Showing papers in "BMJ in 1996"

Evidence based medicine: what it is and what it isn't.

Abstract: It's about integrating individual clinical expertise and the best external evidence Evidence based medicine, whose philosophical origins extend back to mid-19th century Paris and earlier, remains a hot topic for clinicians, public health practitioners, purchasers, planners, and the public. There are now frequent workshops in how to practice and teach it (one sponsored by the BMJ will be held in London on 24 April); undergraduate1 and postgraduate2 training programmes are incorporating it3 (or pondering how to do so); British centres for evidence based practice have been established or planned in adult medicine, child health, surgery, pathology, pharmacotherapy, nursing, general practice, and dentistry; the Cochrane Collaboration and Britain's Centre for Review and Dissemination in York are providing systematic reviews of the effects of health care; new evidence based practice journals are being launched; and it has become a common topic in the lay media. But enthusiasm has been mixed with some negative reaction.4 5 6 Criticism has ranged from evidence based medicine being old hat to it being a dangerous innovation, perpetrated by the arrogant to serve cost cutters and suppress clinical freedom. As evidence based medicine continues to evolve and adapt, now is a useful time to refine the discussion of what it is and what it is not. Evidence based medicine is the conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients. The …

Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures

Abstract: Objective: To determine the ability of measurements of bone density in women to predict later fractures. Design: Meta-analysis of prospective cohort studies published between 1985 and end of 1994 with a baseline measurement of bone density in women and subsequent follow up for fractures. For comparative purposes, we also reviewed case control studies of hip fractures published between 1990 and 1994. Subjects: Eleven separate study populations with about 90000 person years of observation time and over 2000 fractures. Main outcome measures: Relative risk of fracture for a decrease in bone mineral density of one standard deviation below age adjusted mean. Results: All measuring sites had similar predictive abilities (relative risk 1.5 (95% confidence interval 1.4 to 1.6)) for decrease in bone mineral density except for measurement at spine for predicting vertebral fractures (relative risk 2.3 (1.9 to 2.8)) and measurement at hip for hip fractures (2.6 (2.0 to 3.5)). These results are in accordance with results of case-control studies. Predictive ability of decrease in bone mass was roughly similar to (or, for hip or spine measurements, better than) that of a 1 SD increase in blood pressure for stroke and better than a 1 SD increase in serum cholesterol concentration for cardiovascular disease. Conclusions: Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture. We do not recommend a programme of screening menopausal women for osteoporosis by measuring bone density. Key messages Measuring bone mineral density has been suggested as a method of identifying individuals at high risk of fracture in a preventive context Our meta-analysis of prospective studies showed that all studies measuring bone density at any site had similar predictive ability for a decrease of 1 SD in bone density except for measurements at hip and spine, which have better predictive ability for fractures in hip and spine respectively Predictive ability of decrease in bone mass was roughly similar to (or, for hip or spine measurements, better than) that of a 1 SD increase in blood pressure for stroke and better than a 1 SD increase in serum cholesterol concentration for cardiovascular disease Although bone mineral density measurements can predict fracture risk, they cannot identify individuals who will have a fracture, and a screening programme for osteoporosis cannot be recommended

Guidelines for authors and peer reviewers of economic submissions to the BMJ. The BMJ Economic Evaluation Working Party.

Abstract: Over the past decade interest in the economic evaluation of health care interventions has risen1 Reviews of published studies have, however, shown gaps in the quality of work2 3 4 5 As far back as 1974 Williams listed the essential elements of economic evaluations,6 and more recently Drummond and colleagues set out the methodological areas generally agreed among economists7 Guidelines for economic evaluations have been promulgated and reviewed by many bodies,8 9 10 11 12 13 14 but few medical journals have explicit guidelines for peer review of economic evaluations or consistently use economist reviewers for economic papers even though they are a major publication outlet for economic evaluations15 16 17 In January 1995 the BMJ set up a working party on economic evaluation to improve the quality of submitted and published economic articles It was not our intention to be unduly prescriptive or stifle innovative methods; our emphasis is on improving the clarity of economic evaluations We also did not address those issues of conduct that have been emphasised in other guidelines13 14 15 16 17 18 The working party's objectives were to improve the quality of submitted and published economic evaluations by agreeing acceptable methods and their systematic application before, during, and after peer review Its task was to produce: (a) guidelines for economic evaluation, together with a comprehensive supporting statement which could be easily understood by both specialist and non-specialist readers; (b) a checklist for use by referees and authors; and (c) a checklist for use by editors In producing the guidelines the working party has concentrated on full economic evaluations comparing two or more health care interventions and considering both costs and consequences19 Articles sent to the BMJ and other medical journals are often more broadly based “economic …

Why we need observational studies to evaluate the effectiveness of health care

Abstract: The view is widely held that experimental methods (randomised controlled trials) are the “gold standard” for evaluation and that observational methods (cohort and case control studies) have little or no value. This ignores the limitations of randomised trials, which may prove unnecessary, inappropriate, impossible, or inadequate. Many of the problems of conducting randomised trials could often, in theory, be overcome, but the practical implications for researchers and funding bodies mean that this is often not possible. The false conflict between those who advocate randomised trials in all situations and those who believe observational data provide sufficient evidence needs to be replaced with mutual recognition of the complementary roles of the two approaches. Researchers should be united in their quest for scientific rigour in evaluation, regardless of the method used. Despite the essential role of observational methods in shedding light on the effectiveness of many aspects of health care, some scientists believe such methods have little or even nothing to contribute. In his summing up at a major conference held in 1993, the eminent medical epidemiologist Richard Doll concluded that observational methods “provide no useful means of assessing the value of a therapy.”1 The widely held view that experimental methods (randomised controlled trials) are the “gold standard” for evaluation has led to the denigration of non-experimental methods, to the extent that research funding bodies and journal editors automatically reject them. I suggest that such attitudes limit our potential to evaluate health care and hence to improve the scientific basis of how to treat individuals and how to organise services. My main contention is that those who are opposed to the use of observational methods have assumed that they represent an alternative to experimentation rather than a set of complementary approaches. This in turn stems from a misguided notion that everything …

Flavonoid intake and coronary mortality in Finland: a cohort study

Abstract: Objective: To study the association between dietary intake of flavonoids and subsequent coronary mortality. Design: A cohort study based on data collected at the Finnish mobile clinic health examination survey from 1967-72 and followed up until 1992. Settings: 30 communities from different parts of Finland. Subjects: 5133 Finnish men and women aged 30-69 years and free from heart disease at baseline. Main outcome measure: Dietary intake of flavonoids, total mortality, and coronary mortality. Results: In women a significant inverse gradient was observed between dietary intake of flavonoids and total and coronary mortality. The relative risks between highest and lowest quarters of flavonoid intake adjusted for age, smoking, serum cholesterol concentration, blood pressure, and body mass index were 0.69 (95% confidence interval 0.53 to 0.90) and 0.54 (0.33 to 0.87) for total and coronary mortality, respectively. The corresponding values for men were 0.76 (0.63 to 0.93) and 0.78 (0.56 to 1.08), respectively. Adjustment for intake of antioxidant vitamins and fatty acids weakened the associations for women; the relative risks for coronary heart disease were 0.73 (0.41 to 1.32) and 0.67 (0.44 to 1.00) in women and men, respectively. Intakes of onions and apples, the main dietary sources of flavonoids, presented similar associations. The relative risks for coronary mortality between highest and lowest quarters of apple intake were 0.57 (0.36 to 0.91) and 0.81 (0.61 to 1.09) for women and men, respectively. The corresponding values for onions were 0.50 (0.30 to 0.82) and 0.74 (0.53 to 1.02), respectively. Conclusion: The results suggest that people with very low intakes of flavonoids have higher risks of coronary disease. Key messages Key messages The protective effect of flavonoids was associated with a diet high in intake of apples and onions The effect may be mediated through prevention of oxidation of low density lipoproteins but other mechanisms could be involved Flavonoids offer an explanation for the suggested beneficial effect of fruits and vegetables in coronary heart disease Further studies should concentrate on the effects of various flavonoid compounds and on populations with different intakes

Inequality in income and mortality in the United States: analysis of mortality and potential pathways.

Abstract: Objective : To examine the relation between health outcomes and the equality with which income is distributed in the United States. Design : The degree of income inequality, defined as the percentage of total household income received by the less well off 50% of households, and changes in income inequality were calculated for the 50 states in 1980 and 1990. These measures were then examined in relation to all cause mortality adjusted for age for each state, age specific deaths, changes in mortalities, and other health outcomes and potential pathways for 1980, 1990, and 1989-91. Main outcome measure : Age adjusted mortality from all causes. Results : There was a significant correlation (r=0.62, P Conclusions : Variations between states in the inequality of the distribution of income are significantly associated with variations between states in a large number of health outcomes and social indicators and with mortality trends. These differences parallel relative investments in human and social capital. Economic policies that influence income and wealth inequality may have an important impact on the health of countries. Key messages There was a significant correlation (r=0.62) between the proportion of total household income received by the less well off 50% of households and variation between states in death rates for the United States Income inequality was also significantly related to changes in mortality with smaller declines between 1980-90 in those states with greater income inequality Income inequality was associated with a large number of other health outcomes and with measures related to investments in human and social capital Economic policies that increase income inequality may also have a deleterious effect on population health

Review of moderate alcohol consumption and reduced risk of coronary heart disease: is the effect due to beer, wine, or spirits?

Abstract: Objectives: To review the effect of specific types of alcoholic drink on coronary risk. Design: Systematic review of ecological, case-control, and cohort studies in which specific associations were available for consumption of beer, wine, and spirits and risk of coronary heart disease. Subjects: 12 ecological, three case-control, and 10 separate prospective cohort studies. Main outcome measures: Alcohol consumption and relative risk of morbidity and mortality from coronary heart disease. Results: Most ecological studies suggested that wine was more effective in reducing risk of mortality from heart disease than beer or spirits. Taken together, the three case-control studies did not suggest that one type of drink was more cardioprotective than the others. Of the 10 prospective cohort studies, four found a significant inverse association between risk of heart disease and moderate wine drinking, four found such an association for beer, and four for spirits. Conclusions: Results from observational studies, where alcohol consumption can be linked directly to an individual9s risk of coronary heart disease, provide strong evidence that all alcoholic drinks are linked with lower risk. Thus, a substantial portion of the benefit is from alcohol rather than other components of each type of drink. Key messages Key messages We examined the relation between specific alcoholic drinks and reduction of risk of coronary heart disease by summarising published reports from ecological, case-control, and cohort studies Most ecological studies suggested that wine was more effective in reducing risk of mortality than beer or spirits, whereas the three case-control studies together did not suggest that one type of drink was more cardioprotective than others Of the 10 prospective cohort studies, four found a significant inverse association between risk of heart disease and moderate wine drinking, four found the association for beer, and four found it for spirits. The evidence suggests that all alcoholic drinks are linked with lower risk, so that much of the benefit is from alcohol rather than other components of each type of drink

Trials to assess equivalence: the importance of rigorous methods

Abstract: The aim of an equivalence trial is to show the therapeutic equivalence of two treatments, usually a new drug under development and an existing drug for the same disease used as a standard active comparator. Unfortunately the principles that govern the design, conduct, and analysis of equivalence trials are not as well understood as they should be. Consequently such trials often include too few patients or have intrinsic design biases which tend towards the conclusion of no difference. In addition the application of hypothesis testing in analysing and interpreting data from such trials sometimes compounds the drawing of inappropriate conclusions, and the inclusion and exclusion of patients from analysis may be poorly managed. The design of equivalence trials should mirror that of earlier successful trials of the active comparator as closely as possible. Patient losses and other deviations from the protocol should be minimised; analysis strategies to deal with unavoidable problems should not centre on an “intention to treat” analysis but should seek to show the similarity of results from a range of approaches. Analysis should be based on confidence intervals, and this also carries implications for the estimation of the required numbers of patients at the design stage. The gold standard in clinical research is the randomised placebo controlled double blind clinical trial. This design is favoured for confirmatory trials carried out as part of the phase III development of new medicines. Because of the number and range of medicines already available, however, new medicines are increasingly being developed for indications in which a placebo control group would be unethical. In such situations one obvious solution is to use as an active comparator an existing drug already licensed and regularly used for the indications in question. Some authors have questioned whether placebo controlled trials are used excessively and unethically, …

St John's wort for depression—an overview and meta-analysis of randomised clinical trials

Abstract: Objective: To investigate if extracts of Hypericum perforatum (St John9s wort) are more effective than placebo in the treatment of depression, are as effective as standard antidepressive treatment, and have fewer side effects than standard antidepressant drugs. Design: Systematic review and meta-analysis of trials revealed by searches. Trials: 23 randomised trials including a total of 1757 outpatients with mainly mild or moderately severe depressive disorders: 15 (14 testing single preparations and one a combination with other plant extracts) were placebo controlled, and eight (six testing single preparations and two combinations) compared hypericum with another drug treatment. Main outcome measures: A pooled estimate of the responder rate ratio (responder rate in treatment group/responder rate in control group), and numbers of patients reporting and dropping out for side effects. Results: Hypericum extracts were significantly superior to placebo (ratio = 2.67; 95% confidence interval 1.78 to 4.01) and similarly effective as standard antidepressants (single preparations 1.10; 0.93 to 1.31, combinations 1.52; 0.78 to 2.94). There were two (0.8%) drop outs for side effects with hypericum and seven (3.0%) with standard antidepressant drugs. Side effects occurred in 50 (19.8%) patients on hypericum and 84 (52.8%) patients on standard antidepressants. Conclusion: There is evidence that extracts of hypericum are more effective than placebo for the treatment of mild to moderately severe depressive disorders. Further studies comparing extracts with standard antidepressants in well defined groups of patients and comparing different extracts and doses are needed. Key messages There is evidence from randomised trials that such extracts are more effective than placebo for the treatment of depressive disorders, but it is not known whether they are more effective for certain disorders than others Current evidence is inadequate to establish whether hypericum is as effective as other antidepressants and if it has fewer side effects Additional trials should be conducted to compare hypericum with other antidepressants in well defined groups of patients; to investigate long term side effects; and to evaluate the relative efficacy of different preparations and doses

C reactive protein and its relation to cardiovascular risk factors: a population based cross sectional study.

Abstract: Objective: To test the hypothesis that minor chronic insults such as smoking, chronic bronchitis, and two persistent bacterial infections may be associated with increases in C reactive protein concentration within the normal range and that variations in the C reactive protein concentration in turn may be associated with levels of cardiovascular risk factors and chronic coronary heart disease. Design: Population based cross sectional study. Setting: General practices in Merton, Sutton, and Wandsworth. Subjects: A random sample of 388 men aged 50-69 years from general practice registers. 612 men were invited to attend and 413 attended, of whom 25 non-white men were excluded. The first 303 of the remaining 388 men had full risk factor profiles determined. Interventions: Measurements of serum C reactive protein concentrations by in house enzyme linked immunosorbent assay (ELISA); other determinations by standard methods. Coronary heart disease was sought by the Rose angina questionnaire and Minnesota coded electrocardiograms. Main outcome measures: Serum C reactive protein concentrations, cardiovascular risk factor levels, and the presence of coronary heart disease. Results: Increasing age, smoking, symptoms of chronic bronchitis, Helicobacter pylori and Chlamydia pneumoniae infections, and body mass index were all associated with raised concentrations of C reactive protein. C Reactive protein concentration was associated with raised serum fibrinogen, sialic acid, total cholesterol, triglyceride, glucose, and apolipoprotein B values. C Reactive protein concentration was negatively associated with high density lipoprotein cholesterol concentration. There was a weaker positive relation with low density lipoprotein cholesterol concentration and no relation with apolipoprotein A I value. C Reactive protein concentration was also strongly associated with coronary heart disease. Conclusion: The body9s response to inflammation may play an important part in influencing the progression of atherosclerosis. The association of C reactive protein concentration with coronary heart disease needs testing in prospective studies. Key messages Factors that determine levels of inflammatory mediators in the normal general population have not been explored, nor has their relation to cardio- vascular risk factors Among 50-69 year old men many environmental and lifestyle risk factors for cardiovascular disease are associated with raised serum concentrations of C reactive protein Circulating concentrations of lipids, glucose, and clotting factors are also associated with serum C reactive protein concentrations The body9s response to inflammation may influence the development of atherosclerosis

Detecting skewness from summary information.

Abstract: PIP: Many statistical methods of analysis assume that the data have a normal distribution When the data do not, they can often be changed to make them more normal However, readers of published papers may wish to be certain that the authors have conducted a proper analysis One can clearly see whether the distributional assumption is met when data are presented in the form of a histogram or scatter diagram However, when only summary statistics are presented, the task becomes far more difficult An idea of the distribution can be gleaned if the summary statistics include the range of the data For example, a range from 7 to 41 around a mean of 15 suggests that the data are positively skewed Belief in that assumption may be unreliable because the range is based upon the two most extreme, and atypical, values Similar asymmetry affecting the lower and upper quartiles would better indicate a skewed distribution it is suggested that for measurements which must be positive, if the mean is smaller than twice the standard deviation, the data are likely to be skewed A second indicator of skewness can be used when there are data for several groups of individuals Deviations from the normal distribution and a relation between the standard deviation and mean across groups often go together A standard deviation which increases as the mean increases is a strong indication of positively skewed data, and specifically that a log transformation may be needed

Impaired lung function and mortality risk in men and women: findings from the Renfrew and Paisley prospective population study

Abstract: Objective : To assess the relation between forced expiratory volume in one second (FEV1) and subsequent mortality. Design : Prospective general population study. Setting : Renfrew and Paisley, Scotland. Subjects : 7058 men and 8353 women aged 45-64 years at baseline screening in 1972-6. Main outcome measure : Mortality from all causes, ischaemic heart disease, cancer, lung and other cancers, stroke, respiratory disease, and other causes of death after 15 years of follow up. Results : 2545 men and 1894 women died during the follow up period. Significant trends of increasing risk with diminishing FEV1 are apparent for both sexes for all the causes of death examined after adjustment for age, cigarette smoking, diastolic blood pressure, cholesterol concentration, body mass index, and social class. The relative hazard ratios for all cause mortality for subjects in the lowest fifth of the FEV1 distribution were 1.92 (95% confidence interval 1.68 to 2.20) for men and 1.89 (1.63 to 2.20) for women. Corresponding relative hazard ratios were 1.56 (1.26 to 1.92) and 1.88 (1.44 to 2.47) for ischaemic heart disease, 2.53 (1.69 to 3.79) and 4.37 (1.84 to 10.42) for lung cancer, and 1.66 (1.07 to 2.59) and 1.65 (1.09 to 2.49) for stroke. Reduced FEV1 was also associated with an increased risk for each cause of death examined except cancer for lifelong nonsmokers. Conclusions : Impaired lung function is a major clinical indicator of mortality risk in men and women for a wide range of diseases. The use of FEV1 as part of any health assessment of middle aged patients should be considered. Smokers with reduced FEV1 should form a priority group for targeted advice to stop smoking. Key messages These increased risks, with the exception of the cancers, are apparent for lifelong non-smokers FEV1 is second in importance to cigarette smoking as a predictor of subsequent all cause mortality and is as important as cholesterol in predicting mortality from ischaemic heart disease FEV1 should be included in health assessment of middle aged men and women Smokers with a reduced FEV1 should be targeted with advice to stop smoking

Statistics notes: Measurement error

Abstract: Several measurements of the same quantity on the same subject will not in general be the same. This may be because of natural variation in the subject, variation in the measurement process, or both. For example, table 1 shows four measurements of lung function in each of 20 schoolchildren (taken from a larger study1). The first child shows typical variation, having peak expiratory flow rates of 190, 220, 200, and 200 l/min. View this table: Table 1 Repeated peak expiratory flow rate (PEFR) measurements for 20 schoolchildren Let us suppose that the child has a “true” average value over all possible measurements, which is what we really want to know when we make a measurement. Repeated measurements on the same subject will vary around the true value because of measurement error. The standard deviation of repeated measurements on the same subject …

Income distribution and mortality: cross sectional ecological study of the Robin Hood index in the United States

Abstract: Objective : To determine the effect of income inequality as measured by the Robin Hood index and the Gini coefficient on all cause and cause specific mortality in the United States. Design : Cross sectional ecological study. Setting : Households in the United States. Main outcome measures : Disease specific mortality, income, household size, poverty, and smoking rates for each state. Results : The Robin Hood index was positively correlated with total mortality adjusted for age (r=0.54; P Conclusion : Variations between states in the inequality of income were associated with increased mortality from several causes. The size of the gap between the wealthy and less well off—as distinct from the absolute standard of living enjoyed by the poor—seems to matter in its own right. The findings suggest that policies that deal with the growing inequities in income distribution may have an important impact on the health of the population. Key messages The size of the gap between the wealthy and less well off—as distinct from the absolute standard of living enjoyed by the poor—seems to be related to mortality Policies that deal with the growing inequities in income distribution may have a considerable impact on the health of the population

Intersalt revisited: further analyses of 24 hour sodium excretion and blood pressure within and across populations

Abstract: Objectives: To assess further the relation in Intersalt of 24 hour urinary sodium to blood pressure of individuals and populations, and the difference in blood pressure from young adulthood into middle age Design: Standardised cross sectional study within and across populations Setting: 52 population samples in 32 countries Subjects: 10 074 men and women aged 20-59 Main outcome measures: Association of sodium and blood pressure from within population and cross population multiple linear regression analyses with multivariate correction for regression dilution bias Relation of sample median daily urinary sodium excretion to difference in blood pressure with age Results: In within population analyses (n=10 074), individual 24 hour urinary sodium excretion higher by 100 mmol (for example, 170 v 70 mmol) was associated with systolic/diastolic blood pressure higher on average by 3/0 to 6/3 mm Hg (with and without body mass in analyses) Associations were larger at ages 40-59 In cross population analyses (n=52), sample median 24 hour sodium excretion higher by 100 mmol was associated with median systolic/diastolic pressure higher on average by 5-7/2-4 mm Hg, and estimated mean difference in systolic/diastolic pressure at age 55 compared with age 25 greater by 10-11/6 mm Hg Conclusions: The strong, positive association of urinary sodium with systolic pressure of individuals concurs with Intersalt cross population findings and results of other studies Higher urinary sodium is also associated with substantially greater differences in blood pressure in middle age compared with young adulthood These results support recommendations for reduction of high salt intake in populations for prevention and control of adverse blood pressure levels Key messages The within population findings were previously underestimated because of incomplete correction for the regression dilution problem Revised estimates of the within population association of sodium to blood pressure in Intersalt are concordant with the cross population findings for 52 samples Estimates of the effect of median sodium excretion higher by 100 mmol/day over a 30 year period (age 55 minus age 25) were a greater difference of 10-11 mm Hg in systolic blood pressure and 6 mm Hg in diastolic blood pressure These results lend further support to recommendations for mass reduction of high salt intake for the prevention and control of adverse blood pressure levels and high blood pressure in populations

Variability in risk of gastrointestinal complications with individual non-steroidal anti-inflammatory drugs: results of a collaborative meta-analysis.

Abstract: Objective: To compare the relative risks of serious gastrointestinal complications reported with individual non-steroidal anti-inflammatory drugs. Design: Systematic review of controlled epidemiological studies that found a relation between use of the drugs and admission to hospital for haemorrhage or perforation. Setting: Hospital and community based casecontrol and cohort studies. Main outcome measures: (a) Estimated relative risks of gastrointestinal complications with use of individual drugs, exposure to ibuprofen being used as reference; (b) a ranking that best summarised the sequence of relative risks observed in the studies. Results: 12 studies met the inclusion criteria. 11 provided comparative data on ibuprofen and other drugs. Ibuprofen ranked lowest or equal lowest for risk in 10 of the 11 studies. Pooled relative risks calculated with exposure to ibuprofen used as reference were all significantly greater than 1.0 (interval of point estimates 1.6 to 9.2). Overall, ibuprofen was associated with the lowest relative risk, followed by diclofenac. Azapropazone, tolmetin, ketoprofen, and piroxicam ranked highest for risk and indomethacin, naproxen, sulindac, and aspirin occupied intermediate positions. Higher doses of ibuprofen were associated with relative risks similar to those with naproxen and indomethacin. Conclusions: The low risk of serious gastrointestinal complications with ibuprofen seems to be attributable mainly to the low doses of the drug used in clinical practice. In higher doses ibuprofen is associated with a similar risk to other non-steroidal anti-inflammatory drugs. Use of low risk drugs in low dosage as first line treatment would substantially reduce the morbidity and mortality due to serious gastrointestinal toxicity from these drugs. Key messages Because there are no important differences in efficacy, choice of first line treatment with these drugs should be based on their relative toxicity Meta-analysis of the available epidemiological studies shows wide differences between individual drugs in the risk of inducing gastrointestinal bleed- ing and ulcer perforation Of the drugs in common use, ibuprofen and diclofenac rank low in toxicity whereas azapropa- zone, ketoprofen, and piroxicam rank high Some of the differences between drugs may be explained by dose, and the advantage of “low risk” drugs may be lost once their dose is increased

Misdiagnosis of the vegetative state: retrospective study in a rehabilitation unit.

Abstract: Objective: To identify the number of patients who were misdiagnosed as being in the vegetative state and their characteristics. Design: Retrospective study of the clinical records of the medical, occupational therapy, and clinical psychology departments. Setting: 20 bed unit specialising in the rehabilitation of patients with profound brain damage, including the vegetative state. Subjects: 40 patients admitted between 1992 and 1995 with a referral diagnosis of vegetative state. Outcome measures: Patients who showed an ability to communicate consistently using eye pointing or a touch sensitive single switch buzzer. Results: Of the 40 patients referred as being in the vegetative state, 17 (43%) were considered as having been misdiagnosed; seven of these had been presumed to be vegetative for longer than one year, including three for over four years. Most of the misdiagnosed patients were blind or severely visually impaired. All patients remained severely physically disabled, but nearly all were able to communicate their preference in quality of life issues–some to a high level. Conclusions: The vegetative state needs considerable skill to diagnose, requiring assessment over a period of time; diagnosis cannot be made, even by the most experienced clinician, from a bedside assessment. Accurate diagnosis is possible but requires the skills of a multidisciplinary team experienced in the management of people with complex disabilities. Recognition of awareness is essential if an optimal quality of life is to be achieved and to avoid inappropriate approaches to the courts for a declaration for withdrawal of tube feeding. Key messages Many patients who are misdiagnosed as being in the vegetative state are blind or have severe visual handicap; thus lack of eye blink to threat or absence of visual tracking are not reliable signs for diagnosing the vegetative state Any motor activity, no matter how slight, that can be used for communication by the profoundly disabled patient should be identified at an early stage and repeated at regular intervals Identification of awareness in the presence of profound and complex neurological disabilities requires the skills of a multidisciplinary team expe- rienced in long term management of disability due to brain damage

Relation of size at birth to non-insulin dependent diabetes and insulin concentrations in men aged 50-60 years

Abstract: Objective: To establish whether the relation between size at birth and non-insulin dependent diabetes is mediated through impaired β cell function or insulin resistance. Design: Cohort study. Setting: Uppsala, Sweden. Subjects: 1333 men whose birth records were traced from a cohort of 2322 men born during 1920-4 and resident in Uppsala in 1970. Main outcome measures: Intravenous glucose tolerance test at age 50 years and non-insulin dependent diabetes at age 60 years. Results: There was a weak inverse correlation (r=-0.07, P=0.03) between ponderal index at birth and 60 minute insulin concentrations in the intravenous glucose tolerance test at age 50 years. This association was stronger (r=-0.19, P=0.001) in the highest third of the distribution of body mass index than in the other two thirds (P=0.01 for the interaction between ponderal index and body mass index). Prevalence of diabetes at age 60 years was 8% in men whose birth weight was less than 3250 g compared with 5% in men with birth weight 3250 g or more (P=0.08; 95% confidence interval for difference −0.3% to 6.8%). There was a stronger association between diabetes and ponderal index: prevalence of diabetes was 12% in the lowest fifth of ponderal index compared with 4% in the other four fifths (P=0.001; 3.0% to 12.6%). Conclusion: These results confirm that reduced fetal growth is associated with increased risk of diabetes and suggest a specific association with thinness at birth. This relation seems to be mediated through insulin resistance rather than through impaired β cell function and to depend on an interaction with obesity in adult life.

Dietary fat and risk of coronary heart disease in men: cohort follow up study in the United States.

Abstract: Objective : To examine the association between fat intake and the incidence of coronary heart disease in men of middle age and older. Design : Cohort questionnaire study of men followed up for six years from 1986. Setting : The health professionals follow up study in the United States. Subjects : 43 757 health professionals aged 40 to 75 years free of diagnosed cardiovascular disease or diabetes in 1986. Main outcome measure : Incidence of acute myocardial infarction or coronary death. Results : During follow up 734 coronary events were documented, including 505 non-fatal myocardial infarctions and 229 deaths. After age and several coronary risk factors were controlled for significant positive associations were observed between intake of saturated fat and risk of coronary disease. For men in the top versus the lowest fifth of saturated fat intake (median = 14.8% v 5.7% of energy) the multivariate relative risk for myocardial infarction was 1.22 (95% confidence interval 0.96 to 1.56) and for fatal coronary heart disease was 2.21 (1.38 to 3.54). After ajustment for intake of fibre the risks were 0.96 (0.73 to 1.27) and 1.72 (1.01 to 2.90), respectively. Positive associations between intake of cholesterol and risk of coronary heart disease were similarly attenuated after adjustment for fibre intake. Intake of linolenic acid was inversely associated with risk of myocardial infarction; this association became significant only after adjustment for non-dietary risk factors and was strengthened after adjustment for total fat intake (relative risk 0.41 for a 1% increase in energy, P for trend Conclusions : These data do not support the strong association between intake of saturated fat and risk of coronary heart disease suggested by international comparisons. They are compatible, however, with the hypotheses that saturated fat and cholesterol intakes affect the risk of coronary heart disease as predicted by their effects on blood cholesterol concentration. They also support a specific preventive effect of linolenic acid intake. Key messages Diets high in saturated fat and cholesterol are associated with an increased risk of coronary disease, but these adverse effects are at least in part explained by their low fibre content and associations with other risk factors Diets high in linolenic acid (N-3 fatty acid from plants) are associated with a reduced risk of coronary heart disease, independently of other dietary and non-dietary risk factors Uncertainty remains on the optimal amount of polyunsaturated fat in the diet for prevention of coronary heart disease Benefits of reducing intakes of saturated fat and cholesterol are likely to be modest unless accompanied by an increased consumption of foods rich in fibre

A primer on leading the improvement of systems.

Abstract: The nurse called me urgently into the room. The child, she said, was in acute respiratory distress. I had never met either Jimmy (the 6 year old boy) or his mother (an inner city single teenage parent) before. His asthma attack was severe, his peak expiratory flow rate only 35% of normal. Twenty years ago my next steps would have been to begin bronchodilator treatment, call an ambulance, and send the boy to hospital. That also would have been the story 10 years ago, or five, or two. But today, when I entered the room, the mother handed me her up to date list of treatments, including nebuliser treatment with β2 agonists, that she had administered with equipment that had been installed in her home. It continued with her graph of Jimmy's slowly improving peak flow levels, which she had measured and charted at home, having been trained by the asthma outreach nurse. She then gave me the nurse's cellular telephone number, along with a specific recommendation on the next medication to try for her son, one that had worked in the past but was not yet available for her to use at home. My reply was interrupted by a knock on my door. It was the chief of the allergy department in my health maintenance organisation. He worked one floor above me in the health centre and, having been phoned by the outreach nurse, had decided to “pop down” to see if he could help. He also handed me a phial of the same new medication that the mother had just mentioned, suggesting that we try it. Two hours later Jimmy was not in a hospital bed; he was at home breathing comfortably. Just to be safe the allergy nurse would be paying him a visit later that afternoon. …

Physical activity and health

Abstract: “Of all the causes which conspire to render the life of man short and miserable, none have greater influence than the want of proper exercise.”1 Recent epidemiological and clinical evidence support this observation by the 18th century Scottish physician Dr William Buchan. Studies suggest causal associations between regular physical activity and reduced rates of coronary heart disease, hypertension, non-insulin dependent diabetes mellitus, osteoporosis, colon cancer, anxiety, and depression.2 The most persuasive proof concerns coronary heart disease. People who are regularly active have about half the risk of those who are sedentary.3 4 Unfortunately, in the United States, Britain, and most other developed nations fewer than half of adults are regularly active.5 6 7 An estimated third of deaths from coronary heart disease in the United States (about 160 000 deaths per year) are attributable to insufficient physical activity.8 In response to the accumulated research and the widespread recognition that physical inactivity is a major public health issue, the United States National Institutes of Health convened a consensus development conference on physical activity and cardiovascular health last December. After two and a half days of scientific presentations and public …

Genetic influences on osteoarthritis in women: a twin study

Abstract: Objectives: To assess the relative contribution of genetic and environmental factors to common forms of osteoarthritis of the hands and knees Design: Classic twin study with unselected twins who were screened radiologically for osteoarthritis Subjects: 130 identical and 120 non-identical female twins aged 48-70 recruited from a London based twin register and through a national media campaign Main outcome measures: Similarity in identical compared with non-identical twin pairs for radiographic changes at the interphalangeal and first carpometacarpal joints of the hands and the tibiofemoral joint and patellofemoral joint of the knee expressed as intraclass correlations Results: The intraclass correlations of radiographic osteophytes and narrowing at most sites and the presence of Heberden9s nodes and knee pain were higher in the identical pairs The intraclass correlation of the total radiographic osteoarthritis score in identical pairs (rMZ) was 064 (SE 005) compared with 038 (008) in non-identical pairs The proportion of genetic variance of total osteoarthritis score (osteophytes and narrowing) with modelling techniques was estimated at 054 (95% confidence interval 043 to 065) and ranged from 039 to 065 for different sites and features (P Conclusions: These results demonstrate for the first time a clear genetic effect for radiographic osteoarthritis of the hand and knee in women, with a genetic influence ranging from 39-65%, independent of known environmental or demographic confounders The results of this study should lead to further work on isolating the gene or genes involved in the pathogenesis of this common disabling disease Key messages Key messages Although environmental factors have traditionally been thought to be the main influences, there are few data to support this Between 39% and 65% of osteoarthritis in the general population can be attributed to genetic factors Identification of the genes concerned could have a large impact on the disease in terms of prevention and new therapeutic approaches

Role of patients' view of their illness in predicting return to work and functioning after myocardial infarction: longitudinal study

Abstract: Objective: To examine whether patients9 initial perceptions of their myocardial infarction predict subsequent attendance at a cardiac rehabilitation course, return to work, disability, and sexual dysfunction. Design: Patients9 perceptions of their illness were measured at admission with their first myocardial infarction and at follow up three and six months later. Setting: Two large teaching hospitals in Auckland, New Zealand. Subjects: 143 consecutive patients aged under 65 with their first myocardial infarction. Main outcome measures: Attendance at rehabilitation course; time before returning to work; measures of disability with sickness impact profile questionnaire for sleep and rest, social interaction, recreational activity, and home management; and sexual dysfunction. Results: Attendance at the rehabilitation course was significantly related to a stronger belief during admission that the illness could be cured or controlled (t=2.08, P=0.04). Return to work within six weeks was significantly predicted by the perception that the illness would last a short time (t=-2.52, P=0.01) and have less grave consequences for the patient (t=-2.87, P=0.005). Patients9 belief that their heart disease would have serious consequences was significantly related to later disability in work around the house, recreational activities, and social interaction. A strong illness identity was significantly related to greater sexual dysfunction at both three and six months. Conclusions: Patients9 initial perceptions of illness are important determinants of different aspects of recovery after myocardial infarction. Specific illness perceptions need to be identified at an early stage as a basis for optimising outcomes from rehabilitation programmes. Key messages Patients9 beliefs about their illness seem to influence recovery and rehabilitation on discharge from hospital Patients9 ideas about their illness cluster around five cognitive dimensions: identity, cause, time line, consequences, and beliefs about cure or control In this study a belief that the illness could be controlled or cured was related to subsequent attendance at a cardiac rehabilitation course. Perceptions that the illness would last a long time and have serious consequences were associated with a longer delay before returning to work The early identification of illness perceptions could improve the outcome of cardiac rehabilitation programmes

Incidence and prognosis of asthma and wheezing illness from early childhood to age 33 in a national British cohort

Abstract: Objective: To describe the incidence and prognosis of wheezing illness from birth to age 33 and the relation of incidence to perinatal, medical, social, environmental, and lifestyle factors. Design: Prospective longitudinal study. Setting: England, Scotland, and Wales. Subjects: 18 559 people born on 3-9 March 1958. 5801 (31%) contributed information at ages 7, 11, 16, 23, and 33 years. Attrition bias was evaluated using information on 14 571 (79%) subjects. Main outcome measure: History of asthma, wheezy bronchitis, or wheezing obtained from interview with subjects9 parents at ages 7, 11, and 16 and reported at interview by subjects at ages 23 and 33. Results: The cumulative incidence of wheezing illness was 18% by age 7, 24% by age 16, and 43% by age 33. Incidence during childhood was strongly and independently associated with pneumonia, hay fever, and eczema. There were weaker independent associations with male sex, third trimester antepartum haemorrhage, whooping cough, recurrent abdominal pain, and migraine. Incidence from age 17 to 33 was associated strongly with active cigarette smoking and a history of hay fever. There were weaker independent associations with female sex, maternal albuminuria during pregnancy, and histories of eczema and migraine. Maternal smoking during pregnancy was weakly and inconsistently related to childhood wheezing but was a stronger and significant independent predictor of incidence after age 16. Among 880 subjects who developed asthma or wheezy bronchitis from birth to age 7, 50% had attacks in the previous year at age 7; 18% at 11, 10% at 16, 10% at 23, and 27% at 33. Relapse at 33 after prolonged remission of childhood wheezing was more common among current smokers and atopic subjects. Conclusion: Atopy and active cigarette smoking are major influences on the incidence and recurrence of wheezing during adulthood. Key messages Incidence of wheezing illness at all ages was strongly and consistently related to a history of hay fever or eczema (atopy). Associations with maternal smoking during pregnancy, abdominal pain, and migraine were largely confined to those without atopy Active smoking was a powerful and potentially avoidable risk factor for wheeze starting in adult life among both atopic and non-atopic subjects A quarter of the children with a history of asthma or wheezy bronchitis by age 7 reported wheeze in the past year at age 33 Recurrence of wheezing after prolonged remis- sion during late adolescence was strongly associ- ated with atopy and cigarette smoking.

Maternal nutrition in early and late pregnancy in relation to placental and fetal growth

Abstract: Objective: To assess how nutrient intakes of mothers in early and late pregnancy influence placental and fetal growth. Design: Prospective observational study. Setting: Princess Anne Maternity Hospital, Southampton. Subjects: 538 mothers who delivered at term. Main outcome measures: Placental and birth weights adjusted for the infant9s sex and duration of gestation. Results: Mothers who had high carbohydrate intakes in early pregnancy had babies with lower placental and birth weights. Low maternal intakes of dairy and meat protein in late pregnancy were also associated with lower placental and birth weights. Placental weight fell by 49 g (95% confidence interval 16 g to 81 g; P=0.002) for each log g increase in intake of carbohydrate in early pregnancy and by 1.4 g (0.4 g to 2.4 g; P=0.005) for each g decrease in intake of dairy protein in late pregnancy. Birth weight fell by 165 g (49 g to 282 g; P=0.005) for each log g increase in carbohydrate intake in early pregnancy and by 3.1 g (0.3 g to 6.0 g; P=0.03) for each g decrease in meat protein intake in late pregnancy. These associations were independent of the mother9s height and body mass index and of strong relations between the mother9s birth weight and the placental and birth weights of her offspring. Conclusion: These findings suggest that a high carbohydrate intake in early pregnancy suppresses placental growth, especially if combined with a low dairy protein intake in late pregnancy. Such an effect could have long term consequences for the offspring9s risk of cardiovascular disease.

Measurement error and correlation coefficients.

Abstract: Measurement error is the variation between measurements of the same quantity on the same individual.1 To quantify measurement error we need repeated measurements on several subjects. We have discussed the within-subject standard deviation as an index of measurement error,1 which we like as it has a simple clinical interpretation. Here we consider the use of correlation coefficients to quantify measurement error. A common design for the investigation of measurement error is to take pairs of measurements on a group of subjects, as in table 1. When we have pairs of observations it is natural to plot one measurement against the other. The resulting scatter diagram (see figure 1 may tempt us to calculate a correlation coefficient between the first and second measurement. There are difficulties in interpreting this correlation coefficient. In general, the correlation between repeated measurements will depend on the variability between subjects. Samples containing subjects who differ greatly will produce larger correlation coefficients than will samples containing similar …

Compliance therapy in psychotic patients: randomised controlled trial

Abstract: Objective: To determine whether compliance therapy, a cognitive-behavioural intervention, could improve compliance with treatment and hence social adjustment in acutely psychotic inpatients, and if so, whether the effect persisted six months later. Design: Randomised controlled trial of compliance therapy and non-specific counselling, each comprising 4-6 sessions lasting 10-60 minutes. Setting: Acute psychiatric admissions ward serving an inner London catchment area. Subjects: 47 patients with psychosis. Main outcome measures: Informant and observer reported measure of compliance; observer assessed global functioning after intervention and three and six months later; self rated attitudes to drug treatment after the intervention and one month later; symptom scores after intervention and six months later. Results: 25 patients received compliance therapy and showed significantly greater improvements in their attitudes to drug treatment and in their insight into illness and compliance with treatment compared with the control group. These gains persisted for six months. The intervention group was 5.2 times more likely than the control group to reach a criterion level of compliance (95% confidence interval 1.5 to 18.3). Global functioning showed a tendency to improve more in the intervention group after a delay (odds ratio 3.0 (0.8 to 11.5) to reach the criterion level at six months). Four subjects given compliance therapy and six in the control group were readmitted during follow up (odds ratio 2.0 (0.48 to 8.2)). Conclusions: Compliance therapy is a pragmatic method for improving compliance with drug treatment in psychotic inpatients and its gains persist for at least six months. Overall functioning may also be enhanced. Key messages Key messages Compliance is strongly related to attitudes to treatment and to insight The study found that such attitudes may be influenced by a simple and brief intervention known as compliance therapy Compliance therapy compared with non-specific counselling leads to improved compliance The improvement is sustained for at least six months and may lead to improved social functioning

Information needs of cancer patients in west Scotland: cross sectional survey of patients' views.

Abstract: Objective: To assess the needs of patients with cancer for information about their condition. Design: Cross sectional survey of patients9 views by means of semistructured interview with questionnaire. Setting: A regional cancer centre and two university hospitals in west Scotland. Subjects: 250 (93%) of 269 cancer patients invited to participate in study who were selected by age, sex, socioeconomic status, and tumour site to be representative of cancer patients in west Scotland. Main outcome measures: Patients9 need to know whether they had cancer, the medical name of their illness, progress through treatment, how treatment works, side effects, chances of cure, and treatment options. Results: 79% (95% confidence interval 73% to 84%) of patients wanted as much information as possible, and 96% (93% to 98%) had a need or an absolute need to know if they had cancer. Most patients also wanted to know the chance of cure (91% (87% to 94%)) and about side effects of treatment (94% (90% to 97%)). When the replies were cross tabulated with patients9 age, sex, deprivation score, and type of treatment there was a linear trend for patients from more affluent areas to want more information and those from deprived areas to want less. There was a strong preference for diagnosis of cancer to be given by a hospital doctor (60% (53% to 66%). Conclusion: Almost all patients wanted to know their diagnosis, and most wanted to know about prognosis, treatment options, and side effects. Key messages We interviewed 250 patients with cancer to find out what information they wanted Almost all the patients wanted to know their diagnosis, and most also wanted to know the chance of cure and the side effects of their treatment Younger patients, women, and those receiving radical treatment in particular wanted to know more about treatment options The overwhelming preference was for the diagnosis of cancer to be given by a hospital doctor

What clinical information do doctors need

Abstract: Summary points Doctors use some two million pieces of information to manage patients, but little research has been done on the information needs that arise while treating patients Textbooks, journals, and other existing information tools are not adequate for answering the questions that arise: textbooks are out of date, and “the signal to noise” ratio of journals is too low for them to be useful in daily practice Computer systems that have been developed to help doctors are not widely used—perhaps because they have not been developed to meet doctors9 information needs When doctors see patients they usually generate at least one question; more questions arise than the doctors seem to recognise Most of the questions concern treatment Many of the questions are highly complex, simultaneously asking about individual patients and particular areas of medical knowledge Often doctors are asking not simply for information but for support, guidance, affirmation, and feedback Many of the questions go unanswered, but most could be answered; it is, however, time consuming and expensive to answer them Doctors are most likely to seek answers to these questions from other doctors The best information sources provide relevant, valid material that can be accessed quickly and with minimal effort New information tools are needed: they are likely to be electronic, portable, fast, easy to use, connected to both a large valid database of medical knowledge and the patient record, and a servant of patients as well as doctors

Better reporting of randomised controlled trials: the CONSORT statement

Abstract: Randomised controlled trials are the best way to compare the effectiveness of different interventions. Only randomised trials allow valid inferences of cause and effect. Only randomised trials have the potential directly to affect patient care—occasionally as single trials but more often as the body of evidence from several trials, whether or not combined formally by meta-analysis. It is thus entirely reasonable to require higher standards for papers reporting randomised trials than those describing other types of study. Like all studies, randomised trials are open to bias if done badly.1 It is thus essential that randomised trials are done well and reported adequately. Readers should not have to infer what was probably done, they should be told explicitly. Proper methodology should be used and be seen to have been used. Yet reviews of published trials have consistently found major deficiencies in reporting,2 3 4 making the task …