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Social and occupational functioning deficits contribute to overall disability in hoarding disorder (HD), and psychiatric symptoms are likely strong contributors. In turn, social/occupational impairment and psychiatric illness are known to contribute to suicidality. However, few studies have examined the relationship between these factors. We examined these relationships in 313 treatment seeking individuals with HD, measuring hoarding severity with the Saving Inventory, Revised and functional impairment with the Activities of Daily Living for Hoarding Disorder (ADL-H). We created a composite social/occupational function variable assessing employment, cohabitation, and marriage. A path analysis was used to assess the relationship between social functioning, occupational functioning, hoarding related functional impairment in activities of daily living, hoarding severity, psychiatric burden, and suicidality in HD. At least one lifetime psychiatric comorbidity was noted in 61% of participants. High rates of unemployment, living alone, never marrying or being divorced/separated, and lifetime suicide attempts were present. Hoarding severity and hoarding-related functional impairment were associated with social/occupational impairment, and, along with psychiatric burden, with suicidality in this population. These findings suggest that thorough psychiatric evaluation and assessment of suicidality is warranted for those with HD, and that hoarding-related functional impairment is closely related to measures of real-world social functioning.

BackgroundThe unique phenotypic and genetic aspects of obsessive-compulsive (OCD) and attention-deficit/hyperactivity disorder (ADHD) among individuals with Tourette syndrome (TS) are not well characterized. Here, we examine symptom patterns and heritability of OCD and ADHD in TS families.MethodOCD and ADHD symptom patterns were examined in TS patients and their family members (N = 3494) using exploratory factor analyses (EFA) for OCD and ADHD symptoms separately, followed by latent class analyses (LCA) of the resulting OCD and ADHD factor sum scores jointly; heritability and clinical relevance of the resulting factors and classes were assessed.ResultsEFA yielded a 2-factor model for ADHD and an 8-factor model for OCD. Both ADHD factors (inattentive and hyperactive/impulsive symptoms) were genetically related to TS, ADHD, and OCD. The doubts, contamination, need for sameness, and superstitions factors were genetically related to OCD, but not ADHD or TS; symmetry/exactness and fear-of-harm were associated with TS and OCD while hoarding was associated with ADHD and OCD. In contrast, aggressive urges were genetically associated with TS, OCD, and ADHD. LCA revealed a three-class solution: few OCD/ADHD symptoms (LC1), OCD & ADHD symptoms (LC2), and symmetry/exactness, hoarding, and ADHD symptoms (LC3). LC2 had the highest psychiatric comorbidity rates (⩾50% for all disorders).ConclusionsSymmetry/exactness, aggressive urges, fear-of-harm, and hoarding show complex genetic relationships with TS, OCD, and ADHD, and, rather than being specific subtypes of OCD, transcend traditional diagnostic boundaries, perhaps representing an underlying vulnerability (e.g. failure of top-down cognitive control) common to all three disorders.

BackgroundWomen who terminate pregnancies drink more subsequent to the pregnancy than women who give birth, including women who give birth after seeking to terminate a pregnancy.MethodsData are from the Turnaway Study, a prospective, longitudinal study of 956 women who sought to terminate pregnancies at 30 U.S. facilities. This paper focuses on the 452 women who received terminations just below facility gestational limits and 231 who were denied terminations because they presented just beyond facility gestational limits. This study examined whether baseline characteristics moderate the relationship between termination and subsequent binge drinking and whether stress, feelings about the pregnancy, and number of social roles mediate the relationship.ResultsOnly having had a previous live birth modified the termination-binge drinking relationship. Among women with previous live births, binge drinking was reduced among women carrying to term compared to terminating the pregnancy. Among women who had not had a previous live birth, however, the reduction in binge drinking among those denied termination was not sustained over time, and binge drinking of those who had and had not had terminations converged by 2.5 years. Neither stress, negative emotions, nor social roles mediated effects on binge drinking. Positive emotions at one week mediated effects on binge drinking at six months, although positive emotions at two years did not mediate effects on binge drinking at 2.5 years.ConclusionsHigher levels of binge drinking among those who terminate pregnancies do not appear due to stress or to negative emotions. Only parous women - and not nulliparous women - denied terminations experienced sustained reductions in binge drinking over time.

© 2015 Ramo et al.Background: Tobacco use remains the leading cause of premature morbidity and mortality in the United States. Young adults are less successful at quitting, use cessation treatment less often than smokers of other ages, and can be a challen

© 2014 Jiang et al.; licensee BioMed Central Ltd.Background: Without effective treatment, PTSD and depression can cause persistent disability in disaster-affected populations. Methods: Our objective was to test the efficacy of Interpersonal Psychotherapy (

Objective: Much of what we know about the course of alcohol consumption in problem and dependent drinkers comes from studies of in-treatment populations. Less is known about the natural course of alcohol consumption among such drinkers in the general population and what predicts how much they drink.Method: This study examined alcohol consumption over the course of 11 years in a randomly selected sample of 672 problem and dependent drinkers from a single, heterogeneous U.S. county.Results: Alcohol consumption declined and leveled off over time but did not decrease to the average general U.S. population level. Several indicators of ongoing problems with drinking are associated with high levels of drinking over time: having a heavy-drinking network, receiving suggestions to do something about one's drinking, and going to treatment. Factors associated with less drinking include having contact with community agencies and going to Alcoholics Anonymous (AA).Conclusions: Results suggest that problem and dependent drinkers continue to drink at an elevated level over the course of years. Gatekeepers, family members, and policymakers should encourage and facilitate contact with social service agencies and with AA for problem drinkers. Suggestions from others to do something about one's drinking and seeking specialty care occur more often in those with more severe problems and do not appear to be linked to less drinking over time. [ABSTRACT FROM AUTHOR]

Although many individuals applying for political asylum allege maltreatment and sometimes torture in their countries of origin, the utility of medical evaluations in asylum adjudication has not been documented. This study compares the asylum grant rate among US asylum seekers who received medical evaluations from Physicians for Human Rights (PHR), with rates among asylum seekers who did not receive PHR evaluations. Retrospective analysis was carried out on all asylum cases referred to PHR between 2000 and 2004 for medical evaluations for which adjudication outcome was available. Basic demographic information was obtained: age, sex, country of origin, English language ability, US region where adjudication occurred, whether legal representation was pro bono, type of evaluation, provision of oral court testimony, and whether asylum seekers were in detention. Cases were analyzed descriptively and with chi square tests. Between 2000 and 2004, 1663 asylum seekers received medical evaluations from PHR; the adjudication status (either granted or denied) was determined in 746 cases at the time of the study. Of these cases, 89% were granted asylum, compared to the national average of 37.5% among US asylum seekers who did not receive PHR evaluations. Medical evaluations may be critical in the adjudications of asylum cases when maltreatment is alleged. [ABSTRACT FROM AUTHOR]

This study aimed to identify subgroups of pregnant women at imminent (1 year) risk for major depressive episodes. Participants were 84 low-income, predominantly Mexican women using public sector obstetrics services who participated in monthly interviews during pregnancy and up to 6 months postpartum. Participants were designated a priori as 'more vulnerable' or 'less vulnerable' to future perinatal depression based on evidence of mood regulation problems defined as (a) a self-reported history of major depressive episodes, (MDE) and/or (b) high current depressive symptom scores on a continuous depression scale. Two definitions of a major depressive episode based on meeting 2 or 3 DSM-IV MDE criteria, were used to measure the incidence of a new major depressive episode. Results suggest that more vulnerable groups (i.e., with the greatest mood regulation problems) had a higher incidence of major depressive episodes than less vulnerable groups. Implications for screening and developing preventive interventions for postpartum depression are discussed. [ABSTRACT FROM AUTHOR]

I reviewed sample estimation methods for research designs involving nonindependent data and a dichotomous response variable to examine the importance of proper sample size estimation and the need to align methods of sample size estimation with planned methods of statistical analysis. Examples and references to published literature are provided in this article. When the method of sample size estimation is not in concert with the method of planned analysis, poor estimates may result. The effects of multiple measures over time also need to be considered. Proper sample size estimation is often overlooked. Alignment of the sample size estimation method with the planned analysis method, especially in studies involving nonindependent data, will produce appropriate estimates. [ABSTRACT FROM AUTHOR]

Context: Despite evidence that methadone maintenance treatment (MMT) is effective for opioid dependence, it remains a controversial therapy because of its indefinite provision of a dependence-producing medication.Objective: To compare outcomes of patients with opioid dependence treated with MMT vs an alternative treatment, psychosocially enriched 180-day methadone-assisted detoxification.Design: Randomized controlled trial conducted from May 1995 to April 1999.Setting: Research clinic in an established drug treatment service.Patients: Of 858 volunteers screened, 179 adults with diagnosed opioid dependence were randomized into the study; 154 completed 12 weeks of follow-up.Interventions: Patients were randomized to MMT (n = 91), which required 2 hours of psychosocial therapy per week during the first 6 months; or detoxification (n = 88), which required 3 hours of psychosocial therapy per week, 14 education sessions, and 1 hour of cocaine group therapy, if appropriate, for 6 months, and 6 months of (nonmethadone) aftercare services.Main Outcome Measures: Treatment retention, heroin and cocaine abstinence (by self-report and monthly urinalysis), human immunodeficiency virus (HIV) risk behaviors (Risk of AIDS Behavior scale score), and function in 5 problem areas: employment, family, psychiatric, legal, and alcohol use (Addiction Severity Index), compared by intervention group.Results: Methadone maintenance therapy resulted in greater treatment retention (median, 438.5 vs 174.0 days) and lower heroin use rates than did detoxification. Cocaine use was more closely related to study dropout in detoxification than in MMT. Methadone maintenance therapy resulted in a lower rate of drug-related (mean [SD] at 12 months, 2.17 [3.88] vs 3.73 [6.86]) but not sex-related HIV risk behaviors and in a lower severity score for legal status (mean [SD] at 12 months, 0.05 [0.13] vs 0.13 [0.19]). There were no differences between groups in employment or family functioning or alcohol use. In both groups, monthly heroin use rates were 50% or greater, but days of use per month dropped markedly from baseline.Conclusions: Our results confirm the usefulness of MMT in reducing heroin use and HIV risk behaviors. Illicit opioid use continued in both groups, but frequency was reduced. Results do not provide support for diverting resources from MMT into long-term detoxification. [ABSTRACT FROM AUTHOR]

Background: Automated analysis of lung computed tomography (CT) scans may help characterize subphenotypes of acute respiratory illness. We integrated lung CT features measured via deep learning with clinical and laboratory data in spontaneously breathing subjects to enhance the identification of COVID-19 subphenotypes., Methods: This is a multicenter observational cohort study in spontaneously breathing patients with COVID-19 respiratory failure exposed to early lung CT within 7 days of admission. We explored lung CT images using deep learning approaches to quantitative and qualitative analyses; latent class analysis (LCA) by using clinical, laboratory and lung CT variables; regional differences between subphenotypes following 3D spatial trajectories., Results: Complete datasets were available in 559 patients. LCA identified two subphenotypes (subphenotype 1 and 2). As compared with subphenotype 2 (n = 403), subphenotype 1 patients (n = 156) were older, had higher inflammatory biomarkers, and were more hypoxemic. Lungs in subphenotype 1 had a higher density gravitational gradient with a greater proportion of consolidated lungs as compared with subphenotype 2. In contrast, subphenotype 2 had a higher density submantellar-hilar gradient with a greater proportion of ground glass opacities as compared with subphenotype 1. Subphenotype 1 showed higher prevalence of comorbidities associated with endothelial dysfunction and higher 90-day mortality than subphenotype 2, even after adjustment for clinically meaningful variables., Conclusions: Integrating lung-CT data in a LCA allowed us to identify two subphenotypes of COVID-19, with different clinical trajectories. These exploratory findings suggest a role of automated imaging characterization guided by machine learning in subphenotyping patients with respiratory failure., Trial Registration: ClinicalTrials.gov Identifier: NCT04395482. Registration date: 19/05/2020., (© 2024. The Author(s).)

Background: Rapidly improving acute respiratory distress syndrome (RIARDS) is an increasingly appreciated subgroup of ARDS in which hypoxemia improves within 24 h after initiation of mechanical ventilation. Detailed clinical and biological features of RIARDS have not been clearly defined, and it is unknown whether RIARDS is associated with the hypoinflammatory or hyperinflammatory phenotype of ARDS. The purpose of this study was to define the clinical and biological features of RIARDS and its association with inflammatory subphenotypes., Methods: We analyzed data from 215 patients who met Berlin criteria for ARDS (endotracheally intubated) and were enrolled in a prospective observational cohort conducted at two sites, one tertiary care center and one urban safety net hospital. RIARDS was defined according to previous studies as improvement of hypoxemia defined as (i) PaO 2 :FiO 2  > 300 or (ii) SpO2: FiO 2  > 315 on the day following diagnosis of ARDS (day 2) or (iii) unassisted breathing by day 2 and for the next 48 h (defined as absence of endotracheal intubation on day 2 through day 4). Plasma biomarkers were measured on samples collected on the day of study enrollment, and ARDS phenotypes were allocated as previously described., Results: RIARDS accounted for 21% of all ARDS participants. Patients with RIARDS had better clinical outcomes compared to those with persistent ARDS, with lower hospital mortality (13% vs. 57%; p value < 0.001) and more ICU-free days (median 24 vs. 0; p value < 0.001). Plasma levels of interleukin-6, interleukin-8, and plasminogen activator inhibitor-1 were significantly lower among patients with RIARDS. The hypoinflammatory phenotype of ARDS was more common among patients with RIARDS (78% vs. 51% in persistent ARDS; p value = 0.001)., Conclusions: This study identifies a high prevalence of RIARDS in a multicenter observational cohort and confirms the more benign clinical course of these patients. We report the novel finding that RIARDS is characterized by lower concentrations of plasma biomarkers of inflammation compared to persistent ARDS, and that hypoinflammatory ARDS is more prevalent among patients with RIARDS. Identification and exclusion of RIARDS could potentially improve prognostic and predictive enrichment in clinical trials., (© 2024. The Author(s).)

Rationale: Two molecular phenotypes have been identified in acute respiratory distress syndrome (ARDS). In the ROSE (Reevaluation of Systemic Early Neuromuscular Blockade) trial of cisatracurium in moderate to severe ARDS, we addressed three unanswered questions: 1 ) Do the same phenotypes emerge in a more severe ARDS cohort with earlier recruitment; 2 ) Do phenotypes respond differently to neuromuscular blockade? and 3 ) What biological pathways most differentiate inflammatory phenotypes? Methods: We performed latent class analysis in ROSE using preenrollment clinical and protein biomarkers. In a subset of patients ( n  = 134), we sequenced whole-blood RNA using enrollment and Day 2 samples and performed differential gene expression and pathway analyses. Informed by the differential gene expression analysis, we measured additional plasma proteins and evaluated their abundance relative to gene expression amounts. Measurements and Main Results: In ROSE, we identified the hypoinflammatory (60.4%) and hyperinflammatory (39.6%) phenotypes with similar biological and clinical characteristics as prior studies, including higher mortality at Day 90 for the hyperinflammatory phenotype (30.3% vs. 61.6%; P  < 0.0001). We observed no treatment interaction between the phenotypes and randomized groups for mortality. The hyperinflammatory phenotype was enriched for genes associated with innate immune response, tissue remodeling, and zinc metabolism at Day 0 and collagen synthesis and neutrophil degranulation at Day 2. Longitudinal changes in gene expression patterns differed dependent on survivorship. For most highly expressed genes, we observed correlations with their corresponding plasma proteins' abundance. However, for the class-defining plasma proteins in the latent class analysis, no correlation was observed with their corresponding genes' expression. Conclusions: The hyperinflammatory and hypoinflammatory phenotypes have different clinical, protein, and dynamic transcriptional characteristics. These findings support the clinical and biological potential of molecular phenotypes to advance precision care in ARDS.

Background: In sepsis and acute respiratory distress syndrome (ARDS), heterogeneity has contributed to difficulty identifying effective pharmacotherapies. In ARDS, two molecular phenotypes (hypoinflammatory and hyperinflammatory) have consistently been identified, with divergent outcomes and treatment responses. In this study, we sought to derive molecular phenotypes in critically ill adults with sepsis, determine their overlap with previous ARDS phenotypes, and evaluate whether they respond differently to treatment in completed sepsis trials., Methods: We used clinical data and plasma biomarkers from two prospective sepsis cohorts, the Validating Acute Lung Injury biomarkers for Diagnosis (VALID) study (N=1140) and the Early Assessment of Renal and Lung Injury (EARLI) study (N=818), in latent class analysis (LCA) to identify the optimal number of classes in each cohort independently. We used validated models trained to classify ARDS phenotypes to evaluate concordance of sepsis and ARDS phenotypes. We applied these models retrospectively to the previously published Prospective Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis and Septic Shock (PROWESS-SHOCK) trial and Vasopressin and Septic Shock Trial (VASST) to assign phenotypes and evaluate heterogeneity of treatment effect., Findings: A two-class model best fit both VALID and EARLI (p<0·0001). In VALID, 804 (70·5%) of the 1140 patients were classified as hypoinflammatory and 336 (29·5%) as hyperinflammatory; in EARLI, 530 (64·8%) of 818 were hypoinflammatory and 288 (35·2%) hyperinflammatory. We observed higher plasma pro-inflammatory cytokines, more vasopressor use, more bacteraemia, lower protein C, and higher mortality in the hyperinflammatory than in the hypoinflammatory phenotype (p<0·0001 for all). Classifier models indicated strong concordance between sepsis phenotypes and previously identified ARDS phenotypes (area under the curve 0·87-0·96, depending on the model). Findings were similar excluding participants with both sepsis and ARDS. In PROWESS-SHOCK, 1142 (68·0%) of 1680 patients had the hypoinflammatory phenotype and 538 (32·0%) had the hyperinflammatory phenotype, and response to activated protein C differed by phenotype (p=0·0043). In VASST, phenotype proportions were similar to other cohorts; however, no treatment interaction with the type of vasopressor was observed (p=0·72)., Interpretation: Molecular phenotypes previously identified in ARDS are also identifiable in multiple sepsis cohorts and respond differently to activated protein C. Molecular phenotypes could represent a treatable trait in critical illness beyond the patient's syndromic diagnosis., Funding: US National Institutes of Health., Competing Interests: Declaration of interests PS reports funding from the US National Institutes of Health (NIH) and National Institute of General Medical Sciences; and consulting fees from AstraZeneca. LBW reports funding from NIH, Department of Defense (DoD), Genentech, Boehringer Ingelheim, and CSL Behring; consulting fees from Akebia Therapeutics, Santhera, Global Blood Therapeutics, and Boehringer Ingelheim; and stock options in Virtuoso Surgical. CSC reports funding from NIH; research grants from Roche Genentech and Quantum Leap Healthcare Collaborative; consulting fees from Vasomune Therapeutics, GEn1E Lifesciences, NGM Bio, Cellenkos, and Janssen; and a patent on metagenomic sequencing for sepsis diagnosis (co-recipient). MAM reports funding from Roche Genentech, Quantum Therapeutics, NIH/National Heart, Lung, and Blood Institute/National Institute of Allergy and Infectious Diseases, DoD, and California Institute for Regenerative Medicine; and consulting fees from Johnson & Johnson, Gilead Sciences, and Novartis. MMC reports funding from NIH and DoD; and intellectual property royalties from an issued patent (#11 410 777). JAR reports an investigator-initiated grant from Grifols provided to and administered by the University of British Columbia, Canadian Institutes of Health Research; three grants from the St Paul's Foundation; patents owned by the University of British Columbia related to the use of PCSK9 inhibitor(s) in sepsis and the use of vasopressin in septic shock, and by Ferring Pharmaceuticals for use of selepressin in septic shock; formerly being a founder, Director, and shareholder in Cyon Therapeutics (now closed); being a shareholder in Molecular You; receiving consulting fees in the last 3 years from SIB, Ferring Pharmaceuticals, and Par Pharmaceutical; and having been a funded member of the Data and Safety Monitoring Board of an NIH-sponsored trial of plasma in COVID-19 (PASS-IT-ON). KDL reports grants from NIH: National Institute of Diabetes and Digestive and Kidney Diseases; consulting fees from bioMérieux, UpToDate, SeaStar Medical, AM-Pharma, and Baxter; and stock or stock options in Amgen. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Importance: Reducing the duration of untreated psychosis (DUP) is essential to improving outcomes for people with first-episode psychosis (FEP). Current US approaches are insufficient to reduce DUP to international standards of less than 90 days., Objective: To determine whether population-based electronic screening in addition to standard targeted clinician education increases early detection of psychosis and decreases DUP, compared with clinician education alone., Design, Setting, and Participants: This cluster randomized clinical trial included individuals aged 12 to 30 years presenting for services between March 2015 and September 2017 at participating sites that included community mental health clinics and school support and special education services. Eligible participants were referred to the Early Diagnosis and Preventative Treatment (EDAPT) Clinic. Data analyses were performed in September and October 2019 for the primary and secondary analyses, with the exploratory subgroup analyses completed in May 2021., Interventions: All sites in both groups received targeted education about early psychosis for health care professionals. In the active screening group, clients also completed the Prodromal Questionnaire-Brief using tablets at intake; referrals were based on those scores and clinical judgment. In the group receiving treatment as usual (TAU), referrals were based on clinical judgment alone., Main Outcomes and Measures: Primary outcomes included DUP, defined as the period from full psychosis onset to the date of the EDAPT diagnostic telephone interview, and the number of individuals identified with FEP or a psychosis spectrum disorder. Exploratory analyses examined differences by site type, completion rates between conditions, and days from service entry to telephone interview., Results: Twenty-four sites agreed to participate, and 12 sites were randomized to either the active screening or TAU group. However, only 10 community clinics and 4 school sites were able to fully implement population screening and were included in the final analysis. The total potentially eligible population size within each study group was similar, with 2432 individuals entering at active screening group sites and 2455 at TAU group sites. A total of 303 diagnostic telephone interviews were completed (178 [58.7%] female individuals; mean [SD] age, 17.09 years [4.57]). Active screening sites reported a significantly higher detection rate of psychosis spectrum disorders (136 cases [5.6%], relative to 65 [2.6%]; P < .001) and referred a higher proportion of individuals with FEP and DUP less than 90 days (13 cases, relative to 4; odds ratio, 0.30; 95% CI, 0.10-0.93; P = .03). There was no difference in mean (SD) DUP between groups (active screening group, 239.0 days [207.4]; TAU group 262.3 days [170.2])., Conclusions and Relevance: In this cluster trial, population-based technology-enhanced screening across community settings detected more than twice as many individuals with psychosis spectrum disorders compared with clinical judgment alone but did not reduce DUP. Screening could identify people undetected in US mental health services. Significant DUP reduction may require interventions to reduce time to the first mental health contact., Trial Registration: ClinicalTrials.gov Identifier: NCT02841956.

Background: The ventilatory ratio (VR, [minute ventilation × PaCO 2 ]/[predicted body weight × 100 × 37.5]) is associated with mortality in ARDS. The aims of this study were to test whether baseline disease severity or neuromuscular blockade (NMB) modified the relationship between VR and mortality., Methods: This was a post hoc analysis of the PETAL-ROSE trial, which randomized moderate-to-severe ARDS patients to NMB or control. Survival among patients with different VR trajectories or VR cutoff above and below the median was assessed by Kaplan-Meier analysis. The relationships between single-day or 48-h VR trajectories with 28- or 90-day mortality were tested by logistic regression. Randomization allocation to NMB and markers of disease severity were tested as confounders by multivariable regression and interaction term analyses., Results: Patients with worsening VR trajectories had significantly lower survival compared to those with improving VR (n = 602, p < 0.05). Patients with VR > 2 (median) at day 1 had a significantly lower 90-day survival compared to patients with VR ≤ 2 (HR 1.36, 95% CI 1.10-1.69). VR at day 1 was significantly associated with 28-day mortality (OR = 1.40, 95% CI 1.15-1.72). There was no interaction between NMB and VR for 28-day mortality. APACHE-III had a significant interaction with VR at baseline for the outcome of 28-day mortality, such that the relationship between VR and mortality was stronger among patients with lower APACHE-III. There was a significant association between rising VR trajectory and mortality that was independent of NMB, baseline PaO 2 /FiO 2 ratio and generalized markers of disease severity (Adjusted OR 1.81, 95% CI 1.28-2.84 for 28-day and OR 2.07 95% CI 1.41-3.10 for 90-day mortality). APACHE-III and NMB were not effect modifiers in the relationship between VR trajectory and mortality., Conclusions: Elevated baseline and day 1 VR were associated with higher 28-day mortality. The relationship between baseline VR and mortality was stronger among patients with lower APACHE-III. APACHE-III was not an effect modifier for the relationship between VR trajectory and mortality, so that the VR trajectory may be optimally suited for prognostication and predictive enrichment. VR was not different between patients randomized to NMB or control, indicating that VR can be utilized without correcting for NMB., (© 2022. The Author(s).)

Background: Two acute respiratory distress syndrome (ARDS) subphenotypes (hyperinflammatory and hypoinflammatory) with distinct clinical and biological features and differential treatment responses have been identified using latent class analysis (LCA) in seven individual cohorts. To facilitate bedside identification of subphenotypes, clinical classifier models using readily available clinical variables have been described in four randomised controlled trials. We aimed to assess the performance of these models in observational cohorts of ARDS., Methods: In this observational, multicohort, retrospective study, we validated two machine-learning clinical classifier models for assigning ARDS subphenotypes in two observational cohorts of patients with ARDS: Early Assessment of Renal and Lung Injury (EARLI; n=335) and Validating Acute Lung Injury Markers for Diagnosis (VALID; n=452), with LCA-derived subphenotypes as the gold standard. The primary model comprised only vital signs and laboratory variables, and the secondary model comprised all predictors in the primary model, with the addition of ventilatory variables and demographics. Model performance was assessed by calculating the area under the receiver operating characteristic curve (AUC) and calibration plots, and assigning subphenotypes using a probability cutoff value of 0·5 to determine sensitivity, specificity, and accuracy of the assignments. We also assessed the performance of the primary model in EARLI using data automatically extracted from an electronic health record (EHR; EHR-derived EARLI cohort). In Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE; n=2813), a multinational, observational ARDS cohort, we applied a custom classifier model (with fewer variables than the primary model) to determine the prognostic value of the subphenotypes and tested their interaction with the positive end-expiratory pressure (PEEP) strategy, with 90-day mortality as the dependent variable., Findings: The primary clinical classifier model had an area under receiver operating characteristic curve (AUC) of 0·92 (95% CI 0·90-0·95) in EARLI and 0·88 (0·84-0·91) in VALID. Performance of the primary model was similar when using exclusively EHR-derived predictors compared with manually curated predictors (AUC=0·88 [95% CI 0·81-0·94] vs 0·92 [0·88-0·97]). In LUNG SAFE, 90-day mortality was higher in patients assigned the hyperinflammatory subphenotype than in those with the hypoinflammatory phenotype (414 [57%] of 725 vs 694 [33%] of 2088; p<0·0001). There was a significant treatment interaction with PEEP strategy and ARDS subphenotype (p=0·041), with lower 90-day mortality in the high PEEP group of patients with the hyperinflammatory subphenotype (hyperinflammatory subphenotype: 169 [54%] of 313 patients in the high PEEP group vs 127 [62%] of 205 patients in the low PEEP group; hypoinflammatory subphenotype: 231 [34%] of 675 patients in the high PEEP group vs 233 [32%] of 734 patients in the low PEEP group)., Interpretation: Classifier models using clinical variables alone can accurately assign ARDS subphenotypes in observational cohorts. Application of these models can provide valuable prognostic information and could inform management strategies for personalised treatment, including application of PEEP, once prospectively validated., Funding: US National Institutes of Health and European Society of Intensive Care Medicine., Competing Interests: Declaration of interests MC has a patent (ARCD P0535US.P2) pending to the University of Chicago (IL, USA) related to clinical deterioration risk prediction algorithms for patients admitted to hospital. MAM reports grants from Roche/Genentech, and personal fees from Johnson and Johnson, Novartis Pharmaceuticals, Gilead Pharmaceuticals, and Pliant Therapeutics, outside the submitted work. LBW reports grants and personal fees from Boehringer Ingelheim, outside the submitted work; grants from Genentech and CSL Behring, outside the submitted work; and personal fees from Merck, Citius, Quark, and Foresee, outside the submitted work. JGL reports personal fees from GlaxoSmithKline and Baxter, outside of the submitted work. GB reports grants and personal fees from Draeger Medical, and personal fees from Ge Healthcare, Hamilton Medical, and Flowmeter SPA, outside the submitted work. CSC reports grants and personal fees from Roche/Genentech and Bayer, outside the submitted work; personal fees from Quark Pharmaceuticals, Gen1e Life Sciences, and Vasomune, outside the submitted work; and grants from Quantum Leap Healthcare Collaborative, outside the submitted work. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Previous latent class analysis of adults with acute respiratory distress syndrome (ARDS) identified two phenotypes, distinguished by the degree of inflammation. We aimed to identify phenotypes in children with ARDS in whom developmental differences might be important, using a latent class analysis approach similar to that used in adults., Methods: This study was a secondary analysis of data aggregated from the Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE) clinical trial and the Genetic Variation and Biomarkers in Children with Acute Lung Injury (BALI) ancillary study. We used latent class analysis, which included demographic, clinical, and plasma biomarker variables, to identify paediatric ARDS (PARDS) phenotypes within a cohort of children included in the RESTORE and BALI studies. The association of phenotypes with clinically relevant outcomes and the performance of paediatric data in adult ARDS classification algorithms were also assessed., Findings: 304 children with PARDS were included in this secondary analysis. Using latent class analysis, a two-class model was a better fit for the cohort than a one-class model (p<0·001). Latent class analysis identified two classes: class 1 (181 [60%] of 304 patients with PARDS) and class 2 (123 [40%] of 304 patients with PARDS), referred to as phenotype 1 and 2 hereafter. Phenotype 2 was characterised by higher concentrations of inflammatory biomarkers, a higher incidence of vasopressor use, and more frequent diagnosis of sepsis, consistent with the adult hyperinflammatory phenotype. All levels of severity of PARDS were observed across both phenotypes. Children with the hyperinflammatory phenotype (phenotype 2) had worse clinical outcomes than those with the hypoinflammatory phenotype (phenotype 1), with a longer duration of mechanical ventilation (median 10·0 days [IQR 6·3-21·0] for phenotype 2 vs 6·6 days [4·1-10·8] for phenotype 1, p<0·0001), and higher incidence of mortality (17 [13·8%] of 123 patients vs four [2·2%] of 181 patients, p=0·0001). When using adult phenotype classification algorithms in children, the soluble tumour necrosis factor receptor-1 (sTNFr1), vasopressor use, and interleukin (IL)-6 variables gave an area under the curve (AUC) of 0·956, and the sTNFr1, vasopressor use, and IL-8 variables gave an AUC of 0·954, compared with the gold standard of latent class analysis., Interpretation: Latent class analysis identified two phenotypes in children with ARDS with characteristics similar to those in adults, including worse outcomes among patients with the hyperinflammatory phenotype. PARDS phenotypes should be considered in design and analysis of future clinical trials in children., Funding: US National Institutes of Health., Competing Interests: Declaration of interests MKD, MZ, MAQC, AS, KLD, and HF report grants from the US National Institutes of Health. CSC reports grants from the US National Institutes of Health, Roche/Genentech, Bayer, and Quantum Leap Healthcare Collaborative; and consultancy fees from Quark Pharmaceuticals, Prometic, Gen1e Life Sciences, and Vasomune. MWQ reports consultancy fees from Mitchell Leeds, Tanoury, Nauts, and McKinney and Barbarino. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Rationale: Using latent class analysis (LCA), two subphenotypes of acute respiratory distress syndrome (ARDS) have consistently been identified in five randomised controlled trials (RCTs), with distinct biological characteristics, divergent outcomes and differential treatment responses to randomised interventions. Their existence in unselected populations of ARDS remains unknown. We sought to identify subphenotypes in observational cohorts of ARDS using LCA., Methods: LCA was independently applied to patients with ARDS from two prospective observational cohorts of patients admitted to the intensive care unit, derived from the Validating Acute Lung Injury markers for Diagnosis (VALID) (n=624) and Early Assessment of Renal and Lung Injury (EARLI) (n=335) studies. Clinical and biological data were used as class-defining variables. To test for concordance with prior ARDS subphenotypes, the performance metrics of parsimonious classifier models (interleukin 8, bicarbonate, protein C and vasopressor-use), previously developed in RCTs, were evaluated in EARLI and VALID with LCA-derived subphenotypes as the gold-standard., Results: A 2-class model best fit the population in VALID (p=0.0010) and in EARLI (p<0.0001). Class 2 comprised 27% and 37% of the populations in VALID and EARLI, respectively. Consistent with the previously described 'hyperinflammatory' subphenotype, Class 2 was characterised by higher proinflammatory biomarkers, acidosis and increased shock and worse clinical outcomes. The similarities between these and prior RCT-derived subphenotypes were further substantiated by the performance of the parsimonious classifier models in both cohorts (area under the curves 0.92-0.94). The hyperinflammatory subphenotype was associated with increased prevalence of chronic liver disease and neutropenia and reduced incidence of chronic obstructive pulmonary disease. Measurement of novel biomarkers showed significantly higher levels of matrix metalloproteinase-8 and markers of endothelial injury in the hyperinflammatory subphenotype, whereas, matrix metalloproteinase-9 was significantly lower., Conclusion: Previously described subphenotypes are generalisable to unselected populations of non-trauma ARDS., Competing Interests: Competing interests: PS declares no competing interests. CSC has received grant funding from the NIH, US Food and Drug Administration, Roche-Genentech, Quantum Leap Healthcare Collaborative, and Bayer Pharmaceuticals and has served as a consultant to Vasomune, Quark, and Gen1e Life Sciences., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Heterogeneity in Acute Respiratory Distress Syndrome (ARDS), as a consequence of its non-specific definition, has led to a multitude of negative randomised controlled trials (RCTs). Investigators have sought to identify heterogeneity of treatment effect (HTE) in RCTs using clustering algorithms. We evaluated the proficiency of several commonly-used machine-learning algorithms to identify clusters where HTE may be detected., Methods: Five unsupervised: Latent class analysis (LCA), K-means, partition around medoids, hierarchical, and spectral clustering; and four supervised algorithms: model-based recursive partitioning, Causal Forest (CF), and X-learner with Random Forest (XL-RF) and Bayesian Additive Regression Trees were individually applied to three prior ARDS RCTs. Clinical data and research protein biomarkers were used as partitioning variables, with the latter excluded for secondary analyses. For a clustering schema, HTE was evaluated based on the interaction term of treatment group and cluster with day-90 mortality as the dependent variable., Findings: No single algorithm identified clusters with significant HTE in all three trials. LCA, XL-RF, and CF identified HTE most frequently (2/3 RCTs). Important partitioning variables in the unsupervised approaches were consistent across algorithms and RCTs. In supervised models, important partitioning variables varied between algorithms and across RCTs. In algorithms where clusters demonstrated HTE in the same trial, patients frequently interchanged clusters from treatment-benefit to treatment-harm clusters across algorithms. LCA aside, results from all other algorithms were subject to significant alteration in cluster composition and HTE with random seed change. Removing research biomarkers as partitioning variables greatly reduced the chances of detecting HTE across all algorithms., Interpretation: Machine-learning algorithms were inconsistent in their abilities to identify clusters with significant HTE. Protein biomarkers were essential in identifying clusters with HTE. Investigations using machine-learning approaches to identify clusters to seek HTE require cautious interpretation., Funding: NIGMS R35 GM142992 (PS), NHLBI R35 HL140026 (CSC); NIGMS R01 GM123193, Department of Defense W81XWH-21-1-0009, NIA R21 AG068720, NIDA R01 DA051464 (MMC)., Competing Interests: Declaration of Competing Interest Dr Sinha received institutional grants from the National Institute of Health (NIH), Ms Spicer received institutional grant funding from the NIH and Department of Defense. Prof Delucchi declares no relevant conflicts of interest. Prof McAuley received institutional grants from the NIHR, Innovate UK, MRC, Novavax, Northern Ireland HSC R&D Division, Wellcome Trust; royalties/licenses from Queen's University Belfast for a patent of novel treatment for inflammatory diseases (USB962032); consulting fees from Bayer, GlaxoSmithKline, Boehringer Ingelhelm, Novartis, Eli Lilly, SOBI; payment from GlaxoSmithKline as an educational seminary speaker; travel support from Vir Biotechnology Inc and Faron Pharmaceuticals as a member of Data Safety Monitoring Board. His spouse received consultancy fees from Insmed and payments for participation in grant review panel from California Institute for Regenerative Medicine. Prof Calfee received institutional grants from the NIH, Bayer, Roche-Genentech, Quantum Leap Healthcare Collaborative; and personal fees from Quark, Vasomune, and Gen1e Life Science. Dr Churpek received institutional grants from the NIH, Department of Defense, and EarlySense., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: This study examined the impact of a San Francisco City and County ban on all flavoured tobacco products, including menthol cigarettes, among clients in residential substance use disorder (SUD) treatment., Methods: We conducted cross-sectional surveys of clients at two residential SUD programmes before the County began enforcing the ban (n=160) and twice after enforcement began (n=102, n=120). The samples were compared on demographic characteristics, smoking status, smoking behaviours and the proportion reporting menthol as their usual cigarette. Menthol smokers were asked whether they smoked only menthol cigarettes, mostly menthol, both menthol and non-menthol or mostly non-menthol. Post-ban samples were asked about awareness of the ban and access to menthol cigarettes., Results: In multivariate analyses, we found no evidence that the ban was associated with decreased number of cigarettes per day or increased readiness to quit among current smokers. However, odds were lower post-ban for reporting menthol as the usual cigarette (OR=0.80, 95% CI 0.72 to 0.90), and for smoking only menthol cigarettes (OR=0.19, 95% CI 0.18 to 0.19). Perhaps most importantly, and with the ability to influence all other findings, 50% of self-identified menthol smokers reported purchasing menthol cigarettes in San Francisco nearly 1 year after the ban was implemented., Conclusion: In subgroups where smoking has remained elevated, like those receiving SUD treatment, local menthol bans may have only modest impacts on smoking behaviour. Broader regional, state or national bans, that effectively restrict access to menthol products, may be needed to show stronger effects on smoking behaviour., Competing Interests: Competing interests: No, there are no competing interests., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Alveolar epithelial-capillary barrier disruption is a hallmark of acute respiratory distress syndrome (ARDS). Contribution of mitochondrial dysfunction to the compromised alveolar-capillary barrier in ARDS remains unclear. Mesenchymal stromal cells-derived extracellular vesicles (MSC-EVs) are considered as a cell-free therapy for ARDS. Mitochondrial transfer was shown to be important for the therapeutic effects of MSCs and MSC-EVs. Here we investigated the contribution of mitochondrial dysfunction to the injury of alveolar epithelial and endothelial barriers in ARDS and the ability of MSC-EVs to modulate alveolar-capillary barrier integrity through mitochondrial transfer.Primary human small airway epithelial and pulmonary microvascular endothelial cells and human precision cut lung slices (PCLSs) were stimulated with endotoxin or plasma samples from patients with ARDS and treated with MSC-EVs, barrier properties and mitochondrial functions were evaluated. Lipopolysaccharide (LPS)-injured mice were treated with MSC-EVs and degree of lung injury and mitochondrial respiration of the lung tissue were assessed.Inflammatory stimulation resulted in increased permeability coupled with pronounced mitochondrial dysfunction in both types of primary cells and PCLSs. Extracellular vesicles derived from normal MSCs restored barrier integrity and normal levels of oxidative phosphorylation while an extracellular vesicles preparation which did not contain mitochondria was not effective. In vivo , presence of mitochondria was critical for extracellular vesicles ability to reduce lung injury and restore mitochondrial respiration in the lung tissue.In the ARDS environment, MSC-EVs improve alveolar-capillary barrier properties through restoration of mitochondrial functions at least partially via mitochondrial transfer., Competing Interests: Conflict of interest: J. Dutra Silva has nothing to disclose. Conflict of interest: Y. Su has nothing to disclose. Conflict of interest: C.S. Calfee reports grants from NIH, during the conduct of the study; grants and personal fees for consultancy from Roche/Genentech and Bayer, personal fees for advisory board work from Quark Pharmaceuticals and Prometic, personal fees for consultancy from Gen1e Life Sciences and Vasomune, outside the submitted work. Conflict of interest: K.L. Delucchi has nothing to disclose. Conflict of interest: D. Weiss has nothing to disclose. Conflict of interest: D.F. McAuley reports personal fees from consultancy for GlaxoSmithKline, Boehringer Ingelheim and Bayer, outside the submitted work; his institution has received grants from the UK NIHR, Wellcome Trust and others; has a patent issued to his institution for a treatment for ARDS; and is a Director of Research for the Intensive Care Society and NIHR EME Programme Director. Conflict of interest: C. O'Kane reports grants from Wellcome Trust, MRC and NI HSC R& D, outside the submitted work, and that her spouse has received consultancy fees from GlaxoSmithKline, Boehringer Ingelheim and Bayer. Conflict of interest: A.D. Krasnodembskaya reports grants from Medical Research Council, UK, during the conduct of the study., (Copyright ©ERS 2021.)

Background: Childhood trauma (CT) increases the risk of adult depression. Buffering effects require an understanding of the underlying persistent risk pathways. This study examined whether daily psychological stress processes - how an individual interprets and affectively responds to minor everyday events - mediate the effect of CT on adult depressive symptoms., Methods: Middle-aged women (N = 183) reported CT at baseline and completed daily diaries of threat appraisals and negative evening affect for 7 days at baseline, 9, and 18 months. Depressive symptoms were measured across the 1.5-year period. Mediation was examined using multilevel structural equation modeling., Results: Reported CT predicted greater depressive symptoms over the 1.5-year time period (estimate = 0.27, s.e. = 0.07, 95% CI 0.15-0.38, p < 0.001). Daily threat appraisals and negative affect mediated the effect of reported CT on depressive symptoms (estimate = 0.34, s.e. = 0.08, 95% CI 0.22-0.46, p < 0.001). Daily threat appraisals explained more than half of this effect (estimate = 0.19, s.e. = 0.07, 95% CI 0.08-0.30, p = 0.004). Post hoc analyses in individuals who reported at least moderate severity of CT showed that lower threat appraisals buffered depressive symptoms. A similar pattern was found in individuals who reported no/low severity of CT., Conclusions: A reported history of CT acts as a latent vulnerability, exaggerating threat appraisals of everyday events, which trigger greater negative evening affect - processes that have important mental health consequences and may provide malleable intervention targets.

Introduction: This study examined the effects of experimentally manipulated social media exposure on adolescents' willingness and intention to use e-cigarettes., Aims and Methods: Participants were 135 adolescents of age 13-18 (52.6% female, mean age = 15.3) in California. Participants viewed six social media posts online in a 2 (post source: peer or advertisement) × 2 (e-cigarette content exposure: heavy or light) between-subjects design. Analyses were weighted to population benchmarks. We examined adolescents' beliefs, willingness, and intention to use e-cigarettes in association with social media use intensity in daily life and with experimentally manipulated exposure to social media posts that varied by source (peer or advertisement) and content (e-cigarette heavy or light)., Results: Greater social media use in daily life was associated with greater willingness and intention to use e-cigarettes and more positive attitudes, greater perceived norms, and lower perceived danger of e-cigarette use (all p-values <.01). In tests of the experimental exposures, heavy (vs. light) e-cigarette content resulted in greater intention (p = .049) to use e-cigarettes and more positive attitudes (p = .019). Viewing advertisements (vs. peer-generated posts) resulted in greater willingness and intention (p-values <.01) to use e-cigarettes, more positive attitudes (p = .003), and greater norm perceptions (p = .009). The interaction effect of post source by post content was not significant for any of the outcomes (all p-values >.529)., Conclusions: Greater social media use and heavier exposure to advertisements and e-cigarette content in social media posts are associated with a greater risk for e-cigarette use among adolescents. Regulatory action is needed to prohibit sponsored e-cigarette content on social media platforms used by youth., Implications: Adolescents who use social media intensely may be at higher risk for e-cigarette use. Even brief exposure to e-cigarette content on social media was associated with greater intention to use and more positive attitudes toward e-cigarettes. Regulatory action should be taken to prohibit sponsored e-cigarette content on social media used by young people, including posts by influencers who appeal to young people., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To determine the effects of ESRT (an iteratively adapted and tailored MBI) on perceived stress, executive cognitive function, psychosocial well-being (ie, burnout, mindfulness), and pro-inflammatory gene expression in surgical (ESRT-1) and mixed specialty (ESRT-2) PGY-1 volunteers., Summary of Background and Data: Tailored MBIs have proven beneficial in multiple high-stress and high-performance populations. In surgeons, tailored MBIs have been shown to be feasible and potentially beneficial, but whether mindfulness-based cognitive training can improve perceived stress, executive function, well-being or physiological distress in surgical and nonsurgical trainees is unknown., Methods: In 2 small single-institution randomized clinical trials, ESRT, a tailored mindfulness-based cognitive training program, was administered and iteratively adapted for first-year surgical (ESRT-1, 8 weekly, 2-hour classes, n = 44) and mixed specialty (ESRT-2, 6 weekly, 90-minute classes, n = 45) resident trainees. Primary and secondary outcomes were, respectively, perceived stress and executive function. Other prespecified outcomes were burnout (assessed via Maslach Burnout Inventory), mindfulness (assessed via Cognitive Affective Mindfulness Scale - Revised), and pro-inflammatory gene expression (assessed through the leukocyte transcriptome profile "conserved transcriptional response to adversity")., Results: Neither version of ESRT appeared to affect perceived stress. Higher executive function and mindfulness scores were seen in ESRT-1, and lower emotional exhaustion and depersonalization scores in ESRT-2, at pre-/postintervention and/or 50-week follow-up (ESRT-1) or at 32-week follow-up (ESRT-2), compared to controls. Pooled analysis of both trials found ESRT-treated participants had reduced pro-inflammatory RNA expression compared to controls., Conclusions: This pilot work suggests ESRT can variably benefit executive function, burnout, and physiologic distress in PGY-1 trainees, with potential for tailoring to optimize effects., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Co-occurrence of tobacco use and heavy episodic drinking (HED; 5+ drinks for men and 4+ drinks for women per occasion) is common among young adults; both warrant attention and intervention. In a two-group randomized pilot trial, we investigated whether a Facebook-based smoking cessation intervention addressing both alcohol and tobacco use would increase smoking abstinence and reduce HED compared to a similar intervention addressing only tobacco., Methods: Participants were 179 young adults (age 18-25; 49.7% male; 80.4% non-Hispanic white) recruited from Facebook and Instagram who reported smoking 4+ days/week and past-month HED. The Smoking Tobacco and Drinking (STAND) intervention (N = 84) and the Tobacco Status Project (TSP), a tobacco-only intervention (N = 95), both included daily Facebook posts for 90 days and weekly live counseling sessions in private "secret" groups. We verified self-reported 7-day smoking abstinence via remote salivary cotinine tests at 3, 6, and 12 months (with retention at 83%, 66%, and 84%, respectively). Participants self-reported alcohol use., Results: At baseline, the participants averaged 10.4 cigarettes per day (SD = 6.9) and 8.9 HED occasions in the past month (SD = 8.1), with 27.4% in a preparation stage of change for quitting smoking cigarettes. Participants reported significant improvements in cigarette smoking and alcohol use outcomes over time, with no significant differences by condition. At 12 months, intent-to-treat smoking abstinence rates were 3.5% in STAND vs. 0% in TSP (biochemically verified) and 29.4% in STAND vs. 25.5% in TSP (self-reported). Compared to TSP, participants rated the STAND intervention more favorably for supporting health and providing useful information., Conclusions: Adding an alcohol treatment component to a tobacco cessation social media intervention was acceptable and engaging but did not result in significant differences by treatment condition in smoking or alcohol use outcomes. Participants in both conditions reported smoking and drinking less over time, suggesting covariation in behavioral changes., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Hoarding behaviors are positively associated with medical morbidity, however, current prevalence estimates and types of medical conditions associated with hoarding vary. This analysis aims to quantify the medical morbidity of hoarding disorder (HD). Cross-sectional data were collected online using the Brain Health Registry (BHR). Among 20,745 participants who completed the Hoarding and Clutter and Medical History thematic modules, 1348 had HD (6.5%), 1268 had subclinical HD (6.1%), and 18,829 did not meet hoarding criteria (87.4%). Individuals with HD were more likely to report a lifetime history of cardiovascular/metabolic conditions: diabetes (HD adjusted odds ratio (AOR):1.51, 95% confidence interval (CI):[1.20, 1.91]; subclinical HD AOR:1.24, 95% CI:[0.95, 1.61]), and hypercholesterolemia (HD AOR:1.24, 95% CI:[1.06, 1.46]; subclinical HD AOR:1.11, 95% CI:[0.94, 1.31]). Those with HD and subclinical HD were also more to report chronic pain (HD AOR: 1.69, 95% CI:[1.44, 1.98]; subclinical HD AOR: 1.44, 95% CI:[1.22, 1.69]), and sleep apnea (HD AOR: 1.58, 95% CI:[1.31, 1.89]; subclinical HD AOR:1.30, 95% CI:[1.07, 1.58]) than non-HD participants. For most conditions, likelihood of diagnosis did not differ between HD and subclinical HD. Structural equation modeling revealed that more severe hoarding symptomatology was independently associated with increased cardiovascular/metabolic vulnerability. The assessment and management of medical complications in individuals with HD is a fundamental component in improving quality of life, longevity, and overall physical health outcomes., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Importance: Physician well-being is a critical component of sustainable health care. There are few data on the effects of multilevel well-being programs nor a clear understanding of where and how to target resources., Objective: To inform the design of future well-being interventions by exploring individual and workplace factors associated with surgical trainees' well-being, differences by gender identity, and end-user perceptions of these initiatives., Design, Setting, and Participants: This mixed-methods study among surgical trainees within a single US academic surgical department included a questionnaire in January 2019 (98 participants, including general surgery residents and clinical fellows) and a focus group (9 participants, all clinical residents who recently completed their third postgraduate year [PGY 3]) in July 2019. Participants self-reported gender (man, woman, nonbinary)., Exposures: Individual and organizational-level initiatives, including mindfulness-based affective regulation training (via Enhanced Stress Resilience Training), advanced scheduling of time off, wellness half-days, and the creation of a resident-driven well-being committee., Main Outcomes and Measures: Well-being was explored using validated measures of psychosocial risk (emotional exhaustion, depersonalization, perceived stress, depressive symptoms, alcohol use, languishing, anxiety, high psychological demand) and resilience (mindfulness, social support, flourishing) factors. End-user perceptions were assessed through open-ended responses and a formal focus group., Results: Of 98 participants surveyed, 64 responded (response rate, 65%), of whom 35 (55%) were women. Women vs men trainees were significantly more likely to report high depersonalization (odds ratio [OR], 5.50; 95% CI, 1.38-21.85) and less likely to report high mindfulness tendencies (OR, 0.17; 95% CI, 0.05-0.53). Open-ended responses highlighted time and priorities as the greatest barriers to using well-being resources. Focus group findings reflected Job Demand-Resource theory tenets, revealing the value of individual-level interventions to provide coping skills, the benefit of advance scheduling of time off for maintaining personal support resources, the importance of work quality rather than quantity, and the demoralizing effect of inefficient or nonresponsive systems., Conclusions and Relevance: In this study, surgical trainees indicated that multilevel well-being programs would benefit them, but tailoring these initiatives to individual needs and specific workplace elements is critical to maximizing intervention effects.

Objective: To determine if the declining trend in U.S. youth cigarette smoking changed after e-cigarettes were introduced, and if youth e-cigarette users would have been likely to smoke cigarettes based on psychosocial and demographic predictors of smoking., Methods: An interrupted time series analysis was used for cross-sectional data from the 2004 to 2018 National Youth Tobacco Surveys (NYTS) to assess changes in cigarette and e-cigarette use over time. A multivariable logistic regression model used 2004-2009 NYTS data on psychosocial risk factors to predict individual-level cigarette smoking risk from 2011 to 2018. Model-predicted and actual cigarette smoking behavior were compared., Results: The decline in current cigarette smoking slowed in 2014 (-0.75 [95% CI: -0.81, -0.68] to -0.26 [95% CI: -0.40, -0.12] percentage points per year). The decline in ever cigarette smoking accelerated after 2012 (-1.45 [95% CI: -1.59, -1.31] to -1.71 [95% CI: -1.75, -1.66]). Ever and current combined cigarette and/or e-cigarette use declined during 2011-2013 and increased during 2013-2014 with no significant change during 2014-2018 for either variable. The psychosocial model estimated that 69.0% of current cigarette smokers and 9.3% of current e-cigarette users (who did not smoke cigarettes) would smoke cigarettes in 2018., Conclusions: The introduction of e-cigarettes was followed by a slowing decline in current cigarette smoking, a stall in combined cigarette and e-cigarette use, and an accelerated decline in ever cigarette smoking. Traditional psychosocial risk factors for cigarette smoking suggest that e-cigarette users do not fit the traditional risk profile of cigarette smokers., (Published by Elsevier Inc.)

Health behavior theorists and prevention researchers use a variety of measures of adolescent and young adult (AYA) risk and benefit perceptions to predict tobacco-use and marijuana-use behaviors. However, studies have not examined whether and how perception measures that ask about likelihood of more general outcomes such as "harm" versus ask about specific risk or benefit outcomes compare or whether they differentially predict AYA willingness to use if one of your best friends were to offer it and intentions to use in the next year; and if these measures have differential ability to predict actual use of tobacco and marijuana. We used data from a prospective cohort of California AYAs to create and test new scales to measure perceptions of specific health and social outcomes related to risks (e.g., smell bad) and benefits (e.g., look cool) related to tobacco and marijuana, and then addressed three questions: (1) Whether and how measures of perceptions of specific social and health risks and benefits (for our purposes "specific measures") and measures of perceived general harm are differentially associated with measures of willingness, social norms, and intentions to use? (2) Are specific versus general measures differentially associated with and predictive of tobacco and cannabis use behavior? (3) Are specific perceptions measures differentially predictive of behavior compared to measures of willingness, social norms, and behavioral intentions? Our results demonstrate that to better predict AYA tobacco and marijuana use, measures that address general outcomes, such as harmfulness, as well as willingness and behavioral intention should be used. We also found that measures of specific perceived risks (short-term, long-term, social) and benefits were unrelated and correlated differently with different products. For example, adolescents perceived both risks and benefits from using products like e-cigarettes, and perceived greater risk from smokeless tobacco compared to combustible cigarettes. These findings indicate that measures of specific perceived social and health outcomes can be useful to discern nuanced differences in motivation for using different substances. Study implications are important for survey dimension-reduction and assessing relationships among perceptions, motivations, and use of tobacco and marijuana products., Competing Interests: Competing interests The authors declare no competing interests.

Latent class analysis is a probabilistic modeling algorithm that allows clustering of data and statistical inference. There has been a recent upsurge in the application of latent class analysis in the fields of critical care, respiratory medicine, and beyond. In this review, we present a brief overview of the principles behind latent class analysis. Furthermore, in a stepwise manner, we outline the key processes necessary to perform latent class analysis including some of the challenges and pitfalls faced at each of these steps. The review provides a one-stop shop for investigators seeking to apply latent class analysis to their data., (Copyright © 2020 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Background: In acute respiratory distress syndrome (ARDS) unrelated to COVID-19, two phenotypes, based on the severity of systemic inflammation (hyperinflammatory and hypoinflammatory), have been described. The hyperinflammatory phenotype is known to be associated with increased multiorgan failure and mortality. In this study, we aimed to identify these phenotypes in COVID-19-related ARDS., Methods: In this prospective observational study done at two UK intensive care units, we recruited patients with ARDS due to COVID-19. Demographic, clinical, and laboratory data were collected at baseline. Plasma samples were analysed for interleukin-6 (IL-6) and soluble tumour necrosis factor receptor superfamily member 1A (TNFR1) using a novel point-of-care assay. A parsimonious regression classifier model was used to calculate the probability for the hyperinflammatory phenotype in COVID-19 using IL-6, soluble TNFR1, and bicarbonate levels. Data from this cohort was compared with patients with ARDS due to causes other than COVID-19 recruited to a previous UK multicentre, randomised controlled trial of simvastatin (HARP-2)., Findings: Between March 17 and April 25, 2020, 39 patients were recruited to the study. Median ratio of partial pressure of arterial oxygen to fractional concentration of oxygen in inspired air (PaO 2 /FiO 2 ) was 18 kpa (IQR 15-21) and acute physiology and chronic health evaluation II score was 12 (10-16). 17 (44%) of 39 patients had died by day 28 of the study. Compared with survivors, patients who died were older and had lower PaO 2 /FiO 2 . The median probability for the hyperinflammatory phenotype was 0·03 (IQR 0·01-0·2). Depending on the probability cutoff used to assign class, the prevalence of the hyperinflammatory phenotype was between four (10%) and eight (21%) of 39, which is lower than the proportion of patients with the hyperinflammatory phenotype in HARP-2 (186 [35%] of 539). Using the Youden index cutoff (0·274) to classify phenotype, five (63%) of eight patients with the hyperinflammatory phenotype and 12 (39%) of 31 with the hypoinflammatory phenotype died. Compared with matched patients recruited to HARP-2, levels of IL-6 were similar in our cohort, whereas soluble TNFR1 was significantly lower in patients with COVID-19-associated ARDS., Interpretation: In this exploratory analysis of 39 patients, ARDS due to COVID-19 was not associated with higher systemic inflammation and was associated with a lower prevalence of the hyperinflammatory phenotype than that observed in historical ARDS data. This finding suggests that the excess mortality observed in COVID-19-related ARDS is unlikely to be due to the upregulation of inflammatory pathways described by the parsimonious model., Funding: US National Institutes of Health, Innovate UK, and Randox., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Loneliness is a widespread and significant problem on college campuses. Prolonged loneliness in young adulthood is a risk factor for concurrent and future mental health problems and attrition, making college a critical time for support. Cognitive and behavioral interventions show promise for decreasing loneliness and can be widely disseminated through technology., Objective: This pilot randomized controlled trial was conducted to examine the initial efficacy, feasibility, and desirability of a smartphone app, Nod, designed to deliver cognitive and behavioral skill-building exercises to reduce loneliness during the transition to college., Methods: First-year college students (N=221, mean age 18.7 years, 59% female) were recruited online during incoming student orientation, and randomized to either receive immediate access to Nod (experimental group, n=100) or access after 4 weeks (control group, n=121). The app delivered skills via fully automated (1) "social challenges," suggested activities designed to build social connections; (2) reflections, brief cognitive reframing exercises; and (3) student testimonials that encouraged a growth mindset toward social connection building. Main intention-to-treat analyses were used to compare the conditions on self-assessed loneliness, depressive symptoms, and other mental health and college adjustment outcomes at week 4, controlling for baseline values on those variables. Analyses were also performed to test the hypothesis that the treatment benefits would be particularly pronounced for participants with heightened psychological vulnerability at baseline (ie, higher baseline depressive symptoms and loneliness)., Results: Retention was 97% at week 4, and participants viewed an average 36.7 pages of app content. There were no significant condition differences in loneliness at week 4 (F 1, 211 =0.05, P=.82; η p 2 <.001). However, there was a significant condition-by-baseline depression interaction to predict week-4 loneliness (F 1,209 =9.65, P=.002; η p 2 =.04). Simple slope analyses indicated that baseline depression positively predicted week-4 loneliness among control participants (r=0.30, t 209 =3.81, P<.001), but not among experimental participants (r=-0.09, t 209 =-0.84, P=.40), suggesting that Nod buffered participants with high baseline depression scores from experiencing heightened midquarter loneliness. Similarly, there were no significant condition differences in other week-4 outcomes. However, moderation by baseline vulnerability was found for week-4 depressive symptoms, sleep quality, and indices of college adjustment (eg, perceived social support and campus belonging)., Conclusions: Although Nod exposure did not impact outcomes for the full sample, these results provide initial evidence of its benefit for vulnerable students. The results of this trial suggest that cognitive and behavioral skills delivered via a mobile app can buffer psychologically vulnerable college students against heightened loneliness and depressive symptoms, as well as other negative college adjustment outcomes. Future work will aim to improve upon app engagement, and to address loneliness among other key populations., Trial Registration: ClinicalTrials.gov NCT04164654; https://clinicaltrials.gov/ct2/show/NCT04164654., (©Emma Bruehlman-Senecal, Cayce J Hook, Jennifer H Pfeifer, Caroline FitzGerald, Brittany Davis, Kevin L Delucchi, Jana Haritatos, Danielle E Ramo. Originally published in JMIR Mental Health (http://mental.jmir.org), 20.10.2020.)

Introduction: This trial investigated whether a Facebook smoking cessation intervention culturally tailored to young sexual and gender minority (SGM) smokers (versus non-tailored) would increase smoking abstinence., Methods: Participants were 165 SGM young adult US smokers (age 18-25) recruited from Facebook in April 2018 and randomized to an SGM-tailored (POP; N = 84) or non-tailored (TSP-SGM; N = 81) intervention. Interventions delivered weekly live counseling sessions and 90 daily Facebook posts to participants in Facebook groups. Primary analyses compared POP and TSP-SGM on biochemically verified smoking abstinence (yes/no; primary outcome), self-reported 7-day point prevalence abstinence (yes/no), reduction in cigarettes per week by 50+% from baseline (yes/no), making a quit attempt during treatment (yes/no), and stage of change (precontemplation/contemplation vs. preparation/action). Supplemental analyses compared POP to two historical control groups., Results: POP participants were more likely than TSP-SGM participants to report smoking abstinence at 3 (23.8% vs. 12.3%; OR = 2.50; p = .03) and 6 months (34.5% vs. 12.3%; OR = 4.06; p < .001) and reduction in smoking at 3 months (52.4% vs. 39.5%; OR = 2.11; p = .03). Biochemically verified smoking abstinence did not significantly differ between POP and TSP-SGM at 3 (OR = 2.00; p = .33) or 6 months (OR = 3.12; p = .08), potentially due to challenges with remote biochemical verification. In supplemental analyses, POP participants were more likely to report abstinence at 3 (OR = 6.82, p = .01) and 6 (OR = 2.75, p = .03) months and reduced smoking at 3 months (OR = 2.72, p = .01) than participants who received a referral to Smokefree.gov., Conclusions: This pilot study provides preliminary support for the effectiveness of a Facebook smoking cessation intervention tailored to SGM young adults., Implications: SGM individuals have disproportionately high smoking prevalence. It is unclear whether smoking cessation interventions culturally tailored to the SGM community are more effective than non-tailored interventions. This pilot trial found preliminary evidence that an SGM-tailored Facebook smoking cessation intervention increased reported abstinence from smoking, compared to a non-tailored intervention., Trial Registration: NCT03259360., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved.For permissions, please e-mail: journals.permissions@oup.com.)

Background: Using latent class analysis (LCA) in five randomised controlled trial (RCT) cohorts, two distinct phenotypes of acute respiratory distress syndrome (ARDS) have been identified: hypoinflammatory and hyperinflammatory. The phenotypes are associated with differential outcomes and treatment response. The objective of this study was to develop parsimonious models for phenotype identification that could be accurate and feasible to use in the clinical setting., Methods: In this retrospective study, three RCT cohorts from the National Lung, Heart, and Blood Institute ARDS Network (ARMA, ALVEOLI, and FACTT) were used as the derivation dataset (n=2022), from which the machine learning and logistic regression classifer models were derived, and a fourth (SAILS; n=715) from the same network was used as the validation test set. LCA-derived phenotypes in all of these cohorts served as the reference standard. Machine-learning algorithms (random forest, bootstrapped aggregating, and least absolute shrinkage and selection operator) were used to select a maximum of six important classifier variables, which were then used to develop nested logistic regression models. Only cases with complete biomarker data in the derivation dataset were used for variable selection. The best logistic regression models based on parsimony and predictive accuracy were then evaluated in the validation test set. Finally, the models' prognostic validity was tested in two external ARDS clinical trial datasets (START and HARP-2) by assessing mortality at days 28, 60, and 90 and ventilator-free days to day 28., Findings: The six most important classifier variables were interleukin (IL)-8, IL-6, protein C, soluble tumour necrosis factor receptor 1, bicarbonate, and vasopressor use. From the nested models, three-variable (IL-8, bicarbonate, and protein C) and four-variable (3-variable plus vasopressor use) models were adjudicated to be the best performing. In the validation test set, both models showed good accuracy (AUC 0·94 [95% CI 0·92-0·95] for the three-variable model and 0·95 [95% CI 0·93-0·96] for the four-variable model) against LCA classifications. As with LCA-derived phenotypes, the hyperinflammatory phenotype as identified by the classifier model was associated with higher mortality at day 90 (87 [39%] of 223 patients vs 112 [23%] of 492 patients; p<0·0001) and fewer ventilator-free days (median 14 days [IQR 0-22] vs 22 days [0-25]; p<0·0001). In the external validation datasets, three-variable models developed in the derivation dataset identified two phenotypes with distinct clinical features and outcomes consistent with previous findings, including differential survival with simvastatin versus placebo in HARP-2 (p=0·023 for survival at 28 days)., Interpretation: ARDS phenotypes can be accurately identified with parsimonious classifier models using three or four variables. Pending the development of real-time testing for key biomarkers and prospective validation, these models could facilitate identification of ARDS phenotypes to enable their application in clinical trials and practice., Funding: National Institutes of Health., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Importance: Mindfulness meditation training has been shown to be feasible in surgical trainees, but affective, cognitive, and performance benefits seen in other high-stress populations have yet to be evaluated., Objective: To explore potential benefits to stress, cognition, and performance in postgraduate year 1 (PGY-1) surgery residents receiving modified mindfulness-based stress reduction (modMBSR)., Design, Setting, and Participants: This follow-up study is an analysis of the Mindful Surgeon pilot randomized clinical trial of modMBSR (n = 12) vs an active control (n = 9), evaluated at baseline (T1), postintervention (T2), and 1 year (T3), took place at an academic medical center residency training program among PGY-1 surgery residents. Data were collected between June 2016 and June 2017 and analyzed from June 2017 to December 2017., Interventions: Weekly 2-hour modMBSR classes and 20 minutes of daily home practice during an 8-week period vs an active control (different content, same structure)., Main Outcomes and Measures: Preliminary evidence of efficacy was explored, primarily focusing on perceived stress and executive function and secondarily on burnout, depression, motor skill performance, and changes in blood oxygen level-dependent functional neuroimaging during an emotion regulation task. Group mean scores were calculated at T1, T2, and T3 and in linear mixed-effects multivariate analysis. Effect size for analysis of covariance is presented as partial η2 with the following cutoff points: small, less than 0.06; medium, 0.06 to 0.14; large, greater than 0.14., Results: Postgraduate year 1 surgery residents (N = 21; 8 [38%] women) were randomized to a modMBSR arm (n = 12) or an active control arm (n = 9). Linear mixed-effects modeling revealed differences at T2 and T3 in perceived stress (mean [SD] difference at T2: modMBSR, 1.42 [5.74]; control, 3.44 [6.71]; η2 = 0.07; mean [SD] difference at T3: modMBSR, 1.00 [4.18]; control, 1.33 [4.69]; η2 = 0.09) and in mindfulness (mean [SD] difference at T2: modMBSR, 3.08 [3.63]; control, 1.56 [4.28]; η2 = 0.13; mean [SD] difference at T3: modMBSR, 2.17 [3.66]; control, -0.11 [6.19]; η2 = 0.15). Burnout at T2 (mean [SD] difference: modMBSR, 4.50 [9.08]; control, 3.44 [6.71]; η2 = 0.01) and T3 (mean [SD] difference: modMBSR, 5.50 [9.96]; control, 5.56 [9.69]; η2 = 0.01) showed similar increase in both groups. Working memory increased more at T2 in the modMBSR arm (mean [SD] difference, 0.35 [0.60]) than in the control arm (mean [SD] difference, 0.21 [0.74]; η2 = 0.02) and at T3 (modMBSR, 0.68 [0.69]; control, 0.26 [0.58]; η2 = 0.20). Cognitive control decreased more in the control arm at T2 (mean [SD] difference at T2: modMBSR, 0.15 [0.40]; control, -0.07 [0.32]; η2 = 0.13) and at T3 (mean [SD] difference: modMBSR, 0.07 [0.59]; control, -0.26 [0.53]; η2 = 0.16). Mean (SD) circle-cutting time improved more at T2 in the modMBSR arm (-24.08 [63.00] seconds) than in the control arm (-4.22 [112.94] seconds; η2 = 0.23) and at T3 in the modMBSR arm (-4.83 [77.94] seconds) than in the control arm (11.67 [145.17] seconds; η2 = 0.13). Blood oxygen level-dependent functional neuroimaging during an emotional regulation task showed unique postintervention activity in the modMBSR arm in areas associated with executive function control (dorsolateral prefrontal cortex) and self-awareness (precuneus)., Conclusions and Relevance: In this pilot randomized clinical trial, modMBSR in PGY-1 surgery residents showed potential benefits to well-being and executive function, suggesting a powerful role for mindfulness-based cognitive training to support resident well-being and performance, as mandated by the Accreditation Council for Graduate Medical Education., Trial Registration: ClinicalTrials.gov identifier: NCT03141190.

Background: Most states have at least one policy targeting alcohol use during pregnancy. The public health impact of these policies has not been examined. We sought to examine the relationship between state-level policies targeting alcohol use during pregnancy and alcohol use among pregnant women., Methods: Data include state-level alcohol and pregnancy policy data and individual-level U.S. Behavioral Risk Factor Surveillance System data about pregnant women's alcohol use from 1985 to 2016 (N = 57,194). Supportive policies include mandatory warning signs, priority substance abuse treatment, reporting requirements for data and treatment purposes, and prohibitions on criminal prosecution. Punitive policies include civil commitment, Child Protective Services reporting requirements, and child abuse/neglect. Analyses include logistic regression models that adjust for individual- and state-level controls, include fixed effects for state and year, account for clustering by state, and weight by probability of selection., Results: Relative to having no policies, supportive policy environments were associated with more any drinking, but not binge or heavy drinking. Of individual supportive policies, only the following relationships were statistically significant: mandatory warning signs was associated with lower odds of binge drinking, and priority treatment for pregnant women and women with children was associated with higher odds of any drinking. Relative to no policies, punitive policy environments were also associated with more drinking, but not with binge or heavy drinking. Of individual punitive policies, only child abuse/neglect was associated with lower odds of binge and heavy drinking. Mixed policy environments were not associated with any alcohol outcome., Conclusions: Most policies targeting alcohol use during pregnancy do not seem to be associated with less alcohol consumption during pregnancy., (Copyright © 2019 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.)

Objective: Specialty addiction programs treat people who are addicted to alcohol, opioids, stimulants, and other drugs. This study identified the proportion of addiction program clients who received tobacco-related services and factors associated with receipt of such services., Methods: In 2015 and 2016, clients (N=2,119) in 24 programs were surveyed for receipt of services aligning with three of the five As of tobacco cessation: ask, advise, assist. Multivariate analyses examined factors associated with receipt of each service., Results: Most clients (76%) were asked about smoking. Among smokers (N=1,630), 53% were advised to quit, 41% received counseling, 26% received cessation medication, and 17% received counseling and medication. Clients were more likely to receive tobacco-related services if they wanted help quitting smoking or were enrolled in programs with tobacco-free grounds., Conclusions: These correlational findings suggest that increasing client motivation to quit and implementing tobacco-free policies on the grounds of treatment centers may increase tobacco-related services in addiction treatment.

Background: Treatment with bone-marrow-derived mesenchymal stromal cells (MSCs) has shown benefits in preclinical models of acute respiratory distress syndrome (ARDS). Safety has not been established for administration of MSCs in critically ill patients with ARDS. We did a phase 2a trial to assess safety after administration of MSCs to patients with moderate to severe ARDS., Methods: We did a prospective, double-blind, multicentre, randomised trial to assess treatment with one intravenous dose of MSCs compared with placebo. We recruited ventilated patients with moderate to severe ARDS (ratio of partial pressure of oxygen to fractional inspired oxygen <27 kPa and positive end-expiratory pressure [PEEP] ≥8 cm H 2 O) in five university medical centres in the USA. Patients were randomly assigned 2:1 to receive either 10 × 10 6 /kg predicted bodyweight MSCs or placebo, according to a computer-generated schedule with a variable block design and stratified by site. We excluded patients younger than 18 years, those with trauma or moderate to severe liver disease, and those who had received cancer treatment in the previous 2 years. The primary endpoint was safety and all analyses were done by intention to treat. We also measured biomarkers in plasma. MSC viability was tested in a post-hoc analysis. This trial is registered with ClinicalTrials.gov, number NCT02097641., Findings: From March 24, 2014, to Feb 9, 2017 we screened 1038 patients, of whom 60 were eligible for and received treatment. No patient experienced any of the predefined MSC-related haemodynamic or respiratory adverse events. One patient in the MSC group died within 24 h of MSC infusion, but death was judged to be probably unrelated. 28-day mortality did not differ between the groups (30% in the MSC group vs 15% in the placebo group, odds ratio 2·4, 95% CI 0·5-15·1). At baseline, the MSC group had numerically higher mean scores than the placebo group for Acute Physiology and Chronic Health Evaluation III (APACHE III; 104 [SD 31] vs 89 [33]), minute ventilation (11·1 [3·2] vs 9·6 [2·4] L/min), and PEEP (12·4 [3·7] vs 10·8 [2·6] cm H 2 O). After adjustment for APACHE III score, the hazard ratio for mortality at 28 days was 1·43 (95% CI 0·40-5·12, p=0·58). Viability of MSCs ranged from 36% to 85%., Interpretation: One dose of intravenous MSCs was safe in patients with moderate to severe ARDS. Larger trials are needed to assess efficacy, and the viability of MSCs must be improved., Funding: National Heart, Lung, and Blood Institute., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: Sexual and gender minority (SGM) individuals are more likely to smoke than are non-SGM individuals. It is unclear whether smoking cessation interventions for young adults are effective in the SGM population. The purpose of this study was to compare smoking cessation, other health risk behaviors, and intervention usability between SGM and non-SGM young adult smokers participating in a digital smoking cessation intervention trial., Methods: Young adult smokers ( N = 500; 135 SGM) were assigned to a 90-day Facebook smoking cessation intervention (treatment) or referred to Smokefree.gov (control). Intervention participants were assigned to private Facebook groups tailored to their readiness to quit smoking. Participants reported their smoking status and other health risk behaviors at baseline, 3, 6, and 12 months. Usability of the intervention (i.e., perceptions of the intervention and treatment engagement) was assessed in the intervention group at 3 months., Results: Smoking cessation and intervention usability did not significantly differ between SGM participants and non-SGM participants. A greater proportion of SGM participants were at high risk for physical inactivity over the 12-month follow-up period (odds ratio [OR] = 1.55, p = .005)., Conclusion: SGM and non-SGM young adult smokers did not differ in their smoking cessation rates, perceptions of, or engagement in a digital intervention. Health risk behavior patterns were mostly similar; however, the disparity in physical activity between SGM and non-SGM smokers widened over time. Tailored interventions for SGM young adult smokers could increase focus on SGM experiences that can underlie multiple health risk behaviors, such as discrimination and the normativity of smoking. (PsycINFO Database Record (c) 2018 APA, all rights reserved).