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Background: Operative mortality for high-grade liver injury (HGLI) remains 42% to 66%, with near-universal mortality after retrohepatic caval injury. The objective of this study was to evaluate mortality and complications of operative and nonoperative management (OM and NOM) of HGLI at our institution, characterized by a trauma surgery-liver surgery collaborative approach to trauma care., Methods: This was an observational cohort study of adult patients (age ≥16) with HGLI (The American Association for Surgery of Trauma (AAST) grades IV and V) admitted to an urban level I trauma center from January 2010 to November 2021. Data were obtained from the electronic medical record and state trauma registry. Patients were categorized by management strategy: immediate OM or planned NOM. The primary outcome was 30-day mortality., Results: Our institution treated 179 patients with HGLI (78% blunt, 22% penetrating); 122 grade IV (68%) and 57 grade V (32%) injuries. All abdominal gunshot wounds and 49% of blunt injuries underwent initial OM; 51% of blunt injuries were managed initially by NOM. Procedures at the initial operation included hepatorrhaphy±packing (66.4%), nonanatomic resection (5.6%), segmentectomy (9.3%), and hepatic lobectomy (7.5%). Thirty-day mortality in the OM group was substantially lower than prior reports (23.4%). Operative mortality attributable to the liver injury was 15.7%. 19.4% of patients failed NOM with one death (1.4%)., Conclusion: We report an operative mortality of 23.4% for HGLI in a trauma care system characterized by a collaborative approach by trauma surgeons and liver surgeons., Level of Evidence: III., Competing Interests: None declared., (Copyright © Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Background: Frailty increases vulnerability to major health changes because of seemingly small health problems. It affects around 10% of people aged over 65.Older adults with frailty frequently have multiple long-term conditions, personal challenges, and social problems. Personalised Care Planning (PCP) based on 'goal-setting' and 'action planning' is a promising way to address the needs of older adults living with frailty., Aim: To identify and explore factors that influence the implementation of personalised care planning style interventions for older adults., Design & Setting: We conducted a scoping review and identified a small number of interventions that explicitly employed 'goal setting' and 'action planning'., Method: We used a range of sources to identify relevant material. We included all interventions inclusive of patients aged 65 and over and reported in English. We excluded end-of-life care interventions, group education and/or, those that did not involve one-to-one engagement. We explored all related papers which described, examined, or discussed implementation. We constructed a thematic framework in NVivo 11. Findings were narratively synthesised., Results: We identified 18 potentially relevant PCP-style interventions. Within these, were seven main categories of potentially modifiable influences relevant to older adults with frailty related to: Primary care engagement; Delivery staff characteristics; Training; Client engagement; Collaborative working; Organisation and management; Systems., Conclusions: Many modifiable factors can influence the implementation of PCP. We identified several influences which have informed the development and implementation of a novel intervention for older adults with frailty, PROSPER., (Copyright © 2024, The Authors.)

Background -Smoking is associated with arrhythmia and sudden cardiac death, but the biological mechanisms remain unclear. In electrocardiogram (ECG) recordings abnormal durations of ventricular repolarization (QT interval), atrial depolarization (P wave), and atrioventricular depolarization (PR interval and segment), predict cardiac arrhythmia and mortality. Previous analyses of the National Health and Nutrition Examination Survey (NHANES) database for associations between smoking and ECG abnormalities were incomplete. To elucidate how smoking affects cardiac excitation, we assessed in a nationally representative sample (NHANES III) the association between serum cotinine and P duration, PR interval, PR segment, rate-corrected QT (QTc), QRS duration, and JT interval. Methods and Results-We analyzed data from 5,653 adults using survey-weighted multinomial logistic regression to estimate associations between tobacco use (> 15 ng/ml serum cotinine) and short (< 5th percentile) or long (> 95th percentile) ECG intervals, relative to reference (5-95th percentile). After adjustment for demographics, risk factors, and conduction-altering medications, smoking was associated with a higher odds of short PR interval, PR segment, and QRS, and long JT. Broader effects of smoking on ECG were also assessed by survey-weighted linear regression of continuous cotinine and ECG, which revealed cotinine inversely associated with PR segment and QTc. Over a 22-year follow-up, many ECG abnormalities predicted cardiovascular mortality in smokers, including long JT, QRS, and QTc, and short QRS, whereas only short JT predicted mortality in nonsmokers. Conclusions -Smoking increases likelihood for rapid atrioventricular and ventricular depolarization and slow ventricular repolarization, which may promote cardiac arrhythmia and mortality., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Epigenetic control of cell fates is a critical determinant to maintain cell type stability and permit differentiation during embryonic development. However, the epigenetic control mechanisms are not well understood. Here, it is shown that the histone acetyltransferase reader protein BRD8 impairs the conversion of primed mouse EpiSCs (epiblast stem cells) to naive mouse ESCs (embryonic stem cells). BRD8 works by maintaining histone acetylation on promoters and transcribed gene bodies. BRD8 is responsible for maintaining open chromatin at somatic genes, and histone acetylation at naive-specific genes. When Brd8 expression is reduced, chromatin accessibility is unchanged at primed-specific genes, but histone acetylation is reduced. Conversely, naive-specific genes has reduced repressive chromatin marks and acquired accessible chromatin more rapidly during the cell type conversion. It is shown that this process requires active histone deacetylation to promote the conversion of primed to naive. This data supports a model for BRD8 reading histone acetylation to accurately localize the genome-wide binding of the histone acetyltransferase KAT5. Overall, this study shows how the reading of the histone acetylation state by BRD8 maintains cell type stability and both enables and impairs stem cell differentiation., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Objective: This study aimed to examine how Indigenous patients and biomedical healthcare providers understand and experience the Indigenous wellness services at a hospital in the Northwest Territories., Methods: The qualitative study (May 2018-June 2022) was overseen by a regional Indigenous Community Advisory Committee. Guided by Two-Eyed Seeing and post-colonial theory, the study employed a community-engaged research design, and included two strategies for data generation: (1) interviews with Indigenous Elders, patient advocates, biomedical healthcare providers, policy makers, and hospital administrators (n = 41), and (2) iterative sharing circles with Indigenous Elders (n = 4). Data from the interviews and first sharing circle were transcribed, thematically analyzed, and presented to the sharing circle Elders for validation., Results: The study revealed three overarching and related themes: (1) Elders and patient advocates emphasized that while the Indigenous wellness services at the hospital play a pivotal role connecting patients with cultural supports, the hospital was still not effectively bringing Indigenous healing practices into hospital care; (2) participants identified that structural factors (i.e., policy and governance decisions) shaped patients' experiences with the wellness services; and (3) participants underscored that deeply rooted forces (i.e., racism, colonialism, and biomedical dominance) inhibit the integration of Indigenous healing practices., Conclusion: The findings extend understandings of hospital-based Indigenous wellness services by surfacing relationships between deeply rooted forces, organizational structures, and Indigenous patients' experiences. Altogether, they suggest that to advance care for Indigenous patients and improve the integration of Indigenous healing practices, a system-wide transformation is necessary, which includes Indigenous governance at the hospital and a recognition of the value of Indigenous healing practices., Competing Interests: Declarations Ethics approval This study received ethics approval from the University of Toronto’s Research Ethics Board (protocol no. 16705), a northern research licence from Aurora Research Institute (license no. 38649), and a research agreement with the Northwest Territories Health and Social Services Authority (NTHSSA). Consent to participate Informed consent was obtained from all individual participants included in the study. Consent for publication Not applicable. Conflict of interest The authors declare no competing interests., (© 2024. The Author(s).)

The routine introduction of novel anti-inflammatory therapies into the management algorithms of patients with Crohn's disease over the last 2 decades has not substantially changed the likelihood of ultimate surgery. Rather it has delayed the operative need and altered the presentation phenotype. The prospect of complications continues to remain high in this modern era but depending upon the cohort assessed, it remains difficult to make strict comparisons between individual specialist centres. Those patients who present rather late after their diagnosis with a septic complication like an intra-abdominal abscess and a penetrating/fistulizing pattern of disease are more likely to have a complicated course particularly if they have clinical features such as difficult percutaneous access to the collection or multilocularity both of which can make preoperative drainage unsuccessful. Equally, those cases with extensive adhesions where an initial laparoscopic approach needs open conversion and where there is an extended operative time, unsurprisingly will suffer more significant complications that impact their length of hospital stay. The need for a protective stoma also introduces its own derivative costs, utilizing a range of health resources as well as resulting in important alterations in quality of life outcomes. Having established the parameters of the problem can the statistical analysis of the available data identify high-risk cases, promote the notion of centralization of specialist services or improve the allocation of disease-specific health expenditure?, Competing Interests: Conflict-of-interest statement: The author reports no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Lisdexamfetamine dimesylate, a prodrug stimulant, appears to effectively treat Attention-Deficit/Hyperactivity Disorder (ADHD) in children and adults. However, an analysis of the treatment effects of the two subscales (inattentiveness and hyperactivity) within the ADHD Rating Scale-IV (ADHD-RS-IV) has not yet been done to determine if clinical significance may be attributed to either one. Nor has there been a meta-analysis of the individual doses of lisdexamfetamine dimesylate. The current meta-analysis utilizes MEDLINE, Embase, Cochrane, PubMed, and clinicaltrials.gov to identify peer-reviewed studies. Selected studies were eligible if they met the following criteria: English language, randomized-controlled trials, and utilized the ADHD-RS-IV scale to assess the efficacy of lisdexamfetamine on treating ADHD in either children or adults. The primary studies utilized were published between January 2007 and April 2024. Many of these studies calculate effect sizes based on several dosages pooled together rather than by individual dosages. We conducted a random-effects meta-analysis to estimate the effect sizes for these pooled dosages on the full ADHD-RS-IV scale and its subscales, as well as to calculate effect sizes on the same scales based on the individual dosages. Our main outcome measures are the ADHD-RS-IV scale and its subscales in individual doses and pooled results in both children and adults. Adverse events during treatment were also analyzed based on stratified dosages. Eleven publications met our inclusion criteria. The analyses indicate that compared to placebo, lisdexamfetamine effectively alleviates the symptoms outlined by the ADHD-RS-IV. Moreover, there are no differences in the individual subscales or in the safety profile. Lisdexamfetamine demonstrates efficacy in treating the symptoms of ADHD, but we report that differing dosages did not yield significant differences in ADHD symptom management., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Rutledge-Jukes et al.)

Background: Trauma systems save lives by coordinating timely and effective responses to injury. However, trauma system effectiveness varies geographically, with worse outcomes observed in rural settings. Prior data suggest that undertriage may play a role in this disparity. Our aim was to explore potential driving factors for decision making among clinicians for undertriaged trauma patients., Methods: We performed a retrospective analysis of the National Emergency Medical Services Information System database among patients who met physiologic or anatomic national field triage guideline criteria for transport to the highest level of trauma center. Undertriage was defined as transport to a non-level I/II trauma center. Multivariable logistic regression was used to determine demographic, injury, and system characteristics associated with undertriage. Undertriaged patients were then categorized into "recognized" and "unrecognized" groups using the documented reason for transport destination to identify underlying factors associated with undertriage., Results: A total of 36,094 patients were analyzed. Patients in urban areas were more likely to be transported to a destination based on protocol rather than the closest available facility. As expected, patients injured in urban regions were less likely to be undertriaged than their suburban (adjusted odds ratio [aOR], 2.69; 95% confidence interval [95% CI], 2.21-3.31), rural (aOR, 2.71; 95% CI, 2.28-3.21), and wilderness counterparts (aOR, 3.99; 95% CI, 2.93-5.45). The strongest predictor of undertriage was patient/family choice (aOR, 6.29; 5.28-7.50), followed by closest facility (aOR, 5.49; 95% CI, 4.91-6.13) as the reason for hospital selection. Nonurban settings had over twice the odds of recognizing the presence of triage criteria among undertriaged patients (p < 0.05)., Conclusion: Patients with injuries in nonurban settings and those with less apparent causes of severe injury are more likely to experience undertriage. By analyzing how prehospital clinicians choose transport destinations, we identified patient and system factors associated with undertriage. Targeting these at-risk demographics and contributing factors may help alleviate regional disparities in undertriage., Level of Evidence: Diagnostic; Level IV., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: This paper outlines the engagement process that was used to develop the Northwest Territories Alcohol Strategy, based on a recommendation by the developers of the Canadian Alcohol Policy Evaluation report, and how this informed the final actions in the strategy., Methods: A literature review, four targeted engagement activities, and iterative validation by advisory groups and community and Indigenous leadership were used to evaluate, modify, or reject the original recommendations and develop the final actions that were included in the NWT Alcohol Strategy., Results: There are fourteen original CAPE recommendations, four of which had already been implemented in the Northwest Territories before the development of the strategy. On completion of the process, four recommendations had already been implemented in the NWT. Two recommendations were included in the strategy without changes, two were adapted for use in the strategy, and six were not included. One stand-alone alcohol policy measure was created and included., Conclusion: Alcohol strategies are dependent on a variety of contextual factors. Developers need to take into consideration the unique geography, political climate, and cultural context of the region for which they are being developed, in order to produce a strategy that is applicable, acceptable, and feasible at the community level., (© 2024. The Author(s).)

Introduction: Work-related musculoskeletal disorders (WMSDs) are disorders of the musculoskeletal system that have the highest prevalence among workers worldwide. Workers in gas stations usually work in poor ergonomic working conditions, including prolonged standing and repetitive posturing., Objective: The study aimed to investigate the prevalence of WMSDs and fatigue and to identify the predictors of WMSDs among gas station workers., Design: The present study was a cross-sectional study., Setting and Participants: 2962 gas station workers from an oil and gas company in China, with ages ranging from 17 to 75 years old, 55.47% female., Results: The prevalence of WMSDs within the 12 months prior to the study was 73.23%, with the highest prevalence in the neck, shoulders, ankles and feet. Furthermore, a correlation was observed between fatigue, stress and WMSDs. Fatigue and job role were the strongest predictors of WMSDs, with an OR range of 2.211-3.413., Conclusions: This research identified the detrimental impact of WMSDs and fatigue on gas station workers, indicating the critical need for interventions to reduce WMSDs and relieve fatigue., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Genome sequencing (GS)-specific diagnostic rates in prospective tightly ascertained exome sequencing (ES)-negative intellectual disability (ID) cohorts have not been reported extensively., Methods: ES, GS, epigenetic signatures, and long-read sequencing diagnoses were assessed in 74 trios with at least moderate ID., Results: The ES diagnostic yield was 42 of 74 (57%). GS diagnoses were made in 9 of 32 (28%) ES-unresolved families. Repeated ES with a contemporary pipeline on the GS-diagnosed families identified 8 of 9 single-nucleotide variations/copy-number variations undetected in older ES, confirming a GS-unique diagnostic rate of 1 in 32 (3%). Episignatures contributed diagnostic information in 9% with GS corroboration in 1 of 32 (3%) and diagnostic clues in 2 of 32 (6%). A genetic etiology for ID was detected in 51 of 74 (69%) families. Twelve candidate disease genes were identified. Contemporary ES followed by GS cost US$4976 (95% CI: $3704; $6969) per diagnosis and first-line GS at a cost of $7062 (95% CI: $6210; $8475) per diagnosis., Conclusion: Performing GS only in ID trios would be cost equivalent to ES if GS were available at $2435, about a 60% reduction from current prices. This study demonstrates that first-line GS achieves higher diagnostic rate than contemporary ES but at a higher cost., Competing Interests: Conflict of Interest The authors declare no conflicts of interest., (Copyright © 2024 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Although several biomarkers have been studied in thromboembolic stroke, measuring the balance between thrombus formation and thrombolysis and data on its role in predicting stroke and atrial fibrillation (AF)-related stroke is limited. We sought to assess atherothrombotic biomarkers grouped into composite factors that reflect thrombotic and thrombolytic potential, and the balance between these factors as it relates to incident stroke or transient ischemic attack (TIA) and stroke/TIA in AF., Methods: A Thrombotic Factor, derived from fibrinogen, plasmin-antiplasmin complex, factor VIII, D-dimer, and lipoprotein(a); and a Thrombolytic Factor, derived from plasminogen and oxidized phospholipids on plasminogen, were evaluated at baseline in 5,764 Multi-Ethnic Study of Atherosclerosis (MESA) participants. We evaluated the association between these two factors representative of thrombotic and thrombolytic potential and incident stroke/TIA (n = 402), and AF-related stroke/TIA (n = 82) over a median of 13.9 and 3.7 years, respectively. Cox proportional hazard models adjusted for medication use, cardiovascular risk factors and CHA 2 DS 2 -VASc score were utilized. Harrell's C-index was estimated to evaluate model performance., Results: In models including both factors, Thrombotic Factor was positively while Thrombolytic Factor was inversely associated with incident stroke/TIA and AF-related stroke/TIA. Incorporating these factors along with the CHA 2 DS 2 -VASc in adjusted models resulted in a small improvement in risk prediction of incident stroke/TIA and AF-related stroke/TIA compared to models without the factors (C-index from 0.697 to 0.704, and from 0.657 to 0.675, respectively)., Conclusions: Composite biomarker factors, representative of the balance between thrombotic and thrombolytic propensity, provided an improvement in predicting stroke/TIA beyond CHA 2 DS 2 -VASc score., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Recent data show high school students from racial and ethnic minority (REM) backgrounds in the United States confront a twofold challenge, marked by the highest rates of firearm-related homicides since 1994 and increased youth substance use. The pandemic increased online and telehealth usage opportunities for at-risk REM youth. Therefore, this study investigated (1) the frequency and prevalence of co-occurring youth violence and substance use among REM adolescents, (2) racial/ethnic, age, and natal sex (as gender data was not collected) differences in patterns and trends in co-occurring youth violence and substance use among REM adolescents, and (3) the relationship between these syndemic issues and REM adolescent mental telehealth use during the pandemic., Methods: Data was sourced from a nationally representative sample of U.S. 9th-12th students (n = 3241) who completed the CDC's 2021 Adolescent and Behavioral Experiences Survey (ABES). Using univariate (frequency distribution), bivariate (Pearson's chi-squared test), and multivariate logistic regression models, we examined seven violence victimization outcomes, four violence perpetration outcomes, two family violence outcomes, and six substance use outcomes and their associations with telehealth use for mental health (dependent variable) among REM adolescents., Results: This sample was primarily female (50.7%), Black or African American (48.3%), Hispanic or Latinx (20.6%), and identified as straight or heterosexual (69.5%). The study found significant sex-based differences in violence perpetration/victimization, substance use, and telehealth use for mental health. In general, mental telehealth use was significantly associated with substance use among REM adolescents (cigarette smoking, vaping, alcohol, marijuana, prescription meds, and illicit drug use) (p-value = .001). Mental telehealth use was also significantly associated with all peer and family violence outcomes (p < 0.001). Controlling for covariates, gun carrying was associated with 4.8 times higher odds of using mental telehealth. Students in a physical fight or carrying a weapon (gun, knife, or club) on school property had 2.45 times and 8.09 times the odds of utilizing mental telehealth. Bullied students were 2.5 times more likely to use mental telehealth (p-value < 0.05). Illicit drug use (cocaine, heroin, methamphetamines, and ecstasy) was associated with a higher likelihood of mental telehealth use (AOR = 1.3, p-value = .05)., Conclusion: Our results suggest crucial insights for shaping violence and substance use prevention strategies, with implications for the future of online and telehealth behavioral services. Mental telehealth help-seeking emerges as a crucial avenue for supporting adolescents affected by violence and substance use, especially when they face obstacles to accessing traditional services. It can work in tandem with in-person services to address these challenges., (© 2024. W. Montague Cobb-NMA Health Institute.)

This study introduces a hybrid analytical super-resolution (SR) pipeline aimed at enhancing the resolution of medical magnetic resonance imaging (MRI) scans. The primary objective is to overcome the limitations of clinical MRI resolution without the need for additional expensive hardware. The proposed pipeline involves three key steps: pre-processing to re-slice and register the image stacks; SR reconstruction to combine information from three orthogonal image stacks to generate a high-resolution image stack; and post-processing using an artefact reduction convolutional neural network (ARCNN) to reduce the block artefacts introduced during SR reconstruction. The workflow was validated on a dataset of six knee MRIs obtained at high resolution using various sequences. Quantitative analysis of the method revealed promising results, showing an average mean error of 1.40 ± 2.22% in voxel intensities between the SR denoised images and the original high-resolution images. Qualitatively, the method improved out-of-plane resolution while preserving in-plane image quality. The hybrid SR pipeline also displayed robustness across different MRI sequences, demonstrating potential for clinical application in orthopaedics and beyond. Although computationally intensive, this method offers a viable alternative to costly hardware upgrades and holds promise for improving diagnostic accuracy and generating more anatomically accurate models of the human body.

Introduction: The skin of patients with atopic dermatitis (AD) is characterised by elevated pH. As a central homeostatic regulator, an increased pH accelerates desquamation and suppresses lipid processing, resulting in diminished skin barrier function. The aim of this study was to determine whether a novel zinc lactobionate emollient cream can strengthen the skin barrier by lowering skin surface pH., Methods: A double-blind, forearm-controlled cohort study was undertaken in patients with AD. Participants applied the test cream to one forearm and a vehicle cream to the other (randomised allocation) twice daily for 56 days. Skin surface pH and barrier function (primary outcomes) were assessed at baseline and after 28 days and 56 days of treatment, amongst other tests., Results: A total of 23 adults with AD completed the study. During and after treatment, a sustained difference in skin surface pH was observed between areas treated with the test cream and vehicle (4.50 ± 0.38 versus 5.25 ± 0.54, respectively, p < 0.0001). This was associated with significantly reduced transepidermal water loss (TEWL) on the test cream treated areas compared with control (9.71 ± 2.47 versus 11.20 ± 3.62 g/m 2 /h, p = 0.0005). Improvements in skin barrier integrity, skin sensitivity to sodium lauryl sulphate, skin hydration, and chymotrypsin-like protease activity were all observed at sites treated with the test cream compared with the control., Conclusion: Maintenance of an acidic skin surface pH and delivery of physiologic lipids are beneficial for skin health and may help improve AD control by reducing sensitivity to irritants and allergens., (© 2024. The Author(s).)

Introduction: Pelvic mesh was first used for stress urinary incontinence in 1998 following which its usage rapidly expanded to include treatment of pelvic organ prolapse. Numerous complications relating to mesh insertion soon became apparent, culminating in the Independent Medicines and Medical Devices Safety: First Do No Harm Report published by Baroness Cumberlege in 2020. Following this report, the UCLH London Complex Mesh Centre funded by NHS England, was one of a small number of specialist centres set up for mesh-injured women. The Pelvic Pain service of the Pain Management Centre at UCLH provides a service for patients attending the London Complex Mesh Centre. The aim of our study was to distinguish the differing needs of mesh-injured women from those with chronic pelvic pain by comparing patient-reported outcome measures between these two cohorts., Methods: Distribution of data was calculated using the D'Agostino-Pearson normality test. Mann-Whitney tests were used to ascertain statistical difference between the two cohorts. Ethnicity was compared between groups using Fisher's exact test. Quantile regression models were used to assess whether differences in medians between groups remained after adjustment for age and ethnicity. Statistical significance was set at p < .05., Results: Patients with mesh were significantly older than those with chronic pelvic pain and were more likely to be of white ethnicity. After adjustment for age and ethnicity, analysis revealed that bladder interference, sex interference and DAPOS A were significantly higher amongst mesh-injured women, whereas GP and hospital admissions were significantly lower., Discussion: Our data shows the importance of mesh-injured women having access to pain management services with pathways of care integrated within women's and mental health services. It is essential that these programmes include support to discuss ways of returning to sexual relationships and have models to address anxiety such as graded exposure and psychological input., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Background—: Smoking is associated with arrhythmia and sudden cardiac death, but the biological mechanisms remain unclear. Abnormal electrocardiogram (ECG) durations of ventricular repolarization (QT interval), atrial depolarization (P wave), and atrioventricular depolarization (PR interval and segment), predict cardiac arrhythmia and mortality., Objectives—: To elucidate how smoking affects cardiac excitation, we assessed in a nationally representative sample (NHANES III) associations between cotinine, abnormalities in P duration, PR interval, PR segment, rate-corrected QT (QTc), QRS duration, and JT interval, and long-term mortality., Methods—: We analyzed data from 5,633 adults using survey-weighted multinomial logistic regression to estimate associations between tobacco use (>15 ng/ml serum cotinine) and short (<5th percentile) or long (>95th percentile) ECG intervals, relative to reference (5 - 95th percentile)., Results—: After adjustment for demographics, risk factors, and conduction-altering medications, smoking was associated with a higher odds of short PR interval, PR segment, and QRS, and long JT. Broader ECG effects of smoking were also assessed by survey-weighted linear regression of continuous cotinine and ECG intervals, which revealed cotinine inversely associated with PR segment and QTc. Over a 22-year follow-up, many ECG abnormalities predicted cardiovascular mortality in smokers, including long JT, QRS, and QTc, and short QRS., Conclusions—: Smoking increases likelihood for rapid atrioventricular conduction, rapid ventricular depolarization, and slow ventricular repolarization. The ventricular electrophysiologic abnormalities associated with smoking also predict cardiovascular mortality in smokers; however, traditional ECG measures of cardiac risk like QTc can overlook these ventricular defects and their independent predictive value in smokers., Competing Interests: Competing interests The authors have no conflicts or competing interest to disclose.

Background: To improve the quality of care for Indigenous patients, local Indigenous leaders in the Northwest Territories, Canada have called for more culturally responsive models for Indigenous and biomedical healthcare collaboration at Stanton Territorial Hospital. Objective: This study examined how Indigenous patients and biomedical healthcare providers envision Indigenous healing practices working successfully with biomedical hospital care at Stanton Territorial Hospital. Methods: We carried out a qualitative study from May 2018 - June 2022. The study was overseen by an Indigenous Community Advisory Committee and was made up of two methods: (1) interviews ( n  = 41) with Indigenous Elders, patient advocates, and healthcare providers, and (2) sharing circles with four Indigenous Elders. Results: Participants' responses revealed three conceptual models for Indigenous and biomedical healthcare collaboration: the (1) integration; (2) independence; and (2) revisioning relationship models. In this article, we describe participants' proposed models and examine the extent to which each model is likely to improve care for Indigenous patients at Stanton Territorial Hospital. By surfacing new models for Indigenous and biomedical healthcare collaboration, the study findings deepen and extend understandings of hospital-based Indigenous wellness services and illuminate directions for future research.

Following a request from the European Commission, the EFSA Panel on Plant Health performed a quantitative pest risk assessment to assess whether the import of cut roses provides a pathway for the introduction of Thaumatotibia leucotreta (Lepidoptera: Tortricidae) into the EU. The assessment was limited to the entry and establishment steps. A pathway model was used to assess how many T. leucotreta individuals would survive and emerge as adults from commercial or household wastes in an EU NUTS2 region climatically suitable in a specific season. This pathway model for entry consisted of three components: a cut roses distribution model, a T. leucotreta developmental model and a waste model. Four scenarios of timing from initial disposal of the cut roses until waste treatment (3, 7, 14 and 28 days) were considered. The estimated median number of adults escaping per year from imported cut roses in all the climatically suitable NUTS2 regions of the EU varied from 49,867 (90% uncertainty between 5,298 and 234,393) up to 143,689 (90% uncertainty between 21,126 and 401,458) for the 3- and 28-day scenarios. Assuming that, on average, a successful mating will happen for every 435 escaping moths, the estimated median number of T. leucotreta mated females per year from imported cut roses in all the climatically suitable NUTS2 regions of the EU would vary from 115 (90% uncertainty between 12 and 538) up to 330 (90% uncertainty between 49 and 923) for the 3- and 28-day scenarios. Due to the extreme polyphagia of T. leucotreta , host availability will not be a limiting factor for establishment. Climatic suitability assessment, using a physiologically based demographic modelling approach, identified the coastline extending from the northwest of the Iberian Peninsula through the Mediterranean as area suitable for establishment of T. leucotreta . This assessment indicates that cut roses provide a pathway for the introduction of T. leucotreta into the EU., (© 2023 European Food Safety Authority. EFSA Journal published by Wiley‐VCH GmbH on behalf of European Food Safety Authority.)

Megachile amparo (González, Revista Colombiana De Entomología 32(1):93-96, 2006) is the only high Andean leaf-cutter bee reported in Colombia and is possibly endemic to the Colombian Andes. Although it is frequently observed, even in urban areas, its biology and ecology remain unknown. The present study aimed to describe detailed aspects of its bionomy. Trap-nests were installed on the Campus of the Nueva Granada University (Cajicá, Colombia) from June/2018 to March/2020. The trap-nests were wooden blocks (25 × 15 × 14 cm) with 30 cavities of Ø = 1 cm and different lengths (50 mm, 75 mm, and 100 mm) lined with waxed paper straws. During the observations, an increasing number of trap-nests were installed, increasing from 250 to 720 cavities. The trap-nests were monitored three times a week, recording both the date the start and end building by female. Most of the nest were maintained in the field to estimate the sex ratio, cell survival, and total development time under natural conditions. Thirty-two nests were removed at different times of the observation period to establish number of cells per nest, and cells built per female per day. We incubated 20 cells from different nests at 18 °C, 22 °C, 26 °C, and 32 °C to estimate the base temperature, thermal constant k (developmental time in degree days), and cell survival. Young cells of different positions were dissected and weighed to characterize food provision and brood cells. Computerized tomography-CT scans were performed in 30 brood cells to determine if diapause occurred during prepupal stage. Females nested 7- and 10-cm-long cavities and the number of cells per nest varied with cavity length. The brood cells had a length of 1.23 ± 0.12 cm and a diameter of 0.92 ± 0.05 cm. The female spends 1.17 ± 0.29 days to build a brood cell. Food provision varied according to the position of the brood cell in the nest. The adults of M. amparo present a marked seasonality being more active during dry months. Base temperature and thermal constant k were different for males and females. The sex ratio is female biased (1.9:1), and cell survival in the field was 89% with no cleptoparasites or predators recorded., (© 2023. Sociedade Entomológica do Brasil.)

Objective: Evaluate the association of survival with helicopter transport directly to a trauma center compared with ground transport to a non-trauma center (NTC) and subsequent transfer., Summary Background Data: Helicopter transport improves survival after injury. One potential mechanism is direct transport to a trauma center when the patient would otherwise be transported to an NTC for subsequent transfer., Methods: Scene patients 16 years and above with positive physiological or anatomic triage criteria within PTOS 2000-2017 were included. Patients transported directly to level I/II trauma centers by helicopter were compared with patients initially transported to an NTC by ground with a subsequent helicopter transfer to a level I/II trauma center. Propensity score matching was used to evaluate the association between direct helicopter transport and survival. Individual triage criteria were evaluated to identify patients most likely to benefit from direct helicopter transport., Results: In all, 36,830 patients were included. Direct helicopter transport was associated with a nearly 2-fold increase in odds of survival compared with NTC ground transport and subsequent transfer by helicopter (aOR 2.78; 95% CI 2.24-3.44, P <0.01). Triage criteria identifying patients with a survival benefit from direct helicopter transport included GCS≤13 (1.71; 1.22-2.41, P <0.01), hypotension (2.56; 1.39-4.71, P <0.01), abnormal respiratory rate (2.30; 1.36-3.89, P <0.01), paralysis (8.01; 2.03-31.69, P <0.01), hemothorax/pneumothorax (2.34; 1.36-4.05, P <0.01), and multisystem trauma (2.29; 1.08-4.84, P =0.03)., Conclusions: Direct trauma center access is a mechanism driving the survival benefit of helicopter transport. First responders should consider helicopter transport for patients meeting these criteria who would otherwise be transported to an NTC., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Our perception of time plays a critical role in nearly all daily activities and especially in sports. There are no studies that have investigated and compared time perception during exercise in young and older adults. Thus, this study aimed to compare the effects of exercise on time perception between younger and older adult populations. Thirty-three recreationally active participants were recruited and assigned to either the younger (university students, 9 males and 10 females) or older adults (>60 years, 8 males and 6 females). All participants completed four exercise conditions over two sessions on separate days: approximately 30-seconds of knee extensors 100%, 60% and 10% of maximum voluntary isometric contraction (MVIC), and control (no contractions). Prospective time perception was estimated (at 5-, 10-, 20-, and 30-seconds) at the beginning of each session and while performing the exercise. A main effect for condition (p < 0.001, d = 1.06) with subsequent post-hoc tests indicated participants significantly underestimated (estimated time was shorter than chronological time) time in all three exercise conditions compared to the control. There were no significant age group differences. In conclusion, exercise underestimated time estimates regardless of intensity or age. This questions the postulated intensity-dependent relationship between exercise and time perception. While older adults were expected to be less accurate in their time estimates, they may have been able to adopt alternative strategies for age-related changes in their internal clock, resulting in no significant age group differences., (© Journal of Sports Science and Medicine.)

Background: Prehospital resuscitation guidelines vary widely, and blood products, although likely superior, are not available for most patients in the prehospital setting. Our objective was to determine the prehospital crystalloid volume associated with the lowest mortality among patients in hemorrhagic shock., Study Design: This is a secondary analysis of the Prehospital Air Medical Plasma trial. Injured patients from the scene with hypotension and tachycardia or severe hypotension were included. Segmented regression and generalized additive models were used to evaluate nonlinear effects of prehospital crystalloid volume on 24-hour mortality. Logistic regression evaluated the association between risk-adjusted mortality and prehospital crystalloid volume ranges to identify optimal target volumes. Inverse propensity weighting was performed to account for patient heterogeneity., Results: There were 405 patients included. Segmented regression suggested the nadir of 24-hour mortality lay within 377 to 1,419 mL prehospital crystalloid. Generalized additive models suggested the nadir of 24-hour mortality lay within 242 to 1,333 mL prehospital crystalloid. A clinically operationalized range of 250 to 1,250 mL was selected based on these findings. Odds of 24-hour mortality were higher for patients receiving less than 250 mL (adjusted odds ratio [aOR] 2.46; 95% CI 1.31 to 4.83; p = 0.007) and greater than 1,250 mL (aOR 2.57; 95% CI 1.24 to 5.45; p = 0.012) compared with 250 to 1,250 mL. Propensity-weighted regression similarly demonstrated odds of 24-hour mortality were higher for patients receiving less than 250 mL (aOR 2.62; 95% CI 1.34 to 5.12; p = 0.005) and greater than 1,250 mL (aOR 2.93; 95% CI 1.36 to 6.29; p = 0.006) compared with 250 to 1,250 mL., Conclusions: Prehospital crystalloid volumes between 250 and 1,250 mL are associated with lower mortality compared with lower or higher volumes. Further work to validate these finding may provide practical volume targets for prehospital crystalloid resuscitation., (Copyright © 2023 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Although somatic cells can be reprogrammed to pluripotent stem cells (PSCs) with pure chemicals, authentic pluripotency of chemically induced pluripotent stem cells (CiPSCs) has never been achieved through tetraploid complementation assay. Spontaneous reprogramming of spermatogonial stem cells (SSCs) was another non-transgenic way to obtain PSCs, but this process lacks mechanistic explanation. Here, we reconstructed the trajectory of mouse SSC reprogramming and developed a five-chemical combination, boosting the reprogramming efficiency by nearly 80- to 100-folds. More importantly, chemical induced germline-derived PSCs (5C-gPSCs), but not gPSCs and chemical induced pluripotent stem cells, had authentic pluripotency, as determined by tetraploid complementation. Mechanistically, SSCs traversed through an inverted pathway of in vivo germ cell development, exhibiting the expression signatures and DNA methylation dynamics from spermatogonia to primordial germ cells and further to epiblasts. Besides, SSC-specific imprinting control regions switched from biallelic methylated states to monoallelic methylated states by imprinting demethylation and then re-methylation on one of the two alleles in 5C-gPSCs, which was apparently distinct with the imprinting reprogramming in vivo as DNA methylation simultaneously occurred on both alleles. Our work sheds light on the unique regulatory network underpinning SSC reprogramming, providing insights to understand generic mechanisms for cell-fate decision and epigenetic-related disorders in regenerative medicine., (©The Author(s) 2022. Published by Oxford University Press on behalf of Higher Education Press.)

Background: Hemorrhage is the leading cause of preventable death after injury. Others have shown that delays in massive transfusion cooler arrival increase mortality, while prehospital blood product resuscitation can reduce mortality. Our objective was to evaluate if time to resuscitation initiation impacts mortality., Methods: We combined data from the Prehospital Air Medical Plasma (PAMPer) trial in which patients received prehospital plasma or standard care and the Study of Tranexamic Acid during Air and ground Medical Prehospital transport (STAAMP) trial in which patients received prehospital tranexamic acid or placebo. We evaluated the time to early resuscitative intervention (TERI) as time from emergency medical services arrival to packed red blood cells, plasma, or tranexamic acid initiation in the field or within 90 minutes of trauma center arrival. For patients not receiving an early resuscitative intervention, the TERI was calculated based on trauma center arrival as earliest opportunity to receive a resuscitative intervention and were propensity matched to those that did to account for selection bias. Mixed-effects logistic regression assessed the association of 30-day and 24-hour mortality with TERI adjusting for confounders. We also evaluated a subgroup of only patients receiving an early resuscitative intervention as defined above., Results: Among the 1,504 propensity-matched patients, every 1-minute delay in TERI was associated with 2% increase in the odds of 30-day mortality (adjusted odds ratio [aOR], 1.020; 95% confidence interval [CI], 1.006-1.033; p < 0.01) and 1.5% increase in odds of 24-hour mortality (aOR, 1.015; 95% CI, 1.001-1.029; p = 0.03). Among the 799 patients receiving an early resuscitative intervention, every 1-minute increase in TERI was associated with a 2% increase in the odds of 30-day mortality (aOR, 1.021; 95% CI, 1.005-1.038; p = 0.01) and 24-hour mortality (aOR, 1.023; 95% CI, 1.005-1.042; p = 0.01)., Conclusion: Time to early resuscitative intervention is associated with morality in trauma patients with hemorrhagic shock. Bleeding patients need resuscitation initiated early, whether at the trauma center in systems with short prehospital times or in the field when prehospital time is prolonged., Level of Evidence: Therapeutic/Care Management; Level III., (Copyright © 2023 American Association for the Surgery of Trauma.)

Focused ultrasound (FUS) combined with intravenous microbubbles (MBs) has been shown to increase drug delivery to the spinal cord in animal models. Eventual clinical translation of such a technique in the sensitive spinal cord requires robust treatment monitoring to ensure efficacy, localization, safety, and provide key intraprocedural feedback. Here, the use of passive acoustic mapping (PAM) of MB emissions with a spine-specific detector array in the context of transvertebral FUS sonications is investigated in silico. Using computed tomography-derived human vertebral geometry, transvertebral detection of MBs is evaluated over varying source locations with and without phase and amplitude corrections (PACs). The impact of prefocal cavitation is studied by simulating concurrent cavitation events in the canal and pre-laminar region. Spatially sensitive application of phase and amplitude is used to balance signal strengths emanating from different axial depths in combination with multiple dynamic ranges to elicit multisource viewing. Collectively, the results of this study encourage the use of PAM in transvertebral FUS applications with PACs to not only localize sources originating in the spinal canal but also multiple sources of innate amplitude mismatches when corrective methods are applied., (© 2023 Acoustical Society of America.)

Background: Patients with obstructed defecation syndrome may present with a wide spectrum of disorders. The iceberg diagram, which focuses on the underlying occult diseases, has been proposed for an accurate diagnosis. The iceberg diagram deals with lesions, which, if neglected, may worsen the prognosis. The aim of this study was to evaluate the effect of using the iceberg diagram on the clinical results., Methods: Patients operated for obstructed defecation syndrome based on the iceberg diagram between 2008 and 2018 were evaluated pre- and postsurgery. All patients underwent psychosomatic assessment, abdominal and perineal examination, proctoscopy, vaginoscopy, transanal ultrasound, and defecography. Postoperative complications were also evaluated., Results: Of the 80 operated patients, 73 were females; median age was 47 (range 26-78) years. All had a rectal internal mucosal prolapse and 85% had a rectocele. The most frequent occult diseases were functional (mental distress [46%]) or organic (colpo-cysto-enterocele [44%]). Surgery was tailored according to the iceberg diagram with prolapsectomy and rectocele repair the most commonly used among 8 different procedures. A total of 14% of patients had a postoperative complication. Median follow-up was 72 months. Obstructed defecation syndrome score significantly decreased from 10.5 ± 4.8 (mean + standard deviation) to 3.4 ± 3.6 (P < .01) and 68% of patients reported to be either improved or cured., Conclusion: The use of the iceberg diagram in obstructed defecation syndrome patients assists in identifying latent "submerged lesions' that may negatively impact the functional outcome of surgery. A clinical approach to patients with obstructed defecation syndrome tailored according to the iceberg diagram allows the identification of occult lesions and to achieve good long-term results., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Verheij syndrome (VRJS) is a rare craniofacial spliceosomopathy presenting with craniofacial dysmorphism, multiple congenital anomalies and variable neurodevelopmental delay. It is caused by single nucleotide variants (SNVs) in PUF60 or interstitial deletions of the 8q24.3 region. PUF60 encodes a splicing factor which forms part of the spliceosome. To date, 36 patients with a sole diagnosis of VRJS due to disease-causing PUF60 SNVs have been reported in peer-reviewed publications. Although the depth of their phenotyping has varied greatly, they exhibit marked phenotypic heterogeneity. We report 10 additional unrelated patients, including the first described patients of Khmer, Indian, and Vietnamese ethnicities, and the eldest patient to date, with 10 heterozygous PUF60 variants identified through exome sequencing, 8 previously unreported. All patients underwent deep phenotyping identifying variable dysmorphism, growth delay, neurodevelopmental delay, and multiple congenital anomalies, including several unique features. The eldest patient is the only reported individual with a germline variant and neither neurodevelopmental delay nor intellectual disability. In combining these detailed phenotypic data with that of previously reported patients (n = 46), we further refine the known frequencies of features associated with VRJS. These include neurodevelopmental delay/intellectual disability (98%), axial skeletal anomalies (74%), appendicular skeletal anomalies (73%), oral anomalies (68%), short stature (66%), cardiac anomalies (63%), brain malformations (48%), hearing loss (46%), microcephaly (41%), colobomata (38%), and other ocular anomalies (65%). This case series, incorporating three patients from previously unreported ethnic backgrounds, further delineates the broad pleiotropy and mutational spectrum of PUF60 pathogenic variants., (© 2022 Wiley Periodicals LLC.)

Importance: Prehospital needle decompression (PHND) is a rare but potentially life-saving procedure. Prior studies on chest decompression in trauma patients have been small, limited to single institutions or emergency medical services (EMS) agencies, and lacked appropriate comparator groups, making the effectiveness of this intervention uncertain., Objective: To determine the association of PHND with early mortality in patients requiring emergent chest decompression., Design, Setting, and Participants: This was a retrospective cohort study conducted from January 1, 2000, to March 18, 2020, using the Pennsylvania Trauma Outcomes Study database. Patients older than 15 years who were transported from the scene of injury were included in the analysis. Data were analyzed between April 28, 2021, and September 18, 2021., Exposures: Patients without PHND but undergoing tube thoracostomy within 15 minutes of arrival at the trauma center were the comparison group that may have benefited from PHND., Main Outcomes and Measures: Mixed-effect logistic regression was used to determine the variability in PHND between patient and EMS agency factors, as well as the association between risk-adjusted 24-hour mortality and PHND, accounting for clustering by center and year. Propensity score matching, instrumental variable analysis using EMS agency-level PHND proportion, and several sensitivity analyses were performed to address potential bias., Results: A total of 8469 patients were included in this study; 1337 patients (11%) had PHND (median [IQR] age, 37 [25-52] years; 1096 male patients [82.0%]), and 7132 patients (84.2%) had emergent tube thoracostomy (median [IQR] age, 32 [23-48] years; 6083 male patients [85.3%]). PHND rates were stable over the study period between 0.2% and 0.5%. Patient factors accounted for 43% of the variation in PHND rates, whereas EMS agency accounted for 57% of the variation. PHND was associated with a 25% decrease in odds of 24-hour mortality (odds ratio [OR], 0.75; 95% CI, 0.61-0.94; P = .01). Similar results were found in patients who survived their ED stay (OR, 0.68; 95% CI, 0.52-0.89; P < .01), excluding severe traumatic brain injury (OR, 0.65; 95% CI, 0.45-0.95; P = .03), and restricted to patients with severe chest injury (OR, 0.72; 95% CI, 0.55-0.93; P = .01). PHND was also associated with lower odds of 24-hour mortality after propensity matching (OR, 0.79; 95% CI, 0.62-0.98; P = .04) when restricting matches to the same EMS agency (OR, 0.74; 95% CI, 0.56-0.99; P = .04) and in instrumental variable probit regression (coefficient, -0.60; 95% CI, -1.04 to -0.16; P < .01)., Conclusions and Relevance: In this cohort study, PHND was associated with lower 24-hour mortality compared with emergent trauma center chest tube placement in trauma patients. Although performed rarely, PHND can be a life-saving intervention and should be reinforced in EMS education for appropriately selected trauma patients.

DNA switches that can change conformation in response to certain wavelengths of light could enable rapid and noninvasive control of chemical processes for a wide range of applications. However, most current photoresponsive DNA switches are limited by either irreversible switching or reversible switching with impractically slow kinetics. Here, we report the design of an intramolecular triplex photoswitch (TPS) design based on single-stranded DNA that undergoes rapid and reversible photoswitching between folded and unfolded states through isomerization of internal azobenzene modifications. After optimizing the performance of our photoswitch design, we used molecular dynamics simulations to reveal how individual azobenzenes contribute to the stabilization or destabilization of the triplex depending on their photoisomerization state. By coupling our TPS to an existing aptamer, we can reversibly modulate its binding affinity with less than 15 s of UV light exposure. We further demonstrate reproducible shifting in affinity over multiple cycles of UV and blue light irradiation without substantial photobleaching.

Background: Muscle weakness is common after injury in athletes and in the presence of hip pathology. It will cause abnormal hip biomechanics and can predict future injury. However, objective measurement of hip muscle strength is difficult to perform accurately and reliably. Therefore, it is challenging to determine when an athlete has returned to preinjury levels of strength. In addition, there is currently no standardized method of obtaining measurements, which prevents the data being compared or shared between research centers., Purpose: The purpose of this study is to comprehensively assess the inter- and intraobserver reliability of our standardized muscle strength measurement protocol., Study Design: Descriptive laboratory study., Level of Evidence: Level 3, inception cohort study., Methods: A total of 16 healthy male volunteers (age = 28.3 ± 7.9 years) were recruited. Those with a previous history of hip injuries or disorders were excluded. These volunteers underwent strength testing according to the Cambridge Protocol on 4 separate occasions, performed by 2 independent assessors. Maximal voluntary contractions, fatigue torque fluctuations, and electromyography measurements were recorded. Intra- and interobserver reliability was assessed using intraclass correlation coefficient (ICC)., Results: Good-to-excellent correlation was seen for both intra- and interobserver reliability across almost all hip movements for maximal contractions: ICC ranged 0.78 to 0.93 and 0.78 to 0.96, respectively. The standard error of the mean for all hip movements was also extremely low at 2% to 3%., Conclusion: The Cambridge Protocol is a highly reliable method for objective measurement of hip muscle strength. We recommend future studies use this protocol, or the principles underpinning it, to enable data sharing and comparison across different studies., Clinical Relevance: This is a description and analysis of hip muscle strength measurement. If widely used, it will allow for accurate and objective strength assessment and closer monitoring of hip injuries and pathology.

The COVID-19 pandemic raised many challenges for university staff and students, including the need to work from home, which resulted in a greater reliance on technology. We collected questionnaire data from university students (N = 894) in three European countries: Greece, Italy, and the United Kingdom. Data were collected between 7th April 2020 and 19th June 2020, representing a period covering the first lockdown and university closures in these countries and across Europe generally. We tested the hypotheses that technology-related stressors (techno-overload, work-home conflict, techno-ease, techno-reliability, techno-sociality, and pace of change) would be associated with anxiety and depressive symptoms, and that coping styles (problem-focused, emotion-focused, and avoidance) would mediate these relationships. Results showed significant positive associations between techno-overload, work-home conflict and anxiety and depressive symptoms, and significant negative associations between techno-reliability, techno-ease and anxiety and depressive symptoms. A significant negative association was found between techno-sociality and depressive symptoms but not anxiety symptoms. No evidence was found for an association between pace of change and anxiety or depressive symptoms. Multiple mediation analyses revealed significant direct effects of techno-overload, work-home conflict and techno-ease on anxiety symptoms, and of work-home conflict and techno-ease on depressive symptoms. Work-home conflict had significant indirect effects on anxiety and depressive symptoms through avoidance coping. Techno-overload and techno-ease both had significant indirect effects on anxiety symptoms through problem- and emotion-focused coping. Techno-ease also had a significant indirect effect on depressive symptoms through problem-focused coping. The findings add to the body of evidence on technostress amongst university students and provide knowledge on how technostress translates through coping strategies into anxious and depressive symptoms during the disruption caused by the outbreak of a pandemic disease., Competing Interests: The authors have declared that no competing interests exist.

Copy-number variations (CNV) are believed to play an important role in a wide range of complex traits, but discovering such associations remains challenging. While whole-genome sequencing (WGS) is the gold-standard approach for CNV detection, there are several orders of magnitude more samples with available genotyping microarray data. Such array data can be exploited for CNV detection using dedicated software (e.g., PennCNV); however, these calls suffer from elevated false-positive and -negative rates. In this study, we developed a CNV quality score that weights PennCNV calls (pCNVs) based on their likelihood of being true positive. First, we established a measure of pCNV reliability by leveraging evidence from multiple omics data (WGS, transcriptomics, and methylomics) obtained from the same samples. Next, we built a predictor of omics-confirmed pCNVs, termed omics-informed quality score (OQS), using only PennCNV software output parameters. Promisingly, OQS assigned to pCNVs detected in close family members was up to 35% higher than the OQS of pCNVs not carried by other relatives (p < 3.0 × 10 -90 ), outperforming other scores. Finally, in an association study of four anthropometric traits in 89,516 Estonian Biobank samples, the use of OQS led to a relative increase in the trait variance explained by CNVs of up to 56% compared with published quality filtering methods or scores. Overall, we put forward a flexible framework to improve any CNV detection method leveraging multi-omics evidence, applied it to improve PennCNV calls, and demonstrated its utility by improving the statistical power for downstream association analyses., Competing Interests: The authors declare no competing interests., (© 2022 The Author(s).)

Investigating the functions and activities of genes requires proper annotation of the transcribed units. However, transcript assembly efforts have produced a surprisingly large variation in the number of transcripts, and especially so for noncoding transcripts. This heterogeneity in assembled transcript sets might be partially explained by sequencing depth. Here, we used real and simulated short-read sequencing data as well as long-read data to systematically investigate the impact of sequencing depths on the accuracy of assembled transcripts. We assembled and analyzed transcripts from 671 human short-read data sets and four long-read data sets. At the first level, there is a positive correlation between the number of reads and the number of recovered transcripts. However, the effect of the sequencing depth varied based on cell or tissue type, the type of read and the nature and expression levels of the transcripts. The detection of coding transcripts saturated rapidly with both short and long-reads, however, there was no sign of early saturation for noncoding transcripts at any sequencing depth. Increasing long-read sequencing depth specifically benefited transcripts containing transposable elements. Finally, we show how single-cell RNA-seq can be guided by transcripts assembled from bulk long-read samples, and demonstrate that noncoding transcripts are expressed at similar levels to coding transcripts but are expressed in fewer cells. This study highlights the impact of sequencing depth on transcript assembly., (© 2022. The Author(s).)

Background: Growing evidence supports improved survival with prehospital blood products. Recent trials show a benefit of prehospital tranexamic acid (TXA) administration in select subgroups. Our objective was to determine if receiving prehospital packed red blood cells (pRBC) in addition to TXA improved survival in injured patients at risk of hemorrhage., Methods: We performed a secondary analysis of all scene patients from the Study of Tranexamic Acid during Air and ground Medical Prehospital transport trial. Patients were randomized to prehospital TXA or placebo. Some participating EMS services utilized pRBC. Four resuscitation groups resulted: TXA, pRBC, pRBC+TXA, and neither. Our primary outcome was 30-day mortality and secondary outcome was 24-hour mortality. Cox regression tested the association between resuscitation group and mortality while adjusting for confounders., Results: A total of 763 patients were included. Patients receiving prehospital blood had higher Injury Severity Scores in the pRBC (22 [10, 34]) and pRBC+TXA (22 [17, 36]) groups than the TXA (12 [5, 21]) and neither (10 [4, 20]) groups (p < 0.01). Mortality at 30 days was greatest in the pRBC+TXA and pRBC groups at 18.2% and 28.6% compared with the TXA only and neither groups at 6.6% and 7.4%, respectively. Resuscitation with pRBC+TXA was associated with a 35% reduction in relative hazards of 30-day mortality compared with neither (hazard ratio, 0.65; 95% confidence interval, 0.45-0.94; p = 0.02). No survival benefit was observed in 24-hour mortality for pRBC+TXA, but pRBC alone was associated with a 61% reduction in relative hazards of 24-hour mortality compared with neither (hazard ratio, 0.39; 95% confidence interval, 0.17-0.88; p = 0.02)., Conclusion: For injured patients at risk of hemorrhage, prehospital pRBC+TXA is associated with reduced 30-day mortality. Use of pRBC transfusion alone was associated with a reduction in early mortality. Potential synergy appeared only in longer-term mortality and further work to investigate mechanisms of this therapeutic benefit is needed to optimize the prehospital resuscitation of trauma patients., Level of Evidence: Therapeutic/Care Management; Level III., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Eczema (atopic dermatitis; AD) is a very common itchy skin condition affecting 1 in 5 children and up to 1 in 10 adults worldwide. The skin of eczema sufferers is prone to redness, irritation and dryness because it does not form an effective barrier, i.e. the ability of the skin to stop irritants, allergens and microorganisms getting into the body. Skin barrier dysfunction is a hallmark of AD. The regular and liberal (600 g/week for an adult) use of emollients is recommended for all patients with eczema), even between episodes of itching and redness, to soften and soothe the skin. In England alone, almost 9 million prescriptions for emollient creams were issued in 2018, at a cost of over £50 million. Despite this widespread use, relatively little is known about how commonly prescribed emollient creams affect the skin's barrier, and thus the role of moisturizers in AD development and progression remains unclear. We set out to compare three different types of emollient cream and a no-treatment control., Aim: To compare the barrier-strengthening properties of a new moisturizer containing urea and glycerol (urea-glycerol cream; UGC), with those of a glycerol-containing moisturizer (glycerol cream; GC), a simple paraffin cream (PC) with no humectant, and a no-treatment control (NTC)., Methods: This was an observer-blinded prospective Phase 2 within-subject multilateral single-centre randomized controlled trial in adults with AD (Clinical Trials #NCT03901144). The intervention involved 4 weeks of treatment, twice daily, with the three products applied to one of four areas on the forearms the (the fourth area was the untreated control, randomized allocation). Skin properties [dryness, transepidermal water loss (TEWL), hydration and natural moisturizing factor (NMF) levels] were assessed before, during and after treatment to see what happened to the skin's barrier. The primary outcome was skin sensitivity to the irritant sodium lauryl sulfate (SLS) after treatment. We performed tests on the skin before and after treatment to see what happened to the skin's barrier., Results: In total, 49 patients were randomized, completed treatment and included in the analysis. UGC significantly reduced the response to SLS as indicated by a reduction in TEWL compared with NTC (-9.0 g/m 2 /h; 95% CI -12.56 to -5.49), with PC (-9.0 g/m 2 /h; 95% CI -12.60 to -5.44) and with GC -4.2 g/m 2 /h; 95% CI 7.76 to -0.63). Skin moisturization improved at sites treated with UGC compared with NTC and PC, and this was accompanied by concordant changes in dryness and NMF levels. Subgroup analysis suggested FLG-dependent enhancement of treatment effects., Conclusion: The study showed that not all emollient creams for eczema are equal. The simple paraffin-based emollient, which represents the most widely prescribed type of emollient cream in England, had no effect on the skin's barrier and reduced the skin's NMF. UGC markedly improved the skin's barrier and protected against irritation. GC performed better than PC, but not as well as UGC. UGC strengthened the skin barrier through a mechanism involving increased NMF levels in the skin, and imparted protection from SLS-induced irritation. By helping correct a major pathophysiological process, UGC has the potential to improve the long-term control of AD. The results show that different emollient creams have different effects on our skin, and only certain types have the ability to improve the skin's barrier and protect against irritants that trigger eczema., (© 2022 The Authors. Clinical and Experimental Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Background: The skin of patients with atopic dermatitis is characterized by abnormal stratum corneum lipid levels. Consequently, the lamellar matrices are disrupted and skin barrier function is diminished, increasing skin sensitivity to irritants and allergens., Objectives: To determine whether a cream containing ceramides, triglycerides and cholesterol in a multivesicular emulsion can reinforce the skin barrier and protect against skin irritation., Methods: A randomized observer-blind intrapatient-controlled study in 34 adults with dry, eczema-prone skin was conducted. Each participant underwent 4 weeks of treatment with the test cream on one forearm and lower leg and a reference emollient cream on the other. Skin properties were determined before and after treatment. Lipid structure was assessed by Fourier-transform infrared spectroscopy using a novel interface., Results: Skin barrier integrity was greater at sites treated with the test cream [effect size for area under the transepidermal water loss curve -162, 95% confidence interval (CI) -206 to -118]. Skin sensitivity to sodium lauryl sulfate was reduced (-0·5 points visual redness, 97·57% CI -1·00 to -0·25), as was transepidermal water loss (-15·3 g m -2 h -1 , 95% CI -20·3 to -10·4) compared with the reference. Sites treated with the test cream displayed enhanced lipid chain ordering, which was significantly associated with skin barrier integrity (r = 0·61). Compared with the reference, treatment with the test cream increased hydration (8·61 capacitance units, 95% CI 6·61-10·6) and decreased signs of dryness., Conclusions: The test cream facilitates skin barrier restoration and protects the skin from dryness and irritation. Compared with a commonly prescribed emollient in the UK, the test cream is highly suited to the management of dry, sensitive skin., (© 2022 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Background: Social determinants of health (SDOH) impact patient outcomes in trauma. Census data are often used to account for SDOH; however, there is no consensus on which variables are most important. Social vulnerability indices offer the advantage of combining multiple constructs into a single variable. Our objective was to determine if incorporation of SDOH in patient-level risk-adjusted outcome modeling improved predictive performance., Methods: We evaluated two social vulnerability indices at the zip code level: Distressed Community Index (DCI) and National Risk Index (NRI). Individual variable combinations from Agency for Healthcare Research and Quality's SDOH data set were used for comparison. Patients were obtained from the Pennsylvania Trauma Outcomes Study 2000 to 2020. These measures were added to a validated base mortality prediction model with comparison of area under the curve and Bayesian information criterion. We performed center benchmarking using risk-standardized mortality ratios to evaluate change in rank and outlier status based on SDOH. Geospatial analysis identified geographic variation and autocorrelation., Results: There were 449,541 patients included. The DCI and NRI were associated with an increase in mortality (adjusted odds ratio, 1.02; 95% confidence interval, 1.01-1.03 per 10% percentile rank increase; p < 0.01, respectively). The DCI, NRI, and seven Agency for Healthcare Research and Quality variables also improved base model fit but discrimination was similar. Two thirds of centers changed mortality ranking when accounting for SDOH compared with the base model alone. Outlier status changed in 7% of centers, most representing an improvement from worse-than-expected to nonoutlier or nonoutlier to better-than-expected. There was significant geographic variation and autocorrelation of the DCI and NRI (DCI; Moran's I 0.62, p = 0.01; NRI; Moran's I 0.34, p = 0.01)., Conclusion: Social determinants of health are associated with an individual patient's risk of mortality after injury. Accounting for SDOH may be important in risk adjustment for trauma center benchmarking., Level of Evidence: Prognostic/Epidemiologic, level IV., (Copyright © 2021 American Association for the Surgery of Trauma.)

The prevalence of smartwatches and other wearable medical technology has been increasing yearly. These watches offer a sensitive tool for capturing cardiac dysrhythmias and can lead to patients seeking earlier medical advice. This case report highlights the importance of clinicians seeking and using the information provided by wearable medical technology which in this case resulted in both the timely treatment of non-sustained ventricular tachycardia and lung adenocarcinoma., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© 2022 The Author(s).)

Multi-omics data allow us to select a small set of informative markers for the discrimination of specific cell types and study of cellular heterogeneity. However, it is often challenging to choose an optimal marker panel from the high-dimensional molecular profiles for a large amount of cell types. Here, we propose a method called Mixed Integer programming Model to Identify Cell type-specific marker panel (MIMIC). MIMIC maintains the hierarchical topology among different cell types and simultaneously maximizes the specificity of a fixed number of selected markers. MIMIC was benchmarked on the mouse ENCODE RNA-seq dataset, with 29 diverse tissues, for 43 surface markers (SMs) and 1345 transcription factors (TFs). MIMIC could select biologically meaningful markers and is robust for different accuracy criteria. It shows advantages over the standard single gene-based approaches and widely used dimensional reduction methods, such as multidimensional scaling and t-SNE, both in accuracy and in biological interpretation. Furthermore, the combination of SMs and TFs achieves better specificity than SMs or TFs alone. Applying MIMIC to a large collection of 641 RNA-seq samples covering 231 cell types identifies a panel of TFs and SMs that reveal the modularity of cell type association networks. Finally, the scalability of MIMIC is demonstrated by selecting enhancer markers from mouse ENCODE data. MIMIC is freely available at https://github.com/MengZou1/MIMIC., (© The Author(s) 2021. Published by Oxford University Press.)

Background: In primary anterior cruciate ligament (ACL) reconstruction, a bone-patellar tendon-bone (BTB) autograft is associated with lower ipsilateral failure rates. BTB autografts are associated with a higher rate of contralateral ACL injuries, which some clinicians view as a marker of success of the BTB autograft. However, there is a lack of evidence on whether BTB autografts improve the rate of return to activity and sport., Purpose: To compare the rate of return to preinjury activity levels in high-activity patients after ACL reconstruction with BTB autograft or hamstring tendon autograft., Study Design: Cohort study; Level of evidence, 3., Methods: In a high-activity cohort of patients recorded between 2014 and 2018 in the New Zealand ACL Registry, prospectively collected data on preinjury and postoperative Marx activity scores were analyzed. The proportion of patients who returned to their preinjury activity levels at 1- and 2-year follow-up was compared between graft types., Results: Overall, 11.3% (208/1844) of patients returned to their preinjury activity levels at 1-year follow-up, and 15.5% (184/1190) returned at 2-year follow-up. At 1-year follow-up, 17.2% of patients with a BTB autograft returned to their preinjury activity levels compared with 9.3% of patients with a hamstring tendon autograft (adjusted odds ratio, 1.59 [95% CI, 1.16-2.17]; P = .004). At 2-year follow-up, 23.3% of patients with a BTB autograft had returned to their preinjury activity levels compared with 13.3% of patients with a hamstring tendon autograft (adjusted odds ratio, 1.63 [95% CI, 1.14-2.34]; P = .008). Male sex and younger age were associated with a higher rate of return to activity at both follow-up time points., Conclusion: The use of BTB autografts increased the odds of returning to preinjury activity levels at early follow-up. A higher rate of return to activity is a possible explanation for the higher rate of contralateral ACL injuries with the use of BTB autografts.

Tropical fruit flies are considered among the most economically important invasive species detected in temperate areas of the United States and the European Union. Detections often trigger quarantine and eradication programs that are conducted without a holistic understanding of the threat posed. Weather-driven physiologically-based demographic models are used to estimate the geographic range, relative abundance, and threat posed by four tropical tephritid fruit flies (Mediterranean fruit fly, melon fly, oriental fruit fly, and Mexican fruit fly) in North and Central America, and the European-Mediterranean region under extant and climate change weather (RCP8.5 and A1B scenarios). Most temperate areas under tropical fruit fly propagule pressure have not been suitable for establishment, but suitability is predicted to increase in some areas with climate change. To meet this ongoing challenge, investments are needed to collect sound biological data to develop mechanistic models to predict the geographic range and relative abundance of these and other invasive species, and to put eradication policies on a scientific basis., (© 2021. The Author(s).)

Background: Over half of women of reproductive age are now overweight or obese. The impact of maternal high-fat diet (HFD) is emerging as an important factor in the development and health of musculoskeletal tissues in offspring, however there is a paucity of evidence examining its effects on tendon. Alterations in the early life environment during critical periods of tendon growth therefore have the potential to influence tendon health that cross the lifespan. We hypothesised that a maternal HFD would alter biomechanical, morphological and gene expression profiles of adult offspring rotator cuff tendon. Materials and Methods: Female Sprague-Dawley rats were randomly assigned to either: control diet (CD; 10% kcal or 43 mg/g from fat) or HFD (45% kcal or 235 mg/g from fat) 14 days prior to mating and throughout pregnancy and lactation. Eight female and male offspring from each maternal diet group were weaned onto a standard chow diet and then culled at postnatal day 100 for tissue collection. Supraspinatus tendons were used for mechanical testing and histological assessment (cellularity, fibre organisation, nuclei shape) and tail tendons were collected for gene expression analysis. Results: A maternal HFD increased the elasticity (Young's Modulus) in the supraspinatus tendon of male offspring. Female offspring tendon biomechanical properties were not affected by maternal HFD. Gene expression of SCX and COL1A1 were reduced in male and female offspring of maternal HFD, respectively. Despite this, tendon histological organisation were similar between maternal diet groups in both sexes. Conclusion: An obesogenic diet during pregnancy increased tendon elasticity in male, but not female, offspring. This is the first study to demonstrate that maternal diet can modulate the biomechanical properties of offspring tendon. A maternal HFD may be an important factor in regulating adult offspring tendon homeostasis that may predispose offspring to developing tendinopathies and adverse tendon outcomes in later life., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Bolam, Satokar, Konar, Coleman, Monk, Cornish, Munro, Vickers, Albert and Musson.)

Background: Social vulnerability indices were created to measure resiliency to environmental disasters based on socioeconomic and population characteristics of discrete geographic regions. They are composed of multiple validated constructs that can also potentially identify geographically vulnerable populations after injury. Our objective was to determine if these indices correlate with injury fatality rates in the US., Methods: We evaluated three social vulnerability indices: The Hazards & Vulnerability Research Institute's Social Vulnerability Index (SoVI), the Center for Disease Control's Social Vulnerability Index (SVI), and the Economic Innovation Group's Distressed Community Index (DCI). We analyzed SVI subindices and common individual census variables as indicators of socioeconomic status. Outcomes included age-adjusted county-level overall, firearm, and motor vehicle collision deaths per 100,000 population. Linear regression determined the association of injury fatality rates with the SoVI, SVI, and DCI. Bivariate choropleth mapping identified geographic variation and spatial autocorrelation of overall fatality, SoVI, and DCI., Results: A total of 3,137 US counties were included. Only 24.6% of counties fell into the same vulnerability quintile for all three indices. Despite this, all indices were associated with increasing fatality rates for overall, firearm, and motor vehicle collision fatality. The DCI performed best by model fit, explanation of variance, and diagnostic performance on overall injury fatality. There is significant geographic variation in SoVI, DCI, and injury fatality rates at the county level across the United States, with moderate spatial autocorrelation of SoVI (Moran's I, 0.35; p < 0.01) and high autocorrelation of injury fatality rates (Moran's I, 0.77; p < 0.01) and DCI (Moran's I, 0.53; p < 0.01)., Conclusion: While the indices contribute unique information, higher social vulnerability is associated with higher injury fatality across all indices. These indices may be useful in the epidemiologic and geographic assessment of injury-related fatality rates. Further study is warranted to determine if these indices outperform traditional measures of socioeconomic status and related constructs used in trauma research., Level of Evidence: Epidemiological, level IV., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

(Background) Inertial Measurement Units (IMUs) provide a low-cost, portable solution to obtain functional measures similar to those captured with three-dimensional gait analysis, including spatiotemporal gait characteristics. The primary aim of this study was to determine the feasibility of a remote patient monitoring (RPM) workflow using ankle-worn IMUs measuring impact load, limb impact load asymmetry and knee range of motion in combination with patient-reported outcome measures. (Methods) A pilot cohort of 14 patients undergoing primary knee arthroplasty for osteoarthritis was prospectively enrolled. RPM in the community was performed weekly from 2 up to 6 weeks post-operatively using wearable IMUs. The following data were collected using IMUs: mobility (Bone Stimulus and cumulative impact load), impact load asymmetry and maximum knee flexion angle. In addition, scores from the Oxford Knee Score (OKS), EuroQol Five-dimension (EQ-5D) with EuroQol visual analogue scale (EQ-VAS) and 6 Minute Walk Test were collected. (Results) On average, the Bone Stimulus and cumulative impact load improved 52% ( p = 0.002) and 371% ( p = 0.035), compared to Post-Op Week 2. The impact load asymmetry value trended ( p = 0.372) towards equal impact loading between the operative and non-operative limb. The mean maximum flexion angle achieved was 99.25° at Post-Operative Week 6, but this was not significantly different from pre-operative measurements ( p = 0.1563). There were significant improvements in the mean EQ-5D (0.20; p = 0.047) and OKS (10.86; p < 0.001) scores both by 6 weeks after surgery, compared to pre-operative scores. (Conclusions) This pilot study demonstrates the feasibility of a reliable and low-maintenance workflow system to remotely monitor post-operative progress in knee arthroplasty patients. Preliminary data indicate IMU outputs relating to mobility, impact load asymmetry and range of motion can be obtained using commercially available IMU sensors. Further studies are required to directly correlate the IMU sensor outputs with patient outcomes to establish clinical significance.

(1) Background: Passenger vehicles equipped with advanced driver-assistance system (ADAS) functionalities are becoming more prevalent within vehicle fleets. However, the full effects of offering such systems, which may allow for drivers to become less than 100% engaged with the task of driving, may have detrimental impacts on other road-users, particularly vulnerable road-users, for a variety of reasons. (2) Crash data were analysed in two countries (Great Britain and Australia) to examine some challenging traffic scenarios that are prevalent in both countries and represent scenarios in which future connected and autonomous vehicles may be challenged in terms of safe manoeuvring. (3) Road intersections are currently very common locations for vulnerable road-user accidents; traffic flows and road-user behaviours at intersections can be unpredictable, with many vehicles behaving inconsistently (e.g., red-light running and failure to stop or give way), and many vulnerable road-users taking unforeseen risks. (4) Conclusions: The challenges of unpredictable vulnerable road-user behaviour at intersections (including road-users violating traffic or safe-crossing signals, or taking other risks) combined with the lack of knowledge of CAV responses to intersection rules, could be problematic. This could be further compounded by changes to nonverbal communication that currently exist between road-users, which could become more challenging once CAVs become more widespread.

Background: Despite evidence of benefit after injury, helicopter emergency medical services (HEMS) overtriage remains high. Scene and transfer overtriage are distinct processes. Our objectives were to identify geographic variation in overtriage and patient-level predictors, and determine if overtriage impacts population-level outcomes., Methods: Patients 16 years or older undergoing scene or interfacility HEMS in the Pennsylvania Trauma Outcomes Study were included. Overtriage was defined as discharge within 24 hours of arrival. Patients were mapped to zip code, and rates of overtriage were calculated. Hot spot analysis identified regions of high and low overtriage. Mixed-effects logistic regression determined patient predictors of overtriage. High and low overtriage regions were compared for population-level injury fatality rates. Analyses were performed for scene and transfer patients separately., Results: A total of 85,572 patients were included (37.4% transfers). Overtriage was 5.5% among scene and 11.8% among transfer HEMS (p < 0.01). Hot spot analysis demonstrated geographic variation in high and low overtriage for scene and transfer patients. For scene patients, overtriage was associated with distance (odds ratio [OR], 1.03; 95% confidence interval [CI], 1.01-1.06 per 10 miles; p = 0.04), neck injury (OR, 1.27; 95% CI, 1.01-1.60; p = 0.04), and single-system injury (OR, 1.37; 95% CI, 1.15-1.64; p < 0.01). For transfer patients, overtriage was associated with rurality (OR, 1.64; 95% CI, 1.22-2.21; p < 0.01), facial injury (OR, 1.22; 95% CI, 1.03-1.44; p = 0.02), and single-system injury (OR, 1.35; 95% CI, 1.18-2.19; p < 0.01). For scene patients, high overtriage was associated with higher injury fatality rate (coefficient, 1.72; 95% CI, 1.68-1.76; p < 0.01); low overtriage was associated with lower injury fatality rate (coefficient, -0.73; 95% CI, -0.78 to -0.68; p < 0.01). For transfer patients, high overtriage was not associated with injury fatality rate (p = 0.53); low overtriage was associated with lower injury fatality rate (coefficient, -2.87; 95% CI, -4.59 to -1.16; p < 0.01)., Conclusion: Geographic overtriage rates vary significantly for scene and transfer HEMS, and are associated with population-level outcomes. These findings can help guide targeted performance improvement initiatives to reduce HEMS overtriage., Level of Evidence: Therapeutic, level IV., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)