Showing papers in "BMJ in 1997"

Bias in meta-analysis detected by a simple, graphical test

Abstract: Objective: Funnel plots (plots of effect estimates against sample size) may be useful to detect bias in meta-analyses that were later contradicted by large trials. We examined whether a simple test of asymmetry of funnel plots predicts discordance of results when meta-analyses are compared to large trials, and we assessed the prevalence of bias in published meta-analyses. Design: Medline search to identify pairs consisting of a meta-analysis and a single large trial (concordance of results was assumed if effects were in the same direction and the meta-analytic estimate was within 30% of the trial); analysis of funnel plots from 37 meta-analyses identified from a hand search of four leading general medicine journals 1993-6 and 38 meta-analyses from the second 1996 issue of the Cochrane Database of Systematic Reviews . Main outcome measure: Degree of funnel plot asymmetry as measured by the intercept from regression of standard normal deviates against precision. Results: In the eight pairs of meta-analysis and large trial that were identified (five from cardiovascular medicine, one from diabetic medicine, one from geriatric medicine, one from perinatal medicine) there were four concordant and four discordant pairs. In all cases discordance was due to meta-analyses showing larger effects. Funnel plot asymmetry was present in three out of four discordant pairs but in none of concordant pairs. In 14 (38%) journal meta-analyses and 5 (13%) Cochrane reviews, funnel plot asymmetry indicated that there was bias. Conclusions: A simple analysis of funnel plots provides a useful test for the likely presence of bias in meta-analyses, but as the capacity to detect bias will be limited when meta-analyses are based on a limited number of small trials the results from such analyses should be treated with considerable caution. Key messages Systematic reviews of randomised trials are the best strategy for appraising evidence; however, the findings of some meta-analyses were later contradicted by large trials Funnel plots, plots of the trials9 effect estimates against sample size, are skewed and asymmetrical in the presence of publication bias and other biases Funnel plot asymmetry, measured by regression analysis, predicts discordance of results when meta-analyses are compared with single large trials Funnel plot asymmetry was found in 38% of meta-analyses published in leading general medicine journals and in 13% of reviews from the Cochrane Database of Systematic Reviews Critical examination of systematic reviews for publication and related biases should be considered a routine procedure

Cronbach's alpha.

Abstract: Many quantities of interest in medicine, such as anxiety or degree of handicap, are impossible to measure explicitly. Instead, we ask a series of questions and combine the answers into a single numerical value. Often this is done by simply adding a score from each answer. For example, the mini-HAQ is a measure of impairment developed for patients with cervical myelopathy.1 This has 10 items (table 1)) recording the degree of difficulty experienced in carrying out daily activities. Each item is scored from 1 (no difficulty) to 4 (can't do). The scores on the 10 items are summed to give the mini-HAQ score. View this table: Table 1 Mini-HAQ scale in 249 severely impaired subjects When items are used to form a scale they need to have internal consistency. The …

Why the impact factor of journals should not be used for evaluating research

Abstract: Evaluating scientific quality is a notoriously difficult problem which has no standard solution. Ideally, published scientific results should be scrutinised by true experts in the field and given scores for quality and quantity according to established rules. In practice, however, what is called peer review is usually performed by committees with general competence rather than with the specialist's insight that is needed to assess primary research data. Committees tend, therefore, to resort to secondary criteria like crude publication counts, journal prestige, the reputation of authors and institutions, and estimated importance and relevance of the research field,1 making peer review as much of a lottery as of a rational process.2 3 On this background, it is hardly surprising that alternative methods for evaluating research are being sought, such as citation rates and journal impact factors, which seem to be quantitative and objective indicators directly related to published science. The citation data are obtained from a database produced by the Institute for Scientific Information (ISI) in Philadelphia, which continuously records scientific citations as represented by the reference lists of articles from a large number of the world's scientific journals. The references are rearranged in the database to show how many times each publication has been cited within a certain period, and by whom, and the results are published as the Science Citation Index (SCI) . On the basis of the Science Citation Index and authors' publication lists, the annual citation rate of papers by a scientific author or research group can thus be calculated. Similarly, the citation rate of a scientific journal—known as the journal impact factor—can be calculated as the mean citation rate of all the articles contained in the journal.4 Journal impact factors, which are published annually in SCI Journal Citation Reports , are widely regarded as …

Meta-analysis: Principles and procedures

Abstract: Meta-analysis is a statistical procedure that integrates the results of several independent studies considered to be “combinable.”1 Well conducted meta-analyses allow a more objective appraisal of the evidence than traditional narrative reviews, provide a more precise estimate of a treatment effect, and may explain heterogeneity between the results of individual studies.2 Ill conducted meta-analyses, on the other hand, may be biased owing to exclusion of relevant studies or inclusion of inadequate studies.3 Misleading analyses can generally be avoided if a few basic principles are observed. In this article we discuss these principles, along with the practical steps in performing meta-analysis. Meta-analysis should be viewed as an observational study of the evidence. The steps involved are similar to any other research undertaking: formulation of the problem to be addressed, collection and analysis of the data, and reporting of the results. Researchers should write in advance a detailed research protocol that clearly states the objectives, the hypotheses to be tested, the subgroups of interest, and the proposed methods and criteria for identifying and selecting relevant studies and extracting and analysing information. As with criteria for including and excluding patients in clinical studies, eligibility criteria have to be defined for the data to be included. Criteria relate to the quality of trials and to the combinability of treatments, patients, outcomes, and lengths of follow up. Quality and design features of a study can influence the results.4 5 Ideally, researchers should consider including only controlled trials with proper randomisation of patients that report on all initially included patients according to the intention to treat principle and with an objective, preferably blinded, outcome assessment.6 Assessing the quality of a study …

Prospective randomised study of intensive insulin treatment on long term survival after acute myocardial infarction in patients with diabetes mellitus

Abstract: Objectives: To test the hypothesis that intensive metabolic treatment with insulin-glucose infusion followed by multidose insulin treatment in patients with diabetes mellitus and acute myocardial infarction improves the prognosis. Design: Patients with diabetes mellitus and acute myocardial infarction were randomly allocated standard treatment plus insulin-glucose infusion for at least 24 hours followed by multidose insulin treatment or standard treatment (controls). Subjects: 620 patients were recruited, of whom 306 received intensive insulin treatment and 314 served as controls. Main outcome measure: Long term all cause mortality. Results: The mean (range) follow up was 3.4 (1.6-5.6) years. There were 102 (33%) deaths in the treatment group compared with 138 (44%) deaths in the control group (relative risk (95% confidence interval) 0.72 (0.55 to 0.92); P=0.011).The effect was most pronounced among the predefined group that included 272 patients without previous insulin treatment and at a low cardiovascular risk (0.49 (0.30 to 0.80); P=0.004). Conclusion: Insulin-glucose infusion followed by intensive subcutaneous insulin in diabetic patients with acute myocardial infarction improves long term survival, and the effect seen at one year continues for at least 3.5 years, with an absolute reduction in mortality of 11%. This means that one life was saved for nine treated patients. The effect was most apparent in patients who had not previously received insulin treatment and who were at a low cardiovascular risk. Key messages Diabetes mellitus is common among patients with acute myocardial infarction Diabetic patients with myocardial infarction have a poor short and long term prognosis Poor metabolic control is common among diabetic patients with myocardial infarction Improved metabolic control by means of acute insulin-glucose infusion followed by long term intensive insulin treatment improves long term prognosis among these patients

Randomised controlled trial of a general practice programme of home based exercise to prevent falls in elderly women

Abstract: Objective: To assess the effectiveness of a home exercise programme of strength and balance retraining exercises in reducing falls and injuries in elderly women. Design: Randomised controlled trial of an individually tailored programme of physical therapy in the home (exercise group, n=116) compared with the usual care and an equal number of social visits (control group, n=117). Setting: 17 general practices in Dunedin, New Zealand. Subjects: Women aged 80 years and older living in the community and registered with a general practice in Dunedin. Main outcome measures: Number of falls and injuries related to falls and time between falls during one year of follow up; changes in muscle strength and balance measures after six months. Results: After one year there were 152 falls in the control group and 88 falls in the exercise group. The mean (SD) rate of falls was lower in the exercise than the control group (0.87 (1.29) v 1.34 (1.93) falls per year respectively; difference 0.47; 95% confidence interval 0.04 to 0.90). The relative hazard for the first four falls in the exercise group compared with the control group was 0.68 (0.52 to 0.90). The relative hazard for a first fall with injury in the exercise group compared with the control group was 0.61 (0.39 to 0.97). After six months, balance had improved in the exercise group (difference between groups in change in balance score 0.43 (0.21 to 0.65). Conclusions: An individual programme of strength and balance retraining exercises improved physical function and was effective in reducing falls and injuries in women 80 years and older. Key messages Modifiable risk factors for falls in elderly people have been well defined; they include loss of muscle strength and impaired balance A programme to improve strength and balance in women aged 80 years and older can be set up safely with four home visits from a physiotherapist This programme reduced falls and moderate injuries appreciably over the subsequent year in Dunedin, New Zealand The benefit was most noticeable in elderly people who fell often

Randomised controlled trial of aspirin and aspirin plus heparin in pregnant women with recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid antibodies)

Abstract: OBJECTIVE: To determine whether treatment with low dose aspirin and heparin leads to a higher rate of live births than that achieved with low dose aspirin alone in women with a history of recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid antibodies), lupus anticoagulant, and cardiolipin antibodies (or anticardiolipin antibodies). DESIGN: Randomised controlled trial. SETTING: Specialist clinic for recurrent miscarriages. SUBJECTS: 90 women (median age 33 (range 22-43)) with a history of recurrent miscarriage (median number 4 (range 3-15)) and persistently positive results for phospholipid antibodies. INTERVENTION: Either low dose aspirin (75 mg daily) or low dose aspirin and 5000 U of unfractionated heparin subcutaneously 12 hourly. All women started treatment with low dose aspirin when they had a positive urine pregnancy test. Women were randomly allocated an intervention when fetal heart activity was seen on ultrasonography. Treatment was stopped at the time of miscarriage or at 34 weeks' gestation. MAIN OUTCOME MEASURES: Rate of live births with the two treatments. RESULTS: There was no significant difference in the two groups in age or the number and gestation of previous miscarriages. The rate of live births with low dose aspirin and heparin was 71% (32/45 pregnancies) and 42% (19/45 pregnancies) with low dose aspirin alone (odds ratio 3.37 (95% confidence interval 1.40 to 8.10)). More than 90% of miscarriages occurred in the first trimester. There was no difference in outcome between the two treatments in pregnancies that advanced beyond 13 weeks' gestation. Twelve of the 51 successful pregnancies (24%) were delivered before 37 weeks' gestation. Women randomly allocated aspirin and heparin had a median decrease in lumbar spine bone density of 5.4% (range -8.6% to 1.7%). CONCLUSION: Treatment with aspirin and heparin leads to a significantly higher rate of live births in women with a history of recurrent miscarriage associated with phospholipid antibodies than that achieved with aspirin alone.

Low job control and risk of coronary heart disease in whitehall ii (prospective cohort) study

Abstract: OBJECTIVE: To determine the association between adverse psychosocial characteristics at work and risk of coronary heart disease among male and female civil servants. DESIGN: Prospective cohort study (Whitehall II study). At the baseline examination (1985-8) and twice during follow up a self report questionnaire provided information on psychosocial factors of the work environment and coronary heart disease. Independent assessments of the work environment were obtained from personnel managers at baseline. Mean length of follow up was 5.3 years. SETTING: London based office staff in 20 civil service departments. SUBJECTS: 10,308 civil servants aged 35-55 were examined-6895 men (67%) and 3413 women (33%). MAIN OUTCOME MEASURES: New cases of angina (Rose questionnaire), severe pain across the chest, diagnosed ischaemic heart disease, and any coronary event. RESULTS: Men and women with low job control, either self reported or independently assessed, had a higher risk of newly reported coronary heart disease during follow up. Job control assessed on two occasions three years apart, although intercorrelated, had cumulative effects on newly reported disease. Subjects with low job control on both occasions had an odds ratio for any subsequent coronary event of 1.93 (95% confidence interval 1.34 to 2.77) compared with subjects with high job control at both occasions. This association could not be explained by employment grade, negative affectivity, or classic coronary risk factors. Job demands and social support at work were not related to the risk of coronary heart disease. CONCLUSIONS: Low control in the work environment is associated with an increased risk of future coronary heart disease among men and women employed in government offices. The cumulative effect of low job control assessed on two occasions indicates that giving employees more variety in tasks and a stronger say in decisions about work may decrease the risk of coronary heart disease.

An ecological approach to the obesity pandemic

Abstract: The increasing prevalence of obesity in many countries means that it should now be considered a pandemic.1 One estimate from Australia suggests that over the past decade the average adult has been adding 1 gram a day to body weight.2 This has occurred in the face of increasing knowledge, awareness, and education about obesity, nutrition, and exercise. It has been suggested that a paradigm shift is necessary if future progress is to be made.3 Traditionally, weight gain was thought of as caused by eating too much or exercising too little, or both (changes in weight=energy intake-energy expenditure). This led to the search for small deficiencies in energy metabolism such as a reduced thermic effect of food to explain obesity.4 Treatment was dominated by calorie counting, and public health messages extolled people to balance their intake and output. This paradigm has changed with the increasing understanding of the dynamic relations between energy stores, appetite mechanisms, and energy metabolism and of the wider recognition of nutrient partitioning.5 6 From studies which have shown that fat balance is equivalent to energy balance,7 the fat balance equation was developed (rate of change of fat stores=rate of fat intake-rate of fat oxidation).5 This equation is more dynamic than the original static equation and reflects energy balance under normal conditions of free access to foods. Because fat intake and oxidation are not closely balanced,8 this approach does not need metabolic abnormalities or genetic mutations to explain weight gain. Indeed, the differences in body fat between people living in the same environment could be better described as normal physiological variation. This paradigm is more helpful in explaining changes in body fat within an individual over time, but it does not account for the wider influences within and around individuals …

Short term effects of ambient sulphur dioxide and particulate matter on mortality in 12 European cities: Results from time series data from the APHEA project

Abstract: Objectives: To carry out a prospective combined quantitative analysis of the associations between all cause mortality and ambient particulate matter and sulphur dioxide. Design: Analysis of time series data on daily number of deaths from all causes and concentrations of sulphur dioxide and particulate matter (measured as black smoke or particles smaller than 10 μm in diameter (PM10)) and potential confounders. Setting: 12 European cities in the APHEA project (Air Pollution and Health: a European Approach). Main outcome measure: Relative risk of death. Results: In western European cities it was found that an increase of 50 μg/m3 in sulphur dioxide or black smoke was associated with a 3% (95% confidence interval 2% to 4%) increase in daily mortality and the corresponding figure for PM10 was 2% (1% to 3%). In central eastern European cities the increase in mortality associated with a 50 μg/m3 change in sulphur dioxide was 0.8% (-0.1% to 2.4%) and in black smoke 0.6% (0.1% to 1.1%). Cumulative effects of prolonged (two to four days) exposure to air pollutants resulted in estimates comparable with the one day effects. The effects of both pollutants were stronger during the summer and were mutually independent. Conclusions: The internal consistency of the results in western European cities with wide differences in climate and environmental conditions suggest that these associations may be causal. The long term health impact of these effects is uncertain, but today9s relatively low levels of sulphur dioxide and particles still have detectable short term effects on health and further reductions in air pollution are advisable. Key messages Evidence is accumulating that air pollution below the levels of national and international standards has adverse short term health effects In this study data from 12 European cities showed that increases in sulphur dioxide and particulate matter are associated with increased total mortality The effects of the two pollutants seem to be independent Associations were stronger and more consistent in western European cities Current low levelsof sulphur dioxide and particles stillaffect health and further reductions in pollution are needed

Socioeconomic determinants of health. Health inequalities: relative or absolute material standards?

Abstract: That mortality in developed countries is affected more by relative than absolute living standards is shown by three pieces of evidence. Firstly, mortality is related more closely to relative income within countries than to differences in absolute income between them. Secondly, national mortality rates tend to be lowest in countries that have smaller income differences and thus have lower levels of relative deprivation. Thirdly, most of the long term rise in life expectancy seems unrelated to long term economic growth rates. Although both material and social influences contribute to inequalities in health, the importance of relative standards implies that psychosocial pathways may be particularly influential. During the 1980s income differences widened more rapidly in Britain than in other countries; almost a quarter of the population now lives in relative poverty. The effects of higher levels of relative deprivation and lower social cohesion may already be visible in mortality trends among young adults. A “feel bad” factor in the health divide? TONY WALLIS The existence of wide-and widening-socioeconomic differences in health shows how extraordinarily sensitive health remains to socioeconomic circumstances. Twofold, threefold, or even fourfold differences in mortality have been reported within Britain, depending largely on the social classification used.1 2 3 This series will illustrate some of the most important mechanisms involved in the generation of these differences. Fundamental to understanding the causes of these differences in health is the distinction between the effects of relative and absolute living standards. Socioeconomic gradients in health are simultaneously an association with social position and with different material circumstances, both of which have implications for health-but which is more important in terms of causality? Is the health disadvantage of the least well off part of the population mainly a reflection of the direct physiological effects of lower absolute material standards (of bad …

Birth weight and risk of cardiovascular disease in a cohort of women followed up since 1976.

Abstract: Objective: To examine the association between birth weight and non-fatal adult cardiovascular disease while controlling for potential confounders such as socioeconomic group and adult lifestyle. Design: Retrospective self report of birth weight in an ongoing longitudinal cohort of nurses followed up by postal questionnaire every two years. Setting: Nurses9 health study, a cohort of 121 700 women followed up since 1976. Main outcome measures: Non-fatal cardiovascular disease, including myocardial infarction, coronary revascularisation, and stroke. Results: Among the 70 297 women free of cardiovascular disease at baseline who reported birth weight in the 1992 questionnaire there were 1309 first cases of non-fatal cardiovascular disease. Increasing birth weight was associated with decreasing risk of non-fatal cardiovascular disease. There were 1216 first cases of non-fatal cardiovascular disease among women who were singletons and had been born full term; their relative risks adjusted for several cardiovascular risk factors were 1.49 (95% confidence interval 1.05 to 2.10) for birth weight 2495-3175 g (>5 lb 8 oz to 7 lb 0 oz); 1.00 (referent) for birth weight >3175-3856 g (>7 lb 0 oz to 8 lb 8 oz); 0.96 (0.80 to 1.15) for birth weight >3856-4536 g (>8 lb 8 oz to 10 lb 0 oz); and 0.68 (0.46 to 1.00) for birth weight >4536 g (>10 lb 0 oz) (P value for trend=0.0004). The inverse trend was apparent for both coronary heart disease and stroke. Conclusions: These data provide strong evidence of an association between birth weight and adult coronary heart disease and stroke. Key messages Birth weight and mortality from cardiovascular disease are inversely associated in adult women This study found that birth weight and the risk of non-fatal cardiovascular disease is also inversely associated in adult women for both coronary heart disease and stroke This association is driven by the 13% of women born at the extremes of birth weight It seems to be largely independent of established cardiovascular risk factors also associated with birth weight: adult body weight, hypertension, and diabetes It is not weakened by controlling for childhood socioeconomic group or adjusting for adult lifestyle

Personal paper: Beliefs and evidence in changing clinical practice

Abstract: That improvements are possible in many areas of clinical care has become increasingly clear. The different players within health care, however—clinicians, epidemiologists, health services researchers, educationalists, social scientists, economists, health authorities—often have different ideas on the best strategies to improve practice and the best way of making changes. Let us assume that aggregated data, collected by health authorities, disclose that the rate of caesarean section in a specific district is exceptionally high. A committee is formed with experts and representatives of various interests to develop plans for improving obstetric care. Hearing the problem, all are worried. The clinician either denies there is a problem or proposes setting up a well designed course to increase clinicians' knowledge and skills. “OK,” says the clinical epidemiologist, “but we first need to know what the evidence is on the indications for a caesarean section. We should perform a meta-analysis and come up with evidence based guidelines to disseminate among the obstetricians.” “No,” says the educational expert: “that is a top down approach and such strategies will usually fail. Form small groups of doctors and let them discuss the problem, using cases and experiences from their own practices as the basis for local arrangements on new routines.” “We should take a look at the facts first,” says the health services researcher. “Let us set up a multicentre audit first and collect data on actual variation between hospitals and include data on casemix. Feeding this information back to the hospitals will probably stimulate improvement.” “You are all focusing too much on the individual doctor,” says the management expert. “The problem is not the doctor, but the system. We should analyse the process of decision making and performing the caesarean sections and see what structures determine the process. Next we need a quality improvement team.” “This is …

How to read a paper: Papers that go beyond numbers (qualitative research)

Abstract: Epidemiologist Nick Black has argued that a finding or a result is more likely to be accepted as a fact if it is quantified (expressed in numbers) than if it is not1 There is little or no scientific evidence, for example, to support the well known “facts” that one couple in 10 is infertile, or that one man in 10 is homosexual Yet, observes Black, most of us are happy to accept uncritically such simplified, reductionist, and blatantly incorrect statements so long as they contain at least one number Researchers who use qualitative methods seek a deeper truth They aim to “study things in their natural setting, attempting to make sense of, or interpret, phenomena in terms of the meanings people bring to them,”2 and they use “a holistic perspective which preserves the complexities of human behaviour”1 #### Summary points Qualitative methods aim to make sense of, or interpret, phenomena in terms of the meanings people bring to them Qualitative research may define preliminary questions which can then be addressed in quantitative studies A good qualitative study will address a clinical problem through a clearly formulated question and using more than one research method (triangulation) Analysis of qualitative data can and should be done using explicit, systematic, and reproducible methods Questions such as “How many parents would consult their general practitioner when their child has a mild temperature?” or “What proportion of smokers have tried to give up?” clearly need answering through quantitative methods But questions like “Why do parents worry so much about their children's temperature?” and “What stops people giving up smoking?” cannot and should not be answered by leaping in and measuring the first aspect of the problem that we (the outsiders) think might be important Rather, we need to listen to what people have to say, …

Intraoperative intravascular volume optimisation and length of hospital stay after repair of proximal femoral fracture: randomised controlled trial.

Abstract: Objectives: To assess whether intraoperative intravascular volume optimisation improves outcome and shortens hospital stay after repair of proximal femoral fracture. Design: Prospective, randomised controlled trial comparing conventional intraoperative fluid management with repeated colloid fluid challenges monitored by oesophageal Doppler ultrasonography to maintain maximal stroke volume throughout the operative period. Setting: Teaching hospital, London. Subjects: 40 patients undergoing repair of proximal femoral fracture under general anaesthesia. Interventions: Patients were randomly assigned to receive either conventional intraoperative fluid management (control patients) or additional repeated colloid fluid challenges with oesophageal Doppler ultrasonography used to maintain maximal stroke volume throughout the operative period (protocol patients). Main outcome measures: Time declared medically fit for hospital discharge, duration of hospital stay (in acute bed; in acute plus long stay bed), mortality, perioperative haemodynamic changes. Results: Intraoperative intravascular fluid loading produced significantly greater changes in stroke volume (median 15 ml (95% confidence interval 10 to 21 ml)) and cardiac output (1.2 l/min (0.1 to 2.3 l/min)) than in the conventionally managed group (−5 ml (−10 to 1 ml) and −0.4 l/min (−1.0 to 0.2 l/min)) (P Conclusions: Proximal femoral fracture repair constitutes surgery in a high risk population. Intraoperative intravascular volume loading to optimal stroke volume resulted in a more rapid postoperative recovery and a significantly reduced hospital stay. Key messages Patients undergoing hip fracture repair constitute a high risk group with considerable mortality and morbidity and an often protracted postoperative hospital stay These patients often have depleted intravascular volume in the perioperative period and rarely receive either invasive haemodynamic monitoring or high dependency care Haemodynamic optimisation guided by pulmonary artery catheter in the perioperative period has been shown to improve outcome in high risk patients undergoing major surgery, but this is not considered routinely practicable for hip fracture repair Intravascular volume optimisation directed by minimally invasive oesophageal Doppler monitoring in the intraoperative period significantly reduces hospital stay

Publication bias: evidence of delayed publication in a cohort study of clinical research projects

Abstract: Objectives: To determine the extent to which publication is influenced by study outcome. Design: A cohort of studies submitted to a hospital ethics committee over 10 years were examined retrospectively by reviewing the protocols and by questionnaire. The primary method of analysis was Cox9s proportional hazards model. Setting: University hospital, Sydney, Australia. Studies: 748 eligible studies submitted to Royal Prince Alfred Hospital Ethics Committee between 1979 and 1988. Main outcome measures: Time to publication. Results: Response to the questionnaire was received for 520 (70%) of the eligible studies. Of the 218 studies analysed with tests of significance, those with positive results (P v 8.0 years). This finding was even stronger for the group of 130 clinical trials (hazard ratio 3.13 (1.76 to 5.58), P=0.0001), with median times to publication of 4.7 and 8.0 years respectively. These results were not materially changed after adjusting for other significant predictors of publication. Studies with indefinite conclusions (0.05 P Conclusions: This study confirms the evidence of publication bias found in other studies and identifies delay in publication as an additional important factor. The study results support the need for prospective registration of trials to avoid publication bias and also support restricting the selection of trials to those started before a common date in undertaking systematic reviews. Key messages This retrospective cohort study of clinical research projects confirms the findings of publication bias found in previous studies Delay in the publication of studies with negative results has been identified as an additional important factor in publication bias With the recognised importance of evidence based medicine, these results have important implications for the selection of studies included in systematic reviews Prospective registration of clinical research projects will avoid many of the problems associated with publication bias However, it is also important to restrict inclusion in systematic reviews to studies started before a certain date to allow for the delay in completing studies with negative results

Health and social cohesion: why care about income inequality?

Abstract: Throughout the world, wealth and income are becoming more concentrated. Growing evidence suggests that the distribution of income–in addition to the absolute standard of living enjoyed by the poor–is a key determinant of population health. A large gap between rich people and poor people leads to higher mortality through the breakdown of social cohesion. The recent surge in income inequality in many countries has been accompanied by a marked increase in the residential concentration of poverty and affluence. Residential segregation diminishes the opportunities for social cohesion. Income inequality has spillover effects on society at large, including increased rates of crime and violence, impeded productivity and economic growth, and the impaired functioning of representative democracy. The extent of inequality in society is often a consequence of explicit policies and public choice. Reducing income inequality offers the prospect of greater social cohesiveness and better population health.

Socioeconomic determinants of health. The contribution of nutrition to inequalities in health.

Abstract: Social class differences in health are seen at all ages, with lower socioeconomic groups having greater incidence of premature and low birthweight babies, heart disease, stroke, and some cancers in adults. Risk factors including lack of breast feeding, smoking, physical inactivity, obesity, hypertension, and poor diet are clustered in the lower socioeconomic groups. The diet of the lower socioeconomic groups provides cheap energy from foods such as meat products, full cream milk, fats, sugars, preserves, potatoes, and cereals but has little intake of vegetables, fruit, and wholewheat bread. This type of diet is lower in essential nutrients such as calcium, iron, magnesium, folate, and vitamin C than that of the higher socioeconomic groups. New nutritional knowledge on the protective role of antioxidants and other dietary factors suggests that there is scope for enormous health gain if a diet rich in vegetables, fruit, unrefined cereal, fish, and small quantities of quality vegetable oils could be more accessible to poor people.

The accumulated evidence on lung cancer and environmental tobacco smoke.

Abstract: Objective: To estimate the risk of lung cancer in lifelong non-smokers exposed to environmental tobacco smoke. Design: Analysis of 37 published epidemiological studies of the risk of lung cancer (4626 cases) in non-smokers who did and did not live with a smoker. The risk estimate was compared with that from linear extrapolation of the risk in smokers using seven studies of biochemical markers of tobacco smoke intake. Main outcome measure: Relative risk of lung cancer in lifelong non-smokers according to whether the spouse currently smoked or had never smoked. Results: The excess risk of lung cancer was 24% (95% confidence interval 13% to 36%) in non-smokers who lived with a smoker (P Conclusion: The epidemiological and biochemical evidence on exposure to environmental tobacco smoke, with the supporting evidence of tobacco specific carcinogens in the blood and urine of non-smokers exposed to environmental tobacco smoke, provides compelling confirmation that breathing other people9s tobacco smoke is a cause of lung cancer. Key messages A woman who has never smoked has an estimated 24% greater risk of lung cancer if she lives with a smoker Neither bias nor confounding accounted for the association There is a dose-response relation between a non-smoker9s risk of lung cancer and the number of cigarettes and years of exposure to the smoker The increased risk was consistent with that expected from extrapolation of the risk in smokers using biochemical markers Tobacco specific carcinogens are found in the blood and urine of non-smokers exposed to environmental tobacco smoke All the available evidence confirms that exposure to environmental tobacco smoke causes lung cancer

A meta-analysis of cigarette smoking, bone mineral density and risk of hip fracture: recognition of a major effect.

Abstract: Objective: To determine the magnitude and importance of the relation between smoking, bone mineral density, and risk of hip fracture according to age. Design: Meta-analysis of 29 published cross sectional studies reporting the difference in bone density in 2156 smokers and 9705 non-smokers according to age, and of 19 cohort and case-control studies recording 3889 hip fractures reporting risk in smokers relative to non-smokers. Results: In premenopausal women bone density was similar in smokers and non-smokers. Postmenopausal bone loss was greater in current smokers than non-smokers, bone density diminishing by about an additional 2% for every 10 year increase in age, with a difference of 6% at age 80. In current smokers relative to non-smokers the risk of hip fracture was similar at age 50 but greater thereafter by an estimated 17% at age 60, 41% at 70, 71% at 80, and 108% at 90. These estimates of relative risk by age, derived directly from a regression analysis of the studies of smoking and hip fracture, were close to estimates using the difference in bone density between smokers and non-smokers and the association between bone density and risk of hip fracture. The estimated cumulative risk of hip fracture in women in England was 19% in smokers and 12% in non-smokers to age 85; 37% and 22% to age 90. Among all women, one hip fracture in eight is attributable to smoking. Limited data in men suggest a similar proportionate effect of smoking as in women. The association was not explained by smokers being thinner, younger at menopause, and exercising less nor by actions of smoking on oestrogen, but smoking may have a direct action on bone. Conclusions: Hip fracture in old age is a major adverse effect of smoking after the menopause. The cumulative excess bone loss over decades is substantial, increasing the lifetime risk of hip fracture by about half Key messages Smoking has no material effect on bone density in premenopausal women Postmenopausal bone loss is greater in smokers—an additional 0.2% of bone mass each year. The cumulative effect of this over many years is substantial, with a difference of 6% at age 80 In current smokers relative to non-smokers the risk of hip fracture is estimated to be 17% greater at age 60, 41% greater at 70, 71% greater at 80, 108% greater at 90 The data in men are limited but suggest a similar proportionate effect in smokers The cumulative risk of hip fracture to age 85 in women is 19% in smokers and 12% in non-smokers; to age 90 it is 37% and 22% Among all women, one hip fracture in eight is attributable to smoking

Development and evaluation of evidence based risk assessment tool (STRATIFY) to predict which elderly inpatients will fall: case-control and cohort studies

Abstract: Objectives: To identify clinical characteristics of elderly inpatients that predict their chance of falling (phase 1) and to use these characteristics to derive a risk assessment tool and to evaluate its power in predicting falls (phases 2 and 3). Design: Phase 1: a prospective case-control study. Phases 2 and 3: prospective evaluations of the derived risk assessment tool in predicting falls in two cohorts. Setting: Elderly care units of St Thomas9s Hospital (phase 1 and 2) and Kent and Canterbury Hospital (phase 3). Subjects: Elderly hospital inpatients (aged 65 years): 116 cases and 116 controls in phase 1, 217 patients in phase 2, and 331 in phase 3. Main outcome measures: 21 separate clinical characteristics were assessed in phase 1, including the abbreviated mental test score, modified Barthel index, a transfer and mobility score obtained by combining the transfer and mobility sections of the Barthel index, and several nursing judgments. Results: In phase 1 five factors were independently associated with a higher risk of falls: fall as a presenting complaint (odds ratio 4.64 (95% confidence interval 2.59 to 8.33); a transfer and mobility score of 3 or 4 (2.10 (1.22 to 3.61)); and primary nurses9 judgment that a patient was agitated (20.9 (9.62 to 45.62)), needed frequent toileting (2.48 (1.08 to 5.70)), and was visually impaired (3.56 (1.26 to 10.05)). A risk assessment score (range 0-5) was derived by scoring one point for each of these five factors. In phases 2 and 3 a risk assessment score >2 was used to define high risk: the sensitivity and specificity of the score to predict falls during the following week was 93% and 88% respectively in phase 2 and 92% and 68% respectively in phase 3. Conclusion: This simple risk assessment tool predicted with clinically useful sensitivity and specificity a high percentage of falls among elderly hospital inpatients.

Reliability of health information for the public on the World Wide Web: systematic survey of advice on managing fever in children at home.

Abstract: Objective: To assess the reliability of healthcare information on the world wide web and therefore how it may help lay people cope with common health problems. Methods: Systematic search by means of two search engines, Yahoo and Excite, of parent oriented web pages relating to home management of feverish children. Reliability of information on the web sites was checked by comparison with published guidelines. Main outcome measures: Minimum temperature of child that should be considered as fever, optimal sites for measuring temperature, pharmacological and physical treatment of fever, conditions that may warrant a doctor9s visit. Results: 41 web pages were retrieved and considered. 28 web pages gave a temperature above which a child is feverish; 26 pages indicated the optimal site for taking temperature, most recommending rectal measurement; 31 of the 34 pages that mentioned drug treatment recommended paracetamol as an antipyretic; 38 pages recommended non-drug measures, most commonly tepid sponging, dressing lightly, and increasing fluid intake; and 36 pages gave some indication of when a doctor should be called. Only four web pages adhered closely to the main recommendations in the guidelines. The largest deviations were in sponging procedures and how to take a child9s temperature, whereas there was a general agreement in the use of paracetamol. Conclusions: Only a few web sites provided complete and accurate information for this common and widely discussed condition. This suggests an urgent need to check public oriented healthcare information on the internet for accuracy, completeness, and consistency. Key messages Fever in children is a common problem, and accurate information on home management of feverish children could be useful for parents A systematic search on the world wide web for such parent oriented information retrieved 41 web pages, but only four adhered closely to published guidelines for home management of childhood fever These findings suggest the urgent need to check public oriented healthcare information on the internet for accuracy, completeness, and consistency Information on the internet should not be a substitute for routine care by family doctors

Impact of new antiretroviral combination therapies in HIV infected patients in Switzerland: prospective multicentre study. Swiss HIV Cohort Study.

Abstract: OBJECTIVES: To examine trends in disease progression and survival among patients enrolled in the Swiss HIV cohort study during 1988-96 and to assess the influence of new antiretroviral combination therapies. DESIGN: Prospective multicentre study, with follow up visits planned at six monthly intervals. SETTING: Seven HIV units at university centres and cantonal hospitals in Switzerland. PATIENTS: 3785 men (mean age 35.0 years) and 1391 women (30.3 years) infected with HIV. 2023 participants had a history of intravenous drug misuse; 1764 were men who had sex with men; 1261 were infected heterosexually; and 164 had other or unknown modes of transmission. 601 participants had had an AIDS defining illness. RESULTS: During more than 15,000 years of follow up, there were 1456 first AIDS defining diagnoses and 1903 deaths. Compared with those enrolled during 1988-90, the risk of progression to a first AIDS diagnosis was reduced by 18% (relative risk 0.82 (95% confidence interval 0.73 to 0.93)) among participants enrolled in 1991-2, by 23% (0.77 (0.65 to 0.91)) among those enrolled in 1993-4, and by 73% (0.27 (0.18 to 0.39)) among those enrolled in 1995-6. Mortality was reduced by 19% (0.81 (0.73 to 0.90)), 26% (0.74 (0.63 to 0.87)), and 62% (0.38 (0.25 to 0.97)) respectively. Compared with no antiretroviral treatment, the risk of an initial AIDS diagnosis after CD4 lymphocyte counts fell to < 200 cells x 10(6)/1 was reduced by 16% (0.84 (0.73 to 0.97)) with monotherapy, 24% (0.76 (0.63 to 0.91)) with dual therapy, and 42% (0.58 (0.37 to 0.92)) with triple therapy. Mortality was reduced by 23% (0.77 (0.68 to 0.88)), 31% (0.69 (0.60 to 0.80)), and 65% (0.35 (0.20 to 0.60)) respectively. CONCLUSIONS: The introduction of antiretroviral combination therapies outside the selected patient groups included in clinical trials has led to comparable reductions in disease progression and mortality.

Milk intake and bone mineral acquisition in adolescent girls: randomised, controlled intervention trial

Abstract: OBJECTIVES: To investigate the effect of milk supplementation on total body bone mineral acquisition in adolescent girls. DESIGN: 18 month, open randomised intervention trial. SUBJECTS: 82 white girls aged 12.2 (SD 0.3) years, recruited from four secondary schools in Sheffield. INTERVENTION: 568 ml (one pint) of whole or reduced fat milk per day for 18 months. MAIN OUTCOME MEASURES: Total body bone mineral content and bone mineral density measured by dual energy x ray absorptiometry. Outcome measures to evaluate mechanism included biochemical markers of bone turnover (osteocalcin, bone alkaline phosphatase, deoxypyridinoline, N-telopeptide of type I collagen), and hormones important to skeletal growth (parathyroid hormone, oestradiol, insulin-like growth factor I). RESULTS: 80 subjects completed the trial. Daily milk intake at baseline averaged 150 ml in both groups. The intervention group consumed, on average, an additional 300 ml a day throughout the trial. Compared with the control group, the intervention group had greater increases of bone mineral density (9.6% v 8.5%, P = 0.017; repeated measures analysis of variance) and bone mineral content (27.0% v 24.1%, P = 0.009). No significant differences in increments in height, weight, lean body mass, and fat mass were observed between the groups. Bone turnover was not affected by milk supplementation. Serum concentrations of insulin-like growth factor I increased in the milk group compared with the control group (35% v 25%, P = 0.02). CONCLUSION: Increased milk consumption significantly enhances bone mineral acquisition in adolescent girls and could favourably modify attainment of peak bone mass.

Environmental tobacco smoke exposure and ischaemic heart disease: an evaluation of the evidence

Abstract: Objectives: To estimate the risk of ischaemic heart disease caused by exposure to environmental tobacco smoke and to explain why the associated excess risk is almost half that of smoking 20 cigarettes per day when the exposure is only about 1% that of smoking. Design: Meta-analysis of all 19 acceptable published studies of risk of ischaemic heart disease in lifelong non-smokers who live with a smoker and in those who live with a non-smoker, five large prospective studies of smoking and ischaemic heart disease, and studies of platelet aggregation and studies of diet according to exposure to tobacco smoke. Results: The relative risk of ischaemic heart disease associated with exposure to environmental tobacco smoke was 1.30 (95% confidence interval 1.22 to 1.38) at age 65. At the same age the estimated relative risk associated with smoking one cigarette per day was similar (1.39 (1.18 to 1.64)), while for 20 per day it was 1.78 (1.31 to 2.44). Two separate analyses indicated that non-smokers who live with smokers eat a diet that places them at a 6% higher risk of ischaemic heart disease, so the direct effect of environmental tobacco smoke is to increase risk by 23% (14% to 33%), since 1.30/1.06=1.23. Platelet aggregation provides a plausible and quantitatively consistent mechanism for the low dose effect. The increase in platelet aggregation produced experimentally by exposure to environmental tobacco smoke would be expected to have acute effects increasing the risk of ischaemic heart disease by 34%. Conclusion: Breathing other people9s smoke is an important and avoidable cause of ischaemic heart disease, increasing a person9s risk by a quarter. Key messages Analysis of 19 epidemiological studies shows that people who have never smoked have an estimated 30% greater risk of ischaemic heart disease if they live with a smoker (P This is surprisingly large—almost half the risk of smoking 20 cigarettes per day even though the exposure is only 1% of that of a smoker The excess risk from smoking one cigarette per day is 39%—similar to the risk in a non-smoker living with a smoker The effect is mainly explained by a non-linear dose-response relation between expsoure to tobacco smoke and risk of heart disease Detailed analysis shows no significant bias; dietary confounding can account for an excess risk of only 6%, so revising the excess risk from 30% to 23%

Prevalence of gastrointestinal symptoms six months after bacterial gastroenteritis and risk factors for development of the irritable bowel syndrome: postal survey of patients.

Abstract: Objective: To measure the prevalence of gastrointestinal symptoms six months after bacterial gastroenteritis and determine risk factors and associations with postdysenteric symptoms. Design: Postal questionnaire. Setting: Nottingham Health Authority. Subjects: 544 people with microbiologically confirmed bacterial gastroenteritis between July 1994 and December 1994. Main outcome measures: Prevalence of gastrointestinal symptoms and relative risks for development of the irritable bowel syndrome and self reported altered bowel habit. Results: A quarter of subjects reported persistence of altered bowel habit six months after an episode of infective gastroenteritis. Increasing duration of diarrhoea, younger age, and female sex increased this risk, whereas vomiting as part of the illness reduced the risk. One in 14 developed the irritable bowel syndrome with an increased risk seen in women (relative risk 3.4; 95% confidence interval 1.2 to 9.8) and with duration of diarrhoea (6.5; 1.3 to 34 for 15-21 days). Conclusions: Persistence of bowel symptoms commonly occurs after bacterial gastroenteritis and is responsible for considerable morbidity and health care costs.

Lifetime socioeconomic position and mortality: prospective observational study

Abstract: OBJECTIVES: To assess the influence of socioeconomic position over a lifetime on risk factors for cardiovascular disease, on morbidity, and on mortality from various causes. DESIGN: Prospective observational study with 21 years of follow up. Social class was determined as manual or non-manual at three stages of participants' lives: from the social class of their father's job, the social class of their first job, and the social class of their job at the time of screening. A cumulative social class indicator was constructed, ranging from non-manual social class at all three stages of life to manual social class at all three stages. SETTING: 27 workplaces in the west of Scotland. PARTICIPANTS: 5766 men aged 35-64 at the time of examination. MAIN OUTCOME MEASURES: Prevalence and level of risk factors for cardiovascular disease; morbidity; and mortality from broad causes of death. RESULTS: From non-manual social class locations at all three life stages to manual at all stages there were strong positive trends for blood pressure, body mass index, current cigarette smoking, angina, and bronchitis. Inverse trends were seen for height, cholesterol concentration, lung function, and being an ex-smoker. 1580 men died during follow up. Age adjusted relative death rates in comparison with the men of non-manual social class locations at all three stages of life were 1.29 (95% confidence interval 1.08 to 1.56) in men of two non-manual and one manual social class; 1.45 (1.21 to 1.73) in men of two manual and one non-manual social class; and 1.71 (1.46 to 2.01) in men of manual social class at all three stages. Mortality from cardiovascular disease showed a similar graded association with cumulative social class. Mortality from cancer was mainly raised among men of manual social class at all three stages. Adjustment for a wide range of risk factors caused little attenuation in the association of cumulative social class with mortality from all causes and from cardiovascular disease; greater attenuation was seen in the association with mortality from non-cardiovascular, non-cancer disease. Fathers having a manual [corrected] occupation was strongly associated with mortality from cardiovascular disease: relative rate 1.41 (1.15 to 1.72). Participants' social class at the time of screening was more strongly associated than the other social class indicators with mortality from cancer and from non-cardiovascular, non-cancer causes. CONCLUSIONS: Socioeconomic factors acting over the lifetime affect health and risk of premature death. The relative importance of influences at different stages varies for the cause of death. Studies with data on socioeconomic circumstances at only one stage of life are inadequate for fully elucidating the contribution of socioeconomic factors to health and mortality risk.

Impact of covert duplicate publication on meta-analysis: a case study

Abstract: Objective: To quantify the impact of duplicate data on estimates of efficacy. Design: Systematic search for published full reports of randomised controlled trials investigating ondansetron9s effect on postoperative emesis. Abstracts were not considered. Data sources: Eighty four trials (11 980 patients receiving ondansetron) published between 1991 and September 1996. Main outcome measures: Percentage of duplicated trials and patient data. Estimation of antiemetic efficacy (prevention of emesis) of the most duplicated ondansetron regimen. Comparison between the efficacy of non-duplicated and duplicated data. Results: Data from nine trials had been published in 14 further reports, duplicating data from 3335 patients receiving ondansetron; none used a clear cross reference. Intravenous ondansetron 4 mg versus placebo was investigated in 16 reports not subject to duplicate publication, three reports subject to duplicate publication, and six duplicates of those three reports. The number needed to treat to prevent vomiting within 24 hours was 9.5 (95% confidence interval 6.9 to 15) in the 16 non-duplicated reports and 3.9 (3.3 to 4.8) in the three reports which were duplicated (P Conclusions: By searching systematically we found 17% of published full reports of randomised trials and 28% of the patient data were duplicated. Trials reporting greater treatment effect were significantly more likely to be duplicated. Inclusion of duplicated data in meta-analysis led to a 23% overestimation of ondansetron9s antiemetic efficacy. Key messages Although publishing the same data more than once is strongly discouraged, there is no evidence of the impact of duplicate data on meta-analysis Re-analysing an important trial, and cross referencing to original reports (overt duplication), may be necessary and valuable in some circumstances Covert duplication, masked by change of authors, of language, or by adding extra data, causes problems. One danger is that patient data are analysed more than once in meta-analysis 17% of systematically searched randomised trials of ondansetron as a postoperative antiemetic were covert duplicates and resulted in 28% of patient data being duplicated. None of these reports cross references the original source. Duplication lead to an overestimation of ondansetron9s antiemetic efficacy of 23%. Trials reporting greater treatment effect were significantly more likely to be duplicated Covert duplication of data has major implications for the assessment of drug efficacy and safety

Prescribing behaviour in clinical practice: patients' expectations and doctors' perceptions of patients' expectations—a questionnaire study

Abstract: Objectives: To examine the effect of patients9 expectations for medication and doctors9 perceptions of patients9 expectations on prescribing when patients present with new conditions. Design: Questionnaire study of practitioners and patients. Setting: General practice in Newcastle, Australia. Subjects: 22 non-randomly selected general practitioners and 336 of their patients with a newly diagnosed medical condition. Main outcome measures: Prescription of medication and expectation of it. Results: Medication was prescribed for 169 (50%) patients. After controlling for the presenting condition, patients who expected medication were nearly three times more likely to receive medication (odds ratio=2.9, 95% confidence interval 1.3 to 6.3). When the general practitioner thought the patient expected medication the patient was 10 times more likely to receive it (odds ratio=10.1, 5.3 to 19.6). A significant association existed between patients9 expectation and doctors9 perception of patients9 expectation (χ2=52.0, df=4, P=0.001). For all categories of patient expectation, however, patients were more likely to receive medication when the practitioner judged the patient to want medication than when the practitioner ascribed no expectation to the patient. Conclusions: Although patients brought expectations to the consultation regarding medication, the doctors9 opinions about their expectations were the strongest determinants of prescribing. Key messages This study showed that patients who expected medications were three times more likely to be prescribed medicines for new conditions If the general practitioner thought that the patient expected medication, patients were ten times more likely to be prescribed medication Although patients brought expectations to the consultation regarding medication, it was the doctors9 opinions about patients9 expectations that were the strongest determinants of prescribing With the increasing promotion of rational prescribing, practitioners need to be aware of these influences on prescribing