The aprotinin saga and the risks of conducting meta-analyses on small randomised controlled trials – a critique of a Cochrane review

<p>Abstract</p> <p>Background</p> <p>Aprotinin for reducing blood loss during coronary artery bypass surgery was withdrawn from the market after early termination of a large randomised controlled trial (RCT) showing excess mortality for patients receiving aprotinin compared to lysine analogues. Several meta-analyses of small RCTs did not show excess mortality and even indicated reduced mortality, while several observational studies showed excess mortality. The aim of this paper is to review the quality of the meta-analysis of a Cochrane report.</p> <p>Methods</p> <p>The 52 studies included in the meta-analysis of the Cochrane report were reviewed according to whether an objective to study mortality was formulated in advance, whether follow-up method or time were specified, and whether the study had statistical power to show any effect.</p> <p>Results</p> <p>The Cochrane report restricted the analysis to RCTs, but the largest study should not have been included given that it was a prospective observational study with 1 784 patients rather than an RCT. None of the RCTs had sufficient statistical power to detect differences in mortality. Most studies had fewer than 100 patients. Seven out of 51 RCTs had mortality outcome as one of their objectives. Only very few described follow-up method or time.</p> <p>Conclusion</p> <p>It is doubtful whether small studies should be included in meta-analyses if they do not have the purpose of studying the specified outcome and if the follow-up method or time are not adequately described. The aprotinin saga shows overconfidence in small RCTs of inferior quality compared to well-conducted observational studies.</p

Improved survival in both men and women with diabetes between 1980 and 2004 – a cohort study in Sweden

<p>Abstract</p> <p>Background</p> <p>In Sweden, diabetes prevalence is increasing in spite of unchanged incidence, indicating improved survival. In recent US studies mortality in diabetic subjects has decreased over three decades, but only in men. Our aim was to study mortality over time in diabetic subjects.</p> <p>Methods</p> <p>The annual Swedish Living Conditions Survey from 1980 to 2004 has been record-linked to the Cause of Death Register in order to study trends in mortality risk for those reporting diabetes as a chronic illness. Survival and the relative mortality risk within 5 years of follow-up have been calculated for a random sample of men and women aged 40–84 years with (n = 3,589) and without diabetes (n = 85,685) for the period 1980 to 2004. Poisson regression models were used.</p> <p>Results</p> <p>The age-adjusted mortality risk relative to non-diabetics within 5 years of follow-up for men was doubled during all periods. The relative risk for women was initially about 2.5, with a substantial drop in mortality in 1995–1999 to 1.45 although it increased to 1.90 in the last period. Using models that took into consideration the presence of heart disease, hypertension, daily smoking, and socio-economic status at the initial interview did not change the relative mortality risk. The age-adjusted 10-year observed survival rate for men with diabetes increased from 41.4% 1980–1984 to 51.5% in 1995–1999. The observed survival for women increased from 43.7% to 61.0%.</p> <p>Conclusion</p> <p>Survival rates have improved in subjects with diabetes since the early 1980s, more so in women than in men, thereby decreasing the gap to non-diabetic women.</p

Epidemiologisk forskning om barn – vad har gjorts och vad kan göras?

Sverige har en unik internationell konkurrensfördel genom tillgången på personnummer och heltäckande register. Inte minst ger detta en möjlighet att följa hälsoutvecklingen longitudinellt från födelsen och framåt. I denna artikel ges ett antal exempel på epidemiologiska stu- dier som bedrivits kring barn och ungdomar i Sverige. Dessa studier har haft en hög kvalitet och gett många intressanta resultat. Trots detta är potentialen inte utnyttjad till fullo. Artikeln tar därför också upp en del förslag till framtida epidemiologiska studier om barn och ungdomar, bl.a. behovet av att mäta barns- och ungdomars psykiska hälsa.

Does productivity influence priority setting? A case study from the field of CVD prevention.

In this case study, different measures aimed at preventing cardiovascular diseases (CVD) in different target groups have been ranked based on cost per QALY from a health care sector perspective and from a societal perspective, respectively. The innovation in this study is to introduce a budget constraint and thereby show exactly which groups would be included or excluded in treatment or intervention programs based on the two perspectives. Approximately 90% of the groups are included in both perspectives. Mainly elderly women are excluded when the societal perspective is used and mainly middle-aged men are excluded when the health care sector perspective is used. Elderly women have a higher risk of CVD and generally lower income than middle-aged men. Thus the exclusion of older women in the societal perspective is not a trivial consequence since it is in conflict with the general interpretation of the "treatment according to need" rule, as well as societal goals regarding gender equality and fairness. On the other hand, the exclusion of working individuals in the health care perspective undermines a growth of public resources for future health care for the elderly. The extent and consequences of this conflict are unclear and empirical studies of this problem are rare

Premature mortality among lone fathers and childless men

This study focuses on male family situation and premature mortality. For a total of 682,919 men, we analysed mortality from different causes (1991-2000) among lone fathers, with and without custody of their children, and among childless men, with and without partners. Long-term cohabiting fathers with a child in their household were used as comparison group. We employed data from Swedish censuses, national health-data registers, and a Swedish register containing information about known biological relations between children and parents. We investigated the extent to which different kinds of relations were influenced by varying socioeconomic circumstances between groups, and also processes of health selection. The results suggest that lone non-custodial fathers and lone childless men face the greatest increase in risks, especially from injury and addiction, and also from all-cause mortality and ischaemic heart disease. Being a lone custodial father also entails increased risk, although generally to a much lesser extent, and not for all outcomes. The elevated risks found in all the subgroups considered diminished substantially when proxy variables to control for health-selection effects and socioeconomic circumstances were added to the initial model. Risks fell most in response to introduction of the socioeconomic variables, but health selection also played a major role, mostly in the cases of lone non-custodial fathers and lone childless men. However, even following these adjustments, significant risk increases, although greatly attenuated, remained for all the subgroups.Lone parent Single father Mortality Injury Socioeconomic status Family status Health selection Sweden