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There have been numerous studies examining the association between depression and bone mineral density (BMD), but the underlying nature of this relationship remains unclear. Independent of this association, there is a growing body of evidence that depression impacts the risk for fracture in older adults. This article reviews the current epidemiological evidence regarding comorbidity of depression, low bone mineral density, and fracture. A review of the literature on depression, depressive symptoms, low BMD, osteoporosis, and fracture using electronic databases. We reviewed 20 studies of the association between depression and BMD and five reports of the relationship between depression and fractures. Potential mediating mechanisms (both physiological and behavioral) are discussed, as well as potential confounding influences (e.g., medication use). Most studies support the finding that depression is associated with increased risk for both low BMD and fractures, but variation in study design, sample composition, and exposure measurement make comparisons across studies difficult. Researchers should be aware of potential confounders, such as medication use, that may influence results. Future research should focus on identifying mediating pathways and targets for intervention in the relationships between depression, low BMD, and fracture. [ABSTRACT FROM AUTHOR]

Aims To assess the effect of prediabetes (impaired fasting glucose and/or impaired glucose tolerance) on the incidence of chronic kidney disease. Methods PubMed and EMBASE were searched (for studies published up to March 2015). Effects estimated from cohort studies reporting the relationship of prediabetes to incident chronic kidney disease [kidney damage (microalbuminuria, albuminuria or proteinuria) and/or decreased glomerular filtration rate] were pooled using a random-effects model meta-analysis. Results Nine cohort studies with a total of 185 452, mainly Asian and white, participants were followed for a total of 835 146 person-years. In eight cohort studies defining impaired fasting glucose as fasting glucose 6.1-6.9 mmol/l, the summary relative risk of chronic kidney disease after adjustment for established risk factors was 1.11 (95% CI 1.02-1.21). When a study defining impaired fasting glucose as fasting glucose 5.6-6.9 mmol/dl was added, the overall relative risk of chronic kidney disease was 1.12 (95% CI 1.02-1.21). Exclusion of the only study with information on impaired glucose tolerance did not change the relative risk (1.12; 95% CI 1.02-1.21). There was no evidence of publication bias ( P value for Egger test = 0.12). Conclusion Prediabetes is modestly associated with an increase in chronic kidney disease risk, but this remains to be robustly confirmed. Chronic kidney disease screening among people with prediabetes, and aggressive management of prediabetes in those with chronic kidney disease may be warranted. [ABSTRACT FROM AUTHOR]

Chlorination has historically provided microbiologically safe drinking water in public water supplies. Likewise, chlorine has also been introduced as a low-cost disinfection method in rural and marginalized communities, both at community and household level, as well as during emergencies. Although this practice is common and well established for use as a household water treatment technology in the Global South, several challenges in effective and efficient implementation still need to be addressed. Here, we explored these issues by a literature review and narrowed them to the status of three Latin American countries (Mexico, Colombia, and Brazil). Overall, it was found that although guidance on household-based chlorination includes information on health risks and hygiene, this may not create enough incentive for the user to adapt the method satisfactorily. Physicochemical quality of the water influences chlorination efficiency and it is found that variations in quality are rarely considered when recommending chlorine doses during implementation. These are far more often based on a few measurements of turbidity, thereby not considering dissolved organic matter, or seasonal and day-to-day variations. Other factors such as user preferences, chlorine product quality and availability also represent potential barriers to the sustainable use of chlorination. For chlorination to become a sustainable household water treatment, more focus should therefore be given to local conditions prior to the intervention, as well as support and maintenance of behavioural changes during and after the intervention. [ABSTRACT FROM AUTHOR]

OBJECTIVE:Waist-to-hip ratio (WHR) is strongly associated with prevalent atherosclerosis. We analyzed the associations of baseline serum levels of testosterone (T), estradiol (E2), sex-hormone-binding globulin (SHBG) and dehydroepiandrosterone (DHEA) with WHR in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort.SUBJECTS:Baseline data was available for 3144 men and 2038 postmenopausal women, who were non-users of hormone therapy, who were 45-84 years of age, and of White, Chinese, Black or Hispanic racial/ethnic groups. Of these, 2708 men and 1678 women also had longitudinal measurements of WHR measured at the second and/or the third study visits (median follow-up 578 days and 1135 days, respectively).RESULTS:In cross-sectional analyses adjusted for age, race and cardiovascular disease risk factors, T was negatively associated with baseline WHR in men, whereas in both sexes, E2 was positively associated and SHBG was negatively associated with WHR (all P<0.001). In longitudinal analyses, further adjusted for follow-up time and baseline WHR, baseline T was negatively associated with WHR at follow-up (P=0.001) in men, whereas in both sexes, E2 was positively associated (P=0.004) and SHBG was negatively associated with WHR (P<0.001). The longitudinal association of E2, but not T, was independent of SHBG. In cross-sectional or longitudinal analyses, there were no associations between DHEA and WHR in either men or women.CONCLUSION:Sex hormones are associated with WHR at baseline and also during follow-up above and beyond their baseline association. Future research is needed to determine if manipulation of hormones is associated with changes in central obesity. [ABSTRACT FROM AUTHOR]

This study estimated the cost per responder (CPR) of brodalumab at the end of induction period of therapy for adult moderate-to-severe psoriasis patients compared to currently approved biologics: adalimumab, etanercept, guselkumab, infliximab [innovator and subsequent entry biologics (SEB)], ixekizumab, secukinumab and ustekinumab. The CPR was calculated as the drug acquisition costs divided by the proportion of patients with PASI 90, 75, or 100, each outcome separately during the induction period. [Extracted from the article]

Objective: Absence rates remain high in UK schools, with negative implications for attainment, life chances and inequality. Reasons for non-attendance are complex but include psychosocial factors. Few UK-based studies have evaluated psychosocial interventions for school attendance outcomes or its moderators. This pre-post evaluation examined the potential influence of school-based one-to-one counselling on school attendance and possible moderators., Design and Setting: Secondary analysis of routine data, collected by a national mental health provider in primary and secondary schools., Participants: 7405 pupils aged 4-19 years, with complete school attendance records at Time1 (pre-counselling term) and Time2 (the term when counselling ended)., Intervention: All participants received school-based one-to-one counselling with a trained counsellor between August 2016 and December 2019., Outcomes: Percentage of school sessions attended (continuous) and persistent absence (binary; attending ≤90% of sessions) in a term. Potential moderators included sociodemographics, mental health and school engagement/enjoyment., Results: Median Time1 attendance was 96%. 23.6% of participants were persistently absent. The intervention was not associated with improved percentage attendance (0.028%, 95% CI -0.160-0.216%) but was associated with 18.5% reduced odds of persistent absence (OR=0.815, 95% CI 0.729-0.911). We identified five moderators of change in attendance (interaction terms p<0.05): age group (improvements for 4-9 s; worsening for 15-19 s), improvement for some ethnicities and lower parent/carer education. Mental health and school engagement/enjoyment co-varied with attendance in expected directions., Conclusions: One-to-one counselling may improve school attendance among persistently absent pupils, particularly at younger ages. Improving mental health and pupil engagement/enjoyment are potential intervention targets. Our hypotheses require confirmation with controlled designs., Competing Interests: Competing interests: SG, KT, HW and JW declare that they are employed by the implementing organisation. JS was partially funded by Place2Be. There are no other conflicts of interest., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Many Veterans receive Department of Veterans Affairs (VA)-purchased care from non-VA facilities but little is known about factors that Veterans consider for this choice. Between May 2020 and August 2021, we surveyed VA-purchased care-eligible VA patients about barriers and facilitators to choosing where to receive care. We examined the association between travel time to their VA facility and their choice of VA-purchased care (VA-paid health care received in non-VA settings) versus VA facility and whether this association was modified by distrust. We received 1,662 responses and 692 (42%) chose a VA facility. Eighty percent reported quality care was in their top three factors that influenced their decision. Respondents with the highest distrust and who lived >1 hr from the nearest VA facility had the lowest predicted probability (PP) of choosing VA (PP 15%; 95% confidence interval: 10%-20%). Veterans value quality of care. VA and other health care systems should consider patient-centered ways to improve and publicize quality and reduce distrust., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: There is a pressing need to offer more accessible, evidence-based psychological interventions to secondary school students who are increasingly reporting difficulties with anxiety and low mood. The aim of this pragmatic randomised multiple baseline trial is to evaluate the efficacy of a school-based counselling intervention called Knowledge Insight Tools (KIT) for reducing anxiety and low mood in UK secondary school students. KIT is a flexible intervention delivered individually and informed by cognitive behavioural therapy (CBT)., Methods: We will use a randomised multiple baseline design whereby young people will be randomly allocated to a baseline wait period of 3, 4, 5, 6, 7, or 8 weekly measurements, followed by receiving up to 10 weekly sessions of KIT delivered by trained, school-based practitioners. We aim to recruit 60 young people aged 11-18 who are primarily experiencing problems with low mood and/or anxiety from secondary schools across England and Scotland. We will assess child-reported anxiety, mood, and general psychological distress/coping with the Young Person's Clinical Outcomes in Routine Evaluation (YP-CORE), recorded at each session during the baseline and intervention phases. We will also assess child-reported anxiety and low mood with the Revised Children's Anxiety and Depression Scale (RCADS) at the beginning and end of treatment; practitioner-reported treatment fidelity with the KIT Fidelity Checklist; and practitioner-reported feasibility with an end-of-treatment Implementation Survey. We will analyse within-person and between-person change in YP-CORE scores across the baseline and intervention phases using visual analysis and piecewise multilevel growth curve models. We will also analyse pre-post changes in YP-CORE scores using randomisation tests, and reliable and clinically significant change using the RCADS scores., Discussion: The KIT trial is a pragmatic, randomised multiple baseline trial aimed at evaluating a school-based, individual CBT counselling intervention for reducing anxiety and low mood in UK secondary school students. Results will directly inform the provision of KIT in school-based counselling services, as well as the growing evidence-base for school-based CBT interventions., Trial Registration: ClinicalTrials.gov NCT06188962. Retrospectively registered on 02/01/24., (© 2024. The Author(s).)

Background: The use of feedback to address gaps and reinforce skills is a key component of successful competency-based mental health and psychosocial support intervention training approaches. Competency-based feedback during training and supervision for personnel delivering psychological interventions is vital for safe and effective care., Aims: For non-specialists trained in low-resource settings, there is a lack of standardised feedback systems. This study explores perspectives on competency-based feedback, using structured role-plays that are featured on the Ensuring Quality in Psychosocial and Mental Health Care (EQUIP) platform developed by the World Health Organization and United Nations Children's Fund., Method: Qualitative data were collected from supervisors, trainers and trainees from multiple EQUIP training sites (Ethiopia, Kenya, Lebanon, Peru and Uganda), from 18 key informant interviews and five focus group discussions ( N = 41 participants). Qualitative analysis was conducted in Dedoose, using a codebook with deductively and inductively developed themes., Results: Four main themes demonstrated how a competency-based structure enhanced the feedback process: (a) competency-based feedback was personalised and goal-specific, (b) competency-based feedback supported a feedback loop, (c) competency-based feedback supported a comfortable and objective feedback environment, and (d) competency-based feedback created greater opportunities for flexibility in training and supervision., Conclusions: A better understanding of the role of feedback supports the implementation of competency-based training that is systematic and effective for trainers and supervisors, which ultimately benefits the learning process for trainees.

Background: Themes of equity, diversity and inclusion (EDI) arise commonly within healthcare simulation. Though faculty development guidance and standards include increasing reference to EDI, information on how faculty might develop in this area is lacking. With increasingly formal expectations being placed on simulation educators to adhere to EDI principles, we require a better understanding of the developmental needs of educators and clear guidance so that teams can work towards these expectations. Our study had two aims: Firstly, to explore the extent to which an existing competency framework for medical teachers to teach ethnic and cultural diversity is relevant for simulation educator competency in EDI, and secondly, informed by the data gathered, to construct a modified competency framework in EDI for simulation educators., Methods: We engaged our participants (10 simulation faculty) in a 5-month period of enhanced consideration of EDI, using the SIM-EDI tool to support faculty debriefing conversations focussed on EDI within a pre-existing programme of simulation. We interviewed participants individually at two timepoints and analysed transcript data using template analysis. We employed an existing competency framework for medical teachers as the initial coding framework. Competencies were amended for the simulation context, modified based on the data, and new themes were added inductively, to develop a new developmental framework for simulation educators., Results: Interview data supported the relevance of the existing competency framework to simulation. Modifications made to the framework included the incorporation of two inductively coded themes ('team reflection on EDI' and 'collaboration'), as well as more minor amendments to better suit the healthcare simulation context. The resultant Developmental Framework for Simulation Educators in EDI outlines 10 developmental areas we feel are required to incorporate consideration of EDI into simulation programmes during the design, delivery and debriefing phases. We propose that the framework acts as a basis for simulation faculty development in EDI., Conclusions: Simulation faculty development in EDI is important and increasingly called for by advisory bodies. We present a Developmental Framework for Simulation Educators in EDI informed by qualitative data. We encourage simulation teams to incorporate this framework into faculty development programmes and report on their experiences., (© 2024. The Author(s).)

Introduction: In the USA, minoritised communities (racial and ethnic) have suffered disproportionately from COVID-19 compared with non-Hispanic white communities. In a large cohort of patients hospitalised for COVID-19 in a healthcare system spanning five adult hospitals, we analysed outcomes of patients based on race and ethnicity., Methods: This was a retrospective cohort analysis of patients 18 years or older admitted to five hospitals in the mid-Atlantic area between 4 March 2020 and 27 May 2022 with confirmed COVID-19. Participants were divided into four groups based on their race/ethnicity: non-Hispanic black, non-Hispanic white, Latinx and other. Propensity score weighted generalised linear models were used to assess the association between race/ethnicity and the primary outcome of in-hospital mortality., Results: Of the 9651 participants in the cohort, more than half were aged 18-64 years old (56%) and 51% of the cohort were females. Non-Hispanic white patients had higher mortality (p<0.001) and longer hospital length-of-stay (p<0.001) than Latinx and non-Hispanic black patients., Discussion: In this large multihospital cohort of patients admitted with COVID-19, non-Hispanic black and Hispanic patients did not have worse outcomes than white patients. Such findings likely reflect how the complex range of factors that resulted in a life-threatening and disproportionate impact of incidence on certain vulnerable populations by COVID-19 in the community was offset through admission at well-resourced hospitals and healthcare systems. However, there continues to remain a need for efforts to address the significant pre-existing race and ethnicity inequities highlighted by the COVID-19 pandemic to be better prepared for future public health emergencies., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The ventral pallidum (VP) is a central hub in the reward circuitry with diverse projections that have different behavioral roles attributed mostly to the connectivity with the downstream target. However, different VP projections may represent, as in the striatum, separate neuronal populations that differ in more than just connectivity. In this study, we performed in mice of both sexes a multimodal dissection of four major projections of the VP-to the lateral hypothalamus (VP →LH ), ventral tegmental area (VP →VTA ), lateral habenula (VP →LHb ), and mediodorsal thalamus (VP →MDT )-with physiological, anatomical, genetic, and behavioral tools. We also tested for physiological differences between VP neurons receiving input from nucleus accumbens medium spiny neurons (MSNs) that express either the D1 (D1-MSNs) or the D2 (D2-MSNs) dopamine receptor. We show that each VP projection (1) when inhibited during a cocaine conditioned place preference (CPP) test affects performance differently, (2) receives a different pattern of inputs using rabies retrograde labeling, (3) shows differentially expressed genes using RNA sequencing, and (4) has projection-specific characteristics in excitability and synaptic input characteristics using whole-cell patch clamp. VP →LH and VP →VTA projections have different effects on CPP and show low overlap in circuit tracing experiments, as VP →VTA neurons receive more striatal input, while VP →LH neurons receive more olfactory input. Additionally, VP →VTA neurons are less excitable, while VP →LH neurons are more excitable than the average VP neuron, a difference driven mainly by D2-MSN-responding neurons. Thus, VP →VTA and VP →LH neurons may represent largely distinct populations of VP neurons., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 the authors.)

Alkenones are unique lipids produced by certain species of microalgae, well-known for use in paleoclimatology, and more recently pursued to advance sustainability across multiple industries. Beginning in 2018, the biosynthesis of alkenones by commercially grown Tisochrysis lutea ( T - Iso ) microalgae from one of the world's most established producers, Necton S.A., changed dramatically from structures containing 37 and 38 carbons, to unusual shorter-chain C35 and C36 diunsaturated alkenones (C35:2 and C36:2 alkenones). While the exact reasons for this change remain unknown, analysis of alkenones isolated from T-Iso grown in 2021 and 2023 revealed that this change has persisted. The structure of these rare shorter-chain alkenones, including double bond position, produced by Necton T-Iso remained the same over the last five years, which was determined using a new and optimized cross-metathesis derivatization approach with analysis by comprehensive two-dimensional gas chromatography and NMR. However, noticeable differences in the alkenone profiles among the different batches were observed. Combined with fatty acid compositional analysis, the data suggest a connection between these lipid classes ( e.g. , increased DHA corresponds to lower amounts of shorter-chain alkenones) and the ability to manipulate their biosynthesis in T-Iso with changes to cultivation conditions., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Coeliac disease (CeD) is an immunological disease triggered by the consumption of gluten contained in food in individuals with a genetic predisposition. Diagnosis is based on the presence of small bowel mucosal atrophy and circulating autoantibodies (anti-type 2 transglutaminase antibodies). After diagnosis, patients follow a strict, life-long gluten-free diet. Although the criteria for diagnosis of this disease are well defined, the monitoring phase has been studied less and there is a lack of specific guidelines for this phase. To develop a set of clinical guidelines for CeD monitoring, we followed the Grading of Recommendations Assessment, Development and Evaluation methodology. Statements and recommendations with the level of evidence were developed and approved by the working group, which comprised gastroenterologists, pathologists, dieticians and biostatisticians. The proposed guidelines, endorsed by the North American and European coeliac disease scientific societies, make recommendations for best practices in monitoring patients with CeD based on the available evidence. The evidence level is low for many topics, suggesting that further research in specific aspects of CeD would be valuable. In conclusion, the present guidelines support clinicians in improving CeD treatment and follow-up and highlight novel issues that should be considered in future studies., (© 2023. Springer Nature Limited.)

Background: Mepolizumab, the first widely available anti-interleukin 5 biologic, targets eosinophilic inflammation and has been shown in clinical trials to reduce exacerbations, oral corticosteroid dependence, and healthcare utilization in patients with severe asthma. The impact of mepolizumab in a real-world, publicly funded healthcare setting is unknown. The objective of this study was to describe the demographics and clinical characteristics of real-world patients receiving mepolizumab, and to compare asthma-related outcomes and associated asthma-related costs before and during mepolizumab use., Methods: This retrospective, observational study in Ontario, Canada, included patients initiating mepolizumab between February 2016 and March 2019. Patients were identified using the mepolizumab patient support program and linked to the Institute for Clinical Evaluative Sciences database of publicly accessed healthcare. Patient outcomes were obtained for 12 months pre- and post-mepolizumab initiation and compared., Results: A total of 275 patients were enrolled in the overall patient support program cohort (mean [standard deviation] age 57.6 [13.5] years, mean [standard deviation] of the median per-patient eosinophil count 540.4 [491.9] cells/μL). Mepolizumab was associated with reductions in asthma exacerbations (46.1%, P < 0.001) and in the number of asthma-related visits to general practitioners (40.2%, P < 0.001), specialists (27.2%, P < 0.001), and emergency departments (52.1%, P < 0.001). Associated costs were significantly lower post- versus pre-mepolizumab for asthma-related general practitioner and specialist visits, and for all-cause emergency department visits and hospital admissions., Conclusions: In a real-world population of Canadian patients with severe asthma with an eosinophilic phenotype, the use of mepolizumab within a patient support program reduced asthma exacerbations and decreased asthma-related healthcare resource utilization and associated costs., (© 2024. The Author(s).)

Background: The economic impact of perianal fistulas in Crohn's disease (CD) has not been formally assessed in population-based studies in the biologic era., Aim: To compare direct health care costs in persons with and without perianal fistulas., Methods: We performed a longitudinal population-based study using administrative data from Ontario, Canada. Adults (> 17 years) with CD were identified between 2007 and 2013 using validated algorithms. Perianal fistula positive "cases" were matched to up to 4 "controls" with CD without perianal fistulas based on age, sex, geographic region, year of CD diagnosis and duration of follow-up. Direct health care costs, excluding drug costs from private payers, were estimated annually beginning 5 years before (lookback) and up to 9 years after perianal fistula diagnosis (study completion) for cases and a standardized date for matched controls., Results: A total of 581 cases were matched to 1902 controls. The annual per capita direct cost for cases was similar at lookback compared to controls ($2458 ± 6770 vs $2502 ± 10,752; p = 0.952), maximally greater in the first year after perianal fistulas diagnosis ($16,032 ± 21,101 vs $6646 ± 13,021; p < 0.001) and remained greater at study completion ($11,358 ± 17,151 vs $5178 ± 9792; p < 0.001). At perianal fistula diagnosis, the cost difference was driven primarily by home care cost (tenfold greater), publicly-covered prescription drugs (threefold greater) and hospitalizations (twofold greater), whereas at study completion, prescription drugs were the dominant driver (threefold greater)., Conclusion: In our population-based cohort, perianal fistulas were associated with significantly higher direct healthcare costs at the time of perianal fistulas diagnosis and sustained long-term., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: Diabetes is a major public health problem in Canada and requires multifactorial, consistent clinical management. The COVID-19 pandemic has increased challenges in the management of many chronic ailments, including diabetes. Diabetes was associated with a higher risk of severe illness in the context of COVID-19. Pandemic restrictions also impacted diabetes care continuity, which may have contributed to an increased risk of diabetes-related complications and mortality., Methods: This was a retrospective cross-sectional study of prescription patterns of antihyperglycemic medications claimed by individuals with type 2 diabetes (T2D) before and during the COVID-19 pandemic using the IQVIA Canada Longitudinal Prescription Claims database. The study period was from March 1, 2018, to February 28, 2021. The study outcomes are described on a monthly, quarterly, and yearly basis and overall, and by medication, medication class, and insurance coverage type. "New-to-molecule" patients were defined as those claiming a medication during the analysis period that they had no history of claiming in the database. Adults with at least 1 year of prescription history available and claiming their first prescription for an antihyperglycemic drug during the analysis period were classified as newly diagnosed with T2D., Results: A similar number of people had at least 1 non-insulin antihyperglycemic prescription during the baseline, prepandemic, and pandemic periods in Canada (1,778,155, 1,822,403, and 1,797,272, respectively). However, the number of people initiating newer antihyperglycemic medications decreased at the beginning of the pandemic, in contrast to older medications, which remained consistent across the pandemic period. The number of people diagnosed with T2D decreased in the early months of the pandemic but recovered by October 2020., Conclusion: The COVID-19 epidemic in Canada impacted clinical care for at-risk Canadians, with fewer being prescribed newer antihyperglycemic drugs and a reduction in the number of diagnoses of T2D., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: Diabetes requires ongoing monitoring and care to prevent long-term adverse health outcomes. In Canada, quarantine restrictions were put into place to address the coronavirus-2019 (COVID-19) pandemic in March 2020. Primary care diabetes clinics limited their in-person services and were advised to manage type 2 diabetes (T2D) through virtual visits and reduce the frequency of routine diabetes-related lab tests and screening., Methods: This retrospective cross-sectional study used de-identified patient records from a primary care electronic medical records database in Ontario, Canada, to identify people with T2D who had at least 1 health-care touchpoint between March 1, 2018, and February 28, 2021. Outcomes were described on a monthly or yearly basis: 1) number of people with primary care visits (in-person vs virtual); 2) number of people with referrals; 3) number of people with each of the vital/lab measures; and 4) results of the vital/lab measures., Results: A total of 16,845 individuals with T2D were included. Compared with the pre-pandemic period, the COVID-19 period had a 16.8% reduction in the T2D population utilizing any primary care and an increase of 330.4% in the number of people with at least 1 virtual visit. Compared with the pre-pandemic period, fewer people had vital/lab measures in the pandemic period. However, among the people with the test results available, the average values for all tests were similar in the pre- and pandemic periods., Conclusion: Further research is needed to understand the impact of the reduction of in-person clinical care on the entire population with T2D., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: In the United Kingdom, schools play an increasingly important role in supporting young peoples' mental health. While there is a growing evidence base to support the effectiveness of school-based interventions, less is known about how these provisions impact on local Child and Adolescent Mental Health Service (CAMHS) referral rates. There is a concern that an increase in school-based provision might lead to an increase in CAMHS referrals and overwhelm services. We aimed to examine the longitudinal association between Place2Be counselling provision in primary schools on CAMHS referral rates in South London., Method: This was a retrospective cohort study using linked data from the National Pupil Database (NPD) and CAMHS referrals to the South London and Maudsley's NHS Foundation Trust (SLaM) identified through the Clinical Record Interactive Search (CRIS) tool. The cohort included a total of 285 state-maintained primary schools in four London boroughs for the academic years of 2007-2012. During the study period, 23 of these schools received school-based mental health provision from Place2Be. The primary outcome was the incident rate ratio (IRR) of school-level accepted CAMHS referrals in 2012/13 in schools with, or without, Place2Be provision., Results: There was no significant association between elevated rates of CAMHS referral and Place2Be provision, even after comprehensive adjustment for school-level and pupil characteristics (IRR 0.91 (0.67-1.23)). School-level characteristics, including higher proportion of white-British pupils (IRR 1.009 (1.002-1.02)), medical staff ratio (IRR 6.49 (2.05-20.6)) and poorer Ofsted school inspection ratings (e.g. IRR 1.58 (1.06-2.34) for 'Requires Improvement' vs. 'Outstanding') were associated with increased CAMHS referral rates., Conclusions: Place2Be provision did not result in increased specialist mental health referrals; however, other school-level characteristics did. Future research should investigate pupils' Place2Be clinical outcomes, as well the outcomes of individuals referred to CAMHS to better understand which needs are being met by which services., (© 2021 The Authors. Child and Adolescent Mental Health published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

Background: Exclusion from school is a disciplinary tool with an increasingly recognised relationship to poor mental health among children and young people. We explored the relationship between mental health and school exclusion for a cohort of children and young people receiving one to one counselling., Method: We analysed routinely collected data from a diverse UK sample of children and young people aged between four and 16 years old and receiving school-based counselling (n = 6712 students from 308 primary and 61 secondary schools). Fixed period school exclusion rates (number of sessions) were compared between the academic year before and the academic year in which the child attended counselling. Mental health (Strengths and Difficulties Questionnaire) was compared at baseline and at the end of the intervention (after between 16-22 counselling sessions depending on the phase of education)., Results: Despite more complex and severe initial difficulties, and facing greater adversity, children and young people who experienced school exclusion prior to counselling demonstrated a significant reduction in subsequent sessions of school exclusion in the academic year that the counselling took place (from two full school weeks to half a school week). Moreover, over 74% of the students had fewer reported exclusions and more than half (56.14%) did not have any further subsequent exclusions. They also had better mental health measured by the teacher reported SDQ (pre-intervention M = 18.94, SD = 6.83 vs. postintervention M = 15.67, SD = 7.56, t(310) = 8.23, p < .001) or by the parents (pre-intervention M = 18.09, SD = 6.42 vs. postintervention M = 14.0, SD = 6.99, t(171) = 7.71, p < .001)., Conclusions: School-based mental health interventions may positively influence educational engagement as well as mental health. Providers should, therefore, monitor both to explore the impact of their interventions. The identification of poor mental health may alter staff perceptions and management of challenging pupils, which future studies should explore., (© 2022 Association for Child and Adolescent Mental Health.)

The burden of all-cause community-acquired pneumonia (CAP), including pneumococcal pneumonia, is typically estimated using ICD codes where pneumonia is coded as the most responsible diagnosis (MRDx). Pneumonia may also be coded as other than most responsible diagnosis (ODx) based on administrative and reimbursement criteria. Analyses including pneumonia as MRDx only likely underestimate hospitalized CAP incidence. The aim of this study was to estimate the burden of hospitalized all-cause CAP in Canada and to assess the contribution of ODx-coded cases to the overall disease burden. This longitudinal retrospective study obtained data from the Canadian Institutes of Health Information (CIHI) for adults 50+ years hospitalized for CAP between 1 April 2009 and 31 March 2019. Cases were identified as those where pneumonia was either diagnosis code type M (MRDx) or pre-admit comorbidity type 1 (ODx). Reported outcomes include pneumonia incidence rate, in-hospital mortality, hospital length of stay, and cost. Outcomes were stratified by age group, case coding, and comorbidity. Between 2009-2010 and 2018-2019, CAP incidence increased from 805.66 to 896.94 per 100,000. During this time, 55-58% of cases had pneumonia coded as ODx. Importantly, these cases had longer hospital stays, higher in-hospital mortality, and higher cost of hospitalization. The burden of CAP remains substantial and is significantly greater than that estimated by solely focusing on MRDx-coded cases. Our findings have implications for policy decision making related to current and future immunization programs.

Estimated all-cause mortality within 30-days of hypoglycemic emergencies is 0.8 % in adults with type 1 diabetes and 1.7 % with type 2 diabetes; and within 30-days of hyperglycemic emergencies, it is 1.2 % with type 1 diabetes and 2.8 % with type 2 diabetes. These rates changed little between 2011 and 2020., Competing Interests: Declaration of Competing Interest In the past 36 months, Dr. McCoy received support from NIDDK, PCORI, and AARP® for research unrelated to this work. She also serves as a consultant to Emmi® (Wolters Kluwer) on the development of patient education materials related to prediabetes and diabetes. Dr. Galindo received research support to Emory University for investigator-initiated studies outside of this work from Novo Nordisk, Dexcom and Eli Lilly and consulting fees from Sanofi, Eli Lilly, Pfizer, Boehringer, and Weight Watchers. He is also funded by NIDDK. Dr. Umpierrez is partly supported by research grants from the Clinical and Translational Science Award program and NIDDK and has received research support (to Emory University) unrelated to this work from Astra Zeneca, Bayer, Abbott, and Dexcom. Dr. O’Connor has received research support from NIDDK, NHLBI, NCI, NICHD, NIMH, NIDA, and PCORI and has served as an unpaid consultant to the World Health Organization. Dr. Golden has received research support from NIDDK and serves on the Health Equity Advisory for Medtronic, Inc, and for Abbott., (Copyright © 2023 Elsevier B.V. All rights reserved.)

CRISPR RNA-guided detection and degradation of foreign DNA is a dynamic process. Viruses can interfere with this cellular defense by expressing small proteins called anti-CRISPRs. While structural models of anti-CRISPRs bound to their target complex provide static snapshots that inform mechanism, the dynamics and thermodynamics of these interactions are often overlooked. Here, we use hydrogen deuterium exchange-mass spectrometry (HDX-MS) and differential scanning fluorimetry (DSF) experiments to determine how anti-CRISPR binding impacts the conformational landscape of the type IF CRISPR RNA guided surveillance complex (Csy) upon binding of two different anti-CRISPR proteins (AcrIF9 and AcrIF2). The results demonstrate that AcrIF2 binding relies on enthalpic stabilization, whereas AcrIF9 uses an entropy driven reaction to bind the CRISPR RNA-guided surveillance complex. Collectively, this work reveals the thermodynamic basis and mechanistic versatility of anti-CRISPR-mediated immune suppression. More broadly, this work presents a striking example of how allosteric effectors are employed to regulate nucleoprotein complexes., (© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.)