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1. The relationship between blood cyclosporin concentration (CyACb) and a patient's risk of organ rejection following heart-lung (HL) transplantation was investigated. 2. Longitudinal data were collected for 90 days post-operation for 31 HL transplant recipients. Following exploratory analysis, a multiple logistic regression model with a binary outcome variable representing presence or absence of lung rejection (as defined on biopsy findings and/or intention to treat) in the next 5 days was fitted to the data. 3. A significant interaction between time post-transplant and CyACb was found. During weeks 1-3, the relative risk (RR) of rejection per unit increase in log(e) (5-day mean CyACb) was reduced: RR = 0.29, 95% confidence interval (CI) = (0.12, 0.72). After 3 post-operative weeks, this trend was reversed: RR = 1.61, 95% CI = (0.96, 2.70). Increases in cyclosporin dose (CyAD) and in coefficient of variation (CV) for both CyAD and CyACb over the previous 10 days significantly increased the risk of rejection: RR per unit increase in log(e) (5-day mean CyAD) = 2.72, 95% CI = (1.18, 6.25); RR per increase of 10% (i.e. from, say, 20% to 30%) in the CV for CyAD = 1.20, 95% CI = (1.07, 1.36); RR if the CV for CyACb > 40% = 1.51, 95% CI = (1.01, 2.27). Administration of high dose steroids in the previous 5 days was found to protect against further rejection: RR if steroid treatment was given = 0.23, 95% CI = (0.13, 0.38).(ABSTRACT TRUNCATED AT 250 WORDS) [ABSTRACT FROM AUTHOR]

Background: Nodal metastasis from cutaneous squamous cell carcinoma (SCC) is poorly predicted clinically and is associated with a high mortality rate., Methods: From 2010 to 2013, patients with high-risk cutaneous SCC were assessed with sentinel node biopsy (SNB) either at the time of primary cutaneous tumor resection or at secondary wide local excision., Results: Of 57 patients, 8 (14%) had nodal metastasis. Significant predictors of metastasis are the number of high-risk factors (p = .008), perineural invasion (PNI; p = .05), and lymphovascular invasion (LVI; p = .05). During a mean of 19.4 months, 9 patients developed recurrence and 6 died of cutaneous SCC, indicating that over 1300 patients would be required for a randomized controlled trial with 80% power to detect a significant difference in disease-free survival., Conclusion: Lymph node metastasis occurs in 14% of patients with high-risk cutaneous SCC. Larger studies will be required to identify which "high-risk" factors should be considered as an indication for surgical assessment of the nodal basin. © 2015 Wiley Periodicals, Inc. Head Neck 38: E884-E889, 2016., (© 2015 Wiley Periodicals, Inc.)

Background: The purpose of this study was for us to present our findings on the prospectively audited impact of head and neck multidisciplinary team meetings on patient management., Methods: We collected clinical data, the pre-multidisciplinary team meeting treatment plan, the post-multidisciplinary team meeting treatment plans, and follow-up data from all patients discussed at a weekly multidisciplinary team meeting and we recorded the changes in management., Results: One hundred seventy-two patients were discussed in 39 meetings. In 52 patients (30%), changes in management were documented of which 20 (67%) were major. Changes were statistically more likely when the referring physician was a medical or radiation oncologist, when the initial treatment plan did not include surgery, and when the histology was neither mucosal squamous cell cancer nor a skin malignancy. Compliance to the multidisciplinary team meeting treatment recommendation was 84% for all patients and 70% for patients with changes in their treatment recommendation., Conclusion: Head and neck multidisciplinary team meetings changed management in almost a third of the cases., (© 2014 Wiley Periodicals, Inc.)

Background: The purpose of this study was to compare survival and functional outcomes in patients with advanced oral cavity squamous cell carcinoma (SCC) treated with either surgery + adjuvant radiotherapy (RT) or concurrent chemoradiotherapy (CRT)., Methods: Patients treated with curative intent by either surgery + RT or concurrent CRT were identified over a 6-year period (2001-2007). Disease and functional outcomes were analyzed on an intention-to-treat basis., Results: Fifty-four patients underwent surgical excision and received postoperative RT. Fifty patients underwent concurrent CRT. Overall survival (OS) and disease-specific survival (DSS) was significantly higher in the surgically treated group (p < .001). Long-term enteral feeding tube support was more commonly required in those treated with CRT, whereas osteoradionecrosis rates were comparable between the 2 groups., Conclusion: Treatment by surgery + adjuvant RT for advanced oral cavity SCC resulted in better disease control than treatment with CRT. This supports traditional surgical treatment algorithms for oral cavity cancer., (© 2014 Wiley Periodicals, Inc.)

Background: A number of microvascular free-flap tissue transfer techniques exist for reconstruction of head and neck defects. The scapular free flap is a versatile option that can be used for a wide variety of defects in this complex region., Methods: A series of 42 free flaps from 41 patients was retrospectively identified from the senior author's (J.R.C.) [corrected] database between 2006 and 2012. Information regarding patient demographics, indication for surgery, type of flap, reconstructive methods, complications, and prosthodontic outcome were reviewed and have been described., Result: A wide range of defects were reconstructed using the scapular free flap. Of the 42 reconstructions, 24 were for mandibular, 13 were for maxillary, and five were for calvarial reconstruction. The patients' ages ranged from 28 to 82 years, with a median of 70 years. Dental restoration was achieved in eight patients with maxillary reconstruction and two patients with mandibular reconstruction. There were 11 major complications, including two total flap failures., Conclusions: The authors have found the scapular free flap to be a reliable, robust, and versatile flap that provides an unparalleled range of reconstructive options, with minimal donor-site morbidity. Thus, the authors believe that the scapular free flap is a valuable reconstructive option for patients with complex head and neck defects and in patients in whom comorbid disease contraindicates the use of the fibular free flap.

Background: The insertion of sizers in breast augmentation surgery is a common method of predicting the final volume of prosthesis required. However, saline-filled sizers may not accurately represent the shape of the cohesive-gel-augmented breast. PERTHESE cohesive-gel breast implants are produced with matching sets of reusable (sterilizable) cohesive-gel-filled sizers that accurately predict the form of the augmented breast., Objectives: The authors assess the efficacy of PERTHESE sizers and implants in 200 consecutive patients who presented for breast augmentation., Methods: Data were prospectively collected for all patients who underwent bilateral breast augmentation between 2003 and 2010 with the senior author (BGHL), during which time he inserted PERTHESE implants exclusively in his clinical practice. The 200 patients included in this series were analyzed according to demographic details, preoperative findings (including the presence of breast asymmetry), surgical approach, postoperative patient and surgeon satisfaction scores, and complications., Results: Less than 2% of patients in this series experienced complications such as hematoma, seroma formation, or infection. Capsular contracture developed in 7% of patients, but there were no visible or painful capsules. Only 2% of patients elected to undergo surgical revision for aesthetic reasons. A high proportion (87%) of the 27 patients who had significant preoperative breast asymmetry were satisfied with the aesthetic outcome of their surgery. Likewise, a significant percentage (92%) of the 148 patients who had preoperative breast symmetry were satisfied with their outcome., Conclusions: Application of intraoperative form-stable cohesive-gel sizers can enhance the surgeon's ability to predict the final appearance of the augmented breast. The placement of these form-stable sizers and implants is a particular advantage in cases of established breast asymmetry.

Objective: The aim of this procedure was to definitively treat periductal mastitis and periareolar sepsis which was previously resistant to multiple surgical procedures and nonoperative treatment of chronic nipple sepsis., Methods: We employed a multidisciplinary approach to the treatment of end-stage periductal mastitis using a combination of central breast excision and immediate autologous latissimus dorsi flap reconstruction., Results: Clearance of periductal mastitis and infection has been achieved with no recurrence at 3 years. Good symmetry of breast shape and volume has been achieved using this technique., Conclusions: This method of partial breast reconstruction, commonly used for reconstruction of breast cancer ablative defects, may also provide good outcomes in nonmalignant disease.

Triggering in young children is rare. In this report, we describe spontaneous bilateral ring finger triggering in a 7-year-old boy after a viral infection. The pathology completely resolved without intervention. We propose that the triggering resulted from a viral synovitis. Such a case highlights the importance of eliciting evidence of recent infections in children presenting to hand clinics with finger triggering. It also implies that the transient synovitis often described in children may actually occur symptomatically in tenosynovium as well as articular synovium., (Copyright 2010. Published by Elsevier Inc.)

Although deregulated Hedgehog signalling and elevated Gli transcription factor expression are known to promote the development of basal cell carcinoma (BCC), little is known about molecular mechanisms driving the development of specific growth pattern subtypes. Using gene array analysis, we have previously observed that over-expression of GLI1 in human keratinocytes promotes increased expression of the neuronal differentiation markers ARC and ULK1. We asked whether neuronal differentiation is a characteristic of BCC and whether there is any correlation with BCC subtype. Using RT-PCR and immunohistochemistry, we confirmed that the neuronal markers ARC, beta-tubulin III, GAP-43 and Neurofilament are expressed in human BCC but not in normal epidermis. Moreover, we found that expression of these neuronal differentiation markers showed strong correlation to BCC subtype, with more aggressive infiltrative and morphoeic BCC showing low levels or lack of expression compared to nodular, superficial and micronodular subtypes. Primary human keratinocytes retrovirally expressing GLI1(-) and GLI2(-) showed elevated levels of beta-tubulin III and ARC but not Neurofilament or GAP-43, suggesting that beta-tubulin III and Arc may be early targets of aberrant Gli expression in BCC, whereas expression of Neurofilament and GAP-43 are either later, downstream targets or under control of alternative pathways. We propose that neuronal differentiation is a feature of BCC and that expression of these markers is in part due to aberrant Hedgehog signalling. Moreover, we suggest that correlation between loss of expression of neuronal markers in infiltrative and morphoeic BCC subtypes reflects dedifferentiation of more aggressive BCC subtypes.

Extremely large chest wall defects may result following salvage oncological surgery. Typically these defects involve a large skin defect combined with a variable resected area of underlying muscle and ribs. In situations where the skin defect is very large the use of a large latissimus dorsi flap may require skin grafting to the donor site if a myocutaneous flap is used or to the recipient defect if a muscle-only flap is used. Alternatively a transverse rectus abdominis flap is a second option but in certain cases this may not be available. We describe the use of a free anterolateral thigh flap to reconstruct a chest wall defect and demonstrate the principle of side-to-side stacking of separate skin paddles to achieve skin closure of a massive defect whilst permitting primary closure of the donor site. The principle of turbocharging components of a chimaeric flap is also described.

This paper describes a useful way of ensuring complete surgical ablation of the germinal matrix of the nail bed by staining the proximal envelope with Bonney's Blue dye.

Background: Oral rehydration therapy is used to treat dehydration caused by diarrhoea. However the rehydration solution does not reduce stool loss or length of illness. A solution able to do this may lessen the use of ineffective diarrhoea treatments as well as improve morbidity and mortality related to diarrhoea., Objectives: The objective of this review was to assess the effects of rice-based oral rehydration salts solution compared with glucose-based oral rehydration salts solution on reduction of stool output and duration of diarrhoea in patients with acute watery diarrhoea., Search Strategy: We searched the Cochrane Infectious Diseases Group trials register, the Cochrane Controlled Trials Register, Medline, Embase, Lilacs and the reference lists of relevant articles. We also contacted researchers in the field., Selection Criteria: Randomized trials comparing standard World Health Organization oral rehydration solution with an experimental oral rehydration salts solution in which glucose (20 grams per litre) was replaced by 50-80 grams per litre of rice powder, with the electrolytes remaining unchanged., Data Collection and Analysis: Data were extracted independently by a statistician and a clinician., Main Results: Twenty-two trials were included. Concealment of allocation was adequate in 15 of these trials. Irrespective of age, people with cholera who were given rice oral rehydration salts solution had substantially lower rates of stool loss than those given oral rehydration salts solution in the first 24 hours. Mean stool outputs in the first 24 hours were lower by 67 millilitres/kg of body weight (weighted mean difference -67.40, 95% confidence interval -94.26 to -41.53) in children, and by 51 millilitres/kg of body weight (weighted mean difference -51.07, 95% confidence interval -65.87 to -36.27) in adults. The rate of stool loss in infants and children with acute non-cholera diarrhoea was reduced by only four millilitres/kg of body weight (weighted mean difference -4.29, 95% confidence interval -9.36 to 0.78)., Authors' Conclusions: Rice-based oral rehydration appears to be effective in reducing stool output in people with cholera. This effect was not apparent in infants and children with non-cholera diarrhoea.

Polyotia (mirror ear) is an extremely rarely reported congenital anomaly of the external ear. The aetiology of this condition is unclear, and there are few descriptions of surgical techniques used. We aimed to review our experience with this condition by performing a retrospective review of the cases treated in our unit. Eight cases of polyotia treated at a referral centre for ear reconstruction in a 12 year period (1992-2004) were reviewed. Patient demographic data and associated syndromes were recorded. Operative techniques used in the cases were studied. There was an equal number of males and females. Four patients had abnormal contralateral ears and two patients were formally diagnosed as suffering from a congenital developmental syndrome. Five main components of surgical technique were found to be particularly relevant to these cases. These relate to deconstruction of the defect, management of extra cartilage, management of skin, proximity of the facial nerve and the timing of surgery. The authors conclude that a structured surgical approach can lead to successful reconstruction of these difficult abnormalities.

Objectives: To determine the prevalence of HCV antibodies among injecting drug users and to gauge the effectiveness of needle/syringe exchange in preventing the transmission of HCV infection., Methods: Between 1990-1994 and in 1996, annual cross-sectional surveys of injecting drug users in Glasgow were conducted. In order to ensure as representative a sample as possible, the 1949 respondents were recruited from both 'in-treatment' and 'out-of treatment' settings. Injectors were interviewed about their risk behaviours for blood-borne viruses and provided a saliva sample which was initially tested, anonymously, for HIV antibodies, and subsequently tested for hepatitis C infection., Results: Among 1949 injectors, the prevalence of salivary antibodies, indicative of hepatitis C viraemia, was 61%(95%, confidence interval (CI) 59%-63%): the estimated prevalence of serum antibody positivity was 72%. Length of injecting, year of commencing drug injecting and the number of times in prison were predictive of antibody positivity. Thirty-one per cent of injectors who commenced their injecting after 1992, following the full establishment of needle/syringe exchange in the city, were salivary antibody positive, and the majority of their infections were acquired outside the prison setting. Respondents who began injecting after the introduction of needle/syringe exchange in the city were significantly less likely to test HCV antibody positive than those who commenced injecting prior to the advent of needle/syringe exchange, after adjusting for length of injecting career., Conclusion: The prevalence of HCV among injectors in Glasgow has decreased during the era of needle/syringe exchange. However, there is evidence to suggest that the incidence of infection remains high. Since the prevalence of hepatitis C viraemia among the city's injecting population is extremely high, ongoing transmission is inevitable unless more effective interventions are identified and implemented urgently.

Background: Recent concern about drug use has focused attention on the illegal income generated by users., Aims: To investigate factors associated with drugs expenditure and to estimate the cost of illegal acquisitions used to pay for drugs., Method: We collected self-report data from 954 current injectors, interviewed at multiple street, needle/syringe exchange and drug treatment sites throughout Glasgow., Results: Injectors' mean weekly drug spending was 324 Pounds. The mean annual illegal drugs spend was estimated to be 11,000 Pounds per injector. We provide a central estimate--194 million Pounds per annum--of the retail value of goods acquired illegally by injectors in Glasgow in order to pay for drugs. Higher drug spends were associated with having been imprisoned more often and with those reporting acquisitive crime, drug dealing and prostitution. Treatment with methadone, among individuals who injected in the previous two months, was associated with a 20% reduction in a typical spend on drugs., Conclusions: Treatment effectiveness needs to be measured both in terms of health benefit and in terms of reduction in drugs expenditure and recidivism.

Background: Oral rehydration therapy is used to treat dehydration caused by diarrhoea. However the rehydration solution does not reduce stool loss or length of illness. A solution able to do this may lessen the use of ineffective diarrhoea treatments as well as improve morbidity and mortality related to diarrhoea., Objectives: The objective of this review was to assess the effects of rice-based oral rehydration salts solution compared with glucose-based oral rehydration salts solution on reduction of stool output and duration of diarrhoea in patients with acute watery diarrhoea., Search Strategy: We searched the Cochrane Infectious Diseases Group trials register, the Cochrane Controlled Trials Register, Medline, Embase, Lilacs and the reference lists of relevant articles. We also contacted researchers in the field., Selection Criteria: Randomized trials comparing standard World Health Organization oral rehydration solution with an experimental oral rehydration salts solution in which glucose (20 grams per litre) was replaced by 50-80 grams per litre of rice powder, with the electrolytes remaining unchanged., Data Collection and Analysis: Data were extracted independently by a statistician and a clinician., Main Results: Twenty-two trials were included. Concealment of allocation was adequate in 15 of these trials. Irrespective of age, people with cholera who were given rice oral rehydration salts solution had substantially lower rates of stool loss than those given oral rehydration salts solution in the first 24 hours. Mean stool outputs in the first 24 hours were lower by 67 millilitres/kg of body weight (weighted mean difference -67.4, 95% confidence interval -94.3 to -41.0) in children, and by 51 millilitres/kg of body weight (weighted mean difference -51.1, 95% confidence interval -65.9 to -36.3) in adults. The rate of stool loss in infants and children with acute non-cholera diarrhoea was reduced by only four millilitres/kg of body weight (weighted mean difference -4.3, 95% confidence interval -9.3 to 0.8)., Reviewer's Conclusions: Rice-based oral rehydration appears to be effective in reducing stool output in people with cholera. This effect was not apparent in infants and children with non-cholera diarrhoea.

Four years after the occurrence of an outbreak of hepatitis B and HIV infection among injecting drug user inmates at Her Majesty's Prison Glenochil in Scotland, a study design was developed to complete the epidemiological account of the HIV outbreak. Our aim was to identify potential cases of (1) HIV transmission not diagnosed during the original outbreak investigation and (2) the source(s) of the outbreak. Scotland's HIV positive case register was searched for matches to a soundexed list of 636 Glenochil inmates imprisoned during January-June 1993. Eight HIV infections that may have been acquired in Glenochil and four possible sources of the outbreak were identified. The second stage of follow-up molecular epidemiological techniques used on stored sera samples from identified individuals is described in the companion paper. Without breach of medical or prisoner confidentiality, indirect and anonymous follow-up has proved possible for the Glenochil inmates.

In a molecular investigation into the outbreak of HIV in Glenochil during the first 6 months of 1993, we previously demonstrated that 13 out of the 14 HIV positive inmates were infected with a virtually identical strain, and discounted 2 others as potential sources. Here we investigate a further 8 potential contacts and 4 potential sources which were identified in the companion paper. We were able to examine viral sequence from all but one of these 12 and results have revealed them to be distinct both from each other and the original 14. Thus, despite an intensive follow-up investigation, we have been unable to identify any further HIV infections that might have been part of the 1993 outbreak. It is possible that persons who were infected at that time remain undetected; however this and the companion report strongly suggest that if this were the case the likely numbers would be few.

Three hundred and seventy-five out of 575 prisoners (222/299 drug users and 153/267 non-users) who responded to a self-completion health care questionnaire at two prisons in 1997 commented on drugs in prisons. One hundred and forty-eight out of 176 responses expressed negative opinions about mandatory drugs testing (MDT), and 107 said that MDT promoted switching to or increased use of heroin/hard drugs'. Sixty-two prisoners suggested that more help/counselling was needed for drug users, 52 segregation of drug users/drug-free wings, and 50 more security on visits/in corridors after medication. The new Prison Service drug strategy has revised random MDT. It targets those who supply drugs, and supports those who want to stop using drugs, and accords with prisoners' views about the heroin problem in prisons.

Background: The UK Renal Registry quotes a 1-year death rate for patients established on dialysis of 19.4 per 100 patient years. Clinical experience, reflected in the UK Renal Association Standards Document (RASD), recognizes qualitatively that age, diabetes, and other comorbidities increase the risk of death. The aim of this paper is to provide quantitative estimates of the relative risk of death associated with particular patient characteristics., Methods: Quantitative techniques were used to estimate relative risk of death in the seven studies quoted in the RASD document and 17 other papers identified in a systematic literature search. Relative risk data from each study were pooled using a fixed effects model (f). A random effects model (r) was applied to pool relative risks if heterogeneity was found to exist between studies. A meta-regression analysis was also carried out to investigate whether study covariates substantially explained the heterogeneity between studies., Results: Pooling the papers identified in the systematic literature search with those from the RASD gave rise to a relative risk of death of 1.029 (95% CI 1.013-1.045) (r) associated with each year's increase in age. The relative risk associated with the presence of diabetes was 1.91 (95% CI 1.67-2.17) (r), whilst that associated with heart disease was 1.59 (95% CI 1.49-1.69) (f), and with peripheral vascular disease 1.58 (95% CI 1.29-1.93) (r). Heterogeneity was found in the estimates of risk associated with age, diabetes, and peripheral vascular disease. Important study covariates included the use of incident or prevalent cases, the use of routine data sources or data collected specifically for a particular study, the country in which the study was located, the use of a P value to infer the standard error of a relative risk estimate in a particular study, and the method of classifying diabetes., Conclusions: Published studies can be used to quantify the relative risk of death for dialysis patients with various comorbidities. This information is important if attempts are to be made to set standards for the performance of dialysis units, and to compare the performance of one dialysis unit with that of another.

To assess the effect of mutations at the CCR-2 and CCR-5 loci on heterosexual human immunodeficiency virus (HIV) transmission, 144 persons heterosexually exposed to HIV (infected and uninfected [EU]) and 57 HIV-positive index partners were genotyped. A significantly higher frequency of 64I heterozygotes at CCR-2 was observed in HIV-positive than in EU women (P=.02, relative risk=1.6). The allele frequency of 64I in women was 8% in HIV-positive contacts and 1% in EUs (P<.02). At CCR-5, no difference in the frequency of Delta32 was seen between groups, and the CCR-5 genotypes did not differ in accumulated "at-risk" exposure in EUs. Combining the analysis of the Delta32 and 64I mutations in index partners suggested an additive effect on transmission (P=.10). Thus heterozygosity for 64I at CCR-2 acts as a risk factor for HIV infection of women after heterosexual contact but heterozygosity for Delta32 at CCR-5 has no detectable effect.

Transmission of HIV and hepatitis B virus infection has been recognised in prisons, and injecting drug use is a major route of infection. Combined results of two pilot health care surveys showed that 47% of prisoners with a history of injecting drug use wanted help to give up class A drugs but only 11% of non-injecting drug users expressed a similar wish. It would therefore seem appropriate for prisons to estimate the number of inmates with a history of injecting drug use and provide drug rehabilitation places for half that number (47% rounded up). Data from three prisons in England and Scotland for which the numbers of drug rehabilitation places were known showed that they provided less than quarter of the minimum requirement based on this formula. The proportion of inmates with a history of injecting or of non-injecting drug use who want help to give up class A drugs requires further investigation in order to refine the needs formula.

Background: A recent review showed that opioid users' deaths from suicide were 10 times as common as expected on the basis of age and gender. Surveys showing prisoners' high prevalence of injecting or opioid dependence have led to a new statistical approach to prison suicides., Aims: To estimate the expected number of UK prison suicides annually, having taken account of inmates' age, gender and opioid dependence., Method: By gender, estimate the effective number of individuals (in terms of community-equivalent suicide risk) for whom prisons have a duty of care as 10 times the number of opioid-dependent inmates plus the number of non-opioid user inmates. Apply the gender and age-appropriate national suicide rates to work out the expected number of prison suicides., Results: The Scottish Prison Service can expect 7.1 suicides per annum, and annual totals up to 12 without exacerbation of suicides due to incarceration. For the Prison Service in England and Wales, 19.3 suicides per annum can be expected in prisons, and annual totals may range up to 28 without indicating incarceration; the total of self-inflicted deaths was 47 in 1993-94., Conclusions: Prisons cannot prevent all suicides. An alert may be warranted if prison suicides exceed 12 per annum in Scotland, or 28 in England and Wales.

Infant nutrition trials usually require developmental follow-up, often to 18 mon, and sometimes beyond reading ability at age 7 yr. They are therefore logistically complex and costly, and should be conducted to a high statistical standard. With examples, we focus on: good practice in nutrition trials and the goal of a common protocol; how to set plausible trial targets and to work out trial size accordingly; statistical observations on assessing visual maturation; and methods of randomization, including the method known as minimization, which can be adapted to select more appropriately a comparison cohort of breast-fed infants. We end with discussion of analysis and reporting standards, including the give-aways (or tell-tale signs) to be on the look out for. A Cochrane Collaboration for systematic review of randomized trials of infant nutrition is proposed.

Background: Our objective was to develop and test a methodology for inferring the percentage of prisoners currently using opiates from the percentage of prisoners testing positive for opiates in random mandatory drugs testing (rMDT)., Methods: The study used results from Willing Anonymous Salivary HIV (WASH) studies (1994-6) in six adult Scottish prisons, and surveys (1994-5 and 1997) in 14 prisons in England and Wales. For Scottish prisons, the percentage of prisoners currently using opiates was determined by assuming, with varying empirical support, that: current users of opiates in prison were 1.5 times as many as current inside-injectors; and current inside-injectors were 0.75 times as many as ever injectors in prison. We also assumed that current inside-users' frequency of use of opiates (by any route) was equal to the frequency of inside-injecting by current inside-injectors in Aberdeen and Lowmoss Prisons in 1996, namely six times in 4 weeks. We assumed that some scheduling of heroin-use prior to weekends takes place, so that only 50% of current inside-users of opiates would test positive for opiates in rMDT: these assumptions allow us to arrive at WASH-based expectations for the total percentage of prisoners testing positive for opiates in rMDT. For England and Wales, a multiplier of 118/68 was applied which was derived from prisoners' interviews, to convert the results from ever inside-injectors, as determined by WASH studies, to the percentage of current inside users of opiates. We made the same assumptions on frequency of inside-use of opiates as in dealing with the Scottish results., Results: We expected 202.7 opiate positive results in April to September 1997 in rMDTs at six adult prisons in Scotland, 226 were observed. We expected 227.0 at a set of 13 adult prisons and one other in England and Wales; 211 were observed., Conclusions: Further testing of the methodology for prisons in England and Wales will be possible when 1997 WASH data are released. So far, the methodology has performed well. From it, we infer that 24% of inmates at the six adult prisons in Scotland were current inside-users of opiates, compared to 11% at the 14 adult prisons where survey data were available in England and Wales. The corresponding April to September 1997 percentage of opiate positives in rMDT were: 13% (results from the six Scottish prisons) and 5.4% (results from 14 prisons in England and Wales), a two-fold under-estimate of % current users of opiates in prison (24% and 11%). Planning of drug rehabilitation places for prisoners should thus be based on twice the percentage of prisoners testing opiate positive in rMDT. This correction factor of two should be kept under review.

We used cross-sectional willing anonymous salivary hepatitis C (WASH-C) surveillance linked to self-completed risk-factor questionnaires to estimate the prevalence of salivary hepatitis C antibodies (HepCAbS) in five Scottish prisons from 1994 to 1996. Of 2121 available inmates, 1864 (88%) participated and 1532/1864 (82%) stored samples were suitable for testing. Overall 311/1532 (20.3%, prevalence 95% CI 18.3-22.3%) were HepCAbS-positive: 265/536 (49%, 95% CI 45-54%) injector-inmates but only 27/899 (3%, 95% CI 2-4%) non-injector-inmates. Among injectors, HepCAbS positivity was only slightly higher (p = 0.03) in those who had injected inside prison (53%, 162/305) than in those who had not (44%, 98/224). Those who began injecting in 1992-96 were much less likely to be HepCAbS-positive than those who started pre-1992 (31%, 35/114 vs. 55%, 230/422; p < 0.001). Even with injectors who began in 1992-96 but had never injected inside prison, the prevalence of hepatitis C carriage was 17/63 (95% CI 16-38%). The prevalence and potential transmissibility of hepatitis C in injector-inmates are both high. Promoting 'off injecting' before 'off drugs' (both inside and outside prison), methadone prescription during short incarcerations, alternatives to prison, and support of HepCAbS-positive inmates in becoming eligible for treatment, all warrant urgent consideration.

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.