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The desire to support student learning and professional development, in combination with accreditation requirements, necessitates the need to evaluate the learning environment of educational programs. The Health Education Learning Environment Survey (HELES) is a recently-developed global measure of the learning environment for health professions programs. This paper provides evidence of the applicability of the HELES for evaluating the learning environment across four health professions programs: medicine, nursing, occupational therapy and pharmaceutical sciences. Two consecutive years of HELES data were collected from each program at a single university (year 1 = 552 students; year 2 = 745 students) using an anonymous online survey. Reliability analyses across programs and administration years supported the reliability of the tool. Two-way factorial ANOVAs with program and administration year as the independent variables indicated statistically- and practically-significant differences across programs for four of the seven scales. Overall, these results support the use of the HELES to evaluate student perceptions of the learning environment multiple of health professions programs.

Abstract Little is known regarding the relationship between common comorbidities in persons with tuberculosis (TB) (including human immunodeficiency virus [HIV], diabetes, and hepatitis C virus [HCV]) and post-TB mortality. We conducted a retrospective cohort study among persons who initiated treatment for rifampicin-resistant or multi/extensively drug-resistant (RR or M/XDR) TB reported to the country of Georgia’s TB surveillance during 2009–2017. Exposures included HIV serologic status, diabetes, and HCV status. Our outcome was all-cause post-TB mortality determined by cross-validating vital status with Georgia’s death registry through November 2019. We estimated adjusted hazard rate ratios (aHR) and 95% confidence intervals (CI) of post-TB mortality among participants with and without comorbidities using cause-specific hazard regressions. Among 1032 eligible participants, 34 (3.3%) died during treatment and 87 (8.7%) died post-TB treatment. The median time to post-TB death was 21 months (interquartile range 7–39) after TB treatment. After adjusting for confounders, the hazard rates of post-TB mortality were higher among participants with HIV co-infection (aHR = 3.74, 95%CI 1.77–7.91) compared to those without HIV co-infection. In our cohort, post-TB mortality occurred most commonly in the first 3 years post-TB treatment. Linkage to care for common TB comorbidities post-treatment may reduce post-TB mortality rates.

Abstract Background Lipodystrophy syndromes are a heterogeneous group of rare, life-limiting diseases characterized by a selective loss of adipose tissue and severe metabolic complications. There is a paucity of information describing the experiences and challenges faced by physicians who have seen and treated patients with lipodystrophy. This study aimed to provide a better understanding of the physician’s perspective regarding the patient journey in lipodystrophy, including diagnosis, the burden of disease, and treatment approaches. Methods Thirty-three physicians from six countries who had seen or treated patients with lipodystrophy were interviewed using a semi-structured questionnaire. Interviews were transcribed, anonymized, and analyzed for themes and trends. Four main themes were developed: (1) the diagnostic journey in lipodystrophy including the disease features or ‘triggers’ that result in the onward referral of patients to specialist medical centers with experience in managing lipodystrophy; (2) the impact of lipodystrophy on patient quality of life (QoL); (3) the use of standard therapies and leptin replacement therapy (metreleptin) in lipodystrophy, and (4) barriers to metreleptin use. Results Participants reported that, due to their rarity and phenotypic heterogeneity, lipodystrophy cases are frequently unrecognized, leading to delays in diagnosis and medical intervention. Early consultation with multidisciplinary specialist medical teams was recommended for suspected lipodystrophy cases. The development and progression of metabolic complications were identified as key triggers for the referral of patients to specialist centers for follow-up care. Participants emphasized the impact of lipodystrophy on patient QoL, including effects on mental health and self-image. Although participants routinely used standard medical therapies to treat specific metabolic complications associated with lipodystrophy, it was acknowledged that metreleptin was typically required in patients with congenital generalized lipodystrophy and in some acquired generalized and partial lipodystrophy cases. A lack of experience among some participants and restrictions to access remained as barriers to metreleptin use. Conclusions To our knowledge, this is one of the first studies describing the qualitative experiences of physicians regarding the diagnosis and management of lipodystrophy. Other physician-centered studies may help increase the awareness of lipodystrophy among the wider medical community and support clinical approaches to this rare disease.

Summary: Background: BK polyomavirus (BKV) DNAaemia occurs in 10% of recipients of kidney transplants, contributing to premature allograft failure. Evidence suggests disease is donor derived. Hypothetically, recipient infection with a different BKV serotype increases risk due to poorer immunological control. Thus, understanding the composition and activity of the humoral anti-BKV responses in donor/recipient (D/R) pairs is critical. Methods: Using 224 paired pre-transplant D/R samples, BKV VP1 genotype-specific pseudoviruses were employed to define the breadth of the antibody response against different serotypes (ELISA) and, to characterise specific neutralising activity (nAb) using the 50% inhibitory concentration (LogIC50). Mismatch (MM) ratios were calculated using the ratio of recipient ELISA or nAb reactive BKV serotypes relative to the number of donor reactive serotypes. Findings: BKV DNAaemia was observed in 28/224 recipients of kidney transplants. These recipients had lower nAb titres against all the serotypes, with median logIC50 values of 1.19–2.91, compared to non-viraemic recipients’ median logIC50 values of 2.13–3.30. nAb D/R MM ratios >0.67 associated with significantly higher risk of BKV viraemia, with an adjusted odds ratio of 5.12 (95% CI 2.07 to 13.04; p

Background The long-term outcomes of COVID-19 hospitalisation in individuals with pre-existing airway diseases are unknown. Methods Adult participants hospitalised for confirmed or clinically suspected COVID-19 and discharged between 5 March 2020 and 31 March 2021 were recruited to the Post-hospitalisation COVID-19 (PHOSP-COVID) study. Participants attended research visits at 5 months and 1 year post discharge. Clinical characteristics, perceived recovery, burden of symptoms and health-related quality of life (HRQoL) of individuals with pre-existing airway disease (i.e., asthma, COPD or bronchiectasis) were compared to the non-airways group. Results A total of 615 out of 2697 (22.8%) participants had a history of pre-existing airway diseases (72.0% diagnosed with asthma, 22.9% COPD and 5.1% bronchiectasis). At 1 year, the airways group participants were less likely to feel fully recovered (20.4% versus 33.2%, p

Key Clinical Message VEXAS syndrome (vacuoles, E1 enzyme, X‐linked, autoinflammatory, somatic) is a novel autoinflammatory syndrome. We describe a case of VEXAS syndrome with upper airway and oral cavity involvement which are not well described in the literature.

Introduction: Numerous studies have demonstrated the accuracy of point-of-care ultrasound (POCUS). Portable, handheld devices have expanded the clinical scope of POCUS at a fraction of the cost of traditional, cart-based models. There is a paucity of data assessing the diagnostic accuracy of portable devices. Our objective in this study was to compare the diagnostic accuracy of a portable device with a cart-based model. Methods: This was an institutional review board-approved, observational, prospective, randomized clinical trial (NCT05196776) of a convenience sample of adult patients who presented to a university-based health system. Patients who required a cardiac, lung, renal, aorta, or biliary POCUS were randomized to a portable device or to a cart-based model. We hypothesized that the cart-based model would have a 90% diagnostic accuracy vs 70% for the handheld device. To detect a 20% difference, the sample size was calculated to be 98, with 49 patients randomized to each arm. We used standard 2x2 tables to calculate test characteristics with 95% confidence intervals (CI). Results: A total of 110 patients were enrolled, with 56 patients randomized to the cart-based model and 54 to the handheld device. The sensitivity, specificity, and diagnostic accuracy of the cart-based vs handheld were 77.8% (40–97.2) vs 92.9% (66.1–99.8), 91.5% (79.6–97.6) vs 92.3% (79.1–98.4%), and 89.3% (78.1–96) vs 92.5% (81.8–97.9), respectively. Conclusion: The diagnostic accuracy of a portable, handheld device is similar to that of a cart-based model.

Maternal vaccination during pregnancy, in general and against COVID-19 infection, offers protection to both mother and baby, but uptake remains suboptimal. This study aimed to explore the perceptions regarding COVID-19 vaccination in pregnancy, particularly for marginalised populations and those living with social or medical complexity. A total of 96 semi-structured in-depth interviews were conducted with 40 women, 15 partners, 21 HCPs, and 20 policy makers, across all four nations of the United Kingdom (UK), discussing their lived experience of utilising, delivering, or developing policy for COVID-19 vaccination in pregnancy during the pandemic. Three themes were derived: (1) historical and social context, (2) communication of information and guidance, and (3) appraisal and action. Together these captured the participants’ legacy of mistrust in drugs during pregnancy; prior positive experiences; concerns about missing information, conflicting information, or false information about COVID-19 vaccines; and confusing guidance for pregnant women. The final theme describes the participants’ behaviour and actions undertaken consequent to their experiences and the available information. The findings suggest efforts to improve COVID-19 vaccination in pregnancy may be best focused on personalised communication of information. A trusting relationship and prior positive experiences with other vaccines, both in and outside of pregnancy, positively influenced perceptions of COVID-19 vaccination.

Background PRECISE-DYAD is an observational cohort study of mother-child dyads running in urban and rural communities in The Gambia and Kenya. The cohort is being followed for two years and includes uncomplicated pregnancies and those that suffered pregnancy hypertension, fetal growth restriction, preterm birth, and/or stillbirth. Methods The PRECISE-DYAD study will follow up ~4200 women and their children recruited into the original PRECISE study. The study will add to the detailed pregnancy information and samples in PRECISE, collecting additional biological samples and clinical information on both the maternal and child health. Women will be asked about both their and their child’s health, their diets as well as undertaking a basic cardiology assessment. Using a case-control approach, some mothers will be asked about their mental health, their experiences of care during labour in the healthcare facility. In a sub-group, data on financial expenditure during antenatal, intrapartum, and postnatal periods will also be collected. Child development will be assessed using a range of tools, including neurodevelopment assessments, and evaluating their home environment and quality of life. In the event developmental milestones are not met, additional assessments to assess vision and their risk of autism spectrum disorders will be conducted. Finally, a personal environmental exposure model for the full cohort will be created based on air and water quality data, combined with geographical, demographic, and behavioural variables. Conclusions The PRECISE-DYAD study will provide a greater epidemiological and mechanistic understanding of health and disease pathways in two sub-Saharan African countries, following healthy and complicated pregnancies. We are seeking additional funding to maintain this cohort and to gain an understanding of the effects of pregnancies outcome on longer-term health trajectories in mothers and their children.

Objectives Tuberculosis infection (TBI) is marked by dynamic host–pathogen interactions with persistent low-grade inflammation and is associated with increased risk of cardiovascular diseases (CVD) including acute coronary syndrome, myocardial infarction and stroke. However, few studies assess the relationship between TBI and hypertension, an intermediate of CVD. We sought to determine the association between TBI and hypertension using data representative of the adult US population.Methods We performed cross-sectional analyses using data from the 2011–2012 US National Health and Nutrition Examination Survey (NHANES). Eligible participants included adults with valid QuantiFERON-TB Gold In-Tube (QFT-GIT) test results who also had blood pressure measures and no history of TB disease. TBI was defined by a positive QFT-GIT. We defined hypertension by either elevated measured blood pressure levels (ie, systolic ≥130 mm Hg or diastolic ≥80 mm Hg) or known hypertension indications (ie, self-reported previous diagnosis or use of antihypertensive medications). Analyses were performed using robust quasi-Poisson regressions and accounted for the stratified probability sampling design of NHANES.Results The overall prevalence of TBI was 5.7% (95% CI 4.7% to 6.7%) and hypertension was present among 48.9% (95% CI 45.2% to 52.7%) of participants. The prevalence of hypertension was higher among those with TBI (58.5%, 95% CI 52.4% to 64.5%) than those without TBI (48.3%, 95% CI 44.5% to 52.1%) (prevalence ratio (PR) 1.2, 95% CI 1.1 to 1.3). However, after adjusting for confounders, the prevalence of hypertension was similar for those with and without TBI (adjusted PR 1.0, 95% CI 1.0 to 1.1). The unadjusted prevalence of hypertension was higher among those with TBI versus no TBI, especially among individuals without CVD risk factors including those with normal body mass index (PR 1.6, 95% CI 1.2 to 2.0), euglycaemia (PR 1.3, 95% CI 1.1 to 1.5) or non-smokers (PR 1.2, 95% CI 1.1 to 1.4).Conclusions More than half of adults with TBI in the USA had hypertension. Importantly, we observed a relationship between TBI and hypertension among those without established CVD risk factors.Summary The prevalence of hypertension was high (59%) among adults with TBI in the USA. In addition, we found that the prevalence of hypertension was significantly higher among adults with positive QFT without established hypertension risk factors.

Key Clinical Message We report an unusual case presentation of a patient with necrotic tissue changes of the right second and third fingers, found to have myeloid sarcoma with Staphylococcus‐positive tenosynovitis and underlying acute myeloid leukemia, to highlight the importance of comprehensive evaluation in patients with atypical wounds.

Summary: Background: Increasing evidence supports that antibodies can protect against active tuberculosis (TB) but knowledge of potentially protective antigens, especially in the airways, is limited. The main objective of this study was to identify antigen-specific airway and systemic immunoglobulin isotype responses associated with the outcome of controlled latent Mycobacterium tuberculosis (Mtb) infection (LTBI) versus uncontrolled infection (TB) in nonhuman primates. Methods: In a case–control design, using non-parametric group comparisons with false discovery rate adjustments, we assessed antibodies in 57 cynomolgus macaques which, following low-dose airway Mtb infection, developed either LTBI or TB. We investigated airway and systemic IgG, IgA, and IgM responses in paired bronchoalveolar lavage and plasma samples prior to, two-, and 5-6-months post Mtb infection using an antigen-unbiased approach with Mtb glycan and proteome-wide microarrays. Findings: Macaques that developed LTBI (n = 36) had significantly increased airway and plasma IgA reactivities to specific arabinomannan (AM) motifs prior to Mtb infection compared to those that developed TB (n = 21; p

Abstract The current subjective histopathological assessment of cutaneous melanoma is challenging. The application of image analysis algorithms to histological images may facilitate improvements in workflow and prognostication. To date, several individual algorithms applied to melanoma histological images have been reported with variations in approach and reported accuracies. Histological digital images can be created using a camera mounted on a light microscope, or through whole slide image (WSI) generation using a whole slide scanner. Before any such tool could be integrated into clinical workflow, the accuracy of the technology should be carefully evaluated and summarised. Therefore, the objective of this review was to evaluate the accuracy of existing image analysis algorithms applied to digital histological images of cutaneous melanoma. Database searching of PubMed and Embase from inception to 11th March 2022 was conducted alongside citation checking and examining reports from organisations. All studies reporting accuracy of any image analysis applied to histological images of cutaneous melanoma, were included. The reference standard was any histological assessment of haematoxylin and eosin-stained slides and/or immunohistochemical staining. Citations were independently deduplicated and screened by two review authors and disagreements were resolved through discussion. The data was extracted concerning study demographics; type of image analysis; type of reference standard; conditions included and test statistics to construct 2 × 2 tables. Data was extracted in accordance with our protocol and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Diagnostic Test Accuracy (PRISMA-DTA) Statement. A bivariate random-effects meta-analysis was used to estimate summary sensitivities and specificities with 95% confidence intervals (CI). Assessment of methodological quality was conducted using a tailored version of the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. The primary outcome was the pooled sensitivity and specificity of image analysis applied to cutaneous melanoma histological images. Sixteen studies were included in the systematic review, representing 4,888 specimens. Six studies were included in the meta-analysis. The mean sensitivity and specificity of automated image analysis algorithms applied to melanoma histological images was 90% (CI 82%, 95%) and 92% (CI 79%, 97%), respectively. Based on limited and heterogeneous data, image analysis appears to offer high accuracy when applied to histological images of cutaneous melanoma. However, given the early exploratory nature of these studies, further development work is necessary to improve their performance.

COVID-19 vaccination rates are lower in women of reproductive age (WRA), including pregnant/postpartum women, despite their poorer COVID-19-related outcomes. We evaluated the vaccination experiences of 3568 U.K. WRA, including 1983 women (55.6%) experiencing a pandemic pregnancy, recruited through the ZOE COVID Symptom Study app. Two staggered online questionnaires (Oct–Dec 2021: 3453 responders; Aug–Sept 2022: 2129 responders) assessed reproductive status, COVID-19 status, vaccination, and attitudes for/against vaccination. Descriptive analyses included vaccination type(s), timing relative to age-based eligibility and reproductive status, vaccination delay (first vaccination >28 days from eligibility), and rationale, with content analysis of free-text comments. Most responders (3392/3453, 98.2%) were vaccinated by Dec 2021, motivated by altruism, vaccination supportiveness in general, low risk, and COVID-19 concerns. Few declined vaccination (by Sept/2022: 20/2129, 1.0%), citing risks (pregnancy-specific and longer-term), pre-existing immunity, and personal/philosophical reasons. Few women delayed vaccination, although pregnant/postpartum women (vs. other WRA) received vaccination later (median 3 vs. 0 days after eligibility, p < 0.0001). Despite high uptake, concerns included adverse effects, misinformation (including from healthcare providers), ever-changing government advice, and complex decision making. In summary, most women in this large WRA cohort were promptly vaccinated, including pregnant/post-partum women. Altruism and community benefit superseded personal benefit as reasons for vaccination. Nevertheless, responders experienced angst and received vaccine-related misinformation and discouragement. These findings should inform vaccination strategies in WRA.

Introduction Increases in pain and interference with quality of life is a common concern among people with chronic non-cancer pain (CNCP) who are tapering opioid medications. Research indicates that access to social and psychological support for pain self-management may help people to reduce their opioid dose without increasing pain and interference. This study evaluates the efficacy of a text messaging intervention designed to provide people with CNCP with social and psychological support for pain self-management while tapering long-term opioid therapy (LTOT) under the guidance of their prescriber.Methods and analysis A double-blind randomised controlled trial will be conducted. Patients with CNCP (n=74) who are tapering LTOT will be enrolled from across Australia. Participants will continue with their usual care while tapering LTOT under the supervision of their prescribing physician. They will randomly receive either a psychoeducational video and supportive text messaging (two Short Message Service (SMS) per day) for 12 weeks or the video only. The primary outcome is the pain intensity and interference assessed by the Pain, Enjoyment of Life and General Activity scale. Secondary outcomes include mood, self-efficacy, pain cognitions, opioid dose reduction, withdrawal symptoms, and acceptability, feasibility, and safety of the intervention. Participants will complete questionnaires at baseline and then every 4 weeks for 12 weeks and will be interviewed at week 12. This trial will provide evidence for the efficacy of a text messaging intervention to support patients with CNCP who are tapering LTOT. If proven to be efficacious and safe, this low-cost intervention can be implemented at scale.Ethics and dissemination The study protocol was reviewed and approved by the Northern Sydney Local Health District (Australia). Study results will be published in peer-reviewed journals and presented at scientific and professional meetings.Trial registration number ACTRN12622001423707.

Objective To determine current UK medical students’ career intentions after graduation and on completing the Foundation Programme (FP), and to ascertain the motivations behind these intentions.Design Cross-sectional, mixed-methods survey of UK medical students, using a non-random sampling method.Setting All 44 UK medical schools recognised by the General Medical Council.Participants All UK medical students were eligible to participate. The study sample consisted of 10 486 participants, approximately 25.50% of the medical student population.Outcome measures Career intentions of medical students postgraduation and post-FP, motivations behind these career intentions, characterising the medical student population and correlating demographic factors and propensity to leave the National Health Service (NHS).Results The majority of participating students (8806/10 486, 83.98%) planned to complete both years of the FP after graduation, with under half of these students (4294/8806, 48.76%) intending to pursue specialty training thereafter. A subanalysis of career intentions after the FP by year of study revealed a significant decrease in students’ intentions to enter specialty training as they advanced through medical school. Approximately a third of surveyed students (3392/10 486, 32.35%) intended to emigrate to practise medicine, with 42.57% (n=1444) of those students not planning to return. In total, 2.89% of students intended to leave medicine altogether (n=303). Remuneration, work-life balance and working conditions were identified as important factors in decision-making regarding emigration and leaving the profession. Subgroup analyses based on gender, type of schooling, fee type and educational background were performed. Only 17.26% of surveyed students were satisfied or very satisfied with the overall prospect of working in the NHS.Conclusions The Ascertaining the career Intentions of UK Medical Students study highlights UK students’ views and career intentions, revealing a concerning proportion of those surveyed considering alternative careers or emigration. Addressing factors such as remuneration, work-life balance and working conditions may increase retention of doctors and improve workforce planning efforts.

Abstract Background Emerging RNA viruses that target the central nervous system (CNS) lead to cognitive sequelae in survivors. Studies in humans and mice infected with West Nile virus (WNV), a re-emerging RNA virus associated with learning and memory deficits, revealed microglial-mediated synapse elimination within the hippocampus. Moreover, CNS-resident memory T (TRM) cells activate microglia, limiting synapse recovery and inducing spatial learning defects in WNV-recovered mice. The signals involved in T cell-microglia interactions are unknown. Methods Here, we examined immune cells within the murine WNV-recovered forebrain using single-cell RNA sequencing to identify putative ligand-receptor pairs involved in intercellular communication between T cells and microglia. Clustering and differential gene analyses were followed by protein validation and genetic and antibody-based approaches utilizing an established murine model of WNV recovery in which microglia and complement promote ongoing hippocampal synaptic loss. Results Profiling of host transcriptome immune cells at 25 days post-infection in mice revealed a shift in forebrain homeostatic microglia to activated subpopulations with transcriptional signatures that have previously been observed in studies of neurodegenerative diseases. Importantly, CXCL16/CXCR6, a chemokine signaling pathway involved in TRM cell biology, was identified as critically regulating CXCR6 expressing CD8+ TRM cell numbers within the WNV-recovered forebrain. We demonstrate that CXCL16 is highly expressed by all myeloid cells, and its unique receptor, CXCR6, is highly expressed on all CD8+ T cells. Using genetic and pharmacological approaches, we demonstrate that CXCL16/CXCR6 not only is required for the maintenance of WNV-specific CD8 TRM cells in the post-infectious CNS, but also contributes to their expression of TRM cell markers. Moreover, CXCR6+CD8+ T cells are required for glial activation and ongoing synapse elimination. Conclusions We provide a comprehensive assessment of the role of CXCL16/CXCR6 as an interaction link between microglia and CD8+ T cells that maintains forebrain TRM cells, microglial and astrocyte activation, and ongoing synapse elimination in virally recovered animals. We also show that therapeutic targeting of CXCL16 in mice during recovery may reduce CNS CD8+ TRM cells.

BackgroundGlucose-guided eating (GGE) improves metabolic markers of chronic disease risk, including insulin resistance, in adults without diabetes. GGE is a timed eating paradigm that relies on experiencing feelings of hunger and having a preprandial glucose level below a personalized threshold computed from 2 consecutive morning fasting glucose levels. The dawn phenomenon (DP), which results in elevated morning preprandial glucose levels, could cause typically derived GGE thresholds to be unacceptable or ineffective among people with type 2 diabetes (T2DM). ObjectiveThe aim of this study is to quantify the incidence and day-to-day variability in the magnitude of DP and examine its effect on morning preprandial glucose levels as a preliminary test of the feasibility of GGE in adults with T2DM. MethodsStudy participants wore a single-blinded Dexcom G6 Pro continuous glucose monitoring (CGM) system for up to 10 days. First and last eating times and any overnight eating were reported using daily surveys over the study duration. DP was expressed as a dichotomous variable at the day level (DP day vs non-DP day) and as a continuous variable reflecting the percent of days DP was experienced on a valid day. A valid day was defined as having no reported overnight eating (between midnight and 6 AM). ∂ Glucose was computed as the difference in nocturnal glucose nadir (between midnight and 6 AM) to morning preprandial glucose levels. ∂ Glucose ≥20 mg/dL constituted a DP day. Using multilevel modeling, we examined the between- and within-person effects of DP on morning preprandial glucose and the effect of evening eating times on DP. ResultsIn total, 21 adults (59% female; 13/21, 62%) with non–insulin-treated T2DM wore a CGM for an average of 10.5 (SD 1.1) days. Twenty out of 21 participants (95%) experienced DP for at least 1 day, with an average of 51% of days (SD 27.2; range 0%-100%). The mean ∂ glucose was 23.7 (SD 13.2) mg/dL. People who experience DP more frequently had a morning preprandial glucose level that was 54.1 (95% CI 17.0-83.9; P

Objective This study investigated the seroprevalence of SARS-CoV-2 antibodies among adults over 18 years.Design Prospective cohort study.Settings A large public university.Participants This study took volunteers over 5 days and recruited 1064 adult participants.Primary outcome measures Seroprevalence of SARS-CoV-2-specific antibodies due to previous exposure to SARS-CoV-2 and/or vaccination.Results The seroprevalence of the antireceptor binding domain (RBD) antibody was 90% by a lateral flow assay and 88% by a semiquantitative chemiluminescent immunoassay. The seroprevalence for antinucleocapsid was 20%. In addition, individuals with previous natural COVID-19 infection plus vaccination had higher anti-RBD antibody levels compared with those who had vaccination only or infection only. Individuals who had a breakthrough infection had the highest anti-RBD antibody levels.Conclusion Accurate estimates of the cumulative incidence of SARS-CoV-2 infection can inform the development of university risk mitigation protocols such as encouraging booster shots, extending mask mandates or reverting to online classes. It could help us to have clear guidance to act at the first sign of the next surge as well, especially since there is a surge of COVID-19 subvariant infections.

The purpose of this study was to examine psychosocial, experiential, and demographic correlates of firearm ownership, carrying, and storage methods. We used a representative survey of 3,510 people living in five US states (Colorado, Minnesota, Mississippi, New Jersey, and Texas) conducted in 2022. Individuals provided information on past experiences with firearms, perceptions of threat and neighborhood safety, discrimination, and tolerance of uncertainty alongside demographic items. The analysis was conducted in November 2022. Past experiences with firearms and prior victimization are associated with increased firearm ownership and carrying practices. Threat sensitivity is associated with owning more guns while poorer perceptions of neighborhood safety correspond with owning fewer guns but greater risk for unsafe storage practices like storing a loaded gun in a closet or drawer. Intolerance of uncertainty is associated with owning fewer guns and lower risk for carrying outside of the home but greater risk for unsafe storage. Prior experience of discrimination is associated with risk for carrying firearms outside of the home. Demographic characteristics related to sex, rurality, military service, and political conservatism predict risky firearm-related behaviors related to firearm ownership, carrying frequency, and unsecure storage. Taken together, we find firearm ownership and risky firearm behaviors (e.g. carrying, unsafe storage) are more prominent among groups such as politically conservative males living in rural areas while also being influenced by threatening experiences, uncertainty, and perceptions of safety.

Objectives Despite guidelines endorsing statin and single antiplatelet therapy (SAPT) therapy post-carotid endarterectomy (CEA), these medications may be either under or inappropriately prescribed. We determined rates of new statin prescriptions as well as change in antiplatelet therapy (APT) regimen at discharge. We identified characteristics associated with these occurrences.Design We performed a retrospective Vascular Quality Initiative registry analysis of more than 125 000 patients who underwent CEA from 2013 to 2021.Setting The Vascular Quality Initiative is a multicentre registry database including academic and community-based hospitals throughout the USA.Participants Patients age≥18 years undergoing CEA with available statin and APT data (preprocedure and postprocedure) were included.Primary and secondary outcome measures We determined overall rates of statin and APT prescription at discharge. Multivariate logistic regression was used to determine clinical and demographic characteristics that were mostly associated with new statin prescription or changes in APT regimen at discharge.Results Study participants were predominantly male (61%) and White (90%), with a mean age of 70.6±9.1. 13.1% of participants were not on statin therapy pre-CEA, and 48% of these individuals were newly prescribed one. Statin rates steadily increased throughout the study period: 36.2% in 2013 to 62% in 2021. A higher likelihood of new statin prescription was associated with non-race, diabetes, coronary heart disease, stroke, TIA and a non-elective indication. Older age, female gender, chronic obstructive pulmonary disease and prior carotid revascularisation were associated with a lower likelihood of new statin prescription. Nearly all participants were discharged on APT (63% SAPT and 37% dual antiplatelet therapy, DAPT). Among these individuals, 16% were discharged on a regimen that was different from the one on admission (11 947 (10.7%) of patients were upgraded to DAPT and 5813 (5.2%) were downgraded to SAPT).Conclusions Although statin use has substantially improved following CEA, more than half of individuals not on a statin preprocedure remained this way at discharge. In addition, DAPT at discharge was frequent, a quarter of whom were on SAPT preprocedure. Further efforts are needed to improve rates of new statin prescriptions, ensure appropriate APT intensity at discharge and determine how different discharge APT regimens impact outcomes.

Abstract Public access automated external defibrillators (AEDs) represent emergency medical devices that may be used by untrained lay-persons in a life-critical event. As such their usability must be confirmed through simulation testing. In 2020 the novel coronavirus caused a global pandemic. In order to reduce the spread of the virus, many restrictions such as social distancing and travel bans were enforced. Usability testing of AEDs is typically conducted in-person, but due to these restrictions, other usability solutions must be investigated. Two studies were conducted, each with 18 participants: (1) an in-person usability study of an AED conducted in an office space, and (2) a synchronous remote usability study of the same AED conducted using video conferencing software. Key metrics associated with AED use, such as time to turn on, time to place pads and time to deliver a shock, were assessed in both studies. There was no difference in time taken to turn the AED on in the in-person study compared to the remote study, but the time to place electrode pads and to deliver a shock were significantly lower in the in-person study than in the remote study. Overall, the results of this study indicate that remote user testing of public access defibrillators may be appropriate in formative usability studies for determining understanding of the user interface.

Abstract Objectives To determine the efficacy and safety of sildenafil citrate to improve outcomes in pregnancies complicated by early-onset, dismal prognosis, fetal growth restriction (FGR). Eligibility: women ≥ 18 years, singleton, 18 + 0–27 + 6 weeks’ gestation, estimated fetal weight

Abstract Background Plastic and reconstructive surgery (PRS) remains highly relevant to the unmet need for surgery in Malawi. Better understanding the current PRS landscape and its barriers may help address some of these challenges. This scoping review aimed to describe: (1) the scope and focus of the PRS literature being produced in Malawi and (2) the challenges, deficits, and barriers to providing accessible, high-quality PRS in Malawi. Methods This scoping review was conducted on four databases (SCOPUS, PubMed, Web of Science, EMBASE) from inception through September 1, 2020 following the PRISMA-ScR guidelines. Results The database search retrieved 3852 articles, of which 31 were included that examined the burden of PRS-related conditions in Malawi. Of these 31 articles, 25 primarily discussed burn-related care. Burns injuries have a high mortality rate; between 27 and 75% in the studies. The literature revealed that there are only two burn units nationally with one PRS specialist in each unit, compounded by a lack of interest in PRS specialization by Malawian medical students. Congenital anomalies were the only other PRS-related condition examined and reported in the literature, accounting for 23% of all pediatric surgeries in tertiary facilities. Conclusions There is a need to increase the country's capacity to handle burn reconstruction and other PRS-related conditions to reduce overall morbidity and mortality. Additional publicly funded research at the district and community level is warranted to determine the true burden of PRS disease in Malawi to derive health system strengthening and workforce capacity building strategies.

Introduction: Food insecurity (FI) has been associated with adverse health outcomes and increased healthcare expenditures. Many families experienced reduced access to food during the coronavirus disease 2019 (COVID-19) pandemic. A 2019 study revealed that the pre-pandemic prevalence of FI at an urban, tertiary care hospital’s emergency department (ED) was 35.3%. We sought to evaluate whether the prevalence of FI in the same ED patient population increased during the COVID-19 pandemic. Methods: We performed a single-center, observational, survey-based study. Surveys assessing for FI were administered to clinically stable patients presenting to the ED over 25 consecutive weekdays from November–December 2020. Results: Of 777 eligible patients, 379 (48.8%) were enrolled; 158 (41.7%) screened positive for FI. During the pandemic, there was a 18.1% relative increase (or 6.4% absolute increase) in the prevalence of FI in this population (P=0.040; OR=1.309, 95% CI 1.012–1.693). The majority (52.9%) of food-insecure subjects reported reduced access to food due to the pandemic. The most common perceived barriers to access to food were reduced food availability at grocery stores (31%), social distancing guidelines (26.5%), and reduced income (19.6%). Conclusion: Our findings suggest that nearly half of the clinically stable patients who presented to our urban ED during the pandemic experienced food insecurity. The prevalence of FI in our hospital’s ED patient population increased by 6.4% during the pandemic. Emergency physicians should be aware of rising FI in their patient population so that they may better support patients who must choose between purchasing food and purchasing prescribed medications.

Objective To describe the process of community engagement (CE) in northern Karnataka, India and its impact on pre-eclampsia knowledge, birth preparedness and complication readiness, pregnancy-related care seeking and maternal morbidity.Design This study was a secondary analysis of a cluster randomised trial of Community Level Interventions for Pre-eclampsia (CLIP). A total of 12 clusters based on primary health centre catchment areas were randomised to intervention or control. CE was conducted in intervention clusters. CE attendance was summarised according to participant group using both quantitative and qualitative assessment. Pre-eclampsia knowledge, birth preparedness, health services engagement and perinatal outcomes was evaluated within trial surveillance. Outcomes were compared between trial arms using a mixed effects logistic regression model on RStudio (RStudio, Boston, USA). Community feedback notes were thematically analysed on NVivo V.12 (QSR International, Melbourne, Australia).Setting Belagavi and Bagalkote districts in rural Karnataka, India.Participants Pregnant women and women of reproductive age, mothers and mothers-in-law, community stakeholders and male household decision-makers and health workers.Results A total of 1379 CE meetings were conducted with 39 362 participants between November 2014 and October 2016. CE activities may have had an effect on modifying community attitudes towards hypertension in pregnancy and its complications. However, rates of pre-eclampsia knowledge, birth preparedness, health services engagement and maternal morbidities among individual pregnant women were not significantly impacted by CE activities in their area.Conclusion Evaluation of our CE programme in India demonstrates the feasibility of reaching pregnant women alongside household decision-makers, community stakeholders and health workers. More research is needed to explore the pathways of impact between broad community mobilisation to strengthen support for maternal care seeking and clinical outcomes of individual pregnant women.Trial registration number NCT01911494.

Abstract With an average of 26 tropical cyclones (TCs) per year, the western North Pacific (WNP) is the most active TC basin in the world. Considerable exposure lies in the coastal regions of the WNP, which extends from Japan in the north to the Philippines in the south, amplifying TC related impacts, including loss of life and damage to property, infrastructure and environment. This study presents a new location-specific typhoon (TY) and super typhoon (STY) outlook for the WNP basin and subregions, including China, Hong Kong, Japan, Korea, Philippines, Thailand, and Vietnam. Using multivariate Poisson regression and considering up to nine modes of ocean-atmospheric variability and teleconnection patterns that influence WNP TC behaviour, thousands of possible predictor model combinations are compared using an automated variable selection procedure. For each location, skillful TY and STY outlooks are generated up to 6 months before the start of the typhoon season, with rolling monthly updates enabling refinement of predicted TY and STY frequency. This unparalleled lead time allows end-users to make more informed decisions before and during the typhoon season.

BackgroundPeople living with chronic pain report that tapering prescribed opioids is challenging and more support is needed. In our formative research, consumers indicated that mobile health (mHealth) technology could be an acceptable form of support for opioid tapering and may improve tapering self-efficacy. ObjectiveWe aimed to evaluate and improve the content of an mHealth intervention before pilot-testing, based on consumer and clinician feedback. MethodsParticipants were 12 consumers and 12 clinicians who evaluated an initial draft of a video script and 90 SMS text messages. Consumers and clinicians rated the appropriateness and likely usefulness (consumers) or likely effectiveness (clinicians) of a video script and a random selection of 15 SMS text messages using a 5-point Likert-type scale (1=totally disagree; 5=totally agree). Each draft SMS text message was reviewed by 2 consumers and 2 clinicians. Texts were deemed acceptable for inclusion in the pilot intervention only if the summed participant ratings of text appropriateness and usefulness or effectiveness were ≥8. Participants were also invited to provide open-text feedback on the draft script and SMS text messages. ResultsConsumers generally agreed that the draft video script and text content were likely to be appropriate (video: mean 4.4, SD 0.52; text: mean 4.3, SD 0.79) and useful (video: mean 4.3, SD 0.65; text: mean 4.2, SD 0.84). Similarly, clinicians generally agreed that the draft video script and text content were likely to be appropriate (video: mean 4.5, SD 0.67; text: mean 4.4, SD 0.81) and effective (video: mean 4.0, SD 0.43; text: mean 4.3, SD 0.76). Overall, 77% (69/90) of the draft texts met the threshold rating for acceptability for inclusion in the pilot test of mHealth intervention by consumers, and 82% (74/90) met the threshold for acceptability by clinicians. Consumers' and clinicians’ ratings were used to rank order the texts. The top 56 draft texts (all meeting the threshold levels of acceptability) were selected for inclusion in the pilot intervention. When consumer or clinician feedback was provided, the texts meeting the criteria for inclusion in the pilot were further revised and improved. Feedback on the video script was also used to further improve the acceptability of the video script before pilot-testing the intervention. ConclusionsThis study describes the process by which a 28-day mHealth intervention to support patients with chronic pain to taper opioid medications was evaluated and improved before pilot-testing. The mHealth intervention consisted of a 10-minute psychoeducational video about pain and opioid tapering and 56 unique SMS text messages providing information and reassurance (texts delivered twice per day for 28 days). Having established that the content of the mHealth intervention is acceptable to both consumer and clinician groups, the mHealth intervention will be piloted in future research.

Abstract Objective The purpose of this study is to compare the prevalence of latent TB infection (LTBI) among patients with type-2 diabetes mellitus (T2DM) to healthy controls without T2DM. To achieve this objective, we conducted a case-control study in a large hospital in Atlanta from 2016 to 2019. Results We enrolled 98 cases; 119 potential controls were screened, 84 of which had HbA1c ≥ 5.7% and one did not have QFT result, leaving 34 (28.6%) individuals enrolled as controls. LTBI prevalence was 9.2% among cases and 14.7% among controls (crude odds ratio 0.59, 95% CI 0.19–2.04). After adjusting for age and sex, the adjusted odds of LTBI among patients with T2DM was 0.45 (95% CI 0.13, 1.71) times the controls. We did not observe a statistically significant association between LTBI and T2DM. However, we reported a positive correlation between HbA1c level and nil count among individuals with LTBI (R2 = 0.55, p

During atherosclerosis, vascular smooth muscle cells (VSMCs) undergo a phenotypic transition from a healthy contractile state into pathological phenotypes including a proliferative and migratory, synthetic phenotype and osteochondrogenic-like phenotype that exacerbate plaques. Thus, inhibiting the transition of healthy, quiescent VSMCs to atherogenic cell types has the potential to mitigate atherosclerosis. To that end, previously, we reported that delivery of microRNA-145 (miR-145, a potent gatekeeper of the contractile VSMC phenotype) using nanoparticle micelles limited atherosclerotic plaque growth in murine models of atherosclerosis. Building on this preclinical data and toward clinical application, in this study, we tested the therapeutic viability of miR-145 micelles on patient-derived VSMCs and evaluated their effects based on disease severity. We collected vascular tissues from 11 patients with healthy, moderate, or severe stages of atherosclerosis that were discarded following vascular surgery or organ transplant, and isolated VSMCs from these tissues. We found that with increasing disease severity, patient-derived VSMCs had decreasing levels of contractile markers (miR-145, ACTA2, MYH11) and increasing levels of synthetic markers (KLF4, KLF5, and ELK1). Treatment with miR-145 micelles showed that an increase in disease severity correlated with a more robust response to therapy in VSMCs. Notably, miR-145 micelle therapy rescued contractile marker expression to baseline contractile levels in VSMCs derived from the most severely diseased tissues. As such, we demonstrate the use of miR-145 micelles across different stages of atherosclerosis disease and present further evidence of the translatability of miR-145 micelle treatment for atherosclerosis.

Victims of nonfatal shooting (NFS) assaults suffer from emotional and physical trauma; however, little is understood about clinical care utilization patterns among victims. This study examines the healthcare utilization and mental health outcomes before and after an index NFS victimization. A longitudinal dataset of police and clinical data were linked at the individual level to define a cohort of NFS victims with one or more clinical encounter in the 24-months preceding an index NFS injury (N = 2,681) in Indianapolis, Indiana between 2005 and 2018. Mental health was defined using ICD diagnosis codes from any emergency department, inpatient, or outpatient encounter and clinical care utilization was the number of unique encounters within the 24-months preceding and following an index NFS injury. Multivariable logistic regression was conducted to examine factors associated with a mental health diagnosis in the post injury period. Analyses were conducted in October 2021-March 2022. Overall clinical care utilization (Mean: pre = 277.7 (SD 235.3) vs. post = 333.9 (SD 255.1), p

Abstract Methods for predicting circadian phase have been developed for healthy individuals. It is unknown whether these methods generalize to clinical populations, such as delayed sleep–wake phase disorder (DSWPD), where circadian timing is associated with functional outcomes. This study evaluated two methods for predicting dim light melatonin onset (DLMO) in 154 DSWPD patients using ~ 7 days of sleep–wake and light data: a dynamic model and a statistical model. The dynamic model has been validated in healthy individuals under both laboratory and field conditions. The statistical model was developed for this dataset and used a multiple linear regression of light exposure during phase delay/advance portions of the phase response curve, as well as sleep timing and demographic variables. Both models performed comparably well in predicting DLMO. The dynamic model predicted DLMO with root mean square error of 68 min, with predictions accurate to within ± 1 h in 58% of participants and ± 2 h in 95%. The statistical model predicted DLMO with root mean square error of 57 min, with predictions accurate to within ± 1 h in 75% of participants and ± 2 h in 96%. We conclude that circadian phase prediction from light data is a viable technique for improving screening, diagnosis, and treatment of DSWPD.

Abstract We tested whether pregnant and non-pregnant women differ in COVID-19 symptom profile and severity, and we extended previous investigations on hospitalized pregnant women to those who did not require hospitalization. Two female community-based cohorts (18–44 years) provided longitudinal (smartphone application, N = 1,170,315, n = 79 pregnant tested positive) and cross-sectional (web-based survey, N = 1,344,966, n = 134 pregnant tested positive) data, prospectively collected through self-participatory citizen surveillance in UK, Sweden and USA. Pregnant and non-pregnant were compared for frequencies of events, including SARS-CoV-2 testing, symptoms and hospitalization rates. Multivariable regression was used to investigate symptoms severity and comorbidity effects. Pregnant and non-pregnant women positive for SARS-CoV-2 infection were not different in syndromic severity, except for gastrointestinal symptoms. Pregnant were more likely to have received testing, despite reporting fewer symptoms. Pre-existing lung disease was most closely associated with syndromic severity in pregnant hospitalized. Heart and kidney diseases and diabetes increased risk. The most frequent symptoms among non-hospitalized women were anosmia [63% pregnant, 92% non-pregnant] and headache [72%, 62%]. Cardiopulmonary symptoms, including persistent cough [80%] and chest pain [73%], were more frequent among pregnant who were hospitalized. Consistent with observations in non-pregnant populations, lung disease and diabetes were associated with increased risk of more severe SARS-CoV-2 infection during pregnancy.

Introduction Opioid medications are no longer recommended as long-term therapy for chronic non-cancer pain, and many patients are advised to reduce or discontinue opioid medications. Many patients report difficulties in tapering opioid medications, necessitating supporting interventions. This protocol describes a pilot randomised controlled trial (RCT) to investigate the acceptability, feasibility and potential efficacy of a mobile health intervention to improve the opioid tapering self-efficacy of patients with chronic non-cancer pain.Methods and analysis The trial will be a single-blind (clinician, data collector and statistician-blinded) pilot RCT with two parallel arms. Forty adult patients with chronic non-cancer pain who are voluntarily reducing their prescribed opioid medications under medical guidance will be recruited from two tertiary pain clinics (Start date 25 August 2021). Participants will be randomly assigned to an intervention or control group. Both groups will receive usual care, including multidisciplinary pain management. In addition to usual care, the intervention group will receive a short informational and testimonial video about opioid tapering and will receive two specifically text messages per day for 28 days. The intervention is codesigned with patients and clinicians to provide evidence-based informational, motivational and emotional support to patients with chronic pain to taper opioid medications. Feasibility of the intervention and a future definitive RCT will be evaluated by measuring patient acceptability, delivery of the intervention, rates and reasons of exclusions and drop-outs, completion rates and missing data in the study questionnaires, and obtaining estimates for sample size determination. Potential efficacy will be evaluated by comparing changes in opioid tapering self-efficacy between the two groups.Ethics and dissemination The study protocol was reviewed and approved by the Northern Sydney Local Health District (Australia). Study results will be published in peer-reviewed journals and presented at scientific and professional meetings.Trial registration number ACTRN12621000795897.

Objective To examine victimisation rates, geographic patterns and neighbourhood characteristics associated with non-fatal firearm injury rates before and during the COVID-19 pandemic.Design A retrospective cohort study.Setting City of Indianapolis, Indiana, USA, 1 January 2017–30 June 2021.Participants Intentional non-fatal firearm injury victims from Indianapolis Metropolitan Police Department records. The study included information on 2578 non-fatal firearm injury victims between ages 0 and 77 years. Of these victims, 82.5% were male and 77.4% were black.Primary and secondary outcome measures Rates of non-fatal firearm injuries per 100 000 population by victim age, race, sex and incident motive. Prepandemic and peripandemic non-fatal firearm injury rates.Results Non-fatal shooting rates increased 8.60%, from 57.0 per 100 000 person-years in prepandemic years to 65.6 per 100 000 person-years during the pandemic (p

We urgently need answers to basic epidemiological questions regarding SARS-CoV-2 infection in pregnant and postpartum women and its effect on their newborns. While many national registries, health facilities, and research groups are collecting relevant data, we need a collaborative and methodologically rigorous approach to better combine these data and address knowledge gaps, especially those related to rare outcomes. We propose that using a sequential, prospective meta-analysis (PMA) is the best approach to generate data for policy- and practice-oriented guidelines. As the pandemic evolves, additional studies identified retrospectively by the steering committee or through living systematic reviews will be invited to participate in this PMA. Investigators can contribute to the PMA by either submitting individual patient data or running standardized code to generate aggregate data estimates. For the primary analysis, we will pool data using two-stage meta-analysis methods. The meta-analyses will be updated as additional data accrue in each contributing study and as additional studies meet study-specific time or data accrual thresholds for sharing. At the time of publication, investigators of 25 studies, including more than 76,000 pregnancies, in 41 countries had agreed to share data for this analysis. Among the included studies, 12 have a contemporaneous comparison group of pregnancies without COVID-19, and four studies include a comparison group of non-pregnant women of reproductive age with COVID-19. Protocols and updates will be maintained publicly. Results will be shared with key stakeholders, including the World Health Organization (WHO) Maternal, Newborn, Child, and Adolescent Health (MNCAH) Research Working Group. Data contributors will share results with local stakeholders. Scientific publications will be published in open-access journals on an ongoing basis.

Objective In 2017, the National Institute for Health Research (NIHR) academy produced a strategic review of training, which reported the variation in application characteristics associated with success rates. It was noted that variation in applicant characteristic was not independent of one another. Therefore, the aim of this secondary analysis was to investigate the inter-relationships in order to identify factors (or groups of factors) most associated with application numbers and success rates.Design Retrospective data were gathered from 4388 applications to NIHR Academy between 2007 and 2016. Multinominal logistic regression models quantified the likelihood of success depending on changes in the explanatory factors; relative risk ratios with 95% CIs. A classification tree analysis was built using exhaustive χ2 automatic interaction detection to better understand the effect of interactions between explanatory variables on application success rates.Results 936 (21.3%) applications were awarded. Applications from males and females were equally likely to be successful (p=0.71). There was an overall reduction in numbers of applications from females as award seniority increased from predoctoral to professorship. Applications from institutions with a medical school had a 2.6-fold increase in likelihood of success (p

IntroductionCOVID-19 vaccination effectively reduces severe disease and death from COVID-19. However, both vaccine uptake and intention to vaccinate differ amongst population groups. Vaccine hesitancy is highest amongst specific ethnic minority groups. There is very limited understanding of the barriers and facilitators to COVID-19 vaccine uptake in Black and South Asian ethnicities. Therefore, we aimed to explore COVID-19 vaccination hesitancy in primary care patients from South Asian (Bangladeshi/Pakistani) and Black or Black British/African/Caribbean/Mixed ethnicities.MethodsPatients from the above ethnicities were recruited using convenience sampling in four London general practices. Telephone interviews were conducted, using an interpreter if necessary, covering questions on the degree of vaccine hesitancy, barriers and potential facilitators, and decision-making. Interviews were transcribed verbatim and thematically analysed. Data collection and analysis occurred concurrently with the iterative development of the topic guide and coding framework. Key themes were conceptualised through discussion with the wider team.ResultsOf thirty-eight interviews, 55% (21) of these were in Black or Black British/African/Caribbean/Mixed ethnicities, 32% (12) in Asian / British Asian and 13% (5) in mixed Black and White ethnicities. Key themes included concerns about the speed of vaccine roll-out and potential impacts on health, mistrust of official information, and exposure to misinformation. In addition, exposure to negative messages linked to vaccination appears to outweigh positive messages received. Facilitators included the opportunity to discuss concerns with a healthcare professional, utilising social influences via communities and highlighting incentives.ConclusionCOVID-19 has disproportionately impacted ethnic minority groups. Vaccination is an effective strategy for mitigating risk. We have demonstrated factors contributing to vaccine reluctance, hesitancy and refusal and highlighted levers for change.

Learning requires neural adaptations thought to be mediated by activity-dependent synaptic plasticity. A relatively non-standard form of synaptic plasticity driven by dendritic calcium spikes, or plateau potentials, has been reported to underlie place field formation in rodent hippocampal CA1 neurons. Here, we found that this behavioral timescale synaptic plasticity (BTSP) can also reshape existing place fields via bidirectional synaptic weight changes that depend on the temporal proximity of plateau potentials to pre-existing place fields. When evoked near an existing place field, plateau potentials induced less synaptic potentiation and more depression, suggesting BTSP might depend inversely on postsynaptic activation. However, manipulations of place cell membrane potential and computational modeling indicated that this anti-correlation actually results from a dependence on current synaptic weight such that weak inputs potentiate and strong inputs depress. A network model implementing this bidirectional synaptic learning rule suggested that BTSP enables population activity, rather than pairwise neuronal correlations, to drive neural adaptations to experience.

Objectives Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis.Setting Prospective, international, multicentre, observational cohort study.Participants Patients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative).Primary outcome 30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality.Results This study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787).Conclusions Patients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups.Trial registration number NCT04323644

We sought to describe how revenues from sugar-sweetened beverage (SSB) excise taxes in 7 U.S. cities are being allocated, who is benefiting from these investments, and whether allocations are consistent with the original intent of tax legislation. We collected information from public documents and key informants about allocations in the most recent fiscal year available (ranging from 2018 to 2021). Across the 7 U.S. cities with taxes, the average annual revenue from SSB taxes totaled $133.9 M. In the fiscal year studied, cities allocated a total of $133.2 M in SSB tax revenues. Human and community capital investments totaled $89.6 M (67% of all allocations) funding early childhood development, community infrastructure improvements, and youth and workforce development. Health-related investments totaled $36.9 M (28% of total allocations), funding access to healthy foods and beverages; support for physical activity opportunities; promotion of overall physical, mental or social health and wellbeing; health and nutrition education; chronic-disease prevention and management; and reducing SSB consumption. In the 3 cities that specified how tax revenues would be spent, allocations were consistent with promised uses of revenues. In addition, 85% of aggregated revenues ($112.9 M) were targeted to support work and programs in impacted communities (communities that experience health inequities, discrimination and exclusion). SSB tax revenues are supporting initiatives to improve community health, develop human and community capital, and advance equity. These investments may yield additional health benefits beyond those resulting from lower SSB consumption. Consistent tracking and public reporting on revenue allocations would increase transparency and accountability.

Bone marrow adipocytes accumulate with age and in diverse disease states. However, their origins and adaptations in these conditions remain unclear, impairing our understanding of their context-specific endocrine functions and relationship with surrounding tissues. In this study, by analyzing bone and adipose tissues in the lipodystrophic ‘fat-free’ mouse, we define a novel, secondary adipogenesis pathway that relies on the recruitment of adiponectin-negative stromal progenitors. This pathway is unique to the bone marrow and is activated with age and in states of metabolic stress in the fat-free mouse model, resulting in the expansion of bone marrow adipocytes specialized for lipid storage with compromised lipid mobilization and cytokine expression within regions traditionally devoted to hematopoiesis. This finding further distinguishes bone marrow from peripheral adipocytes and contributes to our understanding of bone marrow adipocyte origins, adaptations, and relationships with surrounding tissues with age and disease.

Objectives The psychological impact of the COVID-19 pandemic on doctors is a significant concern. Due to the emergence of multiple pandemic waves, longitudinal data on the impact of COVID-19 are vital to ensure an adequate psychological care response. The primary aim was to assess the prevalence and degree of psychological distress and trauma in frontline doctors during the acceleration, peak and deceleration of the COVID-19 first wave. Personal and professional factors associated with psychological distress are also reported.Design A prospective online three-part longitudinal survey.Setting Acute hospitals in the UK and Ireland.Participants Frontline doctors working in emergency medicine, anaesthetics and intensive care medicine during the first wave of the COVID-19 pandemic in March 2020.Primary outcome measures Psychological distress and trauma measured using the General Health Questionnaire-12 and the Impact of Events-Revised.Results The initial acceleration survey distributed across networks generated a sample of 5440 doctors. Peak and deceleration response rates from the original sample were 71.6% (n=3896) and 56.6% (n=3079), respectively. Prevalence of psychological distress was 44.7% (n=1334) during the acceleration, 36.9% (n=1098) at peak and 31.5% (n=918) at the deceleration phase. The prevalence of trauma was 23.7% (n=647) at peak and 17.7% (n=484) at deceleration. The prevalence of probable post-traumatic stress disorder was 12.6% (n=343) at peak and 10.1% (n=276) at deceleration. Worry of family infection due to clinical work was the factor most strongly associated with both distress (R2=0.06) and trauma (R2=0.10).Conclusion Findings reflect a pattern of elevated distress at acceleration and peak, with some natural recovery. It is essential that policymakers seek to prevent future adverse effects through (a) provision of vital equipment to mitigate physical and psychological harm, (b) increased awareness and recognition of signs of psychological distress and (c) the development of clear pathways to effective psychological care.Trial registration number ISRCTN10666798.

BackgroundPatients with chronic pain who are tapering prescription opioids report a need for greater support for coping with symptoms of pain and withdrawal. Mobile health (mHealth) technologies (SMS text messaging– or app-based) have the potential to provide patients with educational, emotional, and motivational support for opioid tapering beyond what is offered by their health care provider. However, it is not known whether patients with chronic pain who are tapering opioids would be willing or able to engage with technology-based support. ObjectiveThis study aims to examine patients’ use of mobile technologies in health care, interest in using mHealth support, preferences for the form and content of mHealth support, and potential barriers to and facilitators of engagement with mHealth support for opioid tapering. MethodsA total of 21 patients (11 women and 10 men; age range 29-83 years) with chronic noncancer pain on long-term opioid therapy who had recently initiated a voluntary opioid taper were recruited from primary and tertiary care clinics in metropolitan and regional Australia for a larger study of patients’ experiences of opioid tapering. Participants had been taking prescription opioids for a mean duration of 13 (SD 9.6; range 0.25-30) years at the time of the study. Survey items characterized participants’ typical mobile phone use and level of interest in mobile technology–based support for opioid tapering. Semistructured interviews further explored patients’ use of mobile technologies and their interest in, preferences for, and perspectives on potential barriers to and facilitators of engagement with mHealth support for opioid tapering. Two researchers collaborated to conduct a thematic analysis of the interview data. ResultsAll participants reported owning and using a mobile phone, and most (17/21, 81%) participants reported using mobile apps. The majority of participants expressed interest in SMS text messaging–based (17/21, 81%) and app-based (15/21, 71%) support for opioid tapering. Participants expected that messages delivering both informational and socioemotional support would be helpful. Participants expected that access to technology, mobile reception, internet connectivity, vision impairment, and low self-efficacy for using apps may be barriers to user engagement. Patients expected that continuity of care from their health care provider, flexible message dosing, responsivity, and familiarity with pain self-management strategies would increase user engagement. ConclusionsThe results of this study indicate that patients with chronic noncancer pain may be willing to engage with SMS text messaging–based and app-based mHealth interventions to support opioid tapering. However, the feasibility and acceptability of these interventions may depend on how patients’ preferences for functionality, content, and design are addressed.

RationaleMurine syngeneic tumor models have revealed efficacious systemic antitumor responses following primary tumor in situ vaccination combined with targeted radionuclide therapy to secondary or metastatic tumors. Here we present studies on the safety and feasibility of this approach in a relevant translational companion dog model (n = 17 dogs) with advanced cancer.MethodsThe three component of the combination immuno-radiotherapy approach were employed either separately or in combination in companion dogs with advanced stage cancer. In situ vaccination was achieved through the administration of hypofractionated external beam radiotherapy and intratumoral hu14.18-IL2 fusion immunocytokine injections to the index tumor. In situ vaccination was subsequently combined with targeted radionuclide therapy using a theranostic pairing of IV 86Y-NM600 (for PET imaging and subject-specific dosimetry) and IV 90Y-NM600 (therapeutic radionuclide) prescribed to deliver an immunomodulatory 2 Gy dose to all metastatic sites in companion dogs with metastatic melanoma or osteosarcoma. In a subset of dogs, immunologic parameters preliminarily assessed.ResultsThe components of the immuno-radiotherapy combination were well tolerated either alone or in combination, resulting in only transient low grade (1 or 2) adverse events with no dose-limiting events observed. In subject-specific dosimetry analyses, we observed 86Y-NM600 tumor:bone marrow absorbed-dose differential uptakes ≥2 in 4 of 5 dogs receiving the combination, which allowed subsequent safe delivery of at least 2 Gy 90Y-NM600 TRT to tumors. NanoString gene expression profiling and immunohistochemistry from pre- and post-treatment biopsy specimens provide evidence of tumor microenvironment immunomodulation by 90Y-NM600 TRT.ConclusionsThe combination of external beam radiotherapy, intratumoral immunocytokine, and targeted radionuclide immuno-radiotherapy known to have activity against syngeneic melanoma in murine models is feasible and well tolerated in companion dogs with advanced stage, spontaneously arising melanoma or osteosarcoma and has immunomodulatory potential. Further studies evaluating the dose-dependent immunomodulatory effects of this immuno-radiotherapy combination are currently ongoing.

Objectives To determine the need for recovery (NFR) among emergency physicians and to identify demographic and occupational characteristics associated with higher NFR scores.Design Cross-sectional electronic survey.Setting Emergency departments (EDs) (n=112) in the UK and Ireland.Participants Emergency physicians, defined as any registered physician working principally within the ED, responding between June and July 2019.Main outcome measure NFR Scale, an 11-item self-administered questionnaire that assesses how work demands affect intershift recovery.Results The median NFR Score for all 4247 eligible, consented participants with a valid NFR Score was 70.0 (95% CI: 65.5 to 74.5), with an IQR of 45.5–90.0. A linear regression model indicated statistically significant associations between gender, health conditions, type of ED, clinical grade, access to annual and study leave, and time spent working out-of-hours. Groups including male physicians, consultants, general practitioners (GPs) within the ED, those working in paediatric EDs and those with no long-term health condition or disability had a lower NFR Score. After adjusting for these characteristics, the NFR Score increased by 3.7 (95% CI: 0.3 to 7.1) and 6.43 (95% CI: 2.0 to 10.8) for those with difficulty accessing annual and study leave, respectively. Increased percentage of out-of-hours work increased NFR Score almost linearly: 26%–50% out-of-hours work=5.7 (95% CI: 3.1 to 8.4); 51%–75% out-of-hours work=10.3 (95% CI: 7.6 to 13.0); 76%–100% out-of-hours work=14.5 (95% CI: 11.0 to 17.9).Conclusion Higher NFR scores were observed among emergency physicians than reported in any other profession or population to date. While out-of-hours working is unavoidable, the linear relationship observed suggests that any reduction may result in NFR improvement. Evidence-based strategies to improve well-being such as proportional out-of-hours working and improved access to annual and study leave should be carefully considered and implemented where feasible.

BackgroundLoss of smell and taste are commonly reported symptoms associated with coronavirus disease 2019 (COVID-19); however, the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in people with acute loss of smell and/or taste is unknown. The study aimed to determine the seroprevalence of SARS-CoV-2 antibodies in a community-based population with acute loss of smell and/or taste and to compare the frequency of COVID-19 associated symptoms in participants with and without SARS-CoV-2 antibodies. It also evaluated whether smell or taste loss are indicative of COVID-19 infection.Methods and findingsText messages, sent via primary care centers in London, United Kingdom, invited people with loss of smell and/or taste in the preceding month, to participate. Recruitment took place between 23 April 2020 and 14 May 2020. A total of 590 participants enrolled via a web-based platform and responded to questions about loss of smell and taste and other COVID-19-related symptoms. Mean age was 39.4 years (SD ± 12.0) and 69.1% (n = 392) of participants were female. A total of 567 (96.1%) had a telemedicine consultation during which their COVID-19-related symptoms were verified and a lateral flow immunoassay test that detected SARS-CoV-2 immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies was undertaken under medical supervision. A total of 77.6% of 567 participants with acute smell and/or taste loss had SARS-CoV-2 antibodies; of these, 39.8% (n = 175) had neither cough nor fever. New loss of smell was more prevalent in participants with SARS-CoV-2 antibodies, compared with those without antibodies (93.4% versus 78.7%, p < 0.001), whereas taste loss was equally prevalent (90.2% versus 89.0%, p = 0.738). Seropositivity for SARS-CoV-2 was 3 times more likely in participants with smell loss (OR 2.86; 95% CI 1.27-6.36; p < 0.001) compared with those with taste loss. The limitations of this study are the lack of a general population control group, the self-reported nature of the smell and taste changes, and the fact our methodology does not take into account the possibility that a population subset may not seroconvert to develop SARS-CoV-2 antibodies post-COVID-19.ConclusionsOur findings suggest that recent loss of smell is a highly specific COVID-19 symptom and should be considered more generally in guiding case isolation, testing, and treatment of COVID-19.Trials registrationClinicalTrials.gov NCT04377815.