Biomedical subjects
S M Gore
Publications and source records attributed to S M Gore.
Ban on home HIV tests is unjustified.
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Organ donation from intensive care units in England and Wales: two year confidential audit of deaths in intensive care.
OBJECTIVES: Quantify possible increases in cadaveric organ donation from intensive care units; identify major sources of regional variation. DESIGN: Confidential audit of all deaths in intensive care units in England in 1989 and 1990 and in Wales in 1990. SETTING: 15 regional and special health authorities in England; Wales. PATIENTS: 24,023 audited deaths in England; 682 in Wales. MAIN OUTCOME MEASURES: Solid organ and corneal donor rates per 100 deaths; solid organ donor rate per 100 confirmed brain stem deaths; regional variation in (a) whether brain stem death was possible diagnosis, (b) general medical contraindications to donation, (c) relatives' refusal. RESULTS: Confirmed brain stem death accounted for 2389 (10%) audited deaths in England. In 438 (18%) there was a general medical contraindication to organ donation, and of 1829 (94%) families asked about donation, 557 (30%) refused. Data for England suggested that among potential donors the heart is suitable for transplantation in 65% of cases, the kidneys in 95%, the liver in 71%, the lungs in 31%, and the corneas in 92%. Reasons for any shortfall in achievement of transplantation varied with organ type. Solid organ and corneal donor rates per 100 deaths were 5.0 and 3.9 respectively in England and 4.3 and 2.1 respectively in Wales. The solid organ donor rate per 100 confirmed brain stem deaths was 50 in England and 41 in Wales. CONCLUSIONS: A 20% increase in number of cadaveric kidney donors from intensive care could be achieved by prompt testing for brain stem death and a quarter reduction in relatives' refusals.
Impact of rice based oral rehydration solution on stool output and duration of diarrhoea: meta-analysis of 13 clinical trials.
OBJECTIVE: To define the benefit of rice oral rehydration salts solution in relation to the glucose based World Health Organisation oral rehydration salts solution for treating and preventing dehydration in patients with severe dehydrating diarrhoea. DESIGN: Meta-analysis using data from 13 available randomised trials that compared these two formulations. SUBJECTS: The studies compared 1367 patients with cholera, severe cholera-like diarrhoea, or acute non-cholera diarrhoea. 668 received the standard WHO solution and 699 the rice based solution. INTERVENTION: Each trial report was reviewed to determine patient eligibility, the number of patients who were randomised and the number of these excluded from analysis, details of the randomisation procedure, and the precise timing of the outcome measurements. MAIN OUTCOME MEASURES: Stool output during the first 24 hours; weighted estimates of the difference in mean stool output between treatments. RESULTS: The rice solution significantly reduced the rate of stool output during the first 24 hours by 36% (95% confidence interval 28 to 44%) in adults with cholera and by 32% (19 to 45%) in children with cholera. The rate of stool loss in infants and children with acute non-cholera diarrhoea was reduced by only 18% (6 to 30%). CONCLUSIONS: The benefit of rice oral rehydration salts solution for patients with cholera is sufficiently great to warrant its use in such patients. The benefit is considerably smaller for children with acute, noncholera diarrhoea and should be more precisely defined before its practical value can be judged.
Anonymous HIV surveillance in Saughton Prison, Edinburgh.
OBJECTIVES: To estimate the prevalence of HIV by anonymous saliva testing in Her Majesty's Prison, Saughton (Saughton Prison), Edinburgh, UK. To elicit linked anonymous risk factor information from which to estimate risk scores for those who had taken an HIV blood test and, among drug injectors, for those who were HIV-1-antibody-positive on saliva testing. SETTING: Saughton Prison on 15 and 16 August 1991; HIV Immunology and Regional Virus Laboratories, Edinburgh, and the Medical Research Council Biostatistics Unit, Cambridge, UK. PARTICIPANTS: Male inmates (378 out of a total of 499) of Saughton Prison. MAIN OUTCOME MEASURES: Answers to a brief questionnaire about age, usual residence, present and past custodial sentences, drug injecting and sexual behaviour prior to and in prison, HIV testing and history of acute hepatitis. HIV-1-antibody status was established by saliva testing. RESULTS: Eighteen per cent of participants were injecting drug users (IDU), of whom approximately one-half (47%) had injected while inside prison. Ninety men (26%), including 40 (14%) of 278 participants who had never injected drugs and 77% of IDU participants, had taken an HIV blood test. Nine per cent of all participants and 35% of IDU participants had had an acute attack of hepatitis. Forty-one (62%) of 66 IDU had been imprisoned five or more times before their current prison sentence. After taking account of region of residence, injecting drug history and acute hepatitis, aspects of sentencing and sexual behaviour were not determinants of those who had been tested for HIV. On the study days, 18 out of 499 (3.6%) participants were known to prison medical officers to be HIV-infected. Following saliva testing, HIV prevalence was 17 out of 375 (4.5%) inmates tested. All 17 had at some time 'taken the blood test for HIV' and all had injected non-medically prescribed drugs. Edinburgh residence, age 26-30 years, have injected in prison and having first injected before 1983 all contributed to the risk score for whether an IDU was HIV-1-antibody-positive on saliva testing. CONCLUSIONS: Documented HIV prevalence in saliva was 4.5%, which--assuming no volunteer bias (as supported by questionnaire returns)--suggests that actual HIV prevalence was 25% greater than revealed to Saughton's prison medical service. All 17 inmates who were HIV-1-antibody-positive on saliva testing had injected non-medically prescribed drugs. The high reported frequency by inmates of injecting in prison highlights the urgent requirement for drug reduction and rehabilitation programmes for injecting inmates. Linked anonymous voluntary HIV testing of saliva can provide valuable information about HIV prevalence for the planning of prison resources and policy.
Blood cyclosporin concentrations and the short-term risk of lung rejection following heart-lung transplantation.
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)
Rabbit diurnal ocular tension variations.
Ocular tension recorded by pneumatonography was estimated at 4-hour intervals during six consecutive 24-hour periods in 8 New Zealand rabbits. The animals had been acclimatized for more than 8 weeks to artificial light from 08.00 to 20.00 h and dark for the other 12 h. Inter- and intrarabbit consistency was enough to allow the generalization that the lowest pressure occurred at noon (mean -0.8 mm Hg from baseline average), while the highest pressures (mean + 1.2 mm Hg above baseline average) occurred at 16.00 and 20.00 h. Only three other studies have measured rabbit ocular tensions throughout 24 h, but for shorter periods: one observed a light-induced rise as in the present study, but the other two studies found a rise during darkness.
Current status of unrelated-donor bone marrow transplantation. The International Marrow Unrelated Search and Transplant (IMUST) Study.
1. The International Marrow Unrelated Search and Transplant (IMUST) Study 1 provides novel prognostic data on outcome of unrelated-donor (UD) searches for patients with well-defined clinical characteristics. Case-types analyzed by multifactorial methods reveal the importance of HLA phenotype, ethnic mismatching, and stage of disease at search request, in predicting search outcome. White patients, with common HLA types and early disease, were least likely to suffer search failure. In contrast, searches for non-White patients with unusual HLA phenotypes and advanced disease were most likely to fail. Of importance, 70% of patients had HLA phenotypes defined as uncommon. 2. Overall donor yield at the 2 UK registries between 1989 and 1991 was 7%, significantly below expectations. Reasons for this shortfall are that theoretical predictions did not consider ethnic mismatch and logistical delays incurred by outdated UD search routines and most importantly HLA-typing inaccuracies. 3. IMUST Study 2 is a prospective multicenter-controlled cohort study comparing HLA-identical sibling donor (ID) and UD-bone marrow transplantation (BMT) for factors affecting BMT outcome. Generous support was provided by 83 BMT centers worldwide. An interim analysis of 165 UD- and 368 ID-BMT, with at least 6 months follow-up after BMT, is described. Unifactorial analysis showed a probability of engraftment at day 100 of 89% after UD- compared with 98% after ID-BMT (p < 0.001). Probability of Grades II-IV acute graft-versus-host disease (AGvHD) at 100 days was 52% after UD- compared with 42% after ID-BMT (p < 0.01). Probability of overall survival at day 400 was 42% after UD- compared with 63% after ID-BMT (p < 0.001). Survival on day 400 of those patients receiving UD-BMT for early disease was encouraging at 52%. 4. Multifactorial analysis was performed on combined data from UD- and ID-BMT cohorts to identify various factors predicting engraftment, AGvHD, and overall survival. Survival after UD-BMT was increased by center experience of UD-BMT and the use of additional pretransplant immunosuppression. Survival was decreased in UD- compared with ID-BMT, by female donor to male recipient and poor-risk disease. Engraftment was improved in ID- compared with UD-BMT, and after UD-BMT at centers experienced in UD-BMT. Engraftment worsened with the use of ex-vivo T-cell depletion for GvHD prophylaxis, in chronic myeloid leukemia, and in male recipients of female marrow.(ABSTRACT TRUNCATED AT 400 WORDS)
Unrelated bone marrow donor transplantation (UD-BMT): interim results of the IMUST study. International Unrelated Search and Transplant.
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Socio-economic factors associated with HIV infection in pregnant women.
The HIV epidemic in women in Edinburgh has characteristics which enable a total population study. We studied retrospectively all women with a known history of injection drug use or with a seropositive drug-using partner in a five year period from 1985-1990. We sought to quantitate lifestyle and environmental factors associated with HIV infection in pregnant women and to test two hypotheses: that infected women would have more adverse socio-economic features, and that there would be a change in these factors with time. There were 244 pregnant women in the study. They were slightly younger than all Edinburgh City women and much less likely to be married. They were much more likely to live in areas of multiple housing deprivation. Only 16% of women, and 28% of partners, were in paid employment; 90% of women smoked and 76% had a history of injection drug use. Some 28% of previous children were in the care of another, often a relative, 8% of women had a recent prison admission, and 58% of those tested had antibodies to Hepatitis B. Univariate analysis showed that none of these factors was significantly different in HIV seropositive women except for prison admission, previous infection with Hepatitis B, which probably all related to type of drug use. Linear logistic regression suggested two other variables which distinguished between groups, but because these are composite, and dependent on incomplete data, this must be interpreted with caution. The same overall associations were found when only women with a history of injection drug use were considered. There was no statistically significant change in these factors with time.(ABSTRACT TRUNCATED AT 250 WORDS)
Escape from collective denial: HIV transmission during surgery.
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High energy neutron treatment for pelvic cancers: study stopped because of increased mortality.
OBJECTIVE: To compare high energy fast neutron treatment with conventional megavoltage x ray treatment in the management of locally advanced pelvic carcinomas (of the cervix, bladder, prostate, and rectum). DESIGN: Randomised study from February 1986; randomisation to neutron treatment or photon treatment was unstratified and in the ratio of 3 to 1 until January 1988, when randomisation was in the ratio 1 to 1 and stratified by site of tumour. SETTING: Mersey regional radiotherapy centre at Clatterbridge Hospital, Wirral. PATIENTS: 151 patients with locally advanced, non-metastatic pelvic cancer (27 cervical, 69 of the bladder, seven prostatic, and 48 of the rectum). INTERVENTION: Randomisation to neutron treatment was stopped in February 1990. MAIN OUTCOME MEASURES: Patient survival and causes of death in relation to the development of metastatic disease and treatment related morbidity. RESULTS: In the first phase of the trial 42 patients were randomised to neutron treatment and 14 to photon treatment, and in the second phase 48 to neutron treatment and 47 to photon treatment. The relative risk of mortality for photons compared with neutrons was 0.66 (95% confidence interval 0.40 to 1.10) after adjustment for site of tumour and other important prognostic factors. Short term and long term complications were similar in both groups. CONCLUSIONS: The trial was stopped because of the increased mortality in patients with cancer of the cervix, bladder, or rectum treated with neutrons.
Availability of transplantable organs from brain stem dead donors in intensive care units.
OBJECTIVE: By audit from January to June 1989 to quantify, separately for hearts, kidneys, liver, lungs and corneas, the possible increases in transplantable organs from brain stem dead potential donors in intensive care units and to compare them with the increases achieved in October-November 1989, during intense, national publicity about transplantation. DESIGN: Prospective audit of all deaths in intensive care units in England from 1 January to 30 June 1989 and subsequent case study of the impact of publicity on offers and donations during October-November 1989. SETTING: 15 regional and special health authorities in England. PATIENTS: 5803 patients dying in intensive care units, of whom 497 were confirmed as brain stem dead and had no general medical contraindication to organ donation. MAIN OUTCOME MEASURES: Organ specific suitability for transplantation (as reported by intensive care units); consent for donation of specific suitable organs; and procurement of specific organs reported as suitable for transplantation and offered. RESULTS: In the 497 (8.6%) brain stem dead potential donors were estimated the organ specific suitability for heart as 63%, kidneys 95%, liver 70%, lungs 29%, and corneas 91%. Refusal of relatives (30%) accounted for major losses of suitable organs of all types. For kidneys the loss was equivalent to 44% of brain stem dead actual kidney donors. No discussion of organ donation was the second most important reason for missed kidney donors, the loss being equivalent to 10% of brain stem dead actual donors. Non-procurement or difficulties with allocating organs was the second most notable cause of missed suitable liver and lung donors; 29% (55) of the offered total of 189 liver donors and 27% (21) of 78 offered suitable lung donors in six months. Non-procurement of suitable, offered organs was rare for kidneys and modest, of the order of 13% and 10% respectively, for heart and corneas. Corneal donation from brain stem dead potential donors might be improved nearly as much (that is, a 78% increase in brain stem dead actual corneal donors) by specific measures to promote corneal donation when other organs are offered as by reducing the overall refusal rate. Restricted offers, non-procurement, and no discussion of donation accounted for nearly equal numbers of lost donations of hearts (each equivalent to 15% of donated hearts). During October-November 1989 when there was intense, positive publicity about transplantation the rates of refusal and non-discussion fell compared with during January-June (22%, 36/163 v 30%, 138/460; 7%, 33/497 v 2%, 4/167 respectively). Offers of suitable donors increased significantly (p less than 0.02) compared with the first six months of 1989, most notably for heart donors (80 v 60.1 expected) and kidney donors (122 v 102.1 expected) but only for kidneys was there a noticeable 17% increase in actual donors (118 actual audited donors v 100.8 expected donors; p = 0.09). CONCLUSIONS: Four strategies to increase the supply of transplantable organs from brain stem dead potential donors in intensive care units were identified: (a) reducing refusal of relatives (b) avoiding non-procurement of actually suitable organs (by logistical initiatives) and deterioration of initially suitable organs (by donor care initiatives); (c) converting restricted offers to unrestricted offers; and (d) ensuring discussion with families. Early referral to the transplant team or coordinator gives time for discussion about donor care and agreement on medical suitability for donation of specific organs. Solving some of the logistical problems of non-procurement may be a prerequisite for increased offers to be translated into increased donations. The impact of publicity therefore needs to be measured on offers of suitable donors as well as by actual donations.
Organ donation in a neurosurgical unit.
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Predicting match grade and waiting time to kidney transplantation.
We show how to estimate expected waiting time to transplantation and match grade potential for each patient awaiting kidney transplantation on a multicenter waiting list. We predict that some easily well-matched patients may be unlikely to receive a well-matched graft through accepting an earlier offer of a poorly matched kidney. Other patients, who are difficult to match, may be unlikely to receive even a poorly matched kidney within a reasonable time.
Integration of conservative surgery, radiotherapy, and chemotherapy for the treatment of early-stage, node-positive breast cancer: sequencing, timing, and outcome.
The optimal means of combining breast-conserving surgery, radiation therapy, and chemotherapy for the treatment of patients with early-stage, node-positive breast cancer is not known. We reviewed the results in 295 patients treated at the Joint Center for Radiation Therapy and affiliated institutions from 1976 to 1985. All patients had positive axillary nodes on dissection, had no gross residual disease in the breast or axilla after surgery, and received breast irradiation (with or without nodal irradiation) and three or more cycles of a cyclophosphamide, methotrexate, and fluorouracil (CMF)-based or doxorubicin-containing regimen. Median follow-up in patients without any failure was 78 months. Breast failure rates were assessed in relation to the sequencing of radiotherapy and chemotherapy. The different sequences were not randomly assigned, and the characteristics of the sequence groups differed. The actuarial 5-year breast failure rate was 4% in 99 patients receiving radiotherapy before chemotherapy; 8% in 54 patients sequentially receiving some chemotherapy, then radiotherapy without concurrent chemotherapy, then further chemotherapy; and 6% in 116 patients receiving concurrent chemotherapy and radiotherapy. However, the failure rate was 41% in 26 patients who received all chemotherapy before radiotherapy. The crude incidences of local failure within 4 years of treatment in these groups were 3%, 2%, 4%, and 15%, respectively (P = .065 for all four groups not being the same). The actuarial 5-year local failure rate was 5% for 252 patients irradiated within 16 weeks after surgery compared with 35% for 34 patients irradiated more than 16 weeks after surgery. The 4-year crude incidences were 4% and 12% for the two groups, respectively (P = .06). These results suggest that delaying the initiation of radiotherapy may result in an increased likelihood of local failure. Formal randomized controlled trials will be needed to confirm these results and to improve the integration of these treatment modalities.
Unrelated donor marrow transplantation: an interim analysis of the international marrow unrelated search and transplant (IMUST) Study. II.
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