Search

The Deployment and Travel Medicine Knowledge, Attitude, Practice and Outcomes Study investigates the various clinician and traveler contributions to medical outcomes within the U.S. Military Health System. Travelers’ diarrhea is among the most common travel-related illnesses, making travelers’ diarrhea self-treatment (TDST) important for traveler health. A cohort of 80,214 adult travelers receiving malaria chemoprophylaxis for less than 6 weeks of travel were identified within the U.S. Department of Defense Military Health System Data Repository. Associated prescriptions for TDST medications within 2 weeks of chemoprophylaxis prescriptions were identified. Prescription patterns were compared by service member versus beneficiary status and site of care, military facility versus civilian facility. At military facilities, medical provider demographics were analyzed by clinical specialty and categorized as travel medicine specialists versus nonspecialists. Overall, there was low prescribing of TDST, particularly among civilian providers and military nonspecialists, despite guidelines recommending self-treatment of moderate to severe travelers’ diarrhea. This practice gap was largest among service member travelers, but also existed for beneficiaries. Compared with nonspecialists, military travel medicine specialists were more likely to prescribe a combination of an antibiotic and antimotility agent to beneficiaries, more likely to provide any form of TDST to service members, and more likely to prescribe azithromycin than quinolones when using antibiotics. Our study suggests that enhancing provider knowledge and use of travelers’ diarrhea treatment recommendations combined with improved access to formal travel medicine services may be important to increase the quality of care.

This study sought to estimate the net benefits and return on investment (ROI, %) of the Coping and Promoting Strength (CAPS) program to families and insurers, respectively, using data from a multi-year follow up of 136 US families who had participated in a randomized efficacy trial of CAPS. CAPS is a brief parent-focused psychosocial intervention that was compared to information monitoring in the trial. Of the 136 original participants, 113 (83%) completed follow-up interviews 7.1 years, on average, after the CAPS study baseline (mean follow-up age: 15.8 years; range: 13.1 to 20.8 years). Parent-reported willingness-to-pay values and estimates of behavioral healthcare cost savings from delayed onset of anxiety were used to simulate the average net benefits of CAPS to families and insurance plans, respectively, assuming patients pay 20% coinsurance. Psychologists in private offices were expected to charge an average of approximately $195 per CAPS session or $1417 in total in 2020 dollars. The estimated family share of the total CAPS session cost was $283 per youth, while the insurer share was $1134 per youth. Given these costs, the CAPS intervention was estimated to result in average overall net benefits of $1033 per youth (95% CI: -$546 to $2611). Families gained $344 (95% CI: $232 to $455 per family) for an ROI of 121%. Insurance plans on average gained a net savings of $689 per youth (95% CI: -$778 to $2156 per youth) for an average ROI of 61%. In this multiyear follow-up of offspring of anxious parents, exposure to the CAPS pediatric anxiety prevention program was found to be more economically efficient than was waiting for an anxiety disorder to be diagnosed. ClinicalTrials.gov Identifier: NCT00847561.

Child psychiatry access programs (CPAPs) help increase access to mental health services. This study aimed to provide information on the types of pediatric primary care clinicians (PPCCs) who call Maryland's CPAP.Descriptive statistics and multinomial logistic regressions were conducted with data from 676 PPCCs who called Maryland's CPAP at least once between October 2012 and June 2019.On average, PPCCs contacted Maryland's CPAP 6.8 times. Providers who called seven or more times were more likely to have an allopathic or osteopathic medicine degree and to specialize in pediatrics. Providers calling from rural regions were less likely to call only for referrals.Most PPCCs contacted the CPAP for consultation or referrals but not both. PPCCs in rural areas were more likely to call for consultation, suggesting that they may be more likely to manage the care of patients with mental health conditions themselves, because of a lack of resources in their locations.

Maryland's Behavioral Health Integration in Pediatric Primary Care (BHIPP) is a child psychiatry access program offering child-adolescent psychiatry consultation, resource and referral networking, and direct-to-patient mental health intervention. This study investigated characteristics of patients for whom primary care providers sought BHIPP services.Data from 6,939 unique patient contacts between October 2012 and March 2020 were collected on service type, demographic characteristics, presenting concerns, clinical severity, clinicians' diagnostic impressions, current treatments, and BHIPP recommendations. Descriptive statistics and latent class analysis were used.Of the 6,939 patient contacts, 38.6% were for direct-to-patient mental health intervention, 27.3% for child-adolescent psychiatry consultation, and 34.2% for resource and referral networking. In total, 50.3% of patients were female, 58.7% were White, and 32.7% were already receiving mental health services. Latent class analysis identified four classes of presenting concerns: anxiety only (44.2%); behavior problems only (30.7%); mood and anxiety (17.1%); and attention, behavior, and learning problems (8.0%). Compared with patients in the anxiety-only class, those in the attention, behavior, and learning problems class were more likely to receive direct-to-patient mental health intervention (OR=3.59), and BHIPP clinicians were more likely to recommend in-office behavioral interventions for those in the mood and anxiety class (OR=1.62) and behavior problems-only class (OR=1.55).Patients supported through BHIPP varied in presenting concerns, condition severity and complexity, current receipt of services, and BHIPP utilization. Latent class analysis yielded more clinically useful information about the nature and complexity of patients' concerns than did consideration of individual presenting concerns.

BACKGROUND Medication non-adherence is a significant problem that impacts both the patient, as well as the health system. OBJECTIVE The objective of this study was to evaluate the impact of a novel smart phone application with patient response directed clinical intervention on medication adherence and blood glucose control in non-insulin dependent T2DM patients METHODS We enrolled 50 non-insulin dependent T2DM subjects with smart phones, from a rural health care center in Northern Nevada, for participation in this case-crossover study. Subjects underwent a standard of care arm and an intervention arm. Each study arm was 3 months in duration for a total of 6 months of follow up. Subjects had a hemoglobin A1c (HgbA1c) lab draw at enrollment, 3 months, and 6 months. Subjects had monthly Medication Adherence Scores (MAS) and Self-Efficacy for Appropriate Medication Use Scale (SEAMS) questionnaire completed at baseline and monthly for the duration of the study. Our primary outcomes of interest were the change in hemoglobin A1c between study arms. Secondary outcomes were the evaluation of the in proportion of subjects to achieve a clinically meaningful reduction in A1c and that required escalation of diabetes therapy between study arms. Exploratory outcomes included the analysis of the variation in MPR, MAS, and SEAMS during each study arm. RESULTS 30 subjects completed both study arms and were included in the analysis. Dropouts were higher in subjects enrolled in the standard of care arm first (24.0% vs 12.0%). Subjects had a median HbgA1c of 9.1%, had been living with T2DM for 6.0 years, median age of 66 years, and a median of 8.5 medications. HgbA1c reduction was higher during the intervention arm (0.69%, versus 0.35%, p=0.30). More subjects achieved a clinically meaningful reduction in HgbA1c while in the application intervention arm (70.0% versus 40.0%; OR 2.29; 95% CI .94 to 5.6; p=0.09). Subjects had higher odds of a therapy escalation while in the standard of care arm (60.0% versus 16.7%, OR 4.3; 95% CI 1.2 to 15.2; p= 0.021). The median MPR prior to enrollment was 109.0%, 112.0% during the study’s intervention arm, and 102.0% during the standard of care arm. The median Real-time Medication Adherence score was 93.2%. The change in MAS (1.0 versus -0.1) and SEAMS (1.9 versus -0.2) from baseline to month 3 was higher in the intervention arm compared to standard of care. CONCLUSIONS A novel smart phone application with patient response directed provider intervention holds promise in the ability to improve blood glucose control in complex non-insulin dependent T2DM and is worthy of additional study. This system of intervention maybe a viable solution to reduce medication burden by being a non-invasive method of reducing the need for diabetes medication escalation. CLINICALTRIAL 1655381

The objective of this systematic review and meta-analysis was to estimate the proportion of postinfectious reactive arthritis (ReA) after bacterial enteric infection from one of four selected pathogens. We collected studies from PubMed, Web of Science, and Embase, which assessed the proportion of postinfectious ReA published from January 1, 2000 to April 1, 2018. Papers were screened independently by title, abstract, and full text; papers in English, Spanish, and Portuguese utilizing a case-control (CC) or cohort study design, with a laboratory confirmed or probable acute bacterial enteric infection and subsequent ReA, were included. The proportion of ReA cases was pooled between and across pathogens. Factors that can induce study heterogeneity were explored using univariate meta-regression, including region, sample size, study design, and ReA case ascertainment. Twenty-four articles were included in the final review. The estimated percentage of cases across studies describing

Background Persistent motor or vocal tic disorder (PMVT) has been hypothesized to be a forme fruste of Tourette syndrome (TS). Although the primary diagnostic criterion for PMVT (presence of motor or vocal tics, but not both) is clear, less is known about its clinical presentation. Objective The goals of this study were to compare the prevalence and number of comorbid psychiatric disorders, tic severity, age at tic onset, and family history for TS and PMVT. Methods We analyzed data from two independent cohorts using generalized linear equations and confirmed our findings using meta-analyses, incorporating data from previously published literature. Results Rates of obsessive-compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD) were lower in PMVT than in TS in all analyses. Other psychiatric comorbidities occurred with similar frequencies in PMVT and TS in both cohorts, although meta-analyses suggested lower rates of most psychiatric disorders in PMVT compared with TS. ADHD and OCD increased the odds of comorbid mood, anxiety, substance use, and disruptive behaviors, and accounted for observed differences between PMVT and TS. Age of tic onset was approximately 2 years later, and tic severity was lower in PMVT than in TS. First-degree relatives had elevated rates of TS, PMVT, OCD, and ADHD compared with population prevalences, with rates of TS equal to or greater than PMVT rates. Conclusions Our findings support the hypothesis that PMVT and TS occur along a clinical spectrum in which TS is a more severe and PMVT a less severe manifestation of a continuous neurodevelopmental tic spectrum disorder. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

In this study, we aimed to examine the association between gastrointestinal (GI) symptom presence during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the prevalence of GI symptoms and the development of post-infectious irritable bowel syndrome (PI-IBS). We used data from a prospective cohort and logistic regression to examine the association between GI symptom status during confirmed SARS-CoV-2 infection and prevalence of persistent GI symptoms at ≥45 days. We also report the incidence of PI-IBS following SARS-CoV-2 infection. Of the 1475 participants in this study, 33.8% (n = 499) had GI symptoms during acute infection. Cases with acute GI symptoms had an odds of persisting GI symptoms 4 times higher than cases without acute GI symptoms (odds ratio (OR) 4.29, 95% confidence interval (CI) 2.45–7.53); symptoms lasted on average 8 months following infection. Of those with persisting GI symptoms, 67% sought care for their symptoms and incident PI-IBS occurred in 3.0% (n = 15) of participants. Those with acute GI symptoms after SARS-CoV-2 infection are likely to have similar persistent symptoms 45 days and greater. These data indicate that attention to a potential increase in related healthcare needs is warranted.

Obsessive–compulsive disorder (OCD) affects 1–2% of the population, and, as with other complex neuropsychiatric disorders, it is thought that rare variation contributes to its genetic risk. In this study, we performed exome sequencing in the largest OCD cohort to date (1,313 total cases, consisting of 587 trios, 41 quartets and 644 singletons of affected individuals) and describe contributions to disease risk from rare damaging coding variants. In case–control analyses (n = 1,263/11,580), the most significant single-gene result was observed in SLITRK5 (odds ratio (OR) = 8.8, 95% confidence interval 3.4–22.5, P = 2.3 × 10−6). Across the exome, there was an excess of loss of function (LoF) variation specifically within genes that are LoF-intolerant (OR = 1.33, P = 0.01). In an analysis of trios, we observed an excess of de novo missense predicted damaging variants relative to controls (OR = 1.22, P = 0.02), alongside an excess of de novo LoF mutations in LoF-intolerant genes (OR = 2.55, P = 7.33 × 10−3). These data support a contribution of rare coding variants to OCD genetic risk. An analysis of the largest exome sequencing dataset of people with obsessive–compulsive disorder to date (n = 1,313 affected individuals), where both case–control and de novo variant studies support a contribution of rare damaging coding variants to risk.

Background: Youth treated with antipsychotic medications are high risk for weight gain, increased lipids/glucose, and development of metabolic syndrome. Little is known about the dietary intake/nutritional adequacy in this vulnerable population, and effect on weight gain. This secondary data analysis describes the baseline intake and changes in diet after receiving healthy lifestyle education/counseling over 6 months, in a sample of youth with antipsychotic-induced weight gain. Methods: The U.S. Department of Agriculture (USDA) Automated Multiple-Pass Method 24-hour dietary recall was administered to 117 youth at baseline, 3 months, and 6 months. Parent/child received personalized healthy lifestyle education sessions over 6 months. Baseline intake was compared with the USDA Recommended Daily Allowance using independent samples t-tests. Individual dietary covariates were examined for change over 6 months using longitudinal linear mixed modeling. Influence of each on body mass index (BMI) z-score change was tested in a pooled group analysis and then compared by treatment group. Results: Pooled analysis revealed baseline consumption high in carbohydrates, fat, protein, sugar, and refined grains, while low in fruit/vegetables, whole grains, fiber, and water. Change over 6 months demonstrated a statistically significant decrease in daily calories (p = 0.002), carbohydrates (p = 0.003), fat (p = 0.012), protein (p = 0.025), sugar (p = 0.008), refined grains (p = 0.008), total dairy (p = 0.049), and cheese (p = 0.027). Small increases in fruits/vegetables were not statistically significant, although the Healthy Eating Index subscores for total vegetables (p = 0.013) and dark green/orange vegetables (p = 0.034) were. No dietary covariates were predictors of change in BMI z-score. Nondietary predictors were parent weight/BMI and treatment group, with the metformin and switch groups experiencing significant decreases in BMI z-score. Conclusions: Further pediatric studies are necessary to assess the effects of antipsychotic medications on dietary intake, and test efficacy of healthy lifestyle interventions on change in nutrition. The relationship of nutrition to cardiometabolic health in this population must be further investigated. Clinical Trial Registration number: NCT 02877823.

To identify a panel of serum biomarkers that could specifically identify imminent cases of rheumatoid arthritis (RA) before diagnosis.Serum samples were collected at 4 time points from active component US military personnel, including 157 anti-citrullinated protein antibody (ACPA)-seropositive and 50 ACPA-seronegative RA subjects, 100 reactive arthritis (ReA) subjects, and 76 healthy controls. The cohorts were split into 2 phases, with samples tested on independent proteomic platforms for each phase. Classification models of RA diagnosis based on samples obtained within 6 months prior to diagnosis were developed both in univariate analyses and by multivariate random forest modeling of training sample sets and testing sample sets from each phase.Increases in serum analytes, including C-reactive protein levels, serum amyloid A, and soluble programmed cell death 1 (PD-1), were observed in seropositive RA subjects at the time point closest to diagnosis, up to several years before diagnosis. Only a small fraction of RA subjects had levels above the 95th percentile of healthy control levels until the time period within 6 months of diagnosis. For classification of RA diagnosis using samples obtained within 6 months prior to diagnosis, soluble PD-1 provided superior specificity compared to ReA cases (89%), with a sensitivity of 48% for RA classification. An 8-analyte model provided superior sensitivity (69%), with comparable specificity relative to ReA (82%).Our findings demonstrate that imminent RA diagnosis could be classified with high specificity, relative to healthy controls and ReA cases, using a panel of cytokines measured in serum samples collected within 6 months before actual diagnosis.

U.S. military personnel must be ready to deploy to locations worldwide, including environments with heightened risk of infectious disease. Diarrheal illnesses continue to be among the most significant infectious disease threats to operational capability. To better prevent, detect, and respond to these threats and improve synchronization across the Department of Defense (DoD) overseas laboratory network, a multisite Global Travelers' Diarrhea protocol was implemented with standardized case definitions and harmonized laboratory methods to identify enteric pathogens. Harmonized laboratory procedures for detection of Norovirus (NoV), enterotoxigenic Escherichia coli (ETEC), enteroaggregative E. coli, Shiga toxin-producing E. coli, enteropathogenic E. coli, Salmonella enterica, Shigella/enteroinvasive E. coli, and Campylobacter jejuni have been implemented at six DoD laboratories with surveillance sites in Egypt, Honduras, Peru, Nepal, Thailand, and Kenya. Samples from individuals traveling from wealthy to poorer countries were collected between June 2012 and May 2018, and of samples with all variables of interest available (n = 410), most participants enrolled were students (46%), tourists (26%), U.S. military personnel (13%), or other unspecified travelers (11%). One or more pathogens were detected in 59% of samples tested. Of samples tested, the most commonly detected pathogens were NoV (24%), ETEC (16%), and C. jejuni (14%), suggesting that NoV plays a larger role in travelers' diarrhea than has previously been described. Harmonized data collection and methods will ensure identification and characterization of enteric pathogens are consistent across the DoD laboratory network, ultimately resulting in more comparable data for global assessments, preventive measures, and treatment recommendations.

This study examined the effects of a family-based intervention Coping and Promoting Strength (CAPS) relative to a control condition, information-monitoring (IM), to prevent the onset of anxiety disorders in offspring of anxious parents six years after their initial assessment. One hundred thirty six families participated in the original randomized trial; 113 (83%) completed the one time follow-up assessment. Presence of anxiety disorders and severity of symptoms in offspring were assessed by masked evaluators using the Anxiety Disorders Interview Schedule; parents and offspring also completed questionnaires assessing offspring anxiety. Using the intention to treat sample from the original trial, Cox regression models showed significant intervention main effects in the rate of onset of anxiety disorders from baseline to follow-up (anxiety disorder: hazard ratio (HR) = 2.55, 95% CI: 1.54, 4.21) but growth curves suggest effects occurred within the first year after program completion. No group differences were found in the cumulative incidence of anxiety disorders at the six-year follow-up. Additional intervention appears needed to maintain the initial positive effects long-term to reduce the risk for downstream disability.Clinical Trials Registration: NCT00847561.

Purpose of review With its impact on quality of life and increasing awareness, postinfectious irritable bowel syndrome (PI-IBS) is now gaining attention as one of the major health problems commonly encountered in gastrointestinal practice. Literature investigating the various pathogenic mechanisms involved is rapidly emerging. The objective of the current review is to provide an update on recent evidence published in the past 2 years describing advances in our understanding of the epidemiology, pathogenesis, diagnosis, and treatment of PI-IBS. Recent findings Significant proportion of research in the recent past was preclinical in nature. Epidemiological studies continue to highlight the risk of IBS after infection, with recent studies documenting postprotozoal effects. Advances in pathogenic mechanisms included clinical studies, which documented micro-RNA down-regulation and Peroxiredoxin-1 up-regulation in colonic mucosa of PI-IBS patients. Protease-activated receptor-2 (PAR-2) activation in PI-IBS mice models resulted in increase in epithelial permeability, mucosal inflammation, visceral hypersensitivity. Moxibustion and rifamycin reduced intestinal inflammation by inhibiting cytokine and chemokine release via different mechanisms. Miltefosine reduced mast cell degranulation and TRPV1 activation, thereby reducing visceral hypersensitivity. Summary At present, generalization of limited diagnostic and therapeutic strategies across a heterogeneous prevalent patient population impedes the ability to provide effective personalized care in PI-IBS. Further development in pathogenesis discovery, diagnostic tool development are needed in order to design well tolerated and effective therapies that guide treatments based on distinct pathways of disease.

Background & Aims Biomarkers are needed to identify patients at risk for development of inflammatory bowel diseases. We aimed to identify serum biomarkers of Crohn's disease and ulcerative colitis that can be detected and quantified before diagnosis. Methods We obtained serum samples from patients archived before a diagnosis of Crohn's disease (n = 200) or ulcerative colitis (n = 199), as well as from 200 healthy individuals (controls), collected from 1998 through 2013 as part of the US Defense Medical Surveillance System. We measured levels of antibodies against microbes (anti–Saccharomyces cerevisiae IgA or IgG, anti–Escherichia coli outer membrane porin C, anti-CBir1, anti-flagellin 2, anti-flagellin X, and perinuclear anti-neutrophil cytoplasmic antibodies) and 1129 proteins in each sample. We then used functional principal component analysis to derive the time-varying trajectory for each marker, which then was used in a multivariate model to predict disease status. Predictive performances at different prediagnosis timepoints were evaluated using area under the receiver operating characteristic curves (AUROCs). Biological pathways that were up-regulated in serum from patients with Crohn's disease were identified based on changes in protein abundance at different time periods preceding diagnosis. Results We identified a panel of 51 protein biomarkers that were predictive of Crohn's disease within 5 years with an AUROC of 0.76 and a diagnosis within 1 year with an AUROC of 0.87. Based on the proteins included in the panel, imminent development of CD was associated with changes in the complement cascade, lysosomes, innate immune response, and glycosaminoglycan metabolism. Serum antibodies and proteins identified patients who received a diagnosis of ulcerative colitis within 5 years with an AUROC of only 0.56 and within 1 year with an AUROC of 0.72. Conclusions We identified a panel of serum antibodies and proteins that were predictive of patients who will receive a diagnosis of Crohn's disease within 5 years with high accuracy. By contrast we did not identify biomarkers associated with future diagnosis of ulcerative colitis.

BACKGROUND: To strengthen the burden estimates for chronic sequelae of foodborne illness, we conducted a scoping review of the current literature for common foodborne pathogens and their associated sequelae. We aim to describe the current literature and gaps in knowledge of chronic sequelae associated with common foodborne illnesses. METHODS: A comprehensive search was conducted in PubMed, EMBASE, and Web of Science for peer-reviewed articles published January 1, 2000 to April 1, 2018. Articles available in English, of any epidemiological study design, for 10 common foodborne pathogens (Campylobacter, Salmonella, Escherichia coli, Listeria, Shigella, Cryptosporidium, Cyclospora, Giardia, Yersinia, and norovirus) and their associated gastrointestinal (GI)- and joint-related sequelae were included. RESULTS: Of the 6348 titles screened for inclusion, 380 articles underwent full-text review; of those 380, 129 were included for data extraction. Of the bacterial pathogens included in the search terms, the most commonly reported were Salmonella (n = 104) and Campylobacter (n = 99); E. coli (n = 55), Shigella (n = 49), Yersinia (n = 49), and Listeria (n = 15) all had fewer results. Norovirus was the only virus included in our search, with 28 article that reported mostly GI-related sequelae and reactive arthritis (ReA) reported once. For parasitic diseases, Giardia (n = 26) and Cryptosporidium (n = 18) had the most articles, and no results were found for Cyclospora. The most commonly reported GI outcomes were irritable bowel syndrome (IBS; n = 119) and inflammatory bowel disease (n = 29), and ReA (n = 122) or “joint pain” (n = 19) for joint-related sequelae. Salmonella and Campylobacter were most often associated with a variety of outcomes, with ReA (n = 34 and n = 27) and IBS (n = 17 and n = 20) reported most often. CONCLUSIONS: This scoping review shows there are still a relatively small number of studies being conducted to understand specific pathogen/outcome relationships. It also shows where important gaps in the impact of chronic sequelae from common foodborne illnesses still exist and where more focused research would best be implemented.

Vaccine implementation planning in low- and middle-income countries (LMIC) often focuses on children without considering special adult populations. We adapted an economic model developed by the United States Department of Defense (DoD) to evaluate the cost-effectiveness of vaccine acquisition strategies for Campylobacter-, ETEC-, Shigella-, and norovirus-associated gastroenteritis. We compared implementation costs with current medical management in the Peruvian armed forces, a special population of low- and middle-income (LMIC) adults with a high incidence of infectious gastroenteritis. Pathogen-specific vaccine implementation resulted in calculated cost-effectiveness ratio (CER) per duty day lost averted (CER(DDL)) of $13,741; $1,272; $301; and $803, and a CER per diarrhea day averted of $2,130; $215; $51; and $199 for Campylobacter, ETEC, Shigella, and norovirus, respectively. These estimates compare favorably to CER(DDL) estimates from high-income military population and suggest that implementing vaccines gastroenteritis may be cost-effective in the Peruvian military population.

Background Increasing evidence suggests a link between posttraumatic stress disorder (PTSD) and physical health. Stress disorders may lead to impairment of the immune system and subsequent autoimmune disease. This study investigated the association between PTSD and risk of selected autoimmune diseases (i.e. rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel diseases, and multiple sclerosis) among US active duty service members. Methods Using data from the Millennium Cohort Study, incident autoimmune cases between study initiation and September 2015 were identified from medical encounter records in the Military Health System Data Repository (MDR). Participants were classified as having a history of PTSD if they self-reported receiving a health care provider’s diagnosis of PTSD or if they screened positive using the PTSD Checklist−Civilian Version. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox regression models adjusted for demographics and history of another mental health condition. Results Among 120,572 participants followed for a mean of 5.2 years, risk of any of the selected autoimmune diseases was 58% higher for those with a history of PTSD (HR = 1.58, 95% CI: 1.25, 2.01) compared with no history of PTSD. Further adjustment for BMI, smoking status, and alcohol use had little impact on the effect estimates, and results were not appreciably different according to combat experience and history of physical or sexual trauma. Conclusions Active duty military personnel with PTSD may have an elevated risk of a range of autoimmune diseases, regardless of combat experience or prior trauma. Future research is needed to understand potential mechanisms which may inform future mitigative strategies in reducing extra-neuropsychiatric health problems among those with PTSD.

Investment in vaccine product development should be guided by up-to-date and transparent global burden of disease estimates, which are also fundamental to policy recommendation and vaccine introduction decisions. For low- and middle-income countries (LMICs), vaccine prioritization is primarily driven by the number of deaths caused by different pathogens. Enteric diseases are known to be a major cause of death in LMICs. The two main modelling groups providing mortality estimates for enteric diseases are the Institute for Health Metrics and Evaluation (IHME) at the University of Washington, Seattle and the Maternal Child Epidemiology Estimation (MCEE) group, led by Johns Hopkins Bloomberg School of Public Health. Whilst previous global diarrhoea mortality estimates for under five-year-olds from these two groups were closely aligned, more recent estimates for 2016 have diverged, particularly with respect to numbers of deaths attributable to different enteric pathogens. This has impacted prioritization and investment decisions for vaccines in the development pipeline. The mission of the Product Development for Vaccines Advisory Committee (PDVAC) at the World Health Organisation (WHO) is to accelerate product development of vaccines and technologies that are urgently needed and ensure they are appropriately targeted for use in LMICs. At their 2018 meeting, PDVAC recommended the formation of an independent working group of subject matter experts to explore the reasons for the difference between the IHME and MCEE estimates, and to assess the respective strengths and limitations of the estimation approaches adopted, including a review of the data on which the estimates are based. Here, we report on the proceedings and recommendations from a consultation with the working group of experts, the IHME and MCEE modelling groups, and other key stakeholders. We briefly review the methodological approaches of both groups and provide a series of proposals for investigating the drivers for the differences in enteric disease burden estimates.

Objectives: proving causality between an exposure and outcome can be difficult in humans. Here, we utilize the Bradford Hill (BH) criteria to summarize the causal relationship between Campylobacter infection and the development of Irritable Bowel Syndrome (IBS). Methods: we utilized the BH criteria to assess the strength, consistency, specificity, temporality, biological gradient, plausibility, coherence, experiment, and analogy of the current evidence linking Campylobacter to IBS. Through a consensus amongst all authors, the confidence of each criterion was graded as high, moderate, low, or very low. Results: a total of four criteria (strength, temporality, plausibility, and analogy) were graded as high; four criteria (consistency, biological gradient, coherence, and experiment) were graded as moderate; and one criterion (specificity) was graded as low. Large-scale epidemiological studies report a risk ratio of 2.7–5.6 for developing IBS after campylobacter. In rodent models, Campylobacter jejuni 81–176 can cause loose stool months after the infection is cleared and share common pathophysiology as IBS patients such as elevated intestinal TLR-4 and IL-8, antibodies to CdtB and vinculin, increased intraepithelial lymphocytes, and small intestinal bacterial overgrowth. Conclusions: Campylobacter infection appear to cause IBS in a subset of patients. This may hold implication in risk factor identification, public health policy, and possibly treatment.

Background Diarrhoeal infections are one of the leading causes of child’s mortality and morbidity. Vaccines against Shigella, enterotoxigenic E. coli (ETEC), norovirus and invasive non-typhoidal Salmonella are in clinical development, however, their full value in terms of short and long-term health and socio-economic burden needs to be evaluated and communicated, to rationalise investment in vaccine development, and deployment. While estimates of mortality of enteric infections exist, the long-term morbidity estimates are scarce and have not been systematically collected. Methods The World Health Organization (WHO) has convened a Burden of Enteric Diseases Morbidity Working Group (BoED MWG) who identified key workstreams needed to characterise the morbidity burden of enteric infections. The group also identified four criteria for the prioritisation of pathogens of which impact on long-term morbidity needs to be assessed. Results The BoED MWG suggested to identify and analyse the individual level data from historical datasets to estimate the impact of enteric infections and confounders on long-term morbidity, including growth faltering and cognitive impairment in children (workstream 1); to conduct a systematic review of evidence on the association of aetiology specific diarrhoea with short- and long- term impact on growth, including stunting, and possibly cognitive impairment in children, while accounting for potential confounders (workstream 2); and to conduct a systematic review of evidence on the association of aetiology specific diarrhoea with short- and long- term impact on health outcomes in adults. The experts prioritised four pathogens for this work: Campylobacter jejuni, ETEC (LT or ST), norovirus (G1 or G2), and Shigella (dysenteriae, flexneri, sonnei). Conclusions The proposed work will contribute to improving the understanding of the impact of enteric pathogens on long-term morbidity. The timing of this work is critical as all four pathogens have vaccine candidates in the clinical pipeline and decisions about investments in development, manufacturing or vaccine procurement and use are expected to be made soon.

Obsessive-compulsive disorder (OCD) is a heritable disorder, but no definitive, replicated OCD susceptibility loci have yet been identified by any genome-wide association study (GWAS). Here, we report results from a GWAS in the largest OCD case-control sample (N = 14,140 OCD cases and N = 562,117 controls) to date. We explored the genetic architecture of OCD, including its genetic relationships to other psychiatric and non-psychiatric phenotypes. In the GWAS analysis, we identified one SNP associated with OCD at a genome-wide significant level. Subsequent gene-based analyses identified additional two genes as potentially implicated in OCD pathogenesis. All SNPs combined explained 16% of the heritability of OCD. We show sub-stantial positive genetic correlations between OCD and a range of psychiatric disorders, including anxiety disorders, anorexia nervosa, and major depression. We thus for the first time provide evidence of a genome-wide locus implicated in OCD and strengthen previous literature suggesting a polygenic nature of this disorder.

Advancing new O-antigen-based Shigella vaccines is critically dependent on development of an international standard serum and harmonized ELISA, demonstration of field efficacy in young children in low- and middle-income countries, and early engagement with regulators and policy makers.

INTRODUCTION: Small intestine bacterial overgrowth (SIBO) is common in children from low-income countries and has been cross-sectionally associated with growth stunting. We sought to determine whether SIBO was associated with poor growth and neurodevelopmental in a longitudinal analysis. METHODS: We measured SIBO by glucose hydrogen breath test (GHBT) at 18, 52, 78, and 104 weeks of life in a prospective longitudinal birth cohort of Bangladeshi children. Sociodemographic information and measures of enteric inflammation were analyzed as covariates. Diarrheal samples were tested for enteropathogens using polymerase chain reaction. Regression models were created using standardized mean GHBT area under the H2 curve (AUC) to determine associations with linear growth and cognitive, language, and motor scores on the Bayley-III Scales of Infant and Toddler Development at 2 years. We also investigated associations between GHBT AUC and enteropathogen exposure. RESULTS: A 1-ppm increase in standardized mean GHBT AUC was associated with a 0.01-SD decrease in length-for-age Z score (P = 0.03) and a 0.11-point decrease in Bayley language score (P = 0.05) at 2 years of age in adjusted analysis. Enteroaggregative Escherichia coli, Enteropathogenic Escherichia coli, Giardia, and Enterocytozoon bieneusi were associated with increased GHBT AUC, whereas Clostridium difficile, norovirus GI, sapovirus, rotavirus, and Cryptosporidium were associated with decreased GHBT AUC. None were consistent across all 4 time points. DISCUSSION: SIBO in the first 2 years of life is associated with growth stunting and decreased language ability in Bangladeshi infants and may represent a modifiable risk factor in poor growth and neurodevelopment in low-income countries.