APOL1 risk variants in individuals of African genetic ancestry drive endothelial cell defects that exacerbate sepsis.

The incidence and severity of sepsis is higher among individuals of African versus European ancestry. We found that genetic risk variants (RVs) in the trypanolytic factor apolipoprotein L1 (APOL1), present only in individuals of African ancestry, were associated with increased sepsis incidence and severity. Serum APOL1 levels correlated with sepsis and COVID-19 severity, and single-cell sequencing in human kidneys revealed high expression of APOL1 in endothelial cells. Analysis of mice with endothelial-specific expression of RV APOL1 and in vitro studies demonstrated that RV APOL1 interfered with mitophagy, leading to cytosolic release of mitochondrial DNA and activation of the inflammasome (NLRP3) and the cytosolic nucleotide sensing pathways (STING). Genetic deletion or pharmacological inhibition of NLRP3 and STING protected mice from RV APOL1-induced permeability defects and proinflammatory endothelial changes in sepsis. Our studies identify the inflammasome and STING pathways as potential targets to reduce APOL1-associated health disparities in sepsis and COVID-19.

Association between Age and Mortality in Pediatric and Adult Acute Respiratory Distress Syndrome.

Rationale: The epidemiology, management, and outcomes of acute respiratory distress syndrome (ARDS) differ between children and adults, with lower mortality rates in children despite comparable severity of hypoxemia. However, the relationship between age and mortality is unclear.Objective: We aimed to define the association between age and mortality in ARDS, hypothesizing that it would be nonlinear.Methods: We performed a retrospective cohort study using data from two pediatric ARDS observational cohorts (n = 1,236), multiple adult ARDS trials (n = 5,547), and an adult observational ARDS cohort (n = 1,079). We aligned all datasets to meet Berlin criteria. We performed unadjusted and adjusted logistic regression using fractional polynomials to assess the potentially nonlinear relationship between age and 90-day mortality, adjusting for sex, PaO2/FiO2, immunosuppressed status, year of study, and observational versus randomized controlled trial, treating each individual study as a fixed effect.Measurements and Main Results: There were 7,862 subjects with median ages of 4 years in the pediatric cohorts, 52 years in the adult trials, and 61 years in the adult observational cohort. Most subjects (43%) had moderate ARDS by Berlin criteria. Ninety-day mortality was 19% in the pediatric cohorts, 33% in the adult trials, and 67% in the adult observational cohort. We found a nonlinear relationship between age and mortality, with mortality risk increasing at an accelerating rate between 11 and 65 years of age, after which mortality risk increased more slowly.Conclusions: There was a nonlinear relationship between age and mortality in pediatric and adult ARDS.

Net greenhouse gas balance in U.S. croplands: How can soils be part of the climate solution?

Agricultural soils play a dual role in regulating the Earth's climate by releasing or sequestering carbon dioxide (CO2 ) in soil organic carbon (SOC) and emitting non-CO2 greenhouse gases (GHGs) such as nitrous oxide (N2 O) and methane (CH4 ). To understand how agricultural soils can play a role in climate solutions requires a comprehensive assessment of net soil GHG balance (i.e., sum of SOC-sequestered CO2 and non-CO2 GHG emissions) and the underlying controls. Herein, we used a model-data integration approach to understand and quantify how natural and anthropogenic factors have affected the magnitude and spatiotemporal variations of the net soil GHG balance in U.S. croplands during 1960-2018. Specifically, we used the dynamic land ecosystem model for regional simulations and used field observations of SOC sequestration rates and N2 O and CH4 emissions to calibrate, validate, and corroborate model simulations. Results show that U.S. agricultural soils sequestered 13.2 ± 1.16 $$ 13.2\pm 1.16 $$ Tg CO2 -C year-1 in SOC (at a depth of 3.5 m) during 1960-2018 and emitted 0.39 ± 0.02 $$ 0.39\pm 0.02 $$ Tg N2 O-N year-1 and 0.21 ± 0.01 $$ 0.21\pm 0.01 $$ Tg CH4 -C year-1 , respectively. Based on the GWP100 metric (global warming potential on a 100-year time horizon), the estimated national net GHG emission rate from agricultural soils was 122.3 ± 11.46 $$ 122.3\pm 11.46 $$ Tg CO2 -eq year-1 , with the largest contribution from N2 O emissions. The sequestered SOC offset ~28% of the climate-warming effects resulting from non-CO2 GHG emissions, and this offsetting effect increased over time. Increased nitrogen fertilizer use was the dominant factor contributing to the increase in net GHG emissions during 1960-2018, explaining ~47% of total changes. In contrast, reduced cropland area, the adoption of agricultural conservation practices (e.g., reduced tillage), and rising atmospheric CO2 levels attenuated net GHG emissions from U.S. croplands. Improving management practices to mitigate N2 O emissions represents the biggest opportunity for achieving net-zero emissions in U.S. croplands. Our study highlights the importance of concurrently quantifying SOC-sequestered CO2 and non-CO2 GHG emissions for developing effective agricultural climate change mitigation measures.

Analytical and preparative chiral supercritical fluid chromatography resolutions using crown ether-derived column.

In this study, crown ether-derived column Crownpak® CR-I (+) was evaluated under SFC conditions using 12 primary amines, and the chromatographic results were compared against eight immobilized polysaccharide-based columns. Crownpak® CR-I (+) achieved a significantly higher success rate. It was found that the addition of 5% water to the modifier dramatically improved the peak shape for chiral separation of primary amines on Crownpak® CR-I (+). The first reported preparative SFC separations on Crownpak® CR-I (+) are shown, offering a new approach for the preparative resolution of primary amines. The case studies demonstrate that Crownpak® CR-I (+) is a very useful column in the chiral separation of challenging compounds that contain a primary amine group in the pharmaceutical industry.

Investigation into the performance and stability of immobilized and coated polysaccharide columns in supercritical fluid chromatography.

In this study, the performance of the widely used "golden four" coated chiral stationary phases (Chiralpak AD-3, Chiralcel OD-3, Chiralpak AS-3, and Chiralcel OJ-3) was compared with their corresponding immobilized versions (Chiralpak IA-3, Chiralpak IB-3, Chiralpak IB N-3, Chiralpak IH-3, and Chiralpak IJ-3) under supercritical fluid chromatography (SFC) conditions with a set of 30 racemic compounds. Using the traditional modifiers, methanol and isopropanol, the immobilized columns (Chiralpak IB N-3 and Chiralpak IH-3) showed an improved general ability to successfully resolve the enantiomers of the target analytes relative to their coated versions (Chiralcel OD-3 and Chiralpak AS-3), while the coated columns (Chiralpak AD-3, Chiralcel OD-3, and Chiralcel OJ-3) performed better than their immobilized versions (Chiralpak IA-3, Chiralpak IB-3, and Chiralpak IJ-3). An investigation of the non-traditional modifiers, dichloromethane, ethyl acetate, and tetrahydrofuran with immobilized columns, revealed a generally decreased ability to successfully resolve the enantiomers of the target analytes, relative to the use of the traditional modifiers, methanol and isopropanol. The stability of the coated columns (Chiralpak AD-H and Chiralcel OD-H) was evaluated by injecting "forbidden" solvents, including dichloromethane, dimethyl sulfoxide, and tetrahydrofuran. After 200 injections of these solvents on coated columns, the retention factors and resolutions slightly decreased, and a significant increase in column backpressure was observed, indicating some degree of stationary phase degradation.

A systematic evaluation of physical activity and diet policies in Scotland: results from the 2021 Active Healthy Kids Report Card.

BACKGROUND: Policymaking regarding physical activity (PA) and diet plays an important role in childhood health promotion. This study provides a detailed examination of Scottish government and policy for child and adolescent PA and diet and discusses strengths and areas for improvement. METHODS: Scottish policy documents (n = 18 [PA]; n = 10 [diet])-published in 2011-20-were reviewed for grading using an adapted version of the Health-Enhancing Physical Activity Policy Audit Tool Version 2. RESULTS: There is clear evidence of leadership and commitment to improving PA and diet and tackling obesity in children and adolescents. The allocation of funds and resources for policy implementation has increased substantially over the past decade. Progress through early key stages of public policymaking-policy agenda and formation-has improved. However, there is limited information on later key stages, including policy monitoring and evaluation. CONCLUSIONS: Childhood PA and diet are a clear priority in Scotland, and PA and diet policies clearly support the desire to achieve other goals, including reducing inequalities and increasing active travel in Scotland. Nonetheless, future policies should be further strengthened through clear(er) plans of implementation, and monitoring and evaluation to support their societal impact.

Physical Activity Levels During School Recess in a Nationally Representative Sample of 10- to 11-Year-Olds.

PURPOSE: School recess provides a valuable opportunity for children's daily moderate- to vigorous-intensity physical activity (MVPA). This study aimed to quantify MVPA during school recess in a representative sample of Scottish children and examine whether recess MVPA varied by gender, socioeconomic status, season, urban/rural residency, and recess length. METHOD: Five-day accelerometry MVPA data were analyzed from 773 children (53.9% girls, 46.1% boys, 10- to 11-y-olds) from 471 schools. Binary logistic regression explored associations between meeting/not meeting the recommendation to spend 40% of recess time in MVPA and the aforementioned risk factors. Descriptive recess data were also analyzed. RESULTS: Participants spent an average of 3.2 minutes (SD 2.1) in MVPA during recess. Girls engaged in 2.5 minutes (SD 1.7) of MVPA compared with 4.0 minutes (SD 2.2) for boys. Only 6% of children met the recess MVPA recommendation. The odds of girls (odds ratio 0.09; 95% confidence interval, 0.04-0.25) meeting the recommendation was lower (P < .001) compared with boys. No statistically significant differences were observed in meeting the recommendation for the other risk factors. CONCLUSION: Levels of MVPA during school recess are very low in Scottish children, and interventions aimed at increasing MVPA during recess are needed.

Validation of mid-arm circumference for surveillance of obesity in African adolescent girls and adult women.

This study aimed to assess the validity of mid-arm circumference (MAC), also known as mid-upper arm circumference (MUAC), for classification of high body fatness in Namibian adolescent girls and women and to test whether classification accuracy of MUAC was higher than the traditional simple proxy for high fatness, the BMI. In 206 adolescent girls aged 13-19 years and 207 adult women aged 20-40 years, we defined obesity conventionally (BMI-for-age Z score ≥ 2·00, adolescents; adults BMI ≥ 30·0 kg/m2) and also defined obesity using published MAC cut-off values. 2H oxide dilution was used to measure total body water (TBW) to define high body fat percentage (≥ 30 % in the adolescents, ≥ 38 % in the adults), and we compared the ability of BMI and MAC to classify high body fatness correctly using sensitivity, specificity and predictive values. In the adolescents, obesity prevalence was 9·2 % (19/206) using BMI-for-age and 63·2 % (131/206) using TBW; sensitivity of BMI-for-age was 14·5 % (95 % CI 9·1, 22·0 %) but was improved significantly using MAC of 22·6 cm (sensitivity 96·9 %; 95 % CI 92·1 %, 99·3 %). In the adults, obesity prevalence was 30·4 % (63/207) using BMI and 57·0 % (118/207) using TBW, and sensitivity of BMI was 52·5 % (95 % CI 43·6, 62·2 %), but using a MAC of 30·6 cm sensitivity was 72·8 % (95 % CI 66·4, 82·6 %). Surveillance of obesity in African adolescent girls and adult women is likely to be improved substantially by use of MAC as an alternative to the BMI-for-age and BMI.

Substance use disorder screening and brief intervention in routine clinical practice in specialist adult mental health services: A systematic review.

BACKGROUND AND OBJECTIVES: Substance use disorders co-occurring with other mental health disorders are common and harmful. Clinical guidelines often recommend substance use screening and brief intervention though evidence about screening practice in mental health services is limited. This systematic review of routine clinical practice in adult mental health services aims to identify (a) proportions of screening and brief intervention, (b) how they are practised and (c) their outcomes. METHODS: We searched MEDLINE, PsycINFO and Embase and relevant Cochrane databases for articles until 31 July 2021 reporting on adults in English, regardless of geographical location. Backward snowball methods were used to locate additional articles. Screening, brief intervention and mental health services were defined. Data were extracted and variables compared related to setting, period, patient cohort, substances routine substance use disorder care pathways, and study quality was assessed. RESULTS: We identified 17 articles reporting routine screening within adult mental health services. Studies in community settings mainly reported on screening for alcohol and other substance use disorders, while studies from inpatient settings reported mainly on tobacco. There was marked variation in methods and screening proportions. Only two studies reported on brief intervention. CONCLUSION: This systematic review shows marked variation in mental health services routine screening practices with early focus on alcohol but more recently tobacco screening. We suggest approaches to enhancing implementation of screening and brief intervention in routine care, particularly using electronic health records.

Cut-point values for classifying active children and validity and reliability of physical activity questionnaire for children in Morocco.

BACKGROUND: The Physical Activity Questionnaire for Children (PAQ-C) is widely used to assess physical activity in populations; however, there is a lack of information about the psychometric properties (validity and reliability) and about the PAQ-C score meaning in populations from low-middle income countries. AIMS: The aim of this study is to evaluate the reliability and validity of PAQ-C and to determine the cut-point values of PAQ-C using accelerometry as a reference in a group of Moroccan children. METHODS: In a sample of 171 children and adolescents aged 8 to 14 years, physical activity was assessed with the GT3X + accelerometer and the PAQ-C. PAQ-C was administered for a second time (retest) after 1 week for a subsample (n = 73). Reliability was analyzed by intraclass correlation coefficient (ICC). The PAQ-C was compared against count per minute CPM and moderate to vigorous intensity PA (MVPA) obtained by accelerometry. Receiver operating curve analyses were performed to assess the performance of PAQ-C in identifying MVPA as measured by accelerometry (reference method). RESULTS: Test-retest reliability was poor with an ICC = (0.48 [0.27; 0.63] for the whole sample, while for the ≥11 year group, the intra-class correlation coefficient was moderate (0.71 [0.42; 0.86]. PAQ-C scores were significantly related to accelerometry-derived metrics of physical activity, CPM (R = 0.29, P < 0.001) and MVPA (R = 0.26, P < 0.001). For the age group ≥11 years, the associations between PAQ-C Scores and CPM and MVPA were stronger, respectively, R = 0.37 (P < 0.001), R = 0.38 (P < 0.0001). We identified that a PAQ-C Score cut-point of 2.33 (95%CI [0.43-0.68]) discriminated adequately between those who met physical activity guidelines and those that did not in the overall sample. CONCLUSIONS: The PAQ-C is valid and useful to assess population level physical activity in those ≥11 years in Morocco and so might be helpful in population surveillance of physical activity in Moroccan adolescents.

Global Matrix of Para Report Cards on Physical Activity of Children and Adolescents With Disabilities.

This is an overview of the results from 14 countries or jurisdictions in a Global Matrix of Para Report Cards on physical activity (PA) of children and adolescents with disabilities. The methodology was based on the Active Healthy Kids Global Alliance's Global Matrix 4.0. Data were aligned with 10 indicators (Overall PA, Organized Sport, Active Play, Active Transport, Physical Fitness, Sedentary Behavior, Family & Peers, Schools, Community & Environment, and Government) to produce Para Report Cards. Subsequently, there were 139 grades; 45% were incomplete, particularly for Active Play, Physical Fitness, and Family & Peers. Collectively, Overall PA was graded the lowest (F), with Schools and Government the highest (C). Disability-specific surveillance and research gaps in PA were apparent in 14 countries or jurisdictions around the world. More coverage of PA data in Para Report Cards is needed to serve as an advocacy tool to promote PA among children and adolescents with disabilities.

Update on the Features and Measurements of Experimental Acute Lung Injury in Animals: An Official American Thoracic Society Workshop Report.

Advancements in methods, technology, and our understanding of the pathobiology of lung injury have created the need to update the definition of experimental acute lung injury (ALI). We queried 50 participants with expertise in ALI and acute respiratory distress syndrome using a Delphi method composed of a series of electronic surveys and a virtual workshop. We propose that ALI presents as a "multidimensional entity" characterized by four "domains" that reflect the key pathophysiologic features and underlying biology of human acute respiratory distress syndrome. These domains are 1) histological evidence of tissue injury, 2) alteration of the alveolar-capillary barrier, 3) presence of an inflammatory response, and 4) physiologic dysfunction. For each domain, we present "relevant measurements," defined as those proposed by at least 30% of respondents. We propose that experimental ALI encompasses a continuum of models ranging from those focusing on gaining specific mechanistic insights to those primarily concerned with preclinical testing of novel therapeutics or interventions. We suggest that mechanistic studies may justifiably focus on a single domain of lung injury, but models must document alterations of at least three of the four domains to qualify as "experimental ALI." Finally, we propose that a time criterion defining "acute" in ALI remains relevant, but the actual time may vary based on the specific model and the aspect of injury being modeled. The continuum concept of ALI increases the flexibility and applicability of the definition to multiple models while increasing the likelihood of translating preclinical findings to critically ill patients.

Ultrasound renal denervation for hypertension resistant to a triple medication pill (RADIANCE-HTN TRIO): a randomised, multicentre, single-blind, sham-controlled trial.

BACKGROUND: Endovascular renal denervation reduces blood pressure in patients with mild-to-moderate hypertension, but its efficacy in patients with true resistant hypertension has not been shown. We aimed to assess the efficacy and safety of endovascular ultrasound renal denervation in patients with hypertension resistant to three or more antihypertensive medications. METHODS: In a randomised, international, multicentre, single-blind, sham-controlled trial done at 28 tertiary centres in the USA and 25 in Europe, we included patients aged 18-75 years with office blood pressure of at least 140/90 mm Hg despite three or more antihypertensive medications including a diuretic. Eligible patients were switched to a once daily, fixed-dose, single-pill combination of a calcium channel blocker, an angiotensin receptor blocker, and a thiazide diuretic. After 4 weeks of standardised therapy, patients with daytime ambulatory blood pressure of at least 135/85 mm Hg were randomly assigned (1:1) by computer (stratified by centres) to ultrasound renal denervation or a sham procedure. Patients and outcome assessors were masked to randomisation. Addition of antihypertensive medications was allowed if specified blood pressure thresholds were exceeded. The primary endpoint was the change in daytime ambulatory systolic blood pressure at 2 months in the intention-to-treat population. Safety was also assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT02649426. FINDINGS: Between March 11, 2016, and March 13, 2020, 989 participants were enrolled and 136 were randomly assigned to renal denervation (n=69) or a sham procedure (n=67). Full adherence to the combination medications at 2 months among patients with urine samples was similar in both groups (42 [82%] of 51 in the renal denervation group vs 47 [82%] of 57 in the sham procedure group; p=0·99). Renal denervation reduced daytime ambulatory systolic blood pressure more than the sham procedure (-8·0 mm Hg [IQR -16·4 to 0·0] vs -3·0 mm Hg [-10·3 to 1·8]; median between-group difference -4·5 mm Hg [95% CI -8·5 to -0·3]; adjusted p=0·022); the median between-group difference was -5·8 mm Hg (95% CI -9·7 to -1·6; adjusted p=0·0051) among patients with complete ambulatory blood pressure data. There were no differences in safety outcomes between the two groups. INTERPRETATION: Compared with a sham procedure, ultrasound renal denervation reduced blood pressure at 2 months in patients with hypertension resistant to a standardised triple combination pill. If the blood pressure lowering effect and safety of renal denervation are maintained in the long term, renal denervation might be an alternative to the addition of further antihypertensive medications in patients with resistant hypertension. FUNDING: ReCor Medical.

Surveillance to improve physical activity of children and adolescents.

The global transition to current low levels of habitual physical activity among children and adolescents began in the second half of the last century. Low physical activity harms health in both the short term (during childhood and adolescence) and long term (during adulthood). In turn, low physical activity could limit progress towards several sustainable development goals, undermine noncommunicable disease prevention, delay physical and mental health recovery from the coronavirus disease 2019 pandemic, increase health-care costs and hinder responses to climate change. However, despite the importance of physical activity, public health surveillance among children and adolescents is very limited globally and low levels of physical activity in children is not on the public health agenda in many countries, irrespective of their level of economic development. This article details proposals for improvements in global public health surveillance of physical activity from birth to adolescence based on recent systematic reviews, international collaborations and World Health Organization guidelines and strategies. Empirical examples from several countries illustrate how improved surveillance of physical activity can lead to public health initiatives. Moreover, better surveillance raises awareness of the extent of physical inactivity, thereby making an invisible problem visible, and can lead to greater capacity in physical activity policy and practice. The time has arrived for a step change towards more systematic physical activity surveillance from infancy onwards that could help inform and inspire changes in public health policy and practice globally.

Durant la seconde moitié du siècle dernier, l'activité physique des enfants et adolescents a commencé à baisser à l'échelle mondiale pour atteindre le faible niveau actuel. La sédentarité a des effets néfastes sur la santé, tant à court terme (pendant l'enfance et l'adolescence) qu'à long terme (à l'âge adulte). Elle peut également entraver la progression vers de nombreux objectifs de développement durable, compromettre les efforts de prévention des maladies non transmissibles, retarder la guérison physique et mentale liée à la pandémie de maladie à coronavirus 2019, accroître les dépenses en soins de santé et freiner les réactions au changement climatique. Pourtant, malgré l'importance que revêt l'activité physique, rares sont les dispositifs de surveillance de la santé publique mis en place pour les enfants et adolescents dans le monde. En outre, la lutte contre la sédentarité chez les plus jeunes ne figure pas parmi les priorités de santé publique dans la plupart des pays, quel que soit le niveau de développement économique de ces derniers. Le présent article détaille une série de propositions visant à améliorer la surveillance de la santé publique en matière d'activité physique de la naissance à l'adolescence, fondées sur des revues systématiques récentes, des collaborations internationales ainsi que des stratégies et lignes directrices de l'Organisation mondiale de la Santé. Des exemples empiriques provenant de plusieurs pays illustrent comment cette amélioration peut déboucher sur des initiatives de santé publique. De plus, une meilleure surveillance permet de sensibiliser à l'ampleur de cette inactivité, donnant ainsi de la visibilité à un problème jusqu'alors invisible, et peut renforcer les capacités politiques et pratiques relatives à l'activité physique. Il est temps de procéder à un changement en profondeur afin de surveiller plus systématiquement l'activité physique dès le plus jeune âge, en vue d'orienter et d'encourager l'évolution des politiques et pratiques en la matière dans le monde.

La transición mundial hacia los niveles bajos actuales de actividad física regular entre niños y adolescentes comenzó en la segunda mitad del siglo pasado. La disminución de la actividad física perjudica la salud tanto a corto plazo (durante la infancia y la adolescencia) como a largo plazo (durante la edad adulta). A su vez, la falta de actividad física podría limitar el progreso hacia varios objetivos de desarrollo sostenible, socavar la prevención de enfermedades no transmisibles, retrasar la recuperación de la salud física y mental tras la pandemia de la enfermedad por coronavirus de 2019, aumentar los costes de la atención sanitaria y dificultar las respuestas al cambio climático. No obstante, a pesar de la importancia de la actividad física, la vigilancia de la salud pública entre los niños y los adolescentes es muy limitada a nivel mundial y los niveles bajos de actividad física en los niños no se incluyen en la agenda de salud pública de muchos países, sea cual sea su nivel de desarrollo económico. En este artículo, se detallan propuestas para mejorar la vigilancia de la actividad física en la salud pública a nivel mundial, desde el nacimiento hasta la adolescencia, a partir de recientes revisiones sistemáticas, colaboraciones internacionales y directrices y estrategias de la Organización Mundial de la Salud. Ejemplos empíricos de varios países ilustran cómo una mejor vigilancia de la actividad física puede conducir a iniciativas de salud pública. Asimismo, una mejor vigilancia aumenta la concienciación sobre el alcance de la inactividad física, haciendo evidente un problema poco visible, y puede conducir a una mayor capacidad en la política y la práctica de la actividad física. Ha llegado el momento de dar un paso adelante hacia una vigilancia más sistemática de la actividad física desde la infancia que podría ayudar a informar e inspirar cambios en la política y la práctica de la salud pública en todo el mundo.

A genome-wide association study of survival in patients with sepsis.

BACKGROUND: Sepsis is a severe systemic inflammatory response to infections that is accompanied by organ dysfunction and has a high mortality rate in adult intensive care units. Most genetic studies have identified gene variants associated with development and outcomes of sepsis focusing on biological candidates. We conducted the first genome-wide association study (GWAS) of 28-day survival in adult patients with sepsis. METHODS: This study was conducted in two stages. The first stage was performed on 687 European sepsis patients from the GEN-SEP network and 7.5 million imputed variants. Association testing was conducted with Cox regression models, adjusting by sex, age, and the main principal components of genetic variation. A second stage focusing on the prioritized genetic variants was performed on 2,063 ICU sepsis patients (1362 European Americans and 701 African-Americans) from the MESSI study. A meta-analysis of results from the two stages was conducted and significance was established at p < 5.0 × 10-8. Whole-blood transcriptomic, functional annotations, and sensitivity analyses were evaluated on the identified genes and variants. FINDINGS: We identified three independent low-frequency variants associated with reduced 28-day sepsis survival, including a missense variant in SAMD9 (hazard ratio [95% confidence interval] = 1.64 [1.37-6.78], p = 4.92 × 10-8). SAMD9 encodes a possible mediator of the inflammatory response to tissue injury. INTERPRETATION: We performed the first GWAS of 28-day sepsis survival and identified novel variants associated with reduced survival. Larger sample size studies are needed to better assess the genetic effects in sepsis survival and to validate the findings.

Prevalence and novel risk factors for vitamin D insufficiency in elite athletes: systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Vitamin D insufficiency may be common among elite athletes, but prevalence is unclear, and some potentially important risk factors are uncertain. The present study aimed to (a) estimate the prevalence of vitamin D insufficiency in elite athletes, and (b) examine differences in prevalence between the sexes, and between adults and adolescents, from recent studies which used a contemporary definition of insufficiency. METHODS: Four databases (Web of Science, SPORTDiscus, PubMed, and Sports Medicine and Education Index) were searched for studies in elite athletes. Literature selection, data extraction, and risk of bias assessment were conducted independently by two researchers. Vitamin D insufficiency was defined as 25(OH)D < 50 nmol/L. Meta-analysis was conducted, using R software x64 4.0.2, to provide estimates of prevalence of insufficiency for adults and adolescents, and to examine between-sex differences in risk of insufficiency. RESULTS: From the initial 943 literature search hits, 51 studies were eligible with 5456 participants, 33 studies in adults (12/33 in winter and spring), 15 studies in adolescents (6/15 in winter and spring) and 3 studies with age of study participants not given. Prevalence of vitamin D insufficiency from meta-analysis was 30% (95% CI 22-39%) in adults and prevalence was higher, though not significantly so, at 39% (95% CI 25-55%) in adolescents. Differences in the prevalence of insufficiency between the sexes for the eight studies which provided within-study comparisons was not significant (RR = 1.0; 95% CI 0.79-1.26). Evidence quality was moderate. CONCLUSIONS: Prevalence of vitamin D insufficiency (≤ 50 nmol/L) in elite athletes is high, suggesting a need for greater attention to prevention and treatment. Prevalence estimates in the present study are conservative due to a relative lack of studies in winter. While there was no evidence of higher risk among women than men in the present study, there was less evidence on women.

Comorbidity between mood and substance-related disorders: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Evidence indicates that mood disorders often co-occur with substance-related disorders. However, pooling comorbidity estimates can be challenging due to heterogeneity in diagnostic criteria and in the overall study design. The aim of this study was to systematically review and, where appropriate, meta-analyse estimates related to the pairwise comorbidity between mood disorders and substance-related disorders, after sorting these estimates by various study designs. METHODS: We searched PubMed (MEDLINE), Embase, CINAHL and Web of Science for publications between 1980 and 2017 regardless of geographical location and language. We meta-analysed estimates from original articles in 4 broadly defined mood and 35 substance-related disorders. RESULTS: After multiple eligibility steps, we included 120 studies for quantitative analysis. In general, regardless of variations in diagnosis type, temporal order or use of adjustments, there was substantial comorbidity between mood and substance-related disorders. We found a sixfold elevated risk between broadly defined mood disorder and drug dependence (odds ratio = 5.7) and fivefold risk between depression and cannabis dependence (odds ratio = 4.9) while the highest pooled estimate, based on period prevalence risk, was found between broadly defined dysthymic disorder and drug dependence (odds ratio = 11.3). Based on 56 separate meta-analyses, all pooled odds ratios were above 1, and 46 were significantly greater than 1 (i.e. the 95% confidence intervals did not include 1). CONCLUSION: This review found robust and consistent evidence of an increased risk of comorbidity between many combinations of mood and substance-related disorders. We also identified a number of under-researched mood and substance-related disorders, suitable for future scrutiny. This review reinforces the need for clinicians to remain vigilant in order to promptly identify and treat these common types of comorbidity.

Characteristics, Outcomes, and Trends of Patients With COVID-19-Related Critical Illness at a Learning Health System in the United States.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic continues to surge in the United States and globally. OBJECTIVE: To describe the epidemiology of COVID-19-related critical illness, including trends in outcomes and care delivery. DESIGN: Single-health system, multihospital retrospective cohort study. SETTING: 5 hospitals within the University of Pennsylvania Health System. PATIENTS: Adults with COVID-19-related critical illness who were admitted to an intensive care unit (ICU) with acute respiratory failure or shock during the initial surge of the pandemic. MEASUREMENTS: The primary exposure for outcomes and care delivery trend analyses was longitudinal time during the pandemic. The primary outcome was all-cause 28-day in-hospital mortality. Secondary outcomes were all-cause death at any time, receipt of mechanical ventilation (MV), and readmissions. RESULTS: Among 468 patients with COVID-19-related critical illness, 319 (68.2%) were treated with MV and 121 (25.9%) with vasopressors. Outcomes were notable for an all-cause 28-day in-hospital mortality rate of 29.9%, a median ICU stay of 8 days (interquartile range [IQR], 3 to 17 days), a median hospital stay of 13 days (IQR, 7 to 25 days), and an all-cause 30-day readmission rate (among nonhospice survivors) of 10.8%. Mortality decreased over time, from 43.5% (95% CI, 31.3% to 53.8%) to 19.2% (CI, 11.6% to 26.7%) between the first and last 15-day periods in the core adjusted model, whereas patient acuity and other factors did not change. LIMITATIONS: Single-health system study; use of, or highly dynamic trends in, other clinical interventions were not evaluated, nor were complications. CONCLUSION: Among patients with COVID-19-related critical illness admitted to ICUs of a learning health system in the United States, mortality seemed to decrease over time despite stable patient characteristics. Further studies are necessary to confirm this result and to investigate causal mechanisms. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Injury by knife crime amongst children is associated with socioeconomic deprivation: an observational study.

PURPOSE: Children who live in areas of socioeconomic deprivation may be at higher risk of being victims of violent crime such as knife wounds. The current study investigated whether socioeconomic disparity was associated with higher risk of knife crime. METHODS: An observational study included patients aged ≤ 17 years at a UK Major Trauma Centre injured by knife trauma from 2016 to 2022. Indices of deprivation were recorded according to the zip code of residence and compared with those of all of England. These included Index of Multiple Deprivation (IMD); income; employment; education and skills; health and disability; crime; barriers to housing and services; living environment; and Income Deprivation Affecting Children Index (IDACI). RESULTS: There were 139 patients (96% male) with median age of 16 years. When compared with the whole of England, patients had worse indices of IMD (p = 0.021); income (p < 0.001); employment (p < 0.001); education and skills (p < 0.001); health and disability; and IDACI (p < 0.001). There were no significant differences in indices of crime, barriers to housing and services or living environment. CONCLUSIONS: Paediatric knife injury was associated with poor socioeconomic status in multiple domains. Focussed efforts to address socioeconomic disparities should be a priority as a public health measure for vulnerable children.

Results from Scotland's 2021 report card on physical activity and health for children and youth: Grades, secular trends, and socio-economic inequalities.

Background: The 2021 Active Healthy Kids Scotland Report Card aimed to identify secular trends and socio-economic inequalities, and to assess the physical activity and health of children and youth prior to COVID-19. Methods: An expert panel searched for data published in 2018-2020. Grades were assigned to nationally representative data using the Active Healthy Kids Global Alliance methodology. Results: The expert panel, following national consultation, awarded the following grades: Community/Environment B-, Organized Sport and Physical Activity B-, Government/Policy C-/C+, Active Transportation C-, Family/Peers D-, Recreational Screen Time F. Five indicators were graded inconclusive (INC): Overall Physical Activity; Active Play; Physical Fitness; Diet; Obesity. Grades have remained stable or declined, and surveillance has reduced, increasing the number of INC grades. There were marked socio-economic inequalities for eight indicators (Recreational Screen Time; Overall Physical Activity; Organized Sport & Physical Activity; Active Transportation; Diet; Obesity; Family/Peers; Community/Environment). Conclusions: Despite a decade of favorable policy, physical activity and health of children and youth has not improved, and marked socio-economic inequalities continue to persist in Scotland. There is a clear need for greater monitoring of physical activity and health, and improved policy implementation and evaluation, particularly as many indicators and related inequalities may have worsened following the COVID-19 pandemic.