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International time trends in asthma mortality have been strongly affected by changes in management and in particular drug treatments. However, little is known about how asthma mortality has changed over the past decade. In this study, we assessed these international trends. We collated age-standardised country-specific asthma mortality rates in the 5–34 year age group from the online WHO Mortality Database for 46 countries. To be included in the analysis, we specified that a country must have 10 years of complete data in the WHO Mortality Database between 1993 and 2012. In the absence of consistent and accurate asthma prevalence and prescribing data, we chose to use a locally weighted scatter plot smoother (LOESS) curve, weighted by the individual country population in the 5–34-year age group to show the global trends in asthma mortality rates with time. Of the 46 countries included in the analysis of asthma mortality, 36 were high-income countries, and 10 were middle-income countries. The LOESS estimate of the global asthma mortality rate was 0·44 deaths per 100 000 people (90% CI 0·39–0·48) in 1993 and 0·19 deaths per 100 000 people (0·18–0·21) in 2006. Despite apparent further reductions in some countries and regions of the world, there was no appreciable change in global asthma mortality rates from 2006 through to 2012, when the LOESS estimate was also 0·19 deaths per 100 000 people (0·16–0·21). The trend for reduction in global asthma mortality observed since the late 1980s might have stalled, with no appreciable difference in a smoothed LOESS curve of asthma mortality from 2006 to 2012. Although better implementation of established management strategies that have been shown to reduce mortality risk is needed, to achieve a further substantive reduction in global asthma mortality novel strategies will also be required. The Medical Research Institute of New Zealand, which is supported by Health Research Council of New Zealand Independent Research Organisation.

This paper provides an account of a specific operation – the removal of the thymus gland (thymectomy) to treat the rare neurological condition myasthenia gravis – from its first performance in 1936, by the American surgeon Alfred Blalock, to the publication in 2016 of an international multicentre randomised controlled trial (RCT) of the technique. Thymectomy was the subject of a transatlantic controversy in the 1950s, in which the main players were the English surgeon Geoffrey Keynes, and American neurologists and surgeons from New York, Boston, and the Mayo Clinic. The resolution of this controversy involved the use of increasingly sophisticated statistical techniques, but also crucially other influences including the social transformation of thoracic surgery, and competition between the leading American centres. The consensus achieved after this controversy was challenged in the late 1970s, eventually prompting the implementation of a trial acceptable to twenty-first-century evidence-based medicine. This account will demonstrate that surgical innovation in the period covered required increasing attention to the statistical basis of patient selection and outcome evaluation; that the processes of technical innovation cannot be regarded as separate from developments in the professional culture of surgery, and that one of the consequences of these changes has been the gradual eclipse of the prestigious autonomous surgeon.

Abstract The Global Initiative for Asthma guidelines use the traditional terminology of “low,” “medium,” and “high” doses of inhaled corticosteroids (ICS) to define daily maintenance doses of 100 to 250 μg, >250 to 500 μg, and >500 μg, respectively, of fluticasone propionate or equivalent for adults with asthma. This concise clinical review proposes that this terminology is not evidence based and that prescribing practice based on this terminology may lead to the use of inappropriately excessive doses of ICS. Specifically, the ICS dose that achieves 80–90% of the maximum obtainable benefit is currently classified as a low dose, with the description of two higher dose levels of medium and high, which are associated with significant risk of systemic adverse effects. Asthma guidelines and clinician prescribing practice need to be modified in accordance with the currently available evidence of the dose–response relationship of ICS in adult asthma. We propose a reclassification of ICS doses based on a “standard daily dose,” which is defined as 200–250 μg of fluticasone propionate or equivalent, representing the dose at which approximately 80–90% of the maximum achievable therapeutic benefit of ICS is obtained in adult asthma across the spectrum of severity. It is recommended that ICS treatment be started at these standard doses, which then represent the doses at which maintenance ICS are prescribed at step 2 and within ICS/long-acting β-agonist combination therapy at step 3. The opportunity is available to prescribe higher doses within ICS/long-acting β-agonist maintenance therapy in accordance with the stepwise approach to asthma treatment at step 4.

Background In the last decade several authors have reviewed the features of pilot and feasibility studies and advised on the issues that should be addressed within them. We extend this literature by examining published pilot/feasibility trials that incorporate random allocation, examining their stated objectives, results presented and conclusions drawn, and comparing drug and non-drug trials. Methods A search of EMBASE and MEDLINE databases for 2000 to 2009 revealed 3652 papers that met our search criteria. A random sample of 50 was selected for detailed review. Results Most of the papers focused on efficacy: those reporting drug trials additionally addressed safety/toxicity; while those reporting non-drug trials additionally addressed methodological issues. In only 56% (95% confidence intervals 41% to 70%) were methodological issues discussed in substantial depth, 18% (95% confidence interval 9% to 30%) discussed future trials and only 12% (95% confidence interval 5% to 24%) of authors were actually conducting one. Conclusions Despite recent advice on topics that can appropriately be described as pilot or feasibility studies the large majority of recently published papers where authors have described their trial as a pilot or addressing feasibility do not primarily address methodological issues preparatory to planning a subsequent study, and this is particularly so for papers reporting drug trials. Many journals remain willing to accept the pilot/feasibility designation for a trial, possibly as an indication of inconclusive results or lack of adequate sample size.

Objective To determine the Physical Component Summary (PCS) score's minimal clinically important difference (MCID) on the Short Form 36 (SF-36) for people with stroke. Methods We conducted secondary analysis of data from a large randomized controlled trial (N = 400) in the post-hospital discharge phase of stroke rehabilitation with outcome measurement 6 and 12 months following stroke. Three methods were used for estimating the MCID: two anchor and one distribution. Method 1 compared SF-36 PCS scores at 12 months for responses to the SF-36’s Perceived Health Change (PHC) question. Method 2 compared the change in PCS score between 6 and 12 months for responses to the PHC question. Method 3 used Cohen’s method to estimate the MCID from the PCS score distribution. Results Method 1: the mean PCS score increased by 3.0 units (95% confidence interval [CI] 2.2–3.9) for each unit change in the PHC question. Method 2: the mean change in PCS score increased by 2.1 units (95% CI 1.4–2.8) for each unit change in the PHC question. Method 3: the MCID was estimated to be 1.8 units. Conclusions Our estimate of the MCID for the PCS in patients with stroke was 1.8 to 3.0 units.

International guidelines recommend the routine use of oxygen in the initial treatment of myocardial infarction, yet it is uncertain what effect this might have on physiologic and clinical outcomes. We undertook a systematic search of Medline, Cochrane Database of Systematic Reviews, EMBASE, and CINHAL using the key words “oxygen,” “coronary blood flow,” “hyperoxia,” and “coronary circulation” to identify human studies involving a measure of coronary blood flow while breathing oxygen and room air. The primary outcome measure was coronary blood flow; secondary outcomes included coronary vascular resistance and myocardial oxygen consumption. From 2,072 potential publications, there were 6 studies from 4 publications that met the inclusion criteria, with 6 healthy subjects and 61 subjects with cardiac disease. It was not possible to undertake a meta-analysis due to methodological limitations. In the 6 studies, high-concentration oxygen therapy resulted in hyperoxia, with a range in mean Pa o 2 of 273 to 425 mm Hg. Hyperoxia caused a significant reduction in coronary blood flow (mean change −7.9% to −28.9%, n = 6 studies). Hyperoxia caused a significant increase in coronary vascular resistance (mean change 21.5% to 40.9%, n = 4 studies) and a significant reduction in myocardial oxygen consumption (mean change −15.3% to −26.9%, n = 3 studies). Hyperoxia from high-concentration oxygen therapy causes a marked reduction in coronary blood flow and myocardial oxygen consumption. These physiologic effects may have the potential to cause harm and are relevant to the use of high-concentration oxygen therapy in the treatment of cardiac and other disorders.