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This study tested the feasibility and preliminary efficacy of a six-session online class on healthy relationships for autistic individuals ages 18–44 years old ( N = 55). The content of the Healthy Relationships on the Autism Spectrum class was informed by formative research with 25 autistic individuals, and developed collaboratively by two non-autistic professionals and seven autistic self-advocates. Fifty-five autistic people participated in Healthy Relationships on the Autism Spectrum and completed pre- and post-surveys. The study found that it was feasible to deliver Healthy Relationships on the Autism Spectrum online. Pairing an autistic and non-autistic person to co-teach was well-received. Participants decreased hostile automatic thoughts ( p Lay abstract The Healthy Relationships on the Autism Spectrum class is unique because autistic people helped to develop it and co-taught it. It is an online, six-session class. The class was piloted in 2020–2021 with 55 autistic people who were ages 18–44 years old. This feasibility study found that most people who took the class liked it. Surveys filled out by the students before and after the class showed that they became less sensitive to rejection, used more positive thinking skills, and were more interested in being social. However, the class may not have made them feel less lonely. The team that invented the class is using the feedback to improve it. The class holds promise for improving the quality of friendships and dating relationships for autistic adults and should be tested further.

This study evaluated the association between impulsivity and linkage to HIV care among Russians living with HIV recruited from an inpatient narcology hospital. Linking Infectious and Narcology Care (LINC) study participants who completed the Barratt Impulsiveness Scale (BIS) were included in these analyses. The primary independent variable was impulsivity score which was categorized as high impulsivity (BIS score > 71) vs. low impulsivity (BIS score

In this prologue, we introduce readers to the Forum: Clinicians and Researchers Navigating Implementation Science in CSD. Implementation science (IS), or the study of the adoption of evidence-based practice in real-world settings, is a key area of development in communication sciences and disorders (CSD). The goal of this forum was to show by example how researchers and clinicians are collaborating to begin to apply IS in CSD. This goal culminated in a scoping review of IS in CSD, a tutorial on incorporating IS into clinical practice research, three articles on stakeholder engagement, and three examples of IS studies in CSD included in this forum. We hope this forum helps clinicians and researchers to begin wherever they are in their knowledge and understanding of IS in CSD.

Women harboring mutations in breast cancer susceptibility genes are at increased lifetime risk of developing breast cancer and are faced with decisions about risk management, including whether to undergo high-risk screening or risk-reducing mastectomy (RRM). National guidelines recommend BRCA1 or BRCA2 mutation carriers consider RRM, but that carriers of moderate penetrance mutations (e.g., ATM or CHEK2) should be managed based on family history. We aimed to investigate determinants of decision for RRM, and hypothesized that mutation status, age, family history, partner status, and breast cancer would impact RRM decision making.We performed a retrospective study assessing RRM decisions for 279 women.Women with BRCA and moderate penetrance gene mutations, a personal history of breast cancer, or a first degree relative with a history of breast cancer were more likely to undergo RRM. Breast cancer status and age showed an interaction effect such that women with breast cancer were less likely to undergo RRM with increasing age.Although national guidelines do not recommend RRM for moderate penetrance carriers, the rates of RRM for this population approached those for BRCA mutation carriers. Further insights are needed to better support RRM decision-making in this population.

Reproductive outcomes, such as preterm birth, miscarriage/stillbirth, and pre-eclampsia, are understudied in veterans, particularly among Gulf War veterans (GWVs). During deployment, women GWVs were exposed to toxicant and nontoxicant exposures that may be associated with adverse reproductive and developmental outcomes. The data come from a survey of 239 participants from northeastern and southern U.S. cohorts of women veterans. The questionnaire collected information about the service history, current and past general health, reproductive and family health, demographic information, and deployment exposures. Odds ratios were computed with 95% confidence intervals between exposures in theater and reproductive/children’s health outcomes. GWVs experienced adverse reproductive outcomes: 25% had difficulty conceiving, and 31% had a pregnancy that ended in a miscarriage or stillbirth. Pregnancy complications were common among GWVs: 23% had a high-risk pregnancy, and 16% were diagnosed with pre-eclampsia. About a third of GWVs reported their children (38%) had a developmental disorder. Use of pesticide cream during deployment was associated with higher odds of all reproductive and developmental outcomes. The results demonstrate that GWVs experienced reproductive and children’s health outcomes at potentially high rates, and exploratory analyses suggest pesticide exposure as associated with higher odds of adverse reproductive outcomes. Future longitudinal studies of women veterans should prioritize examining reproductive and children’s health outcomes.

The purpose of this study was to evaluate the efficacy of the Escalation Workshop with a sample of US Navy sailors. Escalation is a one-session workshop designed to promote bystander behavior related to dating abuse. We conducted a two-arm RCT with follow-up at 4 and 8 months. Participants were 335 Navy sailors, recruited from two comparable ships based in the USA. The unit of randomization was the ship. The primary outcomes were as follows: (a) attitudes related to intervening as a bystander in dating abuse situations, (b) injunctive norms about dating abuse, (c) dating abuse-related prevention-oriented behaviors (e.g., such as posting dating violence prevention messages online), and (d) bystander behaviors including acting as a bystander to prevent peer self-harm, peer bullying, peer intoxication, or peer dating abuse, or being a proactive bystander and initiating conversations about dating abuse prevention with friends and others. Hierarchal linear models (HLMs) indicated that, compared to participants in the control group, participants in the intervention group demonstrated improvement in attitudes [β = .09, p

Objectives: Understanding associations between psychosocial and physical factors among those who experience food insecu­rity could help design effective food insecu­rity programs for improved cardiovascular health among low-income populations. We examined differences in psychosocial and physical factors between those who were food secure compared with food insecure among public housing residents. Methods: Data were from the baseline survey of a randomized controlled trial of a weight management intervention in Boston, Massachusetts from 2016-2017. Food insecurity and psychosocial and physical factors, including perceived stress, personal problems, social support, and physical symptoms, were measured via interviewer-administered screeners. Results: Mean age of the sample (N=102) was 46.5 years (SD=11.9). The majority were Hispanic (67%), female (88%), with ≤high school degree (62%). Nearly half were food insecure (48%). For psychosocial vari­ables, those who were food insecure had higher ratings of perceived stress (adjusted mean difference 3.39, 95% CI:2.00,4.79), a higher number of personal problems (ad­justed mean difference 1.85, 95% CI: 1.19, 2.51), and lower social support (adjusted mean difference -0.70, 95% CI:-1.30,-0.11) compared with those who were food se­cure. For physical variables, those who were food insecure had higher odds of reporting negative physical symptoms (aOR 4.92, 95% CI:1.84,13.16). Conclusion: Among this sample of public housing residents, food insecurity was as­sociated with higher stress, more personal problems, higher experiences of physical symptoms, and lower social support. Ethn Dis. 2021;31(1):159-164; doi:10.18865/ed.31.1.159

BACKGROUND AND OBJECTIVES Previous findings on the association between hazardous drinking and HIV-risk behavior have been equivocal, varying by population and individual difference factors. This study examined associations between hazardous drinking, impulsivity, and HIV-risk behaviors among HIV-positive Russian patients with a history of injection drug use (IDU), not on antiretroviral therapy. METHODS Negative binomial regression analyses of data from a randomized controlled trial were performed (N = 241). Main independent variables were the Alcohol Use Disorders Identification Test and the Barratt Impulsiveness Scale. Outcomes were number of condomless sexual episodes (CSE; primary), number of sexual partners, and needle-sharing frequency (secondary). RESULTS Hazardous drinking was positively associated with the frequency of CSE (adjusted incidence rate ratio [aIRR] = 2.16, 95% confidence interval [CI], 1.98-2.36). Moderate (aIRR = 0.51, 95% CI, 0.46-0.56) and high (aIRR = 0.66, 95% CI, 0.60-0.73) impulsivity were associated with fewer CSE compared with low impulsivity. Hazardous drinking (aIRR = 0.64, 95% CI, 0.52-0.79) and impulsivity (aIRR = 0.95, 95% CI, 0.94-0.96) were both associated with fewer sexual partners. Hazardous drinking and impulsivity were each associated with increased needle sharing. The association between hazardous drinking and number of needle-shares was strongest at higher impulsivity levels. CONCLUSION AND SCIENTIFIC SIGNIFICANCE Hazardous drinking may be a risk factor for CSE among HIV-positive Russian patients and may influence needle sharing. Findings contribute to our understanding of the interactive associations between hazardous drinking and impulsivity with sexual risk behaviors and needle sharing among HIV-positive Russian patients with a history of IDU. (Am J Addict 2020;00:00-00).

PURPOSEFor the advances of pediatric oncology next-generation sequencing (NGS) research to equitably benefit all children, a diverse and representative sample of participants is needed. However, little is known about demographic and clinical characteristics that differentiate families who decline enrollment in pediatric oncology NGS research.METHODSDemographic and clinical data were retrospectively extracted for 363 pediatric patients (0-21 years) with cancer approached for enrollment in Genomes for Kids (G4K), a study examining the feasibility of comprehensive clinical genomic analysis of tumors and paired normal samples. Demographic and clinical factors that significantly differentiated which families declined were subsequently compared, for 348 families, with enrollment in Clinical Implementation of Pharmacogenetics (PG4KDS), a pharmacogenomics study with more explicit therapeutic benefit examining genes affecting drug responses and metabolism.RESULTSFifty-three families (14.6%) declined enrollment in G4K. Race/ethnicity was the only variable that significantly differentiated study refusal according to multivariable logistic regression, with families of black children more likely to decline enrollment compared with families of non-Hispanic or Hispanic white children. Reasons for declining G4K were generally consistent with other pediatric genomics research: feeling overwhelmed and insurance discrimination fears were most frequently cited. Families of black children were also more likely to decline enrollment in PG4KDS. Thirteen (3.7%) of the 348 families approached for both studies declined PG4KDS.CONCLUSIONRace/ethnicity differentiated study declination across two different pediatric oncology genomics studies, suggesting enrollment disparities in the context of pediatric oncology genomics research. Genomics research participant samples that do not fully represent racial and ethnic minorities risk further exacerbating health disparities. Additional work is needed to understand the nuances of parental decision making in genomic research and facilitate enrollment of diverse patient populations.

Access to HIV services for HIV-positive patients in addiction care is challenging in Russia, because both care systems are organized independently from each other. Strengths-based case management is an effective strategy to connect people with HIV (PHIV) to HIV care. This mixed-methods study’s objective was to investigate implementation of a case management intervention in St. Petersburg, Russia, designed to connect PHIV who inject drugs to HIV care. We analyzed survey data from 118 HIV-positive patients in addiction care and conducted six focus groups (n=38). Quantitative analyses of fidelity and satisfaction outcomes and qualitative text analysis assessed intervention implementation. Participants who linked to HIV services embraced empowerment and motivation resulting from case management as supporting self-efficacy and linkage to services. Among participants who did not link to care, drug use impeded their care engagement. Main levers to implementation were empowerment to cope with challenges of a fragmented health system and persistent stigma. Those who connected to HIV services credited case managers for facilitating linkage; those who did not link attributed it to personal issues. Implementation of case management for HIV care in Russia should focus on effective substance use treatment and empowerment, motivation and support in addressing personal and system factors.

The complex etiology behind Gulf War Illness (GWI) has been attributed to the combined exposure to neurotoxicant chemicals, brain injuries, and some combat experiences. Chronic GWI symptoms have been shown to be associated with intensified neuroinflammatory responses in animal and human studies. To investigate the neuroinflammatory responses and potential causes in Gulf War (GW) veterans, we focused on the effects of chemical/biological weapons (CBW) exposure and mild traumatic brain injury (mTBI) during the war. We applied a novel MRI diffusion processing method, Neurite density imaging (NDI), on high-order diffusion imaging to estimate microstructural alterations of brain imaging in Gulf War veterans with and without GWI, and collected plasma proinflammatory cytokine samples as well as self-reported health symptom scores. Our study identified microstructural changes specific to GWI in the frontal and limbic regions due to CBW and mTBI, and further showed distinctive microstructural patterns such that widespread changes were associated with CBW and more focal changes on diffusion imaging were observed in GW veterans with an mTBI during the war. In addition, microstructural alterations on brain imaging correlated with upregulated blood proinflammatory cytokine markers TNFRI and TNFRII and with worse outcomes on self-reported symptom measures for fatigue and sleep functioning. Taken together, these results suggest TNF signaling mediated inflammation affects frontal and limbic regions of the brain, which may contribute to the fatigue and sleep symptoms of the disease and suggest a strong neuroinflammatory component to GWI. These results also suggest exposures to chemical weapons and mTBI during the war are associated with different patterns of peripheral and central inflammation and highlight the brain regions vulnerable to further subtle microscale morphological changes and chronic signaling to nearby glia.

The study examines the reliability and validity of a 3-item self-report adherence measure among people with HIV (PWH) experiencing homelessness, substance use, and mental health disorders. 336 participants were included from nine sites across the US between September 2013 and February 2017. We assessed the validity of a self-report scale for adherence to antiretroviral therapy by comparing it with viral load (VL) abstracted from medical records at baseline, 6, 12, and 18 months. The items had high internal consistency (Cronbach’s alpha coefficients at each time point were > 0.8). The adherence scale scores were higher in the group that achieved VL suppression compared to the group that did not. The c-statistic for the receiver-operating characteristic curves pooled across time points was 0.77 for each adherence sub-item and 0.78 for the overall score. The self-report adherence measure shows good internal consistency and validity that correlated with VL suppression in homeless populations.

Coffin-Siris syndrome (CSS) is a rare congenital disorder with variable clinical phenotype consisting of developmental delay and characteristic facial features. It is caused by mutations in the chromatin remodeling switch/sucrose nonfermenting complex. Although SWI/SNF genes are widely implicated in tumorigenesis, only 8 cases of neoplasm have been reported in patients with CSS. We report a case of anaplastic astrocytoma (WHO grade III) in an 18-month-old child with CSS due to a de novo germline missense SMARCE1 mutation. Additional molecular features of the tumor are described as well. The role of missense SMARCE1 mutations in tumor predisposition in children with CSS should be further investigated to better inform genetic counselling.

Gulf War illness (GWI) encompasses a constellation of persistent debilitating symptoms associated with significant changes in central nervous system (CNS) and immune functioning. Currently, there is no validated biomarker for GWI risk susceptibility. Given the impact of immune responses linked to GWI symptomology, genetic variability that causes persistent inflammatory/immune alterations may be key. This Boston University-based Gulf War Illness Consortium (GWIC) study investigated the impact of single nucleotide polymorphisms (SNPs) in variants of immune and pain genetic markers IL1B, IL2, IL6, IL6R, IL10, TNF, TGF, TLR2, TLR4, MD2, MYD88, BDNF, CRP, ICE, COMT and OPRM1 on GWI occurrence in a Caucasian subset of Gulf War (GW) veterans with (cases, n = 170) and without (controls, n = 34) GWI. Logistic regression modeling created a prediction model of GWI risk that associated genetic variability in TGF (rs1800469, p = 0.009), IL6R (rs8192284, p = 0.004) and TLR4 (rs4986791, p = 0.013) with GWI occurrence. This prediction model was specific and sensitive, with a receiver operator characteristic area under the curve of 71.4%. This is the first report of immune genetic variability being predictive of GWI and warrants validation in larger independent cohorts. Future reports will present interactions of these genetic risk factors with other characteristics of GW service.

The Boston University-based Gulf War Illness Consortium (GWIC) is a multidisciplinary initiative developed to provide detailed understanding of brain and immune alterations that underlie Gulf War illness (GWI), the persistent multisymptom disorder associated with military service in the 1990–1991 Gulf War. The core GWIC case-control clinical study conducted in-depth brain and immune evaluation of 269 Gulf War veterans (223 GWI cases, 46 controls) at three U.S. sites that included clinical assessments, brain imaging, neuropsychological testing, and analyses of a broad range of immune and immunogenetic parameters. GWI cases were similar to controls on most demographic, military, and deployment characteristics although on average were two years younger, with a higher proportion of enlisted personnel vs. officers. Results of physical evaluation and routine clinical lab tests were largely normal, with few differences between GWI cases and healthy controls. However, veterans with GWI scored significantly worse than controls on standardized assessments of general health, pain, fatigue, and sleep quality and had higher rates of diagnosed conditions that included hypertension, respiratory and sinus conditions, gastrointestinal conditions, and current or lifetime depression and post-traumatic stress disorder. Among multiple deployment experiences/exposures reported by veterans, multivariable logistic regression identified just two significant GWI risk factors: extended use of skin pesticides in theater (adjusted OR = 3.25, p = 0.005) and experiencing mild traumatic brain injury during deployment (OR = 7.39, p = 0.009). Gulf War experiences associated with intense stress or trauma (e.g., participation in ground combat) were not associated with GWI. Data and samples from the GWIC project are now stored in a repository for use by GWI researchers. Future reports will present detailed findings on brain structure and function, immune function, and association of neuroimmune measures with characteristics of GWI and Gulf War service.

Gulf War Illness (GWI) is a chronic, multi-symptom peripheral and CNS condition with persistent microglial dysregulation, but the mechanisms driving the continuous neuroimmune pathology are poorly understood. The alarmin HMGB1 is an autocrine and paracrine pro-inflammatory signal, but the role of circulating HMGB1 in persistent neuroinflammation and GWI remains largely unknown. Using the LPS model of the persistent microglial pro-inflammatory response, male C57Bl/6J mice injected with LPS (5 mg/kg IP) exhibited persistent changes in microglia morphology and elevated pro-inflammatory markers in the hippocampus, cortex, and midbrain 7 days after LPS injection, while the peripheral immune response had resolved. Ex vivo serum analysis revealed an augmented pro-inflammatory response to LPS when microglia cells were cultured with the 7-day LPS serum, indicating the presence of bioactive circulating factors that prime the microglial pro-inflammatory response. Elevated circulating HMGB1 levels were identified in the mouse serum 7 days after LPS administration and in the serum of veterans with GWI. Tail vein injection of rHMGB1 in male C57Bl/6 J mice elevated TNFα mRNA levels in the liver, hippocampus, and cortex, demonstrating HMGB1-induced peripheral and CNS effects. Microglia isolated at 7 days after LPS injection revealed a unique transcriptional profile of 17 genes when compared to the acute 3 H LPS response, 6 of which were also upregulated in the midbrain by rHMGB1, highlighting a distinct signature of the persistent pro-inflammatory microglia phenotype. These findings indicate that circulating HMGB1 is elevated in GWI, regulates the microglial neuroimmune response, and drives chronic neuroinflammation that persists long after the initial instigating peripheral stimulus.

Background Coronavirus disease 2019 (COVID-19) vaccine trials and post-implementation data suggest that vaccination decreases infections. We examine vaccination’s impact on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) case rates and viral diversity among health care workers (HCWs) during a high community prevalence period. Methods In this prospective cohort study, HCW received 2 doses of BNT162b2 or mRNA-1273. We included confirmed cases among HCWs from 9 December 2020 to 23 February 2021. Weekly SARS-CoV-2 rates per 100,000 person-days and by time from first injection (1–14 and ≥15 days) were compared with surrounding community rates. Viral genomes were sequenced. Results SARS-CoV-2 cases occurred in 1.4% (96/7109) of HCWs given at least a first dose and 0.3% (17/5913) of HCWs given both vaccine doses. Adjusted rate ratios (95% confidence intervals) were 0.73 (.53–1.00) 1–14 days and 0.18 (.10–.32) ≥15 days from first dose. HCW ≥15 days from initial dose compared to 1-14 days were more often older (46 vs 38 years, P = .007), Latinx (10% vs 8%, P = .03), and asymptomatic (48% vs 11%, P = .0002). SARS-CoV-2 rates among HCWs fell below the surrounding community, an 18% vs 11% weekly decrease, respectively (P = .14). Comparison of 50 genomes from post–first dose cases did not indicate selection pressure toward known spike antibody escape mutations. Conclusions Our results indicate an early positive impact of vaccines on SARS-CoV-2 case rates. Post-vaccination isolates did not show unusual genetic diversity or selection for mutations of concern.

INTRODUCTION: Medications for opioid use disorder (MOUD) are highly effective, but barriers along the cascade of care for opioid use disorder (OUD) from diagnosis to treatment limit their reach. For individuals desiring MOUD, the final step in the cascade is filling a written prescription, and fill rates have not been described. METHODS: We used data from a large de-identified database linking individuals’ electronic medical records (EMR) and administrative claims data and employed a previously developed algorithm to identify individuals with a new diagnosis of OUD. We included individuals with a prescription for buprenorphine or naltrexone recorded in the EMR. The outcome was a prescription fill within 30 days as reported in claims data. We compared demographic and clinical characteristics between those who did and did not fill the prescription and used a Kaplan-Meier curve to assess whether fill rates differed based on patient copay. RESULTS: We identified 264 individuals with a new diagnosis of OUD who had a prescription written for buprenorphine or oral naltrexone. Of these, 70% (184) filled the prescription within 30 days, and more than half (57%) filled the prescription on the day it was written. Individuals with prescription copay at or below the mean had a 75% fill rate at 30 days compared with 63% for those with copay above the mean (p

Community health worker-led interventions may be an optimal approach to promote behavior change among populations with low incomes due to the community health workers’ unique insights into participants’ social and environmental contexts and potential ability to deliver interventions widely. The objective was to determine the feasibility (implementation, acceptability, preliminary efficacy) of a weight management intervention for adults living in public housing developments. In 2016–2018, in Boston Massachusetts, we conducted a 3-month, two-group randomized trial comparing participants who received a tailored feedback report (control group) to participants who received the same report plus behavioral counseling. Community health workers provided up to 12 motivational interviewing-based counseling sessions in English or Spanish for diet and physical activity behaviors using a website designed to guide standardized content delivery. 102 participants enrolled; 8 (7.8%) were lost at 3-month follow up. Mean age was 46.5 (SD = 11.9) years; the majority were women (88%), Hispanic (67%), with ≤ high school degree (62%). For implementation, among intervention group participants (n = 50), 5 completed 0 sessions and 45 completed a mean of 4.6 (SD = 3.1) sessions. For acceptability, most indicated they would be very likely (79%) to participate again. For preliminary efficacy, adjusted linear regression models showed mean changes in weight (-0.94 kg, p = 0.31), moderate-to-vigorous physical activity (+11.7 min/day, p = 0.14), and fruit/vegetable intake (+2.30 servings/day, p

Objective Our objective was to describe patient-, provider-, and health systems-level factors associated with likelihood of obtaining guideline-recommended follow-up to prevent or mitigate early-onset type 2 diabetes after a birth complicated by gestational diabetes mellitus (GDM). Methods This study presents a retrospective cohort analysis of de-identified demographic and health care system characteristics, and clinical claims data for 12,622 women with GDM who were continuously enrolled in a large, national U.S. health plan from January 31, 2006, to September 30, 2012. Data were obtained from the OptumLabs Data Warehouse. We extracted 1) known predictors of follow-up (age, race, education, comorbidities, GDM severity); 2) novel factors that had potential as predictors (prepregnancy use of preventive measures and primary care, delivery hospital size); and 3) outcome variables (glucose testing within 1 and 3 years and primary care visit within 3 years after delivery). Results Asian ethnicity, higher education, GDM severity, and delivery in a larger hospital predicted greater likelihood of post-GDM follow-up. Women with a prepregnancy primary care visit of any type were two to three times more likely to receive postpartum glucose testing and primary care at 1 year, and 3.5 times more likely to have obtained testing and primary care at 3 years after delivery. Conclusions A history of use of primary care services before a pregnancy complicated by GDM seems to enhance the likelihood of postdelivery surveillance and preventive care, and thus reduce the risk of undetected early-onset type 2 diabetes. An emphasis on promoting early primary care connections for women in their early reproductive years, in addition to its overall value, is a promising strategy for ensuring follow-up testing and care for women after complicated pregnancies that forewarn risk for later chronic illness. Health systems should focus on models of care that connect primary and reproductive/maternity care before, during, and long after pregnancies occur.

Veterans from the 1991 Gulf War (GW) have suffered from Gulf War illness (GWI) for nearly 30 years. This illness encompasses multiple body systems, including the central nervous system (CNS). Diagnosis and treatment of GWI is difficult because there has not been an objective diagnostic biomarker. Recently, we reported on a newly developed blood biomarker that discriminates GWI from GW healthy controls, and symptomatic controls with irritable bowel syndrome (IBS) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The present study was designed to compare levels of these biomarkers between men and women with GWI, as well as sex-specific effects in comparison to healthy GW veterans and symptomatic controls (IBS, ME/CFS). The results showed that men and women with GWI differ in 2 of 10 plasma autoantibodies, with men showing significantly elevated levels. Men and women with GWI showed significantly different levels of autoantibodies in 8 of 10 biomarkers to neuronal and glial proteins in plasma relative to controls. In summary, the present study addressed the utility of the use of plasma autoantibodies for CNS proteins to distinguish among both men and women veterans with GWI and other healthy and symptomatic control groups.

Genomic studies of pediatric cancer have primarily focused on specific tumor types or high-risk disease. Here, we used a three-platform sequencing approach, including whole-genome sequencing (WGS), whole-exome sequencing (WES), and RNA sequencing (RNA-seq), to examine tumor and germline genomes from 309 prospectively identified children with newly diagnosed (85%) or relapsed/refractory (15%) cancers, unselected for tumor type. Eighty-six percent of patients harbored diagnostic (53%), prognostic (57%), therapeutically relevant (25%), and/or cancer-predisposing (18%) variants. Inclusion of WGS enabled detection of activating gene fusions and enhancer hijacks (36% and 8% of tumors, respectively), small intragenic deletions (15% of tumors), and mutational signatures revealing of pathogenic variant effects. Evaluation of paired tumor–normal data revealed relevance to tumor development for 55% of pathogenic germline variants. This study demonstrates the power of a three-platform approach that incorporates WGS to interrogate and interpret the full range of genomic variants across newly diagnosed as well as relapsed/refractory pediatric cancers. Significance: Pediatric cancers are driven by diverse genomic lesions, and sequencing has proven useful in evaluating high-risk and relapsed/refractory cases. We show that combined WGS, WES, and RNA-seq of tumor and paired normal tissues enables identification and characterization of genetic drivers across the full spectrum of pediatric cancers. This article is highlighted in the In This Issue feature, p. 2945

Background Large administrative databases often do not capture gender identity data, limiting researchers' ability to identify transgender people and complicating the study of this population. Objective The objective of this study was to develop methods for identifying transgender people in a large, national dataset for insured adults. Research design This was a retrospective analysis of administrative claims data. After using gender identity disorder (GID) diagnoses codes, the current method for identifying transgender people in administrative data, we used the following 2 strategies to improve the accuracy of identifying transgender people that involved: (1) Endocrine Disorder Not Otherwise Specified (Endo NOS) codes and a transgender-related procedure code; or (2) Receipt of sex hormones not associated with the sex recorded in the patient's chart (sex-discordant hormone therapy) and an Endo NOS code or transgender-related procedure code. Subjects Seventy-four million adults 18 years and above enrolled at some point in commercial or Medicare Advantage plans from 2006 through 2017. Results We identified 27,227 unique transgender people overall; 18,785 (69%) were identified using GID codes alone. Using Endo NOS with a transgender-related procedure code, and sex-discordant hormone therapy with either Endo NOS or transgender-related procedure code, we added 4391 (16%) and 4051 (15%) transgender people, respectively. Of the 27,227 transgender people in our cohort, 8694 (32%) were transmasculine, 3959 (15%) were transfeminine, and 14,574 (54%) could not be classified. Conclusion In the absence of gender identity data, additional data elements beyond GID codes improves the identification of transgender people in large, administrative claims databases.

For the past 30 years, there has been a lack of objective tools for diagnosing Gulf War Illness (GWI), which is largely characterized by central nervous system (CNS) symptoms emerging from 1991 Gulf War (GW) veterans. In a recent preliminary study, we reported the presence of autoantibodies against CNS proteins in the blood of veterans with GWI, suggesting a potential objective biomarker for the disorder. Now, we report the results of a larger, confirmatory study of these objective biomarkers in 171 veterans with GWI compared to 60 healthy GW veteran controls and 85 symptomatic civilian controls (n = 50 myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and n = 35 irritable bowel syndrome (IBS)). Specifically, we compared plasma markers of CNS autoantibodies for diagnostic characteristics of the four groups (GWI, GW controls, ME/CFS, IBS). For veterans with GWI, the results showed statistically increased levels of nine of the ten autoantibodies against neuronal “tubulin, neurofilament protein (NFP), Microtubule Associated Protein-2 (MAP-2), Microtubule Associated Protein-Tau (Tau), alpha synuclein (α-syn), calcium calmodulin kinase II (CaMKII)” and glial proteins “Glial Fibrillary Acidic Protein (GFAP), Myelin Associated Glycoprotein (MAG), Myelin Basic Protein (MBP), S100B” compared to healthy GW controls as well as civilians with ME/CFS and IBS. Next, we summed all of the means of the CNS autoantibodies for each group into a new index score called the Neurodegeneration Index (NDI). The NDI was calculated for each tested group and showed veterans with GWI had statistically significantly higher NDI values than all three control groups. The present study confirmed the utility of the use of plasma autoantibodies for CNS proteins to distinguish among veterans with GWI and other healthy and symptomatic control groups.

Atrial fibrillation (AF) with rapid ventricular response frequently complicates the management of critically ill patients with sepsis and may necessitate the initiation of medication to avoid hemodynamic compromise. However, the optimal medication to achieve rate control for AF with rapid ventricular response in sepsis is unclear.What is the comparative effectiveness of frequently used AF medications (β-blockers, calcium channel blockers, amiodarone, and digoxin) on heart rate (HR) reduction among critically ill patients with sepsis and AF with rapid ventricular response?We conducted a multicenter retrospective cohort study among patients with sepsis and AF with rapid ventricular response (HR110 beats/min). We compared the rate control effectiveness of β-blockers to calcium channel blockers, amiodarone, and digoxin using multivariate-adjusted, time-varying exposures in competing risk models (for death and addition of another AF medication), adjusting for fixed and time-varying confounders.Among 666 included patients, 50.6% initially received amiodarone, 10.1% received a β-blocker, 33.8% received a calcium channel blocker, and 5.6% received digoxin. The adjusted hazard ratio for HR of 110 beats/min by 1 h was 0.50 (95% CI, 0.34-0.74) for amiodarone vs β-blocker, 0.37 (95% CI, 0.18-0.77) for digoxin vs β-blocker, and 0.75 (95% CI, 0.51-1.11) for calcium channel blocker vs β-blocker. By 6 h, the adjusted hazard ratio for HR 110 beats/min was 0.67 (95% CI, 0.47-0.97) for amiodarone vs β-blocker, 0.60 (95% CI, 0.36-1.004) for digoxin vs β-blocker, and 1.03 (95% CI, 0.71-1.49) for calcium channel blocker vs β-blocker.In a large cohort of patients with sepsis and AF with rapid ventricular response, a β-blocker treatment strategy was associated with improved HR control at 1 h, but generally similar HR control at 6 h compared with amiodarone, calcium channel blocker, or digoxin.

Background Guidelines recommend long-term treatment for opioid use disorder including the use of buprenorphine; however, many patients desire to eventually taper off. This study examines the prevalence and patient characteristics of patients that voluntarily taper off buprenorphine. Methods This is a 12-year retrospective cohort study of adults on buprenorphine in a large urban safety-net primary care practice. The primary outcome was completion of a voluntary buprenorphine taper, which was further characterized as a medically supervised or unsupervised taper. The secondary outcome was re-engagement in care after taper. Descriptive statistics and estimated proportions of both taper completion and re-engagement in treatment were calculated using Kaplan-Meier estimates. Results The study sample included 1308 patients with a median follow-up time of 316 days; 48 patients were observed to taper off buprenorphine during the study period, with an estimated proportion of 15% (95%CI: 10%–21%) based on Kaplan Meier analyses. Less than half of the tapers, 45.8% (22/48), were medically supervised. Thirteen of the 48 patients subsequently, re-engaged in buprenorphine treatment (estimated proportion 61%, 95%CI: 27%–96%), based on Kaplan-Meier analyses with median follow-up time of 490 days. Discussion Despite the fact that many patients desire to discontinue buprenorphine, a minority had a documented taper. Among those who tapered, more than half did so unsupervised by the clinic and a majority of those who tapered off returned to buprenorphine treatment within two years. As many patients are unable to successfully taper off buprenorphine, the medical community must work to address any barriers to long-term maintenance.

Background Comprehensive evaluation of dietary interventions depends on effective and efficient measurement to quantify behavior change. To date, little is known regarding which self-reported measure of dietary intake is most feasible and acceptable for use in evaluation of the effectiveness of diet intervention studies among underserved populations. Objective This research focused on evaluating feasibility and acceptability of two self-report measures of diet. Design Cross-sectional. Participants/setting Two interviewer-administered 24-hour recalls and a 110-item food frequency questionnaire (FFQ) were administered to both English- and Spanish-speaking participants (n=36) by native English- and Spanish-speaking research assistants. On completion of both dietary assessments, participants were interviewed regarding their preference of measure. Main outcome measures Feasibility for completion of the dietary assessment measures was determined for contacts and retention. Acceptability of the measures was determined through responses to open- and closed-ended questions. Results During the 5-month trial, 36 participants were enrolled; 29 completed both intake measures, and 26 completed both measures and the interview. Participants were mainly Hispanic/Latina (72%), with a mean age of 37.0 (±7.6) years. Feasibility targets were met for contacts (1.9, 1.6, 1.8 contact attempts to complete each diet assessment measure with a target of ≤2) and for retention with 89% and 91% completing two 24-hour recalls and the FFQ, respectively. Participants indicated both diet assessment methods were generally acceptable; both positive and negative comments were received for use of the FFQ. Conclusion Dietary assessment with the use of 24-hour recalls or an FFQ can be feasible and acceptable among women with low socioeconomic status, although care should be taken to address cultural appropriateness in the selection of the measurement method.

Aims Gulf War Illness (GWI), a chronic debilitating disorder characterized by fatigue, joint pain, cognitive, gastrointestinal, respiratory, and skin problems, is currently diagnosed by self-reported symptoms. The Boston Biorepository, Recruitment, and Integrative Network (BBRAIN) is the collaborative effort of expert Gulf War Illness (GWI) researchers who are creating objective diagnostic and pathobiological markers and recommend common data elements for GWI research. Main methods BBRAIN is recruiting 300 GWI cases and 200 GW veteran controls for the prospective study. Key data and biological samples from prior GWI studies are being merged and combined into retrospective datasets. They will be made available for data mining by the BBRAIN network and the GWI research community. Prospective questionnaire data include general health and chronic symptoms, demographics, measures of pain, fatigue, medical conditions, deployment and exposure histories. Available repository biospecimens include blood, plasma, serum, saliva, stool, urine, human induced pluripotent stem cells and cerebrospinal fluid. Key findings To date, multiple datasets have been merged and combined from 15 participating study sites. These data and samples have been collated and an online request form for repository requests as well as recommended common data elements have been created. Data and biospecimen sample requests are reviewed by the BBRAIN steering committee members for approval as they are received. Significance The BBRAIN repository network serves as a much needed resource for GWI researchers to utilize for identification and validation of objective diagnostic and pathobiological markers of the illness.

Clinical genomic studies of pediatric cancer have primarily focused on specific tumor types or high-risk disease. In the Genomes for Kids study (NCT02530658) we used a three-platform sequencing approach, including whole genome (WGS), whole exome (WES) and RNA sequencing, to examine tumor and paired germline genomes from prospectively identified children with cancer. The goal of the study was to assess the potential of comprehensive next generation sequencing to elucidate the molecular mechanisms underlying tumor formation and investigate the potential of this information to influence clinical decision-making.The cohort, with a median age of 6 yrs, range 0 - 26 yrs, included 301 patients with newly diagnosed (85%) or relapsed/refractory (15%) cancers, unselected for tumor type or stage. Patients with hematologic malignancies accounted for 41% of cases, 31% had CNS tumors, and 28% had other non-CNS solid tumors. This cohort also included 18 patients with very rare tumor types, defined here as occurring in less than 2 cases per million person per year.Two hundred fifty three patients (84%) had sufficient tumor for three-platform sequencing and all 301 had adequate paired germline samples. Following analysis, 86% of patients harbored diagnostic (53%), prognostic (57%), therapeutically relevant (25%), and/or cancer predisposing (18%) variants. The inclusion of WGS enabled detection of oncogenic gene fusions, as well as 22 cases in which oncogenes were activated through enhancer hijacking, a particularly frequent occurrence in hematologic malignancies. In addition, WGS effectively detected clinically relevant small intragenic deletions (15% of tumors) and a variety of mutational signatures, which were not detectable through analysis of whole exome data. Evaluation of 56 pathogenic germline variants in the context of paired tumor sequence data helped establish the disease relevance of several genes that are not typically associated with the cancer type in question, providing critical insights on a case-by-case basis. Examples include a pathogenic germline variant in MUTYH in a patient with retinoblastoma whose tumor exhibited a mutation signature associated with reactive oxygen species indicative of loss of MUTYH function; and conversely, a likely pathogenic variant in PMS2 in a rare brain cancer, which did not exhibit a mutation signature associated with microsatellite instability. This study successfully demonstrated the power of this three-platform approach to interrogate and interpret the full range of genomic variants across newly diagnosed as well as relapsed/refractory pediatric cancers. As a result of these findings, we have incorporated this three-platform approach into our routine real-time clinical service at St. Jude Children's Hospital. Citation Format: David A. Wheeler, Scott Newman, Joy Nakitandwe, Chimene A. Kesserwan, Elizabeth M. Azzato, Michael C. Rusch, Sheila Shurtleff, Armita Bahrami, Brent Orr, Jeffery M. Klco, Dale J. Hedges, Kayla V. Hamilton, Scott G. Foy, Michael N. Edmonson, Andrew Thrasher, Jiali Gu, Lynn W. Harrison, Lu Wang, Roya Mostafavi, Manish Kubal, Jamie Maciaszek, Michael Clay, Annastasia Ouma, Antonina Silkov, Yanling Liu, Zhaojie Zhang, Yu Liu, Samuel W. Brady, Xin Zhou, Mark Wilkinson, Delaram Rahbarinia, Jay Knight, Jian Wang, Charles G. Mullighan, Rose B. McGee, Emily A. Quinn, Elsie L. Gerhardt, Leslie M. Taylor, Regina Nuccio, Jessica M. Valdez, Stacy J. Hines-Dowell, Alberto Pappo, Giles Robinson, Liza-Marie Johnson, Ching-Hon Pui, David W. Ellison, James R. Downing, Jinghui Zhang, Kim E. Nichols. Genomes for Kids: Comprehensive DNA and RNA sequencing defining the scope of actionable mutations in pediatric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 642.

The majority of myeloid malignancies are caused by sporadic somatic events rather than cancer predisposition. Nonetheless, the identification of hereditary cancer predisposition syndromes is critical when caring for patients with myeloid malignancies since detection may direct decisions related to cancer treatment and surveillance. A positive genetic test result also has important implications for other family members who can use this information to undergo their own testing to determine their cancer risk. We review the demographics, genetic mechanisms of disease, diagnostic approach, malignancy risk, and management for the following five cancer predisposition syndromes associated with myeloid malignancies: Li-Fraumeni, constitutional mismatch repair deficiency, Werner, Bloom, and Nijmegen breakage.

Background Guidelines recommend long-term treatment for opioid use disorder with buprenorphine; however, little is known about patients in long-term treatment. The aim of this study is to examine the prevalence and patient characteristics of long-term treatment retention (≥ 1 year) in an Office Based Opioid Treatment (OBOT) program with buprenorphine. Methods This is a retrospective cohort study of adults on buprenorphine from January 2002 to February 2014 in a large urban safety-net primary care OBOT program. The primary outcome was retention in OBOT for at least one continuous year. Potential predictors included age, race, psychiatric diagnoses, hepatitis C, employment, prior buprenorphine, ever heroin use, current cocaine, benzodiazepine and alcohol use on enrollment. Factors associated with ≥ 1 year OBOT retention were identified using generalized estimating equation logistic regression models. Patients who re-enrolled in the program contributed repeated observations. Results There were 1605 OBOT treatment periods among 1237 patients in this study. Almost half, 45% (717/1605), of all treatment periods were ≥ 1 year and a majority, 53.7% (664/1237), of patients had at least one ≥ 1 year period. In adjusted analyses, female gender (Adjusted Odds Ratio [AOR] 1.55, 95% CI [1.20, 2.00]) psychiatric diagnosis (AOR 1.75 [1.35, 2.27]) and age (AOR 1.19 per 10 year increase [1.05, 1.34]) were associated with greater odds of ≥ 1 year retention. Unemployment (AOR 0.72 [0.56, 0.92]), Hepatitis C (AOR 0.59 [0.45, 0.76]), black race/ethnicity (AOR 0.53 [0.36, 0.78]) and Hispanic race/ethnicity (AOR 0.66 [0.48, 0.92]) were associated with lower odds of ≥ 1 year retention. Conclusions Over half of patients who presented to Office Based Opioid Treatment with buprenorphine were ultimately successfully retained for ≥ 1 year. However, significant disparities in one-year treatment retention were observed, including poorer retention for patients who were younger, black, Hispanic, unemployed, or with hepatitis C.

Objectives: To determine the risk of incident cartilage damage in unaffected subregions when one tibiofemoral compartment has a full-thickness vs. partial-thickness focal defects in knees with and without radiographic osteoarthritis. Methods: The Multicenter Osteoarthritis Study participants with semiquantitative MRI readings at baseline and 30-month were included. We estimated the risk of incident cartilage defects developing in tibiofemoral compartments with prevalent partial-thickness and full-thickness cartilage defects in a subregion within the compartment, using tibiofemoral compartments with no baseline cartilage defects as reference. Logistic regression with generalized estimating equations was used for all analyses with adjustments for confounders. Results: 374 compartments (359 knees) were included, of which 140 knees (39%) had radiographic osteoarthritis. Compared to compartments with no baseline cartilage defects, those with partial-thickness (aOR 1.62, 95%CI 1.06-2.47) and full-thickness cartilage defects (aOR 1.92, 95%CI 1.00-3.66) in a subregion had higher risk for incident cartilage defects in other subregions in the same compartment. Conclusions: Prevalent focal cartilage defects, regardless of defect depth, in a single subregion within a tibiofemoral joint compartment increase the risk for development of new cartilage damage in other subregions of the same tibiofemoral joint compartment for middle-aged to elderly persons with or at high risk of knee osteoarthritis. This article is protected by copyright. All rights reserved.

BACKGROUND The incorporation of genomic testing to identify targetable somatic alterations and predisposing germline mutations into the clinical setting is becoming increasingly more common. Despite its potential usefulness, to the authors' knowledge physician confidence with regard to understanding and applying genomic testing remains unclear, particularly within the realm of pediatric oncology. METHODS Before initiating an institutional feasibility study regarding the integration of clinical genomic testing, the authors surveyed pediatric oncologists regarding their confidence around understanding of genomic testing, perceived usefulness of test results, preferences around the disclosure of germline test results, and possible risks and benefits of testing. RESULTS Among survey respondents (52 of 88 contacted; response rate of 59%), only a minority were confident in interpreting, using, and discussing somatic (35%) or germline (27%) genomic test results. Providers who were confident in interpreting somatic results were significantly more likely to anticipate using the results to plan the treatment of patients with relapsed or refractory cancers (P = .009). Similarly, providers who reported confidence in interpreting germline results were significantly more likely to discuss and use these results as part of clinical care (P

Objective Many persons with knee pain have joint pain outside the knee, but despite the impact and high frequency of this pain, its distribution and causes have not been studied. We undertook this study to test the hypothesis of those studying gait abnormalities who have suggested that knee pain causes pain in adjacent joints but that pain adaptation strategies are highly individualized. Methods We studied persons ages 50–79 years with or at high risk of knee osteoarthritis who were recruited from 2 community-based cohorts, the Multicenter Osteoarthritis Study and the Osteoarthritis Initiative, and we followed them up for 5–7 years. We excluded those with knee pain at baseline and compared those who had developed knee pain at the first follow-up examination (the index visit) with those who had not. We examined pain on most days at joint regions outside the knee in examinations after the index visit. Logistic regression analyses examined the risk of joint-specific pain adjusted for age, sex, body mass index, and symptoms of depression, and we performed sensitivity analyses excluding those with widespread pain. Results In the combined cohorts, 693 persons had knee pain at the index visit and 2,793 did not. A total of 79.6% of those with bilateral knee pain and 63.8% of those with unilateral knee pain had pain during follow-up in a joint region outside the knee, compared with 49.9% of those without knee pain. There was an increased risk of pain at most extremity joint sites, without a predilection for specific sites. Results were unchanged when those with widespread pain were excluded. Conclusion Persons with chronic knee pain are at increased risk of pain in multiple joints in no specific pattern.

Objectives Among Russians living with HIV/AIDS who inject drugs, we examined the incidence of fatal and non-fatal overdoses following discharge from a narcology hospital and the associations with more advanced HIV infection. Design Prospective cohort study of data collected at baseline, 3 and 6 months from HIV-infected patients with a history of injection drug use who were not treated with anti-retroviral therapy. Participants were recruited between 2012–2014 from a narcology (addiction) hospital in St. Petersburg, Russia. Methods Fatal overdose was determined based on contact reports to study staff in the year after discharge. Non-fatal overdose was self-reported at the 3- and 6-month assessments. The main independent variable for HIV severity was CD4 cell count at the baseline interview ( 3 ≥200cells/mm 3 ). Secondary analyses assessed time since HIV diagnosis and treated with anti-retroviral treatment (ART) prior to enrolment as independent variables. We fit Cox proportional hazards models to assess whether HIV severity is associated with either fatal or non-fatal overdose. Results Among 349 narcology patients, 18 participants died from overdose within one year after discharge (8.7%, 95% CI 3.4–14.2 by Kaplan–Meier); an estimated 51% [95% CI 34–68%] reported at least one non-fatal overdose within 6 months of discharge. HIV severity, time since HIV diagnosis and ever ART were not significantly associated with either fatal or non-fatal overdose events. Conclusion Fatal and non-fatal overdose are common among Russians living with HIV/AIDS who inject drugs after narcology hospital discharge. Overdose prevention interventions are urgently warranted among Russian narcology patients with HIV infection.

Background Statin pretreatment has been associated with reduced infarct volume in nonlacunar strokes. The effect of statins on functional outcomes of strokes related to atrial fibrillation (AF) is unknown. We aimed to define the influence of prestroke statin use on functional outcome in AF. Methods We assembled a cohort of consecutive ischemic stroke patients from 2006 to 2010. All patients underwent CT or MRI and were adjudicated by site investigators. AF was confirmed by electrocardiogram in 100% of patients. Site neurologists blinded to the study hypothesis affirmed the type of stroke and assessed the severity of disability at the time of hospital discharge. The frequency of death at 30-days was calculated. Results Ischemic stroke ( n =1030) resulted in a severe neurological deficit or death (modified Rankin scale ≥4) at 30days in 711 patients (69%). Using multivariable logistic regression models adjusting for factors associated with statin treatment and factors associated with functional outcome, prestroke statin use was associated with a 32% reduction in frequency of severe stroke (odds ratio [OR], 0.68; 95% confidence interval [CI], 0.50–0.92; P =0.011). Other independent factors associated with severe stroke included older age, female sex, non-White race, diabetes mellitus, prior ischemic stroke, prior venous thromboembolism, and dementia. Conclusion Ischemic strokes in AF are associated with high mortality and morbidity. Statin use at time of stroke onset among patients with AF was associated in this study with less severe stroke and warrant validation.

The prevalence of psychoactive medications (PAMs) use in patients enrolled in Office Based Opioid Treatment (OBOT) and its association with engagement in this care is largely unknown.To describe the use of PAMs, including those medications with emerging evidence of misuse ("emerging PAMs" - gabapentin, clonidine and promethazine) among patients on buprenorphine, and its association with disengagement from OBOT.This is a retrospective cohort study of adults on buprenorphine from January 2002 to February 2014. The association between use of PAMs and 6-month disengagement from OBOT was examined using multivariable logistic regression models. A secondary analysis exploring time-to-disengagement was conducted using Cox regression models.At OBOT entry, 43% of patients (562/1308) were prescribed any PAM; including 17% (223/1308) on an emerging PAM. In separate adjusted analyses, neither the presence of any PAM (adjusted odds ratio [AOR] 1.07, 95% CI [0.78, 1.46]) nor an emerging PAM (AOR 1.28 [0.95, 1.74]) was significantly associated with 6-month disengagement. The results were similar for the Cox model (any PAM (adjusted hazard ratio [AHR] 1.16, 95% CI [1.00, 1.36]), emerging PAM (AHR 1.18 [0.98, 1.41])). Exploratory analyses suggested gabapentin (AHR 1.30 [1.05-1.62]) and clonidine (AHR 1.33 [1.01-1.73]) specifically, may be associated with an overall shorter time to disengagement.Psychoactive medication use is common among patients in buprenorphine treatment. No significant association was found between the presence of any psychoactive medications, including medications with emerging evidence of misuse, and 6-month disengagement from buprenorphine treatment.

Gulf War Illness (GWI) is a chronic multi-symptom disorder affecting the central nervous system (CNS), immune and gastrointestinal (GI) systems of Gulf War veterans (GWV). We assessed the relationships between GWI, GI symptoms, gut microbiome and inflammatory markers in GWV from the Boston Gulf War Illness Consortium (GWIC). Three groups of GWIC veterans were recruited in this pilot study, GWV without GWI and no gastrointestinal symptoms (controls), GWV with GWI and no gastrointestinal symptoms (GWI-GI), GWV with GWI who reported gastrointestinal symptoms (GW+GI). Here we report on a subset of the first thirteen stool samples analyzed. Results showed significantly different gut microbiome patterns among the three groups and within the GWI +/&minus, GI groups. Specifically, GW controls had a greater abundance of firmicutes and the GWI+GI group had a greater abundance of the phyla bacteroidetes, actinobacteria, euryarchaeota, and proteobacteria as well as higher abundances of the families Bacteroidaceae, Erysipelotrichaceae, and Bifidobacteriaceae. The GWI+GI group also showed greater plasma levels of the inflammatory cytokine TNF-RI and they endorsed significantly more chemical weapons exposure during the war and reported significantly greater chronic pain, fatigue and sleep difficulties than the other groups. Studies with larger samples sizes are needed to confirm these initial findings.

BackgroundIf Russia is to achieve the UNAIDS 90-90-90 HIV targets, better approaches to engage, effectively treat, and retain patients in care are needed. This paper describes the protocol of a randomized controlled trial (RCT) testing the effectiveness of LINC-II, a strength-based case management program for HIV-positive people who inject drugs (PWID) to increase rates of HIV viral suppression, ART initiation, and opioid abstinence.MethodsThis RCT will enroll and randomize 240 participants, recruited from a narcology (addiction care) hospital in St. Petersburg, Russia. Participants are randomized to the intervention or control arms. Those in the intervention arm receive: (1) strengths-based HIV case management supporting coordinated care; (2) rapid ART initiation; and (3) pharmacotherapy for opioid use disorder. We will evaluate the intervention’s effectiveness compared to standard of care on the following outcomes: (1) undetectable HIV viral load at 12 months (primary); (2) initiation of ART within 28 days of randomization; (3) change in CD4 count from baseline to 12 months; (4) retention in HIV care (i.e., ≥ 1 visit to medical care in 2 consecutive 6 month periods); (5) undetectable HIV viral load at 6 months; and (6) past 30-day opioid abstinence (at 6 and at 12 months).DiscussionThis RCT will assess the LINC-II intervention in an urban Russian setting. If effective, it will offer a new approach for increasing the uptake of both HIV and opioid use disorder treatment and coordination of these modalities in standard Eastern European clinical settings.Trial registrationThis study was registered with ClinicalTrials.gov through the National Institutes of Health, NCT03290391. Registered 19 September 2017,https://clinicaltrials.gov/ct2/show/NCT03290391

BACKGROUND Cancer predisposition syndromes (CPS) are caused by germline pathogenic variants that put an individual at increased risk of developing cancer throughout their lifetime. It is estimated that approximately 10-15% of children with cancer have an underlying CPS. Although research has investigated the clinical utility of genetic testing for children diagnosed with cancer, this study aimed to gain a deeper understanding of parental attitudes toward genetic testing in this population. PROCEDURE Attitudes toward genetic counseling and testing among parents of children diagnosed with cancer were solicited through questionnaires distributed to a pediatric cancer clinic and online support groups. Quantitative data were analyzed using descriptive statistics and chi-square tests for association. RESULTS The majority of participants had prior knowledge of genetic counseling (64.3%), yet most were not offered genetic counseling (59.5%). Fifty percent of parents reported interest in pursuing genetic counseling/testing and 31.0% reported uncertainty. Statistically significant associations were identified between interest in genetic counseling/testing and the child's age at diagnosis, child's sex, and participant annual income (P

Objective: To determine whether the Linking Infectious and Narcology Care strengths-based case management intervention was more effective than usual care for linking people who inject drugs (PWID) to HIV care and improving HIV outcomes. Design: Two-armed randomized controlled trial. Setting: Participants recruited from a narcology hospital in St. Petersburg, Russia. Participants: A total of 349 HIV-positive PWID not on antiretroviral therapy (ART). Intervention: Strengths-based case management over 6 months. Main outcome measures: Primary outcomes were linkage to HIV care and improved CD4+ cell count. We performed adjusted logistic and linear regression analyses controlling for past HIV care using the intention-to-treat approach. Results: Participants (N = 349) had the following baseline characteristics: 73% male, 12% any past ART use, and median values of 34.0 years of age and CD4+ cell count 311 cells/μl. Within 6 months of enrollment 51% of the intervention group and 31% of controls linked to HIV care (adjusted odds ratio 2.34; 95% confidence interval: 1.49–3.67; P

The contribution of pregnancy interval after gestational diabetes (GDM) to type 2 diabetes (T2DM) onset is a poorly understood but potentially modifiable factor for T2DM prevention. The purpose of this study was to assess the impact of GDM recurrence and/or delivery interval on follow-up care and T2DM onset in a sample of continuously insured women with a term livebirth within 3 years of a GDM-affected delivery. This is a secondary analysis of a cohort of 12,622 women with GDM, 2006–2012, drawn from a national administrative data system (OptumLabs Data Warehouse). We followed 1091 women with GDM who had a subsequent delivery within 3 years of their index delivery. GDM recurred in 49.3% of subsequent pregnancies regardless of the interval to the next conception. Recurrence tripled the odds of early T2DM onset within 3 years of the second delivery. Women with GDM recurrence had greater likelihood of glucose testing in that 3-year interval, but not transition to primary care for continued monitoring, as required by both American Congress of Obstetricians and Gynecologists (ACOG) and the American Diabetes Association (ADA) guidelines. In multivariable analysis, we found a trend toward increased likelihood of T2DM onset for short interpregnancy intervals (≤1 year vs. 3 year, 0.08). Pregnancy interval may play a previously unrecognized role in progression to T2DM. T2DM onset after GDM can be prevented or mitigated, but many women in even this insured sample did not receive recommended follow-up monitoring and preventive care, even after a GDM recurrence. The postpartum visit may be an ideal time to inform patients about T2DM prevention opportunities, and discuss potential benefits of optimal spacing of future pregnancies.

BACKGROUND Patients with cancer are increasingly offered genomic sequencing, including germline testing for cancer predisposition or other disorders. Such testing is unfamiliar to patients and families, and clear communication is needed to introduce genomic concepts and convey risk and benefit information. METHODS Parents of children with cancer were offered the opportunity to have their children's tumor and germline examined with clinical genomic sequencing. Families were introduced to the study with a 2-visit informed consent model. Baseline genetic knowledge and self-reported literacy/numeracy were collected before a study introduction visit, during which basic concepts related to genomic sequencing were discussed. Information was reinforced during a second visit, during which informed consent was obtained and a posttest was administered. RESULTS As reflected by the percentage of correct answers on the pretest and posttest assessments, this model increased genetic knowledge by 11.1% (from 77.8% to 88.9%; P

Objectives. To assess changes in perceived external stigma among people living with HIV (PLWH) experiencing homelessness or unstable housing diagnosed with mental health or substance use disorders following an intervention including care coordination and navigation assistance, building trusting relationships, addressing unmet needs, and reducing barriers to seeking and engaging in care. Methods. This study was part of a national multisite intervention project delivered at 6 geographically diverse sites throughout the United States from September 2013 through February 2017. Participant surveys were conducted at baseline, 6 months, and 12 months. We assessed perceived external stigma, defined as people’s beliefs about others’ attitudes toward them, related to HIV, homelessness, mental health disorders, and substance use disorders with modified stigma scales. Results. A total of 548 individuals participated. At baseline, more participants reported experiencing any perceived external HIV stigma (81%) than any stigma related to homelessness and mental health or substance use disorders (38.9%). Over time, those reporting any HIV stigma decreased significantly from baseline (81%) to 61.4% and 57.8% at 6 and 12 months, respectively. Conclusions. PLWH experiencing homelessness or unstable housing with mental health or substance use disorders are impacted by multilayered stigma. Interventions to engage them in care may help reduce stigma.

Importance Substance use disorders are a major source of morbidity and mortality in the United States. National data comparing the prevalence of substance use disorder diagnoses (SUDDs) among transgender and cisgender individuals are lacking in the United States. Objectives To investigate the prevalence of SUDDs among transgender and cisgender adults and to identify within-group and between-group differences by age, gender, and geographic location. Design, Setting, and Participants This cross-sectional study used the OptumLabs Data Warehouse to analyze deidentified claims from approximately 74 million adults aged 18 years or older enrolled in commercial or Medicare Advantage insurance plans in 2017. A total of 15 637 transgender adults were identified based on a previously developed algorithm using a combination ofInternational Classification of Diseases, Tenth Revision (ICD-10) transgender-related diagnosis and procedure codes and sex-discordant hormone prescriptions. A cohort of 46 911 cisgender adults was matched to the transgender cohort in a 3:1 ratio based on age and geographic location. Main Outcomes and Measures SUDDs, based onICD-10codes, were assessed overall and compared between transgender and cisgender cohorts and by geographic region (ie, Northeast, Midwest, South, and West); age groups (eg, 18-25, 26-30, 31-35 years), and gender (ie, transfeminine [TF; assigned male sex at birth, identify along feminine gender spectrum], transmasculine [TM; assigned female sex at birth, identify along masculine gender spectrum], male, and female). Results In this study of 15 637 transgender adults (4955 [31.7%] TM) and 46 911 cisgender adults (23 664 [50.4%] female), most (8627 transgender adults [55.2%]; 25 882 cisgender adults [55.2%]) were aged between 18 and 40 years, and 6482 transgender adults (41.5%) and 19 446 cisgender adults (41.5%) lived in the South. Comparing transgender to cisgender groups, significant differences were found in the prevalence of a nicotine (2594 [16.6%] vs 2551 [5.4%];P Conclusions and Relevance In this study, the prevalence of SUDDs was significantly elevated among transgender adults relative to their cisgender peers. These findings underscore the need for culturally tailored clinical interventions to treat substance use disorder in transgender populations.

Objective Appropriate tracheostomy and laryngectomy care requires that nurses maintain specific knowledge and a particular skillset, to ensure safe, competent care. Deficiencies in this nursing care remain a persistent problem. The objective of this study was to evaluate the effect of a nurse training program on knowledge and self-efficacy with tracheostomy and laryngectomy care. Study design Prospective, interventional survey design. Setting Academic, tertiary care hospital between September 2014 and April 2015. Subjects and methods 1450 nurses at an academic tertiary care hospital were surveyed on tracheostomy and laryngectomy care at two time points: before and after the implementation and completion of the nurse training program. The nurse training program included a hands-on training session and online tutorial on appropriate tracheostomy and laryngectomy care. 732 nurses completed the hands-on training and were asked to complete the online tutorial. A total of 338 surveys were collected. Survey data were collected through an online survey development platform. Analyses were performed using SAS software. Chi-square tests and t-tests were utilized with a significance level of 0.05. Results 165 pre-training surveys and 173 post-training surveys were completed. Statistical analysis of the post-training data demonstrated statistically significantly higher knowledge and self-efficacy scores of nurses who completed the training than nurses who did not. Conclusions Findings from this study reveal poor overall nursing knowledge and self-efficacy with this care and suggest that optimizing and standardizing nurse training is an effective strategy to improve nursing knowledge and self-efficacy with head and neck surgical airways.