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Summary An important goal of clinical genomics is to be able to estimate the risk of adverse disease outcomes. Between 5% and 10% of individuals with ulcerative colitis (UC) require colectomy within 5 years of diagnosis, but polygenic risk scores (PRSs) utilizing findings from genome-wide association studies (GWASs) are unable to provide meaningful prediction of this adverse status. By contrast, in Crohn disease, gene expression profiling of GWAS-significant genes does provide some stratification of risk of progression to complicated disease in the form of a transcriptional risk score (TRS). Here, we demonstrate that a measured TRS based on bulk rectal gene expression in the PROTECT inception cohort study has a positive predictive value approaching 50% for colectomy. Single-cell profiling demonstrates that the genes are active in multiple diverse cell types from both the epithelial and immune compartments. Expression quantitative trait locus (QTL) analysis identifies genes with differential effects at baseline and week 52 follow-up, but for the most part, differential expression associated with colectomy risk is independent of local genetic regulation. Nevertheless, a predicted polygenic transcriptional risk score (PPTRS) derived by summation of transcriptome-wide association study (TWAS) effects identifies UC-affected individuals at 5-fold elevated risk of colectomy with data from the UK Biobank population cohort studies, independently replicated in an NIDDK-IBDGC dataset. Prediction of gene expression from relatively small transcriptome datasets can thus be used in conjunction with TWASs for stratification of risk of disease complications.

SUMMARYAn important goal of clinical genomics is to be able to estimate the risk of adverse disease outcomes. Between 5% and 10% of ulcerative colitis (UC) patients require colectomy within five years of diagnosis, but polygenic risk scores (PRS) utilizing findings from GWAS are unable to provide meaningful prediction of this adverse status. By contrast, in Crohn’s disease, gene expression profiling of GWAS-significant genes does provide some stratification of risk of progression to complicated disease in the form of a Transcriptional Risk Score (TRS). Here we demonstrate that both measured (TRS) and polygenic predicted gene expression (PPTRS) identify UC patients at 5-fold elevated risk of colectomy with data from the PROTECT clinical trial and UK Biobank population cohort studies, independently replicated in an NIDDK-IBDGC dataset. Prediction of gene expression from relatively small transcriptome datasets can thus be used in conjunction with transcriptome-wide association studies to stratify risk of disease complications.

The Precision Interventions for Severe and/or Exacerbation-prone Asthma (PrecISE) study is an adaptive platform trial designed to investigate novel interventions to severe asthma. The study is conducted under a master protocol and utilizes a crossover design with each participant receiving up to five interventions and at least one placebo. Treatment assignments are based on the patients’ biomarker profiles and precision health methods are incorporated into the interim and final analyses. We describe key elements of the PrecISE study including the multistage adaptive enrichment strategy, early stopping of an intervention for futility, power calculations, and the primary analysis strategy.

Molecular mechanisms driving disease course and response to therapy in ulcerative colitis (UC) are not well understood. Here, we use RNAseq to define pre-treatment rectal gene expression, and fecal microbiota profiles, in 206 pediatric UC patients receiving standardised therapy. We validate our key findings in adult and paediatric UC cohorts of 408 participants. We observe a marked suppression of mitochondrial genes and function across cohorts in active UC, and that increasing disease severity is notable for enrichment of adenoma/adenocarcinoma and innate immune genes. A subset of severity genes improves prediction of corticosteroid-induced remission in the discovery cohort; this gene signature is also associated with response to anti-TNFα and anti-α4β7 integrin in adults. The severity and therapeutic response gene signatures were in turn associated with shifts in microbes previously implicated in mucosal homeostasis. Our data provide insights into UC pathogenesis, and may prioritise future therapies for nonresponders to current approaches., The severity of ulcerative colitis, and response to treatment, is highly variable. Here, the authors examine rectal gene expression signatures and faecal microbiomes of children and adults with the disease and provide new insights in to pathogenesis.

Objectives To examine the association between adverse childhood experiences (ACEs) and pregnancy outcomes; to explore mediators of this association including psychiatric illness and health habits. Methods Exposure to ACEs was determined by the Early Trauma Inventory Self Report Short Form; psychiatric diagnoses were generated by the Composite International Diagnostic Interview administered in a cohort of 2303 pregnant women. Linear regression and structural equation modeling bootstrapping approaches tested for multiple mediators. Results Each additional ACE decreased birth weight by 16.33 g and decreased gestational age by 0.063. Smoking was the strongest mediator of the effect on gestational age. Conclusions ACEs have an enduring effect on maternal reproductive health, as manifested by mothers’ delivery of offspring that were of reduced birth weight and shorter gestational age.

We examined the association between exposure to the U.S. and symptoms of poor mental health among adult Hispanic/Latinos (N = 15,004) overall and by Hispanic/Latino background. Using data from the Hispanic Community Health Study of Latinos (HCHS/SOL), we estimated logistic regressions to model the risk of moderate to severe symptoms of psychological distress, depression, and anxiety as a function of years in the U.S. and six key psychosocial risk and protective factors. In unadjusted models, increased time in the U.S. was associated with higher risk of poor mental health. After adjustment for just three key factors--perceived discrimination, perceived U.S. social standing, and the size of close social networks--differences in the odds of poor mental health by years in the U.S became insignificant for Hispanics/Latinos overall. However, analyses by Hispanic/Latino background revealed different patterns of association with exposure to the U.S. that could not be fully explained.

We aimed to determine which children are prone to non-Escherichia coli urinary tract infection (UTIs). We included 769 children with UTI. We found that circumcised males, Hispanic children, children without fever and children with grades 3 and 4 vesicoureteral reflux were more likely to have a UTI caused by organisms other than E. coli. This information may guide clinicians in their choice of antimicrobial therapy.

BackgroundPrevious retrospective studies of paediatric ulcerative colitis have had limited ability to describe disease progression and identify predictors of treatment response. In this study, we aimed to identify characteristics associated with outcomes following standardised therapy after initial diagnosis.MethodsThe PROTECT multicentre inception cohort study was based at 29 centres in the USA and Canada and included paediatric patients aged 4-17 years who were newly diagnosed with ulcerative colitis. Guided by the Pediatric Ulcerative Colitis Activity Index (PUCAI), patients received initial standardised treatment with mesalazine (PUCAI 10-30) oral corticosteroids (PUCAI 35-60), or intravenous corticosteroids (PUCAI ≥65). The key outcomes for this analysis were week 12 corticosteroid-free remission, defined as PUCAI less than 10 and taking only mesalazine, and treatment escalation during the 12 study weeks to anti-tumour necrosis factor α (TNFα) agents, immunomodulators, or colectomy among those initially treated with intravenous corticosteroids. We identified independent predictors of outcome through multivariable logistic regression using a per-protocol approach. This study is registered with ClinicalTrials.gov, number NCT01536535.FindingsPatients were recruited between July 10, 2012, and April 21, 2015. 428 children initiated mesalazine (n=136), oral corticosteroids (n=144), or intravenous corticosteroids (n=148). Initial mean PUCAI was 31·1 (SD 13·3) in children initiating with mesalazine, 50·4 (13·8) in those initiating oral corticosteroids, and 66·9 (13·7) in those initiating intravenous corticosteroids (p

Objective The purpose of this report was to examine the course of smoking among pregnant women with concurrent substance use, and to assess the impact of depression on smoking. Methods Data were gathered as part of a randomized controlled trial assessing the efficacy of substance abuse treatment in pregnant women. Women (n = 176) were recruited before 28 completed weeks of pregnancy, and followed until 3 months postpartum. Depression was assessed using the Inventory of Depressive Symptomatology and the MINI Neuropsychiatric Interview. Our outcome was the average number of cigarettes smoked per day. Linear mixed effects regression was used to measure differential changes in smoking. Results 66% of women smoked in the three months before pregnancy, 42% of pre-pregnancy smokers achieved abstinence before delivery and 60% of the baseline cohort smoked postpartum. Smoking did not differ significantly between depressed and non-depressed groups. After delivery both groups increased smoking at similar rates. Conclusion Smoking was common among our cohort of pregnant women with a history of substance use. Women were able to discontinue or decrease smoking during pregnancy, but were likely to resume or increase smoking postpartum. Having clinically significant depressive symptoms or a diagnosis of depression did not have an obvious effect on smoking behaviors.

Serotonin reuptake inhibitors and calcium supplements ameliorate symptoms of premenstrual syndrome. A comparison of these agents to placebo may guide treatment selection. The goal of this pilot study was to compare fluoxetine and calcium to placebo.We enrolled 39 women with at least 3 moderate to severe premenstrual symptoms and functional impairment. The trial compared fluoxetine (10 mg twice daily), calcium carbonate (600 mg twice daily), and placebo over the course of 4 menstrual cycles. The Inventory of Depressive Symptomatology, Premenstrual Tension Scale, Clinical Global Impression-Severity and -Improvement scales, and Daily Record of Severity of Problems were used to measure symptoms.Symptom improvement was greatest for the fluoxetine group, although significance was achieved only for the Daily Record of Severity of Problems (β = -0.28; 95% confidence interval, -1.70 to -0.35; P = 0.02) and the Clinical Global Impression-Improvement (β = -1.03; 95% confidence interval= -1.70 to -0.35; P = 0.04). The Cohen d effect sizes for fluoxetine relative to placebo were between 0.80 and 2.08, whereas the effect sizes for calcium were only between 0.10 and 0.44.Fluoxetine had clear therapeutic benefit for premenstrual syndrome, whereas the effect of calcium was much smaller. Results of this pilot do not support the need for a larger study that would compare these compounds.

We examined associations of mild and moderate to severe obstructive sleep apnea (OSA; apnea-hypopnea index ≥5 and ≥15, respectively) with recommended amounts of moderate-vigorous physical activity (MVPA) or vigorous physical activity (VPA) and by type of activity (i.e., recreational, transportation, and work activity). The Hispanic Community Health Study/Study of Latinos (HCHS/SOL), a multicenter population-based study, enrolled individuals from 2008 to 2011 from four U.S. metropolitan areas (Bronx, New York; Chicago, Illinois; Miami, Florida; San Diego, California). Participants in this study included 14,206 self-identified Hispanic/Latino ages 18 to 74 years from theHCHS/SOL. Survey logistic regression analysis was used to compute odds ratios [OR] and 95% confidence intervals [CI], adjusting for sociodemographics, smoking status, and body mass index (BMI). Relative to being inactive, performing some MVPA (>0 to

Background Reduced heart rate variability (HRV), a measure of cardiac autonomic function, is associated with an increased risk of cardiovascular disease (CVD) and mortality. Glucose homeostasis measures are associated with reduced cardiac autonomic function among those with diabetes, but inconsistent associations have been reported among those without diabetes. This study aimed to examine the association of glucose homeostasis measures with cardiac autonomic function among diverse Hispanic/Latino adults without diabetes. Methods The Hispanic community Health Study/Study of Latinos (HCHS/SOL; 2008–2011) used two-stage area probability sampling of households to enroll 16,415 self-identified Hispanics/Latinos aged 18–74 years from four USA communities. Resting, standard 12-lead electrocardiogram recordings were used to estimate the following ultrashort-term measures of HRV: RR interval (RR), standard deviation of all normal to normal RR (SDNN) and root mean square of successive differences in RR intervals (RMSSD). Multivariable regression analysis was used to estimate associations between glucose homeostasis measures with HRV using data from 11,994 adults without diabetes (mean age 39 years; 52 % women). Results Higher fasting glucose was associated with lower RR, SDNN, and RMSSD. Fasting insulin and the homeostasis model assessment of insulin resistance was negatively associated with RR, SDNN, and RMSSD, and the association was stronger among men compared with women. RMSSD was, on average, 26 % lower in men with higher fasting insulin and 29 % lower in men with lower insulin resistance; for women, the corresponding estimates were smaller at 4 and 9 %, respectively. Higher glycated hemoglobin was associated with lower RR, SDNN, and RMSSD in those with abdominal adiposity, defined by sex-specific cut-points for waist circumference, after adjusting for demographics and medication use. There were no associations between glycated hemoglobin and HRV measures among those without abdominal adiposity. Conclusions Impairment in glucose homeostasis was associated with lower HRV in Hispanic/Latino adults without diabetes, most prominently in men and individuals with abdominal adiposity. These results suggest that reduced cardiac autonomic function is associated with metabolic impairments before onset of overt diabetes in certain subgroups, offering clues for the pathophysiologic processes involved as well as opportunity for identification of those at high risk before autonomic control is manifestly impaired.

Objective To determine which children with urinary tract infection are likely to have pathogens resistant to narrow-spectrum antimicrobials. Study design Children, 2-71 months of age (n = 769) enrolled in the Randomized Intervention for Children with Vesicoureteral Reflux or Careful Urinary Tract Infection Evaluation studies were included. We used logistic regression models to test the associations between demographic and clinical characteristics and resistance to narrow-spectrum antimicrobials. Results Of the included patients, 91% were female and 76% had vesicoureteral reflux. The risk of resistance to narrow-spectrum antibiotics in uncircumcised males was approximately 3 times that of females (OR 3.1; 95% CI 1.4-6.7); in children with bladder bowel dysfunction, the risk was 2 times that of children with normal function (OR 2.2; 95% CI 1.2-4.1). Children who had received 1 course of antibiotics during the past 6 months also had higher odds of harboring resistant organisms (OR 1.6; 95% CI 1.1-2.3). Hispanic children had higher odds of harboring pathogens resistant to some narrow-spectrum antimicrobials. Conclusions Uncircumcised males, Hispanic children, children with bladder bowel dysfunction, and children who received 1 course of antibiotics in the past 6 months were more likely to have a urinary tract infection caused by pathogens resistant to 1 or more narrow-spectrum antimicrobials.

BACKGROUND: Little generalizable information is available on the outcomes of children diagnosed with bladder and bowel dysfunction (BBD) after a urinary tract infection (UTI). Our objectives were to describe the clinical characteristics of children with BBD and to examine the effects of BBD on patient outcomes in children with and without vesicoureteral reflux (VUR). METHODS: We combined data from 2 longitudinal studies (Randomized Intervention for Children With Vesicoureteral Reflux and Careful Urinary Tract Infection Evaluation) in which children RESULTS: BBD was present at baseline in 54% of the 181 toilet-trained children included; 94% of children with BBD reported daytime wetting, withholding maneuvers, or constipation. In children not on antimicrobial prophylaxis, 51% of those with both BBD and VUR experienced recurrent UTIs, compared with 20% of those with VUR alone, 35% with BBD alone, and 32% with neither BBD nor VUR. BBD was not associated with any of the other outcomes investigated. CONCLUSIONS: Among toilet-trained children, those with both BBD and VUR are at higher risk of developing recurrent UTIs than children with isolated VUR or children with isolated BBD and, accordingly, exhibit the greatest benefit from antimicrobial prophylaxis.

The study assessed whether overall perceived ethnic discrimination and four unique discrimination types were associated with binge drinking in participants from the Hispanic Community Health Study/Study of Latinos who also completed the Hispanic Community Health Study/Study of Latinos Sociocultural Ancillary Study (n = 5,313). In unadjusted analyses that were weighted for sampling strategy and design, each unit increase in discrimination type was associated with a 12-63% increase in odds of binge drinking; however, after adjusting for important demographic variables including age, sex, heritage group, language, and duration of U.S. residence, there was no longer an association between discrimination and binge drinking. Further research still needs to identify the salient factors that contribute to increased risk for binge drinking among Hispanics/Latinos.

Objective The objective was to compare the efficacy of motivational enhancement therapy coupled with cognitive behavioral therapy (MET-CBT) to brief advice for treatment of substance use in pregnancy. Method This was a randomized, parallel, controlled trial that was yoked to prenatal care and delivered at hospital outpatient clinics. We enrolled 168 substance-using women who had not yet completed an estimated 28 weeks of pregnancy. Obstetrical clinicians provided brief advice, and study nurses administered manualized MET-CBT. The primary outcome was percentage of days in the prior 28 days in which alcohol and/or drugs were used immediately before and 3 months postdelivery. Results There were no significant differences across groups in terms of self-reported percentage of days in which drugs or alcohol were used prior to and 3 months postdelivery. Biological measures showed similar results. There was a trend ( P =.08) for lower risk of preterm birth among those who received MET-CBT. Conclusions The tested interventions had similar therapeutic effects. Hence, both treatments may be suitable for pregnant substance users, depending on the population, setting and provider availability. Interventions that are intensified after delivery may decrease postpartum "rebound" effects in substance misuse.

There are limited studies of generalized anxiety disorder (GAD) across pregnancy.Women (n = 2793) were enrolled in the Yale Pink and Blue study, a cohort enriched with subjects who suffered from major depressive disorder (MDD) within the past five years or used antidepressants in the past year. Subjects were evaluated with the Composite International Diagnostic Interview at three time points: twice in pregnancy and once after delivery. We defined a generalized anxiety disorder (GAD) episode as per DSM IV but with required duration reduced to one month or longer. Course and correlates of GAD were examined in women who had: 1) no GAD during the 6 months prior or in pregnancy (Group A), 2) GAD in the 6 months prior to but not in pregnancy (Group B), 3) GAD in pregnancy only (Group C) and 4) GAD both in the 6 months prior to and during pregnancy (Group D).9.5% of the cohort suffered from GAD at some point in pregnancy. Anxiety symptoms were highest in the first trimester and decreased across pregnancy. Regression analysis revealed that previous GAD episodes, education, social support and a history of child abuse distinguished between membership in the four groups.The sample may not be representational, as it was enhanced with those at risk, and had relatively low representation of socio-economically disadvantaged women.Identification of anxious patients during pregnancy may provide an opportunity to engage those in need of psychiatric treatment.

Evaluating progression risk and determining optimal therapy for ulcerative colitis (UC) is challenging as many patients exhibit incomplete responses to treatment. As part of the PROTECT (Predicting Response to Standardized Colitis Therapy) Study, we evaluated the role of the gut microbiome in disease course for 405 pediatric, new-onset, treatment-naive UC patients. Patients were monitored for one year upon treatment initiation, and microbial taxonomic composition was analyzed from fecal samples and rectal biopsies. Depletion of core gut microbes and expansion of bacteria typical of the oral cavity were associated with baseline disease severity. Remission and refractory disease were linked to species-specific temporal changes that may be implicative of therapy efficacy, and a pronounced increase in microbiome variability was observed prior to colectomy. Finally, microbial associations with disease-associated serological markers suggest host-microbial interactions in UC. These insights will help improve existing treatments and develop therapeutic approaches guiding optimal medical care.

To report on the development of a questionnaire to screen for hazardous substance use in pregnant women and to compare the performance of the questionnaire with other drug and alcohol measures.Pregnant women were administered a modified TWEAK (Tolerance, Worried, Eye-openers, Amnesia, K[C] Cut Down) questionnaire, the 4Ps Plus questionnaire, items from the Addiction Severity Index, and two questions about domestic violence (N=2,684). The sample was divided into "training" (n=1,610) and "validation" (n=1,074) subsamples. We applied recursive partitioning class analysis to the responses from individuals in the training subsample that resulted in a three-item Substance Use Risk Profile-Pregnancy scale. We examined sensitivity, specificity, and the fit of logistic regression models in the validation subsample to compare the performance of the Substance Use Risk Profile-Pregnancy scale with the modified TWEAK and various scoring algorithms of the 4Ps.The Substance Use Risk Profile-Pregnancy scale is comprised of three informative questions that can be scored for high- or low-risk populations. The Substance Use Risk Profile-Pregnancy scale algorithm for low-risk populations was mostly highly predictive of substance use in the validation subsample (Akaike's Information Criterion=579.75, Nagelkerke R=0.27) with high sensitivity (91%) and adequate specificity (67%). The high-risk algorithm had lower sensitivity (57%) but higher specificity (88%).The Substance Use Risk Profile-Pregnancy scale is simple and flexible with good sensitivity and specificity. The Substance Use Risk Profile-Pregnancy scale can potentially detect a range of substances that may be abused. Clinicians need to further assess women with a positive screen to identify those who require treatment for alcohol or illicit substance use in pregnancy.III.

Many factors comprise a patient's decision to disclose use of drugs. Pregnant women may report drug use because they would like help with their addiction but the stigma associated with drug use may dampen their willingness to disclose. Knowledge about the accuracy of self-reported drug use as compared to urine toxicology screens can assist clinicians in the management of substance use in pregnancy.We compared the urine toxicology screens and self-reported use of marijuana or cocaine for 168 women enrolled in an integrated obstetrical/substance abuse treatment program. We stratified by various periods of self-reported useMost women with a positive toxicology screen reported use in the past 28 days (78% for marijuana, 86% for cocaine). However, many women reported their most recent use to be outside of the assays' detection window (14% for marijuana, 57% for cocaine). We did not find differences in self-report for women with positive urine between Whites and non-Whites (p = 1.00). Agreement over the previous month was good (Kappa = 0.74 and 0.70 for marijuana and cocaine, respectively.).A question about use of marijuana or cocaine during the preceding month rather than the prior few days may be a better indicator of use.

Objective The aim of this study was to assess the psychometric properties of the Patient Health Questionnaire (PHQ)-8, and the PHQ-2, a two-item version of the PHQ, respectively, in pregnancy. These screeners were compared to a structured diagnostic interview in a cohort of pregnant women attending prenatal care. B ased upon studies documenting high sensitivity and specificity on the PHQ-8 and PHQ-2 in the general adult population, we hypothesized that both instruments would be effective in this population. Methods Two hundred eighteen women, 13 of them depressed, were given the Composite International Diagnostic Interview and the PHQ-8 before 17 weeks of pregnancy. Receiver Operating Characteristic curves determined optimal thresholds and sensitivity and specificity were calculated using both dimensional and categorical approaches. Agreement between the PHQ-2 and PHQ-8 was measured using Cohen's kappa. Results Optimal cutoffs for the PHQ-8 and PHQ-2 were 11 and 4, respectively. Using these cutoffs, the PHQ-8 had a sensitivity of 77% and a specificity of 62% while the PHQ-2 had a sensitivity of 62% and a specificity of 79%. The categorical method of scoring the PHQ-8 yielded a sensitivity of 54% and a specificity of 84%. Conclusions In our sample, the PHQ-8 and PHQ-2 performed almost equally in detecting probable major depressive disorder in a sample of pregnant women. The categorical scoring method for the PHQ-8 had lower sensitivity but slightly higher specificity than the dimensional version. We found the PHQ-8 and PHQ-2 to have lower sensitivity and specificity in our pregnant population as compared to findings in nonpregnant populations; however, characteristics of our sample and choice of diagnostics instrument could explain these discrepant findings.

Anaerobic and aerobic bacteria were quantitated in respiratory samples across three cystic fibrosis (CF) centres using extended culture methods. Subjects aged 1–69 years who were clinically stable provided sputum (n=200) or bronchoalveolar lavage (n=55). 18 anaerobic and 39 aerobic genera were cultured from 59% and 95% of samples, respectively; 16 out of 57 genera had a ≥5% prevalence across centres.Analyses of microbial communities using co-occurrence networks in sputum samples showed groupings of oral, including anaerobic, bacteria, whereas typical CF pathogens formed distinct entities. Pseudomonas was associated with worse nutrition and F508del genotype, whereas anaerobe prevalence was positively associated with pancreatic sufficiency, better nutrition and better lung function. A higher total anaerobe/total aerobe CFU ratio was associated with pancreatic sufficiency and better nutrition. Subjects grouped by factor analysis who had relative dominance of anaerobes over aerobes had milder disease compared with a Pseudomonas-dominated group with similar proportions of subjects that were homozygous for F508del.In summary, anaerobic bacteria occurred at an early age. In sputum-producing subjects anaerobic bacteria were associated with milder disease, suggesting that targeted eradication of anaerobes may not be warranted in sputum-producing CF subjects.

Objective We sought to determine whether trimester of pregnancy influences the ability to diagnose major depressive disorder (MDD). Method Eight hundred thirty-eight subjects completed a Composite International Diagnostic Interview and the Edinburgh Postnatal Depression Scale (EPDS) before 17 weeks of pregnancy, at 26–30 weeks of pregnancy and at 4–12 weeks postpartum. Subjects responded to a checklist of MDD symptoms regardless of stem question endorsement. We compared rates of symptom expression by response (Y/N) to stem questions, and trimester, using logit analysis. Receiver operating characteristic curves determined optimal EPDS thresholds. Results Most symptoms from the DSM-IV checklist were endorsed significantly more often in the first compared to later trimesters (odds ratios ranged from 1.39 to 14.16 for the first vs. later trimesters), independent of response to depression stem questions or medication treatment. Despite this, stem-positive and stem-negative groups differed significantly for 10 out of 13 symptoms (odds ratios, 2.29–6.89), independent of trimester. The EPDS had an optimal cutoff of 10 and showed acceptable predictive value. Conclusions Pregnant women commonly experience somatic and other symptoms in this first trimester, but depressed women still differ from those who are not depressed. “Appetite increase,” “oversleeping” and “increase in energy” (e.g., agitation) were uninformative with regard to an MDD diagnosis.

Strong social support has been linked with positive mental health and better birth outcomes for pregnant women. Our aim was to replicate the psychometric properties of the Kendler Social Support Interview modified for use in pregnant women and to establish the inventory's relationship to depression in pregnancy.The modified Kendler Social Support Interview (MKSSI) was evaluated using principal components analysis. The association with depression was used as an indicator of external validity and was assessed by logistic regression.Data from 783 subjects were analyzed. One large principal component, termed "global support," (eigenvalue=6.086) represented 22.5% of the total variance. However, 6 of the 27 items (frequency of contact with spouse, siblings, other relatives, and friends, and attendance at church and clubs) had low levels of association (0.4) and thus were excluded from suggested items for a total score. Varimax rotation of the remaining 21 items resulted in subscales that fell into expected groupings: mother, father, siblings, friends, etc. One unit and two unit increases in the global support score were associated with 58.3% (OR=0.417, 95% CI=0.284-0.612) and 82.6% (OR=0.174, 95% CI=0.081-0.374) reductions in odds for depression, respectively.The ability of this social support scale to predict future depression in pregnancy has not yet been established due to cross-sectional design.The MKSSI is reliable and valid for use in evaluating social support and its relationship to depression in pregnant women.

This longitudinal study examined whether youth with high traumatic stress (HTS) respond differently to outpatient substance abuse treatment compared to youth without HTS at intake, and at 3 and 6 months following intake. Data were analyzed using a mixed-effects two-part model to fit repeated data with zero saturation. Clients in both groups significantly increased their odds of abstinence and full symptom remission of substance problems from baseline to 6 months. Of youth still using substances, the group with HTS reduced substance use significantly more than substance users without HTS. Recommendations for future research are provided.

BACKGROUND: The Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) trial found that recurrent urinary tract infections (rUTI) with resistant organisms were more common in the trimethoprim-sulfamethoxazole prophylaxis (TSP) arm. We describe factors associated with trimethoprim-sulfamethoxazole (TMP-SMX) resistance of rUTIs in RIVUR. METHODS: Children aged 2 to 71 months with first or second UTI (index UTI) and grade I to IV vesicoureteral reflux (VUR) were randomized to TSP or placebo and followed for 2 years. Factors associated with TMP-SMX–resistant rUTI were evaluated. RESULTS: Among 571 included children, 48% were CONCLUSIONS: Although TMP-SMX resistance is more common among children treated with TSP versus placebo, resistance decreased over time. Among children treated with TSP, there was no significant difference in UTI recurrence between those with TMP-SMX–resistant index UTI versus TMP-SMX–susceptible UTI.

Background and objectives The prevalence of ESRD among Hispanics/Latinos is 2-fold higher than in non-Hispanic whites. However, little is known about the prevalence of earlier stages of CKD among Hispanics/Latinos. This study estimated the prevalence of CKD in US Hispanics/Latinos. Design, setting, participants, & measurements This was a cross-sectional study of 15,161 US Hispanic/Latino adults of Cuban, Dominican, Mexican, Puerto Rican, Central American, and South American backgrounds enrolled in the multicenter, prospective, population-based Hispanic Community Health Study/Study of Latinos (HCHS/SOL). In addition, the prevalence of CKD in Hispanics/Latinos was compared with other racial/ethnic groups in the 2007–2010 National Health and Nutrition Examination Survey (NHANES). Prevalent CKD was defined as an eGFR 2 (estimated with the 2012 Chronic Kidney Disease Epidemiology Collaboration eGFR creatinine-cystatin C equation) or albuminuria based on sex-specific cut points determined at a single point in time. Results The overall prevalence of CKD among Hispanics/Latinos was 13.7%. Among women, the prevalence of CKD was 13.0%, and it was lowest in persons with South American background (7.4%) and highest (16.6%) in persons with Puerto Rican background. In men, the prevalence of CKD was 15.3%, and it was lowest (11.2%) in persons with South American background and highest in those who identified their Hispanic background as “other” (16.0%). The overall prevalence of CKD was similar in HCHS/SOL compared with non-Hispanic whites in NHANES. However, prevalence was higher in HCHS/SOL men and lower in HCHS/SOL women versus NHANES non-Hispanic whites. Low income, diabetes mellitus, hypertension, and cardiovascular disease were each significantly associated with higher risk of CKD. Conclusions Among US Hispanic/Latino adults, there was significant variation in CKD prevalence among Hispanic/Latino background groups, and CKD was associated with established cardiovascular risk factors.

Due to the continuing prevalence of adolescent substance abuse, promising treatment models need to be developed and evaluated. Thus, the purpose of this study was to evaluate the efficacy of two promising models, Strengths Oriented Family Therapy (SOFT) and The Seven Challenges 1 (7C). Adolescents who qualified for outpatient treatment and agreed to participate in our study were randomly assigned to one of the two treatments and assessed at 3 and 6-months following baseline. Using a two-part, random-effects model, we examined the odds of achieving abstinence or full symptom remission between treatments and over time. For those not achieving full abstinence or full problem remission, we investigated whether frequency of use or symptom severity were reduced at follow-up. Participants in both SOFT and 7C demonstrated significant reductions in substance use and related problems, but treatments did not differ at 3 and 6 months following baseline. Overall, treatment services were delivered as planned. Both SOFT and 7C were efficacious with adolescents who abuse substances, as participants in both conditions were significantly more likely to be in symptom remission or abstinent at follow-up interviews versus at baseline. Replication studies are needed that address this study’s limitations. (Am J Addict 2006;15:131–136)

Purpose To examine the associations between overweight/obesity and occupation among Hispanics/Latinos, the largest minority population in the U.S. Methods This study included 7,409 employed individuals in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), a prospective study of Hispanic/Latino individuals aged 18–74 in four communities in the U.S. We independently examined the relationships between BMI, Occupational Activity (OA), and Total Hours Worked, quantified via self-reported hours worked per week and occupation-assigned Metabolic Equivalents (METs). Results More than three quarters of the participants were either overweight (39.3%) or obese (37.8%). Individuals with a primary occupation and those employed in a secondary occupation worked an average of 36.8 and 14.6 hrs/wk, respectively. The overall adjusted odds for being obese compared to normal weight were 3.2% (AOR = 1.03, 95% CI 1.01, 1.05) and 14.4% (AOR = 1.14 95% Cl 1.07, 1.23) greater for each 10 MET•hrs/wk unit of increased OA, and each 10-hrs/wk unit of Total Hours Worked, respectively. Conclusion This study presents the first findings on the association between OA with overweight/obesity among Hispanic/Latino individuals in the U.S. Increasing OA and Total Hours Worked per week were independently associated with increasing odds of overweight/obesity suggesting that the workplace is only one part of the overall energy expenditure dynamic. Our findings point to the need to emphasize engaging employed individuals in greater levels of PA outside of the work environment to impact overweight/obesity.

Background—Major depressive disorder as well as the use of serotonin reuptake inhibitors in pregnancy have been associated with preterm birth. Studies that have attempted to separate effects of illness from treatment have been inconclusive. We sought to explore the separate effects of serotonin reuptake inhibitor use and major depressive episodes in pregnancy on risk of preterm birth. Methods—We conducted a prospective cohort study of 2793 pregnant women, oversampled for a recent episode of major depression or use of a serotonin reuptake inhibitor. We extracted data on birth outcomes from hospital charts and used binary logistic regression to model preterm birth (

Assess the relative effects of a variety of illicit and licit drugs on risk for adverse birth outcomes.We used data from two large prospective investigations, and a novel analytic method, recursive partitioning class analysis to identify risk factors associated with preterm birth and delivering a small for gestational age infant.Compared to cocaine and opiate non-users, cocaine users were 3.53 times as likely (95% CI: 1.65-7.56; p = 0.001) and opiate users 2.86 times as likely (95% CI: 1.11-7.36; p = 0.03) to deliver preterm. The odds of delivering a small for gestational age infant for women who smoked more than two cigarettes daily was 3.74, (95% CI: 2.47-5.65; p0.0001) compared to women who smoked two or less cigarettes daily and had one previous child. Similarly, less educated, nulliparous women who smoked two or fewer cigarettes daily were 4.12 times as likely (95% CI: 2.04-8.34; p0.0001) to have a small for gestational age infant.Among our covariates, prenatal cocaine and opiate use are the predominant risk factors for preterm birth; while tobacco use was the primary risk factor predicting small for gestational age at delivery. Multi-substance use did not substantially increase risk of adverse birth outcomes over these risk factors.

Context There is substantial information that premenstrual dysphoric disorder (PMDD) is a clinically significant disorder with biological underpinnings that differ from other psychiatric disorders. However, data regarding the symptoms noted in DSM-IV and timing of their expression in the menstrual cycle have had little empirical support. Objective To provide evidence informing the definitional criteria for PMDD. Design Prospective surveys. Setting General community and clinical settings. Participants Two cohorts that included a representative sample and a self-identified treatment-seeking cohort. Main Outcome Measure Daily ratings of perimenstrual symptoms and functioning. Results Mood and physical symptoms were most severe and were accompanied by impairment in the 4 days before through the first 2 days of menses for the self-identified group and in the 3 days before through the first 3 days of menses in the community sample. The most problematic symptoms endorsed were those listed in DSM-IV, but depressed mood was less frequent than other affective symptoms. In the combined sample, 4 or more symptoms was the optimal cutoff point for maximizing both sensitivity and specificity when predicting impairment. Conclusions This is informative for DSM-5 in that the most symptomatic period typically includes the few days before through the first 3 days of menses rather than only the premenstrual phase. Further, we validated the salience of PMDD symptoms included in DSM-IV. Although the number of symptoms most associated with distress and impairment differed between the 2 cohorts, results from the combined cohort suggest that 4 symptoms are linked with impairment from PMDD symptoms.

This longitudinal study examined whether youth with high traumatic stress (HTS) respond differently to outpatient substance abuse treatment compared to youth without HTS at intake, and at 3 and 6 months following intake. Data were analyzed using a mixed-effects two-part model to fit repeated data with zero saturation. Clients in both groups significantly increased their odds of abstinence and full symptom remission of substance problems from baseline to 6 months. Of youth still using substances, the group with HTS reduced substance use significantly more than substance users without HTS. Recommendations for future research are provided.