Biomedical subjects
M McKee
Publications and source records attributed to M McKee.
Huge variation in Russian mortality rates 1984-94: artefact, alcohol, or what?
BACKGROUND: According to published data, between 1984 and 1994 mortality rates in Russia initially underwent a rapid decline followed by an even steeper increase. In 1994, male life expectancy at birth was 57.6 years, having fallen by 6.2 years since 1990. There has been concern that such striking fluctuations in mortality are an artefact, although, among other factors, alcohol consumption has been implicated. METHODS: We analysed the age-specific and cause-specific patterns of mortality decrease and increase by use of data from a newly reconstructed mortality series for Russia so that we could examine the plausibility of various explanations for the mortality trends. FINDINGS: All major causes of death, with the exception of neoplasms, showed declines in mortality between 1984 and 1987 and increases between 1987 and 1994. In relative terms, these tended to be largest for the age-group 40-50 years; surprisingly, they were of the same magnitude among women and men. The largest declines and subsequent increases in proportional terms were observed for alcohol-related deaths and accidents and violence. However, pronounced effects were also seen for deaths from infections, circulatory disease, and respiratory disease. No substantial variations were seen for neoplasms. INTERPRETATION: The stability of mortality from neoplasms in contrast to other causes over the period 1984-94 largely precludes the possibility that the changes in life expectancy are mainly an artefact, particularly one due to underestimation of the population. Although factors such as nutrition and health services may be involved, the evidence is that substantial changes in alcohol consumption over the period could plausibly explain the main features of the mortality fluctuations observed. These results provide a major challenge to public health in Russia and to our understanding of the determinants of alcohol consumption and its role in explaining mortality patterns within and between many other countries.
Indicators of clinical performance.
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Britain's first minister of public health. National centre for public health is needed.
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Intracellular location of thymidylate synthase and its state of phosphorylation.
Thymidylate synthase (TS), an enzyme that is essential for DNA synthesis, was found to be associated mainly with the nucleolar region of H35 rat hepatoma cells, as determined both by immunogold electron microscopy and by autoradiography. In the latter case, the location of TS was established through the use of [6-3H]5-fluorodeoxyuridine, which forms a tight ternary complex of TS with 5-fluorodeoxyuridylate (FdUMP) and 5, 10-methylenetetrahydrofolylpolyglutamate within the cell. However, with H35 cells containing 50-100-fold greater amounts of TS than unmodified H35 cells, the enzyme, although still in the nucleus, was located primarily in the cytoplasm as shown by autoradiography and immunohistochemistry. In addition, TS was also present in mitochondrial extracts of both cell lines, as determined by enzyme activity measurements and by ternary complex formation with [32P]FdUMP and 5,10-methylenetetrahydrofolate. Another unique observation is that the enzyme appears to be a phosphoprotein, similar to that found for other proteins associated with cell division and signal transduction. The significance of these findings relative to the role of TS in cell division remains to be determined, but suggest that this enzyme's contribution to the cell cycle may be more complex than believed previously.
Alcohol policy in the Nordic countries.
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Cognitive and symptom correlates of participation in social skills training groups.
In a study of 19 hospitalized chronic schizophrenic patients participating in a manualized skills training program, neuropsychological functioning was found to be an important mediating variable. Executive functioning capacity was positively associated with level of participation in the training groups, and deficits in sustained attention together with negative symptoms correlated negatively with overall program attendance. Neuropsychological functioning should be considered as an important assessment domain when identifying patients with minimal requirements to begin skills training.
Informing the market: the strengths and weaknesses of information in the British National Health Service.
Many countries are experimenting with planned (or quasi-) markets to discover if they can efficiently deliver health care in keeping with societal objectives. This paper examines the information requirements of this approach. Information is necessary in order to compare the performance of providers, to support billing, and to monitor access to care. It should be accurate, unambiguous, and resistant to manipulation. We draw on a project to find out how information on hospitalisation could be used in contracting in the British National Health Service. We conclude that the existing British system fails to provide robust measures of how many patients are treated, for what conditions, and with what treatments. We identify some promising remedies, others that are more difficult, and some which may be impossible to implement in any planned market, given the uncertainty of clinical practice.
Initial experience with FK506 (tacrolimus) in pediatric renal transplant recipients.
PURPOSE: The efficacy and safety of the new immunosuppressant agent, FK506 (tacrolimus), was assessed in pediatric renal transplant recipients over a mean 12-month follow-up period. METHODS: Twenty pediatric renal transplant recipients received oral FK506 therapy (0.3 mg/kg/d) in combination with azathioprine (1 to 2 mg/kg/d) and low-dose prednisone as primary therapy (n = 11) or were converted from cyclosporine-based therapy (n = 9) for complications including cyclosporine toxicity (n = 2), acute refractory rejection (n = 4), and chronic rejection (n = 3). Patients were then followed-up prospectively to evaluate effectiveness of therapy and complications. RESULTS: In the primary treatment group, 45% of patients had one or more rejection episodes. Two required OKT3 therapy (18%) for persistent rejection, with one (9%) graft loss at 3 months. All other episodes were treated effectively with FK506 dose adjustment and steroid pulses. Patient and graft survival was 100% and 91%, respectively, at 12 months mean follow-up. In the FK506 conversion group, two teenage girls with intractable acne and hirsutism were converted with complete resolution and no change in renal function. Four patients were converted for acute rejection: two who did not respond to steroid pulse and two who did not respond to both steroids and OKT3. All four grafts were salvaged (mean follow-up, 12 months; mean Creatinine [Cr], 1.1). Three patients were converted for biopsy-proven chronic rejection at 3, 10, and 12 years after transplant (mean Cr, 2.4) with two of three of patients stable with functioning grafts at 1 year after conversion. Complications of FK506 therapy included temporary insulin-dependent diabetes mellitus (10%), neurological complications (25%), renal toxicity (15%), and hypertension (85%). There were no cases of gastrointestinal toxicity, hepatic dysfunction, lymphoproliferative disorders, or life threatening viral infection. All symptoms of toxicity responded to dose adjustment. No patient required conversion from FK506 to other agents. CONCLUSION: This early experience indicates that FK506 in combination with low-dose steroids and azathioprine appears to provide safe and effective immunosuppression in the pediatric age group as a primary agent and may salvage grafts in patients with refractory steroid and OKT3 resistant rejection. Graft and patient survival is comparable to that seen with conventional cyclosporine-based immunosuppression.
Steroid withdrawal in tacrolimus (FK506)-treated pediatric liver transplant recipients.
PURPOSE: The use of steroids in pediatric transplant recipients is associated with significant adverse side effects. The authors examined the feasibility of steroid withdrawal in patients who underwent immunosuppression with tacrolimus (FK506; FK). METHODS: All pediatric liver transplant recipients on FK greater than 6 months were evaluated for steroid withdrawal. FK was administered 0.3 mg/kg/d in two divided doses. Steroids were tapered as tolerated with goals of 0.2 to 0.3 mg/kg/d at 6 weeks, 0.2 to 0.3 mg/kg every other day at 3 months, and complete withdrawal after 6 months. Steroid bolus and taper were instituted for enzyme elevation or rejection during biopsy. RESULTS: Twenty-nine patients underwent evaluation for steroid withdrawal. Five patients could not be placed on FK506 monotherapy (chronic, recurrent rejection or LPD). The remaining 24 had steroids withdrawn. Tweleve (50%) had no sequelae and continue on FK monotherapy (mean, 22 months off steroids). The other 12 required intermittent steroid therapy for presumed or biopsy-proven rejection (n = 7), graft dysfunction (FK toxicity, n = 2), lymphoproliferative disease necessitating reduction in FK (n = 2) or exacerbations of asthma (n = 1). Five of these 12 patients are now on FK monotherapy (mean, 6 months) for a total of 17 of the 24 (71%) currently off steroids. CONCLUSION: FK monotherapy can be successfully used to withdraw steroid therapy in the majority of pediatric liver transplant recipients with few sequelae.
Under-the-counter payments for health care: evidence from Bulgaria.
Against a background of falling revenues and increasing expectations, health care systems in central and eastern Europe are facing increasing budgetary gaps. There is extensive anecdotal evidence that these gaps are being filled by informal or 'under-the-table' payments. These are important because of their implications for estimates of future funding requirements, for equity, and for the possible perverse incentives they introduce for those providing and managing health services. There is, however, relatively little information on either their scale or how they are perceived in these countries. We report the results of a small survey from Bulgaria that begins to address these issues. Data were collected by means of an interviewer-administered household survey in which those who had used state-provided health services in the preceding 2 years were identified. The survey took place throughout Bulgaria in 1994. One thousand people were approached and 706 (70.6%) provided information suitable for analysis; 42.9% had paid for services that were officially free. Payments had been for a wide range of services and to differing groups, including medical, nursing and ancillary staff. Payments to individuals during consultations were between 3% and 14% of average monthly income but the average cost of an operation was 83% of mean monthly income. There were large differences in the amounts paid by individuals. Most people were in favour of both official user fees and health care reform, except among the old, the poor, and those in poor health. Despite certain limitations, this study gives some indication of the scale of informal payments in Bulgaria. Several possibilities exist to address them. Contrary to what is often argued, there seems to be a popular willingness for them to be converted into formal co-payments. Before this can be done, there is a need for more research on the impact that this would have on equity and affordability.
Economic evaluation of diagnostic technology. Methodological challenges and viable solutions.
The principles of economic evaluation are increasingly accepted by clinicians and policy makers as evidence from a significant number of studies becomes available to support their decisions. However, methods of assessment still need to be improved. This paper reports a comprehensive review of methodological challenges in the economic evaluation of diagnostic technology, where such challenges are more evident. This review formed the basis for a prioritized research agenda, with four main areas: modeling techniques for dealing with complexity; measures of the opportunity cost of shared resources; techniques for eliciting decision makers' utility functions for diagnostic tests; and ways of assessing the robustness of decisions. A number of methodological solutions are proposed, aimed at capturing elements and relationships that are usually neglected and fully recognizing the presence of an inductive cognitive component in decision-making processes.
Conducting a literature review on the effectiveness of health care interventions.
The dramatic increase in the volume of research based information means that effective policy makers must be able to conduct and interpret literature reviews. This article sets out the steps that should be followed in doing so. They are: explicitly defining the question; locating relevant literature; assessing the quality of studies and deciding whether they should be included; synthesizing and re-analyzing the results; and presenting them in a clear and concise manner. The article identifies the leading sources of information, including electronic databases and useful Internet addresses and describes briefly how each stage should be conducted, highlighting the strengths and weaknesses of different approaches and the ways in which bias may be introduced.
When can the European Union restrict trade on grounds of public health?
The reaction in Britain to the European Union ban on the world-wide export of British beef has highlighted a lack of awareness of the role of European law in restricting trade on grounds of public health. This paper seeks to bring the legal arguments underlying such action to a wider public health audience by exploring the basis for such action in general and for the ban on British beef in particular. In European law, the obstruction of intra-community trade on grounds of public health is extremely limited although, in the case of British beef, there seems little doubt that it is lawful. In contrast, the stated basis for the ban to other countries is more questionable, although it may be acceptable to the European Court because of the objectives it seeks to achieve.
A prospective randomized evaluation of the prophylactic use of low-dose dopamine in cancer patients receiving interleukin-2.
The administration of high-dose interleukin-2 (IL-2) causes tumor regression in 17-25% of patients with metastatic melanoma or renal cell carcinoma. Renal dysfunction is a common dose-limiting toxicity of IL-2 administration, limiting 26% of treatment cycles. We have conducted a prospective randomized trial to evaluate whether the prophylactic administration of low-dose dopamine (2 mg/kg/min) can minimize renal toxicity and thus affect the amount of IL-2 administered. Forty-two patients were randomly assigned to receive systemic high-dose IL-2 with standard supportive measures (group A = 21 patients) or with the addition of prophylactic dopamine (group B = 21 patients) at 2 mg/kg/min. For patients in group B, dopamine was instituted 1 h before the initiation of IL-2 administration and was discontinued 6-12 h after the maximum number of doses of IL-2 were given. There was no difference in the amount of IL-2 administered for each course of therapy for groups A and B. Despite differences in urine flow (milliliters per kilogram per day), fluid balance (liters per day), and overall weight gain, prophylactic low-dose dopamine did not significantly alter maximum plasma urea or creatinine levels in group B when compared with the control group (group A). The overall toxicity profile considering all grade 3 and 4 toxicities for patients in groups A and B was comparable. Thus, there is no evidence to support the routine use of prophylactic low-dose dopamine in patients receiving high-dose IL-2.
Stability of personality traits in schizophrenia and schizoaffective disorder: a pilot project.
This study was performed in an effort to begin characterization of personality traits in schizophrenia. Specific concerns included personality profiles relative to normal adults, personality profile stability over time, and trait-state issues. The authors administered the NEO Personality Inventory as well as symptom ratings at two time points to 21 patients. Patients were all stabilized outpatients attending an adult continuing day treatment program and diagnosed with either schizophrenia or schizoaffective disorder. Personality profiles were determined for all patients. Compared with a normal adult sample, this sample's scores on three out of five of the personality domains assessed were not distinguishable from normal adults. Test-retest correlations were highly significant over an average 28.2-week time interval. In general, the presence of positive symptoms did not appear related to NEO-PI stability, while negative symptoms did show a relationship to the stability of personality profiles. These data suggest that personality profiles can be looked at in schizophrenia, that these profiles do appear stable over time, and that negative symptoms have a strong influence on profile stability and appear to be "trait-like."
Using routine data to evaluate quality of care in British hospitals.
OBJECTIVES: As part of the process of developing an international comparative study of the outcome of hospital care it has been necessary to understand what data on hospital activity are available and how they compare with those in other countries. The authors describe the administrative data collected in British National Health Service Hospitals, with emphasis on how they differ from that available in the United States. METHODS: A description of the content of administrative data and a selective review of published literature related to their uses. RESULTS: Administrative data in the United Kingdom resembles that available in the United States, but it also has some important differences. These include a different system of procedure classification, the use of International Classification of Diseases, 10th Revision (rather than International Classification of Diseases, Ninth Revision, Clinical Modification), and the use of a different denominator ("finished consultant episodes," rather than admission spells). There also are important differences in the completeness and precision of the data that are collected. CONCLUSIONS: British administrative data can be used to describe patterns of care and have the potential to identify possible differences in outcome that can then be subjected to more detailed scrutiny. They are substantially less detailed than US data but are also somewhat less costly to collect.