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Objectives: Traditional methods for medical device post-market surveillance often fail to accurately account for operator learning effects, leading to biased assessments of device safety. These methods struggle with non-linearity, complex learning curves, and time-varying covariates, such as physician experience. To address these limitations, we sought to develop a machine learning (ML) framework to detect and adjust for operator learning effects., Materials and Methods: A gradient-boosted decision tree ML method was used to analyze synthetic datasets that replicate the complexity of clinical scenarios involving high-risk medical devices. We designed this process to detect learning effects using a risk-adjusted cumulative sum method, quantify the excess adverse event rate attributable to operator inexperience, and adjust for these alongside patient factors in evaluating device safety signals. To maintain integrity, we employed blinding between data generation and analysis teams. Synthetic data used underlying distributions and patient feature correlations based on clinical data from the Department of Veterans Affairs between 2005 and 2012. We generated 2494 synthetic datasets with widely varying characteristics including number of patient features, operators and institutions, and the operator learning form. Each dataset contained a hypothetical study device, Device B, and a reference device, Device A. We evaluated accuracy in identifying learning effects and identifying and estimating the strength of the device safety signal. Our approach also evaluated different clinically relevant thresholds for safety signal detection., Results: Our framework accurately identified the presence or absence of learning effects in 93.6% of datasets and correctly determined device safety signals in 93.4% of cases. The estimated device odds ratios' 95% confidence intervals were accurately aligned with the specified ratios in 94.7% of datasets. In contrast, a comparative model excluding operator learning effects significantly underperformed in detecting device signals and in accuracy. Notably, our framework achieved 100% specificity for clinically relevant safety signal thresholds, although sensitivity varied with the threshold applied., Discussion: A machine learning framework, tailored for the complexities of post-market device evaluation, may provide superior performance compared to standard parametric techniques when operator learning is present., Conclusion: Demonstrating the capacity of ML to overcome complex evaluative challenges, our framework addresses the limitations of traditional statistical methods in current post-market surveillance processes. By offering a reliable means to detect and adjust for learning effects, it may significantly improve medical device safety evaluation., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: This systematic review evaluates the effect of audit and feedback (A&F) interventions targeting antibiotic prescribing in primary care and examines factors that may explain the variation in effectiveness., Methods: Randomized controlled trials (RCTs) involving A&F interventions targeting antibiotic prescribing in primary care were included in the systematic review. Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, and ClinicalTrials.gov were searched up to May 2024. Trial, participant, and intervention characteristics were extracted independently by two researchers. Random effects meta-analyses of trials that compared interventions with and without A&F were conducted for four outcomes: 1) total antibiotic prescribing volume; 2) unnecessary antibiotic initiation; 3) excessive prescription duration, and 4) broad-spectrum antibiotic selection. A stratified analysis was also performed based on study characteristics and A&F intervention design features for total antibiotic volume., Results: A total of 56 RCTs fit the eligibility criteria and were included in the meta-analysis. A&F was associated with an 11% relative reduction in antibiotic prescribing volume (N=21 studies, rate ratio [RR]=0.89; 95% confidence interval [CI] 0.84, 0.95; I2=97); 23% relative reduction in unnecessary antibiotic initiation (N=16 studies, RR=0.77; 95%CI 0.68, 0.87; I2=72); 13% relative reduction in prolonged duration of antibiotic course (N=4 studies, RR=0.87 95%CI 0.81, 0.94; I2=86); and 17% relative reduction in broad-spectrum antibiotic selection (N=17 studies, RR=0.83 95%CI 0.75, 0.93; I2=96)., Discussion: A&F interventions reduce antibiotic prescribing in primary care. However, heterogeneity was substantial, outcome definitions were not standardized across the trials, and intervention fidelity was not consistently assessed., Funding: Canadian Institutes of Health Research FRN 173704., Registration: Prospero (CRD42022298297)., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Radiotherapy reduces local recurrence in locally advanced rectal cancer, but may cause harm in patients who do not experience recurrence. The aim was to investigate the impact of radiotherapy on long-term quality of life after curative treatment for rectal cancer, i.e. in patients without a recurrence during the follow-up., Methods: All patients operated on for rectal cancer in Norway under 75 years of age between 30 September 2007 and 1 October 2020 were identified using the Cancer Registry of Norway. Exclusion criteria were distant metastasis, recurrence and dementia. The primary outcome measure was the Gastrointestinal Quality of Life Index. Secondary outcome measures included the 36-item Short Form Survey. Inverse probability weights based on a multiple logistic regression model were used to balance prechosen covariates between the radiotherapy and no radiotherapy groups when assessing differences in outcomes., Results: Of 5014 invited patients, 2142 (43%) eligible patients answered the questionnaires. Of these 762 (36%) were treated with neoadjuvant radiotherapy plus surgery and 1380 (64%) with surgery alone. The mean follow-up time was 6.4 and 7.4 years respectively. After propensity score matching, the Gastrointestinal Quality of Life Index differed significantly between irradiated and non-irradiated patients ((mean(s.d.), mean score 103.8(19.4) versus 110.8(19.6) respectively, mean difference: -6.96 (95% c.i. -8.72 to -5.19); P < 0.001). Among patients without a stoma the mean difference was -8.1 points, whereas it was -5.7 for patients with a stoma. The radiotherapy group also scored significantly lower in 7 of 8 36-item Short Form Survey domains compared with the surgery alone group., Conclusion: Long-term quality of life was significantly lower in patients without a recurrence during the follow-up who received radiotherapy compared with patients who did not. These findings warrant a critical re-evaluation of the use of radiotherapy both in traditional neoadjuvant treatment and in modern organ-preserving treatment regimens., (© The Author(s) 2024. Published by Oxford University Press on behalf of BJS Foundation Ltd.)

Background: For cancer screening programmes to be effective in early detection it is important that those invited can access screening services and understand the benefits of participation. A better understanding of the factors that matter to potential participants of cancer screening programmes can assist in developing strategies to increase current uptake., Methods: We conducted an overview of systematic reviews to answer the question: What factors influence the uptake of cancer screening services (breast, bowel and cervical) in high-income countries? A thematic approach supported by tabular summaries and qualitative heat maps was used to categorize factors, described as 'barriers' or 'facilitators'., Results: A total of 41 systematic reviews met the criteria for inclusion. The barrier with the greatest number of 'hot spots' across all three screening programmes was a fear of the unknown regarding a possible diagnosis of cancer or abnormal screening results, followed closely by a general lack of knowledge surrounding cancer screening programmes. The greatest collective facilitator to uptake was recommendation by a healthcare provider to attend screening., Conclusion: Across all factors 'trust' and 'building trusted relationships' can be seen as integral to the success of cancer screening programmes and must be reflective of collaborative efforts to mitigate barriers and enhance facilitators to uptake. There is future scope to consider interventions that (i) increase demand for screening services, (ii) reduce barriers to uptake of services and/or (iii) are relevant to the healthcare system and those providing services., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Public Health Association.)

Context: It is hypothesized that gut dysbiosis, a typical feature of patients with autism spectrum disorder (ASD), could be involved in the origin of this neurodevelopmental disorder. Therefore, the use of probiotics to restore gastrointestinal (GI) equilibrium might be a promising therapeutic strategy due to its capacity to balance the gut-brain axis and behavioral responses., Objective: To summarize current knowledge on the use of probiotics to treat core clinical ASD symptoms and concomitant GI signs, compare the design of published studies with those of ongoing trials, assess the near future of this field, and provide recommendations for improving novel studies., Data Sources: The literature search was conducted in February 2020 and updated in March 2021, using a broad range of bibliographic and clinical trial-specific databases., Data Extraction: Data were extracted using a standardized form, and articles reporting on 28 clinical studies (already published or still ongoing) were included. The risk of bias in clinical studies was evaluated using the Cochrane Collaboration Risk of Bias Assessment tool for randomized trials and the Risk of Bias in Nonrandomized Studies-Interventions tool for nonrandomized trials., Results: The results suggest that probiotics improve ASD-like social deficits, GI symptoms, and gut microbiota profile. However, inconsistencies among studies and their methodological limitations make it difficult to draw any conclusions regarding the efficacy of probiotics in ASD. This review provides specific suggestions for future research to improve the quality of the studies., Conclusions: Although ongoing studies have improved designs, the available knowledge does not permit solid conclusions to be made regarding the efficacy of probiotics in ameliorating the symptoms (psychiatric and/or GI) associated with ASD. Thus, more high-quality research and new approaches are needed to design effective probiotic strategies for ASD., (© The Author(s) 2024. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: This study aimed to assess whether two established psychosocial predictors of smoking abstinence, nicotine dependence and time-discounting, also apply to a population of predominantly cigarette light smokers, which is the dominant pattern of smoking in countries like Mexico. Relatively infrequent smoking is increasingly prevalent, yet still harmful, making it important to understand the predictors of cessation in this population., Aims and Methods: Mexican adult smokers recruited from an online consumer panel were surveyed every 4 months between November 2018 and July 2020. We considered respondents who reported a quit attempt in between surveys (n = 1288). Dependence was measured with a 10-item version of the Wisconsin Inventory of Smoking Dependence Motives (WISDM). Time-discounting was assessed with five branching questions about hypothetical reward scenarios. Logistic models regressed sustained quit attempts (≥30 days of abstinence) at time t + 1 on study variables at time t., Results: We found strong interitem reliability (α = 0.92) and intraindividual consistency of our brief WISDM (ρ = 0.68), but moderate intraindividual consistency of the time-discounting measure (ρ = 0.48). Forty-eight percent of the sample reported sustained quit attempts, and 79% were non-daily or light daily smokers (≤5 cigarettes per day). Smokers with higher WISDM-10 had lower odds of sustained quitting and this result remained when controlling for smoking frequency and the Heaviness of Smoking Index (adjusted odds ratio [AOR] = 0.768). Time-discounting was unassociated with sustained quitting., Conclusions: Our findings suggest that a brief, 10-item multidimensional measure of dependence is useful for predicting sustained quitting in a context of relatively light smoking; time-discounting appears less relevant, although our results are not conclusive because of the low test-retest reliability of our measure., Implications: Given the increase in non-daily and light daily cigarette smoking in many countries, including in Mexico, and the health risks this still poses, it is important to understand the predictors of cessation among relatively light smokers. The WISDM-10 multidimensional measure seems to be a good instrument to assess dependence and predict successful quitting in this population, and possibly more appropriate than physical dependence measures. As such, it could help design and target more suitable cessation treatments for non-daily and daily light cigarette smokers. While this study did not find time-discounting to be a relevant predictor of smoking abstinence, future studies should explore other measures., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Acute cholecystitis is one of the most common diagnoses presenting to emergency general surgery and is managed either operatively or conservatively. However, operative rates vary widely across the world. This real-world population analysis aimed to describe the current clinical management and outcomes of patients with acute cholecystitis across Scotland, UK., Methods: This was a national cohort study using data obtained from Information Services Division, Scotland. All adult patients with the admission diagnostic code for acute cholecystitis were included. Data were used to identify all patients admitted to Scottish hospitals between 1997 and 2019 and outcomes tracked for inpatients or after discharge through the unique patient identifier. This was linked to death data, including date of death., Results: A total of 47 558 patients were diagnosed with 58 824 episodes of acute cholecystitis (with 27.2 per cent of patients experiencing more than one episode) in 46 Scottish hospitals. Median age was 58 years (interquartile range (i.q.r.) 43-71), 64.4 per cent were female, and most (76.1 per cent) had no comorbidities. A total of 28 741 (60.4 per cent) patients had an operative intervention during the index admission. Patients who had an operation during their index admission had a lower risk of 90-day mortality compared with non-operative management (OR 0.62, 95% c.i. 0.55-0.70)., Conclusion: In this study, 60 per cent of patients had an index cholecystectomy. Patients who underwent surgery had a better survival rate compared with those managed conservatively, further advocating for an operative approach in this cohort., (© The Author(s) 2023. Published by Oxford University Press on behalf of BJS Society Ltd.)

The demand for diagnostic imaging continues to rise. Against the backdrop of rising health care costs and finite resources, this has prompted a paradigm shift toward value-driven patient care. Inappropriate imaging is a barrier toward achieving this goal, which runs counter to prevailing evidence-based guidelines and contributes to rising healthcare costs. Our objective was to evaluate the appropriateness of lumbar spine X-rays in a tertiary referral Emergency Department (ED) and assess whether physicians' specialization and years of experience influence appropriateness. A total of 1030 lumbar spine radiographs performed in the ED of an academic medical center over a consecutive 3-month period were reviewed retrospectively. Referral indications were reviewed for adherence to 2021 American College of Radiology appropriateness guidelines for lower back pain, and referral patterns were evaluated among physician groups based on specialists' training and years in practice. 63.8% of lumbar spine radiographs were appropriate, with trauma being the most common indication. 36.2% of orders were inappropriate, with lower back pain of <6 weeks duration being the most common indication. Significant differences in inappropriate orders were found (P < .001) across physician groups: qualified Emergency Medicine specialists (20.9% inappropriate orders), specialists in training (27.8%), and non-specialists with ≥3 (60.0%) and <3 (36.9%) years in practice, respectively. Approximately one-third of lumbar spine radiographs performed in the ED were inappropriately ordered by American College of Radiology guidelines; specialists training and years in practice affected referral patterns. Integrating evidence-based appropriateness guidelines into the physician order workflow and targeting older non-specialists may promote more judicious imaging and reduce health care costs., (© The Author(s) 2023. Published by Oxford University Press on behalf of International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Antibiotic overuse and misuse in primary care are common, highlighting the importance of antimicrobial stewardship (AMS) efforts in this setting. Audit and feedback (A&F) interventions can improve professional practice and performance in some settings., Objectives and Methods: To leverage the expertise from international members of the Joint Programming Initiative on Antimicrobial Resistance - Primary care Antibiotic Audit and feedback Network (JPIAMR-PAAN). Network members all have experience of designing and delivering A&F interventions to reduce inappropriate antibiotic prescribing in primary care settings. We aim to introduce the network and explore ongoing A&F activities in member regions. An online survey was administered to all network members to collect regional information., Results: Fifteen respondents from 11 countries provided information on A&F activities in their country, and national/regional antibiotic stewardship programmes or policies. Most countries use electronic medical records as the primary data source, antibiotic appropriateness as the main outcome of feedback, and target GPs as the prescribers of interest. Funding sources varied across countries, which could influence the frequency and quality of A&F interventions. Nine out of 11 countries reported having a national antibiotic stewardship programme or policy, which aim to provide systematic support to ongoing AMS efforts and aid sustainability., Conclusions: The survey identified gaps and opportunities for AMS efforts that include A&F across member countries in Europe, Canada and Australia. JPIAMR-PAAN will continue to leverage its members to produce best practice resources and toolkits for antibiotic A&F interventions in primary care settings and identify research priorities., (© Crown copyright 2023.)

Background: Epigenetic alterations may provide valuable insights into gene-environment interactions in the pathogenesis of inflammatory bowel disease [IBD]., Methods: Genome-wide methylation was measured from peripheral blood using the Illumina 450k platform in a case-control study in an inception cohort (295 controls, 154 Crohn's disease [CD], 161 ulcerative colitis [UC], 28 IBD unclassified [IBD-U)] with covariates of age, sex and cell counts, deconvoluted by the Houseman method. Genotyping was performed using Illumina HumanOmniExpressExome-8 BeadChips and gene expression using the Ion AmpliSeq Human Gene Expression Core Panel. Treatment escalation was characterized by the need for biological agents or surgery after initial disease remission., Results: A total of 137 differentially methylated positions [DMPs] were identified in IBD, including VMP1/MIR21 [p = 9.11 × 10-15] and RPS6KA2 [6.43 × 10-13], with consistency seen across Scandinavia and the UK. Dysregulated loci demonstrate strong genetic influence, notably VMP1 [p = 1.53 × 10-15]. Age acceleration is seen in IBD [coefficient 0.94, p < 2.2 × 10-16]. Several immuno-active genes demonstrated highly significant correlations between methylation and gene expression in IBD, in particular OSM: IBD r = -0.32, p = 3.64 × 10-7 vs non-IBD r = -0.14, p = 0.77]. Multi-omic integration of the methylome, genome and transcriptome also implicated specific pathways that associate with immune activation, response and regulation at disease inception. At follow-up, a signature of three DMPs [TAP1, TESPA1, RPTOR] were associated with treatment escalation to biological agents or surgery (hazard ratio of 5.19 [CI: 2.14-12.56], logrank p = 9.70 × 10-4)., Conclusion: These data demonstrate consistent epigenetic alterations at diagnosis in European patients with IBD, providing insights into the pathogenetic importance and translational potential of epigenetic mapping in complex disease., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Objectives: This scoping review evaluates the existing literature on clinical informatics (CI) training in medical schools. It aims to determine the essential components of a CI curriculum in medical schools, identify methods to evaluate the effectiveness of a CI-focused education, and understand its delivery modes., Materials and Methods: This review was informed by the methodological guidance of the Joanna Briggs Institute. Three electronic databases including PubMed, Scopus, and Web of Science were searched for articles discussing CI between January 2010 and December 2021., Results: Fifty-nine out of 3055 articles were included in our final analysis. Components of CI education include its utilization in clinical practice, ethical implications, key CI-related concepts, and digital health. Evaluation of educational effectiveness entails external evaluation by organizations external to the teaching institute, and internal evaluation from within the teaching institute. Finally, modes of delivery include various pedagogical strategies and teaching CI using a multidisciplinary approach., Discussion: Given the broad discussion on the required competencies, we propose 4 recommendations in CI delivery. These include situating CI curriculum within specific contexts, developing evidence-based guidelines for a robust CI education, developing validated assessment techniques to evaluate curriculum effectiveness, and equipping educators with relevant CI training., Conclusion: The literature reveals that CI training in the core curricula will complement if not enhance clinical skills, reiterating the need to equip students with relevant CI competencies. Furthermore, future research needs to comprehensively address current gaps in CI training in different contexts, evaluation methodologies, and delivery modes to facilitate structured training., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Randomized trials of hospital antimicrobial stewardship (AMS) interventions aimed to optimize antimicrobial use contribute less to the evidence base due to heterogeneity in outcome selection and reporting. Developing a core outcome set (COS) for these interventions can be a way to address this problem. The first step in developing a COS is to identify and map all outcomes., Objectives: To identify outcomes reported in systematic reviews of hospital AMS interventions., Methods: Cochrane Database of Systematic Reviews, MEDLINE and Embase were searched for systematic reviews published up until August 2019 of interventions relevant to reducing unnecessary antimicrobial use for inpatient populations in secondary care hospitals. The methodological quality of included reviews was assessed using AMSTAR-2, A (revised) MeaSurement Tool to Assess systematic Reviews. Extracted outcomes were analysed using deductive and inductive thematic analysis. A list of overarching (unique) outcomes reflects the outcomes identified within the systematic reviews., Results: Forty-one systematic reviews were included. Thirty-three (81%) systematic reviews were of critically low or low quality. A long list of 1739 verbatim outcomes was identified and categorized under five core areas of COMET (Core Outcome Measures in Effectiveness Trials) taxonomy: 'resources use' (45%), 'physiological/clinical' (27%), 'life impact' (16%), 'death' (8%) and 'adverse events' (4%). A total of 421 conceptually different outcomes were identified and grouped into 196 overarching outcomes., Conclusions: There is significant heterogeneity in outcomes reported for hospital AMS interventions. Reported outcomes do not cover all domains of the COMET framework and may miss outcomes relevant to patients (e.g. emotional, social functioning, etc.). The included systematic reviews lacked methodological rigour, which warrants further improvements., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Introduction: Flavor capsule cigarettes are rapidly gaining global market share, particularly in Latin America; however, little is known about consumer profiles and perceptions since the diffusion of this product innovation has become more widespread., Aims and Methods: This paper compares profiles and perceptions of smokers who prefer flavor capsule cigarettes and those who do not in Mexico. We analyzed data from six online surveys of adult Mexican smokers (n = 4488) from 2018-2020. Participants identified their preferred brand variety characteristics (no capsule; one capsule; two capsules), and reported perceptions of their brand varieties' flavor, smoothness, harmfulness, and whether they smoke to control their appetite. Separate multinomial logistic models regressed preferred cigarette type on sociodemographic and smoking-related variables, as well as perceived benefits on preferred cigarette type, adjusting for covariates., Results: Most participants preferred capsule cigarettes (single capsule = 47.5%; double capsule = 12.9%). Flavor capsule users reported that their preferred varieties mostly tasted like menthol/mint (59% of single capsule users and 23% of double capsule users), cucumber (12% and 27%, respectively) or berries (10% and 22%, respectively). Females were more likely than males to prefer either single or double capsule cigarettes (AOR = 2.26 and 2.01, respectively). Preference for flavor capsules was also higher among younger smokers, e-cigarette users, those who smoke less frequently, and those who recently tried or plan to quit. Smokers who preferred capsules were more likely than non-capsule smokers to perceive their cigarettes as smoother, less harmful, and to smoke to control their appetite., Conclusions: The high prevalence of capsule use and widespread perceptions of the benefits of capsules over traditional cigarettes may help explain why tobacco control policies have not reduced smoking prevalence in Mexico., Implications: Flavor capsules are rapidly growing in popularity in many countries around the world, including Mexico. This study found that more Mexican adult smokers prefer brand varieties with capsules (60%) than without capsules (40%), that flavor capsule use strongly correlates with menthol cigarette use, and that perceived flavors of capsules range widely. Flavor capsule smokers have more positive smoking expectancies (eg, lower risk perceptions, dietary control) than noncapsule smokers. Capsules appeal particularly to women, young adults, less frequent smokers, and those who recently tried to quit. Policies should consider banning flavors in cigarettes, including capsules and other filter innovations., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aim: To assess the pathobiological and translational importance of whole-blood transcriptomic analysis in inflammatory bowel disease [IBD]., Methods: We analysed whole-blood expression profiles from paired-end sequencing in a discovery cohort of 590 Europeans recruited across six countries in the IBD Character initiative (newly diagnosed patients with Crohn's disease [CD; n = 156], ulcerative colitis [UC; n = 167], and controls [n = 267]), exploring differential expression [DESeq2], co-expression networks [WGCNA], and transcription factor involvement [EPEE, ChEA, DoRothEA]. Findings were validated by analysis of an independent replication cohort [99 CD, 100 UC, 95 controls]. In the discovery cohort, we also defined baseline expression correlates of future treatment escalation using cross-validated elastic-net and random forest modelling, along with a pragmatic ratio detection procedure., Results: Disease-specific transcriptomes were defined in IBD [8697 transcripts], CD [7152], and UC [8521], with the most highly significant changes in single genes, including CD177 (log2-fold change [LFC] = 4.63, p = 4.05 × 10-118), MCEMP1 [LFC = 2.45, p = 7.37 × 10-109], and S100A12 [LFC = 2.31, p = 2.15 × 10-93]. Significantly over-represented pathways included IL-1 [p = 1.58 × 10-11], IL-4, and IL-13 [p = 8.96 × 10-9]. Highly concordant results were obtained using multiple regulatory activity inference tools applied to the discovery and replication cohorts. These analyses demonstrated central roles in IBD for the transcription factors NFE2, SPI1 [PU.1], CEBPB, and IRF2, all regulators of cytokine signalling, based on a consistent signal across cohorts and transcription factor ranking methods. A number of simple transcriptome-based models were associated with the need for treatment escalation, including the binary CLEC5A/CDH2 expression ratio in UC (hazard ratio = 23.4, 95% confidence interval [CI] 5.3-102.0)., Conclusions: Transcriptomic analysis has allowed for a detailed characterisation of IBD pathobiology, with important potential translational implications., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Background: Socioeconomic inequalities in health are well-established, but studies addressing lagged effects of income or of fluctuations in income over the life course are relatively rare. The current study aims to (i) identify and describe life-course income trajectories for men and women who are currently in later life; and (ii) assess the association of income trajectories with self-rated health in older adults., Methods: The study sample consisted of 1625 men and 1634 women born between 1937 and 1955 who participated in the third wave of the Norwegian Life course, Ageing and Generation Study. Latent class growth analyses were used to estimate dominant income trajectories from ages 30 through 62 in men and women. Stepwise logistic regression analyses were specified to analyze the association of income trajectories with self-rated health in later life., Results: Four trajectories in women and three trajectories in men were estimated as dominant patterns of income over the life course. Differences in the level of income were considerable at age 30 and accumulated over time. Continued exposure to low income showed statistically significant higher odds for poor self-rated health in older men and women. This association remained significant after taking differences in educational attainment, working life, family formation and accumulated wealth into account., Conclusion: The findings suggested remarkable rigidity in income groups that had formed by age 30. A significant share of men and women remain mired in relatively low-income status across the life course with negative implications for health in later life., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Public Health Association.)

Osteoporotic hip fractures in older people may confer an increased risk of subsequent hip fractures and death. The aim of this study was to estimate the cumulative incidence of both recurrent hip fracture and death in the Valencia region. We followed a cohort of 34,491 patients aged ≥65 years who were discharged alive from Valencia Health System hospitals after an osteoporotic hip fracture between 2008 and 2015, until death or end of study (December 31, 2016). Two Bayesian illness-death models were applied to estimate the cumulative incidences of recurrent hip fracture and death by sex, age, and year of discharge. We estimated 1-year cumulative incidences of recurrent hip fracture at 2.5% in women and 2.3% in men, and 8.3% and 6.6%, respectively, at 5 years. Cumulative incidences of total death were 18.3% in women and 28.6% in men at 1 year, and 51.2% and 69.8% at 5 years. One-year probabilities of death after recurrent hip fracture were estimated at 26.8% and 43.8%, respectively, and at 57.3% and 79.2% at 5 years. Our analysis showed an increasing trend in the 1-year cumulative incidence of recurrent hip fracture from 2008 to 2015, but a decreasing trend in 1-year mortality. Male sex and age at discharge were associated with increased risk of death. Women showed higher incidence of subsequent hip fracture than men although they were at the same risk of recurrent hip fracture. Probabilities of death after recurrent hip fracture were higher than those observed in the general population. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)., (© 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).)

Context: Sustained hyperglycemia triggers chronic disease, including type 2 diabetes. A considerable volume of research has explored the effects of brown seaweed on plasma glucose control, but equivocal findings have been reported., Objective: A systematic review and meta-analysis was conducted to assess the evidence from human randomized controlled trials (RCTs) on the effects of brown seaweed on plasma glucose in healthy, at-risk, and individuals with type 2 diabetes., Data Sources: MEDLINE/PubMed, EMBASE, and the Cochrane Library were searched for reports published between 2000 and 2020., Data Extraction: Population, intervention, comparator, outcome, and study design data were extracted., Data Analysis: Eighteen RCTs met our inclusion criteria. The reported results varied across and between populations. Meta-analyses showed a significant effect, favoring the intervention group for both fasting (mean difference -4.6 [95% CI -7.88, -1.33]) and postprandial (mean difference -7.1 [95% CI -7.4, -6.9]) plasma glucose., Conclusion: Brown seaweed and its extracts show potential for preventing and managing hyperglycemia. Our meta-analysis confirms that brown seaweed positively affects plasma glucose homeostasis, with particularly promising postprandial plasma glucose effects. However, further research is needed because no high-quality RCT was identified. Species-specific and dose-response research is also required., Systematic Review Registration: PROSPERO registration no. CRD42020187849., (© The Author(s) 2021. Published by Oxford University Press on behalf of the International Life Sciences Institute.)

Background: There is debate about whether the distance from hospital, or rurality, impacts outcomes in patients admitted under emergency general surgery (EGS). The aim of this study was to determine whether distance from hospital, or rurality, affects the mortality of emergency surgical patients admitted in Scotland., Methods: This was a retrospective population-level cohort study, including all EGS patients in Scotland aged 16 years or older admitted between 1998 and 2018. A multiple logistic regression model was created with inpatient mortality as the dependent variable, and distance from hospital (in quartiles) as the independent variable of interest, adjusting for age, sex, co-morbidity, deprivation, admission origin, diagnosis category, operative category, and year of admission. A second multiple logistic regression model was created with a six-fold Scottish Urban Rural Classification (SURC) as the independent variable of interest. Subgroup analyses evaluated patients who required operations, emergency laparotomy, and inter-hospital transfer., Results: Data included 1 572 196 EGS admissions. Those living in the farthest distance quartile from hospital had lower odds of mortality than those in the closest quartile (OR 0.829, 95 per cent c.i. 0.798 to 0.861). Patients from the most rural areas (SURC 6) had higher odds of survival than those from the most urban (SURC 1) areas (OR 0.800, 95 per cent c.i. 0.755 to 0.848). Subgroup analysis showed that these effects were not observed for patients who required emergency laparotomy or transfer., Conclusion: EGS patients who live some distance from a hospital, or in rural areas, have lower odds of mortality, after adjusting for multiple covariates. Rural and distant patients undergoing emergency laparotomy have no survival advantage, and transferred patients have higher mortality., (© The Author(s) 2022. Published by Oxford University Press on behalf of BJS Society Ltd.)

Context: The prevalence of cognitive and mental health disorders are growing, and existing drug therapies do not treat the underlying cause. Grapes are a flavonoid-rich soft fruit and may therefore be beneficial to cognitive and mental health., Objective: To systematically review evidence from randomized controlled trials investigating the acute and chronic effects of grape interventions on measures of cognition and mood in healthy participants and those with mild cognitive impairment., Data Sources: MEDLINE, The Cochrane Library and EMBASE were searched., Data Extraction and Analysis: Eight studies met the inclusion criteria: one considered acute interventions, 6 assessed chronic effects, and one assessed acute and chronic effects of grapes. The chronic studies found improvements in some cognitive domains (eg, memory, motor skills, or executive function). Acute studies found no consistent effect on memory but saw improvements in reaction time., Conclusions: Differences in study design, dosages, and outcome tests hindered between-study comparison. Even so, the results across studies show that grapes can enhance some aspects of cognition, after both acute and chronic interventions., Systematic Review Registration: PROSPERO registration no. CRD42020193062., (© The Author(s) 2021. Published by Oxford University Press on behalf of the International Life Sciences Institute.)

Background: Patients with mental health problems often present with somatic symptoms when visiting their general practitioner (GP). Somatic presentations may challenge correct diagnosing of mental health disorders in general practice, where most of these disorders are treated., Objective: Explore the associations between common psychological diagnoses and somatic symptom diagnoses in Norwegian urban general practice., Methods: A retrospective cohort study including electronic medical data from 15 750 patients aged 16-65 years from 35 GPs in six GP offices in Oslo, Norway, during 12 months in 2014-2015. We explored prevalences and associations between anxiety-, depression-, and stress-related diagnoses, and somatic symptom diagnoses., Results: Patients with anxiety-, depression- and stress-related diagnoses had a mean number of 2.9±3.6 somatic symptom diagnoses during the 12 months, compared to 1.9±2.5 for patients without any psychological diagnoses (P < 0.001). The mean number of somatic symptoms was significantly higher for the different psychological diagnoses viewed separately, for both sexes and different age groups. There was an increase in probability for anxiety, depression, or stress-related diagnoses with an increasing number of somatic symptom diagnoses during the 12 months. We found a significant increase in somatic symptom diagnoses from ICPC-2 chapters: General and unspecified, digestive, cardiovascular, musculoskeletal, neurological, urological, female genital disorders and social problems. Associated symptom patterns were different for each of the included psychological diagnoses., Conclusions: This study shows that patients with anxiety, depression- and stress-related diagnoses present with increased and characteristic somatic symptoms compared to patients without these diagnoses in general practice., (© The Author(s) 2021. Published by Oxford University Press.)

Background: Antibiotics are over-prescribed for upper respiratory tract infection (URTI). It is unclear how factors known to influence prescribing decisions operate 'in the moment': dual process theories, which propose two systems of thought ('automatic' and 'analytical'), may inform this., Objective(s): Investigate cognitive processes underlying antibiotic prescribing for URTI and the factors associated with inappropriate prescribing., Methods: We conducted a mixed methods study. Primary care physicians in Scotland (n = 158) made prescribing decisions for patient scenarios describing sore throat or otitis media delivered online. Decision difficulty and decision time were recorded. Decisions were categorized as appropriate or inappropriate based on clinical guidelines. Regression analyses explored relationships between scenario and physician characteristics and decision difficulty, time and appropriateness. A subgroup (n = 5) verbalized their thoughts (think aloud) whilst making decisions for a subset of scenarios. Interviews were analysed inductively., Results: Illness duration of 4+ days was associated with greater difficulty. Inappropriate prescribing was associated with clinical factors suggesting viral cause and with patient preference against antibiotics. In interviews, physicians made appropriate decisions quickly for easier cases, with little deliberation, reflecting automatic-type processes. For more difficult cases, physicians deliberated over information in some instances, but not in others, with inappropriate prescribing occurring in both instances. Some interpretations of illness duration and unilateral ear examination findings (for otitis media) were associated with inappropriate prescribing., Conclusion: Both automatic and analytical processes may lead to inappropriate prescribing. Interventions to support appropriate prescribing may benefit from targeting interpretation of illness duration and otitis media ear exam findings and facilitating appropriate use of both modes of thinking., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: informal carers provide the majority of the support for persons with dementia living at home. Restrictions imposed due to COVID-19 have had a profound impact on the daily life of the entire population. This study provides insight into the impact of these restrictions on carers of people with dementia living at home., Design: qualitative semi-structured interviews., Participants: purposive sample of carers who provide at least 10 hours of care a week for the person with dementia living at home., Setting: UK., Results: twenty-three carers were interviewed, and thematic analysis identified three main themes-Changes to daily life, impact on carer health and wellbeing and reduced support from health and social support networks. The results highlight the impact of restrictions imposed on daily life and routines due to the pandemic, wellbeing of carers, reduced social support, lack of access to health and care professionals and respite for carers. The restrictions have had negative consequences on carers' wellbeing, and they have experienced difficulties in accessing formal care services and respite care., Conclusion: carers attempt to continue to provide physical, emotional and practical support for persons with dementia in the community throughout the COVID-19 restrictions. To prevent a future carer crisis, carers need better support systems including formal carer services, telecare solutions that work for them and additional support for respite, as the restrictions from this pandemic continue., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Among the strategies developed thus far for promoting physical activity (PA), exercise-referral schemes (ERs) have gained in popularity as an effective means of preventing secondary health conditions such as hypertension. However, information on the factors affecting adherence to these programs is limited. Using a mixed-methods approach, we undertook the present study to determine the factors associated with adherence to a specific ER aimed at increasing PA among the hypertensive patients in a Social Security institution in Mexico. Data were obtained through semi-structured questionnaires and interviews as well as from the clinical records of participants. For the quantitative component, multinomial regression analysis estimated the factors behind the varying levels of adherence. For the qualitative component, we performed a content analysis based on the health belief model. According to our findings, 80% of participants who began the ER exhibited high levels of adherence. Older age and being female were the key demographic characteristics of those showing increased adherence. Meanwhile, financial issues, the investment of time required, low perception of the benefits of PA, lack of confidence in being able to achieve changes in lifestyle, and a reluctance to acknowledge the seriousness of their health condition were the principal factors among those who did not join the program or exhibited low levels of adherence. Our findings can serve as a basis for designing PA interventions that take into account individual, cultural and administrative elements in their efforts to improve adherence to PA programs for those suffering from chronic conditions such as hypertension., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Success in personalized medicine in complex disease is critically dependent on biomarker discovery. We profiled serum proteins using a novel proximity extension assay [PEA] to identify diagnostic and prognostic biomarkers in inflammatory bowel disease [IBD]., Methods: We conducted a prospective case-control study in an inception cohort of 552 patients [328 IBD, 224 non-IBD], profiling proteins recruited across six centres. Treatment escalation was characterized by the need for biological agents or surgery after initial disease remission. Nested leave-one-out cross-validation was used to examine the performance of diagnostic and prognostic proteins., Results: A total of 66 serum proteins differentiated IBD from symptomatic non-IBD controls, including matrix metallopeptidase-12 [MMP-12; Holm-adjusted p = 4.1 × 10-23] and oncostatin-M [OSM; p = 3.7 × 10-16]. Nine of these proteins are associated with cis-germline variation [59 independent single nucleotide polymorphisms]. Fifteen proteins, all members of tumour necrosis factor-independent pathways including interleukin-1 (IL-1) and OSM, predicted escalation, over a median follow-up of 518 [interquartile range 224-756] days. Nested cross-validation of the entire data set allowed characterization of five-protein models [96% comprising five core proteins ITGAV, EpCAM, IL18, SLAMF7 and IL8], which define a high-risk subgroup in IBD [hazard ratio 3.90, confidence interval: 2.43-6.26], or allowed distinct two- and three-protein models for ulcerative colitis and Crohn's disease respectively., Conclusion: We have characterized a simple oligo-protein panel that has the potential to identify IBD from symptomatic controls and to predict future disease course. Further prospective work is required to validate our findings., (© Crown copyright 2020.)

Background and Aims: Patient-reported experience measures [PREMs] are today a core asset to orientate health care quality improvements. They are particularly relevant in clinical situations requiring frequent interactions between patients and the health care system, like inflammatory bowel disease [IBD]. Indeed, IBD chronic care requires continuous therapies, psychological interventions, and follow-ups. The characteristics of health care services play an important role in the life of these patients and in their satisfaction with the care received. The aim of this study was to develop and validate an IBD-specific questionnaire [WE-CARE IBD SCORE] able to capture IBD patients' needs and priorities for their own health care and based on patients' perspectives., Methods: The WE-CARE IBD SCORE was developed and validated through a multistage process [qualitative and quantitative] and administered to 1176 patients with IBD. Psychometric evaluation included an assessment of internal consistency and factor analysis., Results: The WE-CARE IBD SCORE is a short and self-administered questionnaire that includes six items assessing one unique dimension of 'IBD patient-reported high quality of care'. Psychometric evaluations demonstrate the reliability [Cronbach's alpha = 0.93] and validity [invariance to gender and diagnosis] of the questionnaire as an instrument able to detect and assess IBD patients' main psychosocial needs and priorities for receiving health care services., Conclusions: The WE-CARE IBD SCORE contributes to the panorama of existing quality of care patient-reported measures by providing a patient-based, psychosocial perspective in the evaluation of a key aspect for chronic-and particularly for IBD patients-care., (© The Author(s) 2020. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Diabetes is a frequent chronic condition, which can lead to costly complications if not managed well in the primary care setting. Potentially avoidable hospitalizations (PAH) are considered as an indirect measure of primary care. However, the association between primary care use and PAH in diabetic patients has not been investigated in France., Methods: We investigate the association between primary care indicators and PAH at an individual level among persons with diabetes in a population-based cohort study on the French national health insurance database (EGB sample). PAH occurrence in 2013 was modeled as a function of primary care use and access, health status and socio-economic indicators over the exposure period 2011-12 using a cause-specific hazards model with death as a competing event., Results: We included 25 293 diabetics in our cohort, among which 385 (1.5%) experienced at least 1 PAH in 2013. After adjustment on health status indicators, primary care use had a protective effect against PAH. Diabetic patients who had seen a general practitioner (GP) 10-14 times had a reduced hazard of PAH compared to less frequent encounters (HR=0.49, P<0.001). The effect size decreased when the number of encounters increased, suggesting a remaining confounding effect of health status., Conclusions: For the first time in France, this study shows a protective effect of the number of GP encounters against PAH at an individual level and highlights the importance of a frequent monitoring of diabetic patients in the primary care setting to prevent PAH occurrence., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.)

In recent years, it has become commonplace among the Global Burden of Disease (GBD) study authors to regard the disability-adjusted life year (DALY) primarily as a descriptive health metric. During the first phase of the GBD (1990-1996), it was widely acknowledged that the DALY had built-in evaluative assumptions. However, from the publication of the 2010 GBD and onwards, two central evaluative practices- time discounting and age-weighting -have been omitted from the DALY model. After this substantial revision, the emerging view now appears to be that the DALY is primarily a descriptive measure. Our aim in this article is to argue that the DALY, despite changes, remains largely evaluative. Our analysis focuses on the understanding of the DALY by comparing the DALY as a measure of disease burden in the two most significant phases of GBD publications, from their beginning (1990-1996) to the most recent releases (2010-2017). We identify numerous assumptions underlying the DALY and group them as descriptive or evaluative. We conclude that while the DALY model arguably has become more descriptive, it remains, by necessity, largely evaluative., (© The Author(s) 2020. Published by Oxford University Press.)

Background: Recruitment and retention of participants in surgical trials is challenging. Knowledge of the most common and problematic issues will aid future trial design. This study aimed to identify trial staff perspectives on the main issues affecting participant recruitment and retention in UK surgical trials., Methods: An online survey of UK surgical trial staff was performed. Respondents were asked whether or not they had experienced a range of recruitment and retention issues, and, if yes, how relatively problematic these were (no, mild, moderate or serious problem)., Results: The survey was completed by 155 respondents including 60 trial managers, 53 research nurses, 20 trial methodologists and 19 chief investigators. The three most common recruitment issues were: patients preferring one treatment over another (81·5 per cent of respondents); clinicians' time constraints (78·1 per cent); and clinicians preferring one treatment over another (76·8 per cent). Seven recruitment issues were rated moderate or serious problems by a majority of respondents, the most problematic being a lack of eligible patients (60·3 per cent). The three most common retention issues were: participants forgetting to return questionnaires (81·4 per cent); participants found to be ineligible for the trial (74·3 per cent); and long follow-up period (70·7 per cent). The most problematic retention issues, rated moderate or serious by the majority of respondents, were participants forgetting to return questionnaires (56·4 per cent) and insufficient research nurse time/funding (53·6 per cent)., Conclusion: The survey identified a variety of common recruitment and retention issues, several of which were rated moderate or serious problems by the majority of participating UK surgical trial staff. Mitigation of these problems may help boost recruitment and retention in surgical trials., (© 2020 The Authors. BJS Open published by John Wiley & Sons Ltd on behalf of British Journal of Surgery Society.)

Study Question: Is it feasible to undertake a randomised controlled trial to establish whether surgical removal of endometrioma or not, improves live birth rates from IVF?, Summary Answer: A randomised controlled trial (RCT) comparing surgery versus no surgery to endometrioma prior to IVF is only feasible in UK if an adaptive rather than traditional study design is used; this would minimise resource wastage and complete the trial in an acceptable time frame., What Is Known Already: There is wide variation in the management of endometriomas prior to IVF, with decisions about treatment being influenced by personal preferences., Study Design Size and Duration: This was a mixed-methods study consisting of an online survey of clinicians, a focus group and individual interviews with potential trial participants., Participants/materials Setting Methods: Endometriosis and fertility experts across the UK were invited to participate in an online anonymised questionnaire. Potential future trial participants were recruited from a tertiary care fertility centre and invited to participate in either individual interviews or focus groups., Main Results and the Role of Chance: Clinicians and potential trial participants confirmed the need for an RCT to inform the management of an endometrioma prior to IVF. There were 126 clinicians who completed the survey, and the majority (70%) were willing to recruit to a trial. Half of those who responded indicated that they see at least 10 eligible women each year. The main barriers to recruitment were waiting lists for surgery and access to public funding for IVF. One focus group ( n  = 7) and five interviews were conducted with potential trial participants ( n  = 3) and their partners ( n  = 2). The findings from these discussions highlighted that recruitment and retention in a potential RCT could be improved by coordination between IVF and surgical services such that an operation does not delay IVF or affect access to public funding. Live birth was considered the most important outcome with an improvement of at least 10% considered the minimum acceptable by both patients and clinicians., Limitations Reasons for Caution: This feasibility study captured views of clinicians across the UK, but as patients were from a single Scottish centre, their views may not be representative of other areas with limited public funding for IVF., Wider Implications of the Findings: There is a need for an appropriately powered RCT to establish whether or not surgical treatment of endometrioma prior to IVF improves live birth rates. There are logistical issues to be considered due to limited number of participants, funding of IVF and waiting times. These could be overcome in a RCT by using an adaptive design which would include a prospectively planned opportunity for modification of specified aspects of the study design based on interim analysis of the data, coordination of IVF treatments and endometriosis surgeries and international collaboration. Similar principles could be used for other questions in fertility where a traditional approach for randomised trials is not feasible., Study Funding/competing Interests: Funding was received from the NHS Grampian R&D pump priming fund (RG14437-12). S.B. is Editor-in-Chief of HROPEN, and A.W.H. is Deputy Editor of HROPEN. Neither was involved in the review of this manuscript. L.S. reports grants from CSO and NIHR to do endometriosis research, outside the submitted work. K.C. reports grants from NIHR/HTA and CSO during the conduct of the study. J.H.e., A.W.H., J.D., S.B.r., K.B., G.B., J.H.u. and K.G. report no conflict of interest., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.)

Background: Reducing unnecessary antibiotic exposure is a key strategy in reducing the development and selection of antibiotic-resistant bacteria. Hospital antimicrobial stewardship (AMS) interventions are inherently complex, often requiring multiple healthcare professionals to change multiple behaviours at multiple timepoints along the care pathway. Inaction can arise when roles and responsibilities are unclear. A behavioural perspective can offer insights to maximize the chances of successful implementation., Objectives: To apply a behavioural framework [the Target Action Context Timing Actors (TACTA) framework] to existing evidence about hospital AMS interventions to specify which key behavioural aspects of interventions are detailed., Methods: Randomized controlled trials (RCTs) and interrupted time series (ITS) studies with a focus on reducing unnecessary exposure to antibiotics were identified from the most recent Cochrane review of interventions to improve hospital AMS. The TACTA framework was applied to published intervention reports to assess the extent to which key details were reported about what behaviour should be performed, who is responsible for doing it and when, where, how often and with whom it should be performed., Results: The included studies (n = 45; 31 RCTs and 14 ITS studies with 49 outcome measures) reported what should be done, where and to whom. However, key details were missing about who should act (45%) and when (22%). Specification of who should act was missing in 79% of 15 interventions to reduce duration of treatment in continuing-care wards., Conclusions: The lack of precise specification within AMS interventions limits the generalizability and reproducibility of evidence, hampering efforts to implement AMS interventions in practice., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.)

Objective: The triple bottom line (TBL) of sustainability is an important emerging conceptual framework which considers the combined economic, environmental and social impacts of an activity. Despite its clear relevance to the healthcare context, it has not yet been applied to the evaluation of a healthcare intervention. The aim of this study was to demonstrate whether doing so is feasible and useful., Design: Secondary data analysis of a 12-month randomized controlled trial., Setting: Community based mental health care., Participants: Patients with chronic psychotic illnesses (n = 333)., Intervention(s): Community treatment orders., Main Outcome Measure(s): Financial and environmental (CO2 equivalent) costs of care, obtained from healthcare service use data, were calculated using publicly available standard costs; social sustainability was assessed using standardized social outcome measures included in the trial data., Results: Standardized costing and CO2e emissions figures were successfully obtained from publicly available data, and social outcomes were available directly from the trial data., Conclusions: This study demonstrates that TBL assessment can be retrospectively calculated for a healthcare intervention to provide a more complete assessment of the true costs of an intervention. A basic methodology was advanced to demonstrate the feasibility of the approach, although considerable further conceptual and methodological work is needed to develop a generalizable methodology that enables prospective inclusion of a TBL assessment in healthcare evaluations. If achieved, this would represent a significant milestone in the development of more sustainable healthcare services. If increasing the sustainability of healthcare is a priority, then the TBL approach may be a promising way forward., (© The Author(s) 2019. Published by Oxford University Press in association with the International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To translate and cultural adapt the 14-item Communication Assessment Tool (CAT) into Norwegian and Danish, making them as similar as possible., Design: This was a translation and validation study including individual interviews for content and face validity and a patient survey for internal consistency and floor-ceiling effect., Setting: Outpatient clinic at the Department of Internal Medicine, Lillebaelt Hospital, Denmark and a Norwegian general practice., Participants: Ten patients were included for individual interviews and 440 participants completed the survey., Main Outcome Measure: Translation and validation of the CAT., Results: Despite minor differences in the use of words in the translated versions of CAT, the final versions were very similar. Based on the content and face validation and after agreement with the developers, it was decided to include a 'non-applicable' answering option, not a part of the original version. The use of 'non-applicable' for each item ranged from 0% to 30% in Norway and from 0% to 6.1% in Denmark. The overall CAT score, i.e. items rated excellent, were 55.5% in Norway and 50.3% in Denmark. For each item, the CAT score ranged between 31.3% and 69.8% in Norway and 33.7% and 57.4% in Denmark., Conclusion: The translated and validated CAT can be used to measure patients' perspectives on clinicians' communication skills in Denmark and Norway., (© The Author(s) 2019. Published by Oxford University Press in association with the International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Context: Adipocyte fatty acid-binding protein (FABP4) is expressed in adipose tissue and may impair glucose homeostasis and promote atherosclerotic processes., Objective: We examined the association between serum FABP4 and risk of type 2 diabetes (T2D), myocardial infarction (MI), and stroke., Design: Case-cohort study embedded within a sample of 27,548 participants of the EPIC-Potsdam cohort., Participants and Setting: A randomly selected subcohort (n = 2194) of participants who were free of cardiovascular disease and T2D at study baseline and 728 incident T2D cases, 206 incident stroke cases, and 185 incident MI cases with an average 8.2 (±1.7) years of follow-up., Main Outcome Measures: Incident T2D, MI, and stroke., Results: In a multivariable-adjusted model, the hazard ratios (HRs) in the highest vs lowest quartile of FABP4 were 1.81 (95% CI, 1.21 to 2.70; Ptrend = 0.01) for T2D, 0.93 (95% CI, 0.55 to 1.55; Ptrend = 0.68) for MI, and 1.41 (95% CI, 0.80 to 2.49; Ptrend = 0.24) for stroke, respectively. In analyses stratified by sex, no statistically significant differences could be seen for associations between FABP4 and T2D and MI (Pinteraction by sex = 0.27 and 0.84, respectively), whereas a higher risk of stroke was observed in men (HR: 2.70, 95% CI 1.20 to 6.00; P = 0.04), but not in women (HR: 0.70, 95% CI 0.31 to 1.60; P = 0.53; Pinteraction = 0.02)., Conclusions: These data support the hypothesis that elevated FABP4 levels may contribute to T2D risk. In contrast, our data did not support the hypothesis that circulating FABP4 may be relevant for MI, whereas the observed association with stroke in men may need further evaluation., (Copyright © 2019 Endocrine Society.)

Background: Decreasing gender differences in mental health are found largely in countries in which the roles of men and women have improved in terms of opportunities for employment, education, child care and other indicators of increasing gender equality. In this study, we examine how European welfare regimes influence this association between mental health and the social roles that men and women occupy., Methods: The EU-World Mental Health data are used, which covers the general population in 10 European countries (n = 37 289); Countries were grouped into four welfare regions: Liberal regime (Northern Ireland), Bismarckian regime (Belgium, Germany, the Netherlands and France), Southern regime (Spain, Italy, Portugal) and Central-Eastern regime (Romania and Bulgaria). The lifetime prevalence of mood, anxiety and alcohol disorders was determined by using the Composite International Diagnostic Interview 3.0. Overall prevalence rates along with odds ratios by means of bivariate logistic regression models are calculated to compare the presence of common mental disorders in women versus men per welfare regime., Results: Overall prevalence of common mental disorders is highest in the Liberal regime and lowest in the Central/Eastern regime. The gender gap in mental disorders is largest in the Southern regime and smallest in the Liberal regime. Marital status and certain employment positions help to explain variation in mental disorders across and within welfare regimes., Conclusion: Most prominent pathways linking gender to mental ill-health being are related to marital status and certain employment positions. However, these pathways also show substantial variation across welfare regimes., (© The Author 2018. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.)

Background: The health of pregnant women and their fetuses are especially sensitive to socioeconomic conditions. This study analyzes the impact of maternal socioeconomic status (SES), evaluated by occupation and maternal education level, in preterm births (PTBs) and in small for gestational age (SGA) fetuses, considering the effect of the potential mediating factors on the SES and birth outcomes., Methods: A total of 2497 mother/newborn dyads from the INMA-Spain project were studied. We examined maternal occupation and education in relation to PTB and SGA along with covariate data, using logistic regression analysis. Adjusted models for each of the outcome variables in relation to SES indicators were estimated, considering potential mediating factors., Results: About 4.7% of babies were PTB and 9.7% SGA. Full adjusted logistic regression models showed similar odds ratio (OR) for SGA in both SES indicators. Manual working women or without university studies had higher risk of SGA than their counterpart groups (OR = 1.39% CI = 1.03-1.88 and OR = 1.39% CI = 1.00-2.00, respectively). Likewise, mothers with a manual occupation were at more risk of PTB than those with a non-manual occupation (OR = 1.74 95% CI = 1.13-2.74), but there was no association between education and PTB. Smoking, pre-pregnancy BMI and underweight gain during pregnancy were significantly associated to SGA births. The mother's age, presence of complications and overweight gain during pregnancy were related to PTB., Conclusion: The mother's socioeconomic disadvantage was consistently associated with birth outcomes giving rise to intergenerational transmission of health inequalities. Reducing inequalities requires eliminating the upstream causes of poverty itself., (© The Author(s) 2018. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.)

Background: To assess associations between oral health behaviour and physical activity and related factors among adolescents., Methods: The study population (n = 76 529) consisted of a representative sample of 16- to 18-year-old Finnish adolescents (boys: 37 211, girls: 39 318). An anonymous, confidential and voluntary classroom-administered questionnaire included questions about tooth brushing frequency, physical activity, BMI and eating habits. Moderate-to-vigorous physical activity (MVPA) was used to assess the adolescents' physical activity. The chi-square test and multiple binary logistic regression were used for statistical analyses. Adjusted odds ratios (OR) and their 95% confidence intervals (CI) were calculated for MVPA, BMI, breakfast, smoking and socioeconomic factors as parents' education and school type., Results: The prevalence of twice daily tooth brushing was highest among adolescents reporting 4 hours or more of MVPA (51-77%). Obese and smoking adolescents exercised less often than normal weighted and non-smokers. Girls brushed their teeth twice daily significantly more often than boys (P < 0.001), and high-school students brushed their teeth significantly more often than vocational school students (P < 0.001). Logistic regression models showed that obesity (OR = 2.14, 95% CI 1.92-2.37) and irregular breakfast eating (OR = 2.35, 95% CI 2.19-2.52) among boys, and obesity (OR = 2.81, 95% CI 2.48-3.17), physical inactivity (OR = 1.89, 95% CI 1.78-2.00) and irregular breakfast eating (OR = 1.91, 95% CI 1.79-2.04) among girls were strong predictors for poor tooth brushing., Conclusions: Physically active adolescents had better oral health behaviour than less active adolescents. Obesity and smoking were associated with infrequent tooth brushing., (© The Author(s) 2018. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.)

Managers have been neglected in health literacy research. There still is little known about the health-literacy status and needs of commercial industry managers. This article reduces the existing knowledge gap by presenting findings of an exploratory qualitative study. We conducted 23 separate semi-structured interviews of managers from all management levels (low, middle and top) and experts in the field of health management and/or personnel management. The qualitative interviews were analysed according to Mayring's content analytic approach using MAXQDA. The findings indicate that managers do have considerable information levels about existing health topics and relevant problems but have difficulties of discernment as to which sources of information can be activated or accessed in a timely fashion due to work and information overload. Even those who devise strategies often fail in implementing health-literate behavior. Experts and managers had fairly consistent views on the importance of health literacy among managers. Most agreed that mental health was neglected and that company conditions were important in influencing the ability to act in a way that promoted health literacy. The findings also show that strengthening of managerial self-perception, self-regulation and self-control, raising awareness and ability to take personal responsibility for one's own health, developing skills in handling large amounts of information and fostering open and trusting communication are all essential.

Background: Development of a parastomal hernia is common following abdominoperineal excision (APE). The true incidence is difficult to assess fully owing to differing lengths of follow-up and techniques used to assess herniation; radiological or clinical. The primary aim of this study was to evaluate colostomy diameter by studying the rate of change of axial and sagittal trephine diameters, trephine area, and the ratio of the trephine over time. A secondary aim was to investigate variation in trephine area and variables affecting parasternal hernia over time., Methods: Serial CT scans performed after APE from January 2006 to December 2014 were reviewed. Variables analysed included age, sex, trephine position relative to rectus abdominis muscle (RAM), type of incision for stoma creation, and axial and sagittal trephine diameters measured on follow-up CT. A Bayesian hierarchical modelling framework was used to examine the relationship of trephine diameters, area and ratio over time., Results: Of 112 patients undergoing APE, 103 were eligible for analysis; this included 91 colostomies (88·3 per cent) through the RAM and 12 (11·7 per cent) lateral to the RAM. Median age of the patients was 68 years. Sixty patients (58·3 per cent) had a circular and 43 (41·7 per cent) a cruciate incision for stoma creation. The sagittal trephine diameter increased by 0·22 (95 per cent credible interval 0·12 to 0·32) mm/month for both sexes. Women reported a significant increase in axial trephine diameters; the male : female ratio difference was -0·17 (-0·30 to -0·03) mm/month and for trephine areas -6·21 (0·96 to 13·7) mm 2 /month. Patient age, colostomy trephine location and shape of incision were not statistically significant variables for parasternal hernia., Conclusion: Female sex was the only variable affecting the rate of increase in axial trephine diameter and trephine area over time.

Objectives: To develop quality of care (QoC) indicators, evaluate the quality of the processes of care (QPC) and clinical outcomes, and analyze the association between the QPC and severe clinical outcomes of preterm newborns admitted to neonatal intensive care units (NICUs)., Design: Mixed methods approach: (1) development of QoC indicators via modified RAND/UCLA method; (2) cross-sectional study of QoC evaluation and (3) multiple logistic regression analysis to ascertain the association between the QPC and severe clinical outcomes., Setting: Two NICUs belonged to the Mexican Institute of Social Security in Mexico City., Participants: About 489 preterm neonates (<37 weeks of gestation) without severe congenital anomalies., Main Outcome Measure(s): The QoC indicators; ≥60% of recommended QPC and severe clinical outcomes., Results: The QoC included 10 QPC indicators across four domains: respiratory, nutrition and metabolism, infectious diseases, and screening, and five outcome indicators. The lower QPC indicators were for the nutrition and metabolism domain (17.8% started enteral feeding with human milk, and 20.7% received sodium bicarbonate appropriately). The higher QPC indicator was for the screening domain (97.6% of neonates <30 weeks gestation underwent early (≤14 days) transfontanelar ultrasound). The mean recommended QPC that neonates received was 47.5%. Only 26.6% of neonates received ≥60% of recommended QPC. About 60.7% of neonates developed severe clinical outcomes including mortality and healthcare-related major morbidity. Receiving ≥60% of recommended QPC was associated with a decrease of nearly half of odds of severe clinical outcomes., Conclusion: The evaluation of the QoC in NICUs is essential to address modifiable gaps in quality.

Background: Achieving stable closure of complex or contaminated abdominal wall incisions remains challenging. This study aimed to characterize the stage of innovation for biological mesh devices used during complex abdominal wall reconstruction and to evaluate the quality of current evidence., Methods: A systematic review was performed of published and ongoing studies between January 2000 and September 2017. Eligible studies were those where a biological mesh was used to support fascial closure, either prophylactically after midline laparotomy, or for reinforcement after repair of incisional hernia with midline incision. The primary outcome measure was the IDEAL framework stage of innovation. The key secondary outcome measure was the GRADE criteria for study quality., Results: Thirty-five studies including 2681 patients were included. Four studies considered mesh prophylaxis, 23 considered hernia repair, and eight reported on both. There was one published randomized trial (IDEAL stage 3), none of which was of high quality; the others were non-randomized studies (IDEAL stage 2a). A detailed description of surgical technique was provided in most studies (27 of 35); however, no study reported outcomes according to the European Hernia Society consensus statement and only two described quality control of surgical technique during the study. From 21 ongoing randomized trials and observational studies, 11 considered repair of incisional hernia and 10 considered prophylaxis (seven in elective settings)., Conclusion: The evidence base for biological mesh is limited, and better reporting and quality control of surgical techniques are needed. Although results of ongoing trials over the next decade will improve the evidence base, further study is required in the emergency and contaminated settings.

Objectives: The Mexican Institute of Social Security (IMSS) provides a package of health, economic and social benefits to workers employed in private firms within the formal labour market and to their economic dependants. Affiliates have a right to these benefits only while they remain contracted, thus posing a risk for the continuity of healthcare. This study evaluates the association between the time (in days) without the right to healthcare due to job loss in the formal labour market and the quality of healthcare and clinical outcomes among IMSS affiliates with Type 2 diabetes mellitus (T2DM)., Design: Retrospective cohort study 2013-2015., Setting: Six IMSS family medicine clinics (FMC) in Mexico City., Participants: T2DM patients (n = 27 217) affiliated with job-related health insurance and at least one consultation with a family doctor during 2013., Source of Information: IMSS affiliation department database and electronic health records and clinical laboratory databases., Main Outcome Measure(s): Quality of the processes (eight indicators) and outcomes (three indicators) of healthcare., Results: The results indicated that losing IMSS right to healthcare is frequent, occurring to one-third of T2DM patients during the follow-up period. The time without the right to healthcare in the observed period was of 120 days on average and was associated with a 43.2% loss of quality of care and a 19.2% reduction in clinical outcomes of T2DM., Conclusion: Policies aimed at ensuring access and continuity of care, regardless of job status, are critical for improving the quality of processes and outcomes of healthcare for diabetic patients.

Background: Healthcare policies target unplanned hospital admissions and 30-day re-admission as key measures of efficiency, but do not focus on factors that influence trajectories of different types of admissions in the same patient over time., Objectives: To investigate the influence of consumer segmentation and patient factors on the time intervals between different types of hospital admission., Research Design, Subjects and Measures: A cohort design was applied to an anonymised linkage database for adults aged 40 years and over (N = 58 857). Measures included Mosaic segmentation, multimorbidity defined on six chronic condition registers and hospital admissions over a 27-month time period., Results: The shortest mean time intervals between two consecutive planned admissions were: 90 years and over (160 days (95% confidence interval (CI): 146-175)), Mosaic groups 'Twilight subsistence' (171 days (164-179)) or 'Welfare borderline' and 'Municipal dependency' (177 days (172-182)) compared to the reference Mosaic groups (186 days (180-193)), and multimorbidity count of four or more (137 days (130-145)). Mosaic group 'Twilight subsistence' (rate ratio (RR) 1.22 (95% CI: 1.08-1.36)) or 'Welfare borderline' and 'Municipal dependency' RR 1.20 (1.10-1.31) were significantly associated with higher rate to an unplanned admission following a planned event. However, associations between patient factors and unplanned admissions were diminished by adjustment for planned admissions., Conclusion: Specific consumer segmentation and patient factors were associated with shorter time intervals between different types of admissions. The findings support innovation in public health approaches to prevent by a focus on long-term trajectories of hospital admissions, which include planned activity.

Objectives: Effective strategies are needed to translate knowledge (evidence) into practice to improve the quality of community pharmacy services. We report the first step of a novel knowledge translation process which involved the systematic identification and prioritisation of community pharmacy services in Scotland which were perceived to require improvement and/or guideline development., Methods: This process involved three stages and a stakeholder group comprising community pharmacists, policy makers, lay and pharmacy organisation representatives. A modified nominal group technique (NGT) was used for topic generation (August 2013) followed by an electronic Delphi survey (eDelphi), October-December 2013) and topic rationalisation (December 2013) based on feasibility, acceptability, and potential impact for practice improvement., Key Findings: In total, 63 items were identified during the modified NGT which were categorised into 20 topics to form the starting point of the eDelphi. In total, 74 individuals (mostly community pharmacists) indicated an interest in the eDelphi, which achieved response rates of 63.5%, 67.6%, and 70.3%, respectively in Rounds 1, 2, and 3. Consensus was achieved with six topics: promoting the appropriate sale and supply of over-the-counter medicines; patient counselling for prescribed medication; pharmaceutical care to promote medication adherence; promotion and delivery of a Minor Ailment Scheme; pharmaceutical care of vulnerable patients; and effective use of community pharmacy workforce. Of these, the priority topic selected for the next stage of the programme was promoting the appropriate sale and supply of over-the-counter medicines., Conclusions: This study adopted a systematic, inclusive, and rapid approach to identify priorities for community pharmacy practice improvement in Scotland., (© 2017 The Authors. International Journal of Pharmacy Practice published by John Wiley & Sons Ltd on behalf of Royal Pharmaceutical Society.)

Background: Policy encourages health care providers to listen and respond to feedback from patients, expecting that it will enhance care experiences. Enhancement of patients' experiences may not yet be a reality, particularly in primary health care settings., Objective: To identify the issues that influence the use and impact of feedback in this context., Design and Setting: A realist synthesis of studies of the use of patient feedback within primary health care settings., Methods: Structured review of published studies between 1971 and January 2015., Results: Eighteen studies were reported in 20 papers. Eleven studies reported patient survey scores as a primary outcome. There is little evidence that formal patient feedback led to enhanced experiences. The likelihood of patient feedback to health care staff stimulating improvements in future patients' experiences appears to be influenced predominantly by staff perceptions of the purpose of such feedback; the validity and type of data that is collected; and where, when and how it is presented to primary health care teams or practitioners and teams' capacity to change., Conclusions: There is limited research into how patient feedback has been used in primary health care practices or its usefulness as a stimulant to improve health care experience. Using a realist synthesis approach, we have identified a number of contextual and intervention-related factors that appear to influence the likelihood that practitioners will listen to, act on and achieve improvements in patient experience. Consideration of these may support research and improvement work in this area., (© The Author 2017. Published by Oxford University Press.)

With obesity on the rise in the general population, it has also become more prevalent among people of reproductive age. Weight loss has shown benefits in overweight women and men experiencing fertility problems. However, the existing weight-loss interventions for individuals with infertility are associated with high drop-out rates and limited success. In this article, we argue for the development of weight-loss programmes targeting couples, as couples are routinely seen in fertility clinics, rather than individuals. Couples may have correlated weights, and similar eating and activity patterns. Involving both partners may facilitate mutual support, behaviour change, weight loss and programme continuation, at very little additional cost. A successful couple-based intervention could improve the chances of achieving pregnancy and delivering a healthy baby, with a reduction in pregnancy complications. In the longer run, both partners and their baby could benefit from maintained behaviour change with better health across the lifespan. We conclude that there is a need for research to systematically develop a couple-based weight-loss intervention with state-of-the-art design that is tailored to both partners' needs., (© The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)