SF 36 domains: general health, bodily pain, mental health, physical and social ..... of CT and clinical variables with outcomes in CDAD, a simple, cheap, ...
AGA Abstracts
The following baseline variables were asked in the first survey. Demographic factors included nationality, educational, marital and socioeconomic status. Lifestyle factors assessed included smoking, alcohol intake, body mass index, number of live births and a history of a prolapse repair. The number of stressful life events in the past year was assessed as was depression using the Centre for Epidemiological Studies-Depression scale (CES-D). Domains of quality of life were assessed using the valid SF-36. RESULTS: Of the 3716 women who responded to the first and follow-up survey, we found 1501 (40.3%) developed constipation over the 9 year period. Univariately, we found an increased number of live births, increased number of stressful life events, lower socioeconomic status and reduced functioning in the following SF 36 domains: general health, bodily pain, mental health, physical and social functioning, role emotional and physical and vitality to be significantly associated with new onset constipation. However in a multiple regression model that included these significant variables we found the rate of constipation in those women who have given birth versus those who had not (43% vs 34%; OR= 1.1; 95%CI 1.0-1.1, P=0.003) and reduced functioning on the SF36 subscales for vitality (M=6.4 vs M=6.8; OR=0.9; 95%CI 0.9-1.0, P=0.000) and bodily pain (M=6.8 vs M=7.4; OR=0.9; 95%CI0.9-1.0, P=0.001) were independent risk factors for developing constipation among women who did not report constipation on the first survey. CONCLUSIONS: Constipation is an extremely common problem among older community dwelling women and causes decrement in health related quality of life. Our prospective data suggests factors related to childbirth and generally being unwell as reflected by poor quality of life are risk factors for developing new onset constipation among older women.
Conclusions: CDI incidence is rapidly increasing in the US population. Antibiotic associated CDI risk was highest with linezolid and clindamycin, and lowest with macrolides. Azithromycin conferred no significant risk. Almost half of the cases were unrelated to antibiotic exposure. A search for other potential contributing factors is needed. Sa1979 Proteomic Analyses of Emergent Epidemic-Associated Clostridium difficile Strains Identifies Several Proteins With Likely Roles in Intestinal Colonization and Disease Bryan Roxas, Michael Mallozzi, V.K. Viswanathan, Gayatri Vedantam Introduction and Rationale: Clostridium difficile (CD) causes diarrheic disease in humans and non-human mammals. C. difficile infection (CDI) currently affects >400,000 human patients annually in the USA, with an added burden to the healthcare system of $3 billion. The past decade has seen the emergence of CD hypervirulent “variant” strains that are associated with epidemics, severe disease, increased recurrence rate(s) and community onset of disease. Therefore, there is a renewed sense of urgency to define the virulence traits that underlie the robustness of CD epidemic-associated strains. Study methods: CD is difficult to manipulate genetically; therefore, we employed proteomic analyses to rapidly identify molecules unique to epidemic-associated CD strains. A mass spectrometry-based quantitative proteomics approach was used to identify differentially expressed proteins in BI-1, a nonhypervirulent CD strain, as compared with BI-17, a hypervirulent CD strain, at three different growth phases. Once quantitation parameters were optimized, similar experiments were performed with 13 different epidemic- and non-epidemic associated CD clinical isolates. For all strains, both secreted and total cellular proteomes were analyzed. Results: 2D LC MALDI-TOF/TOF analyses revealed that approximately 550 proteins (~15% of the genome; consistent with other bacteria) were expressed by BI-1 and BI-17 in each growth phase. Further analyses, based on stringent two-fold change cut-off, identified a total of 121 proteins that were differentially abundant between BI-1 and BI-17 across the different growth phases. Consistent with our published studies, hypervirulent strains showed only marginal increases, if at all, in toxin (A & B) levels. In contrast, functional classification analyses revealed that non-toxin CD proteins constituted the most differentially abundant molecules; these included surface proteins, transporters and host innate immunity modulators that likely account for the increased virulence of the hyvpervirulent strains. Similar, and extremely consistent results, were obtained for the other epidemic-associated CD strains tested. Conclusions: Epidemic-associated CD strains have dysregulated expression of multiple colonization-associated proteins. These molecules may be attractive targets for interventions based on preventing GI-tract establishment of this dangerous pathogen.
Sa1976 Higher Than Expected Colonoscopy Utilization in a Geriatric Urban Community Dwelling Population Brijen Shah, Fredda Vladeck, Rebecca Segel, Rosanne Leipzig, Steven H. Itzkowitz Background: Screening colonoscopy rates are approximately 50% nationally, and 63% in New York City. Although colorectal cancer disproportionately affects geriatric aged patients, there can be barriers to colonoscopy that are specific to geriatric patients (difficulty with preps, insufficient social support, etc). Within NYC, there are 43 NORC (naturally occurring retirement communities) programs operating in neighborhoods or housing developments with high concentrations of older adults who have geographic proximity to one another, and these programs provide some case management and health and social support services to the seniors living in the NORCs. This provides the opportunity to study colonoscopy utilization among geriatric populations in the community. Aim: To determine colonoscopy utilization among the geriatric populations living in NORC communities. Methods: A 75-item survey developed by the United Hospital Fund Aging-in-Place Initiative was administered to 5,069 seniors aged 60 and older from 2006-2007. Items included demographic information, colonoscopy and other health related behaviors, and medical history. Results: Of 4,301 respondents age 60-84, who were asked to recall when the last time they had a colonoscopy, 71% had an exam in the last 10 years, 2% had an exam more than 10 years ago, 24% had never had a colonoscopy, and 3% did not know. Several NORCs had rather high rates of colonoscopy (above 80%) whereas others had much lower rates (as low as 38%). Many barriers that would be considered challenges to colonoscopy in the geriatric population such as age, gender, race/ethnicity, country of origin, English fluency, and living arrangement (living alone vs living with others) did not explain differences in who underwent colonoscopy. Conclusions: Many NORCs have higher rates of colonoscopy utilization than even the higherthan-average colonoscopy rates of the general NYC population. However, this high rate is not uniform across all NORCs. It is not known, however, what percentage of these are for screening rather than diagnosis. Curiously, common factors which might affect colonoscopy utilization do not appear to explain the differences in colonoscopy completion. This presents an opportunity to learn which factors (personal, societal) might contribute to colonoscopy use that could then be applied to other (non-NORC) community dwelling older adults eligible for screening colonoscopy.
Sa1980 A Sensitive Stool Diagnostic Assay to Study Enterotoxigenic Bacteroides Fragilis in Inflammatory Bowel Disease and Colitis-Associated Cancer Lea Ann Chen, Hong Yu, Emilia Albesiano, Augusto Franco-Mora, Sankar Chirumamilla, Cynthia L. Sears Bacteroides fragilis is a common colonic commensal of which one subtype, enterotoxigenic Bacteroides fragilis (ETBF), is an established cause of inflammatory diarrhea in humans globally. Recent studies have shown ETBF to cause asymptomatic, chronic colitis in C57BL/ 6 mice and increased colon tumorigenesis in multiple intestinal neoplasia (MinApc/+) mice. Additional studies suggest an association between ETBF infection, active inflammatory bowel disease (IBD), and colon cancer, although only small studies in humans are available. The primary ETBF virulence factor, the metalloprotease B. fragilis toxin (BFT), stimulates 3 key pathophysiologic outcomes: increased intestinal permeability, IL-8 secretion, and intestinal epithelial cell proliferation. Each of these outcomes is consistent with our hypothesis that ETBF colonization may trigger or worsen IBD and possibly initiate/promote colitis-associated cancer. Furthermore, the Bacteroides group has been suggested to contribute to human health, such as T cell development and leanness. Thus, additional studies of Bacteroides spp. and ETBF epidemiology are crucial and require sensitive, specific, and reproducible fecal diagnostic assays. In order to conduct such studies, we developed stool-based diagnostic tests using touch-down PCR and multiplex quantitative PCR approaches. These assays use primers targeted to the 16s regions of Bacteroides group and B. fragilis (including nontoxigenic B. fragilis), as well as to bft (to detect ETBF). The touch-down PCR method can reproducibly detect pure ETBF DNA down to 44 CFU/mL (3.9 fg/μL ETBF DNA). The detection limit is 176 CFU/mL (15.6 fg/μL ETBF DNA) for ETBF spiked into negative human carrier DNA and ≤ 1.4 x 104 CFU/gm stool for ETBF spiked into negative mouse stool. Corresponding studies using Taq-man based qPCR demonstrate similar detection limits. Specificity of both assays was confirmed by testing negative mouse stool DNA extracts. Whereas touch-down PCR can be performed in resource limited settings, such as Bangladesh (where ETBF is endemic), clinical laboratories can employ qPCR to provide more rapid, quantitative results. Studies are in progress to apply these sensitive approaches to human samples with quantification of the relationships of Bacteroides spp., B. fragilis, and ETBF. In the future, these diagnostic assays can be used to study the effect of gut microbiota, particularly ETBF colonization, on the pathogenesis of IBD and colon cancer.
Sa1977 Antibiotic Use and Clostridium difficile Infection in the U.S. - A Populatiuon Based Study Narayan Dharel, Sanjay Ghimire, Rudra Pandey, Shiva Gautam Background and Aims: Clostridium difficile infection (CDI) is an important cause of morbidity and mortality among hospitalized patients particularly among elderly and those who receive antimicrobial therapy. Recently, increased incidences of CDI have been reported in populations previously thought to be at low risk, including healthy persons in the community. However, the status of CDI in the general US population and the associated risk factors are still largely unclear. The aim of this study was to estimate the incidence of CDI in the general US population and the risk associated with exposures to commonly used antibiotics. Methods: We searched claims data of 11.2 million commercially insured US individuals between January 2000 and November 2007. The study was approved by the institutional review board of Beth Israel Deaconess Medical Center. A total of 7,023 incident cases of CDI were identified during the 7.9 years of study period. From this cohort, 3,527 cases, who were enrolled for at least 2 years prior to the onset of CDI, were compared with up to 10 controls matched on sex, age within two years, geographic region, and type of insurer, subscriber status (individual, spouse or dependent), and date of enrollment within one year, in a nested case-control study. Exposure to different antibiotics within the preceding 30, 60, and 90 days was studied using conditional logistic regression analyses. Results: The average incidence of CDI in the US population between 2001 and 2007 was 16.4 cases per 100,000 personyears (7,023 cases/42.8 million person-years). Furthermore, the CDI incidence was found to be increasing exponentially from 0.3 per 100,000 persons-years in 2000 to 39.7 per 100,000 person-years in 2006. Antibiotic use increased the risk of CDI, and the risk increased with the number of antibiotics used (trend p
