Bone mineral density and fracture risk with long-term use of inhaled corticosteroids in patients with asthma: systematic review and meta-analysis

Objectives: We aimed to assess the association between long-term use of inhaled corticosteroids (ICS) and bone adverse effects in patients with asthma. Design: Systematic review and meta-analysis of fracture risk and changes in bone mineral density with long-term ICS use in asthma. Methods: We initially searched MEDLINE and EMBASE in July 2013, and performed an updated PubMed search in December 2014. We selected randomised controlled trials (RCTs) and controlled observational studies of any ICS (duration at least 12 months) compared to non-ICS use in patients with asthma. We conducted meta-analysis of ORs for fractures, and mean differences in bone mineral density. Heterogeneity was assessed using the I2 statistic. Results: We included 18 studies (7 RCTs and 11 observational studies) in the systematic review. Meta-analysis of observational studies did not demonstrate any significant association between ICS and fractures in children (pooled OR 1.02, 95% CI 0.94 to 1.10, two studies), or adults (pooled OR 1.09, 95% CI 0.45 to 2.62, four studies). Three RCTs and three observational studies in children reported on bone mineral density at the lumbar spine, and our meta-analysis did not show significant reductions with ICS use. Three RCTs and four observational studies in adults reported on ICS use and bone mineral density at the lumbar spine and femur, with no significant reductions found in the meta-analysis compared to control. Conclusions ICS use for ≥12 months in adults or children with asthma was not significantly associated with harmful effects on fractures or bone mineral density

Cigarette smoking and gastric cancer in the stomach cancer pooling (StoP) project

Tobacco smoking is a known cause of gastric cancer, but several aspects of the association remain imprecisely quantified. We examined the relation between cigarette smoking and the risk of gastric cancer using a uniquely large dataset of 23 epidemiological studies within the ‘Stomach cancer Pooling (StoP) Project’, including 10 290 cases and 26 145 controls. We estimated summary odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) by pooling study-specific ORs using random-effects models. Compared with never smokers, the ORs were 1.20 (95% CI: 1.09–1.32) for ever, 1.12 (95% CI: 0.99–1.27) for former, and 1.25 (95% CI: 1.11–1.40) for current cigarette smokers. Among current smokers, the risk increased with number of cigarettes per day to reach an OR of 1.32 (95% CI: 1.10–1.58) for smokers of more than 20 cigarettes per day. The risk increased with duration of smoking, to reach an OR of 1.33 (95% CI: 1.14–1.54) for more than 40 years of smoking and decreased with increasing time since stopping cigarette smoking (P for trend<0.01) and became similar to that of never smokers 10 years after stopping. Risks were somewhat higher for cardia than noncardia gastric cancer. Risks were similar when considering only studies with information on Helicobacter pylori infection and comparing all cases to H. pylori+ controls only. This study provides the most precise estimate of the detrimental effect of cigarette smoking on the risk of gastric cancer on the basis of individual data, including the relationship with dose and duration, and the decrease in risk following stopping smoking

Menstrual cycle phase does not predict political conservatism

Recent authors have reported a relationship between women's fertility status, as indexed by menstrual cycle phase, and conservatism in moral, social and political values. We conducted a survey to test for the existence of a relationship between menstrual cycle day and conservatism. 2213 women reporting regular menstrual cycles provided data about their political views. Of these women, 2208 provided information about their cycle date, 1260 provided additional evidence of reliability in self-reported cycle date, and of these, 750 also indicated an absence of hormonal disruptors such as recent hormonal contraception use, breastfeeding or pregnancy. Cycle day was used to estimate day-specific fertility rate (probability of conception); political conservatism was measured via direct self-report and via responses to the "Moral Foundations” questionnaire. We also recorded relationship status, which has been reported to interact with menstrual cycle phase in determining political preferences. We found no evidence of a relationship between estimated cyclical fertility changes and conservatism, and no evidence of an interaction between relationship status and cyclical fertility in determining political attitudes. Our findings were robust to multiple inclusion/exclusion criteria and to different methods of estimating fertility and measuring conservatism. In summary, the relationship between cycle-linked reproductive parameters and conservatism may be weaker or less reliable than previously thought

Statistical challenges in the development and evaluation of marker-based clinical tests

Exciting new technologies for assessing markers in human specimens are now available to evaluate unprecedented types and numbers of variations in DNA, RNA, proteins, or biological structures such as chromosomes. These markers, whether viewed individually, or collectively as a 'signature', have the potential to be useful for disease risk assessment, screening, early detection, prognosis, therapy selection, and monitoring for therapy effectiveness or disease recurrence. Successful translation from basic research findings to clinically useful test requires basic, translational, and regulatory sciences and a collaborative effort among individuals with varied types of expertise including laboratory scientists, technology developers, clinicians, statisticians, and bioinformaticians. The focus of this commentary is the many statistical challenges in translational marker research, specifically in the development and validation of marker-based tests that have clinical utility for therapeutic decision-making

The Waiting Time for Inter-Country Spread of Pandemic Influenza

BACKGROUND: The time delay between the start of an influenza pandemic and its subsequent initiation in other countries is highly relevant to preparedness planning. We quantify the distribution of this random time in terms of the separate components of this delay, and assess how the delay may be extended by non-pharmaceutical interventions. METHODS AND FINDINGS: The model constructed for this time delay accounts for: (i) epidemic growth in the source region, (ii) the delay until an infected individual from the source region seeks to travel to an at-risk country, (iii) the chance that infected travelers are detected by screening at exit and entry borders, (iv) the possibility of in-flight transmission, (v) the chance that an infected arrival might not initiate an epidemic, and (vi) the delay until infection in the at-risk country gathers momentum. Efforts that reduce the disease reproduction number in the source region below two and severe travel restrictions are most effective for delaying a local epidemic, and under favourable circumstances, could add several months to the delay. On the other hand, the model predicts that border screening for symptomatic infection, wearing a protective mask during travel, promoting early presentation of cases arising among arriving passengers and moderate reduction in travel volumes increase the delay only by a matter of days or weeks. Elevated in-flight transmission reduces the delay only minimally. CONCLUSIONS: The delay until an epidemic of pandemic strain influenza is imported into an at-risk country is largely determined by the course of the epidemic in the source region and the number of travelers attempting to enter the at-risk country, and is little affected by non-pharmaceutical interventions targeting these travelers. Short of preventing international travel altogether, eradicating a nascent pandemic in the source region appears to be the only reliable method of preventing country-to-country spread of a pandemic strain of influenza

Improving the use of research evidence in guideline development: 7. Deciding what evidence to include

BACKGROUND: The World Health Organization (WHO), like many other organisations around the world, has recognised the need to use more rigorous processes to ensure that health care recommendations are informed by the best available research evidence. This is the seventh of a series of 16 reviews that have been prepared as background for advice from the WHO Advisory Committee on Health Research to WHO on how to achieve this. OBJECTIVES: We reviewed the literature on what constitutes "evidence" in guidelines and recommendations. METHODS: We searched PubMed and three databases of methodological studies for existing systematic reviews and relevant methodological research. We did not conduct systematic reviews ourselves. Our conclusions are based on the available evidence, consideration of what WHO and other organisations are doing and logical arguments. KEY QUESTION AND ANSWERS: We found several systematic reviews that compared the findings of observational studies with randomised trials, a systematic review of methods for evaluating bias in non-randomised trials and several descriptive studies of methods used in systematic reviews of population interventions and harmful effects. What types of evidence should be used to address different types of questions? • The most important type of evidence for informing global recommendations is evidence of the effects of the options (interventions or actions) that are considered in a recommendation. This evidence is essential, but not sufficient for making recommendations about what to do. Other types of required evidence are largely context specific. • The study designs to be included in a review should be dictated by the interventions and outcomes being considered. A decision about how broad a range of study designs to consider should be made in relationship to the characteristics of the interventions being considered, what evidence is available, and the time and resources available. • There is uncertainty regarding what study designs to include for some specific types of questions, particularly for questions regarding population interventions, harmful effects and interventions where there is only limited human evidence. • Decisions about the range of study designs to include should be made explicitly. • Great caution should be taken to avoid confusing a lack of evidence with evidence of no effect, and to acknowledge uncertainty. • Expert opinion is not a type of study design and should not be used as evidence. The evidence (experience or observations) that is the basis of expert opinions should be identified and appraised in a systematic and transparent way

Peripheral blood biomarkers in multiple sclerosis.

Multiple sclerosis is the most common autoimmune disorder affecting the central nervous system. The heteroge-neity of pathophysiological processes in MS contributes to the highly variable course of the disease and unpre-dictable response to therapies. The major focus of the research on MS is the identification of biomarkers inbiologicalfluids, such as cerebrospinalfluid or blood, to guide patient management reliably. Because of the diffi-culties in obtaining spinalfluid samples and the necessity for lumbar puncture to make a diagnosis has reduced,the research of blood-based biomarkers may provide increasingly important tools for clinical practice. However,currently there are no clearly established MS blood-based biomarkers. The availability of reliable biomarkerscould radically alter the management of MS at critical phases of the disease spectrum, allowing for interventionstrategies that may prevent evolution to long-term neurological disability. This article provides an overview ofthis researchfield and focuses on recent advances in blood-based biomarker researc