Refining a Framework to Enhance Communication in the Emergency Department During the Diagnostic Process: An eDelphi Approach.

BACKGROUND: Emergency departments (EDs) are susceptible to diagnostic error. Suboptimal communication between the patient and the interdisciplinary care team increases risk to diagnostic safety. The role of communication remains underrepresented in existing diagnostic decision-making conceptual models. METHODS: The authors used eDelphi methodology, whereby data are collected electronically, to achieve consensus among an expert panel of 18 clinicians, patients, family members, and other participants on a refined ED-based diagnostic decision-making framework that integrates several potential opportunities for communication to enhance diagnostic quality. This study examined the entire diagnostic process in the ED, from prehospital to discharge or transfer to inpatient care, and identified where communication breakdowns could occur. After four iterative rounds of the eDelphi process, including a final validation round by all participants, the project's a priori consensus threshold of 80% agreement was reached. RESULTS: The authors developed a final framework that positions communication more prominently in the diagnostic process in the ED and enhances the original National Academies of Sciences, Engineering, and Medicine (NASEM) and ED-adapted NASEM frameworks. Specific points in the ED journey were identified where more attention to communication might be helpful. Two specific types of communication-information exchange and shared understanding-were identified as high priority for optimal outcomes. Ideas for communication-focused interventions to prevent diagnostic error in the ED fell into three categories: patient-facing, clinician-facing, and system-facing interventions. CONCLUSION: This project's refinement of the NASEM framework adapted to the ED can be used to develop communications-focused interventions to reduce diagnostic error in this highly complex and error-prone setting.

FBH1 deficiency sensitizes cells to WEE1 inhibition by promoting mitotic catastrophe.

WEE1 kinase phosphorylates CDK1 and CDK2 to regulate origin firing and mitotic entry. Inhibition of WEE1 has become an attractive target for cancer therapy due to the simultaneous induction of replication stress and inhibition of the G2/M checkpoint. WEE1 inhibition in cancer cells with high levels of replication stress results in induction of replication catastrophe and mitotic catastrophe. To increase potential as a single agent chemotherapeutic, a better understanding of genetic alterations that impact cellular responses to WEE1 inhibition is warranted. Here, we investigate the impact of loss of the helicase, FBH1, on the cellular response to WEE1 inhibition. FBH1-deficient cells have a reduction in ssDNA and double strand break signaling indicating FBH1 is required for induction of replication stress response in cells treated with WEE1 inhibitors. Despite the defect in the replication stress response, FBH1-deficiency sensitizes cells to WEE1 inhibition by increasing mitotic catastrophe. We propose loss of FBH1 is resulting in replication-associated damage that requires the WEE1-dependent G2 checkpoint for repair.

Assessing Pediatric Rheumatology Fellow Competence in the Milestone Era: Past, Present, and Future.

Starting in 2015, pediatric rheumatology fellowship training programs were required by the Accreditation Council for Graduate Medical Education to assess fellows' academic performance within 21 subcompetencies falling under six competency domains. Each subcompetency had four or five milestone levels describing developmental progression of knowledge and skill acquisition. Milestones were standardized across all pediatric subspecialties. As part of the Milestones 2.0 revision project, the Accreditation Council for Graduate Medical Education convened a workgroup in 2022 to write pediatric rheumatology-specific milestones. Using adult rheumatology's Milestones 2.0 as a starting point, the workgroup revised the patient care and medical knowledge subcompetencies and milestones to reflect requirements and nuances of pediatric rheumatology care. Milestones within four remaining competency domains (professionalism, interpersonal and communication skills, practice-based learning and improvement, and systems-based practice) were standardized across all pediatric subspecialties, and therefore not revised. The workgroup created a supplemental guide with explanations of the intent of each subcompetency, 25 in total, and examples for each milestone level. The new milestones are an important step forward for competency-based medical education in pediatric rheumatology. However, challenges remain. Milestone level assignment is meant to be informed by results of multiple assessment methods. The lack of pediatric rheumatology-specific assessment tools typically result in clinical competency committees determining trainee milestone levels without such collated results as the foundation of their assessments. Although further advances in pediatric rheumatology fellowship competency-based medical education are needed, Milestones 2.0 importantly establishes the first pediatric-specific rheumatology Milestones to assess fellow performance during training and help measure readiness for independent practice.

Using the multiphase optimization strategy to adapt cognitive processing therapy (CPT MOST): study protocol for a randomized controlled factorial experiment.

BACKGROUND: Approximately ten percent of US military veterans suffer from posttraumatic stress disorder (PTSD). Cognitive processing therapy (CPT) is a highly effective, evidence-based, first-line treatment for PTSD that has been widely adopted by the Department of Veterans Affairs (VA). CPT consists of discrete therapeutic components delivered across 12 sessions, but most veterans (up to 70%) never reach completion, and those who discontinue therapy receive only four sessions on average. Unfortunately, veterans who drop out prematurely may never receive the most effective components of CPT. Thus, there is an urgent need to use empirical approaches to identify the most effective components of CPT so CPT can be adapted into a briefer format. METHODS: The multiphase optimization strategy (MOST) is an innovative, engineering-inspired framework that uses an optimization trial to assess the performance of individual intervention components within a multicomponent intervention such as CPT. Here we use a fractional factorial optimization trial to identify and retain the most effective intervention components to form a refined, abbreviated CPT intervention package. Specifically, we used a 16-condition fractional factorial experiment with 270 veterans (N = 270) at three VA Medical Centers to test the effectiveness of each of the five CPT components and each two-way interaction between components. This factorial design will identify which CPT components contribute meaningfully to a reduction in PTSD symptoms, as measured by PTSD symptom reduction on the Clinician-Administered PTSD Scale for DSM-5, across 6 months of follow-up. It will also identify mediators and moderators of component effectiveness. DISCUSSION: There is an urgent need to adapt CPT into a briefer format using empirical approaches to identify its most effective components. A brief format of CPT may reduce attrition and improve efficiency, enabling providers to treat more patients with PTSD. The refined intervention package will be evaluated in a future large-scale, fully-powered effectiveness trial. Pending demonstration of effectiveness, the refined intervention can be disseminated through the VA CPT training program. TRIAL REGISTRATION: ClinicalTrials.gov NCT05220137. Registration date: January 21, 2022.

FBH1 deficiency sensitizes cells to WEE1 inhibition by promoting mitotic catastrophe.

WEE1 kinase phosphorylates CDK1 and CDK2 to regulate origin firing and mitotic entry. Inhibition of WEE1 has become an attractive target for cancer therapy due to the simultaneous induction of replication stress and inhibition of the G2/M checkpoint. WEE1 inhibition in cancer cells with high levels of replication stress results in induction of replication catastrophe and mitotic catastrophe. To increase potential as a single agent chemotherapeutic, a better understanding of genetic alterations that impact cellular responses to WEE1 inhibition is warranted. Here, we investigate the impact of loss of the helicase, FBH1, on the cellular response to WEE1 inhibition. FBH1-deficient cells have a reduction in ssDNA and double strand break signaling indicating FBH1 is required for induction of replication stress response in cells treated with WEE1 inhibitors. Despite the defect in the replication stress response, FBH1-deficiency sensitizes cells to WEE1 inhibition by increasing mitotic catastrophe. We propose loss of FBH1 is resulting in replication-associated damage that requires the WEE1-dependent G2 checkpoint for repair.

Assessing the diagnostic utility of the Cannabis Use Disorder Identification Test - Revised (CUDIT-R) among veterans with medical and non-medical cannabis use.

BACKGROUND: Few studies examine the utility of the Cannabis Use Disorder Identification Test - Revised (CUDIT-R) in relation to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, (DSM-5) criteria for cannabis use disorder (CUD). This study assesses the performance of the CUDIT-R among a sample of Veterans with and without medical cannabis use. METHODS: We approached and consented primary care patients presenting to one of three Department of Veterans Affairs (VA) Medical Centers. Veterans with at least monthly cannabis use and complete CUD data at baseline were included in this analysis (n=234). CUDIT-R scores were compared against Alcohol Use Disorder and Associated Disabilities Interview Schedule-5 (DSM-5) CUD as the standard to calculate measures of validity (sensitivity, specificity), identify optimal CUDIT-R cutoff values, and assess the diagnostic proficiency of the CUDIT-R using receiver operating characteristic (ROC) curves. We further stratified analyses by active medical cannabis card holder status and DSM-5 CUD severity (any, moderate, and severe). RESULTS: Among the entire sample, 38.9% qualified for any DSM-5 CUD, with 10.7% and 3.0% meeting criteria for moderate and severe CUD, respectively. We identified optimal CUDIT-R scores at 10 for any DSM-5 CUD (sensitivity=0.58; specificity=0.80), at 12 for moderate CUD (sensitivity=0.72; specificity=0.82), and at 14 for severe CUD (sensitivity=0.71; specificity=0.87). ROC curves showed higher CUDIT-R validity among non-card holders compared with medical cannabis card holders. CONCLUSION: The present study identified optimal CUDIT-R cutoff scores for Veterans who use cannabis. Varying DSM-5 validity measures inform the need for population-specific CUDIT-R cutoff values.

B lymphocytes in treatment-naive paediatric patients with lupus are epigenetically distinct from healthy children.

BACKGROUND: SLE is likely triggered by gene-environment interactions. We have shown that most SLE-associated haplotypes encompass genomic regions enriched for epigenetic marks associated with enhancer function in lymphocytes, suggesting genetic risk is exerted through altered gene regulation. Data remain scarce on how epigenetic variance contributes to disease risk in paediatric SLE (pSLE). We aim to identify differences in epigenetically regulated chromatin architecture in treatment-naive patients with pSLE compared with healthy children. METHODS: Using the assay for transposase-accessible chromatin with sequencing (ATACseq), we surveyed open chromatin in 10 treatment-naive patients with pSLE, with at least moderate disease severity, and 5 healthy children. We investigated whether regions of open chromatin unique to patients with pSLE demonstrate enrichment for specific transcriptional regulators, using standard computational approaches to identify unique peaks and a false discovery rate of <0.05. Further analyses for histone modification enrichment and variant calling were performed using bioinformatics packages in R and Linux. RESULTS: We identified 30 139 differentially accessible regions (DAR) unique to pSLE B cells; 64.3% are more accessible in pSLE than healthy children. Many DAR are found in distal, intergenic regions and enriched for enhancer histone marks (p=0.027). B cells from adult patients with SLE contain more regions of inaccessible chromatin than those in pSLE. In pSLE B cells, 65.2% of the DAR are located within or near known SLE haplotypes. Further analysis revealed enrichment of transcription factor binding motifs within these DAR that may regulate genes involved in pro-inflammatory responses and cellular adhesion. CONCLUSIONS: We demonstrate an epigenetically distinct profile in pSLE B cells when compared with healthy children and adults with lupus, indicating that pSLE B cells are predisposed for disease onset/development. Increased chromatin accessibility in non-coding genomic regions controlling activation of inflammation suggest that transcriptional dysregulation by regulatory elements controlling B cell activation plays an important role in pSLE pathogenesis.

Testing adaptive interventions to improve PTSD treatment outcomes in Federally Qualified Health Centers: Protocol for a randomized clinical trial.

BACKGROUND: Posttraumatic stress disorder (PTSD) disproportionately affects low-income individuals and is untreated in 70% of those affected. One third of low-income Americans are treated in Federally Qualified Health Centers (FQHCs), which do not have the capacity to provide all patients with first-line treatments such as Prolonged Exposure (PE). To address this problem, FQHCs could use low-intensity interventions (e.g., Clinician-Supported PTSD Coach: CS PTSD Coach) and medium-intensity interventions (e.g., PE for Primary Care: PE-PC) to treat PTSD with fewer resources. However, some patients will still require high-intensity treatments (e.g., full-length PE) for sustained clinical benefit. Thus, there is a critical need to develop stepped-care models for PTSD in FQHCs. METHOD: We are conducting a Sequential, Multiple Assignment, Randomized Trial (SMART) with 430 adults with PTSD in FQHCs. Participants are initially randomized to CS PTSD Coach or PE-PC. After four sessions, early responders step down to lower frequency interaction within their assigned initial treatment strategy. Slow responders are re-randomized to either continue their initial treatment strategy or step up to Full PE for an additional eight weeks. The specific aims are to test the effectiveness of initiating treatment with PE-PC versus CS PTSD Coach in reducing PTSD symptoms and to test the effectiveness of second-stage strategies (continue versus step-up to Full PE) for slow responders. CONCLUSIONS: This project will provide critical evidence to inform the development of an effective stepped-care model for PTSD. Testing scalable, sustainable sequences of PTSD treatments delivered in low-resource community health centers will improve clinical practice for PTSD.

Peer- and web-based interventions for risky drinking among US National Guard members: Mission Strong randomized controlled trial.

AIMS: To test separatel the efficacy of a web-based and a peer-based brief intervention (BI), compared with an expanded usual care control (EUC) group, among military reserve component members using alcohoI in a hazardous and harmful manner. DESIGN: In the randomized controlled trial, participants were assigned to: [1] web-based BI with web-based boosters (BI + web), [2] web-based BI with peer-based boosters (BI + peer) or [3] enhanced usual care (EUC). SETTING: Michigan, USA. PARTICIPANTS: A total of 739 Michigan Army National Guard members who reported recent hazardous alcohol use; 84% were male, the mean age was 28 years. INTERVENTION: The BI consisted of an interactive program guided by a personally selected avatar. Boosters were delivered either on the web or personally by a trained veteran peer. A pamphlet, given to all participants, included information on hazardous alcohol use and military-specific community resources and served as the EUC condition. MEASUREMENTS: The primary outcome measure was binge drinking episodes in the past 30 days, measured at 12 months after the BI. FINDINGS: All randomized participants were included in the outcome analyses. In adjusted analyses, BI + peer [beta = -0.43, 95% confidence interval (CI) = -0.56 to -0.31, P < 0.001] and BI + web (beta = -0.34, 95% CI = -0.46 to -0.23, P < 0.001) reduced binge drinking compared with EUC. CONCLUSION: This satudy was a web-based brief intervention for hazardous alcohol use, with either web- or peer-based boosters, reduced binge alcohol use among Army National Guard members.

The safety of COVID-19 vaccination in immunocompromised children and young adults with immune-mediated inflammatory disease.

AIM: To assess safety of COVID-19 vaccination in paediatric patients with immune-mediated inflammatory disease (IMID). METHODS: Subjects of 5-21 years of age with IMID who received at least one COVID-19 vaccine completed electronic surveys after each vaccine to assess side effects within 1 week of vaccination, current medications and COVID-19 testing after vaccination. Charts were reviewed for COVID-19 polymerase chain reaction and IgG response to SARS-CoV-2 spike protein results and for disease flare during the study period. RESULTS: Among 190 enrolled subjects, 71% were female, with median age 17 (range 6-21) years. The most common diagnosis was juvenile idiopathic arthritis/rheumatoid arthritis (55%). 78% of subjects were taking immunosuppressive medication. At least one side effect was reported in 65% of subjects after any dose of the vaccine; with side effects in 38%, 53% and 55% of subjects after the first, second and third vaccine doses, respectively. The most common side effects were injection site pain (59%), fatigue (54%) and headache (39%). No anaphylaxis or myocarditis was reported. Three subjects (2%) experienced disease flare. CONCLUSION: In our cohort of paediatric patients with IMID, observed side effects were found to be mild and disease flare rates were found to be low following COVID-19 vaccination.

"I wish people could come together like we have," patient and provider perspectives on VA residential PTSD treatment.

Although most posttraumatic stress disorder (PTSD) care in the Veterans health administration (VHA) is provided on an outpatient basis, the VHA has 40 residential rehabilitation treatment programs (RRTPs) designed to treat Veterans who require more intensive and closely monitored care. Unfortunately, the clinical outcomes of these programs are modest, and previous attempts to identify key drivers of outcomes have uncovered few modifiable factors. The present study, informed by the model of resources, life events and changes in psychological state, was designed to identify factors associated with treatment response among RRTP patients and providers. Semistructured interviews were conducted with 24 patients and 12 providers at three regional RRTPs, using interview guides based on the theoretical model. Data were analyzed using rapid analysis. Results showed that patients and providers agreed on several factors critical to RRTP success. These factors included the provision of evidence-based psychotherapy (EBP), support and understanding from fellow patients, and skill and support from providers. Patients and providers also noted the importance of psychological flexibility, openness, and willingness to change. Patients who experienced less symptom improvement over the course of treatment were more likely to report poor therapeutic alliance. These findings underscore the importance of continued emphasis on EBP delivery but also suggest that RRTPs might find additional ways to capitalize on the residential milieu to encourage engagement in treatment and a focus on therapeutic change. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Hypothetical proteins play a role in stage conversion, virulence, and the stress response in the Entamoeba species.

Entamoeba histolytica is a protozoan parasite that causes amoebic dysentery and amoebic liver abscess in humans, affecting millions of people worldwide. This pathogen possesses a two-stage life cycle consisting of an environmentally stable cyst and a pathogenic amoeboid trophozoite. As cysts can be ingested from contaminated food and water, this parasite is prevalent in underdeveloped countries and poses a significant health burden. Until recently there was no reliable method for inducing stage conversion in E. histolytica in vitro. As such, the reptilian pathogen, Entamoeba invadens, has long-served as a surrogate. Much remains unclear about stage conversion in these parasites and current treatments for amoebiasis are lacking, as they cause severe side effects. Therefore, new therapeutic strategies are needed. The genomes of these parasites remain enigmatic as approximately 54% of E. histolytica genes and 66% of E. invadens genes are annotated as hypothetical proteins. In this study, we characterized two hypothetical proteins in the Entamoeba species, EIN_059080, in E. invadens, and its homolog, EHI_056700, in the human pathogen, E. histolytica. EHI_056700 has no homolog in the human host. We used an RNAi-based silencing system to reduce expression of these genes in E. invadens and E. histolytica trophozoites. Loss of EIN_059080 resulted in a decreased rate of encystation and an increased rate of erythrophagocytosis, an important virulence function. Additionally, mutant parasites were more susceptible to oxidative stress. Similarly, loss of EHI_056700 in E. histolytica trophozoites resulted in increased susceptibility to oxidative stress and glucose deprivation, but not to nitrosative stress. Unlike the E. invadens mutants, E. histolytica parasites with decreased reduced expression of EHI_056700 exhibited a decreased rate of erythrophagocytosis of and adhesion to host cells. Taken together, these data suggest that these hypothetical proteins play a role in stage conversion, virulence, and the response to stress in the Entamoebae. Since parasites with reduced expression of EHI_056700 show decreased virulence functions and increased susceptibility to physiologically relevant stressors, EHI_056700 may represent a possible therapeutic target for the treatment of amoebiasis.

Feasibility and Acceptability of Group-Facilitated Prolonged Exposure Therapy for PTSD in VA Residential Rehabilitation Treatment Programs.

Prolonged Exposure therapy (PE) is a first-line treatment for posttraumatic stress disorder (PTSD); however, few VA patients receive this treatment. One of the barriers to PE receipt is that it is only available in an individual (one-on-one) format, whereas many VA mental health clinics provide the majority of their psychotherapy services in group format. In particular, PTSD residential rehabilitation treatment programs (RRTPs) offer most programming in group format. Consequently, strategies are needed to improve the scalability of PE by adapting it to fit the delivery setting. The current study was designed to pilot test a group-facilitated format of PE in RRTPs. Thirty-nine Veterans who were engaged in care in the PTSD RRTP at a Midwestern VA were recruited to participate in a Group-facilitated PE protocol. Participants engaged in twelve 90-minute sessions of Group PE over the course of 6 weeks, plus six 60-minute individual sessions for imaginal exposure. Group treatment followed the PE model and consisted of psychoeducation, treatment rationale, and in vivo exposure to reduce trauma-related avoidance and thereby improve PTSD symptoms. PTSD symptoms were measured via the PTSD Checklist for DSM-5 (PCL-5) and depression symptoms were measured via the Patient Health Questionnaire (PHQ-9) at baseline, endpoint (6 weeks), and at 2-month follow-up. Thirty-nine individuals initiated Group-facilitated PE and 34 completed treatment. The average number of group sessions attended was 11 out of 12. Acceptability ratings were high. Mean change (improvement) in the intent-to-treat sample at 2-month follow-up was 20.0 points on the PCL-5 (CI 18.1, 21.9; Cohen's d = 1.1) and 4.8 points on the PHQ-9 (CI 4.1, 5.5, d = .8). These results suggest that adapted evidence-based interventions for PTSD can improve treatment access and efficiency for the RRTP setting. A group-based approach has the potential to improve the scalability of PTSD treatment by reducing required resources. A fully powered trial is now needed to test the effectiveness of Group-facilitated PE in the RRTP setting.

Eukaryotic Initiation Factor 2α Kinases Regulate Virulence Functions, Stage Conversion, and the Stress Response in Entamoeba invadens.

Entamoeba histolytica is a protozoan parasite that causes amoebic dysentery and liver abscess. This pathogen possesses a two-stage life cycle consisting of an environmentally stable cyst and a pathogenic amoeboid trophozoite. Since infection is acquired by ingestion of cysts from contaminated food and water, this parasite is prevalent in underdeveloped countries. A reptilian pathogen, Entamoeba invadens, which can encyst in culture, has long served as a surrogate to study stage conversion. In the host, Entamoeba species must manage stress, including nutrient deprivation and host immune pressure. In many systems, the stress response is characterized by downregulation of translation, which is initiated by the phosphorylation of eukaryotic initiation factor-2 alpha (eIF2α). In mammalian cells, this phosphorylation is carried out by a family of eIF2α kinases. A canonical eIF2α translational control system exists in Entamoeba species; however, no eIF2α kinases have been characterized. In this study, we identified two eIF2α kinases in E. invadens, EiIF2K-A and EiIF2K-B. Their identity as eIF2α kinases was validated using a heterologous yeast system. We used an RNA interference (RNAi) trigger-mediated silencing system to reduce expression of EiIF2K-A, which also reduced expression of EiIF2K-B. Parasites with decreased kinase expression exhibited decreased phosphorylation of eIF2α and increased sensitivity to oxidative stress. Diminished kinase expression also correlated with an increased rate of encystation, a decreased rate of excystation, and an increase in several virulence functions, erythrophagocytosis and adhesion to host cells. Taken together, these data suggest that EiIF2K-A and EiIF2K-B are authentic eIF2α kinases that may regulate the Entamoeba stress response. IMPORTANCE Entamoeba histolytica is a human pathogen that causes dysentery and affects millions of people worldwide. This parasite possesses a two-stage life cycle: an environmentally stable cyst and the pathogenic trophozoite. Cysts are ingested from contaminated food and water; thus, this parasite in prevalent in underdeveloped countries. Current therapies commonly cause adverse side effects; therefore, new treatments are needed. In the host, Entamoeba experiences stress brought on, in part, by the host immune system. Understanding stage conversion and the stress response of this pathogen may lead to new drug therapies. Using the model organism E. invadens, we identified two kinases similar to those involved in stress and stage conversion in other systems. We determined that these kinases may regulate the oxidative stress response, stage conversion, and virulence. This work is significant, as it will inform future studies on the life cycle and pathogenicity of Entamoeba species.

Feasibility and Acceptability of Prolonged Exposure in Primary Care (PE-PC) for Posttraumatic Stress Disorder in Federally Qualified Health Centers: A Pilot Study.

Posttraumatic stress disorder (PTSD) is a debilitating psychiatric disorder that affects 6% of U.S. adults, yet is treated in only 30% of affected individuals and even fewer low-income individuals. One third of the nation's low-income individuals are treated in Federally Qualified Health Centers (FQHCs). Most of these facilities lack capacity to provide their patients with first-line, evidence-based treatments for PTSD such as Prolonged Exposure (PE). To address this problem, PE has been adapted for use in a primary care setting and demonstrated efficacy in a brief model for military service members (PE in Primary Care: PE-PC). The effectiveness of this treatment in civilian, low-resource settings such as FQHCs is unknown. This pilot study tested the feasibility and acceptability of PE-PC in 30 Michigan FQHC patients. High rates of therapy participation suggest that the intervention was feasible and acceptable. Semi-structured interview data from 10 patients and 5 FQHC providers indicated that the intervention was helpful and filled a critical need for effective PTSD treatment in the FQHC setting. Interviews also elucidated barriers such as transportation, provider training, and time commitment for patients and providers. These findings set the stage for a full-scale randomized controlled trial to test the effectiveness of PE-PC on PTSD symptoms in this low-resource, high-need setting.Trial registry ClinicalTrials.gov Identifier: NCT03711266. October 18, 2018.

A nationally representative sample of veteran and matched non-veteran college students: Mental health symptoms, suicidal ideation, and mental health treatment.

Objective To assess mental health symptoms, suicidal ideation/behaviors, and treatment among a nationally representative probability sample of student veterans. Participants: Student veterans enrolled in post-secondary educational institutions and matched comparison students. Methods: Sampled participants completed an online survey (n = 1,838). Analyses accounted for the complex sample design and non-response. Results: Substantial percentages of student veterans screened positive for: depression (36.9%, 95% CI: 31.1-42.7), PTSD (35.7%, 95% CI 29.9-41.5), anxiety (29.5%, 95% CI 26.8-32.2), and suicidal ideation (14.6%, 95% CI 12.1-17.1), with student veterans having odds ratios between 1.7 to 2.4 for positive screens compared to non-veteran students. Only 41.5% (95% CI 33.0-50.0) of student veterans with positive screens received treatment, although they had 50% higher odds of receiving treatment than non-veteran students. Conclusions: Student veterans have high rates of mental health symptoms and low rates of treatment. However, they are more likely to receive treatment than comparison students.

Seroprevalence and clinical outcomes of SARS-CoV-2 in paediatric patients with rheumatic disease.

OBJECTIVES: Immunosuppressed paediatric patients with rheumatic disease (RD) may be at risk for severe or critical disease related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Data remain scarce on coronavirus disease 2019 (COVID-19) outcomes in paediatric RD patients. The aim of this study was to determine the seroprevalence of SARS-CoV-2 IgG and to describe COVID-19 outcomes in immunosuppressed paediatric RD patients. METHODS: Patients diagnosed with RD before age 18 years and treated with at least one immunosuppressive medication for at least 3 months were enrolled from a tertiary paediatric rheumatology practice in New York and also underwent routine SARS-CoV-2 IgG testing from May to November 2020. A total of 571 patients were screened and 262 were enrolled. SARS-CoV-2 IgG-positive subjects were assessed for symptoms of COVID-19 infection. SARS-CoV-2 PCR results were recorded where available. Demographic, diagnostic, medication and outcome data were collected. RESULTS: Of 262 subjects (186 female), 35 (13%) were SARS-CoV-2 IgG positive; 17 (49%) had symptoms suggestive of COVID-19. Of the 17 patients who had SARS-CoV-2 PCR testing, 11 (65%) were PCR positive, 7 of whom were IgG positive. Most SARS-CoV-2 IgG-positive subjects were not PCR tested. The most common symptoms in IgG- and/or PCR-positive subjects were fever, fatigue and cough. No SARS-CoV-2 IgG- or PCR-positive subject developed severe or critical COVID-19 or required hospitalization. CONCLUSIONS: This is the first report of clinical outcomes of SARS-CoV-2 infection and seroprevalence of SARS-CoV-2 IgG in a large cohort of paediatric RD patients. Most SARS-CoV-2 IgG-positive subjects had no symptoms of COVID-19 infection. Symptomatic subjects all had mild COVID-19 symptoms, suggesting that the risk of severe or critical COVID-19 in immunosuppressed paediatric RD patients is minimal.

Predictors of Booster Engagement Following a Web-Based Brief Intervention for Alcohol Misuse Among National Guard Members: Secondary Analysis of a Randomized Controlled Trial.

BACKGROUND: Alcohol misuse is a major health concern among military members. Reserve component members face unique barriers as they live off base with limited access to behavioral health services. Web and app-based brief interventions are a promising means to improve access to treatment for those who misuse alcohol, with the use of booster sessions to enhance effectiveness, solidify gains, and reinforce changes. However, little is known about who will engage in booster sessions. OBJECTIVE: This study aims to evaluate booster engagement across booster delivery modalities (Web and Peer) and identify participant-specific factors associated with booster session engagement. METHODS: Following a brief web-based alcohol misuse intervention in National Guard members (N=739), we examined engagement in a series of three booster sessions. Using unadjusted and adjusted models, demographic and clinical characteristics that may serve as predictors of booster session engagement were examined across the 2 arms of the trial with different types of booster sessions: peer-delivered (N=245) and web-delivered (N=246). RESULTS: Booster session completion was greater for Peer than Web Booster sessions, with 142 (58%) service members in the Peer Booster arm completing all three boosters compared with only 108 (44%) of participants in the Web Booster arm (χ23=10.3; P=.006). In a model in which the 2 groups were combined, socioeconomic factors predicted booster engagement. In separate models, the demographic and clinical predictors of booster engagement varied between the 2 delivery modalities. CONCLUSIONS: The use of peer-delivered boosters, especially among subsets of reserve members at risk of lack of engagement, may foster greater uptake and improve treatment outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT02181283; https://clinicaltrials.gov/ct2/show/NCT02181283.

Procalcitonin Differs in Children With Infection and Children With Disease Flares in Juvenile Idiopathic Arthritis.

BACKGROUND/OBJECTIVE: Patients with juvenile idiopathic arthritis (JIA) often present with signs and symptoms suggestive of serious bacterial infection (SBI). Procalcitonin (PCT) is a biomarker that is elevated in SBI. We conducted a comparative cohort study to test the hypothesis that PCT levels will differ between active JIA, quiescent JIA, and bacteremic patients and healthy controls. METHODS: From October 2016 to May2018, consecutive children 6 months to 18 years of age with (a) active untreated JIA, (b) quiescent JIA, and (c) healthy elective presurgical candidates were recruited from clinics at a musculoskeletal specialty hospital. Juvenile idiopathic arthritis was defined according to the International League of Associations for Rheumatology criteria. Clinical data and serum samples meeting the same criteria were included from a prior study. Consecutive bacteremic patients were identified over the same period. Procalcitonin and other common measures of inflammation were measured. Descriptive statistics and univariate logistic analyses were performed. RESULTS: Ninety-two study subjects were recruited. Erythrocyte sedimentation rate, C-reactive protein (CRP), and PCT levels were all elevated in bacteremic patients in comparison to the other groups. Erythrocyte sedimentation rate and CRP both had wide ranges that overlapped between groups; however, the PCT concentration was 0.15 µg/mL or greater in 1 of 59 patients with JIA, whereas it was 0.15 µg/mL or less in only 1 bacteremic patient. CONCLUSIONS: Our study indicates that serum erythrocyte sedimentation rate, CRP, and PCT levels are all biomarkers that can be used to distinguish SBI versus active JIA at presentation. However, PCT is the most accurate, with the least overlap between patients with infection and noninfectious inflammatory arthritis. This finding can help clinicians direct therapy.

Reduced expression of a rhomboid protease, EhROM1, correlates with changes in the submembrane distribution and size of the Gal/GalNAc lectin subunits in the human protozoan parasite, Entamoeba histolytica.

Entamoeba histolytica is a food- and waterborne parasite that causes amebic dysentery and amoebic liver abscesses. Adhesion is one of the most important virulence functions as it facilitates motility, colonization of host, destruction of host tissue, and uptake of nutrients by the parasite. The parasite cell surface adhesin, the Gal/GalNAc lectin, facilitates parasite-host interaction by binding to galactose or N-acetylgalactosamine residues on host components. It is composed of heavy (Hgl), intermediate (Igl), and light (Lgl) subunits. Igl is constitutively localized to lipid rafts (cholesterol-rich membrane domains), whereas Hgl and Lgl transiently associate with rafts. When all three subunits are localized to rafts, galactose-sensitive adhesion is enhanced. Thus, submembrane location may regulate the function of this adhesion. Rhomboid proteases are a conserved family of intramembrane proteases that also participate in the regulation of parasite-host interactions. In E. histolytica, one rhomboid protease, EhROM1, cleaves Hgl as a substrate, and knockdown of its expression inhibits parasite-host interactions. Since rhomboid proteases are found within membranes, it is not surprising that lipid composition regulates their activity and enzyme-substrate binding. Given the importance of the lipid environment for both rhomboid proteases and the Gal/GalNAc lectin, we sought to gain insight into the relationship between rhomboid proteases and submembrane location of the lectin in E. histolytica. We demonstrated that EhROM1, itself, is enriched in highly buoyant triton-insoluble membranes reminiscent of rafts. Reducing rhomboid protease activity, either pharmacologically or genetically, correlated with an enrichment of Hgl and Lgl in rafts. In a mutant cell line with reduced EhROM1 expression, there was also a significant augmentation of the level of all three Gal/GalNAc subunits on the cell surface and an increase in the molecular weight of Hgl and Lgl. Overall, the study provides insight into the molecular mechanisms governing parasite-host adhesion for this pathogen.