Study, a review of over 30 000 inpatient medical records from 51 acute-care hospitals in the United States, showed that adverse events occurred in 3.7% of hospitalisations and that many of these were the result of substandard care.3 Both these studies used methods that required substantial resources in time and money to detect adverse patient events, and neither looked at the effect of intervention in preventing recurrence of an adverse event. Limited adverse occurrence screening is a continuous process of retrospective screening and review of inpatient medical records to detect adverse patient occurrences.4 It is referred to as "limited" because only eight general patient outcome criteria are used. When an adverse occurrence is found, appropriate action is taken to prevent its recurrence and the success of the action is determined by ongoing monitoring.4 Thus, the quality assurance feedback loop is securely closed. This study was designed to determine whether limited adverse occurrence screening could reduce the number and rate of adverse occurrences and therefore improve the quality of patient care. Methods The study was undertaken at Wimmera Base Hospital in Horsham, 300 km north-west of Melbourne. There are 11 specialists and 14 general practitioners on the medical staff who treat between 5000 and 6000 inpatients per year. Four doctors were chosen by the Hospital Medical Staff Group to be medical reviewers and to form a Patient Care Committee. All doctors held dual positions in the hospital and had postgraduate clinical qualifications. They were a physician (also Director of Intensive Care), a surgeon (also Chairman of the Medical Staff Group), a general practitioner (also Director of Postgraduate Education) and the Medical Director (also Director of the Accident and Emergency Department). The medical records for all inpatients discharged between 1 July 1991 and 30 June 1994 were screened by medical records staff using eight general patient outcome criteria (Box 1, below). An adverse patient occurrence analysis form was attached to any medical record that met one or more of the criteria. The record was reviewed by the doctor allocated to that criterion, who evaluated the care given to determine if an adverse patient occurrence had arisen before or during admission, and then completed the form. Adverse occurrences for which patients had had previous admissions were excluded. 1: General patient outcome criteria used for screening of medical records Death. Return to operating theatre within 7 days. Transfer from general ward to intensive care unit. Unplanned readmission within 28 days of discharge. Cardiac arrest. Transfer to another acute-care facility. Length of stay greater than 35 days (reduced to 21 days in 1993-1994). Theatre booking cancelled. An adverse patient occurrence was defined as "an untoward patient event which, under optimal conditions, is not a natural consequence of the patient's disease or treatment".1 I have described the limited adverse occurrence screening method in detail in an earlier paper.4 Medical care was evaluated using a six-point scale,5 to help the reviewer decide whether an adverse patient occurrence was caused by medical management: 1 = little or no evidence, 2 = slight evidence, 3 = not likely (less than 50:50 odds but a close call), 4 = more likely than not (greater than 50:50 odds but a close call), 5 = strong evidence, 6 = virtually certain. A score of four or more on this scale was regarded as an adverse patient occurrence. Severity of adverse occurrences was graded on a seven-point scale:1 0 = minor severity, 1 = minor temporary, 2 = minor permanent, 3 = major temporary, 4 = major permanent, 5 = potential major or major continuing, 6 = death. The medical reviewer wrote brief notes about the case for the Patient Care Committee. Adverse occurrences were discussed at the Committee's bimonthly meetings and recommendations for further action relating to patient care were made and forwarded to the Medical Staff Group, which consisted of all visiting medical officers in the hospital and the Director of Medical Services. All data from the adverse patient occurrence analysis forms were entered into a database program developed from the Clipper Dbase Compiler software package.6 A chi-squared test was used for statistical analysis, and confidence intervals were calculated for odds ratios using standard methods.7 Results A total of 15 912 inpatients were discharged between 1 July 1991 and 30 June 1994. Using the eight general patient outcome criteria, 1465 records (9.21%) were screened positive for one or more criteria by medical records staff. The commonest criteria among these were unplanned readmission of a patient within 28 days of discharge (3.4% of all records screened) and transfer of a patient to another acute-care facility (2.8% of all records screened) (Box 2). A medical record was most likely to be subsequently confirmed as containing an adverse patient occurrence when it was selected by the criterion "return to operating theatre within seven days" (odds ratio = 3.98; 95% confidence interval, 2.15-7.37) (Box 2). After medical review, 155 records (0.97% of all records screened) were found to contain an adverse patient occurrence using the six-point scale (Box 3). Of these adverse occurrences, 45 were minor and 110 were major (Box 4). Of the 155 adverse patient occurrences confirmed on medical review, no further action was recommended by the Patient Care Committee in 88 cases (56.8%) (i.e., the adverse occurrence was considered to be not preventable or of minor significance). Recommended action for the other cases included changing the relevant hospital policy; presenting the case at a postgraduate meeting; undertaking a quality assurance program to investigate the adverse occurrence in detail; discussion with, or counselling of, the doctor involved; and, rarely, review of the doctor's clinical privileges or reporting the case to the hospital's insurers. Over the three-year period of the study, 66 recommendations were made by the Patient Care Committee and almost all were accepted by the Medical Staff Group and became hospital policy. Changes in hospital policies were both clinical and administrative. Clinical policy changes included restricting some drug prescribing; revised protocols for reporting vital signs; eliminating use of multidose drug vials; formulating guidelines regarding fitness for general anaesthesia; and developing protocols for managing patients with alcohol withdrawal, haematemesis and melaena, and for patients who have had a cerebrovascular accident or who require analgesia. Administrative policy changes included sending copies of referral letters when patients were transferred to other hospitals; sending private antenatal notes to the obstetric ward before the patient's confinement; redesigning the preadmission form to allow consent for procedures to be obtained in the consultant's room; and routinely including a copy of the death certificate in the medical record (if the patient had died in hospital). (Examples of the types of adverse occurrences, more detailed recommendations for further action and their subsequent reduction in incidence are given in an earlier paper.4) The adverse patient occurrences were grouped by year to determine whether the actions instigated had any effect on the subsequent rate of adverse occurrences. The rate of adverse patient occurrences fell from 69 in the first year (1.35% of all patient discharges in that year) to 33 in the third year (0.58% of all patient discharges in that year) (Box 4). The proportion of adverse occurrences fell significantly with time (chi-squared = 17.11; df = 2; P = 0.0002) and this trend was linear (chi-squared = 16.87; df = 1; P< 0.0001). When the severity rating of adverse events was divided into minor (severity score 0-2) and major (severity score 3-6), there was no significant change in the severity of adverse patient occurrences between the first, second and third years of the study (Box 4). Also, the proportion of adverse patient occurrences detected in each year by screening did not alter significantly over time for patient age, sex or insurance status (Box 5). The commonest major diagnostic categories, using the ICD-9 classification,8 in which patients had adverse occurrences were injury and poisoning, followed by digestive and circulatory disorders (Box 6, below). Patient characteristics such as sex and age did not change significantly during the three years of the study, but the proportion of inpatients privately insured fell from 26.6% to 24.3% (chi-squared = 10.24; df = 2; P< 0.01). Discussion Limited adverse occurrence screening has been shown to be effective in detecting approximately 50% of adverse patient occurrences,9 a much higher proportion than found by traditional medical quality assurance programs. This study has shown that it is also possible to subsequently reduce the number of adverse occurrences by more than 50% over a three-year period. These results indicate that use of a more complex and expensive screening system is not required to achieve a significant reduction in adverse occurrences. Adverse occurrence screening has been shown to be valid and reliable, with a high level of agreement between reviewers as to whether a patient has had an adverse occurrence.10 Although in this study each medical record was reviewed by only one doctor, other studies using a similar methodology and rating scale have shown high agreement.5 Limited adverse occurrence screening is efficient as it requires the review of the medical records of slightly less than 10% of all patients discharged, costs only 0.1% of an acute-care hospital's total budget, and is fast and accurate (false positive rate, 2.0%; false negative rate, 0.4%).9 In this study, 9.21% of medical records were screened positive for one or more of the eight general patient outcome criteria and an adverse occurrence was confirmed in 0.97%. Little or no clinical judgement was required in the screening process. This compares with a rate of 8.4% (confirmed in 0.73%) in a study using similar screening criteria in a medium-sized New South Wales hospital.11 In the Quality in Australian Health Care Study, potential adverse events were detected in 43.7% of the medical records on initial screening (a much higher rate than in other studies) using 18 criteria, some of which required clinical judgement.2 Adverse events were confirmed in 16.6%, although, unlike in this study, 49% of these occurred before the sample admission. An average rate of potential adverse events of 13.2% was found in a study of 146 Veterans Affairs Medical Centers in the United States that used nine screening criteria.12 There was considerable variation between centres, with a 25th percentile of 8.6% (confirmed in 1.7% of records) and a 75th percentile of 27.2% (confirmed in 7.9% of records). In the Harvard Medical Practice Study, potential adverse events were detected on initial screening in 25.9% of medical records using 18 screening criteria.13 Adverse events were confirmed in 0.2% to 7.9%, depending on hospital complexity and location, with the rate in rural hospitals being 1%.13 Limited adverse occurrence screening can be adapted to all sizes of hospital. It has recently been introduced into 10 small hospitals in central western Victoria by the Division of General Practice in that area working with the Monash University Centre for Rural Health in Moe, Victoria. In larger hospitals, limited adverse occurrence screening could be introduced on a departmental basis. The program could be enhanced by combining its retrospective medical record review with prospective critical incident reporting. In the United States, adverse occurrence screening and incident reporting both detected a substantial number of adverse events; however, there was less than a 50% overlap in the adverse events detected by each method when used concurrently.14 Thus, a program that simultaneously uses both methods may detect the largest pool of adverse occurrences for analysis and development of preventive strategies. Acknowledgements I wish to thank Mr Ian Campbell, Dr David Leembruggen and Dr Grant Phelps for their enthusiastic participation in the Patient Care Committee; Mrs Cathy Dooling, Chief Medical Records Administrator, and her staff, for their support with the screening program; Mr Kieran Loughran, Computer Systems Officer, for assistance with data collection; and Mrs Naomi Uytdehaag for preparing the manuscript. References Craddick JW, Bader B. Medical management analysis: a systematic approach to quality assurance and risk management. Auburn (CA): Joyce W. Craddick, 1983. Wilson RM, Runciman WB, Gibberd RW, et al. The Quality in Australian Health Care Study. Med J Aust 1995; 163: 458-471. Brennan TA, Leape LL, Laird NM, et al. Incidence of adverse events and negligence in hospitalized patients. N Engl J Med 1991; 324: 370-376. Wolff A. Limited adverse occurrence screening: a medical quality control system for medium sized hospitals. Med J Aust 1992; 156: 449-452. Hiatt HH, Barnes BA, Brennan TA, et al. A study of medical injury and medical malpractice: an overview. N Engl J Med 1989; 321: 480-484. Clipper [computer program]. Version 5.0. Los Angeles: Nantucket Corporation, 1990. Daly LE, Bourke GJ, McGilbray J. Interpretation and uses of medical statistics. Oxford: Blackwell Scientific Publications, 1991: 398-424. US Department of Health and Human Services. The international classification of diseases. 9th revision. Clinical modification (ICD-9-CM). 3rd ed. Bethesda, Md: DHHS, 1989. Wolff A. Limited adverse occurrence screening: an effective and efficient method of medical quality control. J Qual Clin Pract 1995; 15: 221-233. Panniers TL, Newland J. The adverse patient occurrence inventory: validity, reliability and implications. Qual Rev Bull 1986; 12: 311-315. Britton S. A hospitalwide outcome study. Aust Clin Rev 1991; 11: 132-135. Goldman R, Walder DJ. An initial assessment of the Veterans Affairs Occurrence Screening Program. Qual Rev Bull 1992; 18: 327-332. 13. Brennan TA, Herbert LE, Laird NM, et al. Hospital characteristics associated with adverse events and substandard care. JAMA 1991; 265: 3265-3269. 14. O'Neil AC, Petersen LA, Cook EF, et al. Physician reporting compared with medical record review to identify adverse medical events. Ann Intern Med 1993; 119: 370-376. (Received 2 Sep 1995, accepted 2 Feb 1996) Authors' details Wimmera Base Hospital, Horsham, VIC. Alan M Wolff, FRACGP, MBA, Director of Medical Services, and Director of the Accident and Emergency Department. Reprints: Dr A M Wolff, Medical Administration, Wimmera Base Hospital, Baillie Street, Horsham, VIC 3400. ©MJA 1997 <URL: http://www.mja.com.au/> © 1997 Medical Journal of Australia.

Alan M wolff

Suspected snakebite in children: a study of 156 patients over 10 years Helen J Mead and George A Jelinek Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au/>". Abstract - Introduction - Methods - Results - Discusssion - References - Authors' details - - ©MJA1997 Abstract Objective: To describe the epidemiology and clinical features of children presenting to an emergency department with suspected snakebite. Design: A retrospective study of patient records. Setting: An emergency department of a children's teaching hospital (Princess Margaret Hospital) in Perth, Western Australia. Participants: All children attending the emergency department from 1984 to 1993 with suspected snakebite. Main outcome measure: Clinical and laboratory evidence of envenomation. Results: Over the decade studied, 156 children (mean age, six years and eight months) presented with suspected snakebite; over two-thirds (68%) were boys. In at least 31% of cases, no appropriate first aid had been applied. Only 14 children were envenomed according to clinical and laboratory criteria: 10 of these had coagulopathy; one of the 10 also had rhabdomyolysis. A Venom Detection Kit was used in 117 children. The test gave a positive result in 21 children (13%). Antivenom was given to 18 children, 14 of whom were definitely envenomed. Four of the envenomed children returned a negative result of Venom Detection Kit testing at all sites tested, and in five patients not clinically envenomed the urine specimen tested positive with the Venom Detection Kit (presumably a false positive result or subclinical envenomation). Of the 156 children, 130 were admitted to hospital, and 26 were discharged directly from the emergency department. All children recovered completely. Conclusions: (i) Many children did not receive appropriate first aid for snakebite; (ii) Most children with suspected snakebite presenting to the emergency department were not envenomed; (iii) Envenomation was best diagnosed by clinical features and laboratory investigations, with the Venom Detection Kit being used to determine the appropriate antivenom; (iv) Discharging children directly from the emergency department is not recommended. MJA 1996; 164: 467 Introduction Three major Australian studies of snakebite in children have been published.1-3 Two were from south-east Queensland1,2 and the third from Victoria.3 No similar studies have been reported from Western Australia, but one has been published on patterns of envenomation in 193 adults admitted to Perth teaching hospitals.4 There are also no published data on children presenting to Australian emergency departments with snakebite. Our aim was to describe the presenting features, treatment and outcome in children with suspected snakebite attending an emergency department. We also examined aspects of the use of the Venom Detection Kit, which was widely used as an adjunct in the diagnosis and management of these children. Methods We studied the records of all children presenting to Perth's Princess Margaret Hospital for Children with suspected or definite snakebite between 1 January 1984 and 31 December 1993. If parents or other carers had a reasonable suspicion that a child may have been bitten by a snake, this was classified as "suspected snakebite", and in "definite snakebite" a reliable history was available of a snake striking the child (whether or not envenomation occurred), or there was clinical and/or laboratory evidence of envenomation in circumstances consistent with snakebite. To ensure all records were found, multiple data sources were accessed, including hospital morbidity coding for inpatient admissions; intensive care unit records; and emergency department records. Data extracted from the records were entered onto a Microsoft Access 2.0 database to assist with analysis.5 To facilitate a comparison with the study in adults from Perth hospitals,4 data on patients' snakebite history and envenomation status were extracted and patients were grouped in the categories listed in the Perth study4 and shown in Box 1. Systemic envenomation was deemed present if there was clinical (vomiting, abdominal pain, or neurotoxic effects -- ptosis, convulsions, or difficulty with breathing or swallowing) or laboratory evidence (coagulopathy, haemolysis, rhabdomyolysis or renal failure). Results Over the 10 years, 160 children presented to the Emergency Department at Princess Margaret Hospital with suspected snakebite. Patient records were available for 156 children. The snake was brought in with the patient for identification on 16 occasions (on one occasion the snake was still alive!). Thirty-one children were admitted to the Intensive Care Unit, 87 to a general ward, 12 to the Emergency Department observation ward and 26 were discharged directly from the Emergency Department. Age and sex distribution The mean age of the children was six years and eight months (range, 15 months to 14 years 4 months), and over two-thirds (68%) were boys. Athough there was an even age distribution among children who were envenomed, there were 46 (29%) toddlers (less than three years) among the children presenting. Location Most snakebites occurred in the victims' garden (59 cases; 38%) or surrounding suburban bushland (51 cases; 33%). Eight (5%) occurred in a house or outbuilding and 26 (17%) children were bitten in open country. The location of the remaining 12 (7%) was not specified. Seasonal distribution Most children presented in the summer months, with very few presentations during winter; only three of the 14 children who were envenomed were bitten outside the months of October to April. Bite site Most children were bitten on a limb (lower limb: 103 cases, 66%; upper limb: 43 cases, 28%). There was one bite to the torso and one to the head, with the site not recorded in eight cases. Puncture marks were noted in 81 cases (52%). First aid It was often difficult to determine from the patient records whether first aid had been applied. However, in 39 cases it was clearly documented that no first aid was used, and inappropriate first aid (such as washing the site or use of an arterial tourniquet) was recorded in 10 cases (i.e., at least 49 children [31%] did not have effective first aid). The pressure- immobilisation first aid technique was used in 75 children (48%), although in some it was noted that the bandage had been applied only loosely or the limb was not fully immobilised. There was no record of whether first aid was applied in 32 children (21%). In some cases first aid measures were inappropriately left in place for a prolonged period after reaching hospital. Envenomation Fourteen children had systemic envenomation and 17 possible systemic envenomation according to the criteria used in this study (Box 1). The details of the clinical features, management and outcome of the 14 envenomed children are summarised in Box 2. In two children with possible envenomation, laboratory coagulation tests gave values just outside the normal range; both had an uneventful course and were not given antivenom. Four other child ren classified with possible envenomation received antivenom early for non-specific symptoms, without confirmatory laboratory evidence of envenomation. Venom detection Of the 117 cases in which the Venom Detection Kit was used, a positive result was obtained in 21 children (12 from wound swabs, 10 from urine, and four from blood). In nine of these child ren with no evidence of systemic envenomation, venom was detected in urine in five, and in skin swabs in the other four. In a child with borderline coagulopathy, the Venom Detection Kit gave a positive result in blood, but a negative one in urine. Another child treated for possible envenomation tested positive for venom at the "bite site", but tests of urine and blood gave a negative result with the Venom Detection Kit (Case D under "Use of antivenom"). The venom type detected by the Venom Detection Kit in envenomed patients is shown in Box 2. Use of antivenom Antivenom was given to 18 children (polyvalent in eight cases, brown snake in seven and tiger snake in five; two patients received more than one type of antivenom). Four children who were given antivenom may not have been envenomed. Case A: An eight-year-old boy with a witnessed bite received antivenom for regional lymphaden o pathy and headache. No venom was detected at the bite site, nor in blood or urine. Case B: A 10-year-old girl (no snake was seen) had a negative result of a Venom Detection Kit test of a bite site, and urine and coagulation studies showed no abnormality, but she was given antivenom because of symptoms of tiredness and non-specific weakness. Case C: A nine-month-old girl who was crying and vomiting and noted to have a mark on her arm was given polyvalent antivenom before transfer to Princess Margaret Hospital. No venom detection tests were undertaken. Her symptoms of fever and intermittent vomiting were subsequently thought to be due to a viral illness. Case D: A six-year-old girl had tiger snake venom detected at a possible bite site (but no venom detected in blood or urine). She was given tiger snake antivenom for symptoms of headache, fever, abdominal pain and nausea. A groin abscess was noted the next day, which may possibly have been the cause of her illness. Other supportive treatment Three children were administered fresh frozen plasma. No child required artificial ventilation. Outcome All children were discharged well from hospital; no permanent morbidity was recorded. Discusssion As in the previous epidemiological studies of snakebite in children in Australia,1-3 most of the children who presented to hospital with suspected snakebite were not envenomed (Box 3). In our study the over-representation of toddlers in the children presenting, despite an even age distribution of children with envenomation, probably reflected heightened parental concern and the difficulty obtaining a history from this age group. Patterns of envenomation and treatment for snakebite in Perth children were similar to those reported previously in adults.4 The sex distribution of victims, the seasonal pattern of envenomation and the site of bites were also similar. The venoms of the two snake genera responsible for most bites in Perth, Pseudonaja (brown snake) and Notechis (tiger snake), have powerful procoagulants, and coagulopathy was present in most (71%) of the envenomed patients. Among Perth snakes, only the tiger snake produces myolysis, and only one patient in this series had rhabdomyo lysis. Despite local differences in fauna, these findings are very similar to those in children with snakebite in Victoria.3 Despite continuing confirmation of the great efficacy of the pressure-immobilisation first aid technique in delaying venom spread,6,7 it is disturbing that this method is still not being used widely. In many cases it is also being applied incorrectly. More public education on first aid in snakebite is needed. The role of the Venom Detection Kit in patients with suspected snakebite attending emergency departments is discussed in Box 4. Although it appeared that no child came to harm after discharge from the Emergency Department, this practice is fraught with danger, as a case from 1973 illustrates. A two-year-old girl with restlessness and dry retching presented to hospital with an unclear history; the possibility of snakebite was raised by the parents. The examining medical officer concluded that she had been bitten by an insect, no investigations were ordered and she was discharged. The next morning she was found dead in bed, and it was later confirmed that tiger snake envenomation had been the cause of death. The Coroner found that there had been a lack of care on the part of the hospital, contributing to her death.10 In most children presenting to an emergency department there is no way of determining absolutely whether a venomous snakebite has occurred. There are special difficulties in obtaining a reliable history from young children and it may be tempting to use a negative result of a Venom Detection Kit to facilitate early discharge. Indeed, a number of children in this study were discharged from the Emergency Department without laboratory investigations, apart from use of the Venom Detection Kit. However, all children in whom snakebite is suspected, whether a snake was seen or not, should be admitted to hospital for observation and investigation (including coagulation profiles). In a number of cases of envenomation in our series, no snake bite was observed, and in two cases no snake was seen. Discharging children with suspected snakebite directly from emergency departments without a period of observation is not recommended. References Munro JGC, Pearn JH. Snake bite in children. A five year population study from South-East Queensland. Aust Paediatr J 1978; 14: 248-253. Jamieson R, Pearn J. An epidemiological and clinical study of snake-bites in childhood. Med J Aust 1989; 150: 698-702. Tibballs J. Diagnosis and treatment of confirmed and suspected snake bite. Implications from an analysis of 46 paediatric cases. Med J Aust 1992; 156: 270-274. Jelinek GA, Hamilton T, Hirsch RL. Admissions for suspected snake bite to the Perth adult teaching hospitals, 1979 to 1988. Med J Aust 1991; 155: 761-764. Microsoft Access [database]. Version 2.0. Redmond, WA: Microsoft Corporation, 1989-1994. Howarth DM, Southee AE, Whyte IM. Lymphatic flow rates and first-aid in simulated peripheral snake or spider envenomation. Med J Aust 1994; 161: 695-700. Sutherland SK. The pressure immobilisation technique. Med J Aust 1994; 161: 700-701. CSL Diagnostics. Snake venom detection kit. Product information leaflet. Melbourne: CSL Diagnostics, 1992. Wentworth B, Moisidis A, Jones S. Performance of the new snake venom detection kit at high and low concentrations [abstract]. Proceedings of the 22nd Annual Scientific Meeting of the Australasian Society of Immunology; 1992 Dec 2-4; Auckland. Parkville: Australasian Society of Immunology, 1992. Snake and lack of care killed girl. The West Australian 1973 19 Jun: 3 (col. 3, 4 and 5). (Received 6 Jul, accepted 20 Dec 1995) Authors' details Department of Emergency Medicine, Fremantle Hospital, Fremantle, WA. Helen J Mead, FRACP, FACEM, Staff Specialist; formerly, Senior Registrar, Intensive Care Unit, Princess Margaret Hospital for Children, Perth, WA; George A Jelinek, MD, FACEM, Assistant Director and Staff Specialist. No reprints will be available. Correspondence: Dr George A Jelinek, Department of Emergency Medicine, Fremantle Hospital, PO Box 480, Fremantle, WA 6160. ©MJA 1997 <URL: http://www.mja.com.au/> © 1997 Medical Journal of Australia.

Helen J Mead · George A Jelinek

Teaching hospital medical staff to handwashJames Tibballs Electronically published Tuesday April 30 1996 This article was published in the Medical Journal of Australia on 1 April 1996. Readers may print a single copy for personal use. No further reproduction or distribution of the article in whole or in part should proceed without the permission of the publisher. For copyright permission, contact the Australasian Medical Publishing Company Abstract - Introduction - Methods - Results - Group performance - Cohort performance - Discussion - Author's Details - Figure - Table 1 - Table 2 - - ©MJA1996 AbstractObjective: To increase the frequency of handwashing by medical staff. Design: A prospective study of handwashing before and after patient contact. Setting: A paediatric intensive care unit in a tertiary hospital. Participants: 61 intensive care unit medical staff and visiting medical staff. Interventions: A five-phase behaviour modification program: (i) unobtrusive observation for four weeks to obtain a baseline handwashing rate; (ii) overt observation for five weeks (preceded by written advice); (iii) overt observation continued for four weeks with performance feedback; (iv) all observation and feedback discontinued for seven weeks; and (v) unobtrusive observation for five weeks to obtain a residual rate. Results: 939 patient contacts were observed. The baseline handwashing rates before and after patient contact were 12.4% and 10.6%, respectively. During overt observation, the respective rates increased and plateaued at 32.7% and 33.3%, but increased further (to 68.3% and 64.8%) during the period of performance feedback. The residual handwashing rates, observed unobtrusively seven weeks after the cessation of performance feedback, were 54.6% before and 54.9% after patient contact. Conclusions: Performance feedback is moderately effective in training hospital medical staff to handwash. MJA 1996; 164: 395-398 IntroductionHandwashing is one of the most important measures for preventing and controlling nosocomial infection.1-4 Despite this, handwashing practices before and after patient contact by all hospital staff, and especially by physicians, are poor.5-9 Educational programs to improve handwashing by increasing awareness of nosocomial infection have had limited success,10-12 suggesting that an innovative approach is needed.13 A training program for nurses with observation and performance feedback as a behaviour modification technique was successful in the short term, but the relative effects of observation and performance feedback were inseparable.14 My study assessed the frequency of handwashing by medical officers in association with patient contact and determined the effects of observation and performance feedback. MethodsThe study was conducted over a five-month period in the Intensive Care Unit (ICU), Royal Children's Hospital, Melbourne, and was approved by the hospital ethics committee. The ICU is an 18-bed multidisciplinary unit treating critically ill infants and children. During the study, 807 patients were admitted: 37% had undergone cardiac surgery, 27% had respiratory illnesses, 9% had general medical illnesses, 8% had newborn medical and surgical illnesses, 8% had trauma, and 8% had undergone neurosurgery and 3% general surgery. Mechanical ventilation was provided for 84% of patients. Most had invasive monitoring or therapeutic devices inserted into peripheral arteries, peripheral or central veins, the thoracic cavity, the urinary bladder or the extradural space. The mortality rate was 5.9%. The subjects of the study were any medical officers who made hand contact with any patient in the ICU. The ICU is newly constructed and comprises four rooms adjacent to each other along a corridor. Windows enable vision between rooms and into each room from the corridor. Handwashing basins are located in each room within two to three metres of each bed and in the corridor. A choice of handwashing solutions are provided at each basin. During the study these were: (i) a mixture of 1% chlorhexidine gluconate, 70% ethyl alcohol and emollients; (ii) 2% aqueous chlorhexidine gluconate; (iii) 7.5% aqueous povidone-iodine; and (iv) domestic bar soap. Paper-towel dispensers are located at each basin. I observed patient contact and handwashing practices of medical officers during ward rounds; at other times this observation was by instructed members of the nursing staff. Observations were made between the hours of 7 am and 6 pm on weekdays. Handwashing was regarded as any action to cleanse the hands with water and one of the available handwashing agents, or with a handwashing agent alone. No judgement was made about the duration or efficacy of the handwashing technique. Observations were recorded with the names of subjects and the patients involved. However, anonymity was preserved for data analysis and feedback purposes. Patient contact was defined as any contact by the hands of a medical officer with a patient's skin or an indwelling invasive device during a procedure in which the hands could be contaminated with the patient's blood, secretions or excretions. Contact with bed linen, bed frames, medical records or monitoring equipment was not regarded as patient contact. Typical patient contact involved procedures such as examining wounds, inserting intravenous or arterial catheters, aspirating endotracheal tubes, performing echocardiographic examinations, auscultating the chest, palpating the chest or abdomen, manipulating chest drains or urinary catheters, inserting tracheal or gastric tubes, and withdrawing blood from intravascular catheters. Handwashing was assessed before and after contact with a patient. Handwashing was not recorded if the subject was not observed immediately before patient contact, or could not be observed after contact until handwashing had been performed, or contact with another patient had occurred. Departure from the ICU area without handwashing was regarded as failure to handwash. Contact by the subject with his or her own skin, secretions or a mucous membrane (e.g., nasal mucosa) after handwashing but before patient contact was registered as failure to handwash. Medical officers were not requested to handwash, and the ICU did not have any information about handwashing displayed (other than the performance feedback when this part of the study was reached). The behaviour modification program was divided into five phases1. Weeks 1-4: unobtrusive observation (only hospital personnel involved in the study knew this was happening). At the end of this phase, 19 medical officers who worked in the ICU or visited frequently were requested verbally to estimate their own handwashing rates before patient contact. 2. Weeks 5-9: overt observation; this was preceded by written advice to all medical staff of the intention to study handwashing in ICU. Subjects were not informed which aspect of handwashing was to be studied, although, if requested, information was not to be withheld (no medical staff requested clarification). 3. Weeks 10-13: overt observation with performance feedback; at the beginning of this phase all results collected thus far were displayed as brightly coloured histograms on 40 x 60 cm sheets of paper showing the group percentage handwashing rate before and after patient contact. These were placed in strategic locations used by the medical staff in ICU, but were out of sight of patients and visitors. Data were updated weekly for the four weeks. After two weeks of performance feedback, results of group data collected up to that time were mailed to the medical officers. 4. Weeks 14-20: observations and feedback were discontinued. 5. Weeks 21-25: unobtrusive observation, after which these data were added to the histograms displayed in the ICU. Handwashing by members of the cohort who were requested to estimate their own handwashing rate and who participated in all phases of the program was analysed separately and is also reported here. ResultsGroup performanceSixty-one medical officers were observed making 939 patient contacts. Twelve were full-time senior or junior ICU staff, and the remainder full-time or part-time senior staff from other disciplines or junior full-time staff. Half the observations (470/939) were made by the investigator, and half by nursing staff. The aggregate handwashing rates before and after patient contact during phases of the program are presented in The aggregate handwashing rates before and after patient contact during phases of the program are presented in Table 1. The week-to-week variation within each phase and between each phase is shown in the Figure. During overt observation the handwashing rate rose from the baseline level (determined by unobtrusive observation), with the peak rate occurring in Week 3 of this five-week period. It rose again during performance feedback, peaking in the last week of this phase. During the second period of unobtrusive observation, seven weeks after performance feedback, the handwashing rate was lower but still showed a more than fourfold increase over baseline levels. There was a gradual decline from week to week during this last phase of unobtrusive observation. Cohort performanceNineteen medical officers estimated their own handwashing rate before patient contact after the first phase of covert observation. Their mean estimate was 66% (range, 30%-95%). Several commented that other medical officers washed their hands infrequently. Fourteen of these 19 subjects subsequently participated in the remain- ing phases of the program. Among this cohort, the mean self-estimated handwashing rate was 73% (range, 50%-95%), compared with the covertly observed rate for this cohort of 8.6% before and 10.8% after patient contact, with an individual mean rate of 10% (range, 0-33%). The performance of the cohort during the other phases of the program is shown in Table 2. Significant improvement in handwashing before and after patient contact was observed during overt observation and performance feedback. The improved performance of these 14 subjects was maintained after the period without observation. DiscussionPatients in intensive care units are at greater risk of nosocomial infection than those elsewhere in hospitals: they are already critically ill; are subject to multiple hand contacts from a wide variety of staff; have indwelling invasive therapeutic and monitoring devices; and often receive non-specific antimicrobial therapy. Reports of nosocomial infection in intensive care units show infection rates varying from 13% to 26%,15-19 whereas hospital-wide nosocomial infection rates are about 5%-10%.20-23 Physicians freely acknowledge that handwashing is important in the control of nosocomial infection, and suggest pressure of work, a lack of patient contact, detrimental effects of handwashing agents on skin and the more important needs of the patient as reasons for not handwashing.4 Infection control is rarely taught in medical school,24 and poor handwashing practices may be learnt from peers at the bedside.25 In the first phase of this study, I found the handwashing rate among medical staff to be lower than rates reported previously (13%-28%,5 21%6 and 15%7). Physicians were observed unobtrusively as it is known that observation alone may alter behaviour, a phenomenon otherwise known as the "Hawthorne effect" (after the Hawthorne works of the Western Electric Company, where job performance was improved by the presence of observers).26 This effect was confirmed firstly by the abrupt increase in handwashing which accompanied notification of my intention to observe handwashing and again during the performance feedback phase. Despite the relative lack of handwashing in relation to patient contact by hospital staff and its possible detrimental consequences, few reports of attempts to improve handwashing have been published. "Educational programs" which aim to increase medical staffs' awareness of nosocomial infection and the importance of handwashing have not been successful. In an intensive care unit the handwashing rate among physicians increased to only 17% after an educational program (in-service teaching rounds, poster displays, specific requests to handwash and unspecified performance feedback to all staff).10 Another study, in a paediatric ambulatory setting, found that physicians did not respond to written and verbal requests to handwash before patient contact.27 Moreover, my study showed that medical staff have an inflated impression of their own handwashing performance, which may possibly prejudice learning. Educational programs to teach nurses to handwash have also been unsuccessful. The failure of one consisting of poster displays and the distribution of booklets on isolation policy was attributed to a lack of motivation.11 Another strategy to improve handwashing is the installation of handwashing machines. This was associated with improvement over a short period in a small group of nurses and physicians, but it was abandoned when there was an outbreak of methicillin-resistant Staphylococcus aureus.28 Several "training programs" to increase handwashing have been more successful than educational awareness programs. A program for nurses consisted of observation and daily feedback of handwashing performance from the previous day; the handwashing rate after patient contact rose from 59% to 92% during a three-week period.14 However, the relative effects of observation and performance feedback could not be separated. Among food handlers in a university cafeteria, performance feedback alone was successful in training to handwash.29 Performance feedback is an intervention frequently used in organisational behaviour management to improve performance.30 In my study, it resulted in an increase in handwashing among medical officers which was sustained at a rate six times the baseline in about two-thirds of contacts with patients. Regular programs are required to maintain an acceptable standard of performance among permanent staff10 and to compensate for departure and entry of staff members. In my study the difference in handwashing performance between the whole group of medical officers and a cohort within the group may be attributed to staff turnover outside the cohort or, alternatively, to greater exposure to the program, or may be a consequence of being asked to estimate their own handwashing rate. The cohort achieved and maintained a higher handwashing rate than the group as a whole. For reasons of economy and efficacy, behaviour intervention rather than educational awareness programs appears preferable in educating medical staff to handwash. Acknowledgements I thank Dr Gerald Elsworth, formerly of the Centre for the Study of Higher Education, University of Melbourne, for helpful suggestions concerning the design of the study. I thank the ICU nurses, particularly Sharon Kinney. (©MJA 1996; 164: 14-17) To beginning of this article ReferencesDaschner F. Useful and useless hygienic techniques in intensive care units. Intensive Care Med 1985; 11: 280-283. Davies PA. Please wash your hands. Arch Dis Child 1982; 57: 647-648. Steere AC, Mallison GF. Handwashing practices for the prevention of nosocomial infections. Ann Intern Med 1975; 83: 683-690. Larson E, Killien M. Factors influencing handwashing behaviour of patient care personnel. Am J Infect Control 1982; 10: 93-99. Albert RK, Condie F. Hand-washing patterns in medical intensive care units. N Engl J Med 1981; 304: 1465-1466. Donowitz LG. Handwashing technique in a pediatric intensive care unit. Am J Dis Child 1987; 141: 683-685. De Carvalho M, Lopes JMA, Pellitteri M. Frequency and duration of handwashing in a neonatal intensive care unit. Pediatr Infect Dis J 1989; 8: 179-180. Larson E. Compliance with isolation technique. Am J Infect Control 1983; 11: 221-225. Meengs MR, Giles BK, Chisholm CD, et al. Hand washing frequency in an emergency department. Ann Emerg Med 1994; 23: 1307-1312. Conly JM, Hill S, Ross J, et al. Handwashing practices in an intensive care unit: the effects of an educational program and its relationship to infection rates. Am J Infect Control 1989; 17: 330-339. Williams E, Buckles A. A lack of motivation. Nursing Times 1988; 84: 60-64. Doebbeling BN, Stanley GL, Sheetz CT, et al. Comparative efficacy of alternative hand-washing agents in reducing nosocomial infections in intensive care units. N Engl J Med 1992; 327: 88-93. Goldmann D, Larson E. Hand-washing and nosocomial infections. N Engl J Med 1992; 327: 120-122. Mayer JA, Dubbert PM, Miller M, et al. Increasing handwashing in an intensive care unit. Infect Control 1986; 7: 259-262. Daschner FD, Frey P, Wolff G, et al. Nosocomial infections in intensive care wards: a multicenter prospective study. Intensive Care Med 1982; 8: 5-9. Donowitz LG, Wenzel RP, Hoyt JW. High risk of hospital-acquired infection in the ICU patient. Crit Care Med 1982; 10: 355-357. Potgieter PD, Linton DM, Oliver SO, Forder AA. Nosocomial infections in a respiratory intensive care unit. Crit Care Med 1987; 15: 495-498. Donowitz LG. High risk of nosocomial infection in the pediatric critical care patient. Crit Care Med 1986; 14: 26-28. Craig CB, Connelly S. Effect of intensive care unit nosocomial pneumonia on duration of stay and mortality. Am J Infect Control 1984; 12: 233-238. McLaws M-L, Gold J, King K, et al. The prevalence of nosocomial and community-acquired infections in Australian hospitals. Med J Aust 1988; 149: 582-590. Meers PD, Ayliffe GAJ, Emmerson AM, et al. Report on the national survey of infection in hospitals, 1980. J Hosp Infect 1981; 2(Suppl): 13-17. Haley RW, Culver DH, White JW, et al. The nationwide nosocomial infection rate. A new need for vital statistics. Am J Epidemiol 1985; 121: 159-167. Mayon-White RT, Ducel G, Kereselidze T, Tikomirov E. An international survey of the prevalence of hospital-acquired infection. J Hosp Infect 1988; 11(Suppl A): 43-48. Moss F, Cochrane JPS, Yudkin JS. Introducing medicine to tomorrow's doctors. Lancet 1987; 1: 203-205. Larson E, McGinley KJ, Grove GL, et al. Physiologic, microbiologic and seasonal effects on the skin of health care personnel. Am J Infect Control 1986; 14: 51-59. Roethlisberger FJ, Dickson WJ. Management and the worker. Cambridge, Mass: Harvard University Press, 1942. Lohr JA, Ingram DL, Dudley SM, et al. Handwashing in paediatric ambulatory settings. Am J Dis Child 1991; 145: 1198-1199. Wurtz R, Moye G, Jovanovic B. Handwashing machines, handwashing compliance and potential for cross-contamination. Am J Infect Control 1994; 22: 228-230. Geller ES, Eason SL, Phillips JA, Pierson MD. Interventions to improve sanitation during food preparation. J Organizational Behav Manage 1980; 2: 229-240. Prue DM, Fairbank JA. Performance feedback in organizational behavior management: a review. J Organizational Behav Manage 1981; 3: 1-16. (Received 26 Jun, accepted 5 Dec 1995) Author's detailsIntensive Care Unit, Royal Children's Hospital, Melbourne, VIC. James Tibballs, MEd, FFICANZCA, Deputy Director. Reprints: Dr J Tibballs, Intensive Care Unit, Royal Children's Hospital, Flemington Road, Parkville, VIC 3052. E-mail: tibballjATcryptic.rch.unimelb.edu.au (©MJA 1996; 164: 14-17) < URL: http://www.mja.com.au/> © 1996 Medical Journal of Australia.

James Tibballs

AbstractObjective: To assess the effectiveness of the flashlamp-pumped pulsed dye laser in the treatment of port-wine stains. Design: A retrospective review of medical records and patients. Setting: Royal Perth Hospital (a tertiary referral hospital), August 1989 to December 1992. Subjects: 186 consecutive patients with port-wine stains treated with a flashlamp-pumped pulsed dye laser. Outcome measures: Degree of lesion fading; adverse reactions. Results: Of 131 patients who completed treatment, 78% had better than 50% fading of the lesion and only 9% had less than 25% fading. An average 3.4 treatments were needed to achieve more than 50% fading. The response was better in children than in adults, although the difference was not significant. Anaesthesia was needed for 44% of patients. Pigmentary change (usually transient) occurred in 6.1% of patients and permanent and significant adverse effects in only 4.6%. Conclusion: This study confirms the efficacy of the flashlamp-pumped pulsed dye laser in the treatment of port-wine stains in children and adults. Early treatment of port-wine stains should be encouraged to reduce the physical and psychological morbidity of disfiguring lesions. IntroductionPort-wine stains (now termed capillary malformations) are congenital vascular malformations characterised by ectatic vessels within the cutaneous superficial vascular plexus.1 They affect 0.3% of children at birth, with an equal sex distribution.2 Most port-wine stains are found on the head and neck, with 85% occurring in a unilateral, dermatomal distribution.3 Their natural history is to progress from a pink, macular lesion at birth to a dark red (or even purple), nodular, proportionately larger lesion in adulthood.1,4 Cosmetic disfigurement can cause considerable psychological morbidity, and be socially disadvantageous.5,6 Hypertrophic, nodular lesions may bleed, either spontaneously or after trauma, encroach on essential facial structures or even develop into pyogenic granulomas.7 All port-wine stains should be treated, preferably early in life, to prevent or reduce the potential physical and psychological complications. Before the development of laser technology, treatment for port-wine stains was often unsatisfactory.8 Earlier lasers, including ruby, carbon dioxide and argon lasers, improved the lesions in most patients, but, as they were non-selective in their effects on tissue, the frequency of side effects, such as scarring and pigmentary changes, was unacceptably high.9 The flashlamp-pumped pulsed dye laser (PDL) was the first laser to be based on selective photothermolysis;10 it produces vascular- specific damage without affecting surrounding dermal structures or the epidermis.11-13 Studies have confirmed its effectiveness in the treatment of port-wine stains in adults, children and infants, with an extraordinarily low incidence of side effects.14-19 The PDL is now regarded as the first-line treatment for port-wine stains whenever possible.8,9,20-22 In Australia, the PDL has been in use since the late 1980s for the treatment of cutaneous vascular lesions, especially port-wine stains. However, no Australian study of its effects has been published. Therefore, we undertook a retrospective clinical review of all patients with port-wine stains treated with PDL at Royal Perth Hospital between August 1989 and December 1992. MethodsThe study was a retrospective review of patient medical records. If response to treatment was not recorded, attempts were made to review the patient between January and December 1993. PatientsAll patients (adult and paediatric) with a port-wine stain treated with PDL at Royal Perth Hospital between August 1989 and December 1992 were eligible. Patients attended outpatient clinics, where the site and size of the port-wine stain and demographic data were recorded and the treatment procedure and its risks and benefits were explained. Patients were photographed before treatment by a professional photographer in a studio dedicated to medical photography, with efforts to use the same magnification, lighting and exposure. Laser and techniqueA flashlamp-pumped pulsed dye laser (Candela SPTL-1, Candela Corp, Wayland, Mass, United States) was used. It emitted yellow light at a wavelength of 585 nm, with a pulse duration of 450 µs and a 3 s pause between pulses. The laser beam was transmitted down a 1 mm fibre by a planoconvex lens and focused as a 5 mm spot beam. Energy densities were measured by an energy meter (Ophir, Jerusalem, Israel), calibrated to 10% accuracy. Both the physicians and the patients eyes were protected from laser light during treatment. Some patients had a small initial test patch treated, depending on patient anxiety and time of presentation (before 1991, most had a patch test). Otherwise, the entire lesion was treated at once, unless it involved a large surface area (> 100 cm2). Treatments were repeated at intervals of 23 months. The energy density used varied with the age of the patient and colour, nodularity and location of the lesion and was adjusted according to the degree of purpura produced and the patients response to the previous treatment. Pulses were overlapped by a maximum of 10% across the affected area. The anaesthetic varied according to the site and area to be treated and the level of patient cooperation. EMLA cream (eutectic mixture of 2.5% lignocaine and 2.5% prilocaine cream, Astra Pharmaceuticals, North Ryde, NSW) was used for topical anaesthesia, applied under occlusion for 60120 minutes before treatment. Local anaesthesia involved an injection of 1% lignocaine, either locally or as a regional nerve block. General anaesthesia was given to children who had extensive lesions or were uncooperative with topical or local anaesthesia. The treated area developed purpura within a few minutes, usually persisting for 710 days. No immediate postoperative care was necessary, except for an occasional ice pack to reduce oedema in those with large treatment areas. Postoperative instructions were to protect the area from trauma, avoid excessive exposure to sunlight and use a topical antiseptic cream for any scaling or crusting. Treatment evaluationEach port-wine stain was evaluated, either before the next treatment or 34 months after the final treatment. Lesional lightening was assessed as the percentage reduction in colour compared with the pretreatment photo (fading < 25%, poor; 25% to 50%, fair; > 50% to 75%, good; and > 75%, excellent) (Figures 1-4). Adverse effects, such as scarring and textural or pigmentary changes, were also noted. All patients were individually assessed by one or both investigators. The endpoint of treatment was assessed clinically. Data analysisData were analysed with the Statistical Analysis Systems software package.23 The chi-squared statistic was used to assess the difference in response between age groups. ResultsThere were 186 patients treated by PDL: 131 completed treatment (55 either did not complete treatment or were having ongoing treatment). Patients were either Caucasian or Asian and aged 8 months to 66 years (mean, 25.6 years). There were 59 males (32%) and 127 females (68%). Most of the treated lesions were present from birth (97%). Acquired lesions appeared most commonly between the ages of six and 12. Most lesions were on the face and neck (87%), with the rest distributed unilaterally on the arms (4%), legs (5%), back (2%) and chest (2%). The size of treated lesions ranged from 1 cm2 to 280 cm2 (mean, 42 cm2). All responded to energy fluences between 5 and 10 joules/cm2(mean, 6.7 joules/cm2). Sixty-two per cent of the patients had a patch test before treatment. Anaesthesia was used for 44% of patients (general anaesthesia by 20%, topical by 19% and local or regional block by 5%). Responses of patients who completed treatment are shown in the Box. A good-to-excellent response was achieved in 78% and a poor response in only 9%. An average 3.4 treatments per lesion were required to achieve a good-to-excellent response. Adverse side effects occurred in 11% of patients who completed treatment; all had some fading of the lesion. The most common adverse effect was pigmentary change (6.1%), which was usually transient and resolved in 23 months. Only 4.6% had significant permanent adverse effects; two had scarring (in both the port-wine stain was on the face and neck region). More children than adults had a good or excellent response, but the difference was not significant when compared with a 2 x 2 contingency table and chi-squared test (r = 0.60). Similarly, fewer children than adults had a poor response. DiscussionOur results compare favourably with those of other studies. A good-to-excellent response (more than 50% fading) was obtained in 78% of our patients (including both adults and children, with lesions on sites including the trunk and lower limbs), with an average 3.4 treatments required. Others have found more than 50% fading in 73%-95% of patients after 2.4-2.8 treatments.14-17,24,25 Response to treatment varies between sites: the periorbital area, temple, lateral aspect of the cheek, neck and chin have been observed to be more responsive18,25 and the centrofacial area and lower leg to be less responsive.18,19 We found that a poor response was more common in adults than in children (although the difference was not significant), possibly because port-wine stains become progressively hypertrophied and nodular in adults. We found a higher rate of adverse effects (11%) than in other studies. The most common (usually transient) adverse effect was pigmentary change (increase or decrease), possibly because of excessive sunlight exposure after treatment. This transient change may not have been recorded in other studies; when it was excluded from our figures, the rate of adverse reactions was reduced to less than 5%, which is comparable with that found in other studies. Scarring was seen in two of our patients, with lesions on the face and neck, where damage to dermal structures with fibrosis occurs when excessive energy fluence is used. A low energy fluence should be used initially when treating port-wine stains on the neck and anterior chest. The PDL is the first laser specifically designed for cutaneous vascular malformations. It is based on the theory of selective photothermolysis, which predicts selective destruction of blood vessels without damage to the surrounding tissues.10 Laser light emitted by the PDL is absorbed by oxyhaemoglobin in the dilated vessels of the lesion, producing agglutination of erythrocytes, thrombus formation and eventual destruction of the vessels.11 They are replaced by non-dilated superficial dermal blood vessels with a normal appearance.12 A recent comparison of PDL and the copper vapour laser showed that PDL produced significantly better fading of port-wine stains.22 The characteristics and degree of pain associated with PDL treatment have been well described.26 Initially, there is a sharp stinging pain, very similar to the snap of a rubber band against the skin. Accompanying this is a second distinct heat sensation that can be at least as unpleasant as the initial sting. Pain rapidly subsides but seems to build up if successive pulses are used for a moderately sized lesion. Our current practice is to give general anaesthesia to all children from four weeks of age, until they are able to co-operate with topical or local anaesthesia, usually at eight to 10 years. Young children undergoing multiple painful treatments with inadequate anaesthesia under restraint may develop phobic responses. Furthermore, a struggling child may compromise the clinicians ability to perform the procedure optimally. In conclusion, this study supports the contention that all port-wine stains should be treated with PDL, as it has a high therapeutic index with a low incidence of adverse effects. Patients should preferably be treated in infancy or childhood, under general anaesthesia, to minimise the potential psychological morbidity of disfiguring lesions. In addition, the response to treatment seems better in children than in adults, although the difference was not significant, possibly because of the relatively small sample size. Laser treatment of port-wine stains should no longer be considered just cosmetic, but a medical necessity for a problem that can cause psychological and physical morbidity. References Mulliken JB. Capillary (port-wine) and other telangiectatic stains. In: Mulliken JB, Young AE, editors. Vascular birthmarks -- haemangiomas and malformations. Philadelphia: W B Saunders, 1988: 179-195. Jacobs AH, Walton RG. The incidence of birthmarks in the neonate. Pediatrics 1976; 58: 218-222. Tallman B, Tan OT, Morelli JG, et al. Location of port-wine stains and the likelihood of ophthalmic and/or central nervous system complications. Pediatrics 1991; 87: 323-327. Barsky SH, Rosen S, Geer DE, Noe JM. The nature and evolution of port-wine stains: a computer-assisted study. J Invest Dermatol 1980; 74: 154-157. Lanigan SW, Cotterill JA. Psychological disabilities amongst patients with port wine stains. Br J Dermatol 1989; 121: 209-215. Pickering JW, Butler PH, Ring BJ, Walker EP. Copper vapour laser treatment of port wine stains: a patient questionnaire. Lasers Med Sci 1990; 5: 43-49. Geronemus RG, Ashinoff R. The medical necessity of evaluation and treatment of port-wine stains. J Dermatol Surg Oncol 1991; 17: 76-79. Wheeland RG. Treatment of port-wine stains for the 1990s. J Dermatol Surg Oncol 1993; 19: 348-356. Van Gemert MJ, Carruth JA, Shakespeare PG. Laser treatment of the port-wine stains. BMJ 1993; 306: 4-5. Anderson RR, Parrish JA. Selective photothermolysis: precise microsurgery by selective absorption of pulsed radiation. Science 1983; 220: 524-527. Nakagawa H, Tan OT, Parrish JA. Ultrastructural changes in human skin after exposure to a pulsed laser. J Invest Dermatol 1985; 84: 396-400. Morelli JG, Tan OT, Garden J, et al. Tunable dye laser (577 nm) treatment of port wine stains. Lasers Surg Med 1986; 6: 94-96. Tan OT, Morrison P, Kurban AK. 585 nm for the treatment of port-wine stains. Plast Reconstr Surg 1990; 86: 1112-1117. Garden JM, Polla LL, Tan OT. The treatment of port-wine stains by the pulsed dye laser: analysis of pulse duration and long-term therapy. Arch Dermatol 1988; 124: 889-896. Tan OT, Sherwood K, Gilchrest BA. Treatment of children with port-wine stains using the flashlamp-pulsed tunable dye laser. N Engl J Med 1989; 320: 416-421. Reyes BA, Geronemus RG. Treatment of port-wine stains during childhood with the flashlamp-pumped pulsed dye laser. J Am Acad Dermatol 1990; 23: 1142-1148. Ashinoff R, Geronemus RG. Flashlamp-pumped pulsed dye laser for port-wine stains in infancy: earlier versus later treatment. J Am Acad Dermatol 1991; 24: 467-472. Renfro L, Geronemus RG. Anatomical differences of port-wine stains in response to treatment with the pulsed dye laser. Arch Dermatol 1993; 129: 182-188. Garden JM, Bakus AD. Clinical efficacy of pulsed dye laser in the treatment of vascular lesions. J Dermatol Surg Oncol 1993; 19: 321-326. Geronemus RG. Pulsed dye laser treatment of vascular lesions for children. J Dermatol Surg Oncol 1993; 19: 303-310. Hruza GJ, Geronemus RG, Dover JS, Arndt KA. Lasers in dermatology Ñ 1993. Arch Dermatol 1993; 129: 1026-1035. Sheehan-Dare RA, Cotterill JA. Copper vapour laser (578 nm) and flashlamp-pumped pulsed tunable dye laser (585 nm) treatment of port-wine stains: results of a comparative study using test sites. Br J Dermatol 1994; 130: 478-482. Statistical Analysis Systems [computer program], version 6.08. Cary (NC): SAS Institute Inc, 1994. Goldman MP, Fitzpatrick RE, Ruiz-Esparza J. Treatment of port-wine stains (capillary malformation) with the flashlamp-pumped pulsed dye laser. J Pediatr 1993; 122: 71-77. Holy A, Geronemus RG. Treatment of periorbital port-wine stains with the flashlamp-pumped pulsed dye laser. Arch Ophthalmol 1992; 110: 793-797. Rabinowitz LG, Esterly NB, Frieden IJ, et al. Anesthesia and/or sedation for pulsed dye laser therapy. Pediatr Dermatol 1992; 9: 132-153. Authors detailsDepartment of Dermatology, Royal Perth Hospital, Perth, WA. Ernest Tan, MB BS, Dermatology Registrar; Carl Vinciullo, FACD, Visiting Dermatologist. No reprints will be available. Correspondence: Dr C Vinciullo, Department of Dermatology, Royal Perth Hospital, Wellington Street, WA 6000. E-mail: carlATdermlaser.com.au

Ernest Tan · Carl Vinciullo

Passive smoking and respiratory function in very low birthweight children Lex W Doyle, Geoffrey W Ford, Anthony Olinsky, Annette M L Knoches and Catherine Callanan For editorial comment see Woodward & Jamrozik Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au/>". Abstract - Introduction - Methods - Results - Discussion - Acknowledgement - References - Authors' details - ©MJA1997 Abstract Aim: To determine if an adverse relationship exists between passive smoking and respiratory function in very low birthweight (VLBW) children at 11 years of age. Setting: The Royal Women's Hospital, Melbourne. Patients: 154 consecutive surviving children of less than 1501 g birthweight born during the 18 months from 1 October 1980. Methods: Respiratory function of 120 of the 154 children (77.9%) at 11 years of age was measured. Exposure to passive smoking was established by history; no children were known to be actively smoking. The relationships between various respiratory function variables and the estimated number of cigarettes smoked by household members per day were analysed by linear regression. Results: Most respiratory function variables reflecting airflow were significantly diminished with increasing exposure to passive smoking. In addition, variables indicative of air-trapping rose significantly with increasing exposure to passive smoking. Conclusions: Passive smoking is associated with adverse respiratory function in surviving VLBW children at 11 years of age. Continued exposure to passive smoking, or active smoking, beyond 11 years may lead to further deterioration in respiratory function in these children. MJA 1996; 164: 266-269 Introduction Passive smoking is associated with several adverse health outcomes in children, including higher rates of asthma,1 and infections of the upper2 and lower3 respiratory tract. Further, respiratory function is reduced with passive smoking in children who have no lung disease,4 as well as those with lung diseases such as asthma5 and cystic fibrosis.6 To survive the neonatal period, many very low birthweight (VLBW) children (less than 1500 g at birth) require prolonged periods of assisted ventilation, and some may develop bronchopulmonary dysplasia (BPD) and suffer from ongoing respiratory problems as a consequence. We have previously reported the respiratory health to eight years of age of cohorts of children of birthweight 500-999 g (n = 83), 1000-1500 g (n = 114) and > > 2500 g (n = 51).7 Passive smoking was significantly related to the duration of hospitalisation for respiratory problems up to two years of age for all children in that study, but was not associated with changes in respiratory function at eight years of age. In contrast, in another recent cohort study of respiratory function at seven years of age in children of birthweight less than 2000 g Chan et al.8 reported reduced air-flow rates with maternal smoking, but not with smoking by other household members. Because the effects of passive smoking could increase with increasing duration of exposure, the aim of this study was to determine if an adverse relationship exists between passive smoking and respiratory function at 11 years of age in VLBW children. Methods We studied 154 consecutive surviving children of less than 1501 g birthweight born during the 18 months from 1 October 1980 at the Royal Women's Hospital, Melbourne, the largest of the three tertiary-level perinatal centres in Victoria. Details of the survival rate and early neonatal care of this cohort have been described.9,10 Bronchopulmonary dysplasia (BPD) was diagnosed in children who had required intermittent positive pressure ventilation in the neonatal period, who had respiratory distress and were still having oxygen therapy at 28 days of age, and who had an abnormal chest x-ray consistent with stage III or IV disease (as defined by Northway et al.11 ) at or after 28 days. A previous report of the respiratory function of this cohort at eight years of age7 included data for some children with birthweights of less than 1000 g born before 1 October 1980. We did not have the resources to measure respiratory function at 11 years of age of the children born before October 1980. Respiratory health was determined by history and examination, and measurement of respiratory function. Children who had required bronchodilators within the previous year for attacks of wheezing were considered to have asthma. Data on passive smoking were obtained by asking the parents about the daily consumption of cigarettes by members of the household. We did not distinguish between mothers and other smokers, or between smoking inside or outside the home. Some data on maternal smoking in pregnancy had been collected in the perinatal period, but were obtained for only one-third of mothers. Children were questioned about active smoking in their parents' absence. As some children had changed households in their lifetimes, we considered those who had lived in any household with smokers over the 11-year period to have been passively smoking during childhood. Two categories of social class were determined -- unskilled or unemployed, and other (professional, skilled or semi-skilled) -- based on the occupation of the family breadwinner. Respiratory function was measured in the Department of Thoracic Medicine at the Royal Children's Hospital, Melbourne, as described previously,7 by personnel blinded to the exposure of individual children to passive smoking. Maximum expiratory flow rates were recorded with a pneumotachograph (Fleisch No. 3, Switzerland) and plotted against volume by integrating flow on an X-Y recorder to obtain flow-volume loops. Maximum flow rates at 75% (VEmax75%), 50% (VEmax50%) and 25% (VEmax25%) of forced vital capacity (FVC), and forced expiratory flow between 25% and 75% of FVC (FEF25%-75%), were measured from the loops. Flow rates were corrected for body size by dividing by vital capacity (VC). Vital capacity, FVC and forced expiratory volume in one second (FEV1) were measured with a water-filled spirometer (Godart Expirograph, Bilthoven, Netherlands) in accordance with standard guidelines, and results at body temperature and pressure saturated with water vapour were expressed as a percentage of the predicted value for age, height and sex.12 Total lung capacity (TLC) and residual volume (RV) were measured in a body plethysmograph (Jaeger Bodyscreen 2, Wurzburg, Germany). Children were not subjected to bronchial provocation tests as these are poorly tolerated, and we were eager to maintain a high degree of cooperation with these and with future respiratory function tests. Not all children could complete all respiratory function tests, either because of poor cooperation, or unavailability or malfunction of equipment on the day of testing. Data were edited and analysed using SPSS.13 Dichotomous variables were contrasted by chi-squared analysis, and continuous variables by t test, or Mann-Whitney U test if the data were skewed. The dose-response relationship between the estimated daily number of cigarettes consumed by members of the household and various respiratory function variables was established by linear regression; linear and quadratic relationships were tested. Data were then analysed by linear regression to adjust for the potentially confounding variables of birthweight, gestational age, birthweight ratio (child's birthweight divided by median birthweight for gestational age14 ), sex, BPD, and asthma; all variables were entered simultaneously, even if they were not statistically significant. Durations of intermittent positive pressure ventilation and oxygen therapy were not included as they were strongly related to BPD. For all analyses, P values of less than 0.05 for any test were regarded as statistically significant. Results We measured the respiratory function of 120 of the 154 (77.9%) children at 11 years of age. Of the 34 children not tested, 15 lived in another State, four lived in another country, 10 refused the tests, three were lost to follow-up, and two were too disabled to complete the tests. There were no substantial differences in perinatal variables between children who did and did not have respiratory function tests at 11 years of age. Eighty of the 120 children (66.7%) had been exposed to passive smoking in the household. The only substantial differences in perinatal or subsequent variables between children who were and were not exposed to passive smoking were a significantly longer duration of oxygen therapy and a lower proportion of unskilled or unemployed families in the group not exposed (Table 1). For children exposed to passive smoking, the median number of cigarettes consumed in the household per day was 21 (interquartile range, 15-25). Of the 15 children tested who had developed BPD in the newborn period, three (20%) had asthma at 11 years of age; this proportion was similar for children with asthma at 11 who did not have BPD (22 of 105; 21%). For variables expressed as a percentage of predicted values (FEV1, FVC, RV, TLC), the means of the measured values were all close to their expected values of 100% (Table 2). For all respiratory function variables significantly associated with the dose of passive smoking, a quadratic relationship was more significant than a linear relationship (Table 2, Figures 1 and 2). Most respiratory function variables reflecting airflow (VEmax75%/VC, VEmax50%/VC, FEF25%-75%/VC, FEV1 and FEV1/FVC) were significantly diminished by increasing exposure to passive smoking (Table 2 [below], Figures 1a and 1b). In addition, RV, TLC and RV/TLC rose significantly (consistent with progressive air trapping) with increasing exposure to passive smoking (Table 2 [below], Figure 1c). One child was exposed to 115 cigarettes per day, and the next highest exposure was only 70 cigarettes per day. When the child exposed to 115 cigarettes per day was excluded, most of the statistically significant relationships disappeared, except for the increases in RV and RV/TLC (Figure 2). From the multiple linear regression analyses, some variables reflecting flow (VEmax75%/VC, VEmax50%/VC, VEmax25%/VC, FEF25%-75%/VC and FEV1/FVC) were significantly higher in girls. BPD was significantly associated with reductions in some variables reflecting air-flow (VEmax50%/VC, FEF25%-75%/VC, FEV1 and FEV1/FVC), as was asthma (with significant reductions in FEF25%-75%/VC, FEV1 and FEV1/FVC). FVC was significantly lower and VEmax25%/VC significantly higher with lower social class. Birthweight ratio, birthweight and gestational age were not significantly associated with any lung function variable. None of the statistical conclusions relating respiratory function variables with passive smoking were altered by adjusting for all potentially confounding variables, except that the reduction in VEmax50%/VC was no longer statistically significant. Discussion Passive smoking was associated with reduced airflow and air-trapping in VLBW children at 11 years of age, which is consistent with observations in non-preterm children free of lung disease.4 However, this finding was different from our observations of these children at eight years of age,7 when passive smoking was unassociated with any lung function variable. Chan et al.8 reported reduced flow rates with smoking by mothers in children of less than 2000 g birthweight at seven years of age, but they did not measure variables reflecting air-trapping. We did not distinguish between mothers and other smokers in the household. The association between passive smoking and adverse respiratory function in our VLBW children at 11, but not at eight, years of age suggests that the harmful effects of passive smoking take time to become obvious in VLBW children. Moreover, the adverse response seems to accelerate with increasing dose of passive smoking (Figures 1 and 2). We are concerned that continued exposure to passive smoking, or, even worse, active smoking, beyond 11 years will lead to not only further, but also to an accelerating rate of, deterioration in respiratory function. Our results should not be overinterpreted. They were not substantially altered by adjusting for potentially confounding perinatal or other variables, but we did not have data on a wide range of confounding variables. Moreover, they were heavily influenced by one child who lived in a household whose members consumed 115 cigarettes per day. Excluding this child from the analysis, the only remaining statistically significant associations indicated air-trapping with increasing exposure to passive smoking. However, we consider that this child's data should not be excluded just on the basis of heavier-than-average exposure to passive smoking. To remove any doubt about the association between passive smoking and adverse lung function in VLBW children, lung function could be measured in another cohort of VLBW children, or the same cohort when they are older. Parents of VLBW children, particularly those of children who have received assisted ventilation, frequently ask about long-term lung problems. Many variables, such as family history or duration of assisted ventilation and oxygen therapy, may be related to long-term lung problems, but most cannot be altered by the parents. Exposure to passive smoking is one variable associated with poorer respiratory function in VLBW children they can influence. Until there is evidence to the contrary, families of VLBW children should be encouraged to stop exposing their children to cigarette smoke in the household. As there appears to be a dose-response relationship, those who cannot stop smoking should at least reduce their children's exposure to passive smoking. Acknowledgement This study was supported in part by a grant from the Royal Women's Hospital-3AW Community Services Trust. References Landau L. Smoking and childhood asthma. Med J Aust 1991; 154: 715-716. Wright AL, Holberg C, Martinez FD, et al. Relationship of parental smoking to wheezing and nonwheezing lower respiratory tract illnesses in infancy. J Pediatr 1991; 118: 207-214. Etzel RA, Pattishall EN, Haley NJ, et al. Passive smoking and middle ear effusion among children in day care. Pediatrics 1992; 90: 228-232. Cook DG, Whincup PH, Papacosta O, et al. Relation of passive smoking as assessed by salivary cotinine concentration and questionnaire to spirometric indices in children. Thorax 1993; 48: 14-20. Chilmonczyk BA, Salmon LM, Megathlin KN, et al. Association between exposure to environmental tobacco smoke and exacerbations of asthma in children. N Engl J Med 1993; 328: 1665-1669. Smyth A, O'Hea U, Williams G, et al. Passive smoking and impaired lung function in cystic fibrosis. Arch Dis Child 1994; 71: 353-354. Kitchen WH, Olinsky A, Doyle LW, et al. Respiratory health and lung function in 8-year-old children of very low birth weight: a cohort study. Pediatrics 1992; 89: 1151-1158. Chan KN, Noble-Jamieson CM, Elliman A, et al. Lung function in children of low birth weight. Arch Dis Child 1989; 64: 1284-1293. Kitchen WH, Ford GW, Murton LJ, et al. Mortality and two year outcome of infants of birthweight 500-1500 g: relationship with neonatal cerebral ultrasound data. Aust Paediatr J 1985; 21: 253-259. Kitchen WH, Yu VYH, Lissenden JV, Bajuk B. Collaborative study of very-low-birthweight infants: techniques of perinatal care and mortality. Lancet 1982; i: 1 454-1457. Northway WH Jr, Rosan RC, Porter DY. Pulmonary disease following respirator therapy of hyaline-membrane disease: bronchopulmonary dysplasia. N Engl J Med 1967; 276: 357-368. Hibbert ME, Lanigan A, Landau LI, Phelan PD. Lung function values from a longitudinal study of healthy children and adolescents. Pediatr Pulmonol 1989; 7: 101-109. SPSS for Windows [computer program]. Version 6.1. Chicago, Ill: SPSS Inc, 1994. Kitchen WH, Robinson H, Dickinson AJ. Revised intrauterine growth curves for an Australian hospital population. Aust Paediatr J 1983; 19: 157-161. (Received 8 Jun, accepted 18 Nov 1995) Authors' details Division of Paediatrics, the Royal Women's Hospital, Melbourne, VIC. Lex W Doyle, MD, FRACP, Paediatrician; and Associate Professor, Departments of Obstetrics and Gynaecology, and Paediatrics, the University of Melbourne. Geoffrey W Ford, MB BS, FRACP, Paediatrician. Annette M L Knoches, MB BS, FRCP(C), Paediatrician. Catherine Callanan, RN, Research Nurse. Department of Thoracic Medicine, the Royal Children's Hospital, Melbourne, VIC. Anthony Olinsky, FRACP, Respiratory Physician. No reprints will be available. Correspondence: Associate Professor L W Doyle, Department of Obstetrics and Gynaecology, University of Melbourne, Parkville, VIC 3052. ©MJA 1997 <URL: http://www.mja.com.au/> © 1997 Medical Journal of Australia.

Lex W Doyle · Geoffery W Ford · Anthony Olinsky · Catherine Callanan

Heroin-related deaths in New South Wales, 1992: toxicological findings and circumstances Deborah Zador, Sandra Sunjic and Shane Darke For editorial comment see Hall Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au/>". Abstract - Introduction - Methods - Results - Discussion - Acknowledgements - References - Authors' details - - ©MJA1997 Abstract Objective: To describe the circumstances of death and toxicological findings in all heroin-related deaths in New South Wales in 1992. Design: Coronial files of all cases of heroin-related deaths were reviewed. A standardised form was used to collect information on sociodemographics, history of drug use, circumstances of death, and results of toxicological analysis for each case. Results: 152 heroin-related deaths were identified. Subjects had a mean age of 29.7 years, 82% were male, and 98% were not enrolled in a methadone treatment program at the time of their deaths. Deaths occurred in the home environment in 68% of cases and in the company of at least one other person in 58%. There was intervention before the subject's death in only 21% of cases. Two or more drug classes were detected in 71% of subjects; alcohol was detected in 45%, with a mean blood alcohol concentration of 0.14 g/100mL. Conclusions: Fatal heroin overdose is potentially preventable. Educating users about the risks of co-administering alcohol and other depressant drugs with heroin, the comparative safety of injecting heroin in the company of others and the need to call for intervention sooner may reduce the frequency of heroin-related deaths. MJA 1996; 164: 204 Introduction Over the decade to 1990, mortality from opiate drugs increased by 170% while that from other drugs declined by 8%.1 There is little information available on the circumstances or characteristics of Australian heroin-related deaths. Swensen reviewed 108 opioid drug-caused deaths in Western Australia from 1974 to 1984 and found that propoxyphene was the most common cause, accounting for 36 deaths (33%), followed by methadone in 19 cases (18%), heroin in 12 cases (11%), and morphine in another 12 cases (which may include deaths from heroin).2 Walsh analysed 23 accidental opioid drug deaths in the Newcastle area of New South Wales from 1970 to 1987 and found that most (83%) were caused by heroin/morphine.3 Police reports of cases in this study indicated that in 61% help or intervention by observers was delayed. Both studies found a higher proportion of deaths at weekends, leading both authors to suggest that these deaths involved recreational users rather than "hard-core" addicts. The findings of these two studies cannot be generalised to heroin deaths in Australia because of their relatively small numbers of subjects studied over prolonged periods, the inclusion of all opioid (not just heroin) drug deaths, and the absence of data for Sydney (where most heroin deaths in this country occur). If interventions to reduce the rising mortality rate from opioid drug use are to be developed, then more needs to be known about the circumstances of fatal heroin overdose. Hence, the major aims of this study were to describe the sociodemographic characteristics, circumstances of death and the toxicological findings at autopsy of all cases of fatal heroin overdose in NSW for the year for which the most recent data on drug-caused mortality were available. Methods The approval of the South Western Sydney Area Health Service's Research Ethics Committee was obtained. Permission of the NSW Registry of Births, Deaths and Marriages was obtained to enable the Australian Bureau of Statistics (ABS) to release a list of all heroin-caused deaths in NSW from 1 January to 31 December 1992. ABS records were searched according to the following International Classification of Diseases version 9 (ICD-9) codes: 304.0/304.7 (opiate dependence), E850.0 (accidental opiate poisoning) and E950.0 (opiate-caused suicide).4 Permission was obtained from the Department of Courts Administration to inspect coronial files. A case was identified as a heroin-related death based on the coroner's conclusion alone or in conjunction with results of toxicological analysis. Deaths due to other opiates were excluded from the study. Coronial files contained police reports, ambulance officers' statements, other witnesses' statements, autopsy reports, and results of toxicological analysis. A standardised data collection form was developed to record information on sociodemographic characteristics, history of drug use, circumstances of death, and toxicological findings. Subjects were designated "believed to be a frequent user" if their coronial files provided evidence of two or more criteria indicative of regular heroin use (e.g., known history of heroin use, partner or friends known to be heroin users, history of heroin overdose or treatment for dependence, criminal record and/or unemployment). Subjects were designated "believed to be an infrequent user" if they were known to be primarily dependent on another drug (such as alcohol), were not known to be regular heroin users, and were employed full-time. A "novice" was a person who died from using heroin for the first time. Information on history of admission to methadone maintenance treatment was obtained from data at the Pharmaceutical Services Section, NSW Department of Health. Information on history of admission to other treatment programs for opioid dependence (e.g., detoxification units or residential re habilitation programs) could not be obtained for this study. Data for circumstances of death included the day and date, suburb or town, type of location (e.g., hotel room), time of death, time between injection of heroin and death, presence of other persons, and intervention. A death was considered "instant" if photographs showed a needle and syringe still in situ, if the posture of the body was consistent with a sudden collapse (e.g., slumped against toilet cubicle wall), or if witnesses provided evidence of instant death. "Intervention" was treatment received by the subject while still alive, and did not include treatment by ambulance officers or after admission to hospital if the subject was clinically dead. Information on results of toxicological analysis was obtained from reports of laboratory analyses (by the Division of Analytical Laboratories, NSW Department of Health, Lidcombe) of blood, urine and other tissue specimens taken at autopsy. Statistical analysis For continuous variables, t tests were used, except for highly skewed variables, for which the Mann-Whitney U test (a non-parametric analogue of the t test) was used. Categorical variables were analysed with the chi-squared test and corresponding odds ratios (OR) and 95% confidence intervals (CI) were calculated. To determine which factors were independently associated with blood morphine concentration, we performed multiple linear regressions. SYSTAT was used for all analyses.5 Results Sociodemographic characteristics For the 200 opiate-caused deaths identified by ABS in 1992, one file was unable to be located, one subject was noted to have died on 31 December 1991, one case was found not to be a coroner's case, and seven were found to be misclassifications (i.e., death due to drugs other than opiates). These 10 cases were excluded from the study. The study population thus comprised 190 cases. Of these, 152 (80%) were classified as heroin-related deaths, and the demographic characteristics of the people involved are shown in the Table. They were predominantly male (82%), with a mean age of 29.7 years (SD, 6.7; range, 18-59), and most were unemployed (76%). History of drug use Most (90%) were well known to be heroin users. Eighty per cent were judged to have been frequent heroin users, 17% were considered infrequent heroin users, and two were novice users (1%). Both cases involving novice users were classified as suicides by the coroner. In three cases (2%) it was not possible to estimate the frequency of heroin use from the coronial files. Only 2% were enrolled in a methadone maintenance program at the time of their deaths, with 72% never having been enrolled in methadone treatment in NSW. Some subjects may have been previously enrolled in an interstate program, but this information was not available. Circumstances of death Twenty-six per cent of deaths occurred on Saturdays and Sundays, compared with an expected 29%, assuming a uniform distribution ofdeaths over the seven days of the week. There was also no significant variation between seasons -- summer (18%), autumn (25%), winter (31%) and spring (26%). The times of deaths were distributed as follows: midnight-6am, 23%; 6am- midday, 14%; midday-6pm, 28%; and 6pm-midnight, 35%. Eighty-five per cent of deaths occurred in the Sydney metropolitan region. Fatal heroin overdoses occurred throughout the Sydney area, with the highest frequency (19%) in the East Sydney region (including Kings Cross and Darlinghurst), and the second-highest (16%) in South-Western Sydney (including Cabramatta and Liverpool). Fifty-three per cent of deaths occurred in the subject's usual place of residence or home, and a further 16% in the home of a friend or family member. Thus most (69%) occurred in a home environment. Only 14% of deaths appeared to be "instant" events. The presence of other persons at some time during the interval between the injection of heroin and death was noted in 58% of cases, while 41% of subjects died alone. The presence of others was unable to be determined in 1% of cases. In 79% of cases there was no intervention while the subject was still alive. An ambulance was called while the subject was alive in only 10% of cases and cardiopulmonary resuscitation was attempted by an onlooker in 11%. Toxicological findings Two subjects were deleted from toxicological analyses as they had been maintained on life support systems for two or three days in hospital intensive care units. Morphine was detected in 95% of subjects at autopsy. The second most frequently detected drug was alcohol (45%), with benzodiazepines in 26%. Methadone and amphetamines were each detected in 6% of subjects, and cocaine, antidepressant drugs and barbiturates were detected in 5%, 4% and nil, respectively. A single drug was found in only 27% of subjects -- morphine in 39 of 41, ethanol in one and oxazepam in one. In 71%, two or more different drugs were found at autopsy, and in 18% three or more drugs were detected. Men were more likely to have alcohol detected at autopsy than women (OR, 4.07; 95% CI, 1.44-11.47), while women were more likely to have benzodiazepines detected (OR, 2.82; 95% CI, 1.15-6.93). The distribution of blood morphine concentrations is shown in Figure 1. Twelve subjects were deleted from this analysis because no morphine was found in their blood (although in seven morphine was detected elsewhere, e.g., bile, liver or urine). The median blood morphine level was 0.24 mg/L. Alcohol was detected in 68 subjects (45%); Figure 2 shows the distribution of their blood alcohol concentrations (BACs). The mean BAC was 0.14 g/100 mL (SD, 0.08; range, 0.01-0.35 g/100 mL). Eighty-seven per cent had BACs of 0.05 or higher and 22% had BACs of 0.2 or higher. There were no statistically significant differences between men and women in either median blood morphine concentration (0.25 v. 0.19 mg/L; P < 0.4) or BAC (0.14 v. 0.1 g/100mL; P < 0.25). The median blood morphine concentration in the subjects in whom alcohol was detected was significantly lower than in the group without alcohol detected (0.17 v. 0.34 mg/L; U = 3152; P < 0.001). There was also a statistically significant negative correlation between blood morphine and alcohol concentrations (rs = - 0.28; P < 0.01) The presence of benzo diazepines at autopsy did not significantly affect blood morphine concentrations (0.25 v. 0.24 mg/L; U = 1871; P < 0.7). To determine which individual variables were related to blood morphine concentration, a simultaneous multiple linear regression was performed on log morphine level (because of the skewed distribution of blood morphine levels). Variables used were age, sex, the presence of alcohol and the presence of benzodiazepines. The presence of alcohol at autopsy was the only variable independently associated with lower blood morphine levels (b = - 0.28; P < 0.001); age (P < 0.96), sex (P < 0.2) and the presence of benzodiazepines (P < 0.7) did not significantly predict log blood morphine level. Diagnostic tests of the residuals indicated that the assumptions of the model were met. Classification of deaths Fifty-seven per cent of all death certificates completed by the forensic pathologists reported the cause of death as either "narcotism", "acute narcotism" or "acute intravenous narcotism". Although alcohol was detected in 45% of subjects at time of death, it was noted on the death certificate in only 7% of cases. Most deaths (80%) were classified according to ICD-94 coding as cases of "dependence" (code 304.0), 10% as cases of accidental poisoning (E850.0), 9% as suicides (E950.0) and 1% as opiate drug dependence with contributions from other drugs (304.7). Discussion We found that heroin-related deaths occurred overwhelmingly in people who were male, of an average age of 30 years, and frequent users. Few occurred in those considered to be infrequent users. A recent survey has shown that two-thirds of a large sample of heroin users have had at least one non-fatal overdose and that 86% have been present at another person's overdose.6 This suggests that campaigns designed to reduce the rising mortality rate caused by heroin need to target regular users. The finding that only a minority of cases had ever been in methadone treatment is consistent with other evidence that methadone treatment reduces mortality among the heroin-dependent.7,8 Some of our subjects might be alive today if they had entered and remained in methadone treatment. A striking finding from the toxicological data was the relatively small number of subjects in whom morphine only was detected. Most died with more drugs than heroin alone "on board", with alcohol detected in 45% of subjects and benzodiazepines in just over a quarter. Both of these drugs act as central nervous system depressants and can enhance and prolong the depressant effects of heroin. Our finding (and that of other studies9,10 ) of a significantly lower blood morphine level in subjects who tested positive for alcohol suggests that in the presence of alcohol less heroin is required to exert a fatal effect. Alternatively, alcohol-induced liver enzymes may increase the metabolism of heroin. The very low blood levels of morphine we found may also support these hypotheses. Some pathologists have been reluctant to attribute a heroin-caused death to true overdose because of the frequent finding of a low blood morphine concentration, and prefer to report the death as a case of "narcotism" (Johan Duflou, Deputy Director, Insti tute of Forensic Medicine, Sydney, personal communication, 1993). Further, Monforte showed that in 75% of a group of people who had died from fatal heroin "overdoses" blood morphine concentrations were not higher than in a group of heroin addicts who were victims of homicide.11 Bammer and Sengoz have also challenged the assumption that heroin deaths occur as a result of increased purity of heroin. In a recent paper they identified concomitant consumption of other drugs and reduced tolerance as alternative mechanisms for the cause of death in heroin fatalities.12 The disadvantage of continuing to describe heroin-related fatalities as "overdoses" is that it attributes the cause of death solely to heroin and detracts attention from the contribution of other drugs to the cause of death. Heroin users need to be educated about the potentially dangerous practice of concurrent polydrug and heroin use. Our findings that an ambulance was called while the subject was still alive in only 10% of cases, and that a substantial minority of heroin users died alone, strongly suggest that education campaigns should also emphasise that it is safer to inject heroin in the company of others, and important to call for an ambulance early in the event of an overdose. Consideration should also be given to trialling the distribution of the opioid antagonist naloxone to users to reduce mortality from heroin use. In conclusion, fatal heroin overdose is potentially preventable and research should now focus on reducing its occurrence. The introduction or intensification of education campaigns explaining the risk of polydrug use to heroin users may help to reverse the national trend in heroin-related deaths. Acknowledgements This research was funded by South Western Sydney Area Health Service and the National Drug and Alcohol Research Centre. We would like to thank the following organisations for their assistance: Department of Courts Administration, in particular Glebe Coroners Court and Westmead Coroners Court, and the NSW Registry of Births, Deaths and Marriages. We would also like to thank Mr Stephen Bull of the Australian Bureau of Statistics (NSW office), Dr Johan Duflou, Professor Wayne Hall and Dr Alex Wodak. References Drug Caused Deaths in Australia 1990. Drugs of Dependence Branch statistical update. Number 18. Canberra: Commonwealth Department of Health, Housing and Community Services, August 1992. Swensen G. Opioid deaths in Western Australia: 1974-1984. Aust Drug Alcohol Rev 1988; 7: 181-185. Walsh RA. Opioid drug accidental deaths in the Newcastle area of New South Wales, 1970-1987. Drug Alcohol Rev 1991; 10: 79-83. World Health Organization. International statistical classification of diseases, injuries and causes of death. Vol. 1. Geneva: WHO, 1977. Wilkinson L. SYSTAT: the system for statistics [computer program]. Evanston, Il.: SYSTAT Inc, 1990. Darke S, Ross J, Hall W. Overdose among heroin users in Sydney, Australia: I. Prevalence and correlates of non-fatal overdose. Addiction 1996; 91: 405-411. Gronbladh L, Ohland LS, Gunne LM. Mortality in heroin addiction: impact of methadone treatment. Acta Psychiatr Scand 1990; 82: 223-227. Caplehorn JRM, Dalton MSYM, Cluff MC, Petrenas AM. Retention in methadone maintenance and heroin addicts' risk of death. Addiction 1994; 89: 203-207. Ruttenber AJ, Kalter HD, Santinga P. The role of ethanol abuse in the etiology of heroin related deaths. J Forensic Sci 1990; 35: 891-900. Chan L, Prolov T, Verma S. Morphine tissue concentrations in fatal overdoses in New South Wales, 1986-1987. Proceedings of the 10th Australian International Forensic Science Symposium; 1988 May 23-27; Brisbane. Brisbane: Australian Forensic Science Society, 1988. (Abstract No. 2333.) Monforte JR. Some observations concerning blood morphine concentrations in narcotic addicts. J Forensic Sci 1977; 22: 718-724. Bammer G, Sengoz A. How would the controlled availability of heroin affect the illicit market in the Australian Capital Territory? An examination of the structure of the illicit heroin market and methods to measure changes in price, purity, availability, including heroin-related overdoses. Canberra: National Centre for Epidemiology and Public Health, 1994. (Working Paper No. 10.) (Received 13 Jun, accepted 19 Oct 1995) Authors' details Drug and Alcohol Services, Division of Public Health, South Western Sydney Area Health Service, Sydney, NSW. Deborah Zador, MB BS, FAFPHM, Staff Specialist. Currently, Staff Specialist, Drug and Alcohol Services, Central Sydney Area Health Service, NSW. Sandra Sunjic, BAppSc, MA, Clinical Nurse Specialist. National Drug and Alcohol Research Centre, University of New South Wales, Sydney, NSW. Shane Darke, PhD, Lecturer. No reprints will be available. Correspondence: Dr D Zador, Gladstone Hall Health Services, 114 Ewart Street, Dulwich Hill, NSW 2203. ©MJA 1997 <URL: http://www.mja.com.au/> © 1997 Medical Journal of Australia.

Deborah Zador · Sandra Sunjic · Shane Darke

Research Consumption of oily fish and childhood asthma risk Linda Hodge, Cheryl M Salome, Jennifer K Peat, Michelle M Haby, Wei Xuan and Ann J Woolcock For editorial comment, see Thien et al. Abstract - Authors' details - Introduction - Methods - Results - Discussion - Appendix - Acknowledgements - References - Box 1 - Box 2 - Box 3 - Figure - © MJA 1996 - Abstract Objective: To investigate the association between diet and airway disease in children in the light of epidemiological studies suggesting that consumption of fish more than once a week reduces the risk of developing airway hyperresponsiveness (AHR). Design: Diet was assessed by a detailed food frequency questionnaire and airway disease by respiratory symptoms or airway responsiveness to exercise. Methods: A questionnaire, containing questions about the frequency of eating more than 200 foods, was sent to the parents of 574 children in whom we had measured recent wheeze (by questionnaire), AHR (by exercise) and atopy (by skin prick tests) six months before this study. We defined current asthma as the presence of both recent wheeze and AHR. Results: Response rate to the questionnaire was 81.5% (n = 468). After adjusting for confounders such as sex, ethnicity, country of birth, atopy, respiratory infection in the first two years of life and a parental history of asthma or smoking, children who ate fresh, oily fish (> 2% fat) had a significantly reduced risk of current asthma (odds ratio, 0.26; 95% confidence interval, 0.09-0.72; P < 0.01). No other food groups or nutrients were significantly associated with either an increased or reduced risk of current asthma. Conclusion: These data suggest that consumption of oily fish may protect against asthma in childhood. MJA 1996; 164: 137-140 Introduction The substantial increase in the prevalence of childhood asthma in the past 20 years has affected both rural and urban communities of westernised countries,1,2 suggesting that local environmental factors, such as exposure to allergens or industrial air pollutants, are not the cause. However, the widespread changes in diet may be responsible. Seaton et al.3 have postulated that increases in the prevalence of asthma may be due to a reduced intake of antioxidant vitamins (beta-carotene, vitamins A, C and E) and mineral cofactors essential for antioxidant defence mechanisms (selenium, zinc and copper) as a result of reduced consumption of meat, fresh fish, fruit and vegetables in Western diets. Reduced consumption of magnesium4 and increased consumption of salt5 have been implicated as risk factors for airway hyperresponsiveness (AHR). Our own epidemiological studies of Australian schoolchildren have shown that children who eat fish more than once a week have a third the risk of AHR of children who do not eat fish regularly.6 However, these studies did not include other dietary questions, so that fish consumption may have been a marker for another dietary characteristic. Here, we investigate the association between diet, as assessed by a detailed dietary questionnaire, and airway disease, assessed by respiratory symptoms or airway responsiveness to exercise. Methods Subjects In June 1993, a cross-section of 808 children aged 8-11 years from schools randomly selected from all schools within a 10 km radius of Sydney General Post Office had airway responsiveness to exercise, respiratory symptoms and atopy measured and frequency of fish consumption assessed.7 In October 1993, 584 children were selected from this group in a stratified case-control design and their parents were asked to complete a detailed food frequency questionnaire about their child's eating habits. The selection criteria included all children with AHR, all children who had had wheeze in the last 12 months (recent wheeze) and a three-in-five sample of children with normal airways (no AHR or recent wheeze), who were chosen by excluding two children after every three from numerically ordered lists of children identified by number. The study coordinator who collected the food frequency questionnaires was blind to the respiratory symptom and AHR status of the subjects. Ethical approval for the study was obtained from the Ethics Review Committee of the University of Sydney. Permission to approach schools was obtained from the New South Wales Department of School Education and the Catholic Education Office. Respiratory questionnaire In June 1993 the parents or guardians of the children completed a standard respiratory questionnaire, with questions on age, sex, ethnicity, country of birth, history of asthma or wheeze in the last 12 months, medication use, and also parents' occupations, history of asthma and smoking. The questionnaire included the question used in previous studies about the dietary consumption of fish - "How often does your child eat a meal that contains fish?" - with the options of replying "never or rarely", "once a week", or "more than once a week". Dietary questionnaire In October 1993, a food frequency questionnaire (adapted from that developed and validated by the Commonwealth Scientific and Industrial Research Organisation [CSIRO], Division of Human Nutrition, South Australia8,9) was distributed to the selected children, whose parents were asked to complete this for their child's usual eating habits over the last year. The questionnaire identified consumption patterns (daily, weekly, monthly, rarely or never) of more than two hundred foods commonly consumed in Australia. Additional questions on the type of fresh fish consumed and regular consumption of vitamin, mineral or herbal supplements were included. Estimates of sodium intake included naturally occurring sodium in foods, salt added in cooking, at the table and from processed foods. If questionnaires were not returned after one month the parents were contacted by telephone and offers were made to replace the questionnaires, or to provide assistance. In 11 cases, where neither parent spoke fluent English, an interpreter was commissioned to complete the questionnaire with the parents over the telephone. Returned dietary questionnaires were checked for missing or obviously erroneous information. Parents were contacted by telephone to complete omitted sections or to clarify erroneous information. Each food in the dietary questionnaire was allocated to one of 23 different food groups (see Appendix). Diets were analysed for energy, fibre and 39 nutrients (see Appendix). Definitions of respiratory categories, atopy, and categories of fish, plus a list of fish with more than 2% fat, are given in Box 1. Statistical analyses The questionnaires were analysed by the Division of Human Nutrition, CSIRO, South Australia, using Australian tables of nutrient composition12 for energy, protein, fat, carbohydrates, vitamins and minerals. The total quantity of food in each food group for every child was converted to a common base of weekly serves with Clinical Reporting Systems software.13 Data were analysed with the statistical package SAS.14The association between fish, food or nutrient intake and respiratory category was analysed categorically using chi-squared tests, and continuously using Student's t tests and analysis of variance. Some values obtained from the nutrient analysis were well outside what could reasonably be expected in children of this age group. These outliers were excluded from the statistical analysis. The number of exclusions never exceeded nine subjects in any analysis and were not significantly associated with any of the respiratory groups. Logistic regression was used to adjust estimates for the effects of known confounders for the effect of fish consumption on AHR and symptoms of asthma (e.g., sex, race, country of birth, atopy, early respiratory infection, parental smoking and parental asthma). Only those confounding factors found to be significant or approaching significance (P < 0.1) (atopy, parental asthma, early respiratory infection, country of birth) were included in the model. Results Of the 584 children selected 574 received the dietary questionnaire and 468 completed questionnaires were returned (81.5%). Non-responders were not significantly different from responders in the prevalence of AHR (26.0% v. 27.1%) or fish consumption (46.2% v. 52.1%). Box 2 shows details of the children studied. Children with current asthma did not differ significantly from children with normal airways in the consumption of any nutrient or food group. (Tables showing mean weekly intake in standard serves of food groups and mean daily intake [SD] of nutrients for children with normal airways and children with current asthma are available from the authors.) Children with wheeze only had a significantly higher intake of red meat (P < 0.05), offal meat (P < 0.001) and vitamin B12 (P < 0.03) and a significantly lower intake of mixed vegetables (P < 0.05) than children with normal airways. Children with AHR only consumed significantly more offal meat (P = 0.001) and high fat/high sugar foods (P < 0.001) than children with normal airways. They also had higher intakes of nitrogen, protein, total sugar, cholesterol, potassium nicotinamide, total nicotinamide, calcium, copper, zinc, vitamin B12 (P < 0.05) and refined sugar (P < 0.01). Total fish intake per week did not differ significantly between children with normal airways (1.2 serves per week; 95% confidence interval [CI], 1.0-1.3), AHR only (1.2 serves; CI, 0.9-1.5), wheeze only (1.2 serves; CI, 0.8-1.5) and current asthma (1.0 serve; CI, 0.8-1.2). Fresh fish was eaten by 84% (CI, 79.6%-88.4%) of children with normal airways, and by 72% (CI, 61.6%-82.4%) of children with current asthma. When fresh fish was divided into oily and non-oily types, significantly fewer children with current asthma (15.5%; CI, 7.1%-23.9%) included oily fish in their diet than did children with normal airways (30.8%; CI, 25.2%-36.4%; P < 0.05). There were no significant differences in the proportions of children with current asthma (56.3%; CI, 44.8%-67.8%) and normal children (52.9%; CI, 46.9%-58.9%) who ate exclusively non-oily fish. Neither fresh fish consumption nor respiratory disease was significantly associated with socioeconomic status, as defined by the father's occupation, or with the consumption of vitamin, mineral or other dietary supplements (including fish oil). The unadjusted risk (odds ratio) for children having current asthma was significantly lower in those who consumed any fresh fish or oily fresh fish (Box 3). Current asthma was found in only 8.8% (CI, 3.8%-13.8%) of children who ate oily fish, but in 15.6% (CI, 11.2%-20.0%) of those who ate non-oily fish only and 23% (CI, 14.2%-31.8%) of those who never ate fresh fish (Figure). When the results were adjusted for the effects of other known risk factors such as atopy, parental asthma, parental smoking, ethnicity, country of birth, early respiratory illness and sex, only children who ate oily fresh fish had a significantly reduced risk of current asthma. In these children, the risk was almost a quarter that of children who did not eat oily fish (odds ratio, 0.26; CI, 0.09-0.72) (Box 3). Consumption of any fresh fish, whether or not it was separated into oily fresh fish and non-oily fresh fish, did not significantly reduce the risk of AHR only or wheeze only either before or after adjustment for other risk factors. Discussion Our study shows that regular consumption of fresh, oily fish is associated with a reduced risk of current asthma. This reduced risk remained significant after adjustment for other known risk factors for asthma, including sex, atopy, parental asthma, parental smoking, early respiratory infection, ethnicity and place of birth. The subjects were selected from a random cross-sectional sample of children which was stratified (on the basis of recent respiratory symptoms and AHR to exercise) to increase the proportion of cases in the study group. The response rate was high (81.5%) and non-responders were not different from responders with respect to AHR or fish consumption. Socioeconomic status was not a confounder for either respiratory illness or fish consumption. Current asthma was defined as recent wheeze plus AHR to exercise. We have shown previously that current asthma, defined as recent wheeze plus AHR to histamine, identifies a group with severe, ongoing respiratory impairment, while those with AHR only and wheeze only have a milder condition which differs only slightly from the normal group.15 The diets of children with current asthma differed from those of the normal group only in the consumption of fresh, oily fish. In our previous study, more than one serve of fish per week was associated with a reduced risk of asthma,6 but in that study it was not possible to distinguish the effects of oily and non-oily fish. In the study reported here we were unable to detect differences in total fish consumption, possibly because of the smaller sample size. There were no significant differences between respiratory groups in the consumption of non-oily fish, suggesting that parents had not selectively withheld fish from the diets of asthmatic children. It is unclear why consumption of canned and processed fish was not associated with reduced risk of asthma. Processing may alter the integrity or activity of the fatty acids in fish oils. Several foods and nutrients in the diets of children with AHR only and wheeze only differed significantly from those of the normal group. However, none of these factors differed between the asthmatic and normal groups, suggesting that they are unlikely to have an aetiological role. Intake of offal meats was higher in both the AHR-only and wheeze-only groups, but, as offal meats are eaten by very few children, this may be a type I error. Vitamin B12 intake was also higher in both the AHR-only and wheeze-only groups, but the mechanism by which this could affect respiratory symptoms or AHR is unclear. There were no significant differences between any of the respiratory groups in consumption of sodium, vitamin C, vitamin E, selenium or magnesium. These findings do not support previous evidence that these dietary factors are important in the aetiology of asthma.4,5,16 Reduced risk of current asthma was associated with the consumption of oily fish, but not with non-oily fish. Fish oil contains the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which have anti-inflammatory effects.17 Theoretically, EPA could either prevent the development of asthma or reduce its severity by altering two of the cardinal features of asthma, namely airway inflammation and AHR. Supplementation with EPA reduces production of leukotriene B4,18 a chemical mediator responsible for the recruitment of inflammatory cells, such as neutrophils, into the airways. It also reduces production of the cytokine tumour necrosis factor (TNF),19 which increases airway responsiveness.20 Fish oil supplements given over 6-10 weeks cause a substantial uptake of EPA in neutrophil membrane phospholipids.18,21 In asthmatics, this may reduce the allergen-induced late asthmatic response,22 but does not change severity of asthma.21,22 However, a recent study suggests that a longer period of supplementation may be required to reduce asthma severity.23 Data of recent fish consumption (during the last 12 months) were used in our study, but may also reflect lifetime dietary habits. In conclusion, we have shown that consumption of oily fish is associated with a reduced risk of asthma in childhood. Although further studies are required to confirm these benefits, public health interventions to increase the consumption of oily fish may reduce the morbidity and prevalence of asthma in children. Appendix The 23 food groups were: cereals; dairy products; eggs; red, white, preserved meat and offal; seafood, fried, steamed, canned fish and fish fingers; red, green, white, mixed and other vegetables; legumes; high and low vitamin C fruit and other fruit; high sugar or fat content; and other. The 39 nutrients were: nitrogen; protein; starch; refined, natural and total sugar; total carbohydrate; saturated, monounsaturated, polyunsaturated and total fat; cholesterol; carotene; retinol; vitamin A; thiamine; riboflavin; potassium nicotinic acid and total nicotinic acid; niacin; vitamins B6 and B12; pantothenic acid; biotin; free and total folate; vitamins C, D, E; calcium; copper; iron; magnesium; manganese; phosphorus; potassium; selenium; sodium; and zinc. Acknowledgements This study was supported by the Fisheries Research and Development Corporation, Australia. The authors thank Dr Katrine Baghurst for allowing us to use the dietary questionnaire, Sally Record and Kay Pender for their help with the nutritional analyses, Elena Belooussova for data organisation and Suzanne Gray for her assistance with collecting the questionnaires. We are grateful for the support of the New South Wales Department of School Education, the Catholic Education Office and the Principals and teachers of all the schools involved. We are especially grateful to the parents and the children who participated in the survey. (©MJA 1996; 164: 137-140) References Robertson CF, Bishop J, Sennhauser FH, Mallol J. International comparison of asthma prevalence in children: Australia, Switzerland, Chile. Pediatr Pulmonol 1993; 16: 219-226. Burney P, Chinn S, Rona RJ. Has the prevalence of asthma increased in children? Evidence from the national study of health and growth 1973-86. BMJ 1990; 300: 1306-1310. Seaton A, Godden DJ, Brown K. Increase in asthma: a more toxic environment or a more susceptible population? Thorax 1994; 49: 171-174. Britton J, Pavord I, Richards K, et al. Dietary magnesium, lung function, wheezing, and airway hyperreactivity in a random adult population sample. Lancet 1994; 344: 357-362. Burney PG, Neild JE, Twort CHC, et al. Effect of changing dietary sodium on the airway response to histamine. Thorax 1989; 44: 36-41. Peat JK, Salome CM, Woolcock AJ. Factors associated with bronchial hyperresponsiveness in Australian adults and children. Eur Respir J 1992; 5: 921-929. Haby MM, Peat JK, Mellis CM, et al. An exercise challenge for epidemiological studies of childhood asthma: validity and repeatability. Eur Respir J 1995; 8: 729-736. Baghurst KI, Record SJ. Intake and sources in selected Australian subpopulations of dietary constituents implicated in the etiology of chronic diseases. J Food Nutr 1983; 40: 1-15. Rohan TE, Record SJ, Cook MG. Repeatability of estimates of nutrient and energy intake: the quantitative food frequency approach. Nutr Res 1987; 7: 125-137. Analyses of NSW fish and shellfish. Sydney: Australian Government Analytical Laboratory, 1989. Sinclair A, Dunstan GA, Naughton JM, et al. The lipid content and fatty acid composition of commercial marine and freshwater fish and molluscs from temperate Australian waters. Aust J Nutr Diet 1992; 49: 77-83. English R, Lewis J. Composition of foods Australia. 1st ed. Vols 1-5. Canberra: AGPS, 1989-1990. Clinical Reporting Systems [computer program], version 3.0. Sydney: Clinical Reporting Systems Pty Ltd. 1992. SAS [computer program], version 5. Cary, NC: SAS Institute, 1984. Toelle BG, Peat JK, Salome CM, et al. Toward a definition of asthma for epidemiology. Am Rev Respir Dis 1992; 146: 633-637. Stone J, Hinks LJ, Beasley R, et al. Reduced selenium status of patients with asthma. Clin Sci 1989; 77: 495-500. Kremer JM, Jubiz W, Michalek A, et al. Fish-oil fatty acid supplementation in active rheumatoid arthritis. Ann Intern Med 1987; 106: 497-503. Lee TH, Hoover RL, Williams JD, et al. Effect of dietary enrichment with eicosapentaenoic and docosahexaenoic acids on in vitro neutrophil and monocyte leukotriene generation and neutrophil function. N Engl J Med 1985; 312: 1217-1224. Endres S, Ghorbani R, Kelley VE, et al. The effect of dietary supplementation with n-3 polyunsaturated fatty acids on the synthesis of interleukin-1 and tumor necrosis factor by mononuclear cells. N Engl J Med 1989; 320: 265-271. Thomas PS, Yates DH, Barnes PJ. Tumor necrosis factor-alpha increases airway responsiveness and sputum neutrophilia in normal human subjects. Am J Respir Crit Care Med 1995; 152: 76-80. Arm JP, Horton CE, Mencia-Huerta J-M, et al. Effect of dietary supplementation with fish oil lipids on mild asthma. Thorax 1988; 43: 84-92. Arm JP, Horton CE, Spur BW, et al. The effects of dietary supplementation with fish oil lipids on the airways response to inhaled allergen in bronchial asthma. Am Rev Respir Dis 1989; 139: 1395-1400. Dry J, Vincent D. Effects of fish oil diet on asthma: results of a 1-year double blind study. Int Arch Appl Immunol 1991; 95: 156-157. (Received 31 May, accepted 28 Nov 1995) Authors' details Institute of Respiratory Medicine, Royal Prince Alfred Hospital, Sydney, NSW. Linda Hodge, MSc(Med), GradDipNutr&Diet, Dietitian. Department of Medicine, University of Sydney, Sydney, NSW. Cheryl M Salome, BSc, Senior Research Officer. Jennifer K Peat, PhD, Senior Research Officer. Michelle M Haby, MSc, Research Assistant. Wei Xuan, MSc, MApplStat, Statistician. Ann J Woolcock, MD, FRACP, Professor in Respiratory Medicine. Reprints: Professor A J Woolcock, Institute of Respiratory Medicine, Royal Prince Alfred Hospital, Camperdown, NSW 2050. (©MJA 1996; 164: 137-140)

Linda Hodge · Cheryl M Salome · Jennifer K Peat · Michelle M Haby · Wei Xuan · Ann J Woolcock

Drug-resistant Streptococcus pneumoniae: the beginning of the end for many antibiotics? Peter J Collignon and Jan M Bell, on behalf of the Australian Group on Antimicrobial Resistance (AGAR)* Abstract - Introduction - Methods - Antibiotic sensitivity testing - Statistical analysis - Results - Discussion - Acknowledgements - References - Authors' details - ©MJA1997 Abstract Objective: To determine the levels of antibiotic resistance in Streptococcus pneumoniae in Australia. Design: Prospective, Australia-wide, laboratory-based survey. Setting: 27 hospital and private laboratories around Australia, from January 1994 to August 1995. Subjects: First 100 patients with clinically significant isolates of S. pneumoniae at each laboratory. Outcome measures: Resistance to penicillin (determined from penicillin minimum inhibitory concentration [MIC] measured by the Etest), erythromycin, trimethoprim-sulfamethoxazole, tetracycline, chloramphenicol, cefotaxime and ceftriaxone. Results: A total of 2396 isolates were tested (including 537 invasive isolates and 740 from children). Penicillin resistance was seen in 161 isolates (6.7%), including 17 with high level resistance. Penicillin resistance rates were significantly lower in invasive than in non-invasive strains (3.7% versus 7.6%; odds ratio [OR], 0.47; 95% confidence interval [CI], 0.28-0.77; P = 0.001). There was no significant difference in penicillin resistance rates between children ( < 15 years) and adults (7.3% versus 6.5%; OR, 1.14; 95% CI, 0.80-1.63; P = 0.47). Resistance rates were higher for most other antibiotics than for penicillin (chloramphenicol, 6%; erythromycin, 11%; tetracycline, 15%; and trimethoprim-sulfamethoxazole, 42%). No high level resistance was seen to third generation cephalosporins, but 17 of 109 penicillin-resistant isolates tested (16%) displayed intermediate resistance to cefotaxime. Rates of antibiotic resistance varied between States, with the lowest rates in Tasmania. Conclusions: Antibiotic resistance levels in S. pneumoniae are increasing in Australia and high level penicillin resistance is being encountered for the first time (including in invasive strains). This will lead to an increasing number of therapeutic dilemmas and possible therapeutic failures, especially important in meningitis. MJA 1996; 164: 64 Introduction The pneumococcus (Streptococcus pneumoniae) continues to be a common cause of serious and life-threatening infections, including pneumonia, bacteraemia and meningitis. It is also a frequent cause of respiratory tract infections, such as otitis media and sinusitis.1-4 A major advance was made in the treatment of these infections with the introduction of penicillin 50 years ago. Until relatively recently, pneumococci were considered so uniformly sensitive to penicillin (with minimum inhibitory concentrations [MICs] < 0.02 mg/L) that sensitivity tests were usually not performed. It was from Australia in 1967 that the first clinically significant isolate of a penicillin-resistant pneumococcus was reported.5 However, penicillin resistance was not a major clinical problem in this country, although it caused major problems elsewhere, particularly in Papua New Guinea and South Africa.1-3 In the late 1970s and the 1980s, rates of resistance (including multiple resistance) increased in Western countries, particularly in Spain (with resistance levels of 50%).1,2,3 A recent United States study found 25% of invasive S. pneumoniae isolates were penicillin-resistant.6 Resistance rates are usually higher in children, and the distribution of resistance varies within countries and population groups.1,2,3,6 In an Australia-wide study of over 1800 isolates of S. pneumoniae in 1989, we found that only 1% were penicillin-resistant,7 a lower rate than in most other Western countries. However, some communities (especially Australian Aboriginals) have relatively high rates of resistance.8 Because of the worldwide increase in resistance to many antibiotics and the implications of penicillin resistance in S. pneumoniae for treatment of life-threatening conditions (particularly meningitis), we undertook a further study of resistance to penicillin and other commonly used antibiotics in clinically significant S. pneumoniae isolates from both the community and hospitals. Methods Twenty-seven hospital and private laboratories from around Australia parti cipated. From January 1994, each laboratory tested the first 100 consecutive clinically significant isolates. The rate of collection varied from 5 to 20 months, with all laboratories filling their quota in August 1995. Patients' sex, age, specimen site and inpatient or outpatient status were recorded prospectively. Clinically significant isolates were defined as those isolated either from normally sterile sites (e.g., cerebrospinal fluid and blood [invasive isolates]) or from specimens that made contact with mucosal surfaces (e.g., sputum) if they were associated with an increased white cell count on gram staining and would normally have been reported as clinically significant. Throat or surveillance swabs were excluded, as were duplicates of clinically significant isolates. S. pneumoniae was identified by colonial morphology, a -haemolysis on blood agar plates, susceptibility to optochin and/or bile solubility. Antibiotic sensitivity testing Isolates were tested for susceptibility to penicillin, erythromycin, trimethoprim-sulfamethoxazole, tetracycline and chloramphenicol by the standardised routine method of each laboratory. Methods included disc diffusion with either National Committee for Clinical Laboratory Standards (NCCLS)9 (14 laboratories) or Calibrated Dichotomous Sensitivity (CDS)10,11 (7 laboratories); agar dilution12 with either Isosensitest agar (Oxoid) (2 labora tories) or Mueller-Hinton agar (3 lab oratories); and the ATB system (BioMerieux sa , Marcy-l'Etoile, France) (1 laboratory). The MIC of penicillin was also determined for each isolate by the Etest on Mueller-Hinton agar supplemented with 5% blood;13,14 plates were incubated at 35¡C in 5% CO 2 for 20-24 hours. 14 The interpretive criteria of the NCCLS15 were used for susceptibility categorisation of Etest values (susceptible, MIC < 0.06 mg/L; intermediate resistance, MIC = 0.125-1 mg/L; and high level resistance, MIC > > 2 mg/L). For the study, antibiotic resistance was defined as decreased susceptibility (both intermediate and high level resistance),6,12 and multidrug resistance as decreased susceptibility to two or more of the antibiotic agents tested. Isolates from normally sterile sites and those that appeared resistant to penicillin or chloramphenicol by routine susceptibility testing or had penicillin MICs > > 0.047 mg/L were forwarded to Monash Medical Centre for further susceptibility testing: Etest strips were used to determine cefotaxime and ceftriaxone MICs. Statistical analysis Fisher's two-tailed exact test was used to calculate P values. Calculations were performed with True Epistat software.16 Results A total of 2396 isolates from different patients were tested. The average age of the patients was 41.6 years (range, < 1 day to 98 years); 32% were children ( < 15 years) and 60% were male. The percentage of penicillin-resistant isolates from each specimen site is shown in Box 1; the overall rate of penicillin resistance was 6.7%, with rates in individual laboratories ranging from 0 to 13%. High level resistance was seen in 17 isolates, including two from normally sterile sites. The rate of penicillin resistance was significantly lower among invasive isolates than among non-invasive isolates (3.7% versus 7.6%; odds ratio [OR], 0.47; 95% confidence interval [CI], 0.28-0.77; P = 0.001) (Box 2). The rate of penicillin resistance was slightly higher among children ( < 15 years) than among adults, but the difference was not statistically significant (7.3% versus 6.5%; OR, 1.14; 95% CI, 0.8-1.63; P = 0.47). Resistance to antibiotics other than penicillin was common (Boxes 2 and 3). Rates varied around Australia, with the lowest rates for nearly all antibiotics in Tasmania and the highest in the eastern States, particularly Queensland and New South Wales. The rate of penicillin resistance was highest in South Australia. Very high levels of resistance were seen for trimethoprim-sulfamethoxazole (29%-52%). All five antibiotics were tested on 1895 isolates; 267 (14%) were multi resistant, with 159 (8%) resistant to three or more antibiotics and 31 (1.6%) to all five (Box 3). Of 124 penicillin-resistant isolates tested, 72 (58%) were resistant to three or more non--lactam agents; 40% were resistant to chloramphenicol; 52% to erythromycin; 64% to tetracycline; and 78% to trimethoprim-sulfamethoxazole. Of the 1771 pencillin-susceptible isolates, 101 (6%) were resistant to three or more non--lactam agents; 3% to chloramphenicol; 8% to erythromycin; 12% to tetracycline; and 39% to trimethoprim- sulfamethoxazole . Of 109 penicillin-resistant isolates tested with cefotaxime, 17 (16%) had intermediate resistance (MIC, 1 mg/L). These comprised 12 of 13 isolates with high-level penicillin resistance and 5 of 96 with intermediate penicillin resistance. Only three of the 109 isolates had intermediate resistance to ceftriaxone (all with high-level penicillin resistance). Discussion We found that the level of penicillin resistance among S. pneumoniae isolates was six times higher than that found in 1989 in the only other large multicentre Australian study,7 but fortunately it was still lower than in most other countries. Penicillin resistance rates are very high in Third World countries, and in some areas of Western Europe and the USA.1-3 However, the rate of rise in resistance in Australia appears very similar to that seen in the early 1980s in countries such as Spain1-3 and in the early 1990s in the United States;6 there, only 0.02% of isolates nationally were penicillin-resistant in the early 1980s and still only 1.3% in 1992,6 but a recent study found a rate of 25%, with much higher rates in some subgroups (e.g., 40% in white children). Of equal concern was that 3% of isolates had high level resistance to both penicillin and third generation cephalosporins.6 Over the next few years, we are likely to see similar rates of resistance developing in Australia. The finding of high level penicillin resistance among S. pneumoniae isolates in Australia is of particular concern; in meningitis caused by organisms with any level of penicillin resistance, penicillin treatment is likely to fail.1-3,17,18 Penicillin resistance has consequences for other related drugs, as in S. pneumoniae it is not due to -lactamase production (as in Staphylococcus aureus ), but to changes in the target for penicillin (the penicillin-binding proteins).1,2,19 This change increases the MICs for all -lactams, including the third generation cephalosporins.1,2,19 However, the levels of third generation cephalosporins achieved in cerebrospinal fluid are still high enough to eradicate organisms with intermediate penicillin resistance.1-3,18 Alternative regimens include combination therapy with vancomycin, third generation cephalosporins and rifampicin, as well as newer agents such as meropenem, teicoplanin and quinolones (under investigation),1 but none has been adequately evaluated. Of even greater concern are the implications of the rapid rise in resistance to third generation cephalosporins noted in the United States. Primary resistance to these drugs is less frequent than to penicillin, but requires less genetic change.1,19 In some areas up to 27% of penicillin-resistant pneumococci have high level resistance to cefotaxime.1 This leads to therapeutic failure of these agents, yet they are the main treatment for the increasingly common intermediate penicillin-resistant strains. No high level cefotaxime-resistant strains were seen in our study or have been reported in Australia, to our knowledge. However, given the worldwide spread of resistant pneumococci in the recent past, they will inevitably be seen soon in Australia and leave us with major therapeutic dilemmas in the treatment of meningitis. In life-threatening situations other than meningitis (e.g., bacteraemia), high dose intravenous penicillin appears sufficient to eradicate organisms with intermediate resistance, as drug levels achievable in serum are still much higher than the MIC.1,2,3 There is, however, controversy, and many recommend use of either cefotaxime or ceftriaxone.1,3 For organisms with high level resistance, the most appropriate agent is unclear. However, we would favour vancomycin. In non-life-threatening infections with penicillin-resistant pneumococci, the most appropriate antibiotics are less clear. In otitis media, amoxycillin still appears the best choice,20,21 as drug levels achieved in the middle ear can still exceed the MICs of strains with intermediate resistance (although higher doses may be needed). Other oral agents available in Australia for use in children (cefaclor, trimethoprim, erythromycin and cefpodoxime) do not reach adequate levels to eradicate resistant isolates.20,21 Third generation cephalosporins, such as ceftriaxone, are active, but their parenteral route is likely to preclude their use. Combining clavulanic acid with amoxycillin is no advantage, as the resistance is not due to -lactamase. For high level penicillin-resistant isolates there does not appear to be a satisfactory oral agent. The reasons for the increasing resistance in S. pneumoniae worldwide are not completely understood, although antibiotic pressure appears to be a major factor.1 A few resistant clones were shown to have spread from one continent to others (e.g., from Spain to the United States and Iceland) and then through the local population, undergoing minor genetic changes in the process.1,3,19 The pneumococcus can acquire DNA molecules from other bacteria that probably include viridans group streptococci (e.g., Streptococcus mitis), which form part of the normal flora of the nasopharynx.1,19 While it would probably be impossible to eradicate carriage of these resistant organisms from the population, it may be possible to reduce the rate of increase in resistance by minimising the prescription of unnecessary antibiotics. Other strategies, such as vaccination, may be necessary. Unfortunately, the currently available vaccine is a polysaccharide and therefore a poor immunogen, especially in young children. Studies are under way to assess a conjugated pneumococcal vaccine (i.e., a carbohydrate with protein carrier), but vaccine development is difficult as there are over 80 serotypes of pneumococci (compared with only one commonly invasive serotype of Haemophilus influenzae -- type b). However, at present most of the resistant organisms belong to relatively few serotypes.1,2,3 A vaccine containing most of these might not only decrease life-threatening disease, but might also decrease carriage of the organisms, as was found for the H. influenzae type b (Hib) vaccine.1 However, as the pneumococcus can acquire DNA from other organisms,1,19 the number of resistant serotypes is likely to increase. Our study was one of the largest in the world where all organisms were clinically significant and all were assessed for MIC for penicillin. It is valuable not only for showing the rate of resistance (both intermediate and high level), but also for providing a baseline to assess future changes in resistance and to differentiate subtle shifts in resistance in the whole population of pneumococci from the introduction of resistant clones. In the past, determining MICs was time-consuming, laborious and not routine. The recent development of the Etest (which consists of a strip of paper impregnated with increasing concentrations of antibiotic from one end to the other) has simplified the procedure. This technological advance, along with the willingness of so many laboratories around Australia to participate in the project, has allowed us to obtain information essential for guiding us in making appropriate antibiotic choices and designing empiric therapy for these emerging threats. Acknowledgements We wish to thank the many doctors, scientists and technicians at the participating laboratories who donated their time and resources to carry out this project. The penicillin Etest strips were supplied by Australian Laboratory Services Pty Ltd at cost price. Eli Lilly provided funding for many of the participants to meet at the twice-yearly AGAR meeting. Cefotaxime and ceftriaxone Etest strips were donated by AB Biodisk (Sweden). References Lister PD. Multiply-resistant pneumococcus: therapeutic problems in the management of serious infection. Eur J Clin Microbiol Infect Dis 1995; 14 Supp 1: 18-25. Klugman K. Pneumococcal resistance to antibiotics. Clin Microbiol Rev 1990; 3: 171-196. Schreiber J, Jacobs M. Antibiotic-resistant pneumococci. Pediatr Clin North Am 1995; 42: 519-537. Collignon P. Penicillin-resistant pneumococci: will the recent Olympics bring back to Australia more than gold? Med J Aust 1992; 157: 655-657. Hansman D, Bullen M. A resistant pneumococcus. Lancet 1967; 2: 264-265. Hofmann J, Cetron M, Farley M, et al. The prevalence of drug resistant Streptococcus pneumoniae in Atlanta. N Engl J Med 1995; 333: 481-486. Collignon P, Bell J, on behalf of AGAR. Streptococcus pneumoniae : how common is penicillin resistance in Australia? Aust N Z J Med 1992; 22: 473-476. Hansman D, Morris S, Gregory M, McDonald B. Pneumococcal carriage amongst Australian aborigines in Alice Springs, Northern Territory. J Hyg (Camb) 1985; 95: 677-684. National Committee for Clinical Laboratory Standards. Performance standards for antimicrobial disk susceptibility tests. 5th ed. Approved standard. Document M2-A5. Villanova, Pa: NCCLS, 1993. Bell SM, Gatus BJ, Pham JN, et al. CDS users group newsletter No. 6. Sydney: The Prince of Wales Hospital, 1993. Bell SM. Additions and modifications to the range of antibiotics tested by the CDS method of antibiotic sensitivity testing. Pathology 1988; 20: 303-304. National Committee for Clinical Laboratory Standards. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. 3rd ed. Approved standard. Document M7-A3. Villanova, Pa: NCCLS, 1993. Jorgensen JH, Ferraro MJ, McElmeel ML, et al. Detection of penicillin and extended spectrum cephalosporin resistance among Streptococcus pneumoniae clinical isolates by use of the Etest. J Clin Microbiol 1994; 32: 159-163. AB Biodisk . Etest Technical Guide 5B. Solna, Sweden: AB Biodisk , 1995. National Committee for Clinical Laboratory Standards. Performance standards for antimicrobial susceptibility testing. 5th informational supplement. Document M100-S5. Villanova, Pa: NCCLS, 1994. True Epistat [computer program]. Version 5.0. Richardson, TX: Epistat Services, 1994. Collignon P, Bell J, Hufton I, Mitchell D. Meningitis caused by a penicillin- and chloramphenicol-resistant Streptococcus pneumoniae . Med J Aust 1988; 149: 497-498. Friedland I, McCracken G. Management of infections caused by antibiotic-resistant Streptococcus pneumoniae . N Engl J Med 1994; 331: 377-382. Tomasz A. The pneumococcus at the gates. N Engl J Med 1995; 333: 514-515. Barnett E, Klein J. The problem of resistant bacteria for the management of acute otitis media. Pediatr Clin North Am 1995; 42: 509-517. Nelson C, Mason E, Kaplan S. Activity of oral antibiotics in middle ear and sinus infections caused by penicillin-resistant Streptococcus pneumoniae : implications for treatment. Pediatr Infect Dis J 1994; 13: 585-589. (Accepted 30 Nov 1995) Authors' details Infectious Diseases Unit, Woden Valley Hospital, Canberra, ACT. Peter J Collignon, FRACP, FRCPA, Head of Unit, Microbiologist and Infectious Diseases Physician. Department of Microbiology and Infectious Diseases, Monash Medical Centre, Melbourne, VIC. Jan M Bell, BSc(Hons), BA, Scientist. * Australian Group on Antimicrobial Resistance (AGAR). For this study AGAR consisted of the microbiology laboratories at: ACT: Woden Valley Hospital (Peter Collignon, Linda Halliday). NSW: Concord Hospital (Joan Yap, Tom Gottlieb, Glenn Funnell); Illawarra Regional Hospital (Keith Wise, Rodney Jones); Liverpool Hospital (Denise Daley, Rosemary Munro); Prince of Wales Hospital (Jeanette Pham, Barrie Gatus, Sydney Bell); Royal North Shore Hospital (Clarence Fernandes); Royal Prince Alfred Hospital (Richard Benn, Barbara Yan, Alison Vickery). QLD: Mater Misericordiae Hospital, Brisbane (Martyn Tilse, Janet Montgomery); Princess Alexandra Hospital (Graeme Nimmo, Jacqueline Schooneveldt); Royal Brisbane Hospital (Narelle George, Joan Faoagali); Sullivan, Nicolaides and Partners (Jenny Robson, Sylvia van der Valk); Toowoomba Base Hospital (David Farrell). SA: Flinders Medical Centre (Hendrik Pruul); Institute of Medical and Veterinary Science (Irene Lim, Richard Lumb); Queen Elizabeth Hospital (Peter Lawson, David Grove). TAS: Diagnostic Pathology (which includes Hobart Pathology and Launceston Pathology) (Barbara Henderson, Danny McColl, Gary Fenton); Launceston General Hospital (Erika Cox, Veronica Lyons); Royal Hobart Hospital (Keith Ott, Rob Peterson). VIC: Alfred Hospital (John Spicer, J Clare Franklin); Dorevitch Pathology (Liz Snashall); Heidelberg Repatriation Hospital (Barrie Mayall, Angie Chan, Vicki Moritz); Melbourne Pathology (Christine Hargreaves); Monash Medical Centre (Dianne Olden, Jan Bell, John Turnidge); Royal Children's Hospital and Microbiological Diagnostic Unit (Geoff Hogg, Marion Easton, Janet Strachan). WA: Fremantle Hospital (David McGechie, Neil Stingemore, Graham Francis); Royal Perth Hospital (Keryn Christiansen, Claire Khinsoe, Geoff Coombs). Reprints: Dr P J Collignon, Infectious Diseases Unit, Woden Valley Hospital, PO Box 11, Woden, ACT 2606. ©MJA 1997 <URL: http://www.mja.com.au/> © 1997 Medical Journal of Australia.

Peter J Collignon · Jan M Bell · the AGAR

Research Physical, sexual and emotional violence against women: a general practice-based prevalence study Danielle Mazza, Lorraine Dennerstein and Vicky Ryan Abstract - Authors' details - Introduction - Methods - Results - Discussion - Acknowledgement - References - Box 1 - Box 2 - Box 3 - Box 4 - Box 5 - ©MJA1996 - Abstract Objective: To determine the prevalence of domestic violence, childhood abuse and sexual assult experienced by women attending general practitioners. Design: A cross-sectional, questionnaire-based prevalence survey. Setting: 15 general practices in metropolitan Melbourne between November 1993 and February 1994. Subjects: 3026 women over the age of 18 attending for a consultation. Results: The response rate was 72%. Over a quarter of women in relationships had been victims of physical or emotional partner abuse in the previous year, one in 10 having experienced severe physical violence. Thirteen percent of women had experienced rape or attempted rape, 10% had been severely beaten during childhood and 28% had experienced childhood sexual abuse involving physical contact. The abuse had been disclosed to the woman's doctor by only 27% of those who had experienced partner or childhood physical abuse (mostly because the doctor had never asked) and 9% of those who had experienced sexual abuse (mostly because the woman did not see it as relevant to the consultation). Conclusion: There is a high prevalence of physical, sexual and emotional violence against women as well as poor communication about this violence to their general practitioners. Recommendation: Medical practitioners should be more proactive in questioning women about violence. (MJA 1996; 164: 14-17) Introduction Violence experienced by women results in significant morbidity and, in some cases, mortality. The experience of sexual abuse as a child has been linked to later development of psychological disorders1 and drug abuse and dependence.2,3 Domestic violence has health effects beyond the acute injuries; battered women are more likely to suffer from somatic complaints, anxiety and depression,4 pelvic pain,5 and sexual and gynaecological problems.6 They also use health services more often than women not subjected to domestic violence.7 Because of these associations and because victims of violence are more likely to turn to doctors for help than to any other person,8 they are highly likely to frequent a doctor's surgery. However, doctors are not skilled at recognising them and have been estimated to diagnose only one battered woman in 25.7 This may occur because doctors are unaware of the extent of physical and sexual abuse experienced by their female patients; while the prevalence has been studied in the United States and Europe, Australian data are sparse. The single authoritative study on the prevalence of childhood sexual abuse in Australia was conducted by Goldman and Goldman on a population of university students: 28% of female students and 9% of male students had experienced sexual abuse.9 Two recent studies have looked at the prevalence of domestic violence in Australia, but only in select populations: 23.3% of women attending an emergency department disclosed histories of domestic violence,10 while 8.9% of women in a hospital antenatal clinic stated that they had experienced physical abuse during their pregnancy.11 The aim of our study was to determine the prevalence of domestic violence, childhood abuse and sexual assault experienced by women attending general practitioners and to provide doctors with accurate information on the extent of the problem. Methods The study was a questionnaire-based prevalence survey carried out between November 1993 and February 1994. It was approved by the ethics committee of Monash University. Study population The study population comprised women over the age of 18 attending their general practitioner for a consultation. Fifteen general practices in metropolitan Melbourne were selected in a two-stage random sampling design described previously.12 The design incorporated practices that were broadly representative of all social classes, from all regions of metropolitan Melbourne. A total sample size of about 3000 women was calculated to be necessary to ensure adequate power, based on results of a pilot study; 220 questionnaires were therefore distributed to each practice. Questionnaire Consecutive women attending the practice for a consultation were invited to participate by the practice receptionist. The questionnaire was introduced by a covering letter, which explained the nature of the study, that it was voluntary and confidential, and that the information disclosed would not be entered in their medical file or given to their doctor. It was acknowledged that some questions might cause distress, and the questionnaire could therefore be completed either in the waiting room or at home and returned in a reply-paid envelope. Respondents were also given contact phone numbers of support services for the different forms of abuse, and informed that their doctor was happy to discuss with them any issues that might arise as a result of the survey. Before the study, doctors were given an information package with details of local support services for abused women. The self-administered questionnaire asked first for demographic details. Respondents then completed the Conflict Tactics Scale,13 with the modification that they were asked whether the tactic had occurred never, once or more than once in the last year, and with the addition of questions on emotional abuse. In accordance with the Conflict Tactics Scale, physical violence was classified as minor or severe (see Box 1). Questions about sexual abuse were derived from the studies of Wyatt14 and Russell,both of 15 which used multiple screening questions to allow time for the respondent to become accustomed to the nature of the questions. Childhood sexual abuse was classified as contact or non-contact (Box 1). Data were entered into a Microsoft Access database. Frequency tables were generated and prevalences calculated. Because the data came from 15 different general practices and not a simple random sample, confidence intervals (CIs) were adjusted for the effects of clustering.16 Results Of 3026 questionnaires distributed, 2181 were returned (response rate, 72%). Most questionnaires were completed in the waiting rooms of the practices, with only 18% of those answered returned by post. Domestic violence Prevalences for the different categories of domestic violence in the previous year are shown in Box 2. Only those women in a current relationship were asked to complete the section about domestic violence, so that the sample size was smaller than for other parts of the study. A total of 28% of these women had experienced either physical or emotional partner abuse, or both, in the previous year, and (notably) almost one in 10 had been victims of severe physical violence in that year. Among respondents in a current relationship 6% had been kicked, bitten or hit with a fist; 7% had been hit or their partner had tried to hit them with an object; 4% had been beaten up; 4% had been choked; 2% had been threatened with a knife or a gun; and 1% had actually had a knife or gun used against them. Twenty per cent of those in a current relationship had experienced emotional abuse in the previous year; 4% had their partner threaten or try to kill them; 8% had money withheld; 7% were prevented from leaving their home; 6% were stopped from seeing their friends and family or speaking to them on the phone; and 17% were constantly called names or humiliated. Adult sexual abuse Overall, 30% of women had been victim to some form of sexual abuse since the age of 16. Prevalences of different forms of abuse are shown in Box 3. Just over half of those who reported adult sexual abuse (356/626) had experienced more than one kind. Childhood abuse Overall, 10% of women experienced childhood physical abuse (95% CI, 8%-12%); 3% were severely beaten on one occasion and 7% repeatedly. Almost 40% of women had experienced some form of sexual abuse before the age of 16 (Box 3). Communication in general practice about violence The question about whether respondents had ever discussed the issues of domestic violence or childhood physical abuse with their doctors was answered by 1177 women. Among these only 27% had done so, although it was more likely among victims of domestic violence than among non-victims (Box 4). Most women (73%) said that their doctor had never asked them about these things, although this was less likely for victims than for non-victims. If respondents had experienced either childhood or adult sexual abuse, they were asked if they had ever disclosed this to their doctor; 1009 responded, only 87 (9%) in the affirmative. Reasons given for not disclosing are shown in Box 5. Discussion We believe that this study is the first to show the prevalence of physical, sexual and emotional abuse of women in an Australian general practice population. While we recognise that domestic violence and sexual abuse are not exclusively directed by men against women, the study found a high level of violence against women. Over a quarter of women in relationships had been victims of partner abuse in the previous year and one in 10 had experienced severe physical violence; 13% of women had experienced rape or attempted rape; 10% of women had been severely beaten during childhood; and 28% had experienced contact childhood sexual abuse. Despite these levels, few women disclose these events to their doctors. Our findings are similar to those of a family practice-based study in the United States, which found that 23% of women had been physically assaulted by their partners in the last year.17 In contrast,population-based studies in the United States and Canada estimate that between 10% and 14% of women in relationships experience physical abuse over a one-year period; for 3%-5% of women, the abuse is severe.18-22 Because domestic violence is associated with injury and illness, women sampled in medical environments would be expected to have a higher prevalence than women sampled in community settings. In fact, our findings may underestimate the true prevalence of domestic violence, as women who were separated or divorced were not questioned about their experience of it. We found a slightly higher prevalence of sexual abuse than that in a recent New Zealand community-based study, which found the prevalence of childhood sexual abuse overall to be 32%, with contact abuse in 25% and penetrative abuse in 4%.23 The differences are again probably due to the different populations sampled. Potential sources of bias exist. Because of the secret nature of physical and sexual abuse and the stigma attached, there is much controversy over whether self-disclosure by victims can give a true indication of prevalence. A self-administered questionnaire gives no opportunity for clarification of responses by an interviewer. It is also argued that victims will not respond because they fear that disclosure will cause further trauma. These factors would lower apparent prevalence.24 An alternative argument is that victims respond preferentially to surveys when given the opportunity to disclose; non-victims fail to respond as they feel they have no valid information to contribute.24 This would have the reverse effect on apparent prevalence; the two effects could simultaneously counterbalance each other. Another possible source of bias is that the self-administered questionnaire format may have precluded the participation of women from non-English-speaking backgrounds. However, with a sample size of over 3000 and a response rate of 72% (with over 80% of the surveys completed in the general practitioner's surgery), the questionnaire appears to have been well accepted by the subjects. Importantly, about three-quarters of respondents had never been asked by their doctors about domestic violence or childhood physical abuse. This is consistent with results of studies in other countries, which show physician enquiry rates into spouse abuse to be suboptimal.22,25 Contrary to prevailing belief,26 the main reason women did not discuss these issues with their doctor was not because they were afraid, embarrassed or untrusting, but because they were never asked. In addition, 53% of women had not disclosed their experiences of sexual abuse to their doctor because they had never found it relevant to the consultation. Either women are failing to make the connection between sexual abuse and their symptoms or their doctors lack knowledge of the short and long term health effects of sexual abuse. Doctors are crucially placed to deal with the problem of abuse. Our study suggests that medical practitioners must be more proactive in questioning women about violence. While many may hesitate to identify something they may be unable to directly treat,27 it is important to consider that when a diagnosis of abuse is missed treatment is likely to be inappropriate and potentially harmful.28 Detection is the first step in successful management to deal with both the immediate and long term effects of violence against women. This requires that medical practitioners not only develop the skills to diagnose violence perpetrated against women, but have knowledge of local agencies for referral as well as the legal and criminal options available to the woman. Acknowledgement This work was supported by a grant from the Shepherd Foundation in the Department of Community Medicine at Monash University. (©MJA 1996; 164: 14-17) References Mullen PE, Romans-Clarkson SE, Walton VA, Herbison GP. Impact of sexual and physical abuse on women-s mental health. Lancet 1988; 1: 841-845. Burnam MA, Stein JA, Golding JM, et al. Sexual assault and mental disorders in a community population. J Consult Clin Psychol 1988; 56: 843-850. Winfield I, George LK, Swartz M, Blazer DG. Sexual assault and psychiatric disorders among a community sample of women. Am J Psychiatry 1990; 147: 335-341. Jaffe P, Wolfe DA, Wilson S, Zak L. Emotional and physical health problems of battered women. Can J Psychiatry 1986; 31: 625-629. Schei B. Psycho-social factors in pelvic pain: a controlled study of women living in physically abusive relationships. Acta Obstet Gynecol Scand 1990; 69: 67-71. Schei B, Bakketeig LS. Gynaecological impact of sexual and physical abuse by spouse. A study of a random sample of Norwegian women. Br J Obstet Gynaecol 1989; 96: 1379-1383. Stark E, Flitcraft A, Zuckerman D, et al. Wife abuse in the medical setting. An introduction for health personnel. Domestic Violence Monograph Series No. 7. Washington, DC: US Government Printing Office, 1981. Dobash RE, Dobash RP. Violence against wives - a case against the patriarchy. New York: Free Press, 1979. Goldman R, Goldman J. The prevalence and nature of child sexual abuse in Australia. Aust J Sex Marriage Fam 1988; 9: 94-106. Roberts GL, O-Toole BI, Lawrence JM, Raphael B. Domestic violence victims in a hospital emergency department. Med J Aust 1993; 159: 307-310. Webster J, Sweett S, Stolz TA. Domestic violence in pregnancy. A prevalence study. Med J Aust 1994; 161: 446-470. Mazza D, Dennerstein L, Ryan V. Psychotropic drug use by women: current prevalence and associations. Med J Aust 1995; 163: 86-89. Straus MA. Measuring intrafamily conflict and violence: the Conflict Tactics (CT) Scales. J Marriage Fam 1979; 41: 75-88. Wyatt GE. The sexual abuse of Afro-American and white-American women in childhood. Child Abuse Negl 1985; 9: 507-519. Russell DEH. The incidence and prevalence of intrafamilial and extrafamilial sexual abuse of female children. Child Abuse Negl 1983; 7: 133-146. Rao JNK, Scott AJ. A simple method for the analysis of clustered binary data. Biometrics 1992; 48: 577-585. Hamberger LK, Saunders DG, Hovey M. Prevalence of domestic violence in community practice and rate of physician inquiry. Fam Med 1992; 24: 283-287. Rollins BC, Oheneba-Sakyi Y. Physical violence in Utah households. J Fam Violence 1990; 5: 301-309. Schulman MA. A survey of spousal violence against women in Kentucky. Study No. 792701 conducted for the Kentucky Commission on Women. Washington, DC: US Government Printing Office, 1979. Smith MD. The incidence and prevalence of woman abuse in Toronto. Violence Vict 1987; 2: 173-187. Straus MA, Gelles RJ, Steinmetz SK. Behind closed doors: violence in the American family. New York: Anchor, 1980. Straus MA, Gelles RJ. Societal change and change in family violence rates from 1975 to 1985 as revealed by two national surveys. J Marriage Fam 1986: 48; 465-479. Anderson J, Martin J, Mullen P, et al. Prevalence of childhood sexual abuse in a community sample of women. J Am Acad Child Adolesc Psychiatry 1993; 32: 911-919. Finkelhor D. A sourcebook on child sexual abuse. Beverley Hills: Sage Publications, 1986. Martins R, Holzapfel S, Baker P. Wife abuse: are we detecting it? J Wom Health 1992; 1: 77-80. Queensland Domestic Violence Task Force. Beyond these walls. Brisbane: Queensland Government, 1988. Brown JB, Sas G. Focus groups in family practice research: an example study of family physicians- approach to wife abuse. Fam Pract Res J 1994; 14: 19-28. Council on Ethical and Judicial Affairs, American Medical Association. Physicians and domestic violence. Ethical considerations. JAMA 1992; 267: 3190-3193. (Received 19 May, accepted 6 Oct 1995) Authors' details University of Melbourne, Melbourne, VIC. Danielle Mazza, FRACGP, DRACOG, Lecturer, Key Centre for Women's Health; formerly Assistant Lecturer, Department of Community Medicine, Monash University, Melbourne, VIC. Lorraine Dennerstein, AO, PhD, FRANZCP, Director, Key Centre for Women's Health. Vicky Ryan, MSc, Statistician, Statistical Consulting Centre. (©MJA 1996; 164: 14-17)

Danielle Mazza · Lorraine Dennerstein · Vicky Ryan

Human hydatidosis in New South Wales and the Australian Capital Territory, 1987-1992 David J Jenkins and Karen Power Abstract - Authors' details - Introduction - Methods - Results - Discussion - Acknowledgement - References - Box 1 - Box 2 - Figure 1 - Figure 2 - Figure 3 - ©MJA1996 - For editorial comment, see McCullagh Objective: To determine the prevalence of human hydatidosis in New South Wales and the Australian Capital Territory. Methods: Data on human hydatid infection occurring between 1987 and 1992 were collected retrospectively from 25 hospitals and 13 health services in New South Wales and four hospitals in the Australian Capital Territory. Mean annual prevalences of human hydatidosis were determined for shires in eastern New South Wales and data on infection in immigrants and Australian-born patients were compared. Results: 321 patients were diagnosed with hydatid disease, 1987-1992; 195 were new cases and 117 readmissions (nine cases were not identified as new or recurrent). Most patients lived in the eastern half of New South Wales (which includes the Australian Capital Territory), half in rural areas and half in the major coastal cities. Most Australian-born rural patients lived in 39 shires in the north-eastern and south-eastern Tablelands. Sixty per cent of the patients in major cities were born overseas. Conclusions: Hydatid infection occurs more commonly in south-eastern Australia than the official figures suggest. In rural areas of the north-eastern and south-eastern Tablelands hydatid infection is of public health importance. The national notification system must be improved and control campaigns alerting the public to the dangers of hydatid infection promoted. (MJA 1996; 164: 18-21) Introduction The tapeworm genus Echinococcus is an important zoonosis which is endemic in many parts of the world. The only species occurring in Australia is Echinococcus granulosus. It was probably introduced with infected domestic livestock during European settlement and is now widespread in domestic livestock and wildlife, with wildlife acting as an important reservoir.1 Dogs (domestic and wild) and foxes are the definitive hosts (Figure 1). Humans become infected by the ingestion of eggs passed in faeces of dogs. Oncospheres released from the eggs penetrate the intestinal mucosa and, via the portal system, lodge in the liver, lungs, muscle or other organs, where the hydatid cysts form. Because of inadequate reporting, the prevalence of human hydatid infection in Australia is unknown. From the earliest published studies human hydatidosis in New South Wales has occurred mainly in people living in rural areas in the eastern half of the State associated with the Great Dividing Range.2-4 Dew, in 1928, reported a relatively even distribution of patients with hydatidosis in eastern New South Wales, but subsequent reports showed an increasing trend for patients to be concentrated in the north-eastern and south-eastern Tablelands.3-5 To assess the health risk associated with E. granulosus, a retrospective survey of hydatid infection was conducted between 1987 and 1992 by examining records of patients with hydatidosis from hospitals and health services in New South Wales (NSW) and the Australian Capital Territory (ACT). Methods All the public and private hospitals and area and district health services in NSW and the ACT were asked to supply data of patients with confirmed hydatidosis who were admitted between January 1987 and December 1992. After approval of our written request, all institutions ( four hospitals in the ACT and 25 hospitals and 13 health services in NSW ( supplied data comprising: - Sex; - Date of admission; - Date and country of birth; - Place of residence at admission; - Cyst location; and - Whether the infection was new or recurrent. We maintained patient confidentiality by using initials only for individual identification. Multiple admissions for the same patient were identified from admission dates, initials, age, sex and general location of residence at the time of admission. We calculated mean annual prevalences of infection using 1991 Census data.6 Results Three hundred and twenty-one patients with confirmed hydatidosis were treated between 1987 and 1992. These comprised 195 new cases (107 males and 88 females), 117 recurrent cases (27 cases had their first treatment before this survey began) and nine cases not identified as new or recurrent. Two hundred and eighty-two patients (172 new cases and 110 recurrent cases [including those not classified as new or recurrent]) were treated in NSW and 39 patients (23 new cases and 16 recurrent and unclassified cases) were treated in the ACT (16 and 14, respectively, of those treated in the ACT lived in NSW). Rural patients Except in three cases, hydatid infection in rural patients, most of whom were Australia-born, occurred in the eastern half of NSW at higher altitudes, mainly associated with the Great Dividing Range (Figure 2). There were concentrations of patients in the north-eastern and south-eastern Tablelands, and these two areas were connected by a corridor parallel to the coast where further cases occurred. The mean annual prevalence of human hydatidosis in rural NSW was 2.6 cases per 100 000 rural population. Cases occurred in 15 shires [counties] in the north-east and 24 shires in the south-east. On a shire-to-shire basis, the mean annual prevalence of infection ranged from 0.3 to 17.7 and 0.5 to 23.5 (cases per 100 000 population), respectively, in these two areas (Box 1). Four of the cases (three new and one recurrent) were in Aboriginal people. These four cases represented a mean annual prevalence of hydatid infection of 1.1 cases per 100 000 in the Aboriginal population of NSW. Urban patients There were 152 cases diagnosed from the three major metropolitan centres of NSW (Sydney, Newcastle and Wollongong), which included 98 new cases, mostly in patients born overseas (60%); in rural areas the reverse was evident (85% of rural patients were born in Australia). Of the patients born overseas, all were living in NSW, except one ACT resident. The mean annual prevalence of infection was calculated for 25 ethnic groups (each with a population of over 1000) resident in NSW (Box 2). The highest mean annual prevalence occurred in the Iranian population (6.6 cases/100 000) and the lowest in the German population (0.5 cases/100 000). Most cases came from the Greek and Lebanese communities and communities of people from the former Yugoslavia (13, 10 and 8, respectively), but because of their relatively large populations in NSW, these cases represented only a mean annual prevalence of 4.8, 3.2 and 2.2, respectively. Age distribution Age-group distribution profiles of the patients born in Australia and those born overseas are compared in Figure 3. All age groups are represented among Australian-born patients with hydatidosis, especially the older age groups, whereas the immigrant population, being generally younger, has fewer cases in the older age groups. Cyst location Infection in the liver occurred most commonly (157 of the 195 new cases); 13 cases involved infection in the lungs and four had infection in both liver and lungs. Infection in other less common sites were two each in the spleen, pancreas and leg muscle and one each in the diaphragm, pelvic area, arm muscle, brain, adrenal gland and gallbladder. Discussion Retrospective survey data on human hydatidosis cannot give an accurate picture of the prevalence of infection. A number of cases are not seen in hospitals because the infection is asymptomatic, or does not require surgical intervention, and mistakes in coding may occur. However, these data remain a useful indication of infection prevalence. Our study confirmed the concentration of hydatidosis in the north-eastern and south-eastern Tablelands reported previously.3-5 The narrow corridor parallel to the coast in the central part of the State is an area where there have been few cases reported previously, but where considerable urban development has occurred over the last decade, and previously undiagnosed patients may have moved to this region. Population movement from country areas to cities may also account for many of the Australian-born patients diagnosed in urban areas. However, it is also possible for urban residents to be exposed to eggs of E. granulosus. Recent studies have identified infection with E. granulosus in dogs of a recreational pig hunter living in suburban Perth,7 and in dogs of Perth residents living in uncleared areas on the outskirts of the city.8 Foxes infected with E. granulosus have been found in the suburbs of Canberra.9 The older age of the Australian-born compared with the immigrant patients largely reflects the different age-group structures of the two groups. In 1990, 88.3% of immigrants were aged less than 45 years when they arrived in Australia and 27.4% were less than 14 years of age.10 Migrants may be already infected when they arrive as children, but the long latent period of hydatid disease means it is first detected in adulthood. It is difficult to explain why most Australian-born patients were detected in the age group 31 to 40 years whereas most immigrants were not detected until 41 to 50 years. Infections in immigrants may be caused by a different strain type of E. granulosus with a slower cystic growth rate. Alternatively, there may be a reluctance among newer immigrants to consult local doctors. The migrants infected with hydatid disease origin(Box 2)ated in countries where E. granulosus is endemic. The order of ranking of countries according to the mean annual prevalence of hydatid infection in their migrant populations in NSW closely reflected the relative importance of human hydatidosis in their countries of origin. The range of prevalences in the migrant populations were no higher than those recorded in shire populations in north-eastern and south-eastern NSW. In at least three of these shires the prevalence of human hydatidosis was two to three times higher than the highest level recorded in a migrant population. Three of the urban patients and one of the rural patients born in Australia were Aboriginals. The three urban Aboriginal patients are likely to be from a rural background, but as their place of birth was unknown it was not possible to calculate a prevalence of hydatid infection for rural Aboriginal people. The mean annual prevalence of 1.1 cases per 100 000 for the total Aboriginal population of NSW is about a third of the prevalence in the rural non-Aboriginal population. Few cases of hydatid disease in Aboriginal people have been reported. All the reports are from studies in Western Australia during the 1970s, where Aboriginals were always highly represented: 15/57 cases11 and 13/31 cases.12 Our data represent the first report of hydatid infection in Aboriginal people in NSW; a previous study reported E. granulosus infection in a dog from a NSW Aboriginal community.13 The reason for human hydatidosis not being perceived as a problem in Australia can be attributed largely to under-reporting of this notifiable disease;5 this has been a problem for many years,,5,12,14,15 with no signs of improvement. Only 17 of the 321 new and recurrent cases identified in this study had been notified, and in a retrospective study in Victoria for the 12 months up to July 199116 only two of the 50 new or recurrent cases had been notified. Disease recurrence after operative treatment is an important aspect of human hydatid infection. A carefully conducted follow-up study of 39 patients treated surgically in Australia first drew attention to this problem;17 22% had had recurrent infection by 30 months, mainly caused by cyst rupture before surgery. In our study, 37.5% of patients (for whom information on new or recurrent infection status was supplied) were treated for recurrent infection. Effective chemotherapy of patients with hydatid infection would substantially reduce the cost of treatment. This topic has been reviewed,18 and the most promising drug studied was albendazole. Data from studies on 253 patients indicated that albendazole was an effective cure in 28%, 51% showed improvement, 18% were unchanged and in 2% the cysts continued to grow.19 The most appropriate use of albendazole may be as an adjunct to surgery. Rupture of cysts and spilling of protoscoleces (which can form new cysts) into the body cavity during surgery is a constant risk, but an immediate postoperative course of albendazole will greatly reduce the chance of new cysts developing.20 Hydatid disease is preventable, and education is one of the most effective tools to achieve this. It is important that State and Federal governments take a responsible attitude towards increasing community awareness, and implement control strategies through education, either by themselves or by funding organisations such as the Australian Hydatid Control and Epidemiology Program. Control of this parasite in Australia requires a long term commitment; the alternative is that hydatid disease will continue to incapacitate individuals and be an additional financial drain on an already overstretched health service. Acknowledgements The authors gratefully acknowledge the assistance of the staff of the medical records departments of the following hospitals: Albury, Armidale and New England, Bathurst, Broken Hill, Calvary (ACT), Camperdown, Casino and District, Cooma, Dubbo, Goulburn, Grafton, Grenfell, Griffith, Inverell, John James Memorial (ACT), Lismore, Orange, Parkes District, Prince Henry, Prince of Wales Children's, Queanbeyan, Royal Canberra (ACT, now closed), Royal North Shore, Royal Prince Alfred, St Vincent's, St Vincent's Private, Tamworth, Wagga Wagga, Westmead and Woden Valley (ACT); also the following area and district health services: Brunswick-Byron, Central Coast, Cooma, Hunter, Illawarra, Macleay Valley, Manning Valley, Queanbeyan, South Western Sydney, Southern Sydney and Tumut, Wentworth. We also thank Ms Celia Moss (Australian Bureau of Statistics) and Ms Irene Pasaris (ACT Health Department) for their help and advice and Dr M W Lightowlers, Dr E Bennet, Dr P McCullagh and Professor R C A Thompson for their suggestions in the preparation of the manuscript. This study was funded partly through contributions from the Shire Councils of Bega Valley, Boorowa, Cooma-Monaro, Crookwell, Gunning, Harden, Snowy River, Tumbarumba, Yarrowlumla, Yass and Young, Queanbeyan City Council and the ACT Health Authority. Dr Jenkins' salary was funded by the National Health and Medical Research Council of Australia. (©MJA 1996; 164: 14-17) References Schantz PM, Chai J, Craig PS, et al. Epidemiology and control of hydatid disease. In: Thompson RCA and Lymbery AJ, editors. The biology of Echinococcus and hydatid disease. Wallingford, UK: C A B International, 1995: 233-302. Dew HR. Hydatid disease. Its pathology, diagnosis and treatment. Sydney: The Australasian Medical Publishing Company Ltd, 1928. Christopher PJ, Lopez WA. Hydatid disease notifications in New South Wales. Med J Aust 1970; 1: 54-56. Little JM. Hydatid disease at Royal Prince Alfred Hospital, 1964 to 1974. Med J Aust 1976; 1: 903-908. Schreuder S. Survey of hospital admissions for hydatidosis in New South Wales and the Australian Capital Territory, 1982-1987. Aust Vet J 1990; 67: 149-151. Australian Bureau of Statistics. 1991 Census of population and housing. State comparisons. Canberra: ABS, 1993. (Catalogue No. 2731.0.) Thompson RCA, Lymbery AJ, Hobbs RP, Elliot AD. Hydatid disease in urban areas of Western Australia: an unusual cycle involving western grey kangaroos (Macropus fuliginosus), feral pigs and domestic dogs. Aust Vet J 1988; 65: 188-190. Thompson RCA, Robertson ID, Gasser RB, Constantine CC. Hydatid disease in Western Australia: a novel approach to education and surveillance. Parasitol Today 1993; 9: 431-433. Jenkins DJ, Craig NA. The role of foxes Vulpes vulpes in the epidemiology of Echinococcus granulosus in urban environments. Med J Aust 1992; 157: 754-756. Australian Bureau of Statistics. Migration, Australia. Canberra: ABS, 1994. (Catalogue No. 3412.0.) Joske RA. The changing pattern of hydatid disease, with special reference to hydatid of the liver. Med J Aust 1974; 1: 129-132. Stein GR, McCully DJ. Hydatid disease in Western Australia (1957-1967). Med J Aust 1970; 1: 848-850. Jenkins DJ, Andrew PL. Intestinal parasites in dogs from an Aboriginal community in New South Wales. Aust Vet J 1993; 70: 115-116. Davies P, Nicholas WL, Beard TC. Hospital records of hydatid disease in Victoria for 1970 to 1974. Med J Aust 1977; 2: 493-495. Beard TC. Hydatids in Australia ( the present position in man. Aust Vet J 1979; 55: 131-135. Taylor K. Hydatids in 1992: public health lessons. Update. A quarterly bulletin of infectious diseases. Victoria: Department of Health and Community Services, 1993; 2: 63-64. Little JM, Hollands MJ, Ekberg H. Recurrence of hydatid disease. World J Surg 1988; 12: 700-704. Morris DL, Richards KS. Hydatid disease current medical and surgical management. Oxford: Butterworth-Heinemann Ltd, 1992: 94-118. Horton RJ. Chemotherapy of Echinococcus infection in man with albendazole. Trans R Soc Trop Med Hyg 1989; 83: 97-102. Morris DL, Taylor DH. Optimal timing of postoperative albendazole prophylaxis in E. granulosus. Ann Trop Med Parasitol 1988; 82: 65-66. (Received 11 Apr, accepted 27 Sep 1995) Authors' details Australian Hydatid Control and Epidemiology Program, Canberra, ACT. David J Jenkins, MSc, PhD, Research Officer. Karen Power, BApplSci, Field Officer.

David J Jenkins · Karen Power

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Estrella Munoz BAppSc, RN, FRCNA · Jennifer R Powers BSc · John D Mathews BSc, MD BS, PhD, FRACP, CPA

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Susan M Sayers FRACP, DCH, AmBdNeonatPerinat · Jennifer R Powers BSc, AssocDipAppSc(Comp)

Hereditary pancreatitis causes severe early-onset pain and hospitalisation. In 15 Australian patients undergoing total pancreatectomy and islet auto transplantation (TPIAT), we observed a marked reduction in hospital admissions, inpatient days and emergency visits, complete analgesic cessation by 24 months and durable insulin independence in nearly half of the patients. These findings highlight TPIAT’s potential to improve quality of life and reduce healthcare burden. Our programme aims to build evidence to support public funding and ensure equitable access to this procedure.

Merle Weetra, Denghao Wu, Sanjeev Khurana, Bhanu Mariyappa, Jenny Harrington, Tom Loudovaris, Gordon Thomas, Henry C. C. Pleass, Alex Brown, Thomas W. Kay, Christopher J. Drogemuller, David J. Torpy, Richard Couper, John Chen, Patrick T. Coates