Renal-coloboma syndrome in a Brazilian family.
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Biomedical subjects
Publications and source records attributed to M Eccles.
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BACKGROUND: Clinical guidelines are needed on whether or not to use anticoagulant therapy to prevent stroke in patients with non-valvular atrial fibrillation. We did a Markov decision analysis to model decision-making with regard to warfarin treatment in patients with atrial fibrillation, and used the model to develop evaluative guidelines. METHODS: The decision analysis involved a systematic literature review supplemented by patients' estimates of the quality of life associated with different states of health, secondary analysis of stroke-registry data, and estimation of service costs; it also incorporated a sensitivity analysis. The derived guidelines were subsequently applied to a cohort of patients with atrial fibrillation. FINDINGS: We constructed decision tables for 12 age and sex groups. For most risk combinations, warfarin treatment would have decreased health-care costs and increased quality-of-life years, although the clinical decision was sensitive to patients' preferences and to the estimate of warfarin's effectiveness. 97% of women with atrial fibrillation older than 75 years, and 69% aged 65-74 would have been recommended for treatment; for men, the corresponding figures would have been 75% and 53%. With the upper quartile for the loss of quality of life associated with being on warfarin treatment (1.00), all but two of the 116 patients without contraindications would have been treated, whereas with the lower quartile (0.92), only 27 of 116 would have been treated. INTERPRETATION: Decision analysis is useful in the incorporation of complex probabilistic data into informed decision-making, the identification of factors influencing such decisions, and the subsequent development of evaluative guidelines.
PAX2 mutations cause renal-coloboma syndrome (RCS), a rare multi-system developmental abnormality involving optic nerve colobomas and renal abnormalities. End-stage renal failure is common in RCS, but the mechanism by which PAX2 mutations lead to renal failure is unknown. PAX2 is a member of a family of developmental genes containing a highly conserved 'paired box' DNA-binding domain, and encodes a transcription factor expressed primarily during fetal development in the central nervous system, eye, ear and urogenital tract. Presently, the role of PAX2 during kidney development is poorly understood. To gain insight into the cause of renal abnormalities in patients with PAX2 mutations, kidney anomalies were analyzed in patients with RCS, including a large Brazilian kindred in whom a new PAX2 mutation was identified. In a total of 29 patients, renal hypoplasia was the most common congenital renal abnormality. To determine the direct effects of PAX2 mutations on kidney development fetal kidneys of mice carrying a Pax2 (1Neu)mutation were examined. At E15, heterozygous mutant kidneys were approximately 60% of the size of wild-type littermates, and the number of nephrons was strikingly reduced. Heterozygous 1Neu mice showed increased apoptotic cell death during fetal kidney development, but the increased apoptosis was not associated with random stochastic inactivation of Pax2 expression in mutant kidneys; Pax2 was shown to be biallelically expressed during kidney development. These findings support the notion that heterozygous mutations of PAX2 are associated with increased apoptosis and reduced branching of the ureteric bud, due to reduced PAX2 dosage during a critical window in kidney development.
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BACKGROUND: Cluster randomized trials increasingly are being used in health services research and in primary care, yet the majority of these trials do not account appropriately for the clustering in their analysis. OBJECTIVES: We review the main implications of adopting a cluster randomized design in primary care and highlight the practical application of appropriate analytical techniques. METHODS: The application of different analytical techniques is demonstrated through the use of empirical data from a primary care-based case study. CONCLUSION: Inappropriate analysis of cluster trials can lead to the presentation of inaccurate results and hence potentially misleading conclusions. We have demonstrated that adjustment for clustering can be applied to real-life data and we encourage more routine adoption of appropriate analytical techniques.
The choice of study design for guideline implementation studies will determine the confidence with which the observed effects can be attributed to the interventions under study. In general, cluster randomized trials, of which there are different types, provide the most robust design. However, the use of these designs has implications for the power, conduct and analysis of studies. Wherever possible, designs allowing head-to-head comparisons, which incorporate baseline measures of performance, should be used.
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The aim of this study was to form and test a model of the antecedents and possible moderators of the use of clinical guidelines among healthcare professionals. A postal questionnaire survey of all workers in six health centres around Finland. was carried out in April 1996. The health centres were selected to represent all different areas of Finland. A total of 748 (65.5%) of the healthcare workers completed and returned the questionnaire. Of the respondents 95% were women, 16% physicians or dentists, 31% registered nurses, and 27% practical nurses. It was hypothesized that besides positive attitudes towards guidelines, job characteristics and team climate affect the use of guidelines. Three alternative models of possible main and moderating effects of attitudes, job characteristics, and team climate were formed and tested. These models were tested using hierarchical regression analysis and structural equation modelling (LISREL8). All of the hypothesized main effects and the moderating effect of job characteristics between attitudes towards and the use of guidelines were supported. According to our results important factors behind the general positive or negative attitudes towards guidelines are the usefulness, reliability, practicality, and availability of the guidelines. Also, the overall individual, team, and organizational competence to follow the procedures recommended, seemed to be vital. Moreover, those whose job motivation potential was high were more ready to use clinical guidelines even when their attitudes towards guidelines were the same.
BACKGROUND: New selective serotonin reuptake inhibitors (SSRIs) are perceived to be much safer in use than older tricyclic antidepressants (TCAs). However, previous assessments of association with fatal toxicity were made too soon after the introduction of the new drugs to permit accurate estimation. AIM: To determine the level of association of antidepressant drugs with fatal poisoning in the treatment of depression. METHOD: National data for England and Wales for three years (1993 to 1995) for fatal poisonings associated with antidepressants were obtained and, together with national primary care data on prescribing, were used to calculate fatality association by antidepressant drug. RESULTS: There were substantial variations between drugs in the level of association with fatal poisoning. Assuming an average treatment episode lasted three months, one fatality is associated with 11,800 treatment episodes of antidepressant use (95% CI = 11,120 to 12,580) when only single substance fatalities are considered. For SSRIs as a group the association was one in 411,800 (95% CI = 243,300 to 1.34 million) and for TCAs one in 8130 (95% CI = 7650 to 8670). However, for one of the newer TCAs, lofepramine, the single substance fatality rate associated with its use was one in 233,700 (95% CI = 124,500 to 1.89 million), which is not statistically significantly different from the SSRIs (P = 0.35). CONCLUSIONS: Estimated death rates associated with specific antidepressants should be compared with caution because drugs may be used selectively in patients with differing severity of depression. The proportion of these fatalities that could be prevented by switching to safer antidepressants is unclear when so few deaths are recorded as accidental; when there is intent to do self-harm the potential for switching to other means is unknown. However, this approach to relative toxicity may remain the best available since it is unlikely that a randomised trial will ever be conducted with a large enough sample size to obtain experimental data. Fatalities from antidepressant poisoning are very rare but if safety is paramount then lofepramine or an SSRI are justifiable treatment choices.
This paper describes the implementation of a clinical guideline across three acute Trusts. A Clinical Effectiveness Steering Group identified prevention of venous thromboembolism as a health priority. A local guideline development group adapted the recommendations of an existing review and produced a local guideline. Then, a multidisciplinary implementation group developed the practical aspects of implementing guidelines into routine daily practice. They identified appropriate staff to carry out risk assessment and to administer appropriate prophylaxis, as necessary. They also produced a "guideline pack" containing a training resource manual and implementation aids. Following this a multiple strategy implementation programme was used to introduce the guidelines, and an evaluation was carried out eight to ten months after the introduction of the guidelines. The evaluation identified a number of areas for improving current practice. Guideline implementation is a complex, time-consuming process.
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Explore the source record for details and available documents.
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In England, recent health care reforms emphasise the role of clinical guidelines in promoting effective and efficient health care. Introducing economic data into guidelines raises some methodological issues: specifically, the provision of valid and generalisable cost estimates, the weight placed upon cost 'evidence', and the presentation of cost-effectiveness information in a manner accessible to clinicians. A series of primary care guidelines, explicitly including consideration of health economic information, have recently been published, intended to help clinicians to aggregate the attributes of treatment choices to derive treatment recommendations consistent with both the clinical decision-making process and social objectives. Clinicians involved in developing guidelines responded well to the process and consistently managed to agree treatment recommendations, often after considerable debate about the evidence for treatment. In none of the guideline areas, all of which addressed common diseases, was there adequate information to estimate a cost per quality-adjusted-life-year, and it is unclear how helpful this approach would have been had it been possible. The implications of this method are discussed, guidance offered for economists new to guideline development and future areas of work identified.
There is increasing interest in evaluating the methods used to implement the findings from medical research. This paper describes the Evidence-based OutReach (EBOR) trial, which is the first large randomized study in the United Kingdom that will evaluate the effectiveness and efficiency of educational outreach visits by trained pharmacists who are delivering messages derived from four evidence-based clinical practice guidelines. General practices form the unit of allocation and analysis. The study design addresses important factors that may influence the effectiveness of the intervention, such as the pharmacist who delivers the messages, the health authority in which practices are located, and the size of a practice.
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This paper reports the substantive findings of a study that examined the feasibility of using postal questionnaires to assess the satisfaction of lay caregivers with the care received in the community by those dying of cancer. The focus of the analysis was the quality of information provided by health professionals, health services used in the final year of the dying person's life and the lay carer's views about the quality of these services. The study was a retrospective survey of lay carers identified from death certificates over a 9-month period. Of the 355 people contacted, 156 completed the questionnaires, a 44% response rate. The results of the survey indicate that information provision was deemed unsatisfactory by a large proportion of respondents, and that dissatisfaction with care received from hospital, the district nursing service and the general practitioner was common. Levels of satisfaction with care were clearly related to a range of service factors. Our survey also highlighted clear differences in the perceived quality of specialist and generic services for those dying of cancer. A comparison of the findings from this postal study with those reported in earlier retrospective interview surveys of lay carers suggests that the use of the postal questionnaire is a valid and cost-effective approach for assessing quality of care. The data provide baseline information against which improvements in the quality of care can be measured.