Volume 169 Issue 8

Factors involved in presentation of older people with thick melanoma Pauline F Hanrahan, Peter Hersey and Catherine A D'Este MJA 1998; 169: 410-414 For editorial comment, see Kelly Abstract - Introduction - Methods - Results - Discussion - Acknowledgements - References - Authors' details - - More articles on Oncology - ©MJA1998 Abstract Objective: To examine whether presentation of older people with thick melanoma is a result of the site and histological type or of their reduced ability to identify melanoma. Design and setting: Retrospective analysis of the Newcastle Melanoma Unit patient database. Patients: 2154 patients with melanoma for whom complete data (histological type, thickness and site of melanoma) were available and who presented from February 1981 to April 1997. Main outcome measures: Histological type and site of melanoma in older (≥50 years) versus younger men and women; frequency with which these groups identified melanoma and the first changes of melanoma that were noticed. Results: Patients aged ≥50 years, particularly men, were more likely to present with thicker lesions. Older men and, to a lesser extent, older women were more likely to present with nodular melanoma, which were more frequent on the scalp and face in older, compared with younger, men, and scalp and back in older men compared with older women. Failure to identify melanoma was associated with older age, sites on the scalp and back and histological type of the lesion, but was independent of sex once histological type, age, site and thickness were taken into account. Multivariate analysis indicated that the association of older age of patients with failure to identify melanoma applied irrespective of the site, type and thickness of their melanoma. Conclusion:. The higher frequency of thick melanoma in older people is accounted for by an increased proportion of nodular melanoma and decreased ability to recognise the changes of melanoma. These findings have important implications for examination of older patients by doctors and for design of strategies for early detection of melanoma in this age group. Introduction Survival from melanoma is related to thickness of the tumour. Ninety-six per cent of patients whose lesions are detected early (< 0.75 mm thick) will survive to 10 years,1,2 but this decreases to 50% for patients with lesions 4 mm or greater.3,4 Previous studies have shown that most patients who present with thick lesions are men aged over 50 years.5-7 In New South Wales over 50% of deaths from melanoma involve men over 50, even though this group comprises only 12%-14% of the population.8 Clearly, strategies that facilitate early detection of melanoma in older men may markedly reduce the death rate from this cancer. We have previously investigated the ability of older men to distinguish between benign and malignant pigmented skin lesions in photographs and whether an educational brochure assists this ability;9 the brochure increased knowledge of melanoma, but did not help participants distinguish between benign and malignant pigmented skin lesions. We then investigated whether this age group had inherent difficulties in recognising the changes of melanoma and found that all age groups had difficulty in recognising the appearance of new pigmented lesions and changes in lesions over time.10,11 Older people were no less able than younger people to identify change, but falsely identified changes in unchanged lesions more frequently. In this study we sought to examine factors associated with failure of patients to identify their melanoma and the importance of this in presentation of older patients with thick melanoma. Methods Information for the study was obtained from the database in the Newcastle Melanoma Unit (NMU), which was established in 1981 and is a referral centre for patients from the Hunter region of New South Wales. Over 90% of patients with melanoma in the Hunter region attend the unit. The database contains information obtained by experienced oncology nurses who interview patients, asking questions about changes they had noticed leading to diagnosis of melanoma, for how long they had noticed the changes and whether these were in a pre-existing or new lesion. The age and sex of patients, site of their primary lesion, its histological type and thickness were also recorded. Histological investigation of the lesions was reviewed by at least two pathologists and reported as described previously.12 Patient clinical data were entered into a program developed jointly by the Sydney Melanoma Unit and the Macquarie University using Clinical Reporting Systems software (Brisbane Road, Castle Hill, NSW). We included data for all patients presenting to the NMU between February 1981 and April 1997. The data were categorised for statistical analysis as follows. Patients were divided into two groups by age (< 50 and ≥50). As in a previous study,5 thickness of primary lesions was categorised as < 3 mm, or ≥3 mm. Data on the site of the primary melanoma were divided into seven categories (scalp, face, neck, back, anterior trunk, arm and leg). Melanomas were categorised into seven histological types (superficial spreading melanoma [SSM], nodular melanoma [NM], lentigo maligna [LM], in-situ melanoma, desmoplastic melanoma, unknown, and unclassified) of which we included only the first three relatively common types. Categories for types of changes were: unidentified (including instances where patients were uncertain whether a change had occurred, or said that no change had occurred, but melanoma was detected by their general practitioners or other doctors); size and shape; colour; changes in sensation (eg, itching, tingling); and bleeding. Statistical analysis Data were analysed with SAS13 and STATA14 statistical software. Lesion characteristics (thickness, histological type and site of melanoma) were compared by age and by sex separately using chi-squared analyses. Lesion characteristics and age and sex were also compared for those who had, and had not, identified any changes. Logistic regression analyses were performed to examine factors associated with identification of any changes of melanoma, using any change versus no change, as the outcome variable. All five independent variables were tested for significance by forward stepwise regression analysis. After the final main effects model was obtained, all possible interactions were tested. The likelihood ratio statistic was used to assess statistical significance in the logistic regression analyses. We also tested (by chi-squared analysis) lesion characteristics, age and sex for association with type of changes noticed; 95% confidence intervals (CI) were calculated for each type of change. A significance level of 0.05 was used for all analyses. Subgroups were considered to differ significantly if 95% CIs did not overlap. Results The database included records for 3435 patients who attended the NMU during the study period. Exclusions included: 932 patients for whom there was incomplete data or for whom data could not be appropriately classified; 325 with uncommon, unknown, desmoplastic or unclassified histological types of melanoma; and 22 with melanoma at unusual sites (eg, mucosal regions, buttocks, groin). The final sample of 2154 patients comprised 1144 men (53%) and 1010 women (47%); 1142 patients (53%) were aged 50 years or over and 59% of the men in the study were in this age group, compared with 46% of the women. There were no significant differences in sex or age of patients excluded compared with those included (sex: chi-squared = 0.006, df = 1, P = 0.94; age: chi-squared = 1.7, df = 1, P = 0.18). The site and thickness of melanomas were similar in those excluded and included. Excluded patients had a different distribution of histological types (as this was part of the basis for their exclusion) and a higher proportion of unnoticed changes than those included. More detailed information about excluded patients is available from the authors. Lesion characteristics Thickness: Box 1 shows that patients aged 50 years or over (14.5%; 95% CI, 12%-16%) were significantly more likely to present with thick lesions than younger patients (4.7%; 95% CI, 3%-6%), and men (12%; 95% CI, 10%-14%) were more likely to have thick lesions than women (7%; 95% CI, 6%-9%). Site: Melanoma was found most often on the backs of male patients (47%; 95% CI, 45%-50% v. 24%; 95% CI, 22%-27% for women), whereas the leg was the predominant site in women (38%; 95% CI, 35%-41% v. 16%; 95% CI, 13%-18% for men). The incidence of melanoma on the scalp, face and neck was similar for men and women. Melanoma on the arms was more common in women (19%; 95% CI, 16%-21% v. 12%; 95% CI, 10%-13% for men), while melanoma on the face was more common in older patients and melanoma on the anterior trunk and leg was more common in younger men than older men. Melanomas were more common on the scalp and face in older, compared with younger, men and more common on the scalp and back of older men compared with older women (Box 1). Histological type: SSM was more common in younger patients of both sexes and NM was more common in older male patients. Most thin lesions (80%) were SSM and most thick lesions (72%) were NM. Thicknesses of the three histological types were: SSM, 0.02-10.5 mm (median, 0.63 mm; interquartile range [IQR], 0.4-1.0 mm); NM, 0.2-25 mm (median, 2.46 mm; IQR, 1.4-3.8 mm); and LM, 0.1-8.5 mm (median, 0.4 mm; IQR, 0.25-0.8 mm). Factors associated with failure to identify melanoma Many melanomas were not detected by patients, but were identified by their doctors. Sex and age: Men were more likely to fail to notice changes of melanoma than women (37%; 95% CI, 35%-49% v. 30%; 95% CI, 28%-32%) as were older, compared with younger, people (38%; 95% CI, 35%-41% v. 28%; 95% CI, 25%-31%). As shown in Box 2, a greater proportion of older men failed to identify changes in their lesions than younger men; the same trend was evident in women. Site: Patients most frequently failed to identify changes in lesions on the scalp (42%; 95% CI, 30%-52%) and back (41%; 95% CI, 37%-45%), but even among patients with a lesion on the face, 31% (95% CI, 26%-33%) did not identify it as melanoma. The anterior trunk was the least common site for unidentified change (24%; 95% CI, 20%-28%). Older patients failed to identify changes more often than younger patients for all sites except the face and scalp, where the reverse was the case (Box 2). However, numbers are very small for these groups and results should be interpreted with caution. Histological type: A greater proportion of patients with LM (47%; 95% CI, 40%-55%) failed to identify their melanoma than patients with SSM (33%; 95% CI, 31%-35%) or NM (29%; 95% CI, 25%-33%), although by the time they were detected the NM were much thicker. Older people were less likely than younger people to identify melanoma of all three histological types. Regression analyses: Age, thickness, histological type and site of lesion were significantly associated with identifying changes (Box 3). After these variables were included in the model, sex was no longer statistically significant. After adjustment for other variables in the model, the odds of older people identifying changes was two-thirds the odds of younger people identifying changes, and the odds of those with thicker lesions identifying changes was one-and-a-half times the odds of those with thinner lesions identifying changes. Those with LM had about half the odds of identifying changes as those with NM. As shown in Box 3, those with lesions on the face, arm, anterior trunk and leg had significantly higher odds of identifying changes than those with lesions on the back (reference group). Associations with thick melanoma (≥3 mm) As shown in Box 3, age and nodular melanoma were strongly associated with presentation with thick lesions. Changes of melanoma were more frequently identified in thick lesions, but as shown in Box 2, older people were less able to identify melanoma, irrespective of its thickness. It was also of interest that once the histological type of the lesion was taken into account, the site of the melanoma and sex of the patient were no longer related to thickness (ie, thick melanoma on the back and scalp in men appeared to result from the higher frequency of NM at these sites in men; see Box 3). Types of changes reported by patients Significantly fewer older than younger men reported changes in size and shape (21% v. 30%). The same was true for colour (20% v. 27%), and twice as many older men stated that the first change they were aware of in their skin lesion was bleeding (7% v. 3%). However, these differences were not statistically significant. Similarly, our findings that more younger than older women reported colour changes as the first change noticed (32% v. 25%) and (in contrast to men) older women reported changes in size and shape as the first change as frequently as younger women (30% v. 28%), were also not statistically significant. As shown in Box 4, patients with NM reported changes in colour significantly less frequently than those with SSM, change in sensation significantly more frequently than those with LM, and bleeding significantly more frequently than those with LM and SSM. Changes in size and shape were the most frequent changes reported in thick melanoma (34%), whereas changes in colour were more frequently reported in thin lesions (27%). Bleeding was reported as the first change significantly more frequently in thick than thin lesions (17% v. 4%). Reported changes in sensation were similar for thick or thin lesions. Discussion We excluded approximately one-third of the patients on the NMU database, mainly because of missing information about changes noticed or thickness measurements, or because they had melanoma of unusual histological type or location. However, the excluded patients appeared to have similar age and sex distribution, site and thickness measurements to patients in the study. Nonetheless, our results may not be generalisable to patients with the less common histological types of melanoma. Forty per cent of men and 34% of women aged over 50 failed to identify their melanoma. In contrast, younger patients of both sexes reported changes of melanoma in over 70% of cases. These findings were consistent with those of Koh et al15 who found that 38% of melanomas were not identified by men over the age of 60, compared with 23% in men less than 40 years of age. We also found that failure to detect melanoma was not only related to the age of the patient, but was associated with the site and type of the melanoma. Firstly, older men had lesions at sites which are more difficult to see, such as the back and scalp, with nearly 50% of melanoma in older men (compared with only 20% in older women) occurring on the back. Other series have reported similar differences in site distribution of melanoma between the sexes.16,17 Secondly, compared with younger people, older people, particularly men, had a higher proportion of NM, similar to that reported elsewhere.5,18 Patients also identified NMs when they were much thicker than SSMs (median, 2.46 mm v. 0.63 mm). The higher frequency of bleeding as the first change noted in patients with NM was consistent with this finding.19 The higher proportion of NM in older people and more frequent occurrence in "hard-to-see" sites could solely explain the presentation of older people with thicker melanomas. However, regression analysis indicated that for any given thickness and type of melanoma at a given site, older people were less able to recognise melanoma than younger people. In our examination of the first change that drew the attention of patients to their melanoma, we found that self-reporting of a change in colour was infrequent in patients with thick melanoma, and in patients with NM relative to those with SSM. These results were surprising, as previous studies have shown that changes in colour were one of the most frequent early changes of melanoma.20,21 Most of the thick melanoma were NM, which tend to be relatively homogeneous in colour compared with SSM. Thus, the different patterns of colour between NM and SSM may need to be emphasised in educational material directed at older patients. Bleeding was clearly associated with thick and nodular melanoma, but this is a late rather than an early sign.19 To the best of our knowledge this is the first study that has sought to identify reasons why older people present with thicker melanoma. The finding that older patients had lower ability to detect melanoma than younger people is consistent with our previous findings that older people had difficulty in discriminating early changes of melanoma in photographs of pigmented lesions.10,11 Previous studies have noted that younger people were more likely to rate change in skin lesions as extremely important in diagnosis of melanoma than older respondents.22 Older people may also not inspect their skin as frequently as younger people and this may contribute to their lower rate of detection of melanoma. Our findings raise questions about the likely effectiveness for older people of public health strategies that rely on self-detection of melanoma. It seems that that greater reliance will need to be placed on detection of melanoma in this age group by health professionals, who may need to be made aware of the high frequency of thick melanoma and characteristics of melanoma in this age group. Our previous studies have shown that recognition of change in existing lesions over time or the appearance of new pigmented skin lesions can be very difficult, but is assisted by whole-body photographs.10,11 The feasibility of using whole-body photographs to help general practitioners detect melanoma is currently under evaluation in a project funded by the National Health and Medical Research Council. Acknowledgements We thank the nursing sisters Sue Collins, Debbie Bradley, Donna Owens and Kathy Hall for collection of the data and Vicky Hunter for data entry. Dr Hanrahan was supported in part by the Hunter Melanoma Foundation. References Buttner P, Garbe C, Bertz J, et al. Primary cutaneous melanoma: optimized cutoff points of tumor thickness and importance of Clarks level for prognostic classification. Cancer 1995; 75: 2499-2506. Thorn M, Ponten F, Bergstrom R, et al. Clinical and histopathologic predictors of survival of patients with malignant melanoma: a population based study in Sweden. J Natl Cancer Inst 1994; 86: 761-769. Balch CM, Soong SJ, Shaw HM, et al. An analysis of prognostic factors in 8500 patients with cutaneous melanoma. In: Balch CM, Houghton AN, Milton GW, et al, editors. Cutaneous melanoma. Philadelphia: JB Lippincott Co.; 1992: 165-185. Breslow A. Tumor thickness, level of invasion and node dissection in stage 1 cutaneous melanoma. Ann Surg 1975; 182: 572-578. Hersey P, Sillar R, Howe CG, et al. Factors related to the presentation of patients with thick primary melanomas. Med J Aust 1991; 154: 583-587. McHenry PM, Hole DJ, Mackie RM. Melanoma in people aged over 65 in Scotland, 1979-89. BMJ 1992; 304: 746-749. Cohen HJ, Cox E, Manton K, Woodbury M. Malignant melanoma in the elderly. J Clin Oncol 1987; 5: 100-106. Coates M, Day P, McCredie M, Taylor R. NSW cancer incidence and mortality 1992. In: NSW Central Cancer Registry. Sydney: NSW Cancer Council; June 1995: 87, 97. Hanrahan P, Hersey P, Watson AB, Callaghan TM. The effect of an educational brochure on knowledge and early detection of melanoma. Aust J Public Health 1995; 19: 270-274. Hanrahan P, Hersey P, Menzies SW, et al. Examination of the ability of older people to identify early changes of melanoma in computer-altered pigmented skin lesions. Arch Dermatol 1997; 133: 301-311. Hanrahan P. Early detection of melanoma in older people [PhD thesis]. Sydney: University of NSW, 1998. McGovern VJ, Cochran AJ, Van Der Esch EP, et al. The classification of malignant melanoma, its histological reporting and registration: a revision of the 1972 Sydney classification. Pathology 1986; 18: 12-21. SAS for PC [computer program]. Version 6.11. Cary, NC: SAS Institute Inc., 1995. STATA [computer program]. Version 5.0. Houston, Tx: Stata Corp, 1997. Koh HK, Miller DR, Geler AC, et al. Who discovers melanoma? J Am Acad Dermatol 1992; 26: 914-919. Nguyen HL, Armstrong B, Coates M. Cutaneous melanoma in NSW 1983-1995. In: NSW Central Cancer Registry. Sydney: NSW Cancer Council; June 1997: 40. Green A, MacLennan R, Youl P, Martin N. Site distribution of cutaneous melanoma in Queensland. Int J Cancer 1993; 53: 232-236. Nguyen HL, Armstrong B, Coates M. Cutaneous melanoma in NSW 1983-1995. In: NSW Central Cancer Registry. Sydney: NSW Cancer Council; June 1997: 38. Fitzpatrick TB, Milton GW, Balch CM, et al. Clinical characteristics of primary melanoma. In: Balch CM, Houghton AN, Milton GW, et al, eds. Cutaneous melanoma. 2nd ed. Philadelphia: JB Lippincott Co.; 1992: 225-226. Mackie RM. Clinical recognition of early invasive melanoma. BMJ 1990; 301: 1005-1006. McGovern TW, Litaker MS. Clinical predictors of malignant pigmented lesions. J Dermatol Surg Oncol 1992; 18: 22-26. Baade PD, Balanda KP, Stanton WR, et al. Community perceptions about the important signs of early melanoma. J Am Acad Dermatol 1997; 36: 33-39. (Received 1 Sep 1997, accepted 14 May 1998) Authors' details John Hunter Hospital, Newcastle, NSW. Pauline F Hanrahan, BA, PhD, Research Officer, Newcastle Melanoma Unit and Division of Surgery; Peter Hersey, FRACP, D. Phil, Conjoint Professor of Oncology, Oncology and Immunology Unit, Division of Surgery. Centre for Clinical Epidemiology and Biostatistics, University of Newcastle, Newcastle, NSW. Catherine A D'Este, BMath, PhD, Lecturer in Biostatistics, Faculty of Medicine and Health Sciences. Reprints will not be available from the authors. Correspondence: Dr P Hersey, Room 443, David Maddison Clinical Sciences Building, Cnr King and Watt Streets, Newcastle, NSW 2300. - 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/>

Pauline F Hanrahan · Peter Hersey · Catherine A D'Este

Doctors detected self-administering opioids in New South Wales, 1985-1994: characteristics and outcomes Megan Cadman and James Bell MJA 1998; 169: 419-421 For editorial comment, see Breen & Court Abstract - Introduction - Methods - Results - Discussion - Acknowledgement - References - Authors' details - - More articles on Drugs and alcohol - ©MJA1998 Abstract Objective: To describe the characteristics and outcomes of doctors whose drug authorities were withdrawn as a result of self-administering opioids for non-medical purposes. Design: Retrospective review of New South Wales Health Department information relating to all doctors whose authorities to possess, supply, prescribe or administer drugs of addiction had been withdrawn in the period 1985 to 1994 as a result of confirmed self-administration of opioids. Outcome measures: Age, sex, geographical location and practice category at the time of intervention; drugs used; period of opioid use before authority withdrawal; means of detection; and registration status as at August 1995. Results: From 1985 to 1994, 79 doctors had their drug authorities withdrawn (0.4% of the NSW medical profession in 1994). The groups significantly over-represented were general practitioners and those aged 30-39 years. Pethidine was the main drug used (66 doctors; 84%). Drug use for more than two years before detection was reported by 34 (43%) doctors. Community pharmacists were the source of reports leading to detection of 28 (35%) doctors. As at August 1995, 27 (34%) of the study group were not practising; 10 (13%) had died. Conclusion: Outcomes for these doctors were poor. There was substantial attrition from practice and a high mortality rate. Introduction Medical practitioners have been shown to have a higher rate of drug abuse, mental illness and suicide than either matched controls or the general population.1-4 It is claimed that in the United States up to 10% of physicians at some time during their careers become dependent on psychoactive drugs or alcohol to an extent where their practice is impaired; about 1% become opioid-dependent.5 For these doctors, if placed in highly structured and strictly monitored programs, treatment outcomes are substantially better than for other opioid-dependent people.6,7Few data have been published on the prevalence of drug misuse among Australian healthcare professionals, and even less on the problems experienced by drug-dependent doctors and the extent of their professional impairment. Two studies of doctors with serious drug dependency brought to the attention of the Victorian Medical Board, in 1964-1984 and 1984-1990, indicated a prevalence of about 0.5%.8,9 By comparison, in a recent anonymous survey of 1125 doctors in New South Wales, 1% of those surveyed reported drug abuse problems, a figure closer to estimates from other countries.10 Accurate reporting of the prevalence of drug misuse in healthcare professionals is often undermined by the tendency of colleagues to either protect or ignore the impaired individual, and by treating doctors often anxious to avoid "labelling" a colleague with a potentially damaging diagnosis. Our study uses official records to examine the characteristics, and the limited information about outcomes, of those doctors in NSW whose opioid use had triggered official intervention. Methods Data collection The study group comprised all doctors whose authorities to possess, supply, prescribe or administer drugs of addiction (Schedule 8 authorities) were withdrawn by the NSW Health Department as a result of confirmed self-administration of opioids in the period 1985 to 1994, inclusive. The data for this study were obtained from files held by the Pharmaceutical Services Branch of the NSW Health Department. Information relating to sex, geographical location and main type of practice or specialty at the time of intervention, use of other drugs, period of opioid use before authority withdrawal, means of detection, and reports of psychiatric consultations, was collected from these files. Data relating to date of birth and registration status as at August 1995 were obtained from the NSW Medical Board, and data on the age, sex, specialty and geographical location of all medical practitioners in NSW were obtained from the Workforce Planning Unit of the NSW Health Department. Analysis To determine whether any groups were over-represented in the study group, demographic characteristics of the subjects were compared with those of the profession as a whole in NSW. Where available, data for 1990 were used in comparisons, as this represented a mid-point in the study period. For the number of medical practitioners and general practitioners in NSW, 1994 data were used. Confidence intervals and the χ2 test were used in the analysis of the data. Ethical approval The study was approved by the New South Wales Health Department. Strict confidentiality was maintained throughout the study. Results In the period 1985 to 1994, 79 doctors relinquished their Schedule 8 authorities as a result of confirmed self-administration of opioids. This represents 0.4% of the medical profession in NSW in 1994.11 Demographic characteristics The main characteristics of doctors in the study group at the time their Schedule 8 authorities were withdrawn are shown in Table 1. Ages of doctors in the study group at the time of authority withdrawal ranged from 26 to 69 years (mean, 39 years; 95% confidence interval, 36.8-41.2 years). Fifty-six per cent of the group were aged 30 to 39 years, a significant over-representation of this age group (Table 1). Rural practitioners were significantly over-represented in the group according to the chi-squared test (chi-squared, 4.67; P = 0.031) (Table 1). Four practice categories were identified in the study group: general practice (64; 81%), anaesthetics (3; 4%), psychiatry (3; 4%), and hospital salaried staff (9; 11%). Compared with the profession as a whole for 1994, general practitioners were significantly over-represented; anaesthetists and psychiatrists were not. Comparative data for hospital salaried staff in NSW were not available. Five of the nine doctors employed in salaried positions in hospitals were working in emergency departments. Drugs used Pethidine was the main drug used (66 doctors; 84%), with 31 (39%) apparently using nothing else. Commonly, doctors initially obtained pethidine, and to a lesser extent morphine, from their doctor's bag emergency supply, with prescriptions and surgery or hospital stock accessed as drug use escalated. Other drugs used included mixed opioids, barbiturates, ketamine and benzodiazepines. A concurrent alcohol problem was reported by 13 (16%) doctors, and eight (10%) admitted illicit drug use. All of the illicit drug users were men aged 30 to 43 years. Period of drug use Thirty-four (43%) doctors reported using opioids for more than two years before intervention, with four individuals admitting drug use for more than 10 years (Table 2). Two of these four also reported illicit drug use dating from their late teens. Means of detection Community pharmacists were the primary source of reports (Table 3), often alerted by a large number of opioid prescriptions written by a particular doctor. Common scenarios included prescriptions written for patients being either picked up personally from the pharmacy by the doctor, or requested to be delivered to the doctor's surgery, or patients being asked to collect opioids from the pharmacy and take them to the doctor's surgery, where one or two ampoules were administered to the patient and the balance retained by the doctor for personal use. Other reporting sources were routine inspections of community pharmacy records by departmental officers, and reports by colleagues and by the doctors themselves. Self-reports occurred in 14 cases (18%); most of these were due to the prompting of a treating psychiatrist or therapist as part of a rehabilitation program. Thirty-one doctors (39%) denied self-administration at first contact by the department. Of this group, 15 stated that the drugs were for use by others, usually relatives; 11 denied self-administration, with no other explanation offered; and five insisted that the drugs were used to treat a medical condition. At subsequent interviews, all admitted to self-administration for non-medical purposes and relinquished their drug authorities. Morbidity and mortality Twenty-eight (35%) doctors reported having consulted a psychiatrist before initial contact by the department. Twelve of these had consulted a psychiatrist for a drug abuse problem, the other 16 had consulted for non-drug related problems. Eight individuals in the study group reported that they had taken antidepressants. Ten (13%) of the doctors (nine men) are known to have died in the study period. Three of these are known to have committed suicide, one died of an overdose, two died in motor vehicle accidents, one died of a heart attack, and the cause of death of three individuals is not known. There were also five known suicide attempts by subjects during the study period. Registration status Only 54 (68%) of the subjects remained on the medical register as at August 1995 (Table 4). Two of these, although still on the register, were known to have left the profession. Including these two individuals, there was an overall loss from the medical profession in NSW of 27 (34%) individuals. Twenty-two doctors had continuing conditions placed on their registration by the Medical Board. These included, in addition to the continued withdrawal of the drug authority, requirements such as ongoing treatment by a psychiatrist, regular assessment and monitoring including urinalysis, supervised employment, and regular Board review, in line with the Board's Impairment Program protocols. Discussion From 1985 to 1994, 79 doctors had their authorities to possess, supply, prescribe or administer drugs of addiction withdrawn as a result of confirmed self-administration of opioids. Pethidine was the main drug used, and 43% of the doctors had been self-administering drugs for more than two years before detection. There are several limitations to the data in this study. The data were obtained from a retrospective review of file notes, which had been compiled by different interviewers, and did not follow a systematic data collection format. Data on several variables, including the extent of illicit drug use and period of drug use, relied on self-reporting and therefore introduced a "recall bias", either deliberate or inadvertent. A number of confounders may have influenced detection rates during the study period. These include the frequency and areas of prescription monitoring by the department, and changes in awareness and/or diligence of the reporting groups, such as community pharmacists and medical colleagues, who may have been influenced by articles in professional journals or by mailings by the Doctors' Health Advisory Service, as occurred in 1988. These factors may have varied between regions and over time. Another limitation of the study is that the subjects represent a subset of all drug-using doctors -- those who were detected. The data indicate that some doctors can self-administer drugs for prolonged periods without detection, and it is quite likely that sufficiently careful medical practitioners may self-administer opioids regularly and never be detected. Few doctors in the study sample surrendered their Schedule 8 drug authorities on their own instigation. Since detection of a problem was often based on observations by others, particularly community pharmacists, this could introduce systematic bias. Geographical isolation has been identified as a "marker" for substance abuse.12 However, the apparent correlation between rural practice and drug use may simply indicate that a doctor with a drug problem has a greatly increased chance of detection in a rural town than in the relative anonymity of the city. Among doctors detected self-administering opioids there is considerable attrition from medical practice. Of the 79 doctors in the sample, there was a loss of 27 individuals from the profession, with 10 of these known to have died in the study period. In recent years, the NSW Medical Board has adopted policies aimed at rehabilitating doctors who misuse drugs, while maintaining them in practice wherever possible. These policies include placing conditions on registration, such as supervised employment, restrictions on possessing and prescribing drugs of addiction, attendance for treatment and assessment, urine testing, and regular review by the Board. After a period of such supervision, practitioners who comply satisfactorily may return to full registration.11 There are no published data on the outcomes of these interventions. Attrition from the profession is taken as a poor outcome, but this may be an erroneous assumption. One hypothesis concerning medical practitioners who self-administer opioids is that they are ambivalent about medical practice,13 and this was confirmed by four subjects, two of whom had sought psychiatric treatment. It may be, therefore, that leaving practice was an appropriate decision for some individuals. The misuse of opioids described in this study should be seen within the wider context of the overall medical and psychological needs of medical practitioners. Acknowledgement The authors acknowledge the assistance of Pia Salmelainen, Policy Analyst (Research Officer), Pharmaceutical Services Branch, NSW Health. References Ball JRB. Alcohol and drug use and related problems in the medical profession. Aust Drug Alcohol Rev 1986; 5: 29-32. Murray RM. Psychiatric illness in male doctors and controls: an analysis of Scottish hospitals inpatient data. Br J Psych 1977; 131: 1-10. Preven DW. Physician suicide. In: Scheiber SB, Doyle BB, editors. The impaired physician. New York and London: Plenum Press, 1983; 39-47. Schlicht SM, Gordon IR, Ball JRB, Christies DGS. Suicide and related deaths in Victorian doctors. Med J Aust 1990; 153: 518-521. Webster TG. Problems of drug addiction and alcoholism among physicians. In: Scheiber SB, Doyle BB, editors. The impaired physician. New York and London: Plenum Press, 1983; 27-38. Centrelia M. Physician addiction and impairment -- current thinking: a review. J Addictive Diseases 1994; 13: 91-105. Morse RM, Martin MA, Swenson WM, Niven RG. Prognosis of physicians treated for alcoholism and drug dependence. JAMA 1984; 251: 743-746. Serry N, Ball JRB, Bloch S. Substance abuse among medical practitioners. Drug Alcohol Rev 1991; 10: 331-338. Serry N, Bloch S, Ball R, Anderson K. Drug and alcohol abuse by doctors. Med J Aust 1994; 160: 402-407. Pullen D, Cait EL, Lyle DM, et al. Medical care of doctors. Med J Aust 1995: 162: 481-484. New South Wales Medical Board. Annual report for the period ending 31 March 1994. Sydney: NSW Medical Board, 1994. Talbott GD, Gallegos KV, Wilson PO, Porter TL. The Medical Association of Georgia's impaired physician program, review of the first 1000 physicians: analysis of specialty. JAMA 1987; 257: 2927-2930. Modlin HC, Montes A. Narcotics addiction in physicians. Am J Psych 1964; 121: 358-363. (Received 11 Nov 1997, accepted 23 Jun 1998) Authors' details Pharmaceutical Services Branch, NSW Health, Gladesville, NSW. Megan Cadman, BPharm, MPH, Acting Deputy Chief Pharmacist. The Langton Centre, Surry Hills, NSW. James Bell, BA, FRACP, Director. Reprints will not be available from the authors. Correspondence: Ms M Cadman, Pharmaceutical Services Branch, NSW Health, PO Box 103, Gladesville, NSW 1675. E-mail: mcadmATdoh.health.nsw.gov.au - Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Megan Cadman · James Bell

- - More articles on Obstetrics & gynaecology and women's health Abstract Objectives: To review the evidence from all studies of adverse effects on infant outcome of psychotropic medications taken during pregnancy. Data sources: MEDLINE January 1976 - February 1998, EMBASE 1976 - February 1998, and bibliographies of retrieved articles. Study selection and data extraction: All studies focusing on adverse effects associated with psychotropic drug use during pregnancy, with a particular focus on prospective controlled studies. Outcome criteria: Congenital anomalies, perinatal complications and neurobehavioural sequelae. Data synthesis: 23 studies were identified, nine of which were prospective controlled studies: five involving antidepressants (tricyclic antidepressants [TCAs] and selective serotonin reuptake inhibitors [SSRIs]), one each involving lithium and carbamazepine, and two involving benzodiazepines. As statistical synthesis was not possible given the heterogeneity of outcome criteria, a qualitative review is provided. Neither the SSRIs nor the TCAs appear to cause major congenital anomalies, but both may be associated with a small increased risk of minor anomalies, prematurity and neonatal complications. Benzodiazepines, lithium, anticonvulsants and chlorpromazine do lead to an increased rate of congenital anomalies as well as neonatal problems. Studies of longer-term neurobehavioural sequelae of psychotropic medications are very limited, but at present do not indicate any adverse effects. Conclusions: While some psychotropes are associated with congenital anomalies and perinatal complications, mental illness per se may also be associated with an adverse outcome in the infant. Clearly, the risks to both mother and infant need to be carefully weighed and discussed with the parents. MJA 1998; 169: 428-431 Introduction Almost fifty per cent of pregnancies are unplanned,1 and up to 35% of pregnant women in western societies will be taking psychotropic medication.2 Most psychiatric disorders among women arise in the childbearing years, particularly in the Fperinatal period,3 and the effects of psychotropic medications on the fetus can present dilemmas in the treatment of pregnant women. One solution may be to cease therapy with these medications when pregnancy is contemplated or confirmed. However, women who stop taking medications during pregnancy experience high relapse rates.4 Suicidal behaviour, poor self-care, inadequate nutrition and poor antenatal clinic attendance, with a consequent lack of fetal monitoring, can all present risk to the fetus. Another aspect of mental illness during pregnancy is the possible direct effect of maternal illness per se on the fetus. Some studies have found an association between antenatal anxiety in women and increased obstetric complications such as prematurity, low birth weight,5 smaller head circumference and poorer scores on neonatal neurological examination.6 Women of low socioeconomic status who have depression have higher rates of premature and low birth-weight infants,7 while women with bipolar disorder who are not medicated also have higher rates of neonatal deaths and structural anomalies.8,9 One meta-analysis reports a higher incidence of obstetric complications in women with schizophrenia, regardless of whether the illness (and medications) began before or after delivery.10 This review examines the available evidence on the effects on the fetus of psychotropic medication used during pregnancy and provides some recommendations for treatment. Methods We searched MEDLINE (January 1976 - February 1998) using the following exploded medical subject headings (MeSH): "follow-up studies", "psychotropic drugs", "prenatal exposure", "adverse effects", "anticonvulsants", "pregnancy", "depressive disorder", "antidepressants", "infant" and "child development". A similar strategy was used in our EMBASE search (1976 - February 1998). Searches were limited to the English language. Studies that provide the highest level of evidence -- randomised controlled trials -- are not ethically acceptable in pregnancy. Thus we reviewed abstracts of articles for studies that met the following selection criteria: prospective controlled studies; retrospective studies; and case studies. This review is qualitative as the heterogeneity of outcome indicators means that data could not be analysed statistically. Outcome criteria Psychotropic drug use in pregnancy may be associated with three types of adverse outcome for the infant. Congenital anomalies: both major and minor physical anomalies (ie, those with and without cosmetic or functional importance) may occur with first-trimester exposure. The background incidence for each is 2%-4% and the cause is most often unknown.11 Perinatal complications: including poor obstetric outcome (eg, prematurity or low birth-weight) or syndromes related to drug use late in the third trimester, such as neonatal withdrawal or toxicity in the first few days after birth. Neurobehavioural sequelae: developmental delays, learning difficulties and neurological deficits resulting from drug exposure at any time in pregnancy. Results Of 23 studies identified, nine were prospective, non-randomised controlled studies. Five of these involved antidepressants (tricyclic antidepressants [TCAs]12,13and selective serotonin reuptake inhibitors [SSRIs]12-16), one involved lithium,17one carbamazepine,18 and two, benzodiazepines.1,19 These studies all controlled for maternal age and past obstetric history; some controlled for alcohol and smoking,12,13,15 but none controlled for other drugs. Summaries of the treatment of psychiatric disorders and use of psychotropic medications during pregnancy are shown in Boxes 1-4. Antidepressants Selective serotonin reuptake inhibitors (SSRIs): Fluoxetine was the first SSRI to be marketed and is the subject of most data currently available. Two prospective, controlled, but non-randomised, studies, have examined infant outcome in terms of congenital anomalies and perinatal complications after exposure to fluoxetine during pregnancy.12,14 Pastuzsak et al,12 found that rates of major anomalies and obstetric complications were no greater for women with depression taking fluoxetine, than for two control groups (women with depression exposed to tricyclic antidepressants, and non-depressed women not exposed to antidepressants, or other potential teratogens). Both groups with depression had increased rates of miscarriage and neonatal complications, including jaundice, hypotonia, cyanosis, apnoea and a number of minor physical anomalies (club feet, hydrocele, congenital hip dislocation and lacrimal stenosis). Chambers et al,14 found no increase in the rate of miscarriage and major anomalies, but among 97 infants examined for minor physical anomalies there was a significant increase in the number of infants with three or more such anomalies in the fluoxetine-exposed group. Infants of women exposed to fluoxetine in the third trimester had higher rates of prematurity, admission to special-care nurseries and poor neonatal adaptation than those exposed only in the first- and second-trimesters. In a prospective study of exposure to a variety of other SSRIs, Kulin et al found no increased rate of major congenital malformations, miscarriage, stillbirth or prematurity.15 Results from two non-controlled prospective studies of fluoxetine were conflicting. Goldstein, looking specifically at obstetric and neonatal complications with third-trimester exposure, reported a rate of neonatal complications comparable to that found in a general population survey, but almost double the normal rate of premature births,22 while McElhatton et al reported no increase in perinatal complications.23 Although the study of Chambers et al14 was far more methodologically sophisticated, its conclusions are still limited by its failure to control for use of other medication, smoking or alcohol. Given the lack of use of patients with depression as control subjects, none of these studies were able to separate any effect of depression per se from that of antidepressants on congenital anomalies or perinatal complications. In terms of neurobehavioural sequelae, a well-controlled study of children exposed to fluoxetine in utero and followed-up to the age of four, showed no increase in neurobehavioural deficits or developmental delays compared with non-exposed children of depressed mothers.13 Tricyclic antidepressants (TCAs): In terms of congenital anomalies and perinatal complications, a recent review of pooled results of 338 mothers indicated no increased risk of major structural anomalies with first-trimester exposure.20 Only two prospective studies have examined the potential teratogenic risk of tricyclics.12,23 Their findings were identical to those reported for fluoxetine. There have been some case reports of neonatal TCA withdrawal syndromes (irritabilty, jitteriness and convulsions)24 and anticholinergic effects (constipation and urinary retention).17 For neurobehavioural sequelae, the study of Nulman et al reported no increase in neurobehavioural deficits or developmental delays compared with non-exposed children.13 Other antidepressants (moclobemide, venlafaxine, nefazodone, mianserin, MAOIs): Heinonen et al cite a study of the use of MAOIs during pregnancy,25 reporting a higher rate of congenital anomalies in exposed infants. A report of 48 infants exposed to mianserin found one case of congenital anomaly.23 The lack of data on the newer antidepressants (moclobemide, venlafaxine, nefazodone) probably reflects their more recent entries onto the market. Benzodiazepines Pooled results from retrospective studies based on birth defect registry data on several hundred women indicate that the relative risk of cleft palate and lip is approximately 2-3-fold with first-trimester exposure to diazepam and 7-fold with alprazolam.20 While this increase in risk is statistically significant, the absolute risk remains small (having increased from 0.06% to 0.7%). The risk associated with other benzodiazepines has not been evaluated. Pastuszak et al prospectively examined 137 cases of benzodiazepine exposure in the first trimester and found no increase in congenital anomalies in the exposed group, but almost double the rate of miscarriages.1 Third-trimester exposure to benzodiazepines, especially to those with a long half-life, may lead to neonatal hypotonicity, failure to feed, apnoea and low Apgar scores.20 A small prospective study of 17 infants reported delays in developmental milestones at 18 months.19 However, a review of the literature on 550 infants followed-up to a maximum of four years of age, found no increase in neurobehavioural sequelae.26 Mood stabilisers Lithium: Initial reports from the Danish Register of Lithium Babies indicated significantly increased rates of cardiovascular malformations.27 A recent review of pooled data suggests a more modest risk of Ebstein's anomaly of the tricuspid valve (10-20 times that in the general population where it occurs in 1/20 000 cases).28 A prospective controlled study of 148 women, found a relative risk of 1.2 for all congenital anomalies and of 3.5 for cardiac anomalies in the babies exposed to lithium.29The "floppy baby" syndrome, in which the infant is hypotonic, cyanosed and suckles poorly is thought to be the result of lithium toxicity.30 Lithium has also been reported to affect neonatal thyroid function. A five-year follow-up of 60 children exposed to lithium in the second- and third-trimesters found no significant differences in developmental anomalies compared with non-exposed siblings.31 This was further supported by follow-up of 21 prospectively recruited infants, which found no difference in attainment of developmental milestones with the matched control group.32 Anticonvulsants: Carbamazepine and sodium valproate are effective mood stabilisers often used as alternatives to lithium for bipolar disorder.33 Data on the safety of using anticonvulsants during pregnancy derives from studies of women with epilepsy. Spina bifida occurs in 0.5%-1% of babies exposed to carbamazepine in the first trimester34 and in 1%-5% of those exposed to sodium valproate (compared with 0.03% in the general population).35 The risk may increase with higher serum levels and use of more than one anticonvulsant. Orofacial clefts and a number of minor malformations may also be associated with the use of these drugs. Withdrawal seizures in the infant have been reported with sodium valproate in a small case series.36 A recent small prospective controlled study of 36 infants indicates no developmental delays or cognitive impairment associated with carbamazepine use throughout pregnancy.18 Antipsychotics Among the typical (older) antipsychotics, pooled results of large retrospective and small prospective controlled studies of low dose chlorpromazine in weeks 4-10 indicate that its use in the first trimester may increase congenital anomalies by 0.4%.20 However, this increase in congenital anomalies was not seen with trifluoperazine.37 Two small retrospective studies of haloperidol exposure in utero also failed to show an increased rate of congenital malformations.38,39 Case reports, and one case series of chlorpromazine and other typical antipsychotics used in the third trimester, report neonatal restlessness, tremor, poor suckling, abnormal movements, jaundice and functional bowel obstruction.40 A five-year follow-up study showed no abnormalities in infants exposed to chlorpromazine in utero.41For the atypical (newer) antipsychotics (eg, clozapine, risperidone, olanzapine, zuclopenthixol) the only data currently available are from case reports, and so far there is no evidence of teratogenicity. There are no data available on neonatal complications or neurobehavioural sequelae. Conclusions The TCAs and SSRIs appear to be relatively safe in pregnancy, although they are possibly associated with increased rates of minor physical anomalies, prematurity, and neonatal complications. Chlorpromazine, long-acting benzodiazepines, lithium, and carbamazepine appear to be associated with major physical anomalies and poor neonatal adaptation. There is, however, some evidence to suggest that mental illness per se may be associated with an adverse outcome in the infant, while the risks to both mother and infant of a prolonged untreated episode of mental illness bear a considerable cost. The chain of causal events linking maternal illness and the use of medication to adverse outcomes in the offspring remains a complex issue. Before a decision concerning the use of psychotropic medication in pregnant women can be made, the risk-benefit ratio must be determined and discussed with the parents. References Pastuszak A, Koren G, Milich V, et al. Prospective assessment of pregnancy outcome following first-trimester exposure to benzodiazepines. In: Koren G, editor. Maternal and fetal toxicology. New York: Marcel Dekker, 1994: 77-88. Doering PL, Steward RB. The extent and character of drug consumption during pregnancy. JAMA 1978; 239: 843-846. Weissman MM, Olfson M. Depression in women: implications for health care research. Science 1995; 269: 799-801. Cohen LS, Rosenbaum JF. Psychotropic drug use during pregnancy: weighing the risks. J Clin Psychiatry 1998; 59 (Suppl 2): 18-28. Hedegaard M, Henriksen TB, Sabroe S, et al. Psychological distress in pregnancy and preterm delivery. Br J Psychiatry 1993; 307: 234-238. Lou HC, Hansen D, Nordenfoft M, et al. Prenatal stressors of human life affect fetal brain development. Dev Med Child Neurol 1994; 36: 826-832. Orr S, Miller C. Maternal depressive symptoms and the risk of poor pregnancy outcome: review of the literature and preliminary findings. Epidemiol Rev 1995; 17: 165-171. Kallen B, Tandberg A. Lithium and pregnancy: a cohort study on manic-depressive women. Acta Psychiatr Scand 1983; 68: 134-139. Kinney DK, Yurgelun-Todd DA, Levy DL, et al. Obstetrical complications in patients with bipolar disorder and their siblings. Psychiatry Res 1993; 48: 47-56. Sacker A, Done DJ, Crow TJ. Obstetric complications in children born to parents with schizophrenia: a meta-analysis of case-control studies Psychol Med 1996; 26: 279-287. Nelson K, Holmes LB. Malformations due to presumed spontaneous mutations in newborn infants. New Eng J Med 1989; 320: 19-23. Pastuszak A, Scick-Boschetto B, Zuber C, et al. Pregnancy outcome following first-trimester exposure to fluoxetine. JAMA 1993; 269: 2246-2248. Nulman I, Rovet J, Stewart DE, et al. Neurodevelopment of children exposed in utero to antidepressant drugs. New Engl J Med 1997; 336: 258-262. Chambers CD, Johnson KA, Dick LM, et al. Birth outcomes in pregnant women taking fluoxetine. New Engl J Med 1996; 335: 1010-1015. Kulin N, Pastuszak A, Sage S, et al. Pregnancy outcome following maternal use of new selective serotonin reuptake inhibitors: a prospective controlled multicentre study. JAMA 1998; 279: 609-610. Loebstein R, Koren G. Pregnancy outcome and neurodevelopment of children exposed in utero to psychoactive drugs: the Motherisk experience. J Psychiatry Neurosci 1997; 22: 192-196. Shearer WI, Schreiner RL, Marshall RE. Urinary retention in a neonate secondary to maternal ingestion of nortriptyline. J Paediatr 1972; 81: 570-572. Scolnik D, Nulman I, Rovet J, et al. The effects of phenytoin and carbamazepine monotherapy on infants' development. In: Koren G, editor. Maternal and fetal toxicology. A clinician guide. New York: Marcel Dekker, 1994: 45-58. Laegreid L, Hagberg G, Lundberg A. Neurodevelopment in late infancy after prenatal exposure to benzodiazepines: a prospective study. Neuropaediatr 1992; 23: 60-67. Altshuler LL, Cohen L, Szuba MP, et al. Pharmacologic management of psychiatric illness during pregnancy: Dilemmas and guidelines. Am J Psychiatry 1996; 153: 592-606. McNeil TF. A prospective study of postpartum psychosis in a high risk group: relationship to demographic and psychiatric history characteristics. Acta Psychiatr Scand 1987; 73: 35-43. Goldstein DJ. Effects of third trimester fluoxetine exposure on the newborn. Clin Psychopharmacol 1995; 15: 417-420. McElhatton PR, Garbis HM, Elefant E, et al. The outcome of pregnancy in 689 women exposed to therapeutic doses of antidepressants: a collaborative study of the European Network of Teratology Information Services. Reprod Toxicol 1996; 10: 285-294. Eggermont E. Withdrawal symptoms in neonates associated with maternal imipramine therapy. Lancet 1973; 2: 680. Heinonen OP, Slone D, Shapiro S. Birth defects and drugs in pregnancy. Littleton, Mass.: Publishing Services Group, 1977. McElhatton PR. The effect of benzodiazepine use during pregnancy and lactation. Reprod Toxicol 1994; 8: 461-475. Schou M, Goldfield MD, Weinstein MR, et al. Lithium and pregnancy, I. Report from the Register of Lithium Babies. BMJ 1973; 2: 135-136. Cohen LS, Friedman JM, Jefferson JW, et al. A reevaluation of risk of in utero exposure to lithium. JAMA 1994; 271: 146-150, correction; 271: 1485. Jacobson SJ, Jones K, Johnson K, et al. Prospective multicentre study of pregnancy outcome after lithium exposure during first trimester. Lancet 1992; 339: 530-533. Schou M, Amdisen A. Lithium and the placenta [letter]. Am J Obstet Gynecol 1995; 122: 541. Schou M. What happened to the lithium babies? A follow-up study of children born without malformations. Acta Psychiatr Scand 1976; 54: 193-197. Koren G, Pastuszak A, Jacobson S, et al. The safety of antidepressants in pregnancy. In: Koren G, editor. Maternal and fetal toxicology. A clinician guide. New York: Marcel Dekker, 1994: 59-76. Mitchell PB, Parker G. Treatment of bipolar disorder. Med J Aust 1991; 155: 488-492. Rosa F. Spina bifida in infants of women treated with carbamazepine during pregnancy. New Engl J Med 1991; 324: 674-677. Omtzigt JGC, Los FJ, Grobbee DE, et al. The risk of spina bifida aperta after first-trimester exposure to valproate in a prenatal cohort. Neurol 1992; 42 (suppl 5): 119-125. Thisted E, Ebbesen F. Malformations, withdrawal manifestations and hypoglycemia after exposure to valproate in utero. Arch Dis Childhood 1993; 69: 288-291. Rumeau-Rouquette C, Goujard J, Huel G. Possible teratogenicity effects of phenothiazines in human beings. Teratology 1997; 15: 57-64. Hanson JW, Oakley GP Jr. Haloperidol and limb deformity [letter]. JAMA 1975; 231: 26. Van Waes A, Van de Velde E. Safety evaluation of haloperidol in the treatment of hyperemesis gravidum. J Clin Pharmacol 1969; 9: 224-237. Auebach JG, Hans SL, Marcus J, et al. Maternal psychotropic medication and neonatal behaviour. Neurotoxicol Teratol 1992; 14: 399-406. Edlund MJ, Craig TJ. Antipsychotic drug use and birth defects: an epidemiologic reassessment. Compr Psychiatry 1984; 25: 32-38. (Received 16 Feb, accepted 8 Jul 1998) Authors' details Prince of Wales Hospital, Sydney, NSW. Marie-Paule V Austin, MB BS, FRANZCP, Staff Specialist in Liaison Psychiatry, and Conjoint Lecturer, School of Psychiatry, University of New South Wales; Philip B Mitchell, MD, FRANZCP, Administrative Director, Mood Disorders Unit, and Associate Professor, School of Psychiatry, University of New South Wales. Reprints will not be available from the authors. Correspondence: Dr M-P V Austin, Department of Liaison Psychiatry, Prince of Wales Hospital, Randwick, NSW 2031. E-mail: m.austinATunsw.edu.au 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/> 1: Treatment of depression in pregnancy If a pregnant woman is currently well, but has a history of relapse on withdrawal of medications, or if her current depressive episode is severe, the benefits of medications (direct for the mother and indirect for the infant) will usually outweigh the potential risks to the infant. It is good practice to use the minimum effective dosage and, if the mother does not plan to breast-feed, to halve the dose in the week before delivery to minimise any potential withdrawal in the infant. The infant should then be observed for withdrawal symptoms. The importance of general issues such as ceasing cigarette and alcohol intake, taking folate supplements and regular antenatal clinic attendance should be stressed to all expectant mothers. 2: Treatment of anxiety disorders in pregnancy Mothers taking a benzodiazepine regularly should be advised to taper the dose and to stop taking it before they become pregnant, and to use cognitive-behavioural management techniques and/or a small dose of a sedating tricyclic antidepressant (such as dothiepen) instead. Intermittent use of short-acting benzodiazepines is probably safe, and the long-acting diazepam used infrequently after the first trimester is probably not harmful. However, long-acting benzodiazepines (diazepam, clonazepam) should be avoided in the days before labour as they may compromise the infant's respiratory function during delivery. In mothers taking benzodiazepines on a long-term basis during pregnancy, and who do not plan to breast-feed, the medication should be slowly reduced before delivery to minimise neonatal withdrawal, and the infant will need to be observed for withdrawal symptoms. 3: Treatment of bipolar disorder in pregnancy First trimester Where possible, plan a drug-free first trimester by slowly tapering both lithium and anticonvulsants (to avoid acute relapse and withdrawal seizures, respectively) before conception. If the use of a mood stabiliser is unavoidable, lithium is a safer option. If first-trimester exposure has occured, an ultrasound scan and echocardiogram should be performed at 16-20 weeks to exclude cardiovascular, midline and other defects, and alpha-fetoprotein levels should be measured, as high levels are associated with congenital abnormalities. With inadvertent exposure to anticonvulsants, folate (which may reduce the risk of neural tube defects) should be given until the end of the first trimester.20 Antipsychotic medications may have to be used to achieve control of any disturbed behaviour in cases of manic relapse. Second- and third-trimesters When necessary, mood stabilisers may be recommenced in the second trimester. Lithium requirements will increase in the third trimester, but it is wise to reduce the dose by 25% just before delivery to avoid possible neonatal toxicity, and babies should be monitored for lithium toxicity for up to 10 days after birth. If the mother does not intend to breast-feed, it is best to reduce anticonvulsants before birth to minimise the risk of neonatal withdrawal symptoms. As women with bipolar disorder are at p articular risk of relapse postpartum (50%),21 therapy with mood stabilisers must be recommenced after the birth of the child. 4: Treatment of psychosis in pregnancy Chronic psychosis: depot antipsychotics are probably best avoided, given the potential for accumulation and toxicity in the neonate. For women with chronic psychosis, it is preferable to switch as early as possible to minimum effective doses of oral trifluoperazine or haloperidol and perform an ultrasound at 16-18 weeks to exclude the development of congenital abnormalities. Intensive case management and liaison with obstetric services is essential during this period as these women are at increased risk of relapse and poor antenatal care once they cease depot medication. Acute recurrent psychosis: should be managed as for bipolar disorder. Back to text

Marie-Paule V Austin · Philip B Mitchell

Eating disorders revisited. I: anorexia nervosa Peter N Gilchrist, David I Ben-Tovim, Phillipa J Hay, Ross S Kalucy and M Kay Walker MJA 1998; 169: 438-441 Synopsis - Introduction - Risk factors - Psychopathology - The role of the GP - Diagnosis - Treatment - References - Authors' details - - More articles on Psychiatry - ©MJA1998 Synopsis Anorexia nervosa is a serious psychiatric illness with a high morbidity and a significant lifetime mortality. Recurring themes in such patients centre on issues of self-worth and control. Treatment is difficult and prolonged, and may require hospitalisation. Therapy focuses on altering the misperceptions that patients have of themselves, both psychologically and physically. A multi-disciplinary team based in a specialised unit provides the treatment of choice, but if this is not available, a consistent, supportive relationship with an individual therapist familiar with the condition will be beneficial. Successful outcome should be based not simply on body weight but also on the resolution of anorexic thinking. Introduction Eating disorders have captured the public imagination. Images of severely emaciated young women suffering from anorexia nervosa appear often in glossy women's magazines and current affairs programs, while public disclosure of bulimia nervosa has become commonplace. This publicity tends to obscure the continuing puzzle created by these enduring, hard-to-treat, and sometimes fatal conditions. It is therefore timely to review the clinical dilemmas provided by eating disorders. Anorexia nervosa is not new,1 having first been described in the 17th century. The clinical presentation appears essentially unchanged since the first comprehensive accounts were produced in the late 19th century. Patients with anorexia nervosa are characterised by a relentless pursuit of thinness, resulting in weight loss and a refusal to maintain a normal body weight. This refusal has been described as a "normal weight phobia". Anorexia nervosa is not common. Worldwide, the true point prevalence is certainly no more than 0.5% of the female population over 15 years of age, and may be considerably less. Two studies of prevalence have been conducted in Australia: one reported a prevalence of 0.1% among a large group of schoolgirls,2 and the other reported a lifetime prevalence of 0.4% among a large group of twins.3 Evidence for changes in the incidence of anorexia nervosa is controversial. Reports of recent increased incidence in specific populations have been criticised on methodological grounds.4 Increased use of hospital services may reflect a change in the threshold for admission, as much as changing incidences.5 In our experience, demand for hospital services for these patients has not changed substantially. Anorexia nervosa can be fatal. Although death rates vary between studies and may be falling, a rule of thumb is that one patient per two hundred treated will die as a result of starvation or suicide during each treatment year. For patients who do survive, the burden of disability and distress remains considerable. Overall outcome varies between studies, but about 40% of patients make a good five-year recovery, 40% remain symptomatic but function reasonably well, and 20% remain severely symptomatic and are chronically disabled.6 Risk factors Sex: Anorexia nervosa occurs mainly, but not exclusively, among women; the female to male ratio is at least 10 to one. The origins of this sex difference remain unclear. However, as a society we are continually bombarded with images of impossibly slender young women. This, in part, explains the development of a "normative discontent" about physiologically unremarkable variations in body weight and shape.7 Dieting: Dieting is common in women in Australia and the first world, but only a small proportion of dieters develop anorexia nervosa. Why this proportion is so small remains unclear. However, normal dieting is almost certainly a trigger for the condition, and participation in occupations or sporting activities that require adherence to a strict diet is likely to place individuals at some risk.8,9 Other influences: Factors ranging from family communication characteristics such as blurring of boundaries and over identification, to personality styles such as perfectionism and obsessionality have been implicated as being of aetiological importance, but none have been validated with any scientific rigour.10 Psychopathology and clinical features The clinical features are deeply distressing for the observer; for the patient, the anorexic condition is a solution, but to what problem? The anorexic attitude is more understandable if being fat is seen as not being good enough, and being thinner is being better. In our view, the anorexic belief is: if my weight is right, then I am all right and if I am thinner then I must be a better person. Although the exact origins of such a state are unclear, patients commonly describe a pre-morbid sense of hopelessness, self-hatred and profound unworthiness. As weight loss occurs, individuals feel more disciplined and special. They can do something that their peers often talk about, but rarely succeed at: they can lose weight. In so doing they feel the ultimate triumph of control over their own bodies. Unfortunately, as self-control fails to influence the sense of self, and distress continues, the person displays a rigidity of outlook, and continues to pursue dietary perfection.11 The clinical picture that results is quite typical (Box 1). A change in eating patterns is one of the earliest signs of the disorder. Commonly, patients develop eating routines that have the effect of spreading out whatever enjoyment is to be had from eating, without losing control. Often these give the family and the patient the impression of an adequate dietary intake. Patients may dirty plates and eating utensils to maintain the facade of eating. Although the term "anorexia" implies loss of appetite, this is not correct. Anorexic patients are terrified of losing control of their appetite. Patients regularly describe a fear that meals will immediately be deposited as fat, so they must maintain control over food intake despite continuing hunger. Many abstain from food; others have eating binges followed by self-induced vomiting or purging. Vomiting and purging can also be seen in individuals whose food consumption is minimal. At one time, it was believed that anorexic patients had a distorted perception of themselves, as though they saw an expanded representation of themselves when they looked in the mirror. That view has not held up to scientific examination, but most people with anorexia nervosa do hold deeply negative attitudes towards their own bodies.12 They commonly feel that their hips and thighs are too large, and that their abdomen is too rounded and protuberant. The tenacity with which those feelings persist even in the face of profound emaciation is one of the most disconcerting and puzzling features of the condition. The clinical presentation and underlying problems are similar in men, although there may be a greater concern about health and fitness, rather than appearances.13 Patients with well-established anorexia nervosa are starving, and demonstrate various associated physiological changes (Box 2). These changes are non-specific consequences of the particular form of starvation seen in anorexia nervosa, and reverse with recovery. Anorexic patients may have changes in their menstrual patterns (oligo- or amenorrhoea) that may be concealed by the use of the contraceptive pill. Menses may cease before any substantial weight loss has occurred. Patients with anorexia nervosa are often depressed. There is debate whether the depression is solely related to the weight loss; more often a depressed mood or self-loathing precedes the decision to lose weight. Patients commonly describe a sense of hopelessness and acknowledge suicidal ideation. There may be a decrease in the level of enjoyment of life, although as they begin to lose weight, there may be increased physical activity. Whether this is a reflection of internal agitation or yet another way to burn off calories is not always clear. Patients often give a history of hyperventilation. Alcohol is used at times to decrease anxiety, and food intake is further reduced to compensate for the caloric intake. The role of the general practitioner General practitioners have an essential role in the early recognition and ongoing management of anorexia nervosa. Patients can present with anorexia nervosa at any age, but the onset of the disorder is most often in the mid-teenage years. Patients rarely present themselves for treatment; usually they are brought by family members who do not know what else to do. The family's concerns should be acknowledged, and the severity and potential chronicity of the illness be discussed even if there has not yet been a dramatic weight loss. For younger patients, the effects of starvation on physical development should be conveyed. Initial assessment is often difficult as patients may endeavour to conceal a degree of weight loss, be reluctant to be weighed, and try to minimise their difficulties. Information from other sources, such as family or school authorities, is usually necessary to complete the clinical picture. General practitioners are familiar with the dilemmas of caring for young people who seek to conceal information regarding their reasons for consulting from their families; when these issues relate to weight or diet, they are best seen as part of the illness. Families are commonly disrupted by the behaviour of the anorexic patient, and need support and advice. General practitioners can play a useful role in providing ongoing information and ensuring that families continue to maintain patients' safety despite entreaties by the patients that they will best recover by being left alone. Formal family therapy improves the outcome of adolescent patients still residing with their families, but does not change the outcome of older patients.14 In our experience, relationships that patients began when severely underweight often involve an element of rescue on behalf of the partner, who will then find actual recovery problematic. Anorexia nervosa is a serious condition and in our view specialised assessment, if only for diagnostic purposes, is indicated wherever possible. Further management can then be discussed with the specialist concerned. The therapeutic challenge presented by anorexic patients should never be underestimated. Diagnosis and investigations The diagnosis remains a clinical one. There are no specific investigations diagnostic of the disorder. The most widely used diagnostic criteria for defining anorexia nervosa are those in Box 3. With careful history-taking clinicians can elicit the degree of weight loss, which should be related to the pre-morbid weight. They should ask about the patient's heaviest, lightest and current weight, and the patient's own perceived ideal weight. Weight loss of more than 15% of average body weight is of considerable concern. Younger patients may show a failure to gain weight with developmental maturation, rather than loss of weight. Further enquiry should be made to determine if the weight loss has been voluntary, and to elicit any accompanying disturbances in body and self-related attitudes. While the diagnosis of anorexia nervosa is dependent on accurate history-taking, supporting observations may be made during physical examination and routine investigations (Boxes 2 and 4). The physical findings associated with starvation are quite variable, but the emergence of the biochemical indicators of starvation (Box 4) indicates a serious deterioration in the patient's health.16 Hormonal investigations are not warranted unless pituitary or ovarian dysfunction is seriously considered. Abnormal results such as hypokalaemia, a metabolic acidosis or alkalosis may suggest an eating disorder if the diagnosis was not previously considered. If the anorexic condition has been longstanding, bone densitometry may be useful to define the degree of bone loss and abnormalities. Treatment Treatment must be tailored to the needs of the patient and the severity of the illness. Denial of the severity or even the existence of a problem is extremely common, and the early phases of treatment are often difficult. Anorexia nervosa is a solution and an escape for the patient, so patients must have confidence that support will be available if they are to confront the varied internal and external conflicts that have precipitated the condition. These underlying problems are hard to deal with while patients have access to anorexia nervosa as a means of avoiding or resolving difficulties, so weight restoration and dietary normalisation remain the fundamental touchstones of treatment. However, they should only be one part of a comprehensive program of care, not a substitute for a long term approach. Referral to a specialised eating disorders service should always be contemplated, even for individuals whose weight loss is not yet marked. Referral is more urgent if amenorrhoea or weight loss of more than 10% has already occurred. If the general practitioner is experienced in the treatment of anorexia nervosa, this should continue, if possible, in conjunction with a specialised unit. Provision of such services varies between centres, however, and access may be particularly difficult for patients in country areas. Patients may become acutely medically unwell as a result of severe weight loss and dehydration, and may require resuscitation before any further treatment can be considered. Our unit has a close working relationship with our intensive care physicians, and severely unwell patients are admitted to the Intensive Care Unit for resuscitation before being transferred to our specialised eating disorders unit. The treatment of anorexia nervosa in our unit has evolved from long term inpatient programs with outpatient follow-up, to a predominantly outpatient strategy with hospital backup.17 Treatment begins on an outpatient basis, with inpatient care reserved for those individuals who fail to progress. The guiding principles of treatment are restoration of a normal weight range for height and age and the identification, and resolution, of the contributing family and personal problems. The hospital and staff should be portrayed as a resource that is available to the patient rather than as being able to provide a magical solution to the individual's problems. An eclectic approach is necessary, including individual and family therapy when warranted, dietary advice and, if considered appropriate, pharmacotherapy. A depressed mood may reflect an associated depressive illness and antidepressant medication can be of use. However, antidepressant medication is not recommended as a routine treatment. If a patient is highly agitated, especially when attempting to eat, then a major tranquilliser that does not have the disinhibiting effects of an anxiolytic agent may be useful, but should be instituted as part of the formal treatment program. Supervised weight gain, often involving bed rest, is still used for those who are unable to gain weight outside hospital. Prolonged hospitalisation is now limited to those who have failed in outpatient treatment or who have not benefited from brief admissions, except in young patients, where it is essential to gain weight to allow normal physical development. For patients who refuse active treatment, are treatment-resistant or live in isolated areas, general practitioners can provide an ongoing monitoring of patients' physical health. Insisting on admission to hospital is occasionally required if the patient is at physical risk, but should be avoided if possible. Such admissions should be in consultation with members of the ongoing treatment team. As a long term strategy, treatment orders have not proved helpful. Forced feeding, either naso-gastrically or intravenously, should only be used in life threatening medical situations, again, in conjunction with the treating team. References Kaufman MR, Heiman H. Evolution of psychosomatic concepts: anorexia nervosa. A paradigm. London: Hogarth Press, 1965. Ben-Tovim DI, Morton J. The epidemiology of anorexia nervosa in South Australia. Aust N Z J Psychiatry 1990; 24: 182-186. Wade T, Heath AC, Abraham S, et al. Assessing the prevalence of eating disorders in an Australian twin population. Aust N Z J Psychiatry 1996; 30: 845-851. Frombonne E. Anorexia nervosa. No evidence of an increase. Br J Psychiatry 1995; 166: 462-471. Halmi K. Changing rates of eating disorders: what does it mean? Am J Psychiat 1997; 152: 1256-1257. Herzog DB, Keller MB, Lavori PW. Outcome in anorexia nervosa and bulimia nervosa. A review of the literature. J Nerv Ment Dis 1988; 176: 131-143. Rodin J, Silberstein L, Striegel-Moore R. Women and weight: a normative discontent. Nebr Symp Motiv 1984; 31: 267-307. Richert AJ, Hummers JA. Patterns of physical activity in college students at possible risk for eating disorders. Int J Eating Disorders 1986; 5: 757-763. Gilchrist PN, Burke L. Eating disorders. In: Bloomfield J, Fricker PA, Fitch KD, editors. Textbook of science and medicine in sport. 2nd ed. London: Blackwell Science, 1995; 665-672. Strober M, Morrell W, Burroughs J, et al. A controlled family study of anorexia nervosa. J Psychiatr Res 1985; 19: 239-246. Vitousek KB, Daly J, Heiser C. Reconstructing the internal world of the eating- disordered individual: overcoming denial and distortion in self-report. Int J Eating Disorders 1991; 10: 647-666. Ben-Tovim DI, Walker MK. A quantitative study of body-related attitudes in patients with anorexia and bulimia nervosa. Psychol Med 1992; 22: 961-969. Carlat DJ, Camargo CA, Herzog DB. Eating disorders in males: a report of 135 patients. Am J Psychiat 1997; 154: 1127-1132. Russell GF, Szmukler GI, Dare C, Eisler I. An evaluation of family therapy in anorexia nervosa and bulimia nervosa. Arch Gen Psychiatry 1987; 44: 1047-1056. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Association, 1994. Sharp CW, Freeman CPL. The medical complications of anorexia nervosa. Br J Psychiatry 1993; 162: 452-462. Kalucy RS, Gilchrist PN, McFarlane CM, McFarlane AC. The evolution of a multi therapy orientation. In: Garner DM, Garfinkel PE, editors. Handbook of psychotherapy for anorexia nervosa and bulimia. New York: Guildford Press, 1984; 458-487. Authors' details Weight Disorder Unit, Flinders Medical Centre, Bedford Park, SA. Peter N Gilchrist, MB BS, FRANZCP, Clinical Director; David I Ben-Tovim, PhD, FRANZCP, Director of Research, and Associate Professor, Department of Psychiatry, Flinders University; M Kay Walker, BA(Hons), Research Officer. Department of Psychiatry, The University of Adelaide, Adelaide, SA. Phillipa J Hay, DPhil, FRANZCP, Senior Lecturer. Department of Psychiatry, Flinders University, Adelaide, SA. Ross S Kalucy, FRACP, FRANZCP, Professor. Reprints: Dr P N Gilchrist, Clinical Director, Weight Disorder Unit, Flinders Medical Centre, Bedford Park, SA 5042. - Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Peter N Gilchrist · David I Ben-Tovim · Phillipa J Hay · Ross S Kalucy

Synopsis Teaching and research are not funded directly under a casemix funding system, and individual Australian State and Territory governments have provided teaching and research grants to teaching hospitals to defray these costs. Biomedical research funding in Australia lags far behind that of other countries. The declining per capita expenditure on the health system generally, as well as on universities, is jeopardising teaching and research activities, which are not seen as "core" hospital services. Studies in the United States have shown that healthcare services associated with teaching and research are more costly but result in better patient outcomes. It may be time to promote outcome-based funding of teaching and research in the Australian healthcare system. Introduction Casemix funding models are essentially output-based funding systems which classify patients into different groups according to their clinical characteristics. Each patient's healthcare is funded on the basis of the average cost of providing care to patients with similar characteristics. Under a casemix funding system, teaching and research are not funded directly. It is now recognised -- and this view is supported by two large-scale government funded consultancies (Coopers & Lybrand in 1994 and KPMG Peat Marwick in 1996) -- that the costs of teaching and research, at least in Australian teaching hospitals, cannot be accurately separated from the costs of direct patient care. State and Territory health funding agencies have implemented teaching and research grants to supplement casemix payments in recognition of these activities in teaching hospitals (Box). The first teaching and research grants awarded in Victoria in 1993, based on numbers of trainees and research grants, were clearly a mechanism of providing funds to "top up" the variable casemix payments and ensure continuity of teaching hospitals' historical budgets. The grants were unrelated to the actual costs of teaching and research in the institutions. Teaching and research funding in other States has followed in this direction (Box), but this approach has not been universal, nor has it resulted in similar funding formulas. Teaching and research funding and casemix Biomedical research funding in Australia is inadequate, with government expenditure on research and development being 17% below the average for OECD countries.1 Despite recent increases in funding for medical research announced in the Federal Budget in May 1998, research spending planned by the Federal Government still lags far behind that of other countries. For example, the United States plans to double the budget for the National Institutes of Health (NIH) over the next five years.2 The NIH estimates that the approximately US$4.3 billion invested in research supported by the NIH has the potential to realise annual savings of between US$9.3 and 13.6 billion, which translates into a 200%-300% annual return on this research investment.2 The question of the future of biomedical research funding in Australia is currently being addressed by the Wills Committee established by the Federal Government. The committee's findings are due later this year, and what impact they may have on funding the significant biomedical research role of teaching hospitals remains to be seen. University funding per student is steadily declining (Mr S Hamilton, Australian Vice Chancellors' Committee, personal communication). There is decreasing support in real terms for faculties of health sciences and a greater emphasis on students funding their own tertiary education. Reduced funding and support has put further pressure on the teaching and clinical service loads of clinical academic and hospital staff. All clinical staff are already being asked to reduce costs, which can be done by reducing length of hospital stay for inpatients, and substituting ambulatory services, such as hospital-in-the-home or same-day services, for inpatient services; and by increasing the workload in consulting clinics. This is because payments for services provided are based on State government or Medicare Benefits Schedule fee-for-service, and more services bring in more income. All of these changes have reduced the time available for teaching medical undergraduate and postgraduate trainees, and the number of patients available for clinical teaching. This is not to say that the challenges of changing work practices should not be addressed. However, in times of declining per capita expenditure on the health system generally, as well as on universities, pressure inevitably comes to bear on teaching and research activities, which are not necessarily seen as "core" hospital services. There is no doubt that patients can be treated in an environment that eschews teaching and research, but the logical extension of this -- that no patient care should encompass teaching and research -- is ludicrous. This would require that Australia import the clinical expertise and the research (or products of research) that it might need. Is teaching and research a cost or a benefit? Under current medical student and postgraduate training systems, a significant proportion of teaching must occur in teaching hospitals. This applies to all medical undergraduate courses and all postgraduate training programs (including those for general practitioners). But what evidence is there that this is of benefit to society, apart from the training of doctors? Garber et al3 investigated this issue in the 1980s at Stanford University Hospital, California. They studied 2025 hospital admissions and measured differences in casemix costs and hospital deaths according to whether patients were admitted to services staffed by full time faculty members (with resident medical officers and students) or to non- faculty, community-based services (in which two-thirds of patients received no care from resident medical staff). The faculty service had more patients with costly diagnoses, and their costs were 11% higher (95% confidence interval [CI], 4%-18%) after adjustment for casemix. However, the faculty service provided a much better patient outcome. After adjusting for casemix and socioeconomic characteristics, the community service patients were 34% (95% CI, 1%-66%) more likely to die in hospital. This difference was most pronounced for the highest risk patients, who also had the largest cost differential. The mortality rate advantage for faculty service was maintained for at least six months after discharge, but by nine months there was no difference. More recently, Zimmerman et al4 prospectively surveyed the resource use and outcomes of 15 297 intensive care patients in 35 teaching and non-teaching hospitals in the United States. Patients in teaching hospital intensive care units had more severe illnesses, but these units had a greater staff-patient ratio. Service provision in the teaching hospital intensive care units also came at an extra cost, which was related to an increased use of diagnostic testing and invasive procedures. However, the extra cost was associated with a significantly better risk-adjusted outcome in hospitals that were members of the Council for Teaching Hospitals (odds ratio, 1.21; 95% CI, 1.06-1.38). Obviously, there are differences between these US service provision models and those in Australia, but no similar appropriately controlled studies are available in Australia. What these studies show is that a service associated with academic activities may have an advantage for patient outcomes, but this comes at an extra cost. It is interesting that the extra cost should be so close to the 10%-20% described anecdotally and in various studies5 as the extra cost of teaching hospitals (compared with non-teaching hospitals) in Australia. No one denies that quality of care requires adequate funding. Nor do most people believe that efficiency and cost-effective use of healthcare funding should be ignored. However, it is increasingly recognised within the medical profession, and by external monitoring bodies such as the Victorian State Auditor General,6 that the simultaneous introduction of major budget cuts and casemix funding has had a negative impact on the quality of hospital care. This decrease in quality of care was thought to be related to the budget cuts, with the added pressures on clinical staff6 probably affecting their teaching and research activities.7 Rewarding patient care outcomes The basic rationale for casemix funding of patient services is that it is output based. Teaching and research also need to be recognised as outputs. If they do not receive adequate, appropriate and identifiable funding (over and above the costs of patient care), the marketplace will dictate that staff, facilities and other infrastructure support associated with teaching and research will become eroded so as to preserve the funding of the "core" clinical services. Many clinical academics believe that this is already happening.7 The concept of rewarding patient care outcomes rather than patient care services has been raised in other forums,8 despite difficulties determining the methods by which this could occur. It has not been raised with regard to teaching and research. Perhaps now is the time to promote outcome-based funding of teaching and research so that they become more than just of theoretical value in the Australian healthcare system. Acknowledgements I would like to thank Oon Ying, Deniza Mazevska, Art Huston, Susan Mirls, Danni Caminiti, Ric Marshall, Jim Pearse, Vicki Rundle, and Elizabeth Rohwedder for providing details of their State or Territory teaching and research formulas. References Commonwealth Department of Science, Industry and Tourism. Table of international research and development performance. In: Australian science and technology at a glance. Canberra: AGPS, 1997. Clinton W. Catalyzing scientific progress: special address from the President. Science 1998; 279: 1111. Garber AM, Fuchs VR, Silverman JF. Case mix, costs and outcomes; differences between faculty and community services in a university hospital. N Engl J Med 1984; 310: 1231-1237. Zimmerman JE, Shortell SM, Knaus WA, et al. Value and cost of teaching hospitals: a prospective, multicenter, inception cohort study. Crit Care Med 1993; 21: 1432-1442. New South Wales Department of Health. The costs of teaching hospitals: a review of the literature. Sydney: NSW Department of Health, 1993. Victorian Auditor General. Acute health services under casemix -- a case of mixed priorities. Melbourne: Victorian Auditor General, 1998. (Special Report No. 56.) Phillips PA, Kennedy JT, Segal GR, et al. Perspectives on casemix-based funding in Victoria. Med J Aust 1995; 162: 655-657. Braithwaite J, Hindle D, Phelan PD, Hanson R. Casemix funding in Australia. Med J Aust 1998; 168: 558-562. Authors' details Flinders University of South Australia, and Divisions of Medicine, Flinders Medical Centre and Repatriation General Hospital, Adelaide, SA. Paddy A Phillips, DPhil, FRACP, Professor and Head of Medicine. Reprints will not be available from the author. Correspondence: Professor P A Phillips, Professor and Head of Medicine, Flinders University of South Australia, Bedford Park, SA 5042. E-mail: paddy.phillipsATflinders.edu.au

Med J Aust 1998; 169 (8 Suppl).