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A number of recent climate studies have used univariate parametric statistical models to estimate return periods of extreme weather events based on the method of maximum likelihood. Using simulations over multiple training datasets, we find that using maximum likelihood gives predictions of extreme return levels that are exceeded more often than expected. For instance, when using the generalised extreme value distribution (GEVD) with 50 annual data values, fitted using maximum likelihood, we find that 200-year return levels are exceeded more than twice as often as expected; i.e. they are exceeded in more than 1 in 100 simulated years. This bias, which we refer to as a predictive coverage probability (PCP) bias, would be expected to lead to unreliable predictions. We review the theory related to Bayesian prediction using right Haar priors which gives an objective way to incorporate parameter uncertainty into predictions for some statistical models and which eliminates the bias. We consider a number of commonly used parametric statistical models and give the right Haar priors in each case. Where possible, we give analytical solutions for the resulting predictions. Where analytical solutions are not possible, we apply either an asymptotic approximation for the Bayesian prediction integral or ratio of uniforms sampling. For the fully parameterised GEVD and the generalised Pareto distribution with a known location parameter, neither of which have a right Haar prior, we test a number of methods and find one that gives big reductions in the PCP bias relative to maximum likelihood predictions. Finally, we revisit the De Bilt extreme temperature example considered in a number of previous studies and generate revised, and shorter, estimates for the return period of the 2018 heatwave. Software for fitting predictive distributions with parameter uncertainty has been developed by the first author and will be available as an R package. more...

Transgender (trans) rights are human rights; however, human resource management (HRM) policies often do not consider implications for non-binary gender equity. Instead, trans employees often face adverse working conditions, including discrimination, harassment, and marginalization--a critical HRM issue. As the workforce diversifies, HRM professionals must increase their understanding of identity categories, such as sex and gender. Moreover, HRM professionals must be equipped to critically analyze and uphold or amend workplace policies and practices to protect the rights and address the unique challenges faced by non-gender binary employees. This teaching case study facilitates a discussion on transgender rights and the role of HRM by analyzing issues of access, fairness, safety, and inclusivity in the public sector workplace. Students are challenged to consider how different groups are affected by HRM policy (or lack thereof) and how to balance policies with the needs and safety concerns of various stakeholders. more...

Arianne N Sweeting,1 Eddy Tabet,1 Ian D Caterson,1,2 Tania P Markovic1,2 1Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, NSW, Australia; 2Boden Institute of Obesity, Nutrition, Exercise & Eating Disorders, University of Sydney, NSW, Australia Abstract: The US Food and Drug Administration (FDA) recently approved lorcaserin and the combination of phentermine and extended release topiramate (phentermine/topiramate ER) for the treatment of obesity in conjunction with a lifestyle intervention, expanding the therapeutic options for long-term obesity pharmacotherapy, which was previously limited to orlistat. Combination phentermine/topiramate ER is associated with greater weight loss compared to its constituent monotherapy, with a more favorable adverse effect profile. Phentermine/topiramate ER also appears to have beneficial effects on cardiometabolic risk, although longer-term cardiovascular safety data are required. While there are no head-to-head studies among the currently available obesity pharmacotherapy agents, phentermine/topiramate ER appears to have a superior weight loss profile. This review will discuss the epidemiology, natural history, and cardiometabolic risk associated with obesity, provide an overview on current obesity pharmacotherapy, and summarize the recent clinical efficacy and safety data underpinning the FDA's approval of both phentermine/topiramate ER and lorcaserin as pharmacotherapy for a long-term obesity intervention. Keywords: obesity, phentermine/topiramate extended release, safety and efficacy, review more...

Objectives Incontrovertible evidence surrounds the need to support healthcare professionals after patient safety incidents (PSIs). However, what characterises effective organisational support is less clearly understood and defined. This review aims to determine what support healthcare professionals want for coping with PSIs, what support interventions/approaches are currently available and which have evidence for effectiveness.Design Systematic research review with narrative synthesis.Data sources Medline, Scopus, PubMed and Web of Science databases (from 2010 to mid-2021; updated December 2022), reference lists of eligible articles and Connected Papers software.Eligibility criteria for selecting studies Empirical studies (1) containing information about support frontline healthcare staff want before/after a PSI, OR addressing (2) support currently available, OR (3) the effectiveness of support to help prevent/alleviate consequences of a PSI. Study quality was appraised using the Quality Assessment for Diverse Studies tool.Results Ninety-nine studies were identified. Staff most wanted: peer support (n=28), practical support and guidance (n=27) and professional mental health support (n=21). They mostly received: peer support (n=46), managerial support (n=23) and some form of debrief (n=15). Reports of poor PSI support were common. Eleven studies examined intervention effectiveness. Evidence was positive for the effectiveness of preventive/preparatory interventions (n=3), but mixed for peer support programmes designed to alleviate harmful consequences after PSIs (n=8). Study quality varied.Conclusions Beyond peer support, organisational support for PSIs appears to be misaligned with staff desires. Gaps exist in providing preparatory/preventive interventions and practical support and guidance. Reliable effectiveness data are lacking. Very few studies incorporated comparison groups or randomisation; most used self-report measures. Despite inconclusive evidence, formal peer support programmes dominate. This review illustrates a critical need to fund robust PSI-related intervention effectiveness studies to provide organisations with the evidence they need to make informed decisions when building PSI support programmes.PROSPERO registration number CRD42022325796. more...

ABSTRACT Background The long‐term real‐world effect of immunotherapy (IO) is uncertain in metastatic nonsmall cell lung cancer (mNSCLC). This retrospective observational study aimed to describe treatment patterns following the introduction of IO, estimate real‐world treatment effects of IO compared to standard of care, and evaluate the impact of introduction of IO on a real‐world population, based on a large dataset of over 10 000 patients with several years of follow‐up. Methods Data from routine care of lung cancer patients were extracted from Flatiron Health including those who received either IO or platinum‐based doublet chemotherapy (PBDC) in the first line (1L), or either IO or chemotherapy (CT) in the second line (2L). Real‐world overall survival (rwOS) and real‐world time to next therapy (rwTTNT) were estimated using Cox regression. Flexible parametric models, relaxing proportional hazard assumptions, were used to evaluate long‐term IO effects. Results After 1:1 nearest neighbor matching among 16 754 1L and 6548 2L patients, the hazard ratio (HR) was 0.942 (95% CI, 0.902–0.984) in 1L and 0.853 (95% CI, 0.795–0.915) in 2L. Adjusting for crossover effects, HR was 0.887 in 1L and 0.775 in 2L. Over the 7‐year follow‐up, the mean rwOS benefit was 3.2 months for 1L and 2.7 months for 2L. IO significantly delayed rwTTNT in both 1L and 2L. The IO effects increased and persisted over time, with uncertainty in the time‐varying HR estimate. Conclusion IO improves survival in patients with mNSCLC, though the effect size is smaller than in trials and long‐term survival estimates are uncertain. more...

Objective Fluoropyrimidine chemotherapy is a first-line treatment for many gastrointestinal (GI) cancers, however, cardiotoxicity concerns may limit administration in patients with pre-existing cardiovascular disease (CVD). This study investigated the association of pre-existing CVD with use of fluoropyrimidine chemotherapy in tumour-eligible GI cancer patients.Methods and analysis National cancer registry data from the Virtual Cardio-Oncology Research Initiative from England between 2014 and 2018 was used to identify GI cancer patients eligible to receive fluoropyrimidine chemotherapy. Linkage to Hospital Episode Statistics and CVD registry data were used to ascertain prior CVD and outcomes. Primary outcome was first administration of fluoropyrimidine chemotherapy following cancer diagnosis. Cox proportional hazard models determined HR and 95% CIs for the association between initiation of fluoropyrimidine treatment and prior CVD.Results 112 726 eligible patients were identified (median age 71 years (IQR 62–80), 39.7% female). 33 026 (29.3%) had pre-existing CVD. 73 392 (65.1%) patients had a diagnosis of colorectal, 23 208 (20.6%) oesophageal, 14 788 (13.1%) gastric and 1338 (1.2%) small bowel cancer. Individuals with pre-existing CVD had a 27% reduced rate of receiving fluoropyrimidine chemotherapy (HR, 0.73; 95% CI 0.70 to 0.75) on multivariable analysis. Significantly reduced rates of fluoropyrimidine administration were found across all subtypes of pre-existing CVD.Conclusions GI cancer patients with all types of pre-existing CVD are less likely to receive fluoropyrimidine chemotherapy despite eligibility. This suggests widespread caution regarding administration of fluoropyrimidines across this population; further research is needed to assess whether such conservatism is justified. more...

In this viewpoint, we present evidence of a marked increase in the use of assistive technology (AT) by older adults over the last 25 years. We also explain the way in which this use has expanded not only as an increase in terms of the total number of users but also by going beyond the typical scopes of use from its inception in 1999 to reach new categories of users. We outline our opinions on some of the key driving forces behind this expansion, such as population demographic changes, technological advances, and the promotion of AT as a means to enable older adults to achieve independent living. As well as our review of the evolution of AT over the past 25 years, we also discuss the future of AT research as a field and the need for harmonization of terminology in AT research. Finally, we outline how our experience in North Norfolk (notably the United Kingdom’s most old age–dependent district) suggests that cocreation may be the key to not only successful research trials in the field of AT but also to the successful sustained adoption of AT beyond its original scope of use. more...

In recent decades, 'whole school' approaches to improving health have gained traction, based on settings-based health promotion understandings which view a setting, its actors and processes as an integrated 'whole' system with multiple intervention opportunities. Much less is known about 'whole institution' approaches to improving health in tertiary education settings. We conducted a scoping review to describe both empirical and non-empirical (e.g. websites) publications relating to 'whole settings', 'complex systems' and 'participatory'/'action' approaches to improving the health of students and staff within tertiary education settings. English-language publications were identified by searching five academic and four grey literature databases and via the reference lists of studies read for eligibility. We identified 101 publications with marked UK over-representation. Since the 1970s, publications have increased, spanning a gradual shift in focus from 'aspirational' to 'conceptual' to 'evaluative'. Terminology is geographically siloed (e.g., 'healthy university' (UK), 'healthy campus' (USA)). Publications tend to focus on 'health' generally rather than specific health dimensions (e.g. diet). Policies, arguably crucial for cascading systemic change, were not the most frequently implemented intervention elements. We conclude that, despite the field's evolution, key questions (e.g., insights into who needs to do what, with whom, where and when; or efficacy) remain unanswered. more...

The distinction between wicked and tame problems has been a major influence on design and numerous other fields since it was developed in the late 1960s and early 1970s by design theorist Horst Rittel and urban designer Melvin Webber. The characteristics of wicked problems continue to resonate today, helping make sense of the complexities of contemporary challenges. Wicked and tame refer to types (rather than degrees) of difficulty, but what defines these types is not simply the domains in which problems occur, as in the dichotomy between scientific and social contexts originally put forward by Rittel and Webber. To clarify the distinction between wicked and tame, I ground it in the cybernetic concepts of variety and constraint, building on Rittel’s references to the cybernetician Ross Ashby. Understood in this way, wicked and tame do not refer to problems, or to the situations in which problems arise. Rather, wickedness and tameness are dynamics of possibilities (variety) in how multiple aspects of problems are perceived and responded to across the relationships in which designing (in its broadest senses) is embedded. more...

Abstract Background Both obesity and sleep disorders are common among women during pregnancy. Although prior research has identified a relationship between obesity and sleep disorders, those findings are from women later in pregnancy. Objective To explore the relationships between self‐reported sleep duration, insufficient sleep and snoring with body mass index (BMI) among multiethnic women at risk of gestational diabetes mellitus (GDM)in early pregnancy. Methods Cross‐sectional study of baseline data from women at risk of GDM enrolled in the Treatment of BOoking Gestational diabetes Mellitus (TOBOGM) multicentre trial across 12 Australian/Austrian sites. Participants completed a questionnaire before 20 weeks’ gestation to evaluate sleep. BMI 5 days/month was higher in class II and class III obesity (1.38 (1.03–1.85) and 1.34 (1.01–1.80), respectively), and the risk of snoring increased as BMI increased (1.59 (1.25–2.02), 2.68 (2.07–3.48), 4.35 (3.21–5.88) to 4.96 (3.65–6.74), respectively)). Conclusions Obesity is associated with insufficient sleep among pregnant women at risk of GDM. Snoring is more prevalent with increasing BMI. more...

Abstract Background Perinatal outcomes vary for women with gestational diabetes mellitus (GDM). The precise factors beyond glycemic status that may refine GDM diagnosis remain unclear. We conducted a systematic review and meta-analysis of potential precision markers for GDM. Methods Systematic literature searches were performed in PubMed and EMBASE from inception to March 2022 for studies comparing perinatal outcomes among women with GDM. We searched for precision markers in the following categories: maternal anthropometrics, clinical/sociocultural factors, non-glycemic biochemical markers, genetics/genomics or other -omics, and fetal biometry. We conducted post-hoc meta-analyses of a subset of studies with data on the association of maternal body mass index (BMI, kg/m2) with offspring macrosomia or large-for-gestational age (LGA). Results A total of 5905 titles/abstracts were screened, 775 full-texts reviewed, and 137 studies synthesized. Maternal anthropometrics were the most frequent risk marker. Meta-analysis demonstrated that women with GDM and overweight/obesity vs. GDM with normal range BMI are at higher risk of offspring macrosomia (13 studies [n = 28,763]; odds ratio [OR] 2.65; 95% Confidence Interval [CI] 1.91, 3.68), and LGA (10 studies [n = 20,070]; OR 2.23; 95% CI 2.00, 2.49). Lipids and insulin resistance/secretion indices were the most studied non-glycemic biochemical markers, with increased triglycerides and insulin resistance generally associated with greater risk of offspring macrosomia or LGA. Studies evaluating other markers had inconsistent findings as to whether they could be used as precision markers. Conclusions Maternal overweight/obesity is associated with greater risk of offspring macrosomia or LGA in women with GDM. Pregnancy insulin resistance or hypertriglyceridemia may be useful in GDM risk stratification. Future studies examining non-glycemic biochemical, genetic, other -omic, or sociocultural precision markers among women with GDM are warranted. more...

Introduction There is a lack of evidence that the benefits of screening for atrial fibrillation (AF) outweigh the harms. Following the completion of the Screening for Atrial Fibrillation with ECG to Reduce stroke (SAFER) pilot trial, the aim of the main SAFER trial is to establish whether population screening for AF reduces incidence of stroke risk.Methods and analysis Approximately 82 000 people aged 70 years and over and not on oral anticoagulation are being recruited from general practices in England. Patients on the palliative care register or residents in a nursing home are excluded. Eligible people are identified using electronic patient records from general practices and sent an invitation and consent form to participate by post. Consenting participants are randomised at a ratio of 2:1 (control:intervention) with clustering by household. Those randomised to the intervention arm are sent an information leaflet inviting them to participate in screening, which involves use of a handheld single-lead ECG four times a day for 3 weeks. ECG traces identified by an algorithm as possible AF are reviewed by cardiologists. Participants with AF are seen by a general practitioner for consideration of anticoagulation. The primary outcome is stroke. Major secondary outcomes are: death, major bleeding and cardiovascular events. Follow-up will be via electronic health records for an average of 4 years. The primary analysis will be by intention-to-treat using time-to-event modelling. Results from this trial will be combined with follow-up data from the cluster-randomised pilot trial by fixed-effects meta-analysis.Ethics and dissemination The London—Central National Health Service Research Ethics Committee (19/LO/1597) provided ethical approval. Dissemination will include public-friendly summaries, reports and engagement with the UK National Screening Committee.Trial registration number ISRCTN72104369. more...

Abstract Background Vasovagal reactions (VVRs) are the most common acute complications of blood donation. Responsible for substantial morbidity, they also reduce the likelihood of repeated donations and are disruptive and costly for blood services. Although blood establishments worldwide have adopted different strategies to prevent VVRs (including water loading and applied muscle tension [AMT]), robust evidence is limited. The Strategies to Improve Donor Experiences (STRIDES) trial aims to reliably assess the impact of four different interventions to prevent VVRs among blood donors. Methods STRIDES is a cluster-randomised cross-over/stepped-wedge factorial trial of four interventions to reduce VVRs involving about 1.4 million whole blood donors enrolled from all 73 blood donation sites (mobile teams and donor centres) of National Health Service Blood and Transplant (NHSBT) in England. Each site (“cluster”) has been randomly allocated to receive one or more interventions during a 36-month period, using principles of cross-over, stepped-wedge and factorial trial design to assign the sequence of interventions. Each of the four interventions is compared to NHSBT’s current practices: (i) 500-ml isotonic drink before donation (vs current 500-ml plain water); (ii) 3-min rest on donation chair after donation (vs current 2 min); (iii) new modified AMT (vs current practice of AMT); and (iv) psychosocial intervention using preparatory materials (vs current practice of nothing). The primary outcome is the number of in-session VVRs with loss of consciousness (i.e. episodes involving loss of consciousness of any duration, with or without additional complications). Secondary outcomes include all in-session VVRs (i.e. with and without loss of consciousness), all delayed VVRs (i.e. those occurring after leaving the venue) and any in-session non-VVR adverse events or reactions. Discussion The STRIDES trial should yield novel information about interventions, singly and in combination, for the prevention of VVRs, with the aim of generating policy-shaping evidence to help inform blood services to improve donor health, donor experience, and service efficiency. Trial registration ISRCTN: 10412338. Registration date: October 24, 2019. more...

The current study investigated peer relationship and school climate factors associated with adolescent mental health. Cross-sectional data from 2,571 fifteen-year old students in 22 Scottish secondary schools was used. Multilevel models tested for school differences in mental health, and nested linear regression models estimated peer and school effects. Results demonstrated no significant between-school variation in mental health. Peer victimization was the only peer effect associated with mental health. School-belonging, student-teacher relationships, and a perceived inclusive school climate were associated with better mental health, whereas a perceived school climate of exam pressure was associated with worse mental health. The findings highlight multiple aspects of school climate that could be targeted in school-based interventions for adolescent mental health. more...