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Background and Aims: Posterior wall isolation (PWI) is commonly incorporated into catheter ablation (CA) strategies for persistent atrial fibrillation (AF) in an attempt to improve outcomes. In the CAPLA randomized study, adjunctive PWI did not improve freedom from atrial arrhythmia at 12 months compared with pulmonary vein isolation (PVI) alone. Whether additional PWI reduces arrhythmia recurrence over the longer term remains unknown., Methods: In this multi-centre, international, randomized study patients with persistent AF undergoing index CA using radiofrequency were randomized to PVI + PWI vs. PVI alone. Patients underwent regular follow-up including rhythm monitoring for a minimum of 3 years after CA. Atrial fibrillation burden at 3 years after ablation was evaluated with either 28-day continuous ambulatory electrocardiogram (ECG) monitoring, twice daily single-lead ECG or from cardiac implanted device. Evaluated endpoints included freedom from any documented atrial arrhythmia recurrence after a single procedure, AF burden, need for redo CA, rhythm at last clinical follow-up, healthcare utilization metrics, and AF-related quality of life., Results: Three hundred thirty-three of 338 (98.5%) patients (mean age 64.3 ± 9.4 years, 23% female) completed 3-year follow-up, with 169 patients randomized to PVI + PWI and 164 patients to PVI alone. At a median of 3.62 years after index ablation, freedom from recurrent atrial arrhythmia occurred in 59 patients (35.5%) randomized to PVI + PWI vs. 68 patients (42.1%) randomized to PVI alone (hazard ratio 1.15, 95% confidence interval 0.88-1.51, P = .55). Median time to recurrent atrial arrhythmia was 0.53 years (interquartile range 0.34-1.01 years). Redo ablation was performed in 54 patients (32.0%) in the PVI + PWI group vs. 49 patients (29.9%, P = .68) in the PVI alone group. Pulmonary vein reconnection was present in 54.5% (mean number of reconnected PVs 2.2 ± .9) and posterior wall reconnection in 75%. Median AF burden at 3 years was 0% in both groups (interquartile range 0%-0.85% PVI + PWI vs. 0%-1.43% PVI alone, P = .49). Sinus rhythm at final clinical follow-up was present in 85.1% with PVI + PWI vs. 87.1% with PVI alone (P = .60). Mean AF Effect On Quality-Of-Life (AFEQT) score at 3 years after ablation was 88.0 ± 14.8 with PVI + PWI vs. 88.9 ± 15.4 with PVI alone (P = .63)., Conclusions: In patients with persistent AF, the addition of PWI to PVI alone at index radiofrequency CA did not significantly improve freedom from atrial arrhythmia recurrence at long-term follow-up. Median AF burden remains low and AF quality of life high at 3 years with either ablation strategy., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objectives: Mobile health (mHealth) regimens can improve health through the continuous monitoring of biometric parameters paired with appropriate interventions. However, adherence to monitoring tends to decay over time. Our randomized controlled trial sought to determine: (1) if a mobile app with gamification and financial incentives significantly increases adherence to mHealth monitoring in a population of heart failure patients; and (2) if activity data correlate with disease-specific symptoms., Materials and Methods: We recruited individuals with heart failure into a prospective 180-day monitoring study with 3 arms. All 3 arms included monitoring with a connected weight scale and an activity tracker. The second arm included an additional mobile app with gamification, and the third arm included the mobile app and a financial incentive awarded based on adherence to mobile monitoring., Results: We recruited 111 heart failure patients into the study. We found that the arm including the financial incentive led to significantly higher adherence to activity tracker (95% vs 72.2%, P = .01) and weight (87.5% vs 69.4%, P = .002) monitoring compared to the arm that included the monitoring devices alone. Furthermore, we found a significant correlation between daily steps and daily symptom severity., Discussion and Conclusion: Our findings indicate that mobile apps with added engagement features can be useful tools for improving adherence over time and may thus increase the impact of mHealth-driven interventions. Additionally, activity tracker data can provide passive monitoring of disease burden that may be used to predict future events., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

Background: Participation in paid work after childbirth may have important health and socioeconomic impacts on women and their families. We investigated women's employment patterns at six months postpartum and the factors that influence them., Methods: Using data from a 2018 population-based national maternity survey in England, employment status at six months postpartum was assessed. Logistic regression was used to explore sociodemographic and pregnancy- and birth-related factors associated with being in paid work by six months postpartum. Descriptive analysis was used to explore employment characteristics and motivations of women in paid work., Results: Of the 4313 participants included, 7.7% were in paid work by six months postpartum. Factors associated with being in paid work were age ≥35 years [(adjusted odd ratios (aOR):1.37, 95% confidence interval (CI):1.02-1.84], not living with a partner (aOR:0.50, 95%CI:0.28-0.90), and pre-term birth (aOR:0.38, 95%CI:0.20-0.69). The most frequently reported motivation was financial need (76%), followed by wanting to work (41%). Financial need was associated with younger age, living in a more socioeconomically disadvantaged area, not living with a partner, and lower education level., Conclusion: Postpartum employment patterns and motivations for working vary according to sociodemographic characteristics. These findings have important implications for parental leave and childcare policies, which should be equitable across different groups., (© The Author(s) 2024. Published by Oxford University Press on behalf of Faculty of Public Health.)

Aims: Diagnosis of atrial fibrillation (AF) provides opportunities to reduce stroke risk. This study aimed to compare AF diagnosis rates, participant satisfaction, and feasibility of an electrocardiogram (ECG) self-screening virtual care system with usual care., Methods and Results: This randomized controlled implementation study involving community-dwelling people aged ≥75 years was conducted from May 2021 to June 2023. Participants were given a handheld single-lead ECG device and trained to self-record ECGs once daily on weekdays for 12 months. The control group received usual care with their general practitioners in the first 6 months and participated in the subsequent 6 months. Atrial fibrillation diagnosis and participant satisfaction were assessed at 6 months. Two hundred participants (mean age 79.0 ± 3.4 years; 54.0% female; 72.5% urban) were enrolled. Atrial fibrillation was diagnosed in 10/97 (10.3%) intervention participants and 2/100 (2.0%) in the control group (odds ratio 5.6, 95% confidence interval 1.4-37.3, P = 0.03). In the intervention, 80% of AF cases were diagnosed within 3 months. 91/93 (97.9%) intervention participants and 55/93 (59.1%) control-waitlisted participants (P < 0.001) were satisfied with AF screening. Of the expected 20 days per month, the overall monthly median number of days participants self-recorded ECGs was 20 (interquartile range 17-22). Participants were confident using the device (93%), reported it was easy to use (98%), and found screening efficient (96%)., Conclusion: Patient-led AF self-screening using single-lead ECG devices with a remote central monitoring system was feasible, acceptable, and effective in diagnosing AF among older people. This screening model could be adapted for implementation, interfacing with integrated care models within existing health systems., Registration: Australian New Zealand Clinical Trials Registry identifier: ACTRN12621000184875., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Limited data exist regarding outcomes of cryptococcosis in patients without HIV with few studies having compared outcomes of Cryptococcus gattii, versus C. neoformans, infection., Methods: We conducted a retrospective study in 46 Australian and New Zealand hospitals to determine the outcomes of cryptococcosis in patients without HIV diagnosed between 2015 and 2019, and compared outcomes of C. gattii versus C. neoformans infections. Multivariable analysis identified predictors of mortality within one year., Results: Of 426 patients, one-year all-cause mortality was 21%. C. gattii infection was associated with a lower mortality than C. neoformans (adjusted odds ratio [OR]: 0.47, 95% confidence interval [CI]: 0.23-0.95), whilst severe neurological symptoms at presentation was the strongest predictor of death (adjusted OR: 8.46, 95% CI: 2.99-23.98). Almost all (99.5%) patients with central nervous system (CNS) infection received induction antifungal therapy versus 27.7% of isolated pulmonary cryptococcosis. The commonest regimen in CNS disease was liposomal amphotericin B with flucytosine (93.8%, mean duration 31 ± 13 days). Among patients with CNS cryptococcosis, C. gattii infection was associated with higher risk of immune reconstitution inflammatory response (C-IRIS) than C. neoformans (21% versus 3%, p<0.001). Nineteen patients received amphotericin B-based re-induction therapy for suspected relapse but none had microbiological relapse. Serum cryptococcal antigen positivity and lung imaging abnormalities resolved slowly (resolution at one year in 25% and 34% of patients, respectively)., Conclusion: Compared with C. neoformans, C. gattii infection demonstrated lower mortality but higher C-IRIS risk in CNS infection. Severe neurological symptoms were the strongest predictor of mortality., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Public health actors have expressed concerns over the entry of the tobacco industry into the UK e-cigarette market. It is important to be aware of the tobacco industry's involvement and stated aims for e-cigarettes in the UK, given their historical attempts to divert attention from and escape responsibility for the harms caused by combustible cigarettes. The use of e-cigarettes amongst young people in the UK has remained constant, despite the law prohibiting sales to adolescents and claims by manufacturers and others that they are designed solely as a tool to quit smoking. This study sought to examine how tobacco-related organizations in the UK e-cigarette market frame the use of e-cigarettes. Publicly available materials between September 2015 and June 2023 were collected from four transnational tobacco companies which have invested in the e-cigarette category, and from a UK e-cigarette trade association. A qualitative framing analysis of materials was conducted guided by relevant frameworks from the Commercial Determinants of Health literature. The analysis identified seven framings used by tobacco-related organizations relevant to e-cigarette usage in the UK. These were: co-opting of harm reduction; consumer choice; following the 'evidence'; insufficient evidence; the right kind of regulation; 'us' and 'them' rhetoric and marketing and advertising. By highlighting tobacco-related organizations' e-cigarette framings and contradictions, this study raises awareness of the rhetorical strategies used by the industry which aim to relegitimize tobacco companies in the political and public spheres., (© The Author(s) 2024. Published by Oxford University Press.)

Background: To provide precision cognitive remediation therapy (CR) for schizophrenia, we need to understand whether the mechanism for improved functioning is via cognition improvements. This mechanism has not been rigorously tested for potential moderator effects., Study Design: We used data (n = 377) from a randomized controlled trial using CIRCuiTS, a therapist-supported CR, with participants from first-episode psychosis services. We applied structured equation modeling to test whether: (1) CR hours explain the goal attainment functional outcome (GAS) at posttreatment, (2) global cognitive improvement mediates GAS, and if (3) total symptoms moderate the CR hours to cognitive improvement pathway, and/or negative symptoms moderate the cognition to functioning pathway, testing moderator effects via the mediator or directly on CR hours to functioning path., Study Results: CR produced significant functioning benefit for each therapy hour (Coeff = 0.203, 95% CI 0.101-0.304, P < .001). The mediated path from CR hours to cognition and cognition to functioning was small and nonsignificant (Coeff = 0.014, 95% CI = -0.010, 0.037, P = .256). Total symptoms did not moderate the path to cognition (P = .211) or the direct path to outcome (P = .896). However, negative symptoms significantly moderated the effect of cognitive improvements on functioning (P = .015) with high negative symptoms reducing the functional gains of improved cognition., Conclusions: Although cognitive improvements were correlated with functioning benefit, they did not fully explain the positive effect of increased therapy hours on functioning, suggesting additional CR factors also contribute to therapy benefit. Negative symptoms interfere with the translation of cognitive improvements into functional gains so need consideration., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.)

Background: There is limited evidence on the magnitude of the potential program cost savings associated with the World Health Organization-endorsed single-dose schedule for the human papillomavirus (HPV) vaccine. The objective of this analysis was to model the delivery and vaccine procurement cost implications of the new schedule., Methods: The analysis leveraged primary data during a study evaluating the HPV vaccine delivery costs and operational context in 5 countries (Ethiopia, Guyana, Rwanda, Sri Lanka, and Uganda) implementing a two-dose schedule. To estimate the cost for the single-dose schedule, we adjusted the two-dose schedule cost estimates to account for differences in the frequency of activities, whether activities differed by HPV vaccine dose or session, and differences in relative quantity or storage volume of HPV vaccines delivered. We estimated the cost per dose and cost per adolescent receiving the full (single-dose or two-dose) vaccination schedule in 2019 US dollars from a health system perspective., Results: Modeled results found that cost per dose would increase under a single-dose schedule, whereas cost per adolescent receiving the full schedule would decrease. The financial cost for vaccine procurement and delivery per adolescent receiving the full schedule ranged from $9.64 (Sri Lanka) to $23.43 (Guyana) under a two-dose schedule and decreased to $4.84 and $12.34, respectively, under a single-dose schedule, reflecting savings up to 50%. For economic costs, the range for a single-dose schedule was $7.86 (Rwanda) to $28.53 (Guyana)., Conclusion: A single-dose HPV vaccination schedule could provide cost savings to immunization programs and enhance program affordability and sustainability., (© The Author(s) 2024. Published by Oxford University Press.)

Disclaimer: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time., Purpose: To develop administrative and leadership skills in pharmacy technicians through the implementation of a 6-month advanced technician leadership program., Summary: Health-system pharmacy administrative and leadership (HSPAL) residency programs have been established to develop administrative and leadership skills in pharmacists for more than 60 years. Similar opportunities for pharmacy technicians do not exist despite technicians being placed in leadership positions. Our pharmacy department developed a 6-month advanced pharmacy technician leadership program utilizing the pharmacist HSPAL residency framework and adapting it to focus on pharmacy technicians. Rotations span inpatient and ambulatory leadership, with both pharmacist and technician leaders serving as preceptors. The training program has been established for over 3 years and has produced a total of 6 graduates, of whom 5 have assumed technician leadership roles within our department. The training program has built a pipeline of highly trained technician leaders and decreased the time required to fill technician supervisor openings by 80%. Program graduates have reported the most improvement in management skills, functional skills and knowledge, and communication skills., Conclusion: Creation of an advanced, pharmacy technician-specific leadership program focusing on development of leadership and administrative skills provides short- and long-term benefits to health-system pharmacy departments., (© American Society of Health-System Pharmacists 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Health systems are striving to improve delivery of mechanical thrombectomy (MT) for ischaemic stroke. With the move to 24/7 provision, we aimed to assess (1) the change in referral and procedural frequency and timing, (2) reasons referrals did not proceed to MT, and (3) nocturnal procedural efficacy and safety., Methods: This was an observational study comparing 12-month data for an extended daytime service (2021/2022, hours, 0800-2000) to that for a 12-month period delivering 24/7 cover (2023-2024). Nocturnal and daytime outcomes (rate of recanalisation using modified TICI scoring), extent of postprocedural infarction (using ASPECTS grading), rate of early neurological improvement (using 24-h NIHSS change), 90-day mortality, and complicating symptomatic intracranial haemorrhage (SICH) in the latter period were compared., Results: Both referrals (432 to 851) and procedural caseload (191 to 403) approximately doubled with the move to 24/7 cover; 36% of procedures occurred overnight (n = 145). The dominant reasons for referrals not proceeding to MT were a large core infarct (n = 144) or absence of a large vessel occlusion on baseline imaging (n = 140). There were no significant differences in successful recanalisation (TICI 2B/3: 85.5% vs 87.1%, P = .233), rates of postprocedural ASPECTS≥7 (74.9% vs 75.8%, P = .987), early neurological improvement (NIHSS reduction ≥30%: 43.4% vs 42.4%, P = .917), 90-day mortality (19.6% vs 18.6%, P = .896), or SICH (1.9% vs 4.1%, P = .214) obtained for daytime vs nighttime hours., Conclusion: 24/7 MT provision has resulted in a rapid rise in the number of patients who may benefit from MT. This service can be provided with an acceptable safety profile during nighttime hours in a high-volume comprehensive UK centre., (© The Author(s) 2024. Published by Oxford University Press on behalf of Fellowship of Postgraduate Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: The aims of this scoping review were to summarize the evidence regarding sex, racial, ethnic, geographic, and socioeconomic disparities in post-acute rehabilitation following total hip arthroplasty (THA) and knee arthroplasty (TKA)., Methods: Literature searches were conducted in Ovid MEDLINE, EMBASE, CINAHL, Web of Science, and PEDro. Studies were included if they were original research articles published 1993 or later; used data from the US; included patients after THA and/or TKA; presented results according to relevant sociodemographic variables, including sex, race, ethnicity, geography, or socioeconomic status; and studied the utilization of post-acute rehabilitation as an outcome., Results: Twelve studies met the inclusion criteria. Five examined disparities in inpatient rehabilitation and found that Black patients and women experience longer lengths of stay after arthroplasty, and women are less likely than men to be discharged home after inpatient THA rehabilitation. Four studies examined data from skilled nursing facilities and found that insurance type and dual eligibility impact length of stay and rates of community discharge but found conflicting results regarding racial disparities in skilled nursing facility utilization after TKA. Five studies examined home health data and noted that rural agencies provide less care after TKA. Results regarding racial disparities in home health utilization after arthroplasty were conflicting. Six studies of outpatient rehabilitation noted geographic differences in timing of outpatient rehabilitation but mixed results regarding race differences in outpatient rehabilitation., Conclusion: Current evidence indicates that sex, race, ethnicity, geography, and socioeconomic status are associated with disparities in postacute rehabilitation use after arthroplasty., Impact: Rehabilitation providers across the postacute continuum should be aware of disparities in the population of patients after arthroplasty and regularly assess social determinants of health and other factors that may contribute to disparities. Customized care plans should ensure optimal timing and amount of rehabilitation is provided, and advocate for patients who need additional care to achieve the desired functional outcome., (© 2024 American Physical Therapy Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Transcription factor (TF)-cofactor (COF) interactions define dynamic, cell-specific networks that govern gene expression; however, these networks are understudied due to a lack of methods for high-throughput profiling of DNA-bound TF-COF complexes. Here, we describe the Cofactor Recruitment (CoRec) method for rapid profiling of cell-specific TF-COF complexes. We define a lysine acetyltransferase (KAT)-TF network in resting and stimulated T cells. We find promiscuous recruitment of KATs for many TFs and that 35% of KAT-TF interactions are condition specific. KAT-TF interactions identify NF-κB as a primary regulator of acutely induced histone 3 lysine 27 acetylation (H3K27ac). Finally, we find that heterotypic clustering of CBP/P300-recruiting TFs is a strong predictor of total promoter H3K27ac. Our data support clustering of TF sites that broadly recruit KATs as a mechanism for widespread co-occurring histone acetylation marks. CoRec can be readily applied to different cell systems and provides a powerful approach to define TF-COF networks impacting chromatin state and gene regulation., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Background and Objectives: Female reproductive function flexibly responds to ecological variation in energy availability, but the roles of other ecologically limited resources, such as iron, remain poorly understood. This analysis investigates whether haemoglobin associates with investment in reproductive function in a rural natural fertility population living in the Bolivian altiplano ., Methodology: We conducted a cross-sectional secondary analysis of prospectively collected biomarker and sociodemographic data, comprising 152 menstrual cycles from 96 non-contracepting women living at 3800 m altitude. Multivariable multilevel models were used to investigate (i) whether haemoglobin concentration is associated with ecological variation in subsistence strategy and seasonal conditions, and (ii) whether haemoglobin concentration is associated with the occurrence of ovulation and/or the concentration of luteal progesterone, two biomarkers of current investment in reproduction., Results: Haemoglobin concentrations were lower in arduous seasons among those women more dependent on traditional agropastoral subsistence strategies ( β  = -0.42, 95% CI: -0.80 to -0.04, P  = 0.032). During more arduous seasons, a 1 standard deviation increase in haemoglobin was associated with an over 3-fold increase in the odds of ovulation after adjusting for body fat, breastfeeding status, and age (adjusted odds ratio = 3.27, 95% CI: 1.10 to 9.27, P  = 0.033)., Conclusions and Implications: When conditions are relatively harsh and may be expected to improve, low haemoglobin levels are associated with lower current investment in reproduction and reduced fecundity. These results support the role of iron, independent of energy stores, as a limiting resource in modulating reproductive trade-offs., Competing Interests: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Foundation for Evolution, Medicine, and Public Health.)

Reporting of participants' baseline characteristics in clinical research is important for understanding a given study's context and typically occurs in a tabular format. However, this format incompletely and ambiguously describes included participants, as their identities are more fully represented by an intersecting set of sociodemographic characteristics rather than discrete characteristics in a table. Standard tabular reporting practices therefore introduce limitations in assessing a study's representativeness as well as its internal validity and external validity. To address this, we propose the addition of a simple graph that more clearly shows the joint distribution of baseline sociodemographic characteristics in a given study. We also discuss several practical considerations for the implementation of such graphs in the communication of clinical research., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

Background and Aims: Patterns of atrial fibrillation (AF) recurrence post-catheter ablation for persistent AF (PsAF) are not well described. This study aimed to describe the pattern of AF recurrence seen following catheter ablation for PsAF and the implications for healthcare utilization and quality of life (QoL)., Methods: This was a post-hoc analysis of the CAPLA study, an international, multicentre study that randomized patients with symptomatic PsAF to pulmonary vein isolation plus posterior wall isolation or pulmonary vein isolation alone. Patients underwent twice daily single lead ECG, implantable device monitoring or three monthly Holter monitoring., Results: 154 of 333 (46.2%) patients (median age 67.3 years, 28% female) experienced AF recurrence at 12-month follow-up. Recurrence was paroxysmal in 97 (63%) patients and persistent in 57 (37%). Recurrence type did not differ between randomization groups (P = .508). Median AF burden was 27.4% in PsAF recurrence and .9% in paroxysmal AF (PAF) recurrence (P < .001). Patients with PsAF recurrence had lower baseline left ventricular ejection fraction (PsAF 50% vs. PAF 60%, P < .001) and larger left atrial volume (PsAF 54.2 ± 19.3 mL/m² vs. PAF 44.8 ± 11.6 mL/m², P = .008). Healthcare utilization was significantly higher in PsAF (45 patients [78.9%]) vs. PAF recurrence (45 patients [46.4%], P < .001) and lowest in those without recurrence (17 patients [9.5%], P < .001). Patients without AF recurrence had greater improvements in QoL as assessed by the Atrial Fibrillation Effect on Quality-of-Life (AFEQT) questionnaire (Δ33.3 ± 25.2 points) compared to those with PAF (Δ24.0 ± 25.0 points, P = .012) or PsAF (Δ13.4 ± 22.9 points, P < .001) recurrence., Conclusions: AF recurrence is more often paroxysmal after catheter ablation for PsAF irrespective of ablation strategy. Recurrent PsAF was associated with higher AF burden, increased healthcare utilization and antiarrhythmic drug use. The type of AF recurrence and AF burden may be considered important endpoints in clinical trials investigating ablation of PsAF., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Cryptococcal meningitis is a leading cause of AIDS-related mortality. Cryptococcal antigen (CrAg) predicts the development of meningitis. Historically, despite standard- of-care fluconazole, 25%-30% of asymptomatic CrAg-positive persons develop breakthrough meningitis or death. We evaluated whether adding single high-dose liposomal amphotericin B to standard pre-emptive fluconazole therapy could improve meningitis-free survival., Methods: Participants with human immunodeficiency virus (HIV) and asymptomatic cryptococcal antigenemia in Uganda were randomized to liposomal amphotericin B (10 mg/kg once) with fluconazole or fluconazole alone through 24 weeks. We compared 24-week, meningitis-free survival time between treatment groups. After the second interim review, the Data Safety and Monitoring Board recommended no further enrollment of participants with low plasma CrAg lateral flow assay titers (≤1:80) due to futility. Herein, we present the results of participants with low plasma CrAg titers., Results: 168 participants enrolled into the ACACIA trial had low plasma CrAg titers (≤1:80). During 24 weeks of follow-up, meningitis or death occurred in 14.5% (12/83) of participants randomized to liposomal amphotericin B with fluconazole versus 10.6% (9/85) assigned to fluconazole alone (hazard ratio, 1.42; 95% CI, .60-3.36; P = .431). Adverse events were more frequent in participants assigned to the intervention versus standard-of-care (28% vs 12%; P = .011)., Conclusions: Among CrAg-positive persons with low titers (≤1:80), the addition of single-dose liposomal amphotericin B to fluconazole as pre-emptive therapy provided no additional clinical benefit. This trial provides supportive evidence that, in asymptomatic populations with low plasma CrAg titers, lumbar punctures are likely unnecessary as administration of meningitis treatment did not improve outcomes., Clinical Trials Registration: Clinicaltrials.gov (NCT03945448)., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The assessment of growth during infancy and childhood is an essential component of paediatric medicine, as atypical growth may point to the existence of an underlying health condition. To reduce morbidity, it is vital that treatment for growth disorders is provided in a timely fashion. However, although there are guidelines regarding referral criteria for short stature in Europe and the USA, there are no such guidelines in Canada. To address this, a series of consultations and workshops with paediatricians, paediatric endocrinologists, family physicians and nurses were held, with the aim of developing a consensus-based set of recommendations for children in Canada showing atypical growth and to identify red flags for children who might benefit from early referral. To achieve this, a referral algorithm and referral form for primary care providers were developed to ensure timely and appropriate referrals, and transmission of the most relevant details to the secondary care consultant., Competing Interests: PK has provided consultancy work for Novo Nordisk and Pfizer. NG has participated as a member of advisory boards for Novo Nordisk and Ipsen. RG has participated in advisory boards for the following: Ipsen Pharma Co., Insulet, Pfizer, and Novo Nordisk, and has previously served as an investigator for the following companies Ascendis, NovoNordisk, Neurocrine Biosciences, Inc. SM has participated as a member of Somatrogon Advisory Board (Pfizer Canada) and Somapactitan Advisory Board (Novo Nordisk Canada). IZ has provided consultancy work for Novo Nordisk Canada, Dexcom, and Abbot Diabetes Care. ZS is an employee of Novo Nordisk Canada. SK has provided consultancy work for Novo Nordisk., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Canadian Paediatric Society.)

Background: People with HIV (PHIV) admitted to hospital have high mortality, with tuberculosis (TB) being the major cause of death. Systematic use of new TB diagnostics could improve TB diagnosis and might improve outcomes., Methods: We conducted a cluster randomised trial among adult PHIV admitted to Zomba Central Hospital, Malawi. Admission-days were randomly assigned to: enhanced TB diagnostics using urine lipoarabinomannan (LAM) antigen tests (SILVAMP-LAM, Fujifilm, Japan and Determine-LAM, Alere/Abbot, USA), digital chest X-ray with computer aided diagnosis (dCXR-CAD, CAD4TBv6, Delft, Netherlands), plus usual care ("enhanced TB diagnostics"); or usual care alone ("usual care"). The primary outcome was TB treatment initiation during admission. Secondary outcomes were 56-day mortality, TB diagnosis within 24-hours, and undiagnosed TB at discharge, ascertained by culture of one admission sputum sample., Findings: Between 2 September 2020 and 15 February 2022, we recruited 419 people. Four people were excluded post-recruitment, leaving 415 adults recruited during 207 randomly assigned admission-days in modified intention-to-treat analysis. At admission, 90.8% (377/415) were taking antiretroviral therapy (ART) with median (IQR) CD4 cell count 240 cells/mm3. In the enhanced diagnostic arm, median CAD4TBv6 score was 60 (IQR: 51-71), 4.4% (9/207) had SILVAMP-LAM-positive and 14.4% (29/201) had Determine-LAM positive urine with three samples positive by both urine tests. TB treatment was initiated in 46/208 (22%) in enhanced TB diagnostics arm and 24/207 (12%) in usual care arm (risk ratio [RR] 1.92, 95% CI 1.20-3.08). There was no difference in mortality by 56 days (enhanced TB diagnosis: 54/208, 26%; usual care: 52/207, 25%; hazard ratio 1.05, 95% CI 0.72-1.53); TB treatment initiation within 24 hours (enhanced TB diagnosis: 8/207, 3.9%; usual care: 5/208, 2.4%; RR 1.61, 95% CI 0.53-4.71); or undiagnosed microbiological-confirmed TB at discharge (enhanced TB diagnosis, 0/207 (0.0%), usual care arm 2/208 (1.0%) (p = 0.50)., Interpretation: Urine SILVAMP-LAM/Determine-LAM plus dCXR-CAD diagnostics identified more hospitalised PHIV with TB than usual care. The increase in TB treatment appeared mainly due to greater use of Determine-LAM, rather than SILVAMP-LAM or dCXR-CAD. Poor concordance between Determine-LAM and SILVAMP-LAM urine tests requires further investigation. Inpatient mortality for adults with HIV remains unacceptability high., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Neuroproliferative vestibulodynia (NPV), a provoked genital pain characterized by severe allodynia and hyperalgesia, is confirmed in excised vestibular tissue by immunohistochemical staining (>8 CD117-positive immunostained cells/100× microscopic field) rather than by hematoxylin and eosin staining., Aim: In this study we sought to assess immunostaining of tissue samples obtained during vestibulectomy surgery and to correlate results with patient outcomes., Methods: Patients (n = 65) meeting criteria for NPV who underwent vestibulectomy during the period from June 2019 through December 2022 formed the study cohort. We performed assessment of pathology of vestibular tissues by use of immunohistochemical staining, including quantitation of mast cells by CD117 (mast cell marker) and nerve fibers by protein gene product (PGP) 9.5 (neuronal marker). We analyzed 725 photomicrographs of immunostained tissue sections (100× and 200×) by manual counting and computer-assisted histometry and correlated these data to clinical assessments., Outcomes: Outcomes included density of CD117 and PGP9.5 immunostaining in the 1:00-11:00 o'clock and 12:00 o'clock vestibular regions, and patient-reported outcomes assessing sexual function, pain, distress, and symptom improvement., Results: All 65 NPV patients (median age 26 years), 45 with lifelong and 20 with acquired NPV, had severe pain documented by PROs and vulvoscopy and had >8 CD117-immunopositive cells/100× microscopic field. Median cell count values were similar in the 1:00-11:00 o'clock and 12:00 vestibular regions (28.5 and 29.5/100× field, respectively). Likewise, the marker) and nerve fibers by protein gene product (PGP) 9.5 (neuronal marker). We analyzed 725 photomicrographs of immunostained tissue sections (100× and 200×) by manual counting and computer-assisted histometry and correlated these data to clinical assessments., Outcomes: Outcomes included density of CD117 and PGP9.5 immunostaining in the 1:00-11:00 o'clock and 12:00 o'clock vestibular regions, and patient-reported outcomes assessing sexual function, pain, distress, and symptom improvement., Results: All 65 NPV patients (median age 26 years), 45 with lifelong and 20 with acquired NPV, had severe pain documented by PROs and vulvoscopy and had >8 CD117-immunopositive cells/100× microscopic field. Median cell count values were similar in the 1:00-11:00 o'clock and 12:00 vestibular regions (28.5 and 29.5/100× field, respectively). Likewise, the median area of CD117 immunostaining was similar in both regions (0.69% and 0.73%). The median area of PGP9.5 immunostaining was 0.47% and 0.31% in these same regions. Pain scores determined with cotton-tipped swab testing were nominally higher in lifelong vs acquired NPV patients, reaching statistical significance in the 1:00-11:00 o'clock region (P < .001). The median score for the McGill Pain Questionnaire affective subscale dimension was also significantly higher in lifelong vs acquired NPV patients (P = .011). No correlations were observed between hematoxylin and eosin results and density of mast cells or neuronal markers. Of note, 63% of the patient cohort reported having additional conditions associated with aberrant mast cell activity., Clinical Implications: The pathology of NPV is primarily localized to the vestibular epithelial basement membrane and subepithelial stroma with no visible vulvoscopic findings, making clinical diagnosis challenging., Strengths and Limitations: Strengths of this study include the large number of tissues examined with what is to our knowledge the first-ever assessment of the 12:00 vestibule. Major limitations are specimens from a single timepoint within the disease state and lack of control tissues., Conclusions: Performing immunohistochemical staining of excised vestibular tissue with CD117 and PGP9.5 led to histometric confirmation of NPV, indications that NPV is a field disease involving all vestibular regions, validation for patients whose pain had been ignored and who had experienced negative psychosocial impact, and appreciation that such staining can advance knowledge., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society of Sexual Medicine.)

Background: Vitamin D (Vit D) deficiency has been linked to symptoms of polycystic ovary syndrome (PCOS), yet little is known about Vit D supplementation as a treatment for sexual dysfunction (SDy) in women with PCOS., Aim: To explore the implications of serum total 25-hydroxyvitamin D (25[OH]D) and bioavailable 25[OH]D (bio-25[OH]D) status and replacement on women with PCOS and SDy., Methods: Reproductive-age women with PCOS who were not desiring fertility were eligible provided that they also had SDy, as assessed by the Female Sexual Function Index (FSFI), and were without severe depression, as evaluated by the Beck Depression Inventory II (BDI-II). Participants were given the recommended dietary allowance of Vit D (600 IU daily) plus hormonal contraception (HC; cyclic ethinyl estradiol/drospirenone) or no HC for 6 months. Comparisons between groups were analyzed by chi-square test and t-test, and Pearson's correlation coefficient analyzed correlations between FSFI with demographics, BDI-II, androgen levels, and total and bio-25[OH]D., Outcomes: The outcomes included SDy (FSFI <26.55), total and serum bio-25[OH]D levels, and total and free testosterone., Results: A total of 42 women without severe depression completed the FSFI, with 28 (66.7%) having SDy. All FSFI domains, including arousal, lubrication, orgasm, and pain, were significantly lower as compared with women without SDy, with no associations with respect to demographics, total and free testosterone, or total and bio-25[OH]D. Vit D replacement was initiated with HC (n = 18) or no HC (n = 10), and for those completing the study, FSFI improved (score >26.55) in 61% (11/18) regardless of the treatment group. A time-treatment effect showed a significant change for the domain of orgasm, suggesting that HC had more of an impact than Vit D replacement. Improvement in sexual function as a dichotomous variable was not associated with age, body mass index, other demographics, total and free testosterone, total and bio-25[OH]D, or HC use., Clinical Implications: Due to the prevalence of SDy in women with PCOS, efficacious treatment options are necessary., Strengths and Limitations: This study is the first to analyze the effect of Vit D supplementation on SDy in women with PCOS. Limitations included the small number of participants who completed the study, thus limiting meaningful conclusions and generalizability., Conclusion: Vit D status was not associated with SDy and BDI-II. While HC may have played a role, standard Vit D supplementation could not account for the noted improvement in FSFI in women with PCOS., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society of Sexual Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Exposure to air pollutants has been associated with adverse health outcomes in adults and children who were prenatally exposed. In addition to reducing exposure to air pollutants, it is important to identify their biologic targets in order to mitigate the health consequences of exposure. One molecular change associated with prenatal exposure to air pollutants is DNA methylation (DNAm), which has been associated with changes in placenta and cord blood tissues at birth. However, little is known about how air pollution exposure impacts the sperm epigenome, which could provide important insights into the mechanism of transmission to offspring. In the present study, we explored whether exposure to particulate matter less than 2.5 microns in diameter, particulate matter less than 10 microns in diameter, nitrogen dioxide (NO 2 ), or ozone (O 3 ) was associated with DNAm in sperm contributed by participants in the Early Autism Risk Longitudinal Investigation prospective pregnancy cohort. Air pollution exposure measurements were calculated as the average exposure for each pollutant measured within 4 weeks prior to the date of sample collection. Using array-based genome-scale methylation analyses, we identified 80, 96, 35, and 67 differentially methylated regions (DMRs) significantly associated with particulate matter less than 2.5 microns in diameter, particulate matter less than 10 microns in diameter, NO 2 , and O 3, respectively. While no DMRs were associated with exposure to all four pollutants, we found that genes overlapping exposure-related DMRs had a shared enrichment for gene ontology biological processes related to neurodevelopment. Together, these data provide compelling support for the hypothesis that paternal exposure to air pollution impacts DNAm in sperm, particularly in regions implicated in neurodevelopment., Competing Interests: Dr Ladd-Acosta reports receiving consulting fees from the University of Iowa for providing expertise on autism spectrum disorder epigenetics outside of this work. No other authors have anything to declare., (© The Author(s) 2024. Published by Oxford University Press.)

Motivation: statistics from genome-wide association studies enable many valuable downstream analyses that are more efficient than individual-level data analysis while also reducing privacy concerns. As growing sample sizes enable better-powered analysis of gene-environment interactions, there is a need for gene-environment interaction-specific methods that manipulate and use summary statistics., Results: We introduce two tools to facilitate such analysis, with a focus on statistical models containing multiple gene-exposure and/or gene-covariate interaction terms. REGEM (RE-analysis of GEM summary statistics) uses summary statistics from a single, multi-exposure genome-wide interaction study to derive analogous sets of summary statistics with arbitrary sets of exposures and interaction covariate adjustments. METAGEM (META-analysis of GEM summary statistics) extends current fixed-effects meta-analysis models to incorporate multiple exposures from multiple studies. We demonstrate the value and efficiency of these tools by exploring alternative methods of accounting for ancestry-related population stratification in genome-wide interaction study in the UK Biobank as well as by conducting a multi-exposure genome-wide interaction study meta-analysis in cohorts from the diabetes-focused ProDiGY consortium. These programs help to maximize the value of summary statistics from diverse and complex gene-environment interaction studies., Availability and Implementation: REGEM and METAGEM are open-source projects freely available at https://github.com/large-scale-gxe-methods/REGEM and https://github.com/large-scale-gxe-methods/METAGEM., (© The Author(s) 2023. Published by Oxford University Press.)

Background and Aims: Interventional studies in pulmonary arterial hypertension completed to date have shown to be effective in symptomatic patients with significantly elevated mean pulmonary artery pressure (mPAP) (≥25 mmHg) and pulmonary vascular resistance (PVR) > 3 Wood Unit (WU). However, in health the mPAP does not exceed 20 mmHg and PVR is 2 WU or lower, at rest. The ESC/ERS guidelines have recently been updated to reflect this. There is limited published data on the nature of these newly defined populations (mPAP 21-24 mmHg and PVR >2-≤3 WU) and the role of comorbidity in determining their natural history. With the change in guidelines, there is a need to understand this population and the impact of the ESC/ERS guidelines in greater detail., Methods: A retrospective nationwide evaluation of the role of pulmonary haemodynamics and comorbidity in predicting survival among patients referred to the UK pulmonary hypertension (PH) centres between 2009 and 2017. In total, 2929 patients were included in the study. Patients were stratified by mPAP (<21 mmHg, 21-24 mmHg, and ≥25 mmHg) and PVR (≤2 WU, > 2-≤3 WU, and >3 WU), with 968 (33.0%) in the mPAP <21 mmHg group, 689 (23.5%) in the mPAP 21-24 mmHg group, and 1272 (43.4%) in the mPAP ≥25 mmHg group., Results: Survival was negatively correlated with mPAP and PVR in the population as a whole. Survival in patients with mildly elevated mPAP (21-24 mmHg) or PVR (>2-≤3WU) was lower than among those with normal pressures (mPAP <21 mmHg) and normal PVR (PVR ≤ 2WU) independent of comorbid lung and heart disease [hazard ratio (HR) 1.36, 95% confidence interval (CI) 1.14-1.61, P = .0004 for mPAP vs. HR 1.28, 95% CI 1.10-1.49, P = .0012 for PVR]. Among patients with mildly elevated mPAP, a mildly elevated PVR remained an independent predictor of survival when adjusted for comorbid lung and heart disease (HR 1.33, 95% CI 1.01-1.75, P = .042 vs. HR 1.4, 95% CI 1.06-1.86, P = .019). 68.2% of patients with a mPAP 21-24 mmHg had evidence of underlying heart or lung disease. Patients with mildly abnormal haemodynamics were not more symptomatic than patients with normal haemodynamics. Excluding patients with heart and lung disease, connective tissue disease was associated with a poorer survival among those with PH. In this subpopulation evaluating those with a mPAP of 21-24 mmHg, survival curves only diverged after 5 years., Conclusions: This study supports the change in diagnostic category of the ESC/ERS guidelines in a PH population. The newly included patients have an increased mortality independent of significant lung or heart disease. The majority of patients in this new category have underlying heart or lung disease rather than an isolated pulmonary vasculopathy. Mortality is higher if comorbidity is present. Rigorous phenotyping will be pivotal to determine which patients are at risk of progressive vasculopathic disease and in whom surveillance and recruitment to studies may be of benefit. This study provides an insight into the population defined by the new guidelines., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Comprehensive geriatric assessment (CGA) is the cornerstone of modern geriatric medicine and the framework around which conventional and new models of care for older people are developed. Whilst there are a substantial number of reviews synthesising the evidence on patient and service outcomes from CGA, as an intervention it remains poorly described. There is a lack of detail on how a CGA plan is coordinated, delivered and followed up, especially outside of acute care. This commentary reflects on the authors' experience of extracting data from 57 published studies on CGA. CGA as an intervention is akin to a 'black box' in terms of describing and measuring participants' interactions with CGA activity in terms of time, frequency and amount (dose) received. There is also a lack of detail on how newly established CGA teams become effective, interdisciplinary, high functioning and sustainable teams. The CGA knowledge-do gap persists with a need to draw from complex system theory and implementation science frameworks to better describe the intervention and understand the influence of the organisation and health service within which CGA is operationalised. Equally, the voice of older people, families and staff is critical in the conduct and evaluation of CGA, and how it evolves as a model to meet the growing needs of ageing populations., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Patients without human immunodeficiency virus (HIV) are increasingly recognized as being at risk for cryptococcosis. Knowledge of characteristics of cryptococcosis in these patients remains incomplete., Methods: We conducted a retrospective study of cryptococcosis in 46 Australian and New Zealand hospitals to compare its frequency in patients with and without HIV and describe its characteristics in patients without HIV. Patients with cryptococcosis between January 2015 and December 2019 were included., Results: Of 475 patients with cryptococcosis, 90% were without HIV (426 of 475) with marked predominance in both Cryptococcus neoformans (88.7%) and Cryptococcus gattii cases (94.3%). Most patients without HIV (60.8%) had a known immunocompromising condition: cancer (n = 91), organ transplantation (n = 81), or other immunocompromising condition (n = 97). Cryptococcosis presented as incidental imaging findings in 16.4% of patients (70 of 426). The serum cryptococcal antigen test was positive in 85.1% of tested patients (319 of 375); high titers independently predicted risk of central nervous system involvement. Lumbar puncture was performed in 167 patients to screen for asymptomatic meningitis, with a positivity rate of 13.2% where meningitis could have been predicted by a high serum cryptococcal antigen titer and/or fungemia in 95% of evaluable cases. One-year all-cause mortality was 20.9% in patients without HIV and 21.7% in patients with HIV (P = .89)., Conclusions: Ninety percent of cryptococcosis cases occurred in patients without HIV (89% and 94% for C. neoformans and C. gattii, respectively). Emerging patient risk groups were evident. A high level of awareness is warranted to diagnose cryptococcosis in patients without HIV., Competing Interests: Potential conflicts of interest . T. S. has received consulting fees for serving on advisory boards and steering committees from Biogen. O. M. has received grants from Gilead Sciences and Merck, Sharp and Dohme Australia and honoraria from Gilead Sciences; support for attending meetings from F2G; and participated on data and safety monitoring boards (DSMB) or advisory boards for Gilead Sciences and Merck, Sharp and Dohme Australia. K. J. K. has received payment for expert testimony at the 46th Society of Hospital Pharmacists of Australia National Conference. A. R. T. has received honoraria from the Medical Journal of Australia, paid to institution, and reports grants or contracts from CTRA with the University of Melbourne (reimbursement of costs paid to institution). B. W. T. is supported by a Medical Research Future Fund Investigator Fellowship; has received grants from MSD and Seqirus; has received honoraria from Pfizer, Alexion, and Janssen; and participated on DSMBs or advisory boards for CSL­Behring, Takeda, and Moderna. S. C. A. C. has received educational grants from F2G and MSD Australia; reports untied educational grants from MSD Australia and F2G Pty Ltd; and reports a role as editor-in-chief for Medical Mycology (journal of ISHAM). M. A. S. has received grants from Gilead Sciences, Merck, and F2G; has received honoraria from F2G; and participated on DSMBs or advisory boards for Pfizer, Cidara, and Roche. R. J. L. reports paid participation on a GSK advisory board. S. A. L. reports grants or contracts as principal investigator on 3 projects funded through a Hot North fund grant and a UK Government Fleming Fund Grant (as part of broader funding for the Menzies School of Health Research; no salary, project costs remunerated only); unpaid participation on a DSMB or advisory board for the Australian Academy of Science and the Australian Academy of Health and Medical Sciences roundtable of experts for the House of Representatives Committee on Health and Ageing; and an unpaid role as a National Tuberculosis Advisory Committee member. M. T. B. reports an unpaid role as an Advanced Training Committee member for General Medicine for the Royal Australasian College of Physicians and an unpaid member of the Vocational Training Committee for Medical Registrars in the Auckland region for the Northern Region Alliance. C. L. K. reports an unpaid role on the Australian Society of Infectious Diseases Board of Directors. E. W. reports a role as a committee member of the Australasian Society for Infectious Diseases Equity and Diversity Committee (unpaid). K. C. G. reports a role as a member of the New Zealand Committee of the Australasian Society for Infectious Diseases. All other authors report no potential conflicts. All authors have submitted the International Committee of Medical Journal Editors Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Patients with inflammatory bowel disease (IBD) require accessible, timely, and noninvasive strategies to monitor disease. The aim was to assess the integration of intestinal ultrasound (IUS) on decision-making and endoscopy utilization in a standardized care pathway., Methods: This prospective, multicenter, international, observational cohort study included patients seen within a centralized model for IBD care was conducted during the COVID pandemic. Patients were evaluated with IUS alone or in combination with an in-clinic, unsedated sigmoidoscopy. Demographic, clinical, laboratory, and imaging data, clinical decisions, and need for urgent endoscopy, hospitalization, and surgeries were recorded., Results: Of the 158 patients included, the majority had an established diagnosis of Crohn's disease ( n  = 123, 78%), and 47% ( n  = 75) of patients were on biologic therapy. IUS identified active inflammation in 65% ( n  = 102) of patients, and strictures in 14% ( n  = 22). Fecal calprotectin levels correlated with inflammation detected on IUS (median of 50 μg/g [Q1-Q3: 26-107 μg/g] without inflammation and 270 μg/g [Q1-Q3: 61-556 μg/g] with inflammation; p  = 0.0271). In the majority of patients, clinical assessment with IUS led to an acute change in IBD-specific medications (57%, n  = 90) and avoided or delayed the need for urgent endoscopy (85%, n  = 134). Four patients were referred for urgent surgical consultation., Conclusions: Point-of-care IUS used in a flare clinic pathway is a useful strategy to improve effective IBD care delivery and to assist in therapeutic management decisions, in many cases avoiding the acute need for endoscopy., Competing Interests: K.L.N. reports advisory board fees from AbbVie, Janssen, Pfizer, Ferring; speaker’s fees from AbbVie, Janssen; and research support from AbbVie, Janssen. J.S., H.K., and J.H. report no conflicts. M.D. reports fees for participation on advisory committees from Amgen, Fresenius Kabi, Pendopharm, and Takeda; fees for participation on advisory committees from Bristol Myers Squibb, McKesson, Pendopharm, and Takeda; educational, clinical, or research grants from Abbvie, Amgen, Organon, Pfizer, Sandoz, and Takeda. T.M.G. reports support through provision of an Australian Government research training program scholarship and grant support from Janssen. R.J.M.I. reports travel support from AbbVie and speaker’s fees from Takeda. R.V.B. reports Grant/Research support/Speaker fees (all paid to employer for research support): AbbVie, Ferring, Janssen, Shire, Takeda, Emerge Health; shareholder in Biomebank. B.C. has served as a consultant and advisory board member, and received grants from AbbVie, Ferring, Janssen, Pfizer, Fresenius Kabi, Falk Pharama, Gilead, Celgene, and Takeda. R.V. has served as a consultant for Janssen. A.A.-A. was funded by scholarships from Crohn’s and Colitis Australia, Avant, the Australian Commonwealth Government, and University of Melbourne and received grants from the Gastroenterological Society of Australia/Celltrion Healthcare and Janssen. D.C. reports speaker’s fees and/or research support from Takeda, Janssen, Abbvie, and Tarp and consultancy fees from Takeda, Abbvie, and Taro. C.L. reports consulting or advisory board fees from AbbVie, Ferring, Janssen, and Takeda. C.M. reports consulting or advisory board fees from AbbVie, AVIR Pharma Inc, Janssen, Takeda, Pfizer, Roche, and Robarts Clinical Trials Inc.; speaker’s fees from AbbVie, Janssen, Takeda, and Pfizer., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation.)

Background: The northwestern border of Thailand is an area of low seasonal malaria transmission. Until recent successful malaria elimination activities, malaria was a major cause of disease and death. Historically the incidences of symptomatic Plasmodium falciparum and Plasmodium vivax malaria were approximately similar., Methods: All malaria cases managed in the Shoklo Malaria Research Unit along the Thailand-Myanmar border between 2000 and 2016 were reviewed., Results: There were 80 841 consultations for symptomatic P. vivax and 94 467 for symptomatic P. falciparum malaria. Overall, 4844 (5.1%) patients with P. falciparum malaria were admitted to field hospitals, of whom 66 died, compared with 278 (0.34%) with P. vivax malaria, of whom 4 died (3 had diagnoses of sepsis, so the contribution of malaria to their fatal outcomes is uncertain). Applying the 2015 World Health Organization severe malaria criteria, 68 of 80 841 P. vivax admissions (0.08%) and 1482 of 94 467 P. falciparum admissions (1.6%) were classified as severe. Overall, patients with P. falciparum malaria were 15 (95% confidence interval, 13.2-16.8) times more likely than those with P. vivax malaria to require hospital admission, 19 (14.6-23.8) times more likely to develop severe malaria, and ≥14 (5.1-38.7) times more likely to die., Conclusions: In this area, both P. falciparum and P. vivax infections were important causes of hospitalization, but life-threatening P. vivax illness was rare., Competing Interests: Potential conflicts of interest. M. Stolbrink reports a Clinical PhD fellowship from Wellcome Trust, unrelated to this manuscript or the topic. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

So-called duplex speech stimuli with perceptually ambiguous spectral cues to one ear and isolated low- versus high-frequency third formant "chirp" to the opposite ear yield a coherent percept supporting their phonetic categorization. Critically, such dichotic sounds are only perceived categorically upon binaural integration. Here, we used frequency-following responses (FFRs), scalp-recorded potentials reflecting phase-locked subcortical activity, to investigate brainstem responses to fused speech percepts and to determine whether FFRs reflect binaurally integrated category-level representations. We recorded FFRs to diotic and dichotic stop-consonants (/da/, /ga/) that either did or did not require binaural fusion to properly label along with perceptually ambiguous sounds without clear phonetic identity. Behaviorally, listeners showed clear categorization of dichotic speech tokens confirming they were heard with a fused, phonetic percept. Neurally, we found FFRs were stronger for categorically perceived speech relative to category-ambiguous tokens but also differentiated phonetic categories for both diotically and dichotically presented speech sounds. Correlations between neural and behavioral data further showed FFR latency predicted the degree to which listeners labeled tokens as "da" versus "ga." The presence of binaurally integrated, category-level information in FFRs suggests human brainstem processing reflects a surprisingly abstract level of the speech code typically circumscribed to much later cortical processing., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Psychiatric disorders are 1.5 to 2 times more prevalent in persons with inflammatory bowel disease (IBD) than in the general population, with pooled prevalence estimates of 21% for clinical anxiety and 15% for depression. Rates are even higher when considering mental health symptoms, as nearly one-third of persons with IBD experience elevated anxiety symptoms and one-quarter experience depression symptoms. Rates of these symptoms were much higher during periods of disease activity, more common in women than men, and more common in Crohn's disease than ulcerative colitis. There is robust evidence of the detrimental effects of comorbid depression and anxiety on the subsequent course of IBD based on longitudinal studies tracking outcomes over time. However, psychiatric disorders and IBD have bidirectional effects, with each affecting risk of the other. Elevated mental health concerns have been consistently associated with greater healthcare utilization and costs related to IBD. There is some signal that low resilience in adolescence could be a risk factor for developing IBD and that enhancing resilience may improve mental health and intestinal disease outcomes in IBD. Psychological therapies used to treat anxiety and depression occurring in the context of IBD have been shown to significantly improve the quality of life for persons with IBD and reduce anxiety and depression. There is less evidence in regard to the impact of psychotropic medications on mental health or disease outcomes in persons with IBD. There is consensus, however, that mental health must be addressed as part of comprehensive IBD care for children and adults., Competing Interests: Lesley Graff has been a consultant with Roche Canada. Ellen Kuenzig is a member of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada. Eric Benchimol holds the Northbridge Financial Corporation Chair in Inflammatory Bowel Disease, a joint Hospital-University Chair between the University of Toronto, The Hospital for Sick Children, and the SickKids Foundation. He has acted as a consultant for the Dairy Farmers of Ontario and McKesson Canada for matters unrelated to medications used to treat inflammatory bowel disease. He is Past Chair of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada and Editor-in-Chief of the Journal of the Canadian Association of Gastroenterology (JCAG). Gilaad Kaplan has received honoraria for speaking or consultancy from AbbVie, Janssen, Pfizer and Takeda. He has received research support from Ferring, Janssen, AbbVie, GlaxoSmith Kline, Merck and Shire. He has been a consultant for Gilead. He shares ownership of a patent: TREATMENT OF INFLAMMATORY DISORDERS, AUTOIMMUNE DISEASE, AND PBC. UTI Limited Partnership, assignee. Patent WO2019046959A1. PCT/CA2018/051098. 7 September 2018. He is a member of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada. Alain Bitton has participated in advisory boards with AbbVie, Janssen, Takeda, McKesson, BioJamp, Bristol Myers Squibb Hoffman-LaRoche, Amgen. He has received research support from AbbVie. He is on the speaker’s panel for Janssen, Takeda, AbbVie and has participated in educational activities supported by Viatris, has received educational support from Fresenius Kabi, Amgen and Takeda. Jennifer Jones has received honoraria for speaking and consulting for AbbVie, Janssen, Pfizer, Shire and Takeda. She is the co-chair of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada. Kate Lee has received honoraria from AbbVie Corporation and Bristol Myers Squibb Canada. anjay Murthy has previously participated in advisory board meetings for AbbVie, Janssen, Takeda, Pfizer, Shire and Ferring and as a speaker at educational events sponsored by Janssen, AbbVie and Pfizer. Laura Targownik has received research funding from AbbVie Canada, Takeda Canada, Sandoz Canada, Amgen Canada, Gilead Canada, Roche Canada and Pfizer Canada, and has been on Advisory Boards for Janssen Canada, AbbVie Canada, Takeda Canada, Pfizer Canada, Merck Canada, Roche Canada, Sandoz Canada, Organon Canada, Fresesnius Kabi Canada, Eli Lilly Canada and Amgen Canada. She is a member of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada. Charles Bernstein is supported in part by the Bingham Chair in Gastroenterology. He is on Advisory Boards for AbbVie Canada, Amgen Canada, Bristol Myers Squibb, JAMP Pharmaceuticals, Lilly Canada, Janssen Canada, Pfizer Canada, Roche Canada, Sandoz Canada, Takeda Canada. He is a Consultant for Mylan Pharmaceuticals and Takeda. He has received educational grants from AbbVie Canada, Pfizer Canada, Takeda Canada, Janssen Canada, and Bristol Myers Squibb Canada. He is on the speaker’s panel for AbbVie Canada, Janssen Canada, Pfizer Canada and Takeda Canada. Received research funding from AbbVie Canada, Amgen Canada, Pfizer Canada, Sandoz Canada. None: Joseph Windsor, Stephanie Coward, Rose Geist, Juan-Nicolás Peña-Sánchez, Nazanin Jannati, Tyrel Jones May, Tasbeen Akhtar Sheekha, Tal Davis, Jake Weinstein, Ghaida Dahlwi, James Im, Jessica Amankwah Osei, Noelle Rohatinsky, Sara Ghandeharian, Quinn Goddard, Julia Gorospe, Shira Gertsman, Michelle Louis, Richelle Wagner, Colten Brass, & Rhonda Sanderson., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Canadian Association of Gastroenterology.)

Rates of inflammatory bowel disease (IBD) in Canadian children and adolescents are among the highest in the world, and the incidence is rising most rapidly in children under five years of age. These young children may have either a typical form of IBD with multi-factorial aetiology, or they may have a monogenic form. Despite the growing number of children in Canada living with this important chronic disease, there are few available medical therapies approved by Health Canada due to the omission of children from most clinical trials of newly developed biologics. As a result, off-label use of medications is common, and physicians have learned to use existing therapies more effectively. In addition, most Canadian children are treated in multidisciplinary, specialty clinics by physicians with extra training or experience in IBD, as well as specialist nurses, dietitians, mental health care providers and other allied health professionals. This specialized clinic approach has facilitated cutting edge research, led by Canadian clinicians and scientists, to understand the causes of IBD, the optimal use of therapies, and the best ways to treat children from a biopsychosocial perspective. Canadians are engaged in work to understand the monogenic causes of IBD; the interaction between genes, the environment, and the microbiome; and how to address the mental health concerns and medical needs of adolescents and young adults transitioning from paediatric to adult care., Competing Interests: Matthew Carroll has received speaker fees from AbbVie. Anne Griffiths past holder of the Northbridge Financial Corporation Chair in Inflammatory Bowel Disease, a joint Hospital-University Chair between the University of Toronto, The Hospital for Sick Children, and the SickKids Foundation. She has received research support from AbbVie Canada. She is co-owner of copyright for the Pediatric Ulcerative Colitis Activity Index (PUCAI) and for the TUMMY-UC. She has been an advisory board member or consultant for AbbVie, Amgen, Bristol Myers Squibb, Janssen, Lilly, Merck, Pfizer, Takeda, and has received speaker fees from AbbVie, Janssen, Takeda. She is a member of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada. Ellen Kuenzig is a member of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada. David Mack is co-owner of Biotagenics Inc. Eytan Wine has received honoraria for speaking or consultancy from AbbVie, Janssen, Pfizer, Nestle Health Sciences, Mead Johnson Nutrition, and Biojamp. Gilaad Kaplan has received honoraria for speaking or consultancy from AbbVie, Janssen, Pfizer, and Takeda. He has received research support from Ferring, Janssen, AbbVie, GlaxoSmith Kline, Merck, and Shire. He has been a consultant for Gilead. He shares ownership of a patent: TREATMENT OF INFLAMMATORY DISORDERS, AUTOIMMUNE DISEASE, AND PBC. UTI Limited Partnership, assignee. Patent WO2019046959A1. PCT/CA2018/051098. 7 Sept. 2018. He is a member of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada. Charles Bernstein is supported in part by the Bingham Chair in Gastroenterology. He is on Advisory Boards for AbbVie Canada, Amgen Canada, Bristol Myers Squibb, JAMP Pharmaceuticals, Lilly Canada, Janssen Canada, Pfizer Canada, Roche Canada, Sandoz Canada, Takeda Canada. He is a Consultant for Mylan Pharmaceuticals and Takeda. He has received educational grants from AbbVie Canada, Pfizer Canada, Takeda Canada, Janssen Canada, and Bristol Myers Squibb Canada. He is on the speaker’s panel for AbbVie Canada, Janssen Canada, Pfizer Canada, and Takeda Canada. Received research funding from AbbVie Canada, Amgen Canada, Pfizer Canada, Sandoz Canada. Alain Bitton has participated in advisory boards with AbbVie, Janssen, Takeda, McKesson, BioJamp, Bristol Myers Squibb Hoffman-LaRoche, Amgen. He has received research support from AbbVie. He is on the speaker’s panel for Janssen, Takeda, AbbVie and has participated in educational activities supported by Viatris, has received educational support from Fresenius Kabi, Amgen, and Takeda. Jennifer Jones has received honoraria for speaking and consulting for AbbVie, Janssen, Pfizer, Shire, and Takeda. She is the co-chair of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada. Kate lee has received honoraria from AbbVie Corporation and Bristol Myers Squibb Canada. Sanjay Murthy has previously participated in advisory board meetings for AbbVie, Janssen, Takeda, Pfizer, Shire and Ferring and as a speaker at educational events sponsored by Janssen, AbbVie and Pfizer. Laura Targownik has received research funding from AbbVie Canada, Takeda Canada, Sandoz Canada, Amgen Canada, Gilead Canada, Roche Canada and Pfizer Canada, and has been on Advisory Boards for Janssen Canada, AbbVie Canada, Takeda Canada, Pfizer Canada, Merck Canada, Roche Canada, Sandoz Canada, Organon Canada, Fresesnius Kabi Canada, Eli Lilly Canada, and Amgen Canada. She is a member of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada. Jules Verdugo has received an AbbVie IBD scholarship. Samantha Morin has received an AbbVie IBD scholarship. Taylor Morganstein has received an AbbVie IBD scholarship and is a member of the Patient Adboard of AbbVie Canada. Eric Benchimol holds the Northbridge Financial Corporation Chair in Inflammatory Bowel Disease, a joint Hospital-University Chair between the University of Toronto, The Hospital for Sick Children, and the SickKids Foundation. He has acted as a consultant for the Dairy Farmers of Ontario and McKesson Canada for matters unrelated to medications used to treat inflammatory bowel disease. He is Past Chair of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada and Editor-in-Chief of the Journal of the Canadian Association of Gastroenterology (JCAG). None: Wael El-Matary, Colette Deslandres, Rose Geist, Tal Davis, Jake Weinstein, Justin Chan, Rabia Khan, Priscilla Matthews, Joseph Windsor, Stephanie Coward, Juan-Nicolás Peña-Sánchez, Noelle Rohatinsky, Sara Ghandeharian, James Im, Quinn Goddard, Julia Gorospe, & Lisa Banning., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Canadian Association of Gastroenterology.)

Conditional gene regulation in Drosophila through binary expression systems like the LexA-LexAop system provides a superb tool for investigating gene and tissue function. To increase the availability of defined LexA enhancer trap insertions, we present molecular, genetic, and tissue expression studies of 301 novel Stan-X LexA enhancer traps derived from mobilization of the index SX4 line. This includes insertions into distinct loci on the X, II, and III chromosomes that were not previously associated with enhancer traps or targeted LexA constructs, an insertion into ptc, and seventeen insertions into natural transposons. A subset of enhancer traps was expressed in CNS neurons known to produce and secrete insulin, an essential regulator of growth, development, and metabolism. Fly lines described here were generated and characterized through studies by students and teachers in an international network of genetics classes at public, independent high schools, and universities serving a diversity of students, including those underrepresented in science. Thus, a unique partnership between secondary schools and university-based programs has produced and characterized novel resources in Drosophila, establishing instructional paradigms devoted to unscripted experimental science., Competing Interests: Conflicts of interest statement The author(s) declare no conflict of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Genetics Society of America.)

In the field of rare diseases, progress in molecular diagnostics led to the recognition that variants linked to autosomal-dominant neurodegenerative diseases of later onset can, in the context of biallelic inheritance, cause devastating neurodevelopmental disorders and infantile or childhood-onset neurodegeneration. TOR1A-associated arthrogryposis multiplex congenita 5 (AMC5) is a rare neurodevelopmental disorder arising from biallelic variants in TOR1A, a gene that in the heterozygous state is associated with torsion dystonia-1 (DYT1 or DYT-TOR1A), an early-onset dystonia with reduced penetrance. While 15 individuals with AMC5-TOR1A have been reported (less than 10 in detail), a systematic investigation of the full disease-associated spectrum has not been conducted. Here, we assess the clinical, radiological and molecular characteristics of 57 individuals from 40 families with biallelic variants in TOR1A. Median age at last follow-up was 3 years (0-24 years). Most individuals presented with severe congenital flexion contractures (95%) and variable developmental delay (79%). Motor symptoms were reported in 79% and included lower limb spasticity and pyramidal signs, as well as gait disturbances. Facial dysmorphism was an integral part of the phenotype, with key features being a broad/full nasal tip, narrowing of the forehead and full cheeks. Analysis of disease-associated manifestations delineated a phenotypic spectrum ranging from normal cognition and mild gait disturbance to congenital arthrogryposis, global developmental delay, intellectual disability, absent speech and inability to walk. In a subset, the presentation was consistent with foetal akinesia deformation sequence with severe intrauterine abnormalities. Survival was 71%, with higher mortality in males. Death occurred at a median age of 1.2 months (1 week-9 years), due to respiratory failure, cardiac arrest or sepsis. Analysis of brain MRI studies identified non-specific neuroimaging features, including a hypoplastic corpus callosum (72%), foci of signal abnormality in the subcortical and periventricular white matter (55%), diffuse white matter volume loss (45%), mega cisterna magna (36%) and arachnoid cysts (27%). The molecular spectrum included 22 distinct variants, defining a mutational hotspot in the C-terminal domain of the Torsin-1A protein. Genotype-phenotype analysis revealed an association of missense variants in the 3-helix bundle domain to an attenuated phenotype, while missense variants near the Walker A/B motif as well as biallelic truncating variants were linked to early death. In summary, this systematic cross-sectional analysis of a large cohort of individuals with biallelic TOR1A variants across a wide age-range delineates the clinical and genetic spectrum of TOR1A-related autosomal-recessive disease and highlights potential predictors for disease severity and survival., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Services offering on-demand delivery of unhealthy commodities, such as fast food, alcohol and smoking/vaping products have proliferated in recent years. It is well known that the built environment can be health promoting or harmful to health, but there has been less consideration of the digital environment. Increased availability and accessibility of these commodities may be associated with increased consumption, with harmful public health implications. Policy regulating the supply of these commodities was developed before the introduction of on-demand services and has not kept pace with the digital environment. This paper reports on semi-structured interviews with health policy experts on the health harms of the uptake in on-demand delivery of food, alcohol and smoking/vaping products, along with their views on policies that might mitigate these harms. We interviewed 14 policy experts from central and local government agencies and ministries, health authorities, non-Government Organisations (NGOs) and university research positions in Aotearoa New Zealand using a purposive sampling strategy. Participants concerns over the health harms from on-demand services encompassed three broad themes-the expansion of access to and availability of unhealthy commodities, the inadequacy of existing restrictions and regulations in the digital environment and the expansion of personalized marketing and promotional platforms for unhealthy commodities. Health policy experts' proposals to mitigate harms included: limiting access and availability, updating regulations and boosting enforcement and limiting promotion and marketing. Collectively, these findings and proposals can inform future research and public health policy decisions to address harms posed by on-demand delivery of unhealthy commodities., (© The Author(s) 2023. Published by Oxford University Press.)

Background: Mucosal healing improves clinical outcomes in patients with inflammatory bowel disease (IBD) and is associated with higher infliximab trough levels (ITLs). Transmural healing, assessed by intestinal ultrasound (IUS), is emerging as an objective target in Crohn's disease (CD) and ulcerative colitis (UC). This study explores the correlation between maintenance ITLs and sonographic transmural healing., Methods: Patients on maintenance infliximab therapy were prospectively enrolled to undergo paired IUS examination and serum ITL. Infliximab trough levels were compared between patients with and without sonographic markers of inflammation using the Mann-Whitney U test., Results: A prospective cohort of 103 patients (51% male; 79 CD; 24 UC; median duration of disease 8 years) underwent IUS and serum ITL testing. Forty-one percent of CD and 66% of UC patients demonstrated sonographic healing (bowel wall thickening ≤3 mm with no increase in color Doppler signal). Crohn's disease patients with sonographic healing had higher median ITL compared with those with sonographic inflammation (4.8 μg/mL vs 3.1 μg/mL; P = .049). Additionally, the presence of hyperemia on Doppler was independently associated with lower ITL compared with those without hyperemia (2.1 μg/mL vs 4.2 μg/mL, respectively; P = .003). There was no significant association between ITL and other sonographic markers of inflammation. In UC, lower ITL was associated with hyperemia on Doppler imaging (P = .04). There was no association between ITL and sonographic healing or any other individual sonographic parameter of inflammation., Conclusions: Lower maintenance infliximab levels are associated with sonographic parameters of inflammation in UC and CD. Further studies are needed to determine whether targeting higher infliximab levels can increase sonographic healing., (© The Author(s) 2022. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The COVID-19 pandemic has forced many Americans to adapt their daily routines. In 2020, there was a significant increase in house fires according to the National Fire Prevention Association (NFPA). The objective of this study was to characterize the changes in suspected smoke inhalations (SSIs) during the first year of the pandemic in the National Emergency Medical Services Information System (NEMSIS). The NEMSIS database was queried for all EMS transports captured between 2017 and 2020. Differences in the incidences of SSIs and fire dispatches in 2020 were estimated using Poisson regression models. There was a 13.4% increase in the incidence of fire dispatches and a 15% increase in SSIs transported in 2020 compared to the previous 3 years. The incidence rate ratio of both fire dispatches (1.271; 95% CI: 1.254-1.288; P < .001) and SSI (1.152; 95% CI: 1.070-1.241; P < .001) was significantly elevated in 2020. The increases in fire dispatches and SSIs observed in the NEMSIS database are in concordance with other literature indicating the increase in fire incidence and morbidity observed during the pandemic. These results should inform fire prevention outreach efforts and resource allocation in burn centers in the event of future pandemic., (Published by Oxford University Press on behalf of the American Burn Association 2022.)

Background: It remains unknown why ~30% of patients with psychotic disorders fail to respond to treatment. Previous genomic investigations of treatment-resistant psychosis have been inconclusive, but some evidence suggests a possible link between rare disease-associated copy number variants (CNVs) and worse clinical outcomes in schizophrenia. Here, we identified schizophrenia-associated CNVs in patients with treatment-resistant psychotic symptoms and then compared the prevalence of these CNVs to previously published schizophrenia cases not selected for treatment resistance., Methods: CNVs were identified using chromosomal microarray (CMA) and whole exome sequencing (WES) in 509 patients with treatment-resistant psychosis (a lack of clinical response to ≥3 adequate antipsychotic medication trials over at least 5 years of psychiatric hospitalization). Prevalence of schizophrenia-associated CNVs in this sample was compared to that in a previously published large schizophrenia cohort study., Results: Integrating CMA and WES data, we identified 47 cases (9.2%) with at least one CNV of known or possible neuropsychiatric risk. 4.7% (n = 24) carried a known neurodevelopmental risk CNV. The prevalence of well-replicated schizophrenia-associated CNVs was 4.1%, with duplications of the 16p11.2 and 15q11.2-q13.1 regions, and deletions of the 22q11.2 chromosomal region as the most frequent CNVs. Pairwise loci-based analysis identified duplications of 15q11.2-q13.1 to be independently associated with treatment resistance., Conclusions: These findings suggest that CNVs may uniquely impact clinical phenotypes beyond increasing risk for schizophrenia and may potentially serve as biological entry points for studying treatment resistance. Further investigation will be necessary to elucidate the spectrum of phenotypic characteristics observed in adult psychiatric patients with disease-associated CNVs., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: frailty screening facilitates the stratification of older adults at most risk of adverse events for urgent assessment and subsequent intervention. We assessed the validity of the Identification of Seniors at Risk (ISAR), Clinical Frailty Scale (CFS), Programme on Research for Integrating Services for the Maintenance of Autonomy seven item questionnaire (PRISMA-7) and InterRAI-ED at predicting adverse outcomes at 30 days and 6 months amongst older adults presenting to the Emergency Department (ED)., Methods: a prospective cohort study of adults ≥65 years who presented to the ED was conducted. The ISAR, CFS, PRISMA-7 and InterRAI-ED were assessed. Blinded follow-up telephone interviews were completed at 30 days and 6 months to assess the incidence of mortality, ED re-attendance, hospital readmission, functional decline and nursing home admission. The sensitivity, specificity, negative predictive value and positive predictive value of the screening tools were calculated using 2 × 2 tables., Results: a total of 419 patients were recruited; 47% female with a mean age of 76.9 (Standard deviation = 7.2). The prevalence of frailty varied across the tools (CFS 57% versus InterRAI-ED 70%). At 30 days, the mortality rate was 5.1%, ED re-attendance 18.1%, hospital readmission 14%, functional decline 47.6% and nursing home admission 7.1%. All tools had a high sensitivity and positive predictive value for predicting adverse outcomes., Conclusion: older adults who screened positive for frailty were at significantly increased risk of experiencing an adverse outcome at 30 days with the ISAR being the most sensitive tool. We would recommend the implementation of the ISAR in the ED setting to support clinicians in identifying older adults most likely to benefit from specialised geriatric assessment and intervention., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Using data from 67 Ugandan human immunodeficiency virus (HIV) clinics (July 2019-January 2022), we report a 40% (1005/1662) reduction in the number of people with HIV presenting to care after August 2021 compared to prepandemic levels, with a greater proportion presenting with advanced HIV disease (20% vs 16% in the pre-coronavirus disease 2019 period)., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Health literacy (HL) is a critical asset for 21st century learners to possess given its positive impact on health outcomes and educational attainment. Concerningly, HL is an area that primary school teachers report having a lack of understanding, confidence, and ability to teach. The HealthLit4Kids initiative aimed to address this issue through a series of teacher professional development (PD) workshops. To evaluate how teachers experienced the PD, teacher evaluations collected at the completion of each of the workshops were analysed using a mixed methods approach. According to the teachers, the PD had improved their understanding of HL, including how to implement it into their practice. The study also found that the teachers perceived that collaborative practice was a key strength of the programme, and that at the end of the PD, teachers described valuing HL more in their practice. Teachers reported time as a major barrier to them implementing the professional learning and suggested further resources could help to mitigate this barrier. Additional research is required to help substantiate the claims made in this research. This study also highlights the critical need for additional HL resources for primary school teachers., (© The Author(s) 2022. Published by Oxford University Press.)

Background and Hypothesis: Cognitive remediation (CR) benefits cognition and functioning in psychosis but we do not know the optimal level of therapist contact, so we evaluated the potential benefits of different CR modes., Study Design: A multi-arm, multi-center, single-blinded, adaptive trial of therapist-supported CR. Participants from 11 NHS early intervention psychosis services were independently randomized to Independent, Group, One-to-One, or Treatment-as-usual (TAU). The primary outcome was functional recovery (Goal Attainment Scale [GAS]) at 15-weeks post randomization. Independent and TAU arms were closed after an interim analysis, and three informative contrasts tested (Group vs One-to-One, Independent vs TAU, Group + One-to-One vs TAU). Health economic analyses considered the cost per Quality Adjusted Life Year (QALY). All analyses used intention-to-treat principles., Study Results: We analyzed 377 participants (65 Independent, 134 Group, 112 One-to-One, 66 TAU). GAS did not differ for Group vs One-to-One: Cohen's d: 0.07, -0.25 to 0.40 95% CI, P = .655; Independent vs TAU: Cohen's d: 0.07, -0.41 to 0.55 95% CI, P = .777. GAS and the cognitive score improved for Group + One-to-One vs TAU favoring CR (GAS: Cohen's d: 0.57, 0.19-0.96 95% CI, P = .003; Cognitive score: Cohens d: 0.28, 0.07-0.48 95% CI, P = .008). The QALY costs were £4306 for Group vs TAU and £3170 for One-to-One vs TAU. Adverse events did not differ between treatment methods and no serious adverse events were related to treatment., Conclusions: Both active therapist methods provided cost-effective treatment benefiting functional recovery in early psychosis and should be adopted within services. Some individuals benefited more than others so needs further investigation., Trial Registration: ISRCTN14678860 https://doi.org/10.1186/ISRCTN14678860Now closed., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.)

Objective: Increased social risk data collection in health care settings presents new opportunities to apply this information to improve patient outcomes. Clinical decision support (CDS) tools can support these applications. We conducted a participatory engagement process to develop electronic health record (EHR)-based CDS tools to facilitate social risk-informed care plan adjustments in community health centers (CHCs)., Materials and Methods: We identified potential care plan adaptations through systematic reviews of hypertension and diabetes clinical guidelines. The results were used to inform an engagement process in which CHC staff and patients provided feedback on potential adjustments identified in the guideline reviews and on tool form and functions that could help CHC teams implement these suggested adjustments for patients with social risks., Results: Partners universally prioritized tools for social risk screening and documentation. Additional high-priority content included adjusting medication costs and changing follow-up plans based on reported social risks. Most content recommendations reflected partners' interests in encouraging provider-patient dialogue about care plan adaptations specific to patients' social needs. Partners recommended CDS tool functions such as alerts and shortcuts to facilitate and efficiently document social risk-informed care plan adjustments., Discussion and Conclusion: CDS tools were designed to support CHC providers and staff to more consistently tailor care based on information about patients' social context and thereby enhance patients' ability to adhere to care plans. While such adjustments occur on an ad hoc basis in many care settings, these are among the first tools designed both to systematize and document these activities., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Despite promising results from individual-level studies, state-level studies of the effectiveness of comprehensive background-check (CBC) policies in reducing firearm fatalities have yielded null results in multiple states. These prior studies focused on CBC laws adopted in the 1990s, when record keeping was far less complete. We estimated the effect of the implementation of CBC policies on state-level firearm homicide and suicide rates in states implementing CBC policies from 2013 to 2015 (Colorado, Delaware, Oregon, and Washington). We compared age-adjusted firearm homicide and suicide rates, measured annually from 15 years prior to policy implementation until 2019, in each treated state to rates in control groups constructed using the synthetic control group method. Differences in firearm homicide rates for Colorado, Oregon, and Washington post treatment were all small (0.09 to 0.18 per 100,000 residents per year) and not well distinguished from natural variation. Oregon had on average 0.80 per 100,000 fewer firearm suicides per year than did synthetic Oregon post treatment. However, these results were inconsistent across modeling approaches and not well distinguished from natural variation. Our models produced poor fit for Delaware. Coupled with previous null results from Indiana, California, Maryland, Pennsylvania, and Tennessee, the present results suggest that extending background check requirements to private transfers alone and implementing these policies as is currently done is not sufficient to achieve significant state-level reductions in firearm fatalities., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

Objectives: Racial/ethnic disparities have been found in prior literature examining enrolment in Medicare medication therapy management programs. However, those studies were based on various eligibility scenarios because enrolment data were unavailable. This study tested for potential disparities in enrolment using actual MTM enrolment data., Methods: Medicare Parts A&B claims, Medication Therapy Management Data Files, and the Area Health Resources File from 2013 to 2014 and 2016 to 2017 were analysed in this retrospective analysis. An adjusted logistic regression compared odds of enrolment between racial/ethnic minorities and non-Hispanic Whites (Whites) in the total sample and subpopulations with diabetes, hypertension, or hyperlipidaemia. Trends in disparities were analysed by including interaction terms in regressions between dummy variables for race/ethnic minority groups and period 2016-2017., Key Findings: Disparities in MTM enrolment were detected between Blacks and Whites with diabetes in 2013-2014 (Odds Ratio = 0.78, 95% Confidence Interval = 0.75-0.81). This disparity improved from 2013-2014 to 2016-2017 for Blacks (Odds Ratio=1.08, 95% Confidence Interval = 1.04-1.11) but persisted in 2016-2017 (Odds Ratio = 0.84, 95% Confidence Interval = 0.81-0.87). A disparity was identified between Blacks and Whites with hypertension in 2013-2014 (Odds Ratio = 0.92, 95% Confidence Interval = 0.89-0.95) but not in 2016-2017. Enrolment for all groups, however, declined between periods. For example, in the total sample, the odds of enrolment declined from 2013-2014 to 2016-2017 by 22% (Odds Ratio=0.78, 95% Confidence Interval=0.75-0.81)., Conclusions: Racial disparities in MTM enrolment were found between Blacks and Whites among Medicare beneficiaries with diabetes in both periods and among individuals with hypertension in 2013-2014. As overall enrolment fell between periods, concerns about program enrolment remain., Competing Interests: Joseph Garuccio: None. Chi Chun Steve Tsang: None. Jim Y. Wan: None. Ya Chen Tina Shih: Received consulting fees, travel, and accommodations for serving on a grants review panel for Pfizer Inc and an advisory board for AstraZeneca in 2019. Marie A. Chisholm-Burns: Received funding from Carlos and Marguerite Mason Trust. Samuel Dagogo-Jack: Led clinical trials for AstraZeneca, Boehringer Ingelheim, and Novo Nordisk, Inc., received consulting fees from AstraZeneca, Boehringer Ingelheim, Janssen, Merck & Co. Inc., and Sanofi, and has equity interests in Jana Care, Inc. and Aerami Therapeutics. William C. Cushman: Received grant funding from Eli Lilly. Xiaobei Dong: None. Jamie Browning: None. Rose Zeng: None. Junling Wang: Received funding from AbbVie, Curo, Bristol Myers Squibb, Pfizer, and Pharmaceutical Research and Manufacturers of America (PhRMA), and serves on the Heath Outcomes Research Advisor Committee of the PhRMA Foundation., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Four-and-a-half LIM domains 1 (FHL1) is a muscle-specific protein. Autoantibodies against FHL1 were recently discovered in adults with idiopathic inflammatory myopathies (IIMs) and were found to be associated with clinical features and outcomes indicative of increased disease severity. Anti-FHL1 autoantibodies have not been described in children. Here, the prevalence and clinical features associated with anti-FHL1 autoantibodies were examined in a large North American cohort of juvenile patients with IIM., Methods: Sera from 338 juvenile IIM patients and 91 juvenile healthy controls were screened for anti-FHL1 autoantibodies by ELISA. Clinical characteristics and HLA alleles of those with and without anti-FHL1 autoantibodies were compared among those with juvenile IIM., Results: Anti-FHL1 autoantibodies were present in 10.9% of juvenile IIM patients and 1.1% of controls. The frequency of anti-FHL1 autoantibodies among clinical and serologic subgroups did not differ. A higher percentage of Asian patients had anti-FHL1 autoantibodies (11% vs 0.7%; P = 0.002). Myositis-associated autoantibodies (MAAs) [odds ratio (OR) 2.09 (CI 1.03, 4.32)], anti-Ro52 autoantibodies specifically [OR 4.17 (CI 1.83, 9.37)] and V-sign rash [OR 2.59 (CI 1.22, 5.40)] were associated with anti-FHL1 autoantibodies. There were no differences in other features or markers of disease severity. No HLA associations with anti-FHL1 autoantibodies in Caucasian myositis patients were identified., Conclusion: Anti-FHL1 autoantibodies are present in ∼11% of juvenile IIM patients and commonly co-occur with MAAs, including anti-Ro52 autoantibodies. In contrast to adult IIM, anti-FHL1 autoantibodies in juvenile myositis are associated with V-sign rash but not with other distinctive clinical features or worse outcomes., (Published by Oxford University Press on behalf of the British Society for Rheumatology 2022.)

Background: Persistent genital arousal disorder/genitopelvic dysesthesia (PGAD/GPD) is characterized by distressing, abnormal genitopelvic sensations, especially unwanted arousal. In a subgroup of patients with PGAD/GPD, cauda equina Tarlov cyst-induced sacral radiculopathy has been reported to trigger the disorder. In our evaluation of lumbosacral magnetic resonance images in patients with PGAD/GPD and suspected sacral radiculopathy, some had no Tarlov cysts but showed lumbosacral disc annular tear pathology., Aim: The aims were 2-fold: (1) to utilize a novel multidisciplinary step-care management algorithm designed to identify a subgroup of patients with PGAD/GPD and lumbosacral annular tear-induced sacral radiculopathy who could benefit from lumbar endoscopic spine surgery (LESS) and (2) to evaluate long-term safety and efficacy of LESS., Methods: Clinical data were collected on patients with PGAD/GPD who underwent LESS between 2016 and 2020 with at least 1-year follow-up. LESS was indicated because all had lumbosacral annular tear-induced sacral radiculopathy confirmed by our multidisciplinary management algorithm that included the following: step A, a detailed psychosocial and medical history; step B, noninvasive assessments for sacral radiculopathy; step C, targeted diagnostic transforaminal epidural spinal injections resulting in a temporary, clinically significant reduction of PGAD/GPD symptoms; and step D, surgical intervention with LESS and postoperative follow-up., Outcomes: Treatment outcome was based on the validated Patient Global Impression of Improvement, measured at postoperative intervals., Results: Our cohort included 15 cisgendered women and 5 cisgendered men (mean ± SD age, 40.3 ± 16.8 years) with PGAD/GPD who fulfilled the criteria of lumbosacral annular tear-induced sacral radiculopathy based on our multidisciplinary management algorithm. Patients were followed for an average of 20 months (range, 12-37) post-LESS. Lumbosacral annular tear pathology was identified at multiple levels, the most common being L4-L5 and L5-S1. Twenty-two LESS procedures were performed in 20 patients. Overall, 80% (16/20) reported improvement on the Patient Global Impression of Improvement; 65% (13/20) reported improvement as much better or very much better. All patients were discharged the same day. There were no surgical complications., Clinical Implications: Among the many recognized triggers for PGAD/GPD, this subgroup exhibited lumbosacral annular tear-induced sacral radiculopathy and experienced long-term alleviation of symptoms by LESS., Strengths and Limitations: Strengths include long-term post-surgical follow-up and demonstration that LESS effectively treats patients with PGAD/GPD who have lumbosacral annular tear-induced sacral radiculopathy, as established by a multidisciplinary step-care management algorithm. Limitations include the small study cohort and the unavailability of a clinical measure specific for PGAD/GPD., Conclusion: LESS is safe and effective in treating patients with PGAD/GPD who are diagnosed with lumbosacral annular tear-induced sacral radiculopathy., (© The Author(s) 2023. Published by Oxford University Press on behalf of The International Society of Sexual Medicine.)

Background: It is unknown whether persons with symptomatic cryptococcal meningitis detected during routine blood cryptococcal antigen (CrAg) screening have better survival than persons presenting with overt meningitis., Methods: We prospectively enrolled Ugandans with HIV and cryptocococcal meningitis from December 2018 to December 2021. Participants were treated with amphotericin-based combination therapy. We compared outcomes between persons who were CrAg screened then referred to hospital with those presenting directly to the hospital with symptomatic meningitis., Results: Among 489 participants with cryptococcal meningitis, 40% (194/489) received blood CrAg screening and were referred to hospital (median time to referral 2 days; interquartile range [IQR], 1-6). CrAg-screened persons referred to hospital had lower 14-day mortality than non-CrAg-screened persons who presented directly to hospital with symptomatic meningitis (12% vs 21%; hazard ratio, .51; 95% confidence interval, .32-.83; P = .006). Fewer CrAg-screened participants had altered mental status versus non-CrAg-screened participants (29% vs 41%; P = .03). CrAg-screened persons had lower quantitative cerebrospinal fluid (CSF) culture burden (median [IQR], 4570 [11-100 000] vs 26 900 [182-324 000] CFU/mL; P = .01) and lower CSF opening pressures (median [IQR], 190 [120-270] vs 225 [140-340] mmH2O; P = .004) compared with non-CrAg-screened persons., Conclusions: Survival from cryptococcal meningitis was higher in persons with prior CrAg screening than those without CrAg screening. Altered mental status was the most potent predictor for mortality in a multivariate model. We suggest that CrAg screening detects cryptococcal meningitis at an earlier stage, as evidenced by a favorable baseline risk profile and notably fewer persons with altered mental status., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)