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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.

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.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.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).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.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.

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.

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.

ObjectiveYoung 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.MethodsWe 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.ResultsHigher 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.ConclusionsThe 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.

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.

Critical to the development of improved HIV elimination efforts is a greater understanding of how social networks and their dynamics are related to HIV risk and prevention. In this paper, we examine network stability of confidant and sexual networks among young black men who have sex with men (YBMSM). We use data from uConnect (2013–2016), a population-based, longitudinal cohort study. We use an innovative approach to measure both sexual and confidant network stability at three time points, and examine the relationship between each type of stability and HIV risk and prevention behaviors. This approach is consistent with a co-evolutionary perspective in which behavior is not only affected by static properties of an individual's network, but may also be associated with changes in the topology of his or her egocentric network. Our results indicate that although confidant and sexual network stability are moderately correlated, their dynamics are distinct with different predictors and differing associations with behavior. Both types of stability are associated with lower rates of risk behaviors, and both are reduced among those who have spent time in jail. Public health awareness and engagement with both types of networks may provide new opportunities for HIV prevention interventions.

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.

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.

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.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.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.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.

The epidemic increase in diabetes prevalence (primarily type 2) is a public health crisis. We hypothesized that the rates of movement among diabetic states depend in part on one’s social relationships and environment. Using population-based samples from both NSHAP and HRS, collected in 2005–15, we found that having more friends was associated with a lower risk for acquiring diabetes over the next 4-5 years. As an independent replication, separate logistic models for NSHAP and HRS data yielded similar odds-ratios for the protective effect of having friends (OR = 0.82 and 0.92 respectively), adjusting for gender, age, race/ethnicity, and BMI. This effect was concentrated entirely between 0–4 friends; differences in the number of friends above 4 were not associated with differences in diabetes risk.

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 (rsex, 0.37–0.54) than in the social network (rsocial, 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.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access. Protein-truncating variants protective against human disease provide in vivo validation of therapeutic targets. Here we used targeted sequencing to conduct a search for protein-truncating variants conferring protection against inflammatory bowel disease exploiting knowledge of common variants associated with the same disease. Through replication genotyping and imputation we found that a predicted protein-truncating variant (rs36095412, p.R179X, genotyped in 11,148 ulcerative colitis patients and 295,446 controls, MAF=up to 0.78%) in RNF186, a single-exon ring finger E3 ligase with strong colonic expression, protects against ulcerative colitis (overall P=6.89 × 10(-7), odds ratio=0.30). We further demonstrate that the truncated protein exhibits reduced expression and altered subcellular localization, suggesting the protective mechanism may reside in the loss of an interaction or function via mislocalization and/or loss of an essential transmembrane domain. National Institute of Diabetes and Digestive and Kidney Disease (NIDDK) DK064869 DK062432 National Human Genome Research Institute (NHGRI) DK064869 DK043351 HG005923 Crohns and Colitis Foundation 3765 Leona M. & Harry B. Helmsley Charitable Trust 2015PG-IBD001 Amgen 2013583217 CCFA 3765 Cedars-Sinai F. Widjaja Foundation, info:eu-repo/grantAgreement/EC/FP7/305479, European Union DK062413 AI067068 U54DE023789-01 Leona M. and Harry B. Helmsley Charitable Trust Crohn's and Colitis Foundation of America NIH DK062431 U01 DK062429 U01 DK062422 R01 DK092235 U01 DK062420 Medical Research Council, UK MR/J00314X/1 Wellcome Trust WT091310 098051 Inflammatory Bowel Disease Genetic Research Chair at the University of Pittsburgh PO1DK046763

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.

Item does not contain fulltext 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 x 10(-16), odds ratio approximately 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. 01 november 2011

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.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.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; p0.001). 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.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.

We read with interest the recent paper by Plantinga et al showing a role for the threonine to alanine (T300A)-variant of ATG16L1 in regulating the expression of ATG16L1 and cytokine production in response to a NOD2-ligand.1 ATG16L1 , notably T300A (rs2241880) in exon 9, was first implicated in Crohn's disease (CD) susceptibility in a non-synonymous single nucleotide polymorphism (SNP) study, followed by a tagging SNP study and regression analysis.2 These authors were unable to demonstrate differences in ATG16L1 expression based on T300A-genotype or intestinal inflammation. ATG16L1 consists of a N-terminal Atg5-interacting domain, a coiled-coil domain (involved in self-dimerisation, containing the T300A variant) and seven WD-domains (putatively interacting with NOD2) at the C-terminus. In ATG16L1-deficient and hypomorphic mice, canonical and bacteria-induced autophagy, Paneth-cell homeostasis and interleukin-1β secretion were dependent on ATG16L1.3 ,4 By contrast, studies focusing on T300A have shown conflicting results.1 , …

In response to the 1997 Food and Drug Administration Modernization Act (FDAMA), the National Institutes of Health (NIH) established ClinicalTrials.gov, an online, publicly-accessible registry for clinical trials. The 2007 Food and Drug Administration Amendments Act (FDAAA) broadened the scope of eligible trials, added outcomes reporting as a requirement, and established penalties for non-compliance. Although ClinicalTrials.gov increased the transparency with which clinical trials are conducted in the U.S. and opened up new possibilities for research using the information collected, additional resources, time and effort are required to comply with this mandate. This presentation will introduce -ctgov-, a suite of Stata commands to facilitate the reporting of trial results. By using this tool, researchers will be able to generate results for automatic upload to ClinicalTrials.gov at the same time they are doing their primary analyses, thereby eliminating much of the additional effort and ensuring that the results in ClinicalTrials.gov match those in the official publication or report. Although primarily of interest to clinical researchers, biostatisticians and pharmaceutical companies, the approach taken by -ctgov- also has connections to work being done in the area of reproducible research.

To define the prevalence and relative contributions of BRCA1 and BRCA2 mutations among African American families with breast cancer, we analyzed 28 DNA samples from patients identified through two oncology clinics. The entire coding regions of BRCA1 and BRCA2 were screened by protein truncation test, heteroduplex analysis, or single-stranded conformation polymorphism followed by DNA sequencing of variant bands. Deleterious protein-truncating BRCA1 and BRCA2 mutations were identified in five patients or 18% of the entire cohort. Only 8% (1 of 13) of women with a family history of breast cancer, but no ovarian cancer, had mutations. The mutation rates were higher for women from families with a history of breast cancer and at least one ovarian cancer (three of six, 50%). One woman with a family history of undocumented cancers was also found to carry a deleterious mutation in BRCA2. The spectrum of mutations was unique in that one novel BRCA1 mutation (1625del5) and three novel BRCA2 mutations (1536del4, 6696delTC, and 7795delCT) were identified. No recurrent mutations were identified in this cohort, although one BRCA2 (2816insA) mutation had been previously reported. In addition, two BRCA1 and four BRCA2 missense mutations of unknown significance were identified, one of which was novel. Taken together with our previous report on recurrent mutations seen in unrelated families, we conclude that African Americans have a unique mutation spectrum in BRCA1 and BRCA2 genes, but recurrent mutations are likely to be more widely dispersed and therefore not readily identifiable in this population.

Rates of per-capita prescription medication use have increased considerably over the last several decades,1 as have the rates of use of over-the-counter medications2 and dietary supplements.3 Older adults are the largest per capita consumers of prescription medications1 and the most at risk for medication-related adverse events.4 Implementation of the Medicare Part D Prescription Drug Benefit and efforts by Congress and the US Food and Drug Administration to enhance postmarketing surveillance to better safeguard public health5,6 have also focused attention on use of prescription medications among older adults. Despite concerns about drug safety and new federal policies to improve older adults’ access to medications, current information on their concurrent use of prescription medications, over-the-counter medications, and dietary supplements is limited. Most epidemiologic studies examining medication use among older adults are nearly a decade old and aggregate persons 65 years and older.7,8 More than 200 new drugs have come to market in the United States since most of these studies were conducted.9 In addition, many studies use pharmacy claims or aggregate sales data to approximate use of prescription medications, thus measuring prescription acquisition rather than use.10 These data overestimate prescription medication use due to non-adherence,11,12 are limited to patients who purchase at least 1 prescription medication, and almost always exclude nonprescription therapies. This is important because medication use among older adults commonly involves multiple medications and the concurrent use of prescription medications with nonprescription therapies.13,14 The Slone survey,8,15 an annual telephone-based survey of the US population 18 years and older, does provide information regarding the use of prescription and nonprescription medications. However, the most recent Slone survey, conducted in 2006, reports little change in overall medication use since 1998 but does report that the rate of polypharmacy (ie, the use of ≥5 medicines) has increased.15 In the current study, we build on prior reports with a particular focus on older adults. In addition, we consider the potential impact of medication use on clinical outcomes that may result from drug-drug interactions, including interactions between prescription and nonprescription therapies. To do so, we used data from the National Social life, Health and Aging Project (NSHAP), a recent population-based survey of community-dwelling older adults in the United States.

As web-based and other electronic data collection methods become more widely used in research, the opportunities to use statistical software in conjunction with conventional database systems are increasing. Among such systems, MySQL is particularly well suited for research purposes. For example, MySQL's ENUM and SET column types are ideal for storing data collected via the multiple choice questions typically used in social surveys. At the same time, Stata is uniquely suited for working in conjunction with a database; for example, its implementation of characteristics makes it possible to preserve (in a usable form) important information about how the database and front-end application are constructed (e.g., column types and other attributes). In this presentation, we shall describe a Python script we have developed for translating data from MySQL to Stata, and will indicate briefly how we are using it in the development of tools for the collection and management of research data.

Consider a longitudinal study designed to estimate the difference in the rates of change in some outcome between two different groups. In this case, the variance of the estimator depends on several factors, including the variability in the outcome, the amount of missing data due to dropout, the distribution of additional covariates, and the degree and structure of the within-unit correlation across time. Although it is often possible to compute the variance (or an approximation to it) directly from a mathematical formula, this can be unwieldy for those unfamiliar with such computations. In this presentation, I will demonstrate (using real examples) how -xtgee- can be used to compute the variance, from which an estimate of power may be obtained. By creating an appropriate pseudo-dataset, it is possible to specify virtually any covariate distribution and pattern of dropout. In addition, because -xtgee- will accept an arbitrary fixed correlation matrix, it is easy to specify whatever correlation structure is considered most plausible. This method is intuitive, and makes it easy for researchers to explore the effects that changes in their assumptions have on a study's power. A comparison of the results of this method with those generated by other sample size software will also be presented.

A Meta-Analysis of Genome Wide Association Scans Identifies TAGAP and Pus10 as Shared Risk Loci for Crohn's Disease and Celiac Disease Eleonora A. Festen, Philippe Goyette, Todd Green, Claudine Beauchamp, Caroline Lagace, Gabrielle Boucher, Gosia Trynka, Patrick C. Dubois, Pieter Stokkers, Daniel W. Hommes, Donatella Barisani, Orazio Palmieri, Vito Annese, David van Heel, Rinse K. Weersma, Mark J. Daly, Cisca Wijmenga, John D. Rioux

PURPOSE: To prospectively evaluate performance and quality of life (QOL) in advanced-stage head and neck cancer (HNC) patients on a curative-intent, concomitant-chemoradiotherapy (CT/XRT) (twice-daily radiation, fluorouracil, hydroxyurea, and cisplatin) regimen aimed at improving locoregional control, survival, and QOL. PATIENTS AND METHODS: Sixty-four patients were assessed before, during, and at 3-month intervals after treatment. Standardized measures of QOL (Functional Assessment of Cancer Therapy–Head and Neck), performance (Performance Status Scale for Head and Neck Cancer Patients and Karnofsky Performance Status Rating Scale), and patient-reported symptoms (McMaster University Head and Neck Radiotherapy Questionnaire) were administered. RESULTS: Acute treatment toxicities were severe, with declines in virtually all QOL and functional domains. Marked improvement was seen by 12 months; general functional and physical measures returned to baseline levels of good to excellent. Although up to a third of the patients continued to report problems with swallowing, hoarseness, and mouth pain, these difficulties were present in similar magnitudes before treatment. The following symptoms were more frequent at 12 months: dry mouth (58% v 17%), difficulties tasting (32% v 8%), and soft food diet (82% v 42%). Twelve-month diet was not related to pretreatment functioning, disease, treatment, or patient characteristics. Twelve-month QOL was best predicted by pretreatment QOL, with very little relationship to residual side effects or functional impairments. Small numbers of patients in four of the five disease sites precluded examination of outcome by site. CONCLUSION: These data support the feasibility of intense CT/XRT as primary treatment for advanced HNC. Results confirm acute toxicity but indicate that many of the treatment-related performance and QOL declines resolve by 12 months. The persistent inability to eat a full range of foods warrants further attention and monitoring.

CT colonography studies to date have used a standard CT algorithm. To determine whether nonstandard algorithms may result in better performance of CT colonography, we conducted a prospective, blinded-observer study of the effect of the reconstruction algorithm on the conspicuity of colonic polyps and folds.CT colonography of patients with proven polyps, masses, or polypoid folds was performed on an MDCT scanner, and the images were reconstructed using the standard, soft, lung, and detail algorithms. Two experiments were performed. The first used four patient data sets of a short segment of colon (30-60 images), each reconstructed using all four algorithms and then viewed on a workstation in a four-on-one format that allowed all four reconstructions to be viewed simultaneously. The second used six sets of cut-film images (four or eight images each); images within each set differed only in the reconstruction algorithm used to generate them (eight-image sets were prepared with two different level settings). Twenty-one reviewers with varying levels of experience who were unaware of the purpose of the study were asked to rank the images within each set according to their value in the detection of either polyps or masses.Reviewers showed statistically significant differences in preference for the four algorithms (p = 0.037 in the computer-based experiment; for the cut-film experiment, p = 0.029 for the four-image sets and p = 0.041 for the eight-image sets). In the computer-based experiment, reviewers preferred the detail algorithm to the standard algorithm with an estimated probability of 0.67 (95% confidence interval [CI], 0.57-0.75) and the soft algorithm over the standard algorithm with an estimated probability of 0.59 (95% CI, 0.51-0.66). However, reviewers with the most experience (having interpreted at least 250 cases) preferred the soft algorithm over the standard algorithm by the same two-to-one margin as observed for the detail algorithm. In contrast, the standard and detail algorithms were ranked similarly in the cut-film experiment, with the soft and lung algorithms ranked worst.To our knowledge, ours is the first observer study on the effect of the reconstruction algorithm on conspicuity of folds and polyps in CT colonography. Our results indicate significant differences in the reconstruction algorithms, with the soft and detail algorithms being preferred over the standard algorithm by experienced reviewers when interpreting images on a workstation. These results indicate the need for further research into the effect of reconstruction algorithms on CT colonography.