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To ensure that the science, technology, engineering, and mathematics (STEM) workforce of the future is inclusive of diverse peoples and ideas, there is a need to ensure that STEM outreach activities that encourage students into STEM education and careers are inclusive of and provide equity for people from diverse racial/ethnic, socioeconomic, and academic backgrounds. Since 2004, the National Indigenous Science Education Program (NISEP), based at Macquarie University, Sydney, has been using best ethical and inclusion strategies to engage with Australian Aboriginal and Torres Strait Islander school students and their communities. This publication discusses the inclusion and equity strategies utilized by NISEP, including community consultation, student leadership and autonomy, volunteer mentors, and the respectful and best practice use of Indigenous knowledge. These factors have all contributed to NISEP's success in increasing Aboriginal and Torres Strait Islander students' aspiration toward and engagement with secondary and tertiary education.

INTRODUCTION: Benefits and risks of preventive medication change over time for ageing patients and deprescribing of medication may be needed. Deprescribing of cardiovascular and antidiabetic drugs can be challenging and is not widely implemented in daily practice.OBJECTIVE: The aim of this study was to identify barriers and enablers of deprescribing cardiometabolic medication as seen by healthcare providers (HCPs) of different disciplines, and to explore their views on their specific roles in the process of deprescribing.METHODS: Three focus groups with five general practitioners, eight pharmacists, three nurse practitioners, two geriatricians, and two elder care physicians were conducted in three cities in The Netherlands. Interviews were recorded and transcribed verbatim. Directed content analysis was performed on the basis of the Theoretical Domains Framework. Two researchers independently coded the data.RESULTS: Most HCPs agreed that deprescribing of cardiometabolic medication is relevant but that barriers include lack of evidence and expertise, negative beliefs and fears, poor communication and collaboration between HCPs, and lack of resources. Having a guideline was considered an enabler for the process of deprescribing of cardiometabolic medication. Some HCPs feared the consequences of discontinuing cardiovascular or antidiabetic medication, while others were not motivated to deprescribe when the patients experienced no problems with their medication. HCPs of all disciplines stated that adequate patient communication and involving the patients and relatives in the decision making enables deprescribing. Barriers to deprescribing included the use of medication initiated by specialists, the poor exchange of information, and the amount of time it takes to deprescribe cardiometabolic medication. The HCPs were uncertain about each other's roles and responsibilities. A multidisciplinary approach including the pharmacist and nurse practitioner was seen as the best way to support the process of deprescribing and address barriers related to resources.CONCLUSION: HCPs recognized the importance of deprescribing cardiometabolic medication as a medical decision that can only be made in close cooperation with the patient. To successfully accomplish the process of deprescribing they strongly recommended a multidisciplinary approach.

OBJECTIVE: This study aimed to investigate the association of burnout and vital exhaustion with measures of glycemic control and type 2 diabetes (T2D) in a systematic review and meta-analysis. METHODS: PubMed, Embase, and PsycINFO were searched from inception to April 2, 2020. Data extraction and quality assessment were performed using the Effective Public Health Practice Project tool. When possible, results were meta-analyzed using random-effects models and rated using the Grading of Recommendations, Assessment, Development and Evaluation. RESULTS: A total of 5317 titles/abstracts were screened, 140 articles were read full text, of which 29 studies were included. Eighteen studies were cross-sectional, three prospective and eight were case-control studies. Burnout and vital exhaustion were significantly associated with T2D, with a pooled odds ratio of 1.8 (95% confidence interval [CI] = 1.4 to 2.4, I2 = 79%; 9 studies). Glycated hemoglobin A1c levels were not significantly higher in people with burnout and vital exhaustion, compared to those without, with a pooled standardized mean difference of 0.35 (95% CI = -0.62 to 1.33, I2 = 98%; 7 studies). In addition, no differences in glucose levels were observed (standardized mean difference = 0.02, 95% CI = -0.26 to 0.30, I2 = 90%; 9 studies). Sensitivity analyses showed no decrease in heterogeneity when excluding studies with low quality (I2glucose = 89%) or studies with a study n < 40 population (I2T2D = 77%). The level of Grading of Recommendations, Assessment, Development and Evaluation evidence was moderate to low quality because of 18 studies having a cross-sectional design. CONCLUSIONS: Burnout and vital exhaustion might be associated with a higher risk of T2D, but not with glycemic control. Methodological shortcomings and high heterogeneity of the studies included complicate the interpretation of our results.

Graphical abstract Sleep disorders are linked to development of type 2 diabetes and increase the risk of developing diabetes complications. Treating sleep disorders might therefore play an important role in the prevention of diabetes progression. However, the detection and treatment of sleep disorders are not part of standardised care for people with type 2 diabetes. To highlight the importance of sleep disorders in people with type 2 diabetes, we provide a review of the literature on the prevalence of sleep disorders in type 2 diabetes and the association between sleep disorders and health outcomes, such as glycaemic control, microvascular and macrovascular complications, depression, mortality and quality of life. Additionally, we examine the extent to which treating sleep disorders in people with type 2 diabetes improves these health outcomes. We performed a literature search in PubMed from inception until January 2021, using search terms for sleep disorders, type 2 diabetes, prevalence, treatment and health outcomes. Both observational and experimental studies were included in the review. We found that insomnia (39% [95% CI 34, 44]), obstructive sleep apnoea (55–86%) and restless legs syndrome (8–45%) were more prevalent in people with type 2 diabetes, compared with the general population. No studies reported prevalence rates for circadian rhythm sleep–wake disorders, central disorders of hypersomnolence or parasomnias. Additionally, several cross-sectional and prospective studies showed that sleep disorders negatively affect health outcomes in at least one diabetes domain, especially glycaemic control. For example, insomnia is associated with increased HbA1c levels (2.51 mmol/mol [95% CI 1.1, 4.4]; 0.23% [95% CI 0.1, 0.4]). Finally, randomised controlled trials that investigate the effect of treating sleep disorders in people with type 2 diabetes are scarce, based on a small number of participants and sometimes inconclusive. Conventional therapies such as weight loss, sleep education and cognitive behavioural therapy seem to be effective in improving sleep and health outcomes in people with type 2 diabetes. We conclude that sleep disorders are highly prevalent in people with type 2 diabetes, negatively affecting health outcomes. Since treatment of the sleep disorder could prevent diabetes progression, efforts should be made to diagnose and treat sleep disorders in type 2 diabetes in order to ultimately improve health and therefore quality of life. Supplementary Information The online version contains peer-reviewed but unedited supplementary material including a slideset of the figures for download, available at 10.1007/s00125-021-05541-0.

Objective: To report complication rates following prolapse surgery using polypropylene mesh inlay, polypropylene mesh kit, biological collagen xenografts and native tissue repairs. Design: Secondary analysis of the PROSPECT randomised controlled trial and cohort study. Setting: Thirty-five UK hospitals. Population: A total of 2632 women undergoing anterior and/or posterior vaginal prolapse repair. Methods: Event rates were calculated for all complications. Analysis was by treatment received. Main outcome measures: IUGA/ICS classification of complications and validated patient reported outcome measures. Results: At baseline, 8.4% of women had ‘generic’ pain/discomfort; at 2 years following surgery, there was an improvement in all four groups; however, 3.0% of women developed de novo extreme generic pain. At 24 months de novo vaginal tightness occurred in 1.6% of native tissue, 1.2% of biological xenograft, 0.3% of mesh inlay and 3.6% of mesh kit. Severe dyspareunia occurred in 4.8% of native tissue, 4.2% of biological xenograft, 3.4% of mesh inlay repairs and 13.0% of mesh kits. De novo severe dyspareunia occurred in 3.5% of native tissue, 3.5% of biological xenograft, 1.4% of mesh inlays and 4.8% of mesh kits. Complications requiring re-admission to hospital, unrelated to mesh, affected 1 in 24 women; the most common reasons for re-admission were vaginal adhesions, urinary retention, infection and constipation. Conclusions: This is the first study to address the complications of vaginal mesh used for prolapse surgery alongside data from both native tissue and biological xenograft. It demonstrates the complexity of assessing pain and that all types of prolapse surgery have low surgical morbidity and a low rate of severe complications. Tweetable abstract: A prospective study of 2362 women undergoing vaginal mesh, xenograft or native tissue repair found low surgical morbidity and low rates of severe complications.

Objective To compare standard (native tissue) repair with synthetic mesh inlays or mesh kits. Design Randomised controlled trial. Setting Thirty-three UK hospitals. Population Women having surgery for recurrent prolapse. Methods Women recruited using remote randomisation. Main outcome measures Prolapse symptoms, condition-specific quality-of-life and serious adverse effects. Results A Mean Pelvic Organ Prolapse Symptom Score at 1 year was similar for each comparison (standard 6.6 versus mesh inlay 6.1, mean difference [MD] -0.41, 95% CI -2.92 to 2.11: standard 6.6 versus mesh kit 5.9, MD -1.21 , 95% CI -4.13 to 1.72) but the confidence intervals did not exclude a minimally important clinical difference. There was no evidence of difference in any other outcome measure at 1 or 2 years. Serious adverse events, excluding mesh exposure, were similar at 1 year (standard 7/55 [13%] versus mesh inlay 5/52 [10%], risk ratio [RR] 1.05 [0.66-1.68]: standard 3/25 [12%] versus mesh kit 3/46 [7%], RR 0.49 [0.11-2.16]). Cumulative mesh exposure rates over 2 years were 7/52 (13%) in the mesh inlay arm, of whom four women required surgical revision; and 4/46 in the mesh kit arm (9%), of whom two required surgical revision. Conclusions We did not find evidence of a difference in terms of prolapse symptoms from the use of mesh inlays or mesh kits in women undergoing repeat prolapse surgery. Although the sample size was too small to be conclusive, the results provide a substantive contribution to future meta-analysis. Tweetable abstract There is not enough evidence to support use of synthetic mesh inlay or mesh kits for repeat prolapse surgery.

Objective Out-of-hospital cardiac arrest (OHCA) occurrence has been shown to exhibit a circadian rhythm, following the circadian rhythm of acute myocardial infarction (AMI) occurrence. Diabetes mellitus (DM) is associated with changes in circadian rhythm. We aimed to compare the temporal variation of OHCA occurrence over the day and week between OHCA patients with DM and those without. Methods In two population-based OHCA registries (Amsterdam Resuscitation Studies [ARREST] 2010–2016, n=4163, and Danish Cardiac Arrest Registry [DANCAR], 2010–2014, n=12,734), adults (≥18y) with presumed cardiac cause of OHCA and available medical history were included. Single and double cosinor analysis was performed to model circadian variation of OHCA occurrence. Stratified analysis of circadian variation was performed in patients with AMI as immediate cause of OHCA. Results DM patients (22.8% in ARREST, 24.2% in DANCAR) were older and more frequently had cardiovascular risk factors or previous cardiovascular disease. Both cohorts showed 24h-rhythmicity, with significant amplitudes in single and double cosinor functions (P-rangeP-range 0.13–84). Conclusions In these two population-based OHCA registries, we observed a similar circadian rhythm of OHCA occurrence in DM and non-DM patients.

Background Vitamin K is associated with reduced cardiovascular disease risk such as heart failure, possibly by carboxylation of matrix-gla protein (MGP), a potent inhibitor of vascular calcification. The relationship of vitamin K intake or status with cardiac structure and function is largely unknown. Therefore this study aims to investigate the prospective association of vitamin K status and intake with echocardiographic measures. Methods This study included 427 participants from the Hoorn Study, a population-based cohort. Vitamin K status was assessed at baseline by plasma desphospho-uncarboxylated MGP (dp-ucMGP) with higher concentrations reflecting lower vitamin K status. Vitamin K intake was assessed at baseline with a validated food-frequency questionnaire. Echocardiography was performed at baseline and after a mean follow-up time of 7.6, SD=±0.7 years. We used linear regression for the association of vitamin K status and intake with left ventricular ejection fraction (LVEF), left atrial volume index (LAVI) and left ventricular mass index (LVMI), adjusted for potential confounders. Results The mean age was 66.8, SD=±6.1 years (51% were male). A high vitamin K status was prospectively associated with decreased LVMI (change from baseline to follow-up: -5.0, 95% CI: -10.5;0.4 g/m2.7) for the highest quartile compared to the lowest in women (P-interaction sex=0.07). No association was found in men. Vitamin K status was not associated with LVEF or LAVI. Vitamin K intake was not associated with any of the echocardiographic measures. Conclusions This study showed a high vitamin K status being associated with decreased LVMI only in women, while intakes of vitamin K were not associated with any cardiac structure or function measures. These results extend previous findings for a role of vitamin K status to decrease heart failure risk.

Objectives To identify and assess the quality and accuracy of prognostic models for nephropathy and to validate these models in external cohorts of people with type 2 diabetes. Design Systematic review and external validation. Data sources PubMed and Embase. Eligibility criteria Studies describing the development of a model to predict the risk of nephropathy, applicable to people with type 2 diabetes. Methods Screening, data extraction, and risk of bias assessment were done in duplicate. Eligible models were externally validated in the Hoorn Diabetes Care System (DCS) cohort (n=11 450) for the same outcomes for which they were developed. Risks of nephropathy were calculated and compared with observed risk over 2, 5, and 10 years of follow-up. Model performance was assessed based on intercept adjusted calibration and discrimination (Harrell’s C statistic). Results 41 studies included in the systematic review reported 64 models, 46 of which were developed in a population with diabetes and 18 in the general population including diabetes as a predictor. The predicted outcomes included albuminuria, diabetic kidney disease, chronic kidney disease (general population), and end stage renal disease. The reported apparent discrimination of the 46 models varied considerably across the different predicted outcomes, from 0.60 (95% confidence interval 0.56 to 0.64) to 0.99 (not available) for the models developed in a diabetes population and from 0.59 (not available) to 0.96 (0.95 to 0.97) for the models developed in the general population. Calibration was reported in 31 of the 41 studies, and the models were generally well calibrated. 21 of the 64 retrieved models were externally validated in the Hoorn DCS cohort for predicting risk of albuminuria, diabetic kidney disease, and chronic kidney disease, with considerable variation in performance across prediction horizons and models. For all three outcomes, however, at least two models had C statistics >0.8, indicating excellent discrimination. In a secondary external validation in GoDARTS (Genetics of Diabetes Audit and Research in Tayside Scotland), models developed for diabetic kidney disease outperformed those for chronic kidney disease. Models were generally well calibrated across all three prediction horizons. Conclusions This study identified multiple prediction models to predict albuminuria, diabetic kidney disease, chronic kidney disease, and end stage renal disease. In the external validation, discrimination and calibration for albuminuria, diabetic kidney disease, and chronic kidney disease varied considerably across prediction horizons and models. For each outcome, however, specific models showed good discrimination and calibration across the three prediction horizons, with clinically accessible predictors, making them applicable in a clinical setting. Systematic review registration PROSPERO CRD42020192831.

© 2021 Elsevier B.V. The prevalence of multimorbidity and polypharmacy increases significantly with age and are associated with negative health consequences. However, most current interventions to optimize medication have failed to show significant effects on patient-relevant outcomes. This may be due to ineffectiveness of interventions themselves but may also reflect other factors: insufficient sample sizes, heterogeneity of population. To address this issue, the international PROPERmed collaboration was set up to obtain/synthesize individual participant data (IPD) from five cluster-randomized trials. The trials took place in Germany and The Netherlands and aimed to optimize medication in older general practice patients with chronic illness. PROPERmed is the first database of IPD to be drawn from multiple trials in this patient population and setting. It offers the opportunity to derive prognostic models with increased statistical power for prediction of patient-relevant outcomes resulting from the interplay of multimorbidity and polypharmacy. This may help patients from this heterogeneous group to be stratified according to risk and enable clinicians to identify patients that are likely to benefit most from resource/time-intensive interventions. The aim of this manuscript is to describe the rationale behind PROPERmed collaboration, characteristics of the included studies/participants, development of the harmonized IPD database and challenges faced during this process.

ObjectiveTo develop an algorithm (sCOVID) to predict the risk of severe complications of COVID- 19 in a community-dwelling population to optimise vaccination scenarios.DesignPopulation based cohort studySetting264 Dutch general practices contributing to the NL-COVID databaseParticipants6074 people aged 0-99 diagnosed with COVID-19Main outcome measuresSevere complications (hospitalisation, institutionalisation, death). The algorithm was developed from a training dataset comprising 70% of the patients and validated in the remaining 30%. Potential predictor variables included age, sex, a chronic co-morbidity score (CCS) based on risk factors for COVID-19 complications as defined by the National Institute of Public Health and the Environment (RIVM), obesity, neighborhood deprivation score (NDS), first or second COVID wave, and confirmation test. Six different population vaccination scenarios were explored: 1) random (naive), 2) random for persons above 60 years (60plus), 3) oldest patients first in age bands of five years (oldest first), 4) target population of the annual influenza vaccination program (influenza) and 5) those 25-65 years of age first (worker), and 6) risk-based using the prediction algorithm (sCOVID). For each vaccination strategy the amount of vaccinations needed to reach a 50% reduction of severe complications was calculated.ResultsSevere complications were reported in 243 (4.8%) people with 59 (20.3%) nursing home admissions, 181 (62.2%) hospitalisations and 51 (17.5%) deaths. The algorithm included age, sex, CCS, NDS, wave, and confirmation test with a c statistic of 0.91 (95% CI 0.88-0.94) in the validation set. Applied to different vaccination scenarios, the proportion of people needed to be vaccinated to reach a 50% reduction of severe complications was 67.5%, 50.0%, 26.1%, 16.0%, 10.0%, and 8.4% for the worker, naive, infuenza, 60plus, oldest first, and sCOVID scenarios respectively.ConclusionCOVID-19 related severe complications will be reduced most efficiently when vaccinations are risk-based, prioritizing the highest risk group using the sCOVID algorithm. The vaccination scenario, prioritising oldest people in age bands of 5 years down to 60 years of age, performed second best. The sCOVID algorithm can readily be applied to identify persons with highest risks from data in the electronic health records of GPs.What is already known on this topic?Severe COVID-19 complications may be reduced when persons at the highest risk will be vaccinated first.To identify persons at a high risk for hospitalization or death in the general population, a limited number of prediction algorithms have been developed.Most of these algorithms were based on data from the first wave of infections (spring 2020) when widespread testing was not always possible, limiting the usefulness of these algorithms.What this study addsIncluding data up to January 2021, we developed and validated a prediction algorithm (sCOVID) with a c-statistic of 0.91 (95% CI 0.88-0.94) based on age, sex, chronic comorbidity score, economic status, wave, and a confirmation test to identify patients in the general population that are at risk of severe COVID-19 complication.Using the algorithm, a 50% reduction of patients with severe complications could be obtained with a vaccination coverage of only 8%. This vaccination scenario based on this algorithm was superior to other calculated vaccination scenarios.The sCOVID algorithm can readily be implemented in the electronic health records of general practitioners.

OBJECTIVE We investigated the processes underlying glycemic deterioration in type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS A total of 732 recently diagnosed patients with T2D from the Innovative Medicines Initiative Diabetes Research on Patient Stratification (IMI DIRECT) study were extensively phenotyped over 3 years, including measures of insulin sensitivity (OGIS), β-cell glucose sensitivity (GS), and insulin clearance (CLIm) from mixed meal tests, liver enzymes, lipid profiles, and baseline regional fat from MRI. The associations between the longitudinal metabolic patterns and HbA1c deterioration, adjusted for changes in BMI and in diabetes medications, were assessed via stepwise multivariable linear and logistic regression. RESULTS Faster HbA1c progression was independently associated with faster deterioration of OGIS and GS and increasing CLIm; visceral or liver fat, HDL-cholesterol, and triglycerides had further independent, though weaker, roles (R2 = 0.38). A subgroup of patients with a markedly higher progression rate (fast progressors) was clearly distinguishable considering these variables only (discrimination capacity from area under the receiver operating characteristic = 0.94). The proportion of fast progressors was reduced from 56% to 8–10% in subgroups in which only one trait among OGIS, GS, and CLIm was relatively stable (odds ratios 0.07–0.09). T2D polygenic risk score and baseline pancreatic fat, glucagon-like peptide 1, glucagon, diet, and physical activity did not show an independent role. CONCLUSIONS Deteriorating insulin sensitivity and β-cell function, increasing insulin clearance, high visceral or liver fat, and worsening of the lipid profile are the crucial factors mediating glycemic deterioration of patients with T2D in the initial phase of the disease. Stabilization of a single trait among insulin sensitivity, β-cell function, and insulin clearance may be relevant to prevent progression.

How long does the average person sleep? Here, Kocevska et al. conducted a meta-analysis including over 1.1 million people to produce age- and sex-specific population reference charts for sleep duration and efficiency.We aimed to obtain reliable reference charts for sleep duration, estimate the prevalence of sleep complaints across the lifespan and identify risk indicators of poor sleep. Studies were identified through systematic literature search in Embase, Medline and Web of Science (9 August 2019) and through personal contacts. Eligible studies had to be published between 2000 and 2017 with data on sleep assessed with questionnaires including >= 100 participants from the general population. We assembled individual participant data from 200,358 people (aged 1-100 years, 55% female) from 36 studies from the Netherlands, 471,759 people (40-69 years, 55.5% female) from the United Kingdom and 409,617 people (>= 18 years, 55.8% female) from the United States. One in four people slept less than age-specific recommendations, but only 5.8% slept outside of the 'acceptable' sleep duration. Among teenagers, 51.5% reported total sleep times (TST) of less than the recommended 8-10 h and 18% report daytime sleepiness. In adults (>= 18 years), poor sleep quality (13.3%) and insomnia symptoms (9.6-19.4%) were more prevalent than short sleep duration (6.5% with TST < 6 h). Insomnia symptoms were most frequent in people spending >= 9 h in bed, whereas poor sleep quality was more frequent in those spending = 41 years) reported sleeping shorter times or slightly less efficiently than men, whereas with actigraphy they were estimated to sleep longer and more efficiently than man. This study provides age- and sex-specific population reference charts for sleep duration and efficiency which can help guide personalized advice on sleep length and preventive practices.

Background: A low vitamin D and K status has been associated with increased cardiovascular disease (CVD) risk but the evidence of their combined effect on cardiovascular health is limited.Objectives: Our study aimed to investigate the prospective association of vitamin D and K status with subclinical measures of cardiovascular health and all-cause mortality among a population of Dutch Caucasians.Methods: We performed an observational prospective study on 601 participants of the Hoorn Study (mean +/- SD age: 70 +/- 6 y, 50.4% women, BMI: 27.2 +/- 4.0 kg/m(2)), of whom 321 underwent an echocardiogram in 2000-2001 and 2007-2009. Vitamin D and K status was assessed at baseline by serum 25-hydroxyvitamin D [25(OH)D] and plasma desphospho-uncarboxylated matrix-gla protein (dp-ucMGP)-high concentrations indicate low vitamin K status. Vital status was assessed from baseline until 2018. We studied the association of categories of 25(OH)D (stratified by the clinical cutoff of 50 mmol/L) and dp-ucMGP (stratified by the median value of 568 pmol/L) with echocardiographic measures using linear regression and with all-cause mortality using Cox regression, adjusted for confounders.Results: Compared with markers of normal vitamin D and K status, markers of low vitamin D and K status were prospectively associated with increased left ventricular mass index (5.9 g/m(2.7); 95% CI: 1.8, 10.0 g/m(2.7)). Participants with low vitamin D and K status were also at increased risk of all-cause mortality with an HR of 1.64 (95% CI: 1.12, 2.39) compared with normal vitamin D and K status.Conclusions: A combination of low vitamin D and K status is associated with adverse cardiac remodeling and increased risk of all-cause mortality in men and women. Future studies should investigate whether vitamin D and K supplementation could help to improve cardiovascular health and to decrease CVD risk.

IntroductionSex differences in cardiometabolic risk factors and their management in type 2 diabetes (T2D) have not been fully identified. Therefore, we aimed to examine differences in cardiometabolic risk factor levels, pharmacological treatment and achievement of risk factor control between women and men with T2D.Research design and methodsCross-sectional data from the Dutch Diabetes Pearl cohort were used (n=6637, 40% women). Linear and Poisson regression analyses were used to examine sex differences in cardiometabolic risk factor levels, treatment, and control.ResultsCompared with men, women had a significantly higher body mass index (BMI) (mean difference 1.79 kg/m2 (95% CI 1.49 to 2.08)), while no differences were found in hemoglobin A1c (HbA1c) and systolic blood pressure (SBP). Women had lower diastolic blood pressure (−1.94 mm Hg (95% CI −2.44 to −1.43)), higher total cholesterol (TC) (0.44 mmol/L (95% CI 0.38 to 0.51)), low-density lipoprotein cholesterol (LDL-c) (0.26 mmol/L (95% CI 0.22 to 0.31)), and high-density lipoprotein cholesterol (HDL-c) sex-standardized (0.02 mmol/L (95% CI 0.00 to 0.04)), and lower TC:HDL ratio (−0.29 (95% CI −0.36 to −0.23)) and triglycerides (geometric mean ratio 0.91 (95% CI 0.85 to 0.98)). Women had a 16% higher probability of being treated with antihypertensive medication in the presence of high cardiovascular disease (CVD) risk and elevated SBP than men (relative risk 0.84 (95% CI 0.73 to 0.98)), whereas no sex differences were found for glucose-lowering medication and lipid-modifying medication. Among those treated, women were less likely to achieve treatment targets of HbA1c (0.92 (95% CI 0.87 to 0.98)) and LDL-c (0.89 (95% CI 0.85 to 0.92)) than men, while no differences for SBP were found.ConclusionsIn this Dutch T2D population, women had a slightly different cardiometabolic risk profile compared with men and a substantially higher BMI. Women had a higher probability of being treated with antihypertensive medication in the presence of high CVD risk and elevated SBP than men, and were less likely than men to achieve treatment targets for HbA1c and LDL levels.

BackgroundIn 2016, 26% of UK men were estimated to be obese. Systematic reviews suggest that few men engage in formal weight loss interventions that support weight reduction and improve health.ObjectiveTo co-produce, with patient and public involvement, an acceptable and feasible randomised controlled trial design to test a men-only weight management intervention.DesignThis was a two-phase feasibility study. Phase 1 was the development of intervention components, study procedures and materials including a discrete choice experiment with survey questions. Phase 2 was an individually randomised three-arm feasibility trial over 12 months. Qualitative interviews were conducted at 3 and 12 months.SettingThe setting was two sites in Scotland that had disadvantaged urban and rural areas and differed in employment levels and ethnic groups.ParticipantsIn phase 1, 1045 men with obesity were recruited by Ipsos MORI (London, UK;www.ipsos.com/ipsos-mori/en-uk) to represent the UK population. In phase 2, 105 men with obesity were recruited in the community or through general practice obesity registers. Qualitative interviews were conducted with 50 men at 3 months and with 33 men at 12 months.InterventionsThe trial arms were narrative short message service (SMS) for 12 months (SMS only), financial endowment incentive informed by loss aversion and linked to achievement of weight loss targets plus narrative SMS for 12 months (SMS + I), and waiting list control group for 12 months followed by 3 months of an alternative SMS style developed based on feedback from men who had received the narrative SMS (control).Main outcome measuresThe main outcome measures were acceptability and feasibility of recruitment, retention, engagement, intervention components and trial procedures. Outcomes were assessed by examining procedural, quantitative and qualitative data at 3, 6 and 12 months.ResultsThe most acceptable incentive strategy, based on the discrete choice experiment results, was to verify weight loss of 5% at 3 months, verify weight loss of 10% at 6 months and maintain weight loss of 10% at 12 months. Overall, 105 men with obesity from across the socioeconomic spectrum were successfully recruited to target, 59% of whom lived in more disadvantaged areas. Retention at 12 months was acceptable (74%) and was higher among individuals from disadvantaged areas. Narrative SMS were acceptable to many men, with a minority reporting negative reactions. Incentives were acceptable but were not the primary motivation for behaviour change. Twelve men in the incentive arm (33%) secured at least some money and three (8%) secured the full amount. Both intervention arms lost some weight, with greater weight loss in the arm that received SMS and incentives. The alternative SMS based on men’s feedback received no strong negative reactions.LimitationsFewer participants from the SMS + I arm (64%) completed the study at 12 months than did those in the SMS-only (79%) and control (83%) arms. The reasons for this difference were complex.ConclusionsThe men-only weight management intervention consisting of narrative SMS and financial incentives was acceptable and feasible, meeting the progression criteria for a full trial. Tailoring of SMS may improve acceptability and retention.Future workMinor refinements to the intervention components based on the study findings will be made prior to testing in a multisite definitive randomised controlled trial.Trial registrationClinicalTrials.gov NCT03040518.FundingThis project was funded by the National Institute for Health Research (NIHR) Public Health Research programme and will be published in full inPublic Health Research; Vol. 8, No. 11. See the NIHR Journals Library website for further project information.

Extracellular matrix protein turnover may play an important role in left atrial (LA) remodelling. The aim is to investigate the associations between matrix metalloproteinase (MMPs), tissue inhibitor of metalloproteinase (TIMP-1) and LA volume index (LAVI) and if these associations are independent of TIMP-1 levels. Participants from The Hoorn Study, a population-based cohort study (n = 674), underwent echocardiography. Serum MMPs (i.e. MMP-1, MMP-2, MMP-3, MMP-9, and MMP-10) and TIMP-1 levels were measured with ELISA. Multiple linear regression analyses were used. MMP-1 levels were not associated with LAVI. Higher MMP-2 levels were associated with larger LAVI (regression coefficient per SD increase in MMP (95% CI), 0.03 (0.01, 0.05). Higher MMP-3 and MMP-9 levels were associated with smaller LAVI, &minus, 0.04 (&minus, 0.07, 0.01) and &minus, 0.06, 0.02) respectively. Only in women were higher MMP-10 levels associated with larger LAVI, 0.04 (0.00, 0.07, p-interaction 0.04). Additionally, only in women were higher TIMP-1 levels associated with smaller LAVI, 0.05 (&minus, 0.09, 0.01, p-interaction 0.03). The associations between MMPs and LAVI were independent of TIMP-1 levels. In conclusion, serum MMPs are associated with LAVI, independent of CVD risk factors and TIMP-1 levels. In addition, these associations differ according to sex and within MMP subgroups. This shows that the role of MMPs in LA remodelling is complex.

AIM: To investigate the relative contribution of phenotypic and lifestyle factors to HbA1c, independent of fasting plasma glucose (FPG) and 2h post-load glucose (2hPG), in the general population. METHODS: The study populations included 2309 participants without known diabetes from the first wave of the Hoorn Study (1989) and 2619 from the second wave (2006). Multivariate linear regression models were used to analyze the relationship between potential determinants and HbA1c in addition to FPG and 2hPG. The multivariate model was derived in the first wave of the Hoorn Study, and replicated in the second wave. RESULTS: In both cohorts, independent of FPG and 2hPG, higher age, female sex, larger waist circumference, and smoking were associated with a higher HbA1c level. Larger hip circumference, higher BMI, higher alcohol consumption and vitamin C intake were associated with a lower HbA1c level. FPG and 2hPG together explained 41.0% (first wave) and 53.0% (second wave) of the total variance in HbA1c. The combination of phenotypic and lifestyle determinants additionally explained 5.7% (first wave) and 3.9% (second wave). CONCLUSIONS: This study suggests that, independent of glucose, phenotypic and lifestyle factors are associated with HbA1c, but the contribution is relatively small. These findings contribute to a better understanding of the low correlation between glucose levels and HbA1c in the general population.

Progress in high-throughput metabolic profiling provides unprecedented opportunities to obtain insights into the effects of drugs on human metabolism. The Biobanking BioMolecular Research Infrastructure of the Netherlands has constructed an atlas of drug-metabolite associations for 87 commonly prescribed drugs and 150 clinically relevant plasma-based metabolites assessed by proton nuclear magnetic resonance. The atlas includes a meta-analysis of ten cohorts (18,873 persons) and uncovers 1,071 drug-metabolite associations after evaluation of confounders including co-treatment. We show that the effect estimates of statins on metabolites from the cross-sectional study are comparable to those from intervention and genetic observational studies. Further data integration links proton pump inhibitors to circulating metabolites, liver function, hepatic steatosis and the gut microbiome. Our atlas provides a tool for targeted experimental pharmaceutical research and clinical trials to improve drug efficacy, safety and repurposing. We provide a web-based resource for visualization of the atlas (http://bbmri.researchlumc.nl/atlas/).

Aims This study aimed to establish whether higher levels of glycated haemoglobin (HbA1c) are associated with increased sudden cardiac arrest (SCA) risk in non-diabetic individuals. Methods and results Case–control study in non-diabetic individuals (HbA1c six-fold increased VF risk [adjusted odds ratio (ORadj) 6.74 (5.00–9.09)] and that 0.1% increase in HbA1c level was associated with 1.4-fold increase in VF risk, independent of concomitant cardiovascular risk factors. Increased VF risk at higher HbA1c is associated with acute myocardial infarction (MI) as cause of VF [OR 1.14 (1.04–1.24)], but the association between HbA1c and VF was similar in non-MI patients [OR 1.32 (1.21–1.44)] and MI patients [OR 1.47 (1.37–1.58)]. Conclusion Among non-diabetic individuals, risk of VF increased with rising HbA1c levels, independent of concomitant cardiovascular disease. Future studies should establish whether HbA1c level may be used as biomarker to recognize individuals at risk for VF.

Good clinical care depends on accurate and precise measurement and is essential throughout medicine. Many decisions about patient care in ophthalmology are based on changes in the measurement of characteristics over time (intraocular pressure in glaucoma, central retinal thickness in medical retina studies, Kmax readings in keratoconus) or differences between the measurements for an individual and the ‘normal’ population (or more strictly speaking those without the condition of interest). We want to know the true value of the characteristic, but this is obtained with measurement error. Measurement error is the difference between the known measured quantity and its unknown true value. It has two main components: random error due to chance and systematic error (sometimes known as systematic bias) not due to chance. Precision is related to random error while accuracy is related to systematic error. Measurement error may cause inappropriate patient management or harm.1 No method of measurement is completely without measurement error. Often less invasive and cheaper methods of measurement have more measurement error. One has to balance the desire for an accurate measurement, against being overly invasive to the patient or too time-consuming to incorporate in a routine clinical setting. Medicine moves at a rapid rate and new measurement technologies frequently arrive in the marketplace. While once there was a single method to measure intraocular pressure (Goldmann Applanation Tonometry), now there are many different methods and different machines on the market for example, non-contact tonometers, hand-held devices, etc. Newer methods may be more accurate and precise than older methods or may be cheaper or quicker to use. Some methods may be more convenient to use, but can have greater measurement error. The regulatory framework for devices within the UK is very different to that of medicines and while safety of the new instrument must be demonstrated, …

Structural analysis of the Indian Merge 3D seismic survey identified three populations of normal faults within the Exmouth Sub-basin of the North West Shelf volcanic margin of Australia. They comprise (1) latest-Triassic to Middle Jurassic N-NNE-trending normal faults (Fault Population I); (2) Late Jurassic to Early Cretaceous NE-trending normal faults (Fault Population II); and (3) latest-Triassic to Early Cretaceous N-NNE faults (Fault Population III). Quantitative evaluation of >100 faults demonstrates that fault displacement occurred during two time periods (210–163 and 145–138 Ma) separated by ∼20 Myr of tectonic quiescence. Latest Jurassic to Early Cretaceous (145–138 Ma) evolution comprises magmatic addition and contemporaneous domal uplift ∼70 km wide characterised by ≥ 900 m of denudation. The areally restricted subcircular uplift centred on the southern edge of the extended continental promontory of the southern Exmouth Sub-basin supports latest Jurassic mantle plume upwelling that initiated progradation of the Barrow Delta. This polyphase and bimodal structural evolution impacts current hydrocarbon exploration rationale by defining the nature of latest Jurassic to Early Cretaceous fault nucleation and reactivation within the southern Exmouth Sub-basin.

In this article, findings of a qualitative study of an Indigenous widening participation program are presented. The program, River of Learning, has been in existence since 2010 and represents a pow...

Background: The use of transvaginal mesh and biological graft material in prolapse surgery is controversial and has led to a number of enquiries into their safety and efficacy. Existing trials of these augmentations are individually too small to be conclusive. We aimed to compare the outcomes of prolapse repair involving either synthetic mesh inlays or biological grafts against standard repair in women.Methods: We did two pragmatic, parallel-group, multicentre, randomised controlled trials for our study (PROSPECT [PROlapse Surgery: Pragmatic Evaluation and randomised Controlled Trials]) in 35 centres (a mix of secondary and tertiary referral hospitals) in the UK. We recruited women undergoing primary transvaginal anterior or posterior compartment prolapse surgery by 65 gynaecological surgeons in these centres. We randomly assigned participants by a remote web-based randomisation system to one of the two trials: comparing standard (native tissue) repair alone with standard repair augmented with either synthetic mesh (the mesh trial) or biological graft (the graft trial). We assigned women (1:1:1 or 1:1) within three strata: assigned to one of the three treatment options, comparison of standard repair with mesh, and comparison of standard repair with graft. Participants, ward staff, and outcome assessors were masked to randomisation where possible; masking was obviously not possible for the surgeon. Follow-up was for 2 years after the surgery; the primary outcomes, measured at 1 year and 2 years, were participant-reported prolapse symptoms (i.e. the Pelvic Organ Prolapse Symptom Score [POP-SS]) and condition-specific (ie, prolapse-related) quality-of-life scores, analysed in the modified intention-to-treat population. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN60695184.Findings: Between Jan 8, 2010, and Aug 30, 2013, we randomly allocated 1352 women to treatment, of whom 1348 were included in the analysis. 865 women were included in the mesh trial (430 to standard repair alone, 435 to mesh augmentation) and 735 were included in the graft trial (367 to standard repair alone, 368 to graft augmentation). Because the analyses were carried out separately for each trial (mesh trial and graft trial) some women in the standard repair arm assigned to all treatment options were included in the standard repair group of both trials. 23 of these women did not receive any surgery (15 in the mesh trial, 13 in the graft trial; five were included in both trials) and were included in the baseline analyses only. Mean POP-SS at 1 year did not differ substantially between comparisons (standard 5·4 [SD 5·5] vs mesh 5·5 [5·1], mean difference 0·00, 95% CI −0·70 to 0·71; p=0·99; standard 5·5 [SD 5·6] vs graft 5·6 [5·6]; mean difference −0·15, −0·93 to 0·63; p=0·71). Mean prolapse-related quality-of-life scores also did not differ between groups at 1 year (standard 2·0 [SD 2·7] vs mesh 2·2 [2·7], mean difference 0·13, 95% CI −0·25 to 0·51; p=0·50; standard 2·2 [SD 2·8] vs graft 2·4 [2·9]; mean difference 0·13, −0·30 to 0·56; p=0·54). Mean POP-SS at 2 years were: standard 4·9 (SD 5·1) versus mesh 5·3 (5·1), mean difference 0·32, 95% CI −0·39 to 1·03; p=0·37; standard 4·9 (SD 5·1) versus graft 5·5 (5·7); mean difference 0·32, −0·48 to 1·12; p=0·43. Prolapse-related quality-of-life scores at 2 years were: standard 1·9 (SD 2·5) versus mesh 2·2 (2·6), mean difference 0·15, 95% CI −0·23 to 0·54; p=0·44; standard 2·0 (2·5) versus graft 2·2 (2·8); mean difference 0·10, −0·33 to 0·52; p=0·66. Serious adverse events such as infection, urinary retention, or dyspareunia or other pain, excluding mesh complications, occurred with similar frequency in the groups over 1 year (mesh trial: 31/430 [7%] with standard repair vs 34/435 [8%] with mesh, risk ratio [RR] 1·08, 95% CI 0·68 to 1·72; p=0·73; graft trial: 23/367 [6%] with standard repair vs 36/368 [10%] with graft, RR 1·57, 0·95 to 2·59; p=0·08). The cumulative number of women with a mesh complication over 2 years in women actually exposed to synthetic mesh was 51 (12%) of 434.Interpretation: Augmentation of a vaginal repair with mesh or graft material did not improve women's outcomes in terms of effectiveness, quality of life, adverse effects, or any other outcome in the short term, but more than one in ten women had a mesh complication. Therefore, follow-up is vital to identify any longer-term potential benefits and serious adverse effects of mesh or graft reinforcement in vaginal prolapse surgery.Funding: UK National Institute of Health Research.

Objectives Oral malignant melanomas carry a poor-to-guarded prognosis because of their local invasiveness and high metastatic propensity. The Oncept melanoma vaccine is licensed to treat dogs with stage II or III locally-controlled oral malignant melanoma and this retrospective study aimed to assess survival of affected dogs treated with the vaccine in the UK. Material and Methods Medical records of dogs with histopathologically-confirmed oral malignant melanoma that received the vaccine as part of their treatment were evaluated. Survival analyses for potential prognostic factors were performed. Results Sixty-nine dogs were included; 56 dogs, staged I to III, and with previous locoregional therapy, had a median survival time of 455 days (95% CI: 324 to 586 days). Based on Kaplan-Meier survival analysis with associated log-rank testing, no significant prognostic factors were identified for this population. Of the 13 patients with macroscopic disease treated with vaccine alone or in combination therapy, eight showed clinical response. Three patients with stage IV oral malignant melanoma survived 171, 178 and 288 days from diagnosis. Clinical Significance Patients treated with the melanoma vaccine in our study had survival times similar to their counterparts receiving the vaccine in the USA. There were observed responses in patients with macroscopic disease and so the vaccine could be considered as palliative treatment in dogs with stage IV disease.

Introduction: The role of insufficient glucagon suppression after an oral load in the development of type 2 diabetes mellitus is unclear. The aim of this study was to examine the association between glucagon responses at baseline and fasting glucose levels 7 years later. Methods: Data of the Hoorn Meal Study were used, an observational cohort study among 121 persons without diabetes with a mean age of 61.1 ± 6.7 years and 50% being female. The glucagon response to an oral glucose tolerance test and mixed meal test was expressed as early and late incremental area under the curve. The association with change in fasting glucose levels at follow-up was assessed by linear regression analysis. Results: The early glucagon response following the mixed meal test was associated with an increase in fasting glucose levels of 0.18 mmol/L (95%-CI: 0.04-0.31, P = 0.01), per unit increase in the incremental area under the curve of glucagon, adjusted for confounders. No significant associations were observed for the late response after the mixed meal test or oral glucose tolerance test. Conclusions: Within a population without diabetes, relative lack of glucagon suppression early after a meal was associated with increased glucose levels over time, suggesting a role of insufficient glucagon suppression in the deterioration of glycaemic control.

Introduction Accidental urine leakage is a distressing problem that affects around one in three women. The main types of urinary incontinence (UI) are stress, urgency and mixed, with stress being most common. Current UK guidelines recommend that women with UI are offered at least 3 months of pelvic floor muscle training (PFMT). There is evidence that PFMT is effective in treating UI, however it is not clear how intensively women have to exercise to give the maximum sustained improvement in symptoms, and how we enable women to achieve this. Biofeedback is an adjunct to PFMT that may help women exercise more intensively for longer, and thus may improve continence outcomes when compared with PFMT alone. A Cochrane review was inconclusive about the benefit of biofeedback, indicating the need for further evidence. Methods and analysis This multicentre randomised controlled trial will compare the effectiveness and cost-effectiveness of PFMT versus biofeedback-mediated PFMT for women with stress UI or mixed UI. The primary outcome is UI severity at 24 months after randomisation. The primary economic outcome measure is incremental cost per quality-adjusted life-year at 24 months. Six hundred women from UK community, outpatient and primary care settings will be randomised and followed up via questionnaires, diaries and pelvic floor assessment. All participants are offered six PFMT appointments over 16 weeks. The use of clinic and home biofeedback is added to PFMT for participants in the biofeedback group. Group allocation could not be masked from participants and healthcare staff. An intention-to-treat analysis of the primary outcome will estimate the mean difference between the trial groups at 24 months using a general linear mixed model adjusting for minimisation covariates and other important prognostic covariates, including the baseline score. Ethics and dissemination Approval granted by the West of Scotland Research Ethics Committee 4 (16/LO/0990). Written informed consent will be obtained from participants by the local research team. Serious adverse events will be reported to the data monitoring and ethics committee, the ethics committee and trial centres as required. A Standard Protocol Items: Recommendations for Interventional Trials checklist and figure are available for this protocol. The results will be published in international journals and included in the relevant Cochrane review. Trial registration number ISRCTN57746448; Pre-results.

IntroductionAccidental urine leakage is a distressing problem that affects around one in three women. The main types of urinary incontinence (UI) are stress, urgency and mixed, with stress being most common. Current UK guidelines recommend that women with UI are offered at least 3 months of pelvic floor muscle training (PFMT). There is evidence that PFMT is effective in treating UI, however it is not clear how intensively women have to exercise to give the maximum sustained improvement in symptoms, and how we enable women to achieve this. Biofeedback is an adjunct to PFMT that may help women exercise more intensively for longer, and thus may improve continence outcomes when compared with PFMT alone. A Cochrane review was inconclusive about the benefit of biofeedback, indicating the need for further evidence.Methods and analysisThis multicentre randomised controlled trial will compare the effectiveness and cost-effectiveness of PFMT versus biofeedback-mediated PFMT for women with stress UI or mixed UI. The primary outcome is UI severity at 24 months after randomisation. The primary economic outcome measure is incremental cost per quality-adjusted life-year at 24 months. Six hundred women from UK community, outpatient and primary care settings will be randomised and followed up via questionnaires, diaries and pelvic floor assessment. All participants are offered six PFMT appointments over 16 weeks. The use of clinic and home biofeedback is added to PFMT for participants in the biofeedback group. Group allocation could not be masked from participants and healthcare staff. An intention-to-treat analysis of the primary outcome will estimate the mean difference between the trial groups at 24 months using a general linear mixed model adjusting for minimisation covariates and other important prognostic covariates, including the baseline score.Ethics and disseminationApproval granted by the West of Scotland Research Ethics Committee 4 (16/LO/0990). Written informed consent will be obtained from participants by the local research team. Serious adverse events will be reported to the data monitoring and ethics committee, the ethics committee and trial centres as required. A Standard Protocol Items: Recommendations for Interventional Trials checklist and figure are available for this protocol. The results will be published in international journals and included in the relevant Cochrane review.Trial registration numberISRCTN57746448; Pre-results.

Key Points Question To what extent are established cardiovascular risk factors associated with risk of venous thromboembolism (VTE)? Findings In this analysis of individual participant data from the Emerging Risk Factors Collaboration and the UK Biobank including 1.1 million participants, among a panel of several established cardiovascular risk factors, older age, smoking, and greater adiposity were consistently associated with higher VTE risk. Meaning There is overlap in at least some of the major population determinants of important venous and arterial thrombotic diseases., This analysis of data from the Emerging Risk Factors Collaboration and the UK Biobank estimates the associations of major cardiovascular risk factors with venous thromboembolism., Importance It is uncertain to what extent established cardiovascular risk factors are associated with venous thromboembolism (VTE). Objective To estimate the associations of major cardiovascular risk factors with VTE, ie, deep vein thrombosis and pulmonary embolism. Design, Setting, and Participants This study included individual participant data mostly from essentially population-based cohort studies from the Emerging Risk Factors Collaboration (ERFC; 731 728 participants; 75 cohorts; years of baseline surveys, February 1960 to June 2008; latest date of follow-up, December 2015) and the UK Biobank (421 537 participants; years of baseline surveys, March 2006 to September 2010; latest date of follow-up, February 2016). Participants without cardiovascular disease at baseline were included. Data were analyzed from June 2017 to September 2018. Exposures A panel of several established cardiovascular risk factors. Main Outcomes and Measures Hazard ratios (HRs) per 1-SD higher usual risk factor levels (or presence/absence). Incident fatal outcomes in ERFC (VTE, 1041; coronary heart disease [CHD], 25 131) and incident fatal/nonfatal outcomes in UK Biobank (VTE, 2321; CHD, 3385). Hazard ratios were adjusted for age, sex, smoking status, diabetes, and body mass index (BMI). Results Of the 731 728 participants from the ERFC, 403 396 (55.1%) were female, and the mean (SD) age at the time of the survey was 51.9 (9.0) years; of the 421 537 participants from the UK Biobank, 233 699 (55.4%) were female, and the mean (SD) age at the time of the survey was 56.4 (8.1) years. Risk factors for VTE included older age (ERFC: HR per decade, 2.67; 95% CI, 2.45-2.91; UK Biobank: HR, 1.81; 95% CI, 1.71-1.92), current smoking (ERFC: HR, 1.38; 95% CI, 1.20-1.58; UK Biobank: HR, 1.23; 95% CI, 1.08-1.40), and BMI (ERFC: HR per 1-SD higher BMI, 1.43; 95% CI, 1.35-1.50; UK Biobank: HR, 1.37; 95% CI, 1.32-1.41). For these factors, there were similar HRs for pulmonary embolism and deep vein thrombosis in UK Biobank (except adiposity was more strongly associated with pulmonary embolism) and similar HRs for unprovoked vs provoked VTE. Apart from adiposity, these risk factors were less strongly associated with VTE than CHD. There were inconsistent associations of VTEs with diabetes and blood pressure across ERFC and UK Biobank, and there was limited ability to study lipid and inflammation markers. Conclusions and Relevance Older age, smoking, and adiposity were consistently associated with higher VTE risk.

Background Previous studies have investigated the association between sleep duration, insomnia, day-time napping and metabolic syndrome individually, but never conjointly. In addition, the association with sleep medication use has yet to be investigated. We aimed to examine the associations between these sleep-related characteristics and the metabolic syndrome, individually and conjointly, in a population-based cohort. Material and methods We used cross-sectional data of 1679 participants from the New Hoorn study, 52.6% women and age 60.8 + 6.4y. Sleep duration, insomnia, and day-time napping were measured using validated questionnaires. The use of sleep medication was documented by the registration of dispensing labels. The metabolic syndrome was defined according to ATP III. Linear and Poisson regressions were used, and all analyses were adjusted for age, sex, education level, job status, smoking, physical activity, depression and BMI. Results In our population-based cohort, 447 (26.6%) persons had the metabolic syndrome. Individual associations showed that, after correction, day-time napping for ≤30 min and >30 min was associated with a prevalence ratio for the metabolic syndrome of 1.28 (95% CI: 1.1–1.5) and 1.74 (95% CI: 1.4–2.2), respectively, compared to participants who did not nap. Sleep duration, insomnia, and sleep medication use were not associated with the metabolic syndrome individually. However, conjointly analyses showed that, after correction, having ≥2 sleep-related characteristics was associated with a PR of 1.36 (95% CI: 1.0–1.8) of having the metabolic syndrome, compared to having no sleep-related characteristics. Conclusion Sleep-related characteristics were associated with a higher prevalence of the metabolic syndrome in the general population.

Trabecular bone score (TBS) is a grey-level textural index of bone microarchitecture derived from lumbar spine dual-energy X-ray absorptiometry (DXA) images. TBS is a BMD-independent predictor of fracture risk. The objective of this meta-analysis was to determine whether TBS predicted fracture risk independently of FRAX probability and to examine their combined performance by adjusting the FRAX probability for TBS. We utilized individual level data from 17,809 men and women in 14 prospective population-based cohorts. Baseline evaluation included TBS and the FRAX risk variables and outcomes during follow up (mean 6.7 years) comprised major osteoporotic fractures. The association between TBS, FRAX probabilities and the risk of fracture was examined using an extension of the Poisson regression model in each cohort and for each sex and expressed as the gradient of risk (GR; hazard ratio per 1SD change in risk variable in direction of increased risk). FRAX probabilities were adjusted for TBS using an adjustment factor derived from an independent cohort (the Manitoba Bone Density Cohort). Overall, the GR of TBS for major osteoporotic fracture was 1.44 (95% CI: 1.35-1.53) when adjusted for age and time since baseline and was similar in men and women (p > 0.10). When additionally adjusted for FRAX 10-year probability of major osteoporotic fracture, TBS remained a significant, independent predictor for fracture (GR 1.32, 95%CI: 1.24-1.41). The adjustment of FRAX probability for TBS resulted in a small increase in the GR (1.76, 95%CI: 1.65, 1.87 vs. 1.70, 95%CI: 1.60-1.81). A smaller change in GR for hip fracture was observed (FRAX hip fracture probability GR 2.25 vs. 2.22). TBS is a significant predictor of fracture risk independently of FRAX. The findings support the use of TBS as a potential adjustment for FRAX probability, though the impact of the adjustment remains to be determined in the context of clinical assessment guidelines. This article is protected by copyright. All rights reserved.

Background and aims: Data on the prospective relationship of alcohol consumption at more moderate levels with systolic and diastolic function are scarce. We aimed to examine the prospective association of alcohol consumption with echocardiographic measures of cardiac structure and function, in individuals with and without type 2 diabetes (T2DM).Methods and results: We included 778 participants from the Hoorn Study (aged 68.4 +/- 7.2 years, 49% women), a population-based prospective cohort study, oversampled for people with impaired glucose metabolism or T2DM. Self-reported alcohol consumption was collected at baseline with a validated food-frequency questionnaire and categorized into: none (0/week), light (>0-30-70-140 g/week). Echocardiography was performed at baseline (N = 778) and after 8 years follow-up (N = 404). Multiple linear regression was used to study the association between alcohol consumption and echocardiographic measures (left ventricular ejection fraction (LVEF), left atrial volume index (LAVI) and left ventricular mass index (LVMI)), adjusted for confounders. Moderate and heavy alcohol consumption were associated with a decreased LVEF of -3.91% (CI: -7.13;-0.69) for moderate and -4.77% (-8.18;-1.36) for heavy drinkers compared to light drinkers. No associations were found between alcohol consumption, LVMI and LAVI. Modified Poisson regression showed a trend that higher alcohol consumption amounts were associated with a higher risk of incident systolic dysfunction (LVEFConclusion: The findings provide longitudinal evidence that moderate and heavy alcohol consumption are associated with decreased LVEF and trend towards a higher risk of incident LV systolic dysfunction, compared to light drinkers. (C) 2019 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Introduction This article discusses a blueprint for a sexual health communication curriculum to facilitate undergraduate medical student acquisition of sexual history taking skills and includes recommendations for important elements of a thorough sexual history script for undergraduate medical students. Aim To outline the fundamentals, objectives, content, timing, and teaching methods of a gold standard curriculum in sexual health communication. Methods Consensus expert opinion was documented at the 2012, 2014, and 2016 Summits in Medical Education in Sexual Health. Additionally, the existing literature was reviewed regarding undergraduate medical education in sexual health. Main Outcome Measures This article reports expert opinion and a review of the literature on the development of a sexual history taking curriculum. Results First-year curricula should be focused on acquiring satisfactory basic sexual history taking skills, including both assessment of sexual risk via the 5 Ps (partners, practices, protection from sexually transmitted infections, past history of sexually transmitted infections, and prevention of pregnancy) as well as assessment of sexual wellness—described here as a sixth P (plus), which encompasses the assessment of trauma, violence, sexual satisfaction, sexual health concerns/problems, and support for gender identity and sexual orientation. Second-year curricula should be focused on incorporating improved clinical reasoning, emphasizing sexual history taking for diverse populations and practices, and including the impact of illness on sexual health. Teaching methods must include varied formats. Evaluation may be best as a formative objective structured clinical examination in the first year and summative in the second year. Barriers for curriculum development may be reduced by identifying faculty champions of sexual health/medicine. Clinical Implications Medical students will improve their skills in sexual history taking, which will ultimately impact patient satisfaction and clinical outcomes. Future research is needed to validate this proposed curriculum and assess the impact on clinical skills. Strengths & Limitations This article assimilates expert consensus and existing clinical guidelines to provide a novel structured approach to curriculum development in sexual health interviewing in the pre-clinical years. Conclusion The blueprint for developing sexual history taking skills includes a spiral curriculum with varied teaching formats, incorporation of a sexual history script that incorporates inquiry about sexual wellness, and longitudinal assessment across the pre-clinical years. Ideally, sexual health communication content should be incorporated into existing clinical interviewing and physical examination courses.

Background: People with aphasia present with different of demographic, language, stroke, and impairment profiles. A Cochrane review found that two-thirds of included trials had comparison data on p...

Topic To compare the accuracy of optical coherence tomography (OCT) with alternative tests for monitoring neovascular age-related macular degeneration (nAMD) and detecting disease activity among eyes previously treated for this condition. Clinical Relevance Traditionally, fundus fluorescein angiography (FFA) has been considered the reference standard to detect nAMD activity, but FFA is costly and invasive. Replacement of FFA by OCT can be justified if there is a substantial agreement between tests. Methods Systematic review and meta-analysis. The index test was OCT. The comparator tests were visual acuity, clinical evaluation (slit lamp), Amsler chart, color fundus photographs, infrared reflectance, red-free images and blue reflectance, fundus autofluorescence imaging, indocyanine green angiography (ICGA), preferential hyperacuity perimetry, and microperimetry. We searched the following databases: MEDLINE, MEDLINE In-Process, EMBASE, Biosis, Science Citation Index, the Cochrane Library, Database of Abstracts of Reviews of Effects, MEDION, and the Health Technology Assessment database. The last literature search was conducted in March 2013. We used the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) to assess risk of bias. Results We included 8 studies involving more than 400 participants. Seven reported the performance of OCT (3 time-domain [TD] OCT, 3 spectral-domain [SD] OCT, 1 both types) and 1 reported the performance of ICGA in the detection of nAMD activity. We did not find studies directly comparing tests in the same population. The pooled sensitivity and specificity of TD OCT and SD OCT for detecting active nAMD was 85% (95% confidence interval [CI], 72%–93%) and 48% (95% CI, 30%–67%), respectively. One study reported ICGA with sensitivity of 75.9% and specificity of 88.0% for the detection of active nAMD. Half of the studies were considered to have a high risk of bias. Conclusions There is substantial disagreement between OCT and FFA findings in detecting active disease in patients with nAMD who are being monitored. Both methods may be needed to monitor patients comprehensively with nAMD.

© 2017 The Author(s). Background: Several drugs have become available for the treatment of osteoporosis. However, screening and treatment of patients with a high fracture risk is currently not recommended in the Netherlands, because the effectiveness of bone sparing drugs has not been demonstrated in the general primary care population. Here we describe the design of the SALT Osteoporosis study, which aims to examine whether the screening and treatment of older, female patients in primary care can reduce fractures, in comparison to usual care. Methods: A randomised pragmatic trial has been designed using a stepwise approach in general care practices in the Netherlands. Women aged ≥65 years, who are not prescribed bone sparing drugs or corticosteroids are eligible for the study. First, women with at least one clinical risk factor for fractures, as determined by questionnaires, are randomly assigned to the intervention or control group. Second, women in the intervention group having a high fracture risk according to our screening program, including an adapted fracture risk assessment (FRAX) tool, combined with dual-energy x-ray absorptiometry (DXA), and instant vertebral assessment (IVA), are offered a structured treatment program. The women in the control group receive care as usual and will undergo the same screening as the intervention group at the end of the trial. The follow-up duration will be three years and the primary outcome is time to first incident fracture and the total number of fractures. Discussion: The results of the current study will be very important for underpinnings of the prevention strategy of the osteoporosis guidelines. Trial registration: ID NTR2430. Registered 26 July 2010.

Only a few studies have investigated the metabolic consequences of social jetlag. Therefore, we examined the association of social jetlag with the metabolic syndrome and type 2 diabetes mellitus in a population-based cohort. We used cross-sectional data from the New Hoorn Study cohort ( n = 1585, 47% men, age 60.8 ± 6 years). Social jetlag was calculated as the difference in midpoint sleep (in hours) between weekdays and weekend days. Poisson and linear regression models were used to study the associations, and age was regarded as a possible effect modifier. We adjusted for sex, employment status, education, smoking, physical activity, sleep duration, and body mass index. In the total population, we only observed an association between social jetlag and the metabolic syndrome, with prevalence ratios adjusted for sex, employment status, and educational levels of 1.64 (95% CI 1.1-2.4), for participants with >2 h social jetlag, compared with participants with 2 h social jetlag, compared with participants with

Psychosocial stress is associated with chronic disease. We evaluated whether in the general population the number of stressful life events is associated with risk of mortality and whether this association is mediated by behavioral factors and morbidities. We conducted this study in the Hoorn cohort; a population-based cohort study among older men and women. Our main variable of interest was the number of stressful life events experienced during the previous 5 years, which were assessed by questionnaire. We calculated Cox proportional hazard ratios (HRs) for all-cause and cause-specific mortality during follow-up for those who experienced stressful life events compared to those who did not. We included 2385 participants (46% male; 62 ± 7 years). During 20 years of follow-up 834 (35%) participants died, of whom 239 (28.6%) died of cardiovascular disease. Compared to the group with no stressful life events, the age, sex and socioeconomic status adjusted HRs (with 95% confidence intervals) for all-cause mortality, for the groups who had 1 event, 2 events, 3 events and ≥4 events were 0.89 (0.72–1.09), 1.01 (0.81–1.24), 1.29 (1.00–1.66) and 1.44 (1.08–1.92), respectively. Similar results were observed for cardiovascular mortality. Mediation analysis showed that smoking, prevalent type 2 diabetes and cardiovascular disease were statistically significant mediators of the association between the number of stressful life events and mortality. Having 3 or more stressful life events is associated with a significantly increased risk for mortality in an elderly population-based cohort. This association is mediated by smoking, type 2 diabetes and cardiovascular disease.

Objective To compare long-term outcomes following microwave endometrial ablation (MEA™) and thermal balloon ablation (TBall). Design Follow up of a prospective, double-blind randomised controlled trial at 5 years. Setting A teaching hospital in the UK. Population A total of 320 women eligible for and requesting endometrial ablation. Methods Eligible women were randomised in a 1:1 ratio to undergo MEA or Tball. Postal questionnaires were sent to participants at a minimum of 5 years postoperatively to determine satisfaction with outcome, menstrual status, bleeding scores and quality of life measurement. Subsequent surgery was ascertained from the women and the hospital operative database. Main outcome measures The primary outcome measure was overall satisfaction with treatment. Secondary outcomes included evaluation of menstrual loss, change in quality of life scores and subsequent surgery. Results Of the women originally randomised 217/314 (69.1%) returned questionnaires. Nonresponders were assumed to be treatment failures for data analysis. The primary outcome of satisfaction was similar in both groups (58% for MEA™ versus 53% for TBall, difference 5%; 95% CI −6 to 16%). Amenorrhoea rates were high following both techniques (51% versus 45%, difference 6%; 95% CI −5 to 17%). There was no significant difference in the hysterectomy rates between the two arms (9% versus 7%, difference 2%; 95% CI −5 to 9%). Conclusions At 5 years post-treatment there were no significant clinical differences in patient satisfaction, menstrual status, quality of life scores or hysterectomy rates between MEA™ and Thermachoice 3, thermal balloon ablation.

This is the protocol for a review and there is no abstract. The objectives are as follows: To synthesise Cochrane reviews of conservative interventions, as described above, for the prevention or treatment of female urinary incontinence. Outcomes are described below.

OBJECTIVES: The objectives of this study were to determine the prevalence of carriage of ESBL-producing Enterobacteriaceae (ESBL-E) in a representative sample of the general adult Dutch community, to identify risk factors and to gain understanding of the epidemiology of these resistant strains.METHODS: Adults enrolled in five general practices in Amsterdam were approached by postal mail and asked to fill in a questionnaire and to collect a faecal sample. Samples were analysed for the presence of ESBL-E. ESBL genes were characterized by PCR and sequencing. Strains were typed using MLST and amplified fragment length polymorphism (AFLP) and plasmids were identified by PCR-based replicon typing. Risk factors for carriage were investigated by multivariate analysis.RESULTS: ESBL-E were found in 145/1695 (8.6%) samples; 91% were Escherichia coli. Most ESBL genes were of the CTX-M group (blaCTX-M-1 and blaCTX-M-15). MLST ST131 was predominant and mainly associated with CTX-M-15-producing E. coli. One isolate with reduced susceptibility to ertapenem produced OXA-48. In multivariate analyses, use of antimicrobial agents, use of antacids and travel to Africa, Asia and Northern America were associated with carriage of ESBL-E, in particular strains with blaCTX-M-14/15.CONCLUSIONS: This study showed a high prevalence of ESBL-E carriage in the general Dutch community. Also, outside hospitals, the use of antibiotics was a risk factor; interestingly, use of antacids increased the risk of carriage. A major risk factor in the general population was travel to countries outside Europe, in particular to Asia, Africa and Northern America.

Background An expertise-based randomised trial design, where participating health professionals only provide the intervention in which they have expertise, has been proposed to overcome challenges faced when evaluating skill based interventions. Health professionals (e.g. surgeons/therapists) often have differing levels of expertise in the interventions, conduct only one routinely and/or have strong preferences. However understanding of this design is limited.

Hospitality management students, a community partner, and an instructor planned and conducted a festival related to sustainable tourism that showcased local products and heritage in a small Appalachian village as an authentic learning, community engagement project. The project was conceptualized and completed within a framework of the scholarship of engagement, place-based education, and sustainability. Student reflections revealed growth in their understanding of sustainability. Suggestions are offered for future research and learning opportunities regarding student attitudes toward and participation in sustainable tourism, authentic learning, and community engagement projects.

Sexually active adolescents need contraceptives. Nearly half of all 15- to 18-year-olds have engaged in sexual activity before finishing high school and >70% are sexually active by the age of 20 years. The consequences of adolescents having unprotected sex are devastating. Availability of contraceptives for adolescents in the United States is affected by multiple factors including individuals knowledge about contraceptives access to services and supplies affordability complex social and moral attitudes and governmental policies and regulations. Efforts in the United States (unlike those in other developed countries) to address adolescent sex have been directed toward preventing teenage sex as opposed to preventing its adverse consequences. Abstinence-only programs violate the fundamental human right of adolescents to accurate and comprehensive sexual health information. Preventing the adverse consequences of unprotected adolescent sex requires a broad-based approach that begins with the recognition that adolescents are both valued and vulnerable. (excerpt)

The use of computers in education in general and in medical education in particular is nowadays well established, but the use of computer-based assessment (CBA) in higher education lags behind. In this article we explore the reasons for this situation and provide tips for teachers to guide the introduction of CBA, based on our experiences. Attention is given to benefits and drawbacks of CBA hardware solutions, the choice of software, types of test questions, security, instructing students and teachers and evaluation.

Depressive symptoms and decreased physical functioning are interrelated conditions and common in older persons, causing significant individual and societal burden. Evidence suggests that vitamin D supplementation may be beneficial for both mental and physical functioning. However, previous randomized controlled trials have yielded inconsistent results and often had suboptimal designs. This study examines the effect of vitamin D supplementation on both depressive symptoms and physical functioning in a high-risk population of older persons with low vitamin D status. The D-Vitaal study is a randomized, double-blind, placebo-controlled trial investigating the effects of a daily dose of 1200 IU vitamin D3 versus placebo for one year on depressive symptoms and physical functioning (primary outcomes) in older adults. Participants (N = 155, age 60–80 years) were recruited from the general population. Eligibility criteria included the presence of depressive symptoms, ≥1 functional limitation and serum 25-hydroxyvitamin D levels between 15 and 50/70 nmol/L (depending on season). Secondary outcomes include incidence of major depressive disorder, anxiety symptoms, health-related quality of life, cognitive function and cost-effectiveness of the intervention. With this study, we aim to elucidate the effects of vitamin D supplementation on depressive symptoms and physical functioning in older persons who are at high risk of developing more substantial mental and physical problems. If effective, vitamin D supplementation can be a preventive intervention strategy that is easy to implement in the primary care setting. Netherlands Trial Register NTR3845 . Registered 6 February 2013.