Showing papers by "Keele University published in 2017"

Controlled Interventions to Reduce Burnout in Physicians A Systematic Review and Meta-analysis

Abstract: Importance Burnout is prevalent in physicians and can have a negative influence on performance, career continuation, and patient care. Existing evidence does not allow clear recommendations for the management of burnout in physicians. Objective To evaluate the effectiveness of interventions to reduce burnout in physicians and whether different types of interventions (physician-directed or organization-directed interventions), physician characteristics (length of experience), and health care setting characteristics (primary or secondary care) were associated with improved effects. Data Sources MEDLINE, Embase, PsycINFO, CINAHL, and Cochrane Register of Controlled Trials were searched from inception to May 31, 2016. The reference lists of eligible studies and other relevant systematic reviews were hand searched. Study Selection Randomized clinical trials and controlled before-after studies of interventions targeting burnout in physicians. Data Extraction and Synthesis Two independent reviewers extracted data and assessed the risk of bias. The main meta-analysis was followed by a number of prespecified subgroup and sensitivity analyses. All analyses were performed using random-effects models and heterogeneity was quantified. Main Outcomes and Measures The core outcome was burnout scores focused on emotional exhaustion, reported as standardized mean differences and their 95% confidence intervals. Results Twenty independent comparisons from 19 studies were included in the meta-analysis (n = 1550 physicians; mean [SD] age, 40.3 [9.5] years; 49% male). Interventions were associated with small significant reductions in burnout (standardized mean difference [SMD] = −0.29; 95% CI, −0.42 to −0.16; equal to a drop of 3 points on the emotional exhaustion domain of the Maslach Burnout Inventory above change in the controls). Subgroup analyses suggested significantly improved effects for organization-directed interventions (SMD = −0.45; 95% CI, −0.62 to −0.28) compared with physician-directed interventions (SMD = −0.18; 95% CI, −0.32 to −0.03). Interventions delivered in experienced physicians and in primary care were associated with higher effects compared with interventions delivered in inexperienced physicians and in secondary care, but these differences were not significant. The results were not influenced by the risk of bias ratings. Conclusions and Relevance Evidence from this meta-analysis suggests that recent intervention programs for burnout in physicians were associated with small benefits that may be boosted by adoption of organization-directed approaches. This finding provides support for the view that burnout is a problem of the whole health care organization, rather than individuals.

Chronic exposure to neonicotinoids reduces honey bee health near corn crops

Abstract: Experiments linking neonicotinoids and declining bee health have been criticized for not simulating realistic exposure. Here we quantified the duration and magnitude of neonicotinoid exposure in Canada’s corn-growing regions and used these data to design realistic experiments to investigate the effect of such insecticides on honey bees. Colonies near corn were naturally exposed to neonicotinoids for up to 4 months—the majority of the honey bee’s active season. Realistic experiments showed that neonicotinoids increased worker mortality and were associated with declines in social immunity and increased queenlessness over time. We also discovered that the acute toxicity of neonicotinoids to honey bees doubles in the presence of a commonly encountered fungicide. Our work demonstrates that field-realistic exposure to neonicotinoids can reduce honey bee health in corn-growing regions.

Meta-analysis using individual participant data: one-stage and two-stage approaches, and why they may differ.

Abstract: Meta-analysis using individual participant data (IPD) obtains and synthesises the raw, participant-level data from a set of relevant studies. The IPD approach is becoming an increasingly popular tool as an alternative to traditional aggregate data meta-analysis, especially as it avoids reliance on published results and provides an opportunity to investigate individual-level interactions, such as treatment-effect modifiers. There are two statistical approaches for conducting an IPD meta-analysis: one-stage and two-stage. The one-stage approach analyses the IPD from all studies simultaneously, for example, in a hierarchical regression model with random effects. The two-stage approach derives aggregate data (such as effect estimates) in each study separately and then combines these in a traditional meta-analysis model. There have been numerous comparisons of the one-stage and two-stage approaches via theoretical consideration, simulation and empirical examples, yet there remains confusion regarding when each approach should be adopted, and indeed why they may differ. In this tutorial paper, we outline the key statistical methods for one-stage and two-stage IPD meta-analyses, and provide 10 key reasons why they may produce different summary results. We explain that most differences arise because of different modelling assumptions, rather than the choice of one-stage or two-stage itself. We illustrate the concepts with recently published IPD meta-analyses, summarise key statistical software and provide recommendations for future IPD meta-analyses. © 2016 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd.

A guide to systematic review and meta-analysis of prediction model performance

Abstract: Validation of prediction models is highly recommended and increasingly common in the literature. A systematic review of validation studies is therefore helpful, with meta-analysis needed to summarise the predictive performance of the model being validated across different settings and populations. This article provides guidance for researchers systematically reviewing and meta-analysing the existing evidence on a specific prediction model, discusses good practice when quantitatively summarising the predictive performance of the model across studies, and provides recommendations for interpreting meta-analysis estimates of model performance. We present key steps of the meta-analysis and illustrate each step in an example review, by summarising the discrimination and calibration performance of the EuroSCORE for predicting operative mortality in patients undergoing coronary artery bypass grafting.

Incidence, clinical management, and mortality risk following self harm among children and adolescents: cohort study in primary care.

Abstract: Objectives To examine temporal trends in sex and age specific incidence of self harm in children and adolescents, clinical management patterns, and risk of cause specific mortality following an index self harm episode at a young age. Design Population based cohort study. Setting UK Clinical Practice Research Datalink—electronic health records from 674 general practices, with practice level deprivation measured ecologically using the index of multiple deprivation. Patients from eligible English practices were linked to hospital episode statistics (HES) and Office for National Statistics (ONS) mortality records. Participants For the descriptive analytical phases we examined data pertaining to 16 912 patients aged 10-19 who harmed themselves during 2001-14. For analysis of cause specific mortality following self harm, 8638 patients eligible for HES and ONS linkage were matched by age, sex, and general practice with up to 20 unaffected children and adolescents (n=170 274). Main outcome measures In the first phase, temporal trends in sex and age specific annual incidence were examined. In the second phase, clinical management was assessed according to the likelihood of referral to mental health services and psychotropic drug prescribing. In the third phase, relative risks of all cause mortality, unnatural death (including suicide and accidental death), and fatal acute alcohol or drug poisoning were estimated as hazard ratios derived from stratified Cox proportional hazards models for the self harm cohort versus the matched unaffected comparison cohort. Results The annual incidence of self harm was observed to increase in girls (37.4 per 10 000) compared with boys (12.3 per 10 000), and a sharp 68% increase occurred among girls aged 13-16, from 45.9 per 10 000 in 2011 to 77.0 per 10 000 in 2014. Referrals within 12 months of the index self harm episode were 23% less likely for young patients registered at the most socially deprived practices, even though incidences were considerably higher in these localities. Children and adolescents who harmed themselves were approximately nine times more likely to die unnaturally during follow-up, with especially noticeable increases in risks of suicide (deprivation adjusted hazard ratio 17.5, 95% confidence interval 7.6 to 40.5) and fatal acute alcohol or drug poisoning (34.3, 10.2 to 115.7). Conclusions Gaining a better understanding of the mechanisms responsible for the recent apparent increase in the incidence of self harm among early-mid teenage girls, and coordinated initiatives to tackle health inequalities in the provision of services to distressed children and adolescents, represent urgent priorities for multiple public agencies.

Exercise to prevent falls in older adults: an updated systematic review and meta-analysis

Abstract: Objective Previous meta-analyses have found that exercise prevents falls in older people. This study aimed to test whether this effect is still present when new trials are added, and it explores whether characteristics of the trial design, sample or intervention are associated with greater fall prevention effects. Design Update of a systematic review with random effects meta-analysis and meta-regression. Data sources Cochrane Library, CINAHL, MEDLINE, EMBASE, PubMed, PEDro and SafetyLit were searched from January 2010 to January 2016. Study eligibility criteria We included randomised controlled trials that compared fall rates in older people randomised to receive exercise as a single intervention with fall rates in those randomised to a control group. Results 99 comparisons from 88 trials with 19 478 participants were available for meta-analysis. Overall, exercise reduced the rate of falls in community-dwelling older people by 21% (pooled rate ratio 0.79, 95% CI 0.73 to 0.85, p<0.001, I 47%, 69 comparisons) with greater effects seen from exercise programmes that challenged balance and involved more than 3 hours/ week of exercise. These variables explained 76% of the between-trial heterogeneity and in combination led to a 39% reduction in falls (incident rate ratio 0.61, 95% CI 0.53 to 0.72, p<0.001). Exercise also had a fall prevention effect in community-dwelling people with Parkinson’s disease (pooled rate ratio 0.47, 95% CI 0.30 to 0.73, p=0.001, I 65%, 6 comparisons) or cognitive impairment (pooled rate ratio 0.55, 95% CI 0.37 to 0.83, p=0.004, I 21%, 3 comparisons). There was no evidence of a fall prevention effect of exercise in residential care settings or among stroke survivors or people recently discharged from hospital. Summary/conclusions Exercise as a single intervention can prevent falls in community-dwelling older people. Exercise programmes that challenge balance and are of a higher dose have larger effects. The impact of exercise as a single intervention in clinical groups and aged care facility residents requires further investigation, but promising results are evident for people with Parkinson’s disease and cognitive impairment. INTRODUCTION Falls are a leading cause of morbidity and mortality in older adults. 2 Approximately one in three community-dwelling people aged 65 years or older will fall at least once per year, and the risk of falling increases with age. Falls impose a significant social and economic burden for individuals, their families, community health services and the economy. As the proportion of older people is rising globally, the costs associated with falls will increase. The prevention of falls is therefore an urgent public health challenge. National health bodies and international guidelines are promoting the implementation of appropriately designed intervention programmes that are known to prevent falls in older people. 6 There is strong evidence that appropriately designed intervention programmes can prevent falls in older people. A Cochrane systematic review established that exercise interventions reduce the rate of falls (number of falls per person) and risk of falling (proportion of people having one or more falls) in community-dwelling older people. Furthermore, exercise as a single intervention has a fall prevention effect similar to multifaceted interventions, 10 suggesting implementation of exercise as a stand-alone intervention may be the optimal and potentially most cost-effective approach to fall prevention at a population level. Trials of exercise for fall prevention are heterogeneous in risk of bias, populations involved and content of exercise programmes. Meta-regression enables investigation of between-trial variability, that is, whether certain trial-level factors are associated with greater effects of intervention programmes. Our previous meta-analyses with meta-regression, which included 44 trials in 2008 and 54 trials in 2011, found greater fall prevention effects in trials where exercise programmes included balance training, were undertaken more frequently (ie, exceeded 2 hours a week over the study period) and did not include walking exercise. Recent publication of additional trials necessitates an update of the previous systematic review, meta-analyses and meta-regression. This systematic review and meta-analysis aimed to: (1) determine the effects of exercise on fall rates in older people when compared with no exercise in randomised controlled trials (RCTs), and (2) explore whether characteristics of the trial design, sample or intervention are associated with greater fall prevention effects.

Do Board’s Corporate Social Responsibility Strategy and Orientation Influence Environmental Sustainability Disclosure? UK Evidence

Abstract: The environmental implications of corporate economic activities have led to growing demands for firms and their boards to adopt sustainable strategies and to disseminate more useful information about their activities and impacts on environment. This paper investigates the impact of board’s corporate social responsibility (CSR) strategy and orientation on the quantity and quality of environmental sustainability disclosure in UK listed firms. We find that effective board CSR strategy and CSR-oriented directors have a positive and significant impact on the quality of environmental sustainability disclosure, but not on the quantity. Our findings also suggest that the existence of a CSR committee and issuance of a stand-alone CSR report are positively and significantly related to environmental sustainability disclosure. When we distinguish between firms with high and low environmental risk, we find that the board CSR/sustainability practices that affect the quantity (quality) of environmental sustainability disclosure appear to be driven more by highly (lowly) environmentally sensitive firms. These results suggest that the board CSR/sustainability practices play an important role in ensuring a firm’s legitimacy and accountability towards stakeholders. Our findings shed new light on this under-researched area and could be of interest to companies, policy-makers and other stakeholders.

Effects of antenatal diet and physical activity on maternal and fetal outcomes: Individual patient data meta-analysis and health economic evaluation

Abstract: Background: Diet- and physical activity-based interventions in pregnancy have the potential to alter maternal and child outcomes. Objectives: To assess whether or not the effects of diet and lifestyle interventions vary in subgroups of women, based on maternal body mass index (BMI), age, parity, Caucasian ethnicity and underlying medical condition(s), by undertaking an individual patient data (IPD) meta-analysis. We also evaluated the association of gestational weight gain (GWG) with adverse pregnancy outcomes and assessed the cost-effectiveness of the interventions. Data sources: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects and Health Technology Assessment database were searched from October 2013 to March 2015 (to update a previous search). Review methods: Researchers from the International Weight Management in Pregnancy Collaborative Network shared the primary data. For each intervention type and outcome, we performed a two-step IPD random-effects meta-analysis, for all women (except underweight) combined and for each subgroup of interest, to obtain summary estimates of effects and 95% confidence intervals (CIs), and synthesised the differences in effects between subgroups. In the first stage, we fitted a linear regression adjusted for baseline (for continuous outcomes) or a logistic regression model (for binary outcomes) in each study separately; estimates were combined across studies using random-effects meta-analysis models. We quantified the relationship between weight gain and complications, and undertook a decision-analytic model-based economic evaluation to assess the cost-effectiveness of the interventions. Results: Diet and lifestyle interventions reduced GWG by an average of 0.70 kg (95% CI-0.92 to-0.48 kg; 33 studies, 9320 women). The effects on composite maternal outcome [summary odds ratio (OR) 0.90, 95% CI 0.79 to 1.03; 24 studies, 8852 women] and composite fetal/neonatal outcome (summary OR 0.94, 95% CI 0.83 to 1.08; 18 studies, 7981 women) were not significant. The effect did not vary with baseline BMI, age, ethnicity, parity or underlying medical conditions for GWG, and composite maternal and fetal outcomes. Lifestyle interventions reduce Caesarean sections (OR 0.91, 95% CI 0.83 to 0.99), but not other individual maternal outcomes such as gestational diabetes mellitus (OR 0.89, 95% CI 0.72 to 1.10), pre-eclampsia or pregnancy-induced hypertension (OR 0.95, 95% CI 0.78 to 1.16) and preterm birth (OR 0.94, 95% CI 0.78 to 1.13). There was no significant effect on fetal outcomes. The interventions were not cost-effective. GWG, including adherence to the Institute of Medicine-recommended targets, was not associated with a reduction in complications. Predictors of GWG were maternal age (summary estimate-0.10 kg, 95% CI-0.14 to-0.06 kg) and multiparity (summary estimate-0.73 kg, 95% CI-1.24 to-0.23 kg). Limitations: The findings were limited by the lack of standardisation in the components of intervention, residual heterogeneity in effects across studies for most analyses and the unavailability of IPD in some studies. Conclusion: Diet and lifestyle interventions in pregnancy are clinically effective in reducing GWG irrespective of risk factors, with no effects on composite maternal and fetal outcomes. Future work: The differential effects of lifestyle interventions on individual pregnancy outcomes need evaluation. Study registration: This study is registered as PROSPERO CRD42013003804.

Informing efficient randomised controlled trials: exploration of challenges in developing progression criteria for internal pilot studies.

Abstract: Objectives: Designing studies with an internal pilot phase may optimise the use of pilot work to inform more efficient randomised controlled trials (RCTs). Careful selection of preagreed decision or 'progression' criteria at the juncture between the internal pilot and main trial phases provides a valuable opportunity to evaluate the likely success of the main trial and optimise its design or, if necessary, to make the decision not to proceed with the main trial. Guidance on the appropriate selection and application of progression criteria is, however, lacking. This paper outlines the key issues to consider in the optimal development and review of operational progression criteria for RCTs with an internal pilot phase. Design: A structured literature review and exploration of stakeholders' opinions at a Medical Research Council (MRC) Hubs for Trials Methodology Research workshop. Key stakeholders included triallists, methodologists, statisticians and funders. Results: There is considerable variation in the use of progression criteria for RCTs with an internal pilot phase, although 3 common issues predominate: trial recruitment, protocol adherence and outcome data. Detailed and systematic reporting around the decisionmaking process for stopping, amending or proceeding to a main trial is uncommon, which may hamper understanding in the research community about the appropriate and optimal use of RCTs with an internal pilot phase. 10 top tips for the development, use and reporting of progression criteria for internal pilot studies are presented. Conclusions: Systematic and transparent reporting of the design, results and evaluation of internal pilot trials in the literature should be encouraged in order to facilitate understanding in the research community and to inform future trials.

Robust Statistical Methods for Empirical Software Engineering

Abstract: There have been many changes in statistical theory in the past 30 years, including increased evidence that non-robust methods may fail to detect important results. The statistical advice available to software engineering researchers needs to be updated to address these issues. This paper aims both to explain the new results in the area of robust analysis methods and to provide a large-scale worked example of the new methods. We summarise the results of analyses of the Type 1 error efficiency and power of standard parametric and non-parametric statistical tests when applied to non-normal data sets. We identify parametric and non-parametric methods that are robust to non-normality. We present an analysis of a large-scale software engineering experiment to illustrate their use. We illustrate the use of kernel density plots, and parametric and non-parametric methods using four different software engineering data sets. We explain why the methods are necessary and the rationale for selecting a specific analysis. We suggest using kernel density plots rather than box plots to visualise data distributions. For parametric analysis, we recommend trimmed means, which can support reliable tests of the differences between the central location of two or more samples. When the distribution of the data differs among groups, or we have ordinal scale data, we recommend non-parametric methods such as Cliff's ź or a robust rank-based ANOVA-like method.

Viologens and Their Application as Functional Materials

Abstract: Organic materials have recently gained considerable attention for electronic applications, improving performance and sustainability to current technologies. Commercialized metal-based systems are generally expensive, toxic and difficult to recycle, however organic materials offer promising solutions. Viologens, N,N' di-quaternized bipyridyl salts, are a well-studied species exhibiting three reversible redox states, possessing valuable electrochromic and electron-accepting properties. These properties can be fine-tuned through synthesis by altering the nitrogen substituents and various counteranions. Currently, viologens have become of great interest as functional materials in a wide array of applications; a few to name include electrochromic devices, molecular machines, and organic batteries. This review highlights representative recent work and advances towards utilizing viologens in practical applications that currently compete with metal-based technologies. Additionally, modified viologens that can be further fine-tuned will be discussed.

Do patients have worse outcomes in heart failure than in cancer? A primary care-based cohort study with 10-year follow-up in Scotland.

Abstract: MS and IB were supported by the University of Manchester's Health eResearch Centre (HeRC) funded by the Medical Research Council (MRC) Grant MR/K006665/1.

Designing Pd–N-Heterocyclic Carbene Complexes for High Reactivity and Selectivity for Cross-Coupling Applications

Abstract: ConspectusOver the past decade, the use of Pd–NHC complexes in cross-coupling applications has blossomed, and reactions that were either not previously possible or possible only under very forcing conditions (e.g., > 100 °C, strong base) are now feasible under mild conditions (e.g., room temperature, weak base). Access to tools such as computational chemistry has facilitated a much greater mechanistic understanding of catalytic cycles, which has enabled the design of new NHC ligands and accelerated advances in cross-coupling. With these elements of rational design, highly reactive Pd–NHC complexes have been invented to catalyze the selective formation of single products in a variety of transformations that have the potential to afford multiple compounds (e.g., isomers).Pd–NHC catalysts may be prepared as stable Pd(II) precatalysts that are readily reduced to the active Pd(0) species in the presence of an organometallic cross-coupling partner or nucleophile possessing β-hydrogens. It has been found from co...

Multivariate and network meta-analysis of multiple outcomes and multiple treatments: rationale, concepts, and examples

Abstract: Organisations such as the National Institute for Health and Care Excellence require the synthesis of evidence from existing studies to inform their decisions—for example, about the best available treatments with respect to multiple efficacy and safety outcomes. However, relevant studies may not provide direct evidence about all the treatments or outcomes of interest. Multivariate and network meta-analysis methods provide a framework to address this, using correlated or indirect evidence from such studies alongside any direct evidence. In this article, the authors describe the key concepts and assumptions of these methods, outline how correlated and indirect evidence arises, and illustrate the contribution of such evidence in real clinical examples involving multiple outcomes and multiple treatments

Performance of methods for meta-analysis of diagnostic test accuracy with few studies or sparse data

Abstract: Hierarchical models such as the bivariate and hierarchical summary receiver operating characteristic (HSROC) models are recommended for meta-analysis of test accuracy studies. These models are challenging to fit when there are few studies and/or sparse data (for example zero cells in contingency tables due to studies reporting 100% sensitivity or specificity); the models may not converge, or give unreliable parameter estimates. Using simulation, we investigated the performance of seven hierarchical models incorporating increasing simplifications in scenarios designed to replicate realistic situations for meta-analysis of test accuracy studies. Performance of the models was assessed in terms of estimability (percentage of meta-analyses that successfully converged and percentage where the between study correlation was estimable), bias, mean square error and coverage of the 95% confidence intervals. Our results indicate that simpler hierarchical models are valid in situations with few studies or sparse data. For synthesis of sensitivity and specificity, univariate random effects logistic regression models are appropriate when a bivariate model cannot be fitted. Alternatively, an HSROC model that assumes a symmetric SROC curve (by excluding the shape parameter) can be used if the HSROC model is the chosen meta-analytic approach. In the absence of heterogeneity, fixed effect equivalent of the models can be applied.

EULAR recommendations for the use of imaging in the clinical management of peripheral joint osteoarthritis

Abstract: The increased information provided by modern imaging has led to its more extensive use. Our aim was to develop evidence-based recommendations for the use of imaging in the clinical management of the most common arthropathy, osteoarthritis (OA). A task force (including rheumatologists, radiologists, methodologists, primary care doctors and patients) from nine countries defined 10 questions on the role of imaging in OA to support a systematic literature review (SLR). Joints of interest were the knee, hip, hand and foot; imaging modalities included conventional radiography (CR), MRI, ultrasonography, CT and nuclear medicine. PubMed and EMBASE were searched. The evidence was presented to the task force who subsequently developed the recommendations. The strength of agreement for each recommendation was assessed. 17 011 references were identified from which 390 studies were included in the SLR. Seven recommendations were produced, covering the lack of need for diagnostic imaging in patients with typical symptoms; the role of imaging in differential diagnosis; the lack of benefit in monitoring when no therapeutic modification is related, though consideration is required when unexpected clinical deterioration occurs; CR as the first-choice imaging modality; consideration of how to correctly acquire images and the role of imaging in guiding local injections. Recommendations for future research were also developed based on gaps in evidence, such as the use of imaging in identifying therapeutic targets, and demonstrating the added value of imaging. These evidence-based recommendations and related research agenda provide the basis for sensible use of imaging in routine clinical assessment of people with OA.

Health literacy, associated lifestyle and demographic factors in adult population of an English city: a cross-sectional survey

Abstract: Background Lower health literacy is a public health issue that follows a social gradient, potentially reinforcing existing health inequalities. However, levels of health literacy in particular populations can be unclear and are a key to identifying effective public health interventions. This research examined health literacy levels in Stoke-on-Trent, where 31.2% of the population live in areas classified amongst the 10% most deprived in England. Methods A cross-sectional survey using the Newest Vital Sign examined associations with demographic factors, lifestyle behaviours, Internet use and self-rated health. The sample (n = 1046) took account of variance in levels of health literacy by age, educational attainment and deprivation. Bivariate logistic regression and multivariate logistic regression were used to estimate associations with health literacy when adjusted for other demographic factors and lifestyle behaviours. Results Nine hundred and seventy-two respondents completed the health literacy measure (93%): 277 (28.5%) scored low, 228 (23.5%) scored marginal and 467 (48.0%) scored adequate. Associations with higher rates of limited health literacy included older age, lower educational level, lower income, perceived poor health and lack of access to the Internet. Conclusions Given the complexity of factors influencing health literacy interdisciplinary approaches across health and social care and the voluntary sector are essential in identifying and developing appropriate interventions.

Variation in GP decisions on antihypertensive treatment in oldest-old and frail individuals across 29 countries

Abstract: In oldest-old patients (>80), few trials showed efficacy of treating hypertension and they included mostly the healthiest elderly. The resulting lack of knowledge has led to inconsistent guidelines, mainly based on systolic blood pressure (SBP), cardiovascular disease (CVD) but not on frailty despite the high prevalence in oldest-old. This may lead to variation how General Practitioners (GPs) treat hypertension. Our aim was to investigate treatment variation of GPs in oldest-olds across countries and to identify the role of frailty in that decision. Using a survey, we compared treatment decisions in cases of oldest-old varying in SBP, CVD, and frailty. GPs were asked if they would start antihypertensive treatment in each case. In 2016, we invited GPs in Europe, Brazil, Israel, and New Zealand. We compared the percentage of cases that would be treated per countries. A logistic mixed-effects model was used to derive odds ratio (OR) for frailty with 95% confidence intervals (CI), adjusted for SBP, CVD, and GP characteristics (sex, location and prevalence of oldest-old per GP office, and years of experience). The mixed-effects model was used to account for the multiple assessments per GP. The 29 countries yielded 2543 participating GPs: 52% were female, 51% located in a city, 71% reported a high prevalence of oldest-old in their offices, 38% and had >20 years of experience. Across countries, considerable variation was found in the decision to start antihypertensive treatment in the oldest-old ranging from 34 to 88%. In 24/29 (83%) countries, frailty was associated with GPs’ decision not to start treatment even after adjustment for SBP, CVD, and GP characteristics (OR 0.53, 95%CI 0.48–0.59; ORs per country 0.11–1.78). Across countries, we found considerable variation in starting antihypertensive medication in oldest-old. The frail oldest-old had an odds ratio of 0.53 of receiving antihypertensive treatment. Future hypertension trials should also include frail patients to acquire evidence on the efficacy of antihypertensive treatment in oldest-old patients with frailty, with the aim to get evidence-based data for clinical decision-making.

Signatures of internal rotation discovered in the Kepler data of five slowly pulsating B stars

Abstract: Context. Massive stars are important building blocks of the Universe, and their stellar structure and evolution models are fundamental cornerstones of various fields in modern astrophysics. The precision of these models is strongly limited by our lack of understanding of various internal mixing processes that significantly influence the lifetime of these objects, such as core overshoot, chemical mixing, or the internal differential rotation.Aims. Our goal is to calibrate models by extending the sample of available seismic studies of slowly pulsating B (SPB) stars, providing input for theoretical modelling efforts that will deliver precise constraints on the parameters describing the internal mixing processes in these objects.Methods. We used spectral synthesis and disentangling techniques to derive fundamental parameters and to determine precise orbital parameters from high-resolution spectra. We employed custom masks to construct light curves from the virtually uninterrupted four year long Kepler pixel data and used standard time-series analysis tools to construct a set of significant frequencies for each target. These sets were first filtered from combination frequencies, and then screened for period spacing patterns.Results. We detect gravity mode period series of modes, of the same degree l with consecutive radial order n, in four new and one revisited SPB star. These series (covering typically 10 to 40 radial orders) are clearly influenced by moderate to fast rotation and carry signatures of chemical mixing processes. Furthermore, they are predominantly prograde dipole series. Our spectroscopic analysis, in addition to placing each object inside the SPB instability strip and identifying KIC 4930889 as an SB2 binary, reveals that KIC 11971405 is a fast rotator that shows very weak Be signatures. Together with the observed photometric outbursts this illustrates that this Be star is a fast rotating SPB star. We hypothesise that the outbursts might be connected to its very densely compressed oscillation spectrum.

The effects of care bundles on patient outcomes: A systematic review and meta-analysis

Abstract: Care bundles are a set of three to five evidence-informed practices performed collectively and reliably to improve the quality of care. Care bundles are used widely across healthcare settings with the aim of preventing and managing different health conditions. This is the first systematic review designed to determine the effects of care bundles on patient outcomes and the behaviour of healthcare workers in relation to fidelity with care bundles. This systematic review is reported in line with the PRISMA statement for reporting systematic reviews and meta-analyses. A total of 5796 abstracts were retrieved through a systematic search for articles published between January 1, 2001, to February 4, 2017, in the Cochrane Central Register for Controlled Trials, MEDLINE, EMBASE, British Nursing Index, CINAHL, PsychInfo, British Library, Conference Proceeding Citation Index, OpenGrey trials (including cluster-randomised trials) and non-randomised studies (comprising controlled before-after studies, interrupted time series, cohort studies) of care bundles for any health condition and any healthcare settings were considered. Following the removal of duplicated studies, two reviewers independently screen 3134 records. Three authors performed data extraction independently. We compared the care bundles with usual care to evaluate the effects of care bundles on the risk of negative patient outcomes. Random-effect models were used to further explore the effects of subgroups. In total, 37 studies (6 randomised trials, 31 controlled before-after studies) were eligible for inclusion. The effect of care bundles on patient outcomes is uncertain. For randomised trial data, the pooled relative risk of negative effects between care bundle and control groups was 0.97 [95% CI 0.71 to 1.34; 2049 participants]. The relative risk of negative patient outcomes from controlled before-after studies favoured the care bundle treated groups (0.66 [95% CI 0.59 to 0.75; 119,178 participants]). However, using GRADE, we assessed the certainty of all of the evidence to be very low (downgraded for risk of bias, inconsistency, indirectness). Very low quality evidence from controlled before-after studies suggests that care bundles may reduce the risk of negative outcomes when compared with usual care. By contrast, the better quality evidence from six randomised trials is more uncertain. PROSPERO, CRD42016033175

Effect of Routine Low-Dose Oxygen Supplementation on Death and Disability in Adults With Acute Stroke: The Stroke Oxygen Study Randomized Clinical Trial

Abstract: Importance Hypoxia is common in the first few days after acute stroke, is frequently intermittent, and is often undetected. Oxygen supplementation could prevent hypoxia and secondary neurological deterioration and thus has the potential to improve recovery. Objective To assess whether routine prophylactic low-dose oxygen therapy was more effective than control oxygen administration in reducing death and disability at 90 days, and if so, whether oxygen given at night only, when hypoxia is most frequent, and oxygen administration is least likely to interfere with rehabilitation, was more effective than continuous supplementation. Design, Setting, and Participants In this single-blind randomized clinical trial, 8003 adults with acute stroke were enrolled from 136 participating centers in the United Kingdom within 24 hours of hospital admission if they had no clear indications for or contraindications to oxygen treatment (first patient enrolled April 24, 2008; last follow-up January 27, 2015). Interventions Participants were randomized 1:1:1 to continuous oxygen for 72 hours (n = 2668), nocturnal oxygen (21:00 to 07:00 hours) for 3 nights (n = 2667), or control (oxygen only if clinically indicated; n = 2668). Oxygen was given via nasal tubes at 3 L/min if baseline oxygen saturation was 93% or less and at 2 L/min if oxygen saturation was greater than 93%. Main Outcomes and Measures The primary outcome was reported using the modified Rankin Scale score (disability range, 0 [no symptoms] to 6 [death]; minimum clinically important difference, 1 point), assessed at 90 days by postal questionnaire (participant aware, assessor blinded). The modified Rankin Scale score was analyzed by ordinal logistic regression, which yields a common odds ratio (OR) for a change from one disability level to the next better (lower) level; OR greater than 1.00 indicates improvement. Results A total of 8003 patients (4398 (55%) men; mean [SD] age, 72 [13] years; median National Institutes of Health Stroke Scale score, 5; mean baseline oxygen saturation, 96.6%) were enrolled. The primary outcome was available for 7677 (96%) participants. The unadjusted OR for a better outcome (calculated via ordinal logistic regression) was 0.97 (95% CI, 0.89 to 1.05; P = .47) for oxygen vs control, and the OR was 1.03 (95% CI, 0.93 to 1.13; P = .61) for continuous vs nocturnal oxygen. No subgroup could be identified that benefited from oxygen. At least 1 serious adverse event occurred in 348 (13.0%) participants in the continuous oxygen group, 294 (11.0%) in the nocturnal group, and 322 (12.1%) in the control group. No significant harms were identified. Conclusions and Relevance Among nonhypoxic patients with acute stroke, the prophylactic use of low-dose oxygen supplementation did not reduce death or disability at 3 months. These findings do not support low-dose oxygen in this setting. Trial Registration ISRCTN Identifier:ISRCTN52416964

Drug development: Lessons from nature (Review)

Abstract: Natural products have been acknowledged for numerous years as a vital source of active ingredients in therapeutic agents. In particular, the use of active ingredients derived from plants for use in microbial natural products have long been used before the dawn of modern medicine. From ancient times, the efficacy of natural products has been associated with the chemistry, biochemistry and synthetic activities of natural products. Thus, with scientific advancement in modern molecular and cellular biology, analytical chemistry and pharmacology, the unique properties of these natural products are being harnessed in order to exploit the chemical and structural diversity and biodiversity of these types of products in relation to their therapeutic effect. Often, new molecules of interest in drug design units focus on the rearrangement of chemical entities or structural isomers of naturally occurring products in order to generate new molecules; these may be formulated into clinically useful therapies.