Common carotid intima-media thickness does not add to Framingham risk score in individuals with diabetes mellitus: the USE-IMT initiative.

AIMS/HYPOTHESIS: The aim of this work was to investigate whether measurement of the mean common carotid intima-media thickness (CIMT) improves cardiovascular risk prediction in individuals with diabetes. METHODS: We performed a subanalysis among 4,220 individuals with diabetes in a large ongoing individual participant data meta-analysis involving 56,194 subjects from 17 population-based cohorts worldwide. We first refitted the risk factors of the Framingham heart risk score on the individuals without previous cardiovascular disease (baseline model) and then expanded this model with the mean common CIMT (CIMT model). The absolute 10 year risk for developing a myocardial infarction or stroke was estimated from both models. In individuals with diabetes we compared discrimination and calibration of the two models. Reclassification of individuals with diabetes was based on allocation to another cardiovascular risk category when mean common CIMT was added. RESULTS: During a median follow-up of 8.7 years, 684 first-time cardiovascular events occurred among the population with diabetes. The C statistic was 0.67 for the Framingham model and 0.68 for the CIMT model. The absolute 10 year risk for developing a myocardial infarction or stroke was 16% in both models. There was no net reclassification improvement with the addition of mean common CIMT (1.7%; 95% CI -1.8, 3.8). There were no differences in the results between men and women. CONCLUSIONS/INTERPRETATION: There is no improvement in risk prediction in individuals with diabetes when measurement of the mean common CIMT is added to the Framingham risk score. Therefore, this measurement is not recommended for improving individual cardiovascular risk stratification in individuals with diabetes.

Exploring the relationship between alcohol consumption and non-fatal or fatal stroke: a systematic review.

OBJECTIVE: Alcohol consumption has been reported to have both beneficial and harmful effects on stroke occurrence. Several studies have demonstrated a significant association with heavy drinking, but the evidence linking light-to-moderate alcohol consumption still remains unclear. This study, using a systematic review of the published literature, aimed to explore the dose-response relationship between alcohol and stroke, the effect of irregular drinking and the effect of beverage types on the risk of stroke. METHODS: A structured search for English-language published literature since 1966 was made using several electronic databases. This was supplemented using a hand search of references in review articles and additional searches on key authors. From the 153 eligible articles, 41 studies were selected according to study design, categorization of the exposure and outcome measures. FINDINGS: An association between recent alcohol use and stroke was consistently reported. There was also some evidence for a linear positive association for haemorrhagic stroke and alcohol consumption. Inconsistent results emerged on the J-shaped relationship between alcohol and ischaemic stroke, and the association between alcohol and non-fatal or fatal stroke combined. The importance of the pattern of drinking was also demonstrated, indicating a higher risk for irregular drinkers. CONCLUSIONS: There is insufficient evidence to conclude that light-to-moderate alcohol drinking and wine intake have beneficial effects on stroke occurrence. On the contrary, findings from this review suggest the opportunity for a primary prevention regarding heavy drinking and binge drinking. More information regarding the risk of stroke associated with irregular alcohol drinking, and the joint effects of alcohol with other risk factors, would clarify the complex interaction between alcohol and stroke.

Why do women doctors in the UK take hormone replacement therapy?

STUDY OBJECTIVES: To ascertain the determinants and experiences of hormone replacement therapy (HRT) use by menopausal women doctors. DESIGN: Postal questionnaire. SETTING: UK. PATIENTS: A randomized stratified sample of women doctors who obtained full registration between 1952 and 1976, taken from the current Principal List of the UK Medical Register. MAIN OUTCOME MEASURES: Current and previous use of HRT; reasons for and against HRT use; menopausal status; hormonal contraceptive use; lifestyle patterns; family and personal history of disease. MAIN RESULTS: While 73.2% of 471 users had started HRT for symptom relief, 60.9% cited prevention of osteoporosis and 32.7 prevention of cardiovascular disease. Altogether 18.7% had started for preventive purposes alone. Significant predisposing factors to starting HRT were the presence and severity of menopausal symptoms, surgical menopause, past use of hormonal contraception, and a family history of osteoporosis. HRT users were also more likely to use skimmed rather than full fat milk, to try to increase their intake of fruit, vegetables, and fibre, and to undertake vigorous physical activity at least once a week. They were less likely to have had breast cancer. Long duration users were more likely than short duration users to be past users of hormonal contraception and to be using HRT for prevention of osteoporosis as well as symptom relief; they were less likely to have experienced side effects. CONCLUSIONS: The high usage of HRT by women doctors reflects the fact that many started HRT on their own initiative and with long term prevention in mind. The results may become generalisable to the wider population as information on the potential benefits of HRT is disseminated and understood. However, HRT users may differ slightly from non-users in health-related behaviour and a substantial minority may never take up HRT, at least until the benefit-risk ratio is more clearly established.

Thromboprophylaxis and death after total hip replacement.

The recommendation that patients having a total hip replacement should receive pharmacological thromboprophylaxis is based on the belief that fatal pulmonary embolism is common, and that prophylaxis will decrease the death rate. To investigate these assumptions we performed a meta-analysis of all studies on hip replacement which included information about death or fatal pulmonary embolism. A total of 130 000 patients was included. The studies were so varied in content and quality that the results of our analysis must be interpreted with some caution. The fatal pulmonary embolism rate was 0.1% to 0.2% even in patients who received no prophylaxis. This is an order of magnitude lower than that which is generally quoted, and therefore the potential benefit of prophylaxis is small and may not justify the risks. To balance the risks and benefits we must consider the overall death rate. This was 0.3% to 0.4%, and neither heparin nor any other prophylactic agent caused a significant decrease. Our study demonstrates that there is not enough evidence in the literature to conclude that any form of pharmacological thromboprophylaxis decreases the death rate after total hip replacement. For this reason guidelines which recommend their routine use to prevent death after hip replacement are not justified.

Loss to follow-up matters.

Survival analysis of joint replacement relies on the assumption that surgical procedures in patients lost to follow-up have the same chance of failing as those in patients who continue to be assessed. Our study questions that assumption. During the 16-year follow-up of 2268 patients who had received total hip replacements 142 (6%) were lost to follow-up. The cumulative loss at 15 years was 20%. At their last assessment, patients who subsequently failed to attend for follow-up had significantly worse pain, range of movement and opinion of their progress (p < 0.001) and significantly worse radiological features than a matched control group (p < 0.01). Patients lost to follow-up have a worse outcome than those who continue to be assessed. Consequently, a survival analysis that does not take into account such patients is likely to give falsely optimistic results. It is therefore essential that vigorous attempts are made to minimise loss to follow-up, and that the rate of such loss is quoted. The overall loss to follow-up disguises the magnitude of the problem, which is best quantified by a cumulative rate of follow-up. The reliability of a study can be assessed by a loss-to-follow-up quotient, calculated by the number of failures: the lower the quotient the more reliable the data. Ideally, the quotient should be less than 1.

Long-term comparison of Charnley and Stanmore design total hip replacements.

We reviewed the records of the long-term outcome of 208 Charnley and 982 Stanmore total hip replacements (THR) performed by or under the supervision of one surgeon from 1973 to 1987. The Stanmore implant had a better survival rate before revision at 14 years (86% to 79%, p = 0.004), but the difference only became apparent at ten years. The later Stanmore implants did better than the early ones (97% to 92% at ten years, p = 0.005), the improvement coinciding with the introduction of a new cementing technique using a gun. Most of the Charnley implants were done before most of the Stanmore implants so that the difference between the results may in part be explained by improved methods, but this is not the complete explanation since a difference persisted for implants carried out during the same period of time. We conclude that improved techniques have reduced failure rates substantially. This improvement was much greater than that observed between these two designs of implant. Proof of the difference would require a very large randomised controlled trial over a ten-year period.

Pain levels after total hip replacement: their use as endpoints for survival analysis.

We have assessed the relative value of various outcome measures after THR, by the analysis of follow-up data from over 2000 patients. They had been reviewed clinically and radiologically six months after operation, at one year, and then every two years, some for 16 years. At each review their pain level, stiffness and opinion of progress were scored and a radiograph taken. We found that pain level was the most informative outcome as a predictor of revision and correlated well with the patients' opinions. We made a comparison between the six types of implant in the series, using survival analysis and log-rank testing with different pain levels as endpoints. This analysis revealed differences which were not detected by survival analysis using the traditional endpoint of revision. We therefore recommend the use of different levels of pain as the main outcome measures after total hip replacement.

Are randomized controlled trials controlled? Patient preferences and unblind trials.

The most reliable information about treatment effects comes from randomized controlled trials (RCTs). However, the possibility of subtle interactions--for example, between treatment preferences and treatment effects--is generally subordinated in the quest for evidence about main treatment effects. If patient preferences can influence the effectiveness of treatments through poorly understood (psychological) pathways, then RCTs, particularly when unblinded, may wrongly attribute effects solely to a treatment's physiological/pharmacological properties. To interpret the RCT evidence base it is important to know whether any preference effects exist and, if so, by how much they affect outcome. Reliable measurement of these effects is difficult and will require new approaches to the conduct of trials. In view of the fanciful image with which such effects are portrayed and the uncertainties about their true nature and biological mechanisms, existing evidence is unlikely to provide sufficient justification for investment in trials. This is a Catch 22. Until an escape is found we might never know, even approximately, how much of modern medicine is attributable to psychological processes.

Utilisation of hormone replacement therapy by women doctors.

OBJECTIVES: To ascertain the prevalence and duration of use of hormone replacement therapy by menopausal women doctors. DESIGN: Postal questionnaire. SETTING: General practices in the United Kingdom. SUBJECTS: Randomised stratified sample of women doctors who obtained full registration between 1952 and 1976, taken from the current principal list of the Medical Register. MAIN OUTCOME MEASURES: Prevalence and duration of use of hormone replacement therapy; menopausal status. RESULTS: Overall, 45.7% (436/954) of women doctors aged between 45 and 65 years had ever used hormone replacement therapy. When the results from women still menstruating regularly were excluded, 55.2% (428) were ever users and 41.2% (319) current users. The cumulative probability of remaining on hormone replacement therapy was 0.707 at five years and 0.576 at 10 years. CONCLUSIONS: Women doctors have a higher prevalence of use of hormone replacement therapy than has been reported for other women in the United Kingdom, and most users seem to be taking hormone replacement therapy for more than five years. The results may become generalisable to the wider population as information on the potential benefits of hormone replacement therapy is disseminated.

Echolocation behaviour and prey-capture success in foraging bats: laboratory and field experiments on Myotis daubentonii.

During prey-capture attempts, many echolocating bats emit a 'terminal buzz', when pulse repetition rate is increased and pulse duration and interpulse interval are shortened. The buzz is followed by a silent interval (the post-buzz pause). We investigated whether variation in the structure of the terminal buzz, and the calls and silent periods following it, may provide information about whether the capture attempt was successful and about the size of prey detected - detail that is valuable in studies of habitat use and energetics. We studied the trawling bat Myotis daubentonii. The time between the first call of the approach phase and the end of the terminal phase was not related to prey size in the laboratory. The last portion of the terminal buzz (buzz II) was shortened or omitted during aborted capture attempts. Both in the laboratory and in the field, the mean interpulse interval immediately after the terminal buzz (post-buzz interpulse interval) was longer in successful captures than in unsuccessful attempts. In the laboratory, the post-buzz pause was longer after successful captures than for unsuccessful attempts, and the minimum frequency of the first search-phase call emitted after the buzz (Fmin) was higher than that of the last such call prior to the buzz. These effects were not apparent in field data. Both in the laboratory (85%) and in the field (74%), significant discrimination between successful and unsuccessful capture attempts was possible when the duration of the post-buzz pause, post-buzz interpulse interval and Fmin were entered into a discriminant analysis. Thus, variation in the echolocation calls of bats during prey-capture attempts can reveal substantial information about capture success and prey size.