Comprehensive Association Analyses of Extraintestinal Manifestations in Inflammatory Bowel Disease.

BACKGROUND & AIMS: Patients with inflammatory bowel disease (IBD) frequently develop extraintestinal manifestations (EIMs) that contribute substantially to morbidity. We assembled the largest multicohort data set to date to investigate the clinical, serologic, and genetic factors associated with EIM complications in IBD. METHODS: Data were available in 12,083 unrelated European ancestry IBD cases with presence or absence of EIMs (eg, ankylosing spondylitis [ankylosing spondylitis and sacroiliitis], primary sclerosing cholangitis [PSC], peripheral arthritis, and skin and ocular manifestations) across 4 cohorts (Cedars-Sinai Medical Center, National Institute for Diabetes and Digestive and Kidney Diseases IBD Genetics Consortium, Sinai Helmsley Alliance for Research Excellence Consortium, and Risk Stratification and Identification of Immunogenetic and Microbial Markers of Rapid Disease Progression in Children with Crohn's Disease cohort). Clinical and serologic parameters were analyzed by means of univariable and multivariable regression analyses using a mixed-effects model. Within-case logistic regression was performed to assess genetic associations. RESULTS: Most EIMs occurred more commonly in female subjects (overall EIM: P = 9.0E-05, odds ratio [OR], 1.2; 95% CI, 1.1-1.4), with CD (especially colonic disease location; P = 9.8E-09, OR, 1.7; 95% CI, 1.4-2.0), and in subjects who required surgery (both CD and UC; P = 3.6E-19, OR, 1.7; 95% CI, 1.5-1.9). Smoking increased risk of EIMs except for PSC, where there was a "protective" effect. Multiple serologic associations were observed, including with PSC (IgG and IgA, perinuclear anti-nuclear cytoplasmic antibody; anti-Saccharomyces cerevisiae antibodies; and anti-flagellin) and any EIM (IgG and IgA, perinuclear anti-nuclear cytoplasmic antibody; anti-Saccharomyces cerevisiae antibodies; and anti-Pseudomonas fluorescens-associated sequence). We identified genome-wide significant associations within major histocompatibility complex (ankylosing spondylitis and sacroiliitis, P = 1.4E-15; OR, 2.5; 95% CI, 2.0-3.1; PSC, P = 2.7E-10; OR, 2.8; 95% CI, 2.0-3.8; ocular, P = 2E-08, OR, 3.6; 95% CI, 2.3-5.6; and overall EIM, P = 8.4E-09; OR, 2.2; 95% CI, 1.7-2.9) and CPEB4 (skin, P = 2.7E-08; OR, 1.5; 95% CI, 1.3-1.8). Genetic associations implicated tumor necrosis factor, JAK-STAT, and IL6 as potential targets for EIMs. Contrary to previous reports, only 2% of our subjects had multiple EIMs and most co-occurrences were negatively correlated. CONCLUSIONS: We have identified demographic, clinical, and genetic associations with EIMs that revealed underlying mechanisms and implicated novel and existing drug targets-important steps toward a more personalized approach to IBD management.

Clinical predictors of early and late endoscopic recurrence following ileocolonic resection in Crohn's disease.

BACKGROUND AND AIM: Multiple factors are suggested to place Crohn's disease patients at risk of recurrence after ileocolic resection with conflicting associations. We aimed to identify clinical predictors of recurrence at first (early) and further (late) postoperative colonoscopy. METHODS: Crohn's disease patients undergoing ileocolic resection were prospectively recruited at six North American centers. Clinical data was collected and endoscopic recurrence was defined as Rutgeerts score ≥i2. A multivariable model was fitted to analyze variables independently associated with recurrence. RESULTS: A total of 365 patients undergoing 674 postoperative colonoscopies were included with a median age of 32 years, 189 (51.8%) were male and 37 (10.1%) non-Whites. Postoperatively, 133 (36.4%) used anti-TNF and 30 (8.2%) were smokers. At first colonoscopy, 109 (29.9%) had recurrence. Male gender (OR = 1.95, 95% CI 1.12 - 3.40), non-White ethnicity (OR = 2.48, 95% CI 1.09 - 5.63), longer interval between surgery and colonoscopy (OR = 1.09, 95% CI 1.002 - 1.18), and postoperative smoking (OR = 2.78, 95% CI 1.16 - 6.67) were associated with recurrence, while prophylactic anti-TNF reduced the risk (OR = 0.28, 95% CI 0.14 - 0.55). Postoperative anti-TNF prophylaxis had a protective effect on anti-TNF experienced patients but not on anti-TNF naïve patients. Among patients without recurrence at first colonoscopy, Rutgeerts score i1 was associated with subsequent recurrence (OR = 4.43, 95% CI 1.73 - 11.35). CONCLUSIONS: We identified independent clinical predictors of early and late Crohn's disease postoperative endoscopic recurrence. Clinical factors traditionally used for risk stratification failed to predict recurrence and need to be revised.

Breast sensorisexual function: a novel patient-reported outcome measure of sexual sensory functions of the breast.

BACKGROUND: A validated measure assessing sexual sensory functions of the breast is needed to optimize sexual and other health outcomes after breast procedures. AIM: To describe the development of a patient-reported outcome measure (PROM) to assess breast sensorisexual function (BSF). METHODS: We applied the PROMIS standards (Patient Reported Outcomes Measurement Information System) for measure development and evaluation of validity. An initial conceptual model of BSF was developed with patients and experts. A literature review yielded a pool of 117 candidate items that underwent cognitive testing and iteration. Forty-eight items were administered to an ethnically diverse, national panel-based sample of sexually active women with breast cancer (n = 350) or without (n = 300). Psychometric analyses were performed. OUTCOMES: The main outcome was BSF, a measure that assesses affective (satisfaction, pleasure, importance, pain, discomfort) and functional (touch, pressure, thermoreception, nipple erection) sensorisexual domains. RESULTS: A bifactor model fit to 6 domains-excluding 2 domains with only 2 items each and 2 pain-related domains-revealed a single general factor representing BSF that may be adequately measured by the average of the items. This factor, with higher values denoting better function and with the standard deviation set to 1, was highest among women without breast cancer (mean, 0.24), intermediate among women with breast cancer but not bilateral mastectomy and reconstruction (-0.01), and lowest among those with bilateral mastectomy and reconstruction (-0.56). Between women with and without breast cancer, the BSF general factor accounted for 40%, 49%, and 100% of the difference in arousal, ability to orgasm, and sexual satisfaction, respectively. Items in each of 8 domains demonstrated unidimensionality (ie, they measured 1 underlying BSF trait) and high Cronbach's alphas for the entire sample (0.77-0.93) and the cancer group (0.71-0.95). Correlations with sexual function, health, and quality of life were positive for the BSF general factor and mostly negative for the pain domains. CLINICAL IMPLICATIONS: The BSF PROM can be used to assess the impact of breast surgery or other procedures on the sexual sensory functions of the breast in women with and without breast cancer. STRENGTHS AND LIMITATIONS: The BSF PROM was developed by using evidence-based standards, and it applies to sexually active women with and without breast cancer. Generalizability to sexually inactive women and other women warrants further study. CONCLUSION: The BSF PROM is a measure of women's breast sensorisexual function with evidence of validity among women affected and unaffected by breast cancer.

Serum Lipidomic Screen Identifies Key Metabolites, Pathways, and Disease Classifiers in Crohn's Disease.

BACKGROUND: There is an unmet medical need for biomarkers that capture host and environmental contributions in inflammatory bowel diseases (IBDs). This study aimed at testing the potential of circulating lipids as disease classifiers given their major roles in inflammation. METHODS: We applied a previously validated comprehensive high-resolution liquid chromatography-mass spectrometry-based untargeted lipidomic workflow covering 25 lipid subclasses to serum samples from 100 Crohn's disease (CD) patients and 100 matched control subjects. Findings were replicated and expanded in another 200 CD patients and 200 control subjects. Key metabolites were tested for associations with disease behavior and location, and classification models were built and validated. Their association with disease activity was tested using an independent cohort of 42 CD patients. RESULTS: We identified >70 metabolites with strong association (P < 1 × 10-4, q < 5 × 10-4) to CD. Highly performing classification models (area under the curve > 0.84-0.97) could be built with as few as 5 to 9 different metabolites, representing 6 major correlated lipid clusters. These classifiers included a phosphatidylethanolamine ether (O-16:0/20:4), a sphingomyelin (d18:1/21:0) and a cholesterol ester (14:1), a very long-chain dicarboxylic acid [28:1(OH)] and sitosterol sulfate. These classifiers and correlated lipids indicate a dysregulated metabolism in host cells, notably in peroxisomes, as well as dysbiosis, oxidative stress, compromised inflammation resolution, or intestinal membrane integrity. A subset of these were associated with disease behavior or location. CONCLUSIONS: Untargeted lipidomic analyses uncovered perturbations in the circulating human CD lipidome, likely resulting from multiple pathogenic mechanisms. Models using as few as 5 biomarkers had strong disease classifier characteristics, supporting their potential use in diagnosis or prognosis.

This study reports a comprehensive untargeted lipidomic analysis of 600 serum samples from patients with Crohn's disease and matched control subjects, identified and replicated ~70 metabolites associated with Crohn's disease, and developed highly performing classification models (area under the curve > 0.84-0.97) with as few as 5 metabolites.

Short-interval pregnancy in the Illinois Medicaid population following delivery in Catholic vs non-Catholic hospitals.

OBJECTIVE: Catholic hospitals restrict access to comprehensive reproductive health services that could impact patient outcomes. We sought to determine whether delivery at a Catholic hospital is associated with shorter pregnancy intervals among patients insured by Medicaid in Illinois. STUDY DESIGN: We used Illinois Medicaid data files to conduct a retrospective cohort study. We used billing codes to identify deliveries in 2010 and 2011 and classified each by a hospital of delivery, maternal age, race/ethnicity, and residential zip code. We calculated the interval from index birth to subsequent conception using an established method and used Cox proportional hazards regression to compare the rate of subsequent pregnancy between enrollees who delivered in Catholic vs non-Catholic hospitals, adjusting for individual characteristics. We also computed differences in the rates of conception within 6-, 12-, and 18-month intervals. RESULTS: We identified 96,293 index births and 18,627 subsequent conceptions. Twenty-eight percent (26,775) of index births occurred in a Catholic hospital. Women who delivered in a Catholic hospital had a 12% greater risk of conception in the following 18 months (HR 1.12, 95% CI 1.09-1.16) after adjusting for age, race/ethnicity, and rural residence. At 18 months, 23.9% of enrollees delivering in a Catholic hospital had become pregnant as compared to 21.2% for enrollees delivering in a non-Catholic hospital (difference of 2.6%, 95% CI 1.8-3.6). CONCLUSION: Illinois Medicaid enrollees who deliver at Catholic hospitals have an increased risk of short-interval pregnancy. As the market share of Catholic hospitals grows, providers must work with patients to acknowledge and address these potential impacts on reproductive health outcomes and policies must change to promote equitable access. IMPLICATIONS: Delivery at a Catholic hospital is associated with an increased risk of short-interval pregnancy. Further attention from providers, researchers, and policymakers alike, is necessary to identify the mechanisms through which these differences manifest such that effective interventions can be developed.

A Role for CXCR3 Ligands as Biomarkers of Post-Operative Crohn's Disease Recurrence.

BACKGROUND AND AIMS: Crohn's disease [CD] recurrence following ileocolic resection [ICR] is common. We sought to identify blood-based biomarkers associated with CD recurrence. METHODS: CD patients undergoing ICR were recruited across six centres. Serum samples were obtained at post-operative colonoscopy. A multiplex immunoassay was used to analyse 92 inflammation-related proteins [Olink Proteomics]. Bayesian analysis was used to identify proteins associated with increasing Rutgeerts score. Identified proteins were used in receiver operating characteristic [ROC] analysis to examine the ability to identify CD recurrence [Rutgeerts score ≥i2]. Existing single cell data were interrogated to further elucidate the role of the identified proteins. RESULTS: Data from 276 colonoscopies in 213 patients were available. Median time from surgery to first and second colonoscopy was 7 (interquartile range [IQR] 6-9) and 19 [IQR 16-23] months, respectively. Disease recurrence was evident at 60 [30%] first and 36 [49%] second colonoscopies. Of 14 proteins significantly associated with Rutgeerts score, the strongest signal was seen for CXCL9 and MMP1. Among patients on anti-tumour necrosis factor drugs, CXCL9 and CXCL11 were most strongly associated with Rutgeerts score. Both are CXCR3 ligands. Incorporation of identified proteins into ROC analysis improved the ability to identify disease recurrence as compared to C-reactive protein alone: area under the curve [AUC] 0.75 (95% confidence interval [CI]: 0.66-0.82] vs 0.64 [95% CI 0.56-0.72], p = 0.012. Single cell transcriptomic data provide evidence that innate immune cells are the primary source of the identified proteins. CONCLUSIONS: CXCR3 ligands are associated with CD recurrence following ICR. Incorporation of novel blood-based candidate biomarkers may aid in identification of CD recurrence.

Socio-Structural and Neighborhood Predictors of Incident Criminal Justice Involvement in a Population-Based Cohort of Young Black MSM and Transgender Women.

Black men who have sex with men (MSM) and transgender women are disproportionately affected by criminal justice involvement (CJI) and HIV. This study recruited 618 young Black MSM and transgender women in Chicago, IL, using respondent-driven sampling between 2013 and 2014. Random effects logistic regression evaluated predictors of incident CJI over 18 months of follow-up. Controlling for respondent age, gender and sexual identity, spirituality (aOR 0.56, 95% CI 0.33-0.96), and presence of a mother figure (aOR 0.41, 95% CI 0.19-0.89) were protective against CJI. Economic hardship (financial or residential instability vs. neither aOR 2.23, 95% CI 1.10-4.51), two or more past episodes of CJI vs. none (aOR 2.66, 95% CI 1.40-5.66), and substance use (marijuana use vs. none aOR 2.79, 95% CI 1.23-6.34; other drug use vs. none aOR 4.49, 95% CI 1.66-12.16) were associated with CJI during follow-up. Research to identify and leverage resilience factors that can buffer the effects of socioeconomic marginalization may increase the effectiveness of interventions to address the socio-structural factors that increase the risk for CJI among Black MSM and transgender women. Given the intersection of incarceration, HIV and other STIs, and socio-structural stressors, criminal justice settings are important venues for interventions to reduce health inequities in these populations.

Neighbourhoods, networks and pre-exposure prophylaxis awareness: a multilevel analysis of a sample of young black men who have sex with men.

OBJECTIVE: Young black men who have sex with men (YBMSM) in the USA represent a subgroup that has the highest HIV incidence among the overall population. In the USA, pre-exposure prophylaxis (PrEP) is an effective prevention intervention to prevent HIV acquisition when taken regularly. Neighbourhood and network factors may relate to PrEP awareness, but have not been studied in YBMSM. This study aimed to examine the relationship of neighbourhood and network characteristics with PrEP awareness among YBMSM. METHODS: We used data collected from a sample of 618 YBMSM in Chicago (2013-2014). Home addresses were collected for participants and enumerated network members. Administrative data (eg, 2014 American Community Survey, Chicago Department of Public Health) were used to describe residence characteristics. Network member characteristics were also collected (eg, sexual partners' sex-drug use, confidant network members who were also MSM). Multilevel analysis was performed to examine the relationships of neighbourhood and network characteristics to PrEP awareness. RESULTS: Higher neighbourhood-level educational attainment (adjusted odds ratio (aOR) 1.02, p=0.03) and greater primary care density (aOR 1.38, p=0.01) were associated with greater PrEP awareness; greater neighbourhood alcohol outlet density (aOR 0.52, p=0.004) was associated with less PrEP awareness. Sexual network members residing in the same neighbourhood as the participants (aOR 2.58, p=0.03) and discussions around avoiding HIV acquisition with confidants (aOR 2.26, p=0.04) were associated with greater PrEP awareness. CONCLUSIONS: The results suggest that neighbourhood and network characteristics can influence PrEP awareness in YBMSM. Additional studies are needed to understand the influences of neighbourhood (eg, MSM serving venues) and network (eg, peer to peer communication) characteristics on dissemination of PrEP information, uptake and adherence and the related mechanisms behind the associations.

PrEP Chicago: A randomized controlled peer change agent intervention to promote the adoption of pre-exposure prophylaxis for HIV prevention among young Black men who have sex with men.

BACKGROUND/AIMS: Advances in biomedical prevention strategies such as pre-exposure prophylaxis (PrEP) represent a new opportunity for reducing HIV incidence among young Black men who have sex with men, for whom the number of new HIV infections continues to rise. However, studies have documented low rates of PrEP uptake in this community. Research suggests that the peer networks of young Black men who have sex with men play important roles in their sexual health decisions. PrEP Chicago is a randomized controlled trial network intervention designed to increase PrEP uptake among young Black men who have sex with men living in Chicago. The aims of this study are twofold. Aim 1 is to estimate the effectiveness of a peer change agent intervention for (1) increasing the number of referrals made to a PrEP information line, (2) increasing the rate of PrEP adoption among non-participant peers, and (3) increasing PrEP knowledge, attitudes, and intentions among participants. Aim 2 is to determine the individual and network variables that explain peer change agent effectiveness. METHODS: PrEP Chicago is a social network intervention that utilizes the influence of peer change agents to link young Black men who have sex with men in Chicago to PrEP. Young Black men who have sex with men were recruited using respondent-driven sampling. Once screened for eligibility, participants were randomly assigned to either one of two treatment sequences: (1) intervention treatment in Year 1 followed by a minimal contact attention control in Year 2 or (2) the minimal contact attention control in Year 1 followed by treatment in Year 2. The treatment consists of a PrEP/peer change agent training workshop followed by booster calls for 12 months. The attention control consists of a sex diary activity designed to help participants assess sexual risk. Psychosocial, sexual health, and network data are collected from all participants at baseline and at 12- and 24-month follow-ups. RESULTS: In total, 423 participants aged 18-35 have been enrolled (more than 100% target enrollment) and have completed baseline data collection. A majority of participants in both intervention and control groups reported having heard of PrEP before enrolling in the study, yet also reported having had no current or prior experience taking PrEP. Statistical analyses await completion of Year 1 of the trial in March 2018. CONCLUSION: PrEP Chicago addresses a gap in HIV prevention research and intervention design by utilizing the existing social networks among young Black men who have sex with men as mechanisms for information diffusion, behavioral influence, social support, and empowerment. Therefore, interventions that leverage peer influence processes to facilitate PrEP uptake are promising strategies to improve sexual health engagement and overcome disparities in outcomes among this at-risk population.

Appendectomy does not decrease the risk of future colectomy in UC: results from a large cohort and meta-analysis.

OBJECTIVES: Early appendectomy is inversely associated with the development of UC. However, the impact of appendectomy on the clinical course of UC is controversial, generally favouring a milder disease course. We aim to describe the effect appendectomy has on the disease course of UC with focus on the timing of appendectomy in relation to UC diagnosis. DESIGN: Using the National Institute of Diabetes and Digestive and Kidney Diseases Inflammatory Bowel Disease Genetics Consortium database of patients with UC, the risk of colectomy was compared between patients who did and did not undergo appendectomy. In addition, we performed a meta-analysis of studies that examined the association between appendectomy and colectomy. RESULTS: 2980 patients with UC were initially included. 111 (4.4%) patients with UC had an appendectomy; of which 63 were performed prior to UC diagnosis and 48 after diagnosis. In multivariable analysis, appendectomy performed at any time was an independent risk factor for colectomy (OR 1.9, 95% CI 1.1 to 3.1), with appendectomy performed after UC diagnosis most strongly associated with colectomy (OR 2.2, 95% CI 1.1 to 4.5). An updated meta-analysis showed appendectomy performed either prior to or after UC diagnosis had no effect on colectomy rates. CONCLUSIONS: Appendectomy performed at any time in relation to UC diagnosis was not associated with a decrease in severity of disease. In fact, appendectomy after UC diagnosis may be associated with a higher risk of colectomy. These findings question the proposed use of appendectomy as treatment for UC.

Facebook network structure and awareness of preexposure prophylaxis among young men who have sex with men.

BACKGROUND: Young Black men who have sex with men (YBMSM) are the only population in the United States who have experienced rising human immunodeficiency virus incidence over the past decade. Consistent pre-exposure prophylaxis (PrEP) use can substantially reduce the risk of human immunodeficiency virus acquisition. What differentiates those who become aware of PrEP, and those who do not, remains largely unknown. METHODS: The social networks of YBMSM can impact their awareness of PrEP; to examine this impact, we used two waves of Facebook data from "uConnect"-a longitudinal cohort study of YBMSM in Chicago (n = 266). RESULTS: While PrEP awareness increased from 45% at baseline to 75% at follow-up, its use remained low (4% and 6%). There were 88 PrEP-unaware individuals at baseline who became aware (BA) by follow-up, and 56 who remained persistently unaware. While the persistently unawares had a higher median number of total Facebook friends, the BAs had a higher median numbers of friends who participated in uConnect, who were PrEP-aware, and who practiced behaviors previously found to be associated with individual-level awareness of PrEP at baseline. The BAs also had substantially more "influential" friends. CONCLUSION: These findings demonstrate the potential of social networks in raising PrEP awareness and use among YBMSM.

Criminal justice involvement history is associated with better HIV care continuum metrics among a population-based sample of young black MSM.

OBJECTIVE: To examine how history of criminal justice involvement (CJI) is related to HIV care continuum metrics among young black MSM 16-29 years of age. DESIGN: Population-based survey. METHODS: From 2013 to 2014, a representative sample of young black MSM was generated using respondent-driven sampling (RDS) in Chicago (n = 618). HIV antibody/antigen and RNA testing were performed using dry blood spots. Factors assessed in the care continuum included HIV testing, HIV diagnosis, linkage to care within 6 months, retention in care, adherence to antiretrovirals, and viral suppression. RDS-weighted regression models examined the associations between history of CJI, including frequency of CJI and durations of stay and each of the continuum metrics. RESULTS: A final analytic sample of 618 participants was generated through RDS chains of up to 13 waves in length and with a mean of 2.1 recruits per participant. At enrollment, 40.8% had prior history of CJI and 34.6% were HIV seropositive. Of persons reporting HIV seropositive status, 58.4% were linked to care, 40.2% were retained in care, 32.2% were adherent to antiretrovirals, and 24.3% were virally suppressed. Any CJI history was associated with the overall care continuum (adjusted odds ratio = 2.35; 95% confidence interval 1.13-4.88) and was most associated with increased retention in care [adjusted odds ratio = 3.72 (1.77-7.84)]. Having one CJI experience and detention for only 1 day was associated with better retention in care compared with no or more frequent CJI. CONCLUSION: Those with a previous history of CJI were more successful in achieving most HIV care continuum metrics. Frequent and cycling CJI, however, was detrimental to HIV care.

Network Characteristics of People Who Inject Drugs Within a New HIV Epidemic Following Austerity in Athens, Greece.

BACKGROUND: Greece experienced an unprecedented increase in HIV cases among drug injectors in 2011 after economic crisis. Network-level factors are increasingly understood to drive HIV transmission in emerging epidemics. METHODS: We examined the relationship between networks, risk behaviors, and HIV serostatus among 1404 people who inject drugs in Athens, Greece. We generated networks using the chain-referral structure within a large HIV screening program. Network proportions, the proportion of a respondent's network with a given characteristic, were calculated. Multiple logistic regression models were used to assess the relationship between network proportions and individual HIV seroprevalence, injection frequency and unprotected sex. RESULTS: Of note, 1030 networks were generated. Respondent HIV seroprevalence was associated with greater proportions of network members who were HIV infected (ie, those with ≥ 50% of network members HIV positive vs. those with no network members HIV positive) (AOR: 3.11; 95% CI: 2.10 to 4.62), divided drugs (AOR: 1.60; 95% CI: 1.10 to 2.35), or injected frequently (AOR: 1.50; 95% CI: 1.02 to 2.21). Homelessness was the only sociodemographic characteristic associated with a risk outcome measure--high-frequency injecting (AOR: 1.41; 95% CI: 1.03 to 1.93). These associations were weaker for more distal second- and third-degree networks and not present when examined within random networks. CONCLUSIONS: Networks are an independently important contributor to the HIV outbreak in Athens, Greece. Network associations were strongest for the immediate network, with residual associations for distal networks. Homelessness was associated with high-frequency injecting. Prevention programs should consider including network-level interventions to prevent future emerging epidemics.

A digital network approach to infer sex behavior in emerging HIV epidemics.

PURPOSE: Improve the ability to infer sex behaviors more accurately using network data. METHODS: A hybrid network analytic approach was utilized to integrate: (1) the plurality of reports from others tied to individual(s) of interest; and (2) structural features of the network generated from those ties. Network data was generated from digitally extracted cell-phone contact lists of a purposeful sample of 241 high-risk men in India. These data were integrated with interview responses to describe the corresponding individuals in the contact lists and the ties between them. HIV serostatus was collected for each respondent and served as an internal validation of the model's predictions of sex behavior. RESULTS: We found that network-based model predictions of sex behavior and self-reported sex behavior had limited correlation (54% agreement). Additionally, when respondent sex behaviors were re-classified to network model predictions from self-reported data, there was a 30.7% decrease in HIV seroprevalence among groups of men with lower risk behavior, which is consistent with HIV transmission biology. CONCLUSION: Combining the relative completeness and objectivity of digital network data with the substantive details of classical interview and HIV biomarker data permitted new analyses and insights into the accuracy of self-reported sex behavior.

Network mixing and network influences most linked to HIV infection and risk behavior in the HIV epidemic among black men who have sex with men.

OBJECTIVES: We evaluated network mixing and influences by network members upon Black men who have sex with men. METHODS: We conducted separate social and sexual network mixing analyses to determine the degree of mixing on risk behaviors (e.g., unprotected anal intercourse [UAI]). We used logistic regression to assess the association between a network "enabler" (would not disapprove of the respondent's behavior) and respondent behavior. RESULTS: Across the sample (n = 1187) network mixing on risk behaviors was more assortative (like with like) in the sexual network (r(sex), 0.37-0.54) than in the social network (r(social), 0.21-0.24). Minimal assortativity (heterogeneous mixing) among HIV-infected men on UAI was evident. Black men who have sex with men reporting a social network enabler were more likely to practice UAI (adjusted odds ratio = 4.06; 95% confidence interval = 1.64, 10.05) a finding not observed in the sexual network (adjusted odds ratio = 1.31; 95% confidence interval = 0.44, 3.91). CONCLUSIONS: Different mixing on risk behavior was evident with more disassortativity among social than sexual networks. Enabling effects of social network members may affect risky behavior. Attention to of high-risk populations' social networks is needed for effective and sustained HIV prevention.

The influence of stress, depression, and anxiety on PSA screening rates in a nationally representative sample.

BACKGROUND: Prostate-specific antigen (PSA) testing for prostate cancer is controversial, with concerning rates of both overscreening and underscreening. The reasons for the observed rates of screening are unknown, and few studies have examined the relationship of psychological health to PSA screening rates. Understanding this relationship can help guide interventions to improve informed decision-making for screening. METHODS: A nationally representative sample of men 57-85 years old without prostate cancer (N = 1169) from the National Social life, Health and Aging Project was analyzed. The independent relationship of validated psychological health scales measuring stress, anxiety, and depression to PSA testing rates was assessed using multivariable logistic regression analyses. RESULTS: PSA screening rates were significantly lower for men with higher perceived stress [odds ratio (OR) = 0.76, P = 0.006], but not for higher depressive symptoms (OR = 0.89, P = 0.22) when accounting for stress. Anxiety influences PSA screening through an interaction with number of doctor visits (P = 0.02). Among the men who visited the doctor once those with higher anxiety were less likely to be screened (OR = 0.65, P = 0.04). Conversely, those who visited the doctor 10+ times with higher anxiety were more likely to be screened (OR = 1.71, P = 0.04). CONCLUSIONS: Perceived stress significantly lowers PSA screening likelihood, and it seems to partly mediate the negative relationship of depression with screening likelihood. Anxiety affects PSA screening rates differently for men with different numbers of doctor visits. Interventions to influence PSA screening rates should recognize the role of the patients' psychological state to improve their likelihood of making informed decisions and improve screening appropriateness.

Deep resequencing of GWAS loci identifies independent rare variants associated with inflammatory bowel disease.

More than 1,000 susceptibility loci have been identified through genome-wide association studies (GWAS) of common variants; however, the specific genes and full allelic spectrum of causal variants underlying these findings have not yet been defined. Here we used pooled next-generation sequencing to study 56 genes from regions associated with Crohn's disease in 350 cases and 350 controls. Through follow-up genotyping of 70 rare and low-frequency protein-altering variants in nine independent case-control series (16,054 Crohn's disease cases, 12,153 ulcerative colitis cases and 17,575 healthy controls), we identified four additional independent risk factors in NOD2, two additional protective variants in IL23R, a highly significant association with a protective splice variant in CARD9 (P < 1 × 10(-16), odds ratio ≈ 0.29) and additional associations with coding variants in IL18RAP, CUL2, C1orf106, PTPN22 and MUC19. We extend the results of successful GWAS by identifying new, rare and probably functional variants that could aid functional experiments and predictive models.

Use of prescription and over-the-counter medications and dietary supplements among older adults in the United States.

CONTEXT: Despite concerns about drug safety, current information on older adults' use of prescription and over-the-counter medications and dietary supplements is limited. OBJECTIVE: To estimate the prevalence and patterns of medication use among older adults (including concurrent use), and potential major drug-drug interactions. DESIGN, SETTING, AND PARTICIPANTS: Three thousand five community-residing individuals, aged 57 through 85 years, were drawn from a cross-sectional, nationally representative probability sample of the United States. In-home interviews, including medication logs, were administered between June 2005 and March 2006. Medication use was defined as prescription, over-the-counter, and dietary supplements used "on a regular schedule, like every day or every week." Concurrent use was defined as the regular use of at least 2 medications. MAIN OUTCOME MEASURE: Population estimates of the prevalence of medication use, concurrent use, and potential major drug-drug interactions, stratified by age group and gender. RESULTS: The unweighted survey response rate was 74.8% (weighted response rate, 75.5%). Eighty-one percent (95% confidence interval [CI], 79.4%-83.5%) used at least 1 prescription medication, 42% (95% CI, 39.7%-44.8%) used at least 1 over-the-counter medication, and 49% (95% CI, 46.2%-52.7%) used a dietary supplement. Twenty-nine percent (95% CI, 26.6%-30.6%) used at least 5 prescription medications concurrently; this was highest among men (37.1%; 95% CI, 31.7%-42.4%) and women (36.0%; 95% CI, 30.2%-41.9%) aged 75 to 85 years. Among prescription medication users, concurrent use of over-the-counter medications was 46% (95% CI, 43.4%-49.1%) and concurrent use of dietary supplements was 52% (95% CI, 48.8%-55.5%). Overall, 4% of individuals were potentially at risk of having a major drug-drug interaction; half of these involved the use of nonprescription medications. These regimens were most prevalent among men in the oldest age group (10%; 95% CI, 6.4%-13.7%) and nearly half involved anticoagulants. No contraindicated concurrent drug use was identified. CONCLUSIONS: In this sample of community-dwelling older adults, prescription and nonprescription medications were commonly used together, with nearly 1 in 25 individuals potentially at risk for a major drug-drug interaction.

Phenotype-stratified genetic linkage study demonstrates that IBD2 is an extensive ulcerative colitis locus.

OBJECTIVES: The complete elucidation of genetic variants that contribute to inflammatory bowel disease (IBD) will likely include variants that increase risk to both Crohn's disease and ulcerative colitis as well as variants that increase risk for particular phenotypic subsets. The purpose of this study was to assess phenotypic subsets that contribute to the major IBD susceptibility loci. METHODS: This linkage study encompassed 904 affected relative pairs, representing the largest combined phenotyped cohort to date, and allowing for meaningful subset analyses. Genetic linkage data were stratified by disease location and age at diagnosis. RESULTS: We establish that some loci, notably the IBD3 and chromosome 3q linkage regions demonstrate contributions from both small intestine and colon cohorts, whereas others, notably the IBD1 (NOD2/CARD15) and IBD2 regions increase risk for small intestine or colon inflammation, respectively. The strongest linkage evidence in this study was for the subset of extensive ulcerative colitis in the region of IBD2 (lod 3.27; p < 0.001). Evidence for linkage in the region of NOD2/CARD15 (IBD1) was stronger for the subset of Crohn's patients with ileal disease (lod 2.56; p= 0.035) compared to the overall Crohn's group, consistent with previous findings that NOD2/CARD15 variants are associated with ileal disease. CONCLUSIONS: Analyses incorporating disease location in IBD increase the power and enhance the accuracy of genomic localization. Our data provide strong evidence that extensive ulcerative colitis represents a pathophysiologic subset of IBD.