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Objective: To estimate Hepatitis C prevalence in 1983-1984, and survivorship to 1 January 1995, of patients who tested were for Hepatitis B surface antigen in 1983-1984; and to do so according to risk of blood-borne virus transmission, including injector status., Setting: Regional Virus Laboratory in Edinburgh., Samples: Sera from 1983-1984 which were originally received for hepatitis B surface antigen testing and were classified as being at high, medium, or low risk for blood-borne virus transmission., Results: Available 1983-1984 sera were tested from: (i) all 246 patients aged 15-55 years who were Hepatitis B surface antigen positive in 1983-1984; and (ii) a 10% systematic sample of 355 patients aged 15-55 years who had tested Hepatitis B surface antigen negative in 1983-1984. Patients' survival status at 1 January 1995 was established via the records of the Registrar General for Scotland. A Hepatitis C prevalent case cohort of 500 survivors to 1 January 1995- who were already infected with Hepatitis C in 1983-1984--could be established from group (i) and high or medium risk group (ii) patients with, as controls, 1460 individuals of similar age and risk group whose 1983-1984 sample was negative when tested retrospectively for Hepatitis C antibodies. Two hundred out of these 500 cases are not known to be injecting drug users, and the total would rise to 300 out of 600 if the case cohort were expanded to include low risk group (ii) surviving patients who were Hepatitis C antibody positive in 1983-1984. Between 82% (40/49) and 97% of injectors (57/59 if also HIV-infected) who were Hepatitis B surface antigen positive in 1983-1984 were already Hepatitis C antibody positive; and 72% (95% confidence interval (CI) 51%-93%) of injectors who were Hepatitis B surface antigen negative in 1983-1984 were nonetheless infected with Hepatitis C. Known drug user/contacts (excluding the major group of 59 identified HIV-infecteds) had Hepatitis C prevalence in 1983-1984 of 79% (53/67, with 95% CI 69%-89%), substantially higher than our prior assumption, which was 50%. Hepatitis C prevalence in 1983-1984 for patients who were not known to be injectors, were Hepatitis B surface antigen negative and were rated as moderate risk for blood-borne virus transmission was 13% (95% CI 4%-23%) and 8% (95% CI 3%-14%) even for low risk patients. Deaths by end December 1994 in 1983-1984 prevalent Hepatitis C infections were low: 2/35 (6%) for patients who were Hepatitis B surface antigen negative in 1983-1984 and 2/40 (5%) for Hepatitis B surface antigen positive injectors who were not HIV-infected. The latter rate with upper 95% confidence limit of 12% is modest when compared to the 10% mortality that would be expected of injectors over 11 years., Conclusion: Retrospective Hepatitis C testing of 1700 stored sera from high or medium risk group (ii) patients who were not known to be injectors will identify an estimated 200 (11.7%) who were already Hepatitis C infected in 1983-1984 and still alive on 1 January 1995. Retrospective Hepatitis C testing of 1300 low risk samples is expected to yield 100 (7.6%) apparently non-injector patients who were already Hepatitis C infected in 1983-1984 and still alive on 1 January 1995.

Objective: To estimate the early death-rate in HIV infected injectors whose HIV infection was during the injection-related HIV outbreak in Lothian region in Scotland in 1983-1984, which was coincident with Hepatitis B transmissions., Setting: Regional Virus Laboratory in Edinburgh., Samples: Sera from 1983-1984, originally received for Hepatitis B surface antigen testing, from individuals aged 15-55 years who were positive for Hepatitis B surface antigen in 1983-1984 (group A: census) or tested negative but were at high risk for blood-borne virus transmission according to their reason for testing (group B: 50% sample)., Methods: Survival status of individuals in groups A and B who had not been diagnosed with HIV disease by the end of December 1995 was checked against the deaths' records of the Registrar General for Scotland. Stored sera from 1983-1984 for patients who had died early (that is: in 1983-1984) were tested anonymously for HIV and Hepatitis C antibodies; and prior to testing, causes of death were scored by RPB according to the likelihood of their being HIV or drugs related., Results: Three early deaths were found in group A patients who were not known to be HIV infected. None of the deaths was likely to be HIV-related; the sera were not tested in order not to risk deductive disclosure. Twenty-four early deaths were found in group B patients who were not known to be HIV-infected, five of whom were both HIV and Hepatitis C antibody positive, and one other was HIV antibody negative but Hepatitis C positive. Reclassification after unlinked anonymous testing and multiplying up of the group B results (to account for 50% sample) gave the early death rate (that is: in 1983-1986) as 15/155 (10%) for HIV-infected drug users (95% CI: 6%-13%)., Conclusion: Injection-related outbreaks of HIV infection in Lothian in 1983-1984 and at Glenochil Prison in 1993 were each associated with substantial--estimated 10%--early death-rate in HIV-infected injectors. Both HIV outbreaks were coincident with Hepatitis B transmissions, which may be relevant. Further investigations of the death-rate within 2 years of HIV infection are warranted in other exposure categories than injection-related and for injectors who have been immunized against Hepatitis B.

This data linkage study examined the extent of hepatitis B transmission and co-infection with HIV among 636 former inmates of Glenochil prison, Scotland, during an outbreak of bloodborne diseases in 1993 which was related to needle sharing. Eleven inmates imprisoned during the first half of 1993 presented with hepatitis B infection, of whom co-infection with HIV was detected in six. Based on dates of test results in relation to time of imprisonment, seven definitely acquired their hepatitis B infection within the prison. Only two infections were reported to Scotland's hepatitis B register and neither could be prison-linked. This outbreak of hepatitis B is the first of its kind to be reported but not the first to have occurred. It not only highlights the urgency for measures to prevent further spread of infection among prisoners but also illustrates the need for comprehensive surveillance of hepatitis B infection, and the need for a protocol on how to manage such outbreaks and on how to establish the extent of transmissions when acute hepatitis B occurs in prison.

We used existing data on hepatitis C prevalence, injection-related hepatitis C transmission and needle use in prisons and new data on infectiousness, to estimate the size of study required to detect injection-related hepatitis C in UK prisons. A pilot study of 500 prisoners followed for 10 weeks would have a 65% chance of detecting a hepatitis C seroconversion, conservatively assuming one injection per prisoner per week, and a 3% transmission rate per injection, but uncertainty might persist as to whether transmission had occurred during a short incarceration or before it. If the actual transmission rate was 10%, as recently documented, then such a study would have more adequate statistical power. A definitive study of 3000 prisoners for 10 weeks would expect to detect about six seroconversions, even with conservative estimates of injection frequency and transmission rate. Adequate design and power of these studies is important because of the complacency that could result from false-negative findings. We suggest six risk-factor themes that studies should document.

Objective: To assess whether injecting drug users have a higher than usual risk of death from overdose in the 2 weeks after release from prison., Design: Soundex coding of surnames and information on date of birth were used to link entry and release dates from the local prison between 1983 and 1994 with clinical data from Edinburgh City Hospital's cohort of male injecting drug users who are infected with HIV., Setting: Edinburgh City Hospital and Edinburgh Prison., Subjects: 316/332 male injecting drug users infected with HIV in the City Hospital HIV cohort; 16 were excluded because they were enrolled after developing AIDS or because their precise date of death was not available., Main Outcome Measure: Relative risk of dying from overdose before developing AIDS and relative risk of dying of all causes before developing AIDS during the 2 weeks after release from prison; this was compared with relative risks of death during other time at liberty., Results: 238/316 (75%) injecting drug users served time in the prison between 1983 and 1994. 33 out of 316 injecting drug users who were infected with HIV died before developing AIDS during 517,177 days at risk. 20 of these men died of an overdose; 6 of these deaths occurred within 2 weeks of release during 5903 days at risk. Death rates from overdose before the development of AIDS were 1.02/1000 days during the 2 weeks after release (recently released) and 0.029/1000 days during other times of liberty. The relative risk of death from overdose became 7.7 (1.5 to 39.1) after temporal matching (when the comparison was limited to the first 2 weeks after release v the next 10 weeks). The crude relative risk in an analysis combining stratified prison term and the 2 weeks after release was 4.5 (1.7 to 11.7) for death from overdose. After temporal matching these risks became 1.8 (0.4 to 9.2)., Conclusion: Prisons should evaluate interventions to reduce the risk of death from overdose after release.

In this paper, we look at the incidence and predictive factors of pre-AIDS mortality among HIV-infected individuals, and injecting drug users (IDUs) in particular, and compare IDUs with non-IDUs. 627 patients (73 per cent IDUs) of the Edinburgh City Hospital HIV Cohort were enrolled pre-AIDS and followed up until September 1994. Analyses were performed using cumulative hazard and cumulative incidence estimators for a competing risks model, the Cox proportional hazards model and the non-parametric hazard estimator of Fusaro et al. (1993). The effects of age and CD4 T-lymphocyte cell count, progressively depleted during HIV progression, were investigated. 60 deaths occurred in AIDS-free patients during follow-up; 25 were drug-related deaths in IDUs. Pre-AIDS mortality was higher among IDUs than non-IDUs (p = 0.07). The cumulative incidences of pre-AIDS death after five years from enrollment were 11 per cent in IDUs and 6 per cent in non-IDUs; the cumulative AIDS incidences were, respectively, 19 per cent and 32 per cent. After eight years, cumulative pre-AIDS death incidence was 15 per cent among IDUs; cumulative AIDS incidence among IDUs was 35 per cent. Both groups had similar risks of medically-related (non-AIDS)-MRNA-death. Age and CD4 count were both individually predictive of MRNA death (relative risks (RRs); 2.1 per decade of life, p < 0.01; and 1.9 for each 100 cells per 100 microliters lost, p < 0.0001), although when used together age was less significant (RR 1.6, p = 0.07). Neither was statistically significant for drug-related mortality, although hazard may be lower in older individuals and may increase with falling CD4 count. The drug-related mortality was 1.1 per cent: 2.3 per cent in the first two years after enrollment, and 0.4 per cent thereafter. We conclude that older HIV-infected individuals are at greater risk of medically-related death before AIDS. This risk increases as CD4 count declines. Drug-related hazard may be greater in younger individuals and may increase as CD4 counts fall, but neither effect was formally significant.

We tested the validity of a previously-published AIDS staging system by examining AIDS-defining diseases (ADDs) and CD4 counts as prognostic factors for survival of the 248 AIDS patients in the Edinburgh City Hospital Cohort, of whom 56% were injecting drug-users (IDUs). Cox regression was used to model the proportionality of risk of death as the CD4 count declined and more ADDs were experienced, and dependence upon post-AIDS treatment. Using the system of Mocroft et al. (Lancet 1995; 346:12-17) to grade severity, our data were well enough modelled, but we suggest: (i) regrading of HIV dementia (RR 3.9, 95% CI 2.5-6.0), mainly attributed to the drug users, to a very severe ADD; (ii) reduction in risk from zidovudine (RR 0.7, 95% CI 0.5-1.0) during AIDS follow-up for patients starting treatment at or after AIDS diagnosis; (iii) improved management of first mild ADDs (from 1987-89 to 1994-95: 40% reduction in IDUs appearing with mild index diseases, and an approximate three-fold reduction in risk associated with a mild ADD). This study supports previous findings on the significance of ADDs and lowest CD4 count in predicting the lifetime of AIDS patients.

Aim: On the basis of finalised data from the Corneal Transplant Follow up Study to identify and quantify factors influencing corneal graft outcome in terms of graft survival, rejection, visual acuity, and astigmatism., Methods: Multifactorial analysis of 2777 grafts registered by the UK Transplant Support Service from July 1987 to June 1991., Results: Several recipient factors influencing graft survival, rejection, and visual acuity were identified, but no donor factors. Of the operative factors amenable to change, mixed suturing was associated with reduced graft survival, and larger grafts with increased risk of rejection but better visual acuity when surviving. There was increased risk of rejection with poor matching at HLA class I antigens, but mismatched HLA-DR grafts suffered less rejection than those with zero HLA-DR mismatches. Recipient age below 10 years was associated with increased risk of both rejection and graft failure. However, whereas increasing age above 10 years was not associated with differential graft survival, it was significantly associated with decreasing risk of rejection., Conclusions: While confirming possible benefits of HLA-A and B matching, the expense and delay involved in awaiting matched HLA-DR tissue is unlikely to be justified. Other donor factors are unrelated to graft outcome following screening of tissue by eye banks. The highest rates of graft failure and rejection happen in the early postoperative period, and factors influencing visual outcome are also apparent at this stage.

434 male and 145 female prisoners were available to participate in cross-sectional, voluntary anonymous HIV surveillance (using saliva samples) with linked self-completion questionnaire at HMP (Her Majesty's Prison) Perth on 17 May and at HMP Cornton Vale on 18 May 1995. Three hundred and four men (70%) and 136 women (94%) completed a risk-factor questionnaire and 304 and 135 samples were received for HIV antibody testing. Two hundred and eighty-two and 132 questionnaires passed logical checks. Six saliva samples from Perth (all injectors) out of 304 and none from Cornton Vale out of 134 tested were HIV antibody positive. Four were presumptively from known HIV-infected male inmates; the other 2 were local men, under 26 years, who began injecting in 1989-91, and both reported having had a recent HIV test. Overall HIV prevalence was estimated at 2% compared to a known prevalence of 1.4% (6/434), giving a 1.5 ratio of overall: disclosed HIV prevalence at HMP Perth. HIV prevalence was estimated at 7% (6/82) for injector-participants and 14% (5/35) for local injector participants. At Cornton Vale, where both known HIV-infected inmates abstained, overall and disclosed HIV prevalence, were equal at 1.4%. At Perth Prison, 29% of prisoners had injected drugs (82/278); 85% of injector-inmates reported having injected inside (some prison and 31% (25/80) had started to inject while inside, 7 during their present sentence. Of all 21 injector-inmates who first injected after 1991, 10 had started to inject inside, including one of 69 male inmates who had never been inside before. The corresponding figures for Cornton Vale, where 46% of inmates were injectors (58/132), were that 57% of injector-inmates had injected inside (32/56) but only one woman, for whom this was not her first sentence, had started to inject inside. Twenty-eight per cent of male prisoners (78/277) and 57% of male injector-inmates (47/82) had had a personal HIV test since January 1993, as had 35% of female prisoners (43/124) and 57% of female injector-inmates (30/53). A much higher proportion of Glasgow's female prisoners (64%: 38/60) were injectors than of women prisoners from the Edinburgh, Dundee and Fife area (21%: 5/26) or from elsewhere (34%: 15/45). Rape was reported by 23% of women (30/130). Women who had been raped had a more polarized distribution of male sexual partners (none to 2 plus) in the year before sentencing than other women and were more likely to report anal sex (11/30 vs 11/100, P < 0.001). Prostitution had been engaged in by 19% of female injector-inmates (11/57) and was acknowledged by one other woman. However, only 5% of women (6/130) reported ever having been treated for an STD.

Objective: To examine the impact of age, year and region of AIDS diagnosis on early (up to 12 months) and late survival of AIDS patients in different exposure categories; to describe the hazard pattern from 12 months after AIDS diagnosis., Patients: A total of 4577 UK adult AIDS diagnoses to the end of 1991 in men who have sex with men, 273 AIDS cases in injecting drug users, 411 AIDS patients infected by blood products, and 535 other adult AIDS cases, mainly ascribed to heterosexual transmission. Deaths have been recorded for 4739 of these 5796 AIDS patients., Results: The influence of calendar year and region of AIDS diagnosis on survival were short-term, for the most part operative only within the first year of follow-up. The monthly death-rate was roughly constant from 12 to 48 months post-AIDS [pooled estimate, 0.055 with 95% confidence interval (CI), 0.053-0.057] but was more than halved for 4-year survivors (pooled estimate, 0.022; 95% CI, 0.017-0.027). About 7% of AIDS cases diagnosed in 1990-1991 survive for at least 48 months. Survival after AIDS diagnosis shortens with advancing age at AIDS diagnosis: the relative hazard per decade of age (1.35; 95% CI, 1.29-1.41 in the first year after AIDS) is significantly greater (P < 0.001) in the first year after AIDS diagnosis than from 12 to 48 months (1.19; 95% CI, 1.13-1.25 in the second epoch)., Conclusions: The influence of covariates, including age, is strongest in the first year of follow-up after AIDS diagnosis. Monthly death-rate is roughly constant at 0.055 from 12 to 48 months post-AIDS and at 0.022 thereafter.

Background: Compulsory urine testing of prisoners for drugs, a control initiative, was introduced in eight prisons in England and Wales early in 1995. Despite no evidence of effectiveness, testing was extended to all prisons in England and Wales by March 1996. We consider the cost of testing., Methods: We combined the costs of refusals, confirmatory tests, punishment of confirmed positives for cannabis or for class A drugs to estimate the average costs of random compulsory drugs testing. These costs were then compared to: i) the healthcare budget for a prison; and ii) the cost of putting in place a credible prisons' drugs reduction programme. We then used Scottish data on incarceration and regional prevalence of injecting drug users to estimate the extent of the injecting drug use problem that prisons face., Findings: Costs per 28 days of the random mandatory drugs testing control initiative in an establishment for 500 inmates where refusal rate is a) 10% or b) nil; and 35% of urine samples test positive, one tenth of them for class A drugs were estimated at between a) 22,800 UK pounds and b) 16,000 UK pounds per 28 days [a) $US35,100 and b) $US24,600]. This cost was equivalent to twice the cost of running a credible drugs reduction and rehabilitation programme, and around half the total healthcare expenditure for a prison of 500 which averaged 41,114 UK pounds per 28 days [$US64,860]. Major cost-generating events were the punishment of refusals--over one third of cost a)--and testing positive for cannabis--over 50% of cost a). In Scotland, around 5% of injecting drug users (IDUs) are incarcerated at any time: 5% of Lothian's drugs care, treatment and prevention costs and 2.5% of its HIV/AIDS prevention budget in 1993-94 amounted to 101,300 UK pounds per annum--or 7770 UK pounds per 28 days ($US11,970)--and about 35% of monthly MDT costs., Interpretation: We suggest that 5% of current resources for drugs prevention and treatment and for IDU-targetted HIV/AIDS prevention should be directed towards the prisons because in the prisons, where 5% of the clients are at any time, injectors have less access to harm reduction measures than on the outside.

Mandatory drugs testing of prisoners applies throughout England and Wales. Data from the 1995 pilot study in eight prisons show that the proportion testing positive for opiates or benzodiazepines rose from 4.1% to 7.4% between the first and second phase of random testing and that there was a 20% increase over 1993-4 in the provisional total of assaults for 1995. Interpretation of these data is difficult, but this is no excuse for prevarication over the danger that this policy may induce inmates to switch from cannabis (which has a negligible public health risk) to injectable class A drugs (a serious public health risk) in prison. The performance indicators for misuse of drugs that are based on the random mandatory drugs testing programme lack relevant covariate information about the individuals tested and are not reliable or timely for individual prisons.

Objective: To describe progression and survival of individuals infected with HIV by injecting drug use in Edinburgh., Design and Methods: From 313 HIV-infected patients with retrospectively estimated narrow seroconversion intervals, 260 infected via injecting drug use in the years 1983-1985 were selected for the study group., Main Outcome Measures: The effects of gender, age, human leukocyte antigen (HLA) type and zidovudine (ZDV) treatment on progression and survival from seroconversion; Weibull estimates of the AIDS incubation distribution and the overall survival distribution; slopes of absolute CD4 lymphocyte loss (on the square root scale) and loss of CD4 percentage., Results: The cumulative progression rates at 10 years were 68% to CDC stage IV and 31% to AIDS with a mortality rate of 25%. Three-year survival rates for AIDS and CDC stage IV cases were 25 and 72%, respectively. Gender and age effects on progression or overall survival were not found, although those aged over 30 years experienced poorer survival from AIDS. A strong HLA (A1, B8, DR3) association with faster progression and poorer survival was found. Median survival was estimated by Weibull distribution to be 12.6 years; median AIDS-free time was estimated to be 11.6 years. CD4 cell loss was approximately linear when transformed to the square root scale as was the decline in CD4 percentage. Only HLA effects on slopes were found: A1,B8, DR3 was significantly associated with faster loss of both absolute CD4 cells and CD4 percentage (P < 0.001) and B27 was significantly associated with slower loss of CD4 percentage (P = 0.01)., Conclusions: Edinburgh IDU do not seem to progress more rapidly than other cohorts with predominantly different risk activities. Older age was associated with poorer survival from AIDS but no gender effect was found for progression or overall survival. The clearest significant association with AIDS progression, mortality and loss of CD4 cells was the phenotype HLA A1,B8,DR3. In contrast HLA B27 was associated with slower loss of CD4 cells.

We examined how HLA types A1-B8-DR3 and B27 were related to progression of clinical disease and rate of loss of CD4 lymphocytes in the Edinburgh City Hospital cohort of HIV-positive patients, mainly injection drug users. Patients (n = 692) were prospectively followed from 1985 through March 1994. Accurately estimated seroconversion times were determined retrospectively for a subgroup of 313 (45%). Of 262 patients (39%) who were fully or partially HLA typed, 155 (50%) had known seroconversions. Of 34 patients typed positive for A1-B8-DR3, 29 progressed to CDC stage IV, 22 to AIDS and 20 died. Twelve patients were typed positive for B27; six of these progressed to CDC stage IV, one to AIDS and none died. In a proportional hazards analysis of the 313 patients with known seroconversions, A1-B8-DR3 was significantly associated with covariate-adjusted relative risks of 3.7 (95% CI 1.9-7.2), 3.1 (1.6-6.0) and 1.9 (1.1-3.2) for progression from seroconversion to death, AIDS and CDC stage IV, respectively. Events for B27 were too rare to include B27 in analyses to death and AIDS, but B27 was significantly associated with slower progression to CDC stage IV (0.3, CI 0.1-0.9). Random effects growth curve models were used to estimate individual rates of loss of square root CD4 count and loss of CD4 percentage, for 603 and 617 patients, respectively. A1-B8-DR3 was associated with rapid loss of both markers (p = 0.02 and p = 0.01, respectively); B27 was associated with slow loss of both markers (p = 0.04 and p < 0.005).

We fit a class of random effects linear growth curve models for the square root of CD4 count to serial marker data from 164 HIV-positive individuals with known (or accurately estimated) dates of seroconversion and at least 10 CD4 measurements each (median 16). We do so by adopting a Bayesian viewpoint and using the Markov chain Monte Carlo technique Gibbs sampling. In particular, we examine the effect of the antiretroviral treatment zidovudine on the square root of CD4 series for the 136 patients who took the drug. Treatment effects are modelled by positing recoveries in square root of CD4 level proportional to current immuno-competence and changes in slope proportional to current rate of square root of CD4 loss. Both fixed and random treatment effects are considered and models are criticized and compared using Bayesian predictive methodology and checking data which comprise 424 new observations. Results indicate re-elevation of square root of CD4 level is associated with treatment but the effect, though significant, is mostly of small magnitude and is possibly transient; models neglecting consideration of treatment fit the checking data almost as well. Best overall model estimates mean rate of square root of CD4 loss per annum to be 2.1 (standard error 0.12); mean seroconversion value of square root of CD4 is 28.4 (SE 0.65). The estimated variance of individual slopes is 1.9 (SE 0.28), there being considerable individual variation in rate of CD4 loss, and a recovery in level of 0.047 (SE 0.014) times current square root of CD4 level is estimated at treatment uptake.

Purpose: To quantify clinical and operative factors that influence corneal graft outcome., Methods: A multifactorial analysis was done on 2242 corneal grafts registered by the United Kingdom Transplant Service from July 1987 to June 1991., Results: There was an increased risk of graft failure in patients with preoperative diffuse and other noncentral stromal edema, less-common eye diseases, small trephine size, difference in donor and recipient sizes greater than 0.25 mm, and use of mixed continuous and interrupted sutures. Visual acuity 3 months after surgery was poorer in patients who had glaucoma and low visual acuity preoperatively, small trephine size, and combined vitreous surgery. Use of interrupted sutures resulted in higher astigmatism at 3 months., Conclusions: After allowing for the effects of recipient factors, surgical factors significantly affected corneal graft outcome. No factors that showed significant benefits for graft survival also adversely affected visual performance. Details of medical history, clinical condition, and surgical method failed to predict more than a small proportion of observed variability in visual performance of functioning grafts.

The pattern of sudden explosive outbreaks of HIV infection among drug users has been seen in several countries but is as yet incompletely understood. The epidemic of injecting drugs in Edinburgh was associated with at least four overlapping epidemics of blood-borne viruses (hepatitis B, C, D and HIV). Only hepatitis B was initially recognized, being followed by HIV and latterly hepatitis C. Retrospective HIV testing of stored samples of serum from clinically diagnosed patients with HIV has allowed the HIV epidemic to be delineated and more accurate seroconversion dates identified for most of the patients. There is evidence to suggest that the explosive drug-related Edinburgh HIV epidemic may have been self-terminating and that the epidemic in male drug users preceded that in female drug users by around 3 months. We suggest that the self-terminating nature of this epidemic may have been related to changes in drug injecting behaviour or to varying infectivity of the virus. This latter possibility should be explored in future studies of HIV transmission.

Objective: To describe the influence of pregnancy on immunological marker paths and progression of HIV-infected women., Design: Analysis of prospectively collected immunological and clinical data collected on 145 women reviewed at the City Hospital, Edinburgh, between 1985 and 1992 using a two-level random-effects model that allows for within- and between-patient variance., Results: There were differences between the marker paths of women according to risk activity; women who had acquired HIV via injecting drug use (in addition to heterosexual intercourse) had a higher level of absolute CD4 cells, CD4% and total lymphocytes at seroconversion than those who had acquired HIV via heterosexual intercourse alone; however, immunological markers declined more steeply after seroconversion. There was no evidence that pregnancy, either before or after HIV seroconversion had an adverse effect on marker paths of HIV disease. There was a significant association between pregnancy after HIV seroconversion and post-pregnancy changes in immunological markers: an increase in the CD4% and a decrease in CD8%. However, causality cannot be implied as pregnancy itself may be associated with considerable lifestyle changes. During pregnancy the total white blood count rose due to an increase in the number of granulocytes, whereas the total lymphocyte numbers fell. The absolute CD4 lymphocyte subset counts fell progressively but the effect was due to the fall in the total lymphocyte counts, there being no influence of pregnancy on either CD4% or CD8%., Conclusions: In asymptomatic HIV infection, changes in the absolute levels of CD4 and CD8 lymphocyte counts are primarily related to changes in the other components of the white cell count because there were no changes in CD4% and CD8%. Pregnancy itself has no adverse effect on immunological markers of HIV.

Objective: To determine prevalence of HIV infection and risk behaviours among male inmates of Her Majesty's Prison (HMP) Barlinnie, Glasgow, Scotland on 8-9 September 1994., Design: Cross-sectional study: voluntary, anonymous HIV surveillance (using saliva samples) of all inmates and linked self-completion risk-factor questionnaire., Subjects: Of 1073 prisoners available to participate, 985 (92%) completed a risk-factor questionnaire and 982 salivettes were received for testing, of which 978 were tested for HIV antibodies (four were dry samples); 928 questionnaires passed logical checks for consistency., Main Outcome Measures: HIV prevalence on saliva testing, related risk behaviours and ratio of overall-to-disclosed HIV prevalence. Proportion of all inmates who have ever injected drugs, ever injected inside prison, started injecting inside, ever had acute hepatitis, had a recent personal HIV test (since January 1993)., Results: Nine saliva samples [eight injecting drug users (IDU), one recognized other risk] out of 978 were HIV-antibody-positive (three presumptively from known HIV-infected inmates). Overall HIV prevalence was estimated at 1% compared with a known prevalence of 0.4%, giving an overall-to-disclosed HIV prevalence ratio of 2.6 in HMP Barlinnie in September 1994. A higher proportion of prisoners from Glasgow (48%) than elsewhere (19%) were IDU. Year of first injection was also different by residence with 23% of Glasgow IDU having first injected after 1988 compared with 45% of IDU from elsewhere, mainly West and South Scotland. Half the IDU inmates reported having injected while incarcerated and 6% had started to inject while incarcerated. Ten per cent of all prisoners and 20% of IDU inmates had had a personal HIV test since January 1993. Logistic regression showed that there was a significant deficit of recent HIV test uptake by Glasgow residents (odds ratio, 0.5; 95% confidence interval, 0.27-0.89), that IDU were more likely to have had treatment for a sexually transmitted disease, and that IDU who had injected inside and those whose injecting career began prior to 1989 were more likely to have had acute hepatitis., Conclusion: A consistent harm-reduction policy is needed across prisons in the United Kingdom to avoid transmission of blood-borne viral infections. Drug injecting inside prison is common, a proportion of IDU inmates having first injected drugs while in prison, and much higher rates of hepatitis have been reported in association with injecting while incarcerated compared with that for IDU who only injected outside prison.

We describe baseline characteristics, enrollment, progression and mortality of the Edinburgh City Hospital HIV cohort. There were 431 men and 191 (31%) women; 439 (71%) infected via injection drug use (IDU); 92 (15%) via homosexual intercourse; 84 (13%) via heterosexual intercourse and 7 from blood products. Median annual rate of CD4 cell loss was 49 (90% range: 15-146); Both homosexual men and patients aged > 40 years at enrollment lost CD4 cells significantly more quickly. In multifactorial analysis controlled for baseline CD4 count and IgA, there was no gender effect, but young patients (< 25 years) progressed significantly more slowly to AIDS (RR 0.4, p = 0.00). Homosexual men progressed significantly more quickly than IDUs, with adjusted relative risks (RR) of 2.9 (p = 0.00), 2.5 (p = 0.01) and 1.5 (p = 0.1) for progression to CDC stage IV, AIDS and death, respectively. The three-year survival rate post-AIDS was 25% (SE 4.3) and there was no gender effect on survival. There was, however, an age effect whereby individuals diagnosed with AIDS in their 40s or later showed poorer survival (RR 1.9, p = 0.04). Zidovudine treatment after an AIDS diagnosis significantly lengthened post-AIDS survival (RR 0.5, p = 0.08).

A longitudinal analysis of a partner study is compared with a cross-sectional analysis which identify behavioural and biological risk factors for heterosexual transmission of HIV. Using generalized estimating equations (GEEs) a random effects logistic model is used for the longitudinal analysis. These approaches are illustrated by the Edinburgh heterosexual partner study. The longitudinal analysis finds that 'high-risk' sexual practices, unprotected intercourse for HIV and a low CD4 count in the index case significantly increase the risk of HIV transmission. The cross-sectional analysis, however, only indicates 'high-risk' sexual practices as favourable for HIV transmission.

Unrelated donor bone marrow transplantation is increasingly used to treat haemopoietic disorders where no HLA-identical sibling is available. The International Marrow Unrelated Search and Transplant Study has collected core data on consecutive unrelated donor BMT (UD-BMT) and HLA-identical sibling donor BMT (ID-BMT) performed in 46 participating centres world-wide between March 1989 and February 1993. Eighteen UD-BMT were performed in the first 6-month period in 14 participating centres, while in the last period there were 103 UD-BMT in 46 centres. The percentage of BMT recipients with the following diagnoses were: bone marrow failure UD-BMT 15% and ID-BMT 11%; AML 13% and 27%; ALL 18% and 17%; CML 48% and 31%; and other diseases 7% and 14%. Thirty-eight per cent of UD-BMT recipients had advanced disease compared with only 23% of ID-BMT recipients. Thirty six per cent of UD-BMT compared with 21% of ID-BMT recipients were under 16 years old. More extreme differences in pre-transplant clinical characteristics between UD and ID-BMT recipients were found when diagnosis and stage of disease were considered together. This survey indicates how UD and ID-BMT are currently used in the treatment of haematological disease; however, longer follow-up is required to assess the value of UD-BMT in the management of patients with bone marrow disorders.

Objective: To determine prevalence of HIV infection and drug injecting behaviour among inmates of Glenochil Prison on a specified date a year after an outbreak of hepatitis B and HIV infection., Design: Cross sectional: voluntary, anonymous HIV salivary antibody surveillance and linked self completion questionnaire on risk factors., Setting: Glenochil prison, Scotland, a year after an outbreak of hepatitis B and HIV transmission related to drug injection., Subjects: 352 prisoners, of whom 295 (84%) took part; 284 questionnaires (96%) passed logical checks., Main Outcome Measures: HIV prevalence; proportion of all inmates who had ever injected drugs, had ever injected inside prison, had started injecting drugs while inside prison., Results: More than half (150/284) the current inmates were also in Glenochil Prison during the critical period of January to June 1993, when hepatitis B and HIV were transmitted. Similar proportions of current inmates and men who were also in Glenochil during the critical period were drug users (27% (75/278) v 30% (44/149)). A quarter of injecting drug users (18/72) had first injected inside prison, irrespective of whether they were in Glenochil in January to June 1993 and regardless of the calendar period when they first injected. Significantly more inmates from Glasgow (41%; 56/138) than from Edinburgh (21%; 7/34) or elsewhere (11%; 12/106) were injecting drug users. On testing for HIV, seven saliva samples out of 293 gave positive results--four were presumed to be from inmates known to be infected with HIV, and the others from injecting drug users from Glasgow, all of whom had been in Glenochil during January to June 1993, when two of the three had injected drugs and had been tested for HIV, with negative results. The ratio of overall (2.4%) to disclosed (1.4%) HIV prevalence was 1.7. For men who had injected drugs in Glenochil during January to June 1993, HIV prevalence was estimated at 29%., Conclusion: Between a quarter and a third of prisoners who injected drugs in Glenochil in January to June 1993 were infected with HIV. There is widespread ongoing risk of bloodborne virus infection within prisons, which is probably long standing but demands urgent attention.

Objective: To estimate HIV prevalence and risks in university students., Design: Anonymous self-completion questionnaire and HIV survey with saliva samples., Setting: University students at matriculation., Participants: All first and third year undergraduates and newly registering postgraduates at the University of Edinburgh, Scotland., Main Outcome Measures: HIV prevalence, sexual behaviour, condom use, drug use., Results: The questionnaire responses were used to classify the 4665 respondents into four groups, ordered by risk of HIV positivity, and a sample of 2041 was selected for testing. All of the top two risk groups were tested (217 and 758 tests, respectively) as well as a random sample of the others. Five positive HIV-antibody tests were detected, all from the highest risk group. This gives an estimated rate of 1.2 per 1000 (95% confidence interval, 0.4-2.9) for all respondents. Only one of the five HIV-positives had been tested for HIV. The factors associated with HIV positivity were residence in Africa, intravenous drug use and male homosexuality. Overall, 74% of respondents reported ever having had sexual intercourse and this rate was the same for men and women. Reported intravenous drug use was very low: 0.5% for men and 0.1% for women. Condom use was more common for partners of short acquaintance, but unrelated to the number of sexual partners in the last year., Conclusions: There was no evidence of the spread of HIV infection beyond known high-risk groups in this population. This may be a result of relatively low levels of HIV risk-taking behaviour in the majority of respondents.

Some implications of the use of the back-calculation method for estimating future trends in HIV infections and AIDS incidence in England and Wales are explored. "This paper explores in...detail some aspects of the latest projections which have only been hinted at in the report published by the Public Health Laboratory Service in 1993. The value of additional information on the HIV epidemic in discriminating between different, otherwise equally plausible, scenarios is demonstrated. The role of the backcalculation approach in determining whether, and how, the incubation distribution has been affected by increased uptake of pre-AIDS prophylaxis and treatment is discussed.", (excerpt)

The Corneal Transplant Follow-up Study has followed 2311 penetrating keratoplasties for up to 450 days after transplant. A total of 207 failures were observed, including 65 classical rejections and 35 endothelial decompensations. At 12 months, graft survival was 89%, and survival free from rejection was 87%. For surviving grafts, risk of failure reduced from 4.8% in the first 75 days and stabilized after 5 months at 1.2% in each 75-day interval. Risk of rejection initially followed a similar pattern, but then increased after 12 months. Multifactorial analyses accounted for differences in recipient characteristics and interrelationships of donor factors. Donor age, sex, cause of death, and method of corneal storage were not found to influence significantly either time to graft failure or time to first rejection. Grafts in prospectively tissue-typed donor-recipient pairs were generally considered before surgery to be at increased risk of either graft failure or rejection. With due allowance, increasing risk of rejection was associated with increasing numbers of mismatches at HLA-A and HLA-B broad antigens. The opposite was true at HLA-DR broad antigens, where increased risk of rejection was observed with no mismatches.

Outcomes of searches for unrelated bone marrow donors were analysed to identify factors influencing the probability of identifying an HLA-matched donor and proceeding to an unrelated donor bone marrow transplant (UD-BMT). Between March 1989 and January 1991, 649 unrelated marrow donor searches were entered into the study. Searches were referred from transplant centres in Europe and North America to the Anthony Nolan Research Centre panel and/or the British Bone Marrow and Platelet Donor Panel, two predominantly Caucasian donor registries. Patient immunogenetic and clinical characteristics were documented on study search request forms and search outcomes were monitored at the donor registry. Data were analysed using proportional hazards regression. Major factors predicting favourable search outcomes were patient common Caucasian HLA phenotype and Caucasian ethnic group. Probability of search failure was increased by advanced disease, rare Caucasian HLA phenotype and referral to the smaller registry. Search failure frequently occurred at the mixed lymphocyte reaction stage. This study illustrates the relative roles of clinical, immunogenetic and registry factors in determining the outcome of searches. The information may be used to devise strategies to locate HLA-matched donors for a higher proportion of patients for whom UD-BMT is the preferred treatment.

Whether breast milk influences later neurodevelopment has been explored in non-randomised studies, potentially confounded by social and demographic differences between feed groups. Here in a strictly randomised prospective multicentre trial, Bayley psychomotor and mental development indices (PDI and MDI) were assessed at 18 months postterm in survivors of 502 preterm infants assigned to receive, during their early weeks, mature donor breast milk or a preterm formula. These diets were compared as sole enteral feeds or as supplements to the mother's expressed breast milk. No differences in outcome at 18 months were seen between the two diet groups despite the low nutrient content of donor milk in relation to the preterm formula and to the estimated needs of preterm infants. These results contrast with those reported from our parallel two centre study that compared infants randomly assigned a standard term formula or the preterm formula during their early weeks; those fed standard formula, now regarded as nutritionally insufficient for preterm infants, were substantially disadvantaged in PDI and MDI at 18 months post-term. It is shown here that infants from that study fed solely on standard formula had significantly lower developmental scores at 18 months than those fed on donor breast milk in the present study; yet the standard formula had a higher nutrient content than the donor milk. Thus, donor milk feeding was associated with advantages for later development that may have offset any potentially deleterious effects of its low nutrient content for preterm infants. As these outcome advantages were not confounded by the social and educational biases usually associated with mothers' choice to breast feed, our data add significant support to the view that breast milk promotes neurodevelopment.

This retrospective study used a postal questionnaire to measure occupational risks and to assess infection control procedures among 310 dental practitioners. The study comprised general dental practices in the Lothian region of Scotland, Lothian Health Board Community Dental Service and Edinburgh Dental Hospital. Altogether, 217 dental practitioners responded by the due date giving recall of inoculation injuries within the previous 5 years and infection control measures employed. The study revealed that 191 practitioners (88%) had completed a course of hepatitis B vaccination but one-third of them had not been tested for post-vaccination antibody. In 1991, two thirds of dentists (66%: 137 of 207 respondents) wore the same pair of gloves, and 80% of dentists (142 of 177 respondents) wore the same mask, for dealing with more than one patient. The usual practice was to change gloves during sessions (44%: out of 71 dentists) and to change masks for each session or less often (75%: 73 out of 97 dentists). The proportion of dentists who never used gloves fell from 56% in 1981 to 1% in 1991. An autoclave was used for sterilisation by 85% of practitioners in 1991. Reported non-sterile inoculation injuries averaged 1.7 (S.D. = 3.2) injuries per dentist in the previous year with 56% of practitioners having had an injury. The average was 6.8 (S.D. = 15.9) injuries per dentist in the previous 5 years with 76% of practitioners having had an injury. Of recent non-sterile inoculation injuries described by dental practitioners, 30% constituted a moderate or high risk of transmission of infection to the practitioner (43 of 141 described injuries). Combined with HIV seroprevalance rates, probabilities of transmission and numbers of practising dentists, the mean reported number of non-sterile inoculation injuries in the previous 5 years may be used to provide estimates of expected numbers of dental practitioners occupationally infected with HIV in the previous 5 years. U.K. estimates were 0.004 dentists in Lothian region and 0.05 dentists in the Thames region occupationally infected with HIV in the previous five years. Non-sterile inoculation injuries appear to be a common hazard of dental practice. In any year, most dentists are exposed to the risk of blood-borne viral infection. Despite a high reported incidence of such injuries, dental practice within the U.K. appears to carry a low risk of acquiring HIV infection from occupational exposure.

Purpose: The Corneal Transplant Follow-up Study has followed 2385 corneal transplants performed in the United Kingdom and the Republic of Ireland for up to 450 days to quantify factors influencing corneal graft survival and visual outcome 3 and 12 months postoperatively., Methods: Multifactorial analyses of grafts registered by United Kingdom Transplant Support Service from July 1987 to June 1990 were used. Corrected visual acuity of functioning grafts was assessed at 3 and 12 months., Results: Of 2385 corneal transplants followed, 214 failures were observed: graft survival was 95% at 3 months and 89% at 1 year. Similar factors affected outcome at each time. Decreased risk of failure was associated with surgeons reporting most grafts, and increased risk was associated with regrafts, patients younger than 10 years of age, nonvisual reasons for grafting, endothelial failure, and deep vascularization. Visual outcome was worse in older patients and was associated with cosmetic reasons for grafting, superficial vascularization preoperatively, and secondary endothelial failure. Visual acuity was better when the other eye had been grafted previously, or when the diagnosis was keratoconus or stromal dystrophy., Conclusions: Primary endothelial failure was associated with high failure rates but good visual results when functioning. Most other factors had similar effects on both outcome measures. Improved outcome under highest-reporting surgeons was slight, and indicated possible differences in postoperative care.

Using combined medical and drug clinics, by the end of 1990 we had initiated contact with 511 HIV positive individuals, 75% injection drug use (IDU) related. We have previously reported a significant reduction in the number of missed appointments from 1985-89 following the introduction of methadone and an all day clinic, but between 1989 and 1990 the appointment default rate rose from 17 to 25%. A significant percentage increase in missed appointments was, however, only seen in those not attending the all day clinic (chi 2(3) = 121.3, p < 0.001). An analysis of the patients missing appointments during 1989-90 revealed that 36-45% of patients attending each year missed only 1 or 2 appointments, that the majority of missed appointments each year were accounted for by less than 20% of the patients, around 60% of these patients missed appointments in both years and that only 2% of patients attending both years consistently miss 3 or more appointments per year. Laboratory monitoring of HIV, that is at least one sampling episode in a year, was achieved, however, in 92-95% of the patients attending each year. The annual number of patients lost to follow-up varied between 7 and 11% per year, but did not change significantly over time, whilst the cumulative number of HIV infected individuals lost to follow-up after 5 years was only 14%. Between 1986 and 1990 self-reported reduction in IDU was more likely in HIV positive than negative individuals; the number of HIV positive individuals who reported injecting for more than 50% of the year fell from 40 to 5% (chi 2(4) = 15.23, p < 0.01) whilst the number who reported at least one injection per year fell from 51 to 23% (chi 2(4) = 62.06, p < 0.001). By comparison amongst non-HIV-infected patients the percentage who reported opiate use for more than 50% of the visits during a year rose from 54% in 1986 to a peak of 70% in 1989 (chi 2(4) = 10.22, p < 0.05) and those who reported opiate use at least once during the year rose from 57% in 1986 to a peak of 75% in 1989 (chi 2(4) = 14.3, p = 0.006). Combined medical and drug clinics from 1986 to 1990 together with a multi-disciplinary team approach to medical care was successful in delivering health care to HIV-infected injection drug users.(ABSTRACT TRUNCATED AT 400 WORDS)