Souradet Y. Shaw

Association Between the Use of Antibiotics in the First Year of Life and Pediatric Inflammatory Bowel Disease

OBJECTIVES:The development of commensal flora in infants has been shown to be sensitive to antibiotic use. Altered intestinal flora is thought to contribute to the etiology of inflammatory bowel disease (IBD), an idiopathic chronic condition. We aimed to determine if early use of antibiotics was associated with the development of IBD in childhood.METHODS:Nested case–control analysis of the population-based University of Manitoba Inflammatory Bowel Disease Epidemiologic Database was carried out. IBD status was determined from a validated administrative database definition. A total of 36 subjects diagnosed between 1996 and 2008 were matched to 360 controls, on the basis of age, sex, and geographic region. Antibiotic data were drawn from the Manitoba Drug Program Information Network, a comprehensive population-based database of all prescription drugs for all Manitobans dating back to 1995. Antibiotic use in the first year of life was compared between IBD cases and controls.RESULTS:The mean age at IBD diagnosis was 8.4 years. Twenty-one cases (58%) had one or more antibiotic dispensations in their first year of life compared with 39% of controls. Crohns disease was diagnosed in 75% of IBD cases. Those receiving one or more dispensations of antibiotics were at 2.9 times the odds (95% confidence interval: 1.2, 7.0) of being an IBD case.CONCLUSIONS:Subjects diagnosed with IBD in childhood are more likely to have used antibiotics in their first year of life.

Association Between the Use of Antibiotics and New Diagnoses of Crohn's Disease and Ulcerative Colitis

OBJECTIVES:The objective of this study was to determine if the use of antibiotics 2–5 years before diagnosis was associated with the development of inflammatory bowel disease (IBD).METHODS:This was a nested case–control analysis of the population-based University of Manitoba Inflammatory Bowel Disease Epidemiologic Database. A total of 2,234 subjects diagnosed with IBD between 2001 and 2008 were matched to 22,346 controls, based on age, sex, and geographic region. Antibiotic data were drawn from the Manitoba Drug Program Information Network, a comprehensive database of all prescription drugs for all Manitobans dating back to 1995.RESULTS:The mean age at diagnosis was 43.4 years. In all, 12% of cases had ≥3 prescriptions 2 years before the case date, compared with 7% of controls. The odds ratio for those receiving ≥3 dispensations 2 years before their study inclusion was 1.5 (95% confidence interval: 1.3,1.8; P<0.0001) of being an IBD case. This difference in ≥3 dispensations between cases and controls was fairly consistent at 3, 4, and 5 years before IBD case date. Antibiotic dispensations were associated with both Crohns disease (CD) and ulcerative colitis (UC), with the association nominally stronger in CD cases for ≥1 and ≥2 dispensations, while the association was stronger in UC cases for ≥3 dispensations. A dose-dependent relationship between the number of antibiotic dispensations, and the risk of IBD was observed across all years investigated.CONCLUSIONS:Subjects diagnosed with IBD were more likely to have been prescribed antibiotics 2–5 years before their diagnosis. This possibly implicates antibiotic use as a predisposing factor in IBD etiology.

Antibiotics Associated With Increased Risk of New-Onset Crohn's Disease But Not Ulcerative Colitis: A Meta-Analysis

OBJECTIVES:The objective of this study was to perform a meta-analysis investigating antibiotic exposure as a risk factor for developing inflammatory bowel disease (IBD).METHODS:A literature search using Medline, Embase, and Cochrane databases was performed to identify studies providing data on the association between antibiotic use and newly diagnosed IBD. Included studies reported Crohn’s disease (CD), ulcerative colitis (UC), or a composite of both (IBD) as the primary outcome and evaluated antibiotic exposure before being diagnosed with IBD. A random-effects meta-analysis was conducted to determine overall pooled estimates and 95% confidence intervals (CIs).RESULTS:A total of 11 observational studies (8 case–control and 3 cohort) including 7,208 patients diagnosed with IBD were analyzed. The pooled odds ratio (OR) for IBD among patients exposed to any antibiotic was 1.57 (95% CI 1.27–1.94). Antibiotic exposure was significantly associated with CD (OR 1.74, 95% CI 1.35–2.23) but was not significant for UC (OR 1.08, 95% CI 0.91–1.27). Exposure to antibiotics most markedly increased the risk of CD in children (OR 2.75, 95% CI 1.72–4.38). All antibiotics were associated with IBD, with the exception of penicillin. Exposure to metronidazole (OR 5.01, 95% CI 1.65–15.25) or fluoroquinolones (OR 1.79, 95% CI 1.03–3.12) was most strongly associated with new-onset IBD.CONCLUSIONS:Exposure to antibiotics appears to increase the odds of being newly diagnosed with CD but not UC. This risk is most marked in children diagnosed with CD.

Outcomes of patients with Crohn's disease improved from 1988 to 2008 and were associated with increased specialist care.

BACKGROUND & AIMS We investigated factors that affect long-term outcomes in Crohns disease (CD). METHODS We performed a retrospective study of 3403 patients with CD, diagnosed between 1988 and 2008 in Manitoba, Canada. Subjects were assigned to cohorts based on diagnosis year: cohort I (before 1996), cohort II (1996-2000), or cohort III (2001 and after). We compared risks for surgery and hospitalization among the cohorts and assessed use of immunomodulators and specialists. RESULTS The 5-year risks of first surgery were 30%, 22%, and 18% for cohorts I, II, and III, respectively. The adjusted hazard ratios for first surgery in cohorts II and III, compared with cohort I, were 0.72 (95% confidence interval [CI], 0.62-0.84) and 0.57 (95% CI, 0.48-0.68), respectively. The adjusted hazard ratio for cohort III, compared with cohort II, was 0.79 (95% CI, 0.65-0.97). There was a higher prevalence of visits to a gastroenterologist within the first year of diagnosis among cohorts II and III (cohort I, 53%; cohort II, 72%; and cohort III, 88%; P<.0001), which was associated with a reduced need for surgery (hazard ratio, 0.83; 95% CI, 0.71-0.98) and contributed to differences in surgery rates among the cohorts. The association between early gastroenterology care and lower risk for surgery was most evident 2 years after diagnosis (hazard ratio, 0.66; 95% CI, 0.53-0.82). Use of immunomodulators within the first year of diagnosis was higher in cohort III than in cohort II (20% vs 11%; P<.0001). CONCLUSIONS Risk of surgery decreased among patients with CD diagnosed after, compared with before, 1996, and was associated with specialist care. Specialist care within 1 year of diagnosis might improve outcomes in CD.

Condom use within non-commercial partnerships of female sex workers in southern India

BackgroundAlthough female sex workers (FSWs) report high levels of condom use with commercial sex clients, particularly after targeted HIV preventive interventions have been implemented, condom use is often low with non-commercial partners. There is limited understanding regarding the factors that influence condom use with FSWs’ non-commercial partners, and of how programs can be designed to increase condom use with these partners. The main objectives of this study were therefore to describe FSWs’ self-reported non-commercial partners, along with interpersonal factors characterizing their non-commercial partnerships, and to examine the factors associated with consistent condom use (CCU) within non-commercial partnerships.MethodsThis study used data collected from cross-sectional questionnaires administered to 988 FSWs in four districts in Karnataka state in 2006-07. We used bivariate and multivariable logistic regression analysis to examine the relationship between CCU (i.e., ‘always’ compared to ‘never’, ‘sometimes’ or ‘frequently’) with non-commercial partners of FSWs (including the respondents’ husband or main cohabiting partner [if not married] and their most recent non-paying partner [who is neither a husband nor the main cohabiting partner, and with whom the FSW had sex within the previous year]) and interpersonal factors describing these partnerships, as well as social and environmental factors. Weighting and survey methods were used to account for the cluster sampling design.ResultsOverall, 511 (51.8%) FSWs reported having a husband or cohabiting partner and 247 (23.7%) reported having a non-paying partner. CCU with these partners was low (22.6% and 40.3% respectively). In multivariable analysis, the odds of CCU with FSWs’ husband or cohabiting partner were 1.8-fold higher for FSWs whose partner knew she was a sex worker (adjusted odds ratio [AOR]: 1.84, 95% confidence intervals[CI]: 1.02-3.32) and almost 6-fold higher if the FSW was unmarried (AOR: 5.73, 95%CI: 2.79-11.76]. CCU with FSWs’ non-paying partner decreased by 18% for each one-year increase in the duration of the relationship (AOR: 0.82, 95%CI: 0.68-0.97).ConclusionsThis study revealed important patterns and interpersonal determinants of condom use within non-commercial partnerships of FSWs. Integrated structural and community-driven HIV/STI prevention programs that focus on gender and reduce sex work stigma should be investigated to increase condom use in non-commercial partnerships.

Using multiple data features improved the validity of osteoporosis case ascertainment from administrative databases

OBJECTIVES The aim was to construct and validate algorithms for osteoporosis case ascertainment from administrative databases and to estimate the population prevalence of osteoporosis for these algorithms. STUDY DESIGN AND SETTING Artificial neural networks, classification trees, and logistic regression were applied to hospital, physician, and pharmacy data from Manitoba, Canada. Discriminative performance and calibration (i.e., error) were compared for algorithms defined from different sets of diagnosis, prescription drug, comorbidity, and demographic variables. Algorithms were validated against a regional bone mineral density testing program. RESULTS Discriminative performance and calibration were poorer and sensitivity was generally lower for algorithms based on diagnosis codes alone than for algorithms based on an expanded set of data features that included osteoporosis prescriptions and age. Validation measures were similar for neural networks and classification trees, but prevalence estimates were lower for the former model. CONCLUSION Multiple features of administrative data generally resulted in improved sensitivity of osteoporosis case-detection algorithm without loss of specificity. However, prevalence estimates using an expanded set of features were still slightly lower than estimates from a population-based study with primary data collection. The classification methods developed in this study can be extended to other chronic diseases for which there may be multiple markers in administrative data.

Prevention of mother-to-child transmission of HIV in Kenya: challenges to implementation.

BackgroundThe prevention of mother-to-child transmission of human immunodeficiency virus (HIV) is lauded as one of the more successful HIV prevention measures. However, despite some gains in the prevention of mother-to-child transmission of HIV (PMTCT) in sub-Saharan Africa, mother-to-child transmission rates are still high. In Kenya, mother-to-child transmission is considered one of the greatest health challenges and scaling up PMTCT services is crucial to its elimination by 2015. However, guideline implementation faces barriers that challenge scale-up of services. The objective of this paper is to identify barriers to PMTCT implementation in the context of a randomized control trial on the use of structured mobile phone messages in PMTCT.MethodsThe preliminary analysis presented here is based on survey data collected during enrolment in PMTCT services at one of two health facilities in Nairobi, Kenya, with overall number of antenatal care (ANC) visits determined from 48 hour follow up data.ResultsData was collected for 503 women. Despite significant differences in the type of facility and sample characteristics between sites, all women presented to care at 20 weeks gestation or later and 88.8% attended less than four ANC visits. PMTCT counselling at first visit had high coverage (86%), however less than a third of women (31.34%) reported receiving contraception counselling. Although 60.8% of women had reportedly disclosed their status to their partners, only 40% were aware of their partner’s status. Very few women had been tested for TB (10%) or received single dose nevirapine during their first antenatal care appointment (20%).ConclusionRevised PMTCT guidelines aim to reduce the inequity between PMTCT services in high and low resource settings in efforts to eliminate mother-to-child transmission. However, guideline implementation in low resource settings continues to be confronted with challenges related to late presentation, less than four ANC visits, low screening rates for opportunistic infections, and limited contraception counselling. These challenges are further complicated by lack of disclosure to partners. Effective scale up and implementation of PMTCT services requires that such ongoing program challenges be identified and appropriately addressed within the local context.RésuméContexteLa prévention de la transmission du virus de l’immunodéficience humaine (VIH) de la mère à l’enfant est reconnue comme l’une des méthodes de prévention du VIH les plus efficaces. Cependant, bien que l’on ait réalisé certains gains au chapitre de la prévention de la transmission du VIH de la mère à l’enfant (PTME) en Afrique subsaharienne, les taux de transmission de la mère à l’enfant demeurent élevés. Au Kenya, la transmission de la mère à l’enfant est considérée comme l’un des plus grands problèmes de santé, et il est crucial de faire passer à grande échelle les services de PTME si l’on veut arriver à éliminer la transmission d’ici 2015. Toutefois, la mise en oeuvre de lignes directrices est entravée par des obstacles qui freinent le passage à grande échelle des services. L’objectif du présent article est de présenter les facteurs qui font obstacle à la mise en oeuvre de la PTME dans le contexte d’un essai comparatif avec répartition aléatoire sur l’utilisation d’un système de messages uniformisés pour la PTME.MéthodesL’analyse préliminaire présentée ici s’appuie sur des données d’enquête recueillies durant l’inscription aux services de PTME à l’un de deux établissements de santé de Nairobi, au Kenya, où le nombre de visites en soins prénataux. Les données de suivi recueillies dans les 48 heures ont permis de déterminer le nombre de visites en soins prénataux.RésultatsLes données recueillies portaient sur 503 femmes. Si les deux établissements étaient très différents et que les caractéristiques de l’échantillon variaient beaucoup d’un établissement à l’autre, toutes les femmes se sont présentées à 20 semaines de gestation ou plus tard, et 88,8 % d’entre elles se sont présentées à moins de quatre visites en soins prénataux. Bien que 86 % des femmes aient reçu des services de counselling en PTME, moins du tiers (31,4 %) ont indiqué avoir reçu des conseils sur la contraception. De plus, tandis que 60,8 % des femmes ont dit avoir révélé leur statut sérologique à leur partenaire, seulement 40 % d’entre elles connaissaient celui de leur partenaire. Très peu de femmes avaient subi un test de dépistage de la tuberculose (10 %) ou reçu une dose unique de névirapine à l’occasion de leur premier rendez-vous en soins prénataux (20 %).ConclusionLes lignes directrices en matière de PTME visent à réduire l’écart en matière de services de PTME entre les milieux favorisés et les milieux démunis afin d’éliminer la transmission de la mère à l’enfant. Cependant, la mise en oeuvre de ces lignes directrices dans les milieux défavorisés continue d’être entravée par des obstacles reliés aux premiers rendez-vous tardifs, au nombre limité de visites (moins de quatre), aux faibles taux de dépistage des infections opportunistes et au manque de services de counselling en contraception. Le fait que certaines femmes ignorent le statut sérologique de leur partenaire ne fait qu’aggraver ces problèmes. Le passage à grande échelle et la mise en oeuvre des services de PTME exigent que ces problèmes récurrents soient ciblés et abordés adéquatement en fonction du contexte local.

Factors Associated with Sexual Violence against Men Who Have Sex with Men and Transgendered Individuals in Karnataka, India

Objectives There is a lack of information on sexual violence (SV) among men who have sex with men and transgendered individuals (MSM-T) in southern India. As SV has been associated with HIV vulnerability, this study examined health related behaviours and practices associated with SV among MSM-T. Design Data were from cross-sectional surveys from four districts in Karnataka, India. Methods Multivariable logistic regression models were constructed to examine factors related to SV. Multivariable negative binomial regression models examined the association between physician visits and SV. Results A total of 543 MSM-T were included in the study. Prevalence of SV was 18% in the past year. HIV prevalence among those reporting SV was 20%, compared to 12% among those not reporting SV (p = .104). In multivariable models, and among sex workers, those reporting SV were more likely to report anal sex with 5+ casual sex partners in the past week (AOR: 4.1; 95%CI: 1.2–14.3, p = .029). Increased physician visits among those reporting SV was reported only for those involved in sex work (ARR: 1.7; 95%CI: 1.1–2.7, p = .012). Conclusions These results demonstrate high levels of SV among MSM-T populations, highlighting the importance of integrating interventions to reduce violence as part of HIV prevention programs and health services.

Identifying Heterogeneity Among Injection Drug Users : A Cluster Analysis Approach

OBJECTIVES We used cluster analysis to subdivide a population of injection drug users and identify previously unknown behavioral heterogeneity within that population. METHODS We applied cluster analysis techniques to data collected in a cross-sectional survey of injection drug users in Winnipeg, Manitoba. The clustering variables we used were based on receptive syringe sharing, ethnicity, and types of drugs injected. RESULTS Seven clusters were identified for both male and female injection drug users. Some relationships previously revealed in our study setting, such as the known relationship between Talwin (pentazocine) and Ritalin (methylphenidate) use, injection in hotels, and hepatitis C virus prevalence, were confirmed through our cluster analysis approach. Also, relationships between drug use and infection risk not previously observed in our study setting were identified, an example being a cluster of female crystal methamphetamine users who exhibited high-risk behaviors but an absence or low prevalence of blood-borne pathogens. CONCLUSIONS Cluster analysis was useful in both confirming relationships previously identified and identifying new ones relevant to public health research and interventions.

Molecular Signatures of Immune Activation and Epithelial Barrier Remodeling Are Enhanced during the Luteal Phase of the Menstrual Cycle: Implications for HIV Susceptibility

ABSTRACT The variable infectivity and transmissibility of HIV/SHIV has been recently associated with the menstrual cycle, with particular susceptibility observed during the luteal phase in nonhuman primate models and ex vivo human explant cultures, but the mechanism is poorly understood. Here, we performed an unbiased, mass spectrometry-based proteomic analysis to better understand the mucosal immunological processes underpinning this observed susceptibility to HIV infection. Cervicovaginal lavage samples (n = 19) were collected, characterized as follicular or luteal phase using days since last menstrual period, and analyzed by tandem mass spectrometry. Biological insights from these data were gained using a spectrum of computational methods, including hierarchical clustering, pathway analysis, gene set enrichment analysis, and partial least-squares discriminant analysis with LASSO feature selection. Of the 384 proteins identified, 43 were differentially abundant between phases (P < 0.05, ≥2-fold change). Cell-cell adhesion proteins and antiproteases were reduced, and leukocyte recruitment (interleukin-8 pathway, P = 1.41E–5) and extravasation proteins (P = 5.62E–4) were elevated during the luteal phase. LASSO/PLSDA identified a minimal profile of 18 proteins that best distinguished the luteal phase. This profile included cytoskeletal elements and proteases known to be involved in cellular movement. Gene set enrichment analysis associated CD4+ T cell and neutrophil gene set signatures with the luteal phase (P < 0.05). Taken together, our findings indicate a strong association between proteins involved in tissue remodeling and leukocyte infiltration with the luteal phase, which may represent potential hormone-associated mechanisms of increased susceptibility to HIV. IMPORTANCE Recent studies have discovered an enhanced susceptibility to HIV infection during the progesterone-dominant luteal phase of the menstrual cycle. However, the mechanism responsible for this enhanced susceptibility has not yet been determined. Understanding the source of this vulnerability will be important for designing efficacious HIV prevention technologies for women. Furthermore, these findings may also be extrapolated to better understand the impact of exogenous hormone application, such as the use of hormonal contraceptives, on HIV acquisition risk. Hormonal contraceptives are the most widely used contraceptive method in sub-Saharan Africa, the most HIV-burdened area of the world. For this reason, research conducted to better understand how hormones impact host immunity and susceptibility factors important for HIV infection is a global health priority.