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Boursi B.,University of Pennsylvania | Boursi B.,Integrated Cancer Prevention Center | Boursi B.,Tel Aviv University | Mamtani R.,University of Pennsylvania | And 2 more authors.
European Journal of Endocrinology | Year: 2015

Objective: Gut microbiota influence metabolic pathways related to the pathogenesis of obesity, insulin-resistance and diabetes. Antibiotic therapy can alter the microbiota, and is commonly used in western countries. We sought to evaluate whether past antibiotic exposure increases diabetes risk. Research design and methods: We conducted a nested case-control study using a large population-based database from the UK. The cases were defined as those with incident diagnosis of diabetes. For every case, four eligible controls matched on age, sex, practice-site, and duration of follow-up before index-date were selected using incidence-density sampling. Exposure of interest was antibiotic therapy O1 year before index-date. Odds ratios (ORs) and 95% CIs were estimated using conditional logistic regression. The risk was adjusted for BMI, smoking, last glucose level, and number of infections before index-date, as well as past medical history of coronary artery disease and hyperlipidaemia. Results: The study included 208 002 diabetic cases and 815 576 matched controls. Exposure to a single antibiotic prescription was not associated with higher adjusted diabetes risk. Treatment with two to five antibiotic courses was associated with increase in diabetic risk for penicillin, cephalosporins, macrolides and quinolones with adjusted OR ranging from 1.08 (95% CI 1.05-1.11) for penicillin to 1.15 (95% CI 1.08-1.23) for quinolones. The risk increased with the number of antibiotic courses and reached 1.37 (95% CI 1.19-1.58) for more than 5 courses of quinolones. There was no association between exposure to anti-virals and anti-fungals and diabetes risk. Conclusions: Exposure to certain antibiotic groups increases diabetes risk. © 2015 European Society of Endocrinology. Source


Lurie I.,Tel Aviv University | Lurie I.,Shalvata Mental Health Center | Yang Y.-X.,University of Pennsylvania | Yang Y.-X.,Center for Clinical Epidemiology and Biostatistics | And 7 more authors.
Journal of Clinical Psychiatry | Year: 2015

Objective: Changes in the microbiota (dysbiosis) were suggested to increase the risk of several psychiatric conditions through neurologic, metabolic, and immunologic pathways. Our aim was to assess whether exposure to specific antibiotic groups increases the risk for depression, anxiety, or psychosis. Method: We conducted 3 nested case-control studies during the years 1995-2013 using a large population-based medical record database from the United Kingdom. The study included 202,974 patients with depression, 14,570 with anxiety, and 2,690 with psychosis and 803,961, 57,862, and 10,644 matched controls, respectively. Cases were defined as individuals aged 15-65 years with any medical Read code for depression, anxiety, or psychosis. Subjects with diagnosis-specific psychotropic prescriptions > 90 days before index date were excluded. For every case, 4 controls were selected using incidence density sampling, matching on age, sex, practice site, calendar time, and duration of follow-up before index date. The primary exposure of interest was therapy with 1 of 7 antibiotic classes > 1 year before index date. Odds ratios (ORs) and 95% CIs were calculated for the association between each psychiatric disorder and exposure to individual classes of antibiotics using conditional logistic regression analysis. The risk was adjusted for obesity, smoking history, alcohol consumption, socioeconomic status, and number of infectious events before diagnosis. Results: Treatment with a single antibiotic course was associated with higher risk for depression with all antibiotic groups, with an adjusted OR (AOR) of 1.23 for penicillins (95% CI, 1.18-1.29) and 1.25 (95% CI, 1.15-1.35) for quinolones. The risk increased with recurrent antibiotic exposures to 1.40 (95% CI, 1.35-1.46) and 1.56 (95% CI, 1.46-1.65) for 2-5 and > 5 courses of penicillin, respectively. Similar association was observed for anxiety and was most prominent with exposures to penicillins and sulfonamides, with an AOR of 1.17 (95% CI, 1.01-1.36) for a single course of penicillin and 1.44 (95% CI, 1.18-1.75) for > 5 courses. There was no change in risk for psychosis with any antibiotic group. There was a mild increase in the risk of depression and anxiety with a single course of antifungals; however, there was no increase in risk with repeated exposures. Conclusion: Recurrent antibiotic exposure is associated with increased risk for depression and anxiety but not for psychosis. © 2015 Physicians Postgraduate Press, Inc. Source


Boursi B.,Center for Clinical Epidemiology and Biostatistics | Boursi B.,University of Pennsylvania | Boursi B.,Integrated Cancer Prevention Center | Boursi B.,Tel Aviv University | And 5 more authors.
European Journal of Gastroenterology and Hepatology | Year: 2014

Background Previous studies have shown an association between height and colorectal cancer (CRC). None of those studies adjusted the association for known risk factors, such as diabetes mellitus and chronic exposure to aspirin/ NSAIDs. Only two studies evaluated the risk among male individuals. Methods We conducted a nested case-control study using a large population-based medical record database from the UK. Studied cases had any CRC code after the age of 40 years. Participants with a known family history of CRC syndromes or inflammatory bowel disease were excluded from the study. For every case, up to four eligible controls matched for age, sex, practice site, and duration of follow-up before the index date were selected by incidence-density sampling. Height was defined as the last measurement before the index date. The odds ratios (ORs) and 95% confidence intervals (CIs) for CRC were calculated for height quartiles, as well as for every 10-cm increase in height, using conditional logistic regression analysis, and adjusted for potential confounders. Results A total of 9978 cases and 26 847 controls were identified. The adjusted OR for CRC in the participants at the highest compared with the lowest height quartiles was 1.25 for male (95% CI 1.14-1.37) and 1.25 for female (95% CI 1.12-1.39) individuals. The adjusted OR associated with each 10-cm increase in height was 1.10 (95% CI 1.05-1.15) for male and 1.16 (95% CI 1.10-1.23) for female individuals. The risk remained persistent when analyzing different age groups. Conclusion Height is an independent risk factor for CRC in both male and female individuals. © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins. Source


Boursi B.,University of Pennsylvania | Boursi B.,Integrated Cancer Prevention Center | Haynes K.,University of Pennsylvania | Mamtani R.,University of Pennsylvania | Yang Y.-X.,University of Pennsylvania
Journal of the National Cancer Institute | Year: 2015

Background: Current screening guidelines for colorectal cancer (CRC) do not consider thyroid dysfunction as a risk factor for disease development. We sought to determine the risk of developing CRC in patients with thyroid dysfunction, with and without thyroid hormone replacement (THR). Methods: We conducted a nested case-control study using a large population-based medical records database from the United Kingdom. Study case patients were defined as those with any medical code of CRC. Subjects with familial colorectal cancer syndromes or inflammatory bowel disease (IBD) were excluded. For every case patient, four eligible control patients matched on age, sex, practice site, and duration of follow-up before index date were selected using incidence density sampling. Exposure was THR therapy before index date. We further divided the THR unexposed group into patients with hypothyroidism (TSH > 4mg/dl), patients with hyperthyroidism (TSH < 0.4mg/dl), and subjects without documented thyroid abnormality. The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for CRC were estimated using conditional logistic regression. All statistical tests were two-sided. Results: We identified 20990 CRC patients and 82054 control patients. The adjusted odds ratio for CRC associated with THR was 0.88 (95% CI = 0.79 to 0.99, P =. 03) and 0.68 (95% CI = 0.55 to 0.83, P <. 001) for treatment initiated five to 10 years and more than 10 years before index date, respectively. This protective association increased with cumulative duration of therapy. In contrast, hyperthyroidism (adjusted OR = 1.21, 95% CI = 1.08 to 1.36, P =. 001) or untreated hypothyroidism (adjusted OR = 1.16, 95% CI = 1.08 to 1.24, P <. 001) were associated with increased risk of CRC. Conclusion: Long-term THR is associated with a decreased risk of CRC. Hyperthyroidism and untreated hypothyroidism are associated with modestly elevated risk of CRC. © 2015 The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com. Source


Hahn E.,University of Toronto | Kraus S.,Integrated Cancer Prevention Center | Kraus S.,Tel Aviv University | Arber N.,Integrated Cancer Prevention Center | Arber N.,Tel Aviv University
Digestive Diseases | Year: 2010

Chemoprevention of colorectal cancer is a promising science that has particular importance due to the limited success of current treatments for most advanced common malignancies. Many chemopreventive agents have been studied including cyclooxygenase (COX) inhibitors. Two isoforms of the COX enzymes are COX-1 and COX-2. COX-1 is constitutively expressed in normal tissue, serving an important role in tissue homeostasis, whereas COX-2 is an inducible enzyme, which is markedly overexpressed at sites of inflammation and colorectal neoplasms. The preventive efficacy of traditional nonsteroidal anti-inflammatory drugs (NSAIDs), which inhibit COX-1 and/or COX-2, has considerable support from animal and epidemiological studies; however, there are well-documented toxicities associated with NSAID use. These adverse effects are attributed to NSAIDs' inhibition of COX-1. The development of COX-2 specific inhibitors gave hopes of bypassing the associated traditional NSAID toxicities while better targeting tissues sustaining inflammation and neoplasia. The PrsSAP, APC and APPROVe trials demonstrated the efficacy of COX-2 specific inhibitors in preventing the recurrence of sporadic colorectal polyps. However, the trials were terminated early due to discovery of significant cardiovascular toxicity, although the exact extent of this toxicity remains unclear. The exact mechanisms through which NSAIDs exert their cancer preventing effects are currently unknown; inhibition of COX-2 is of great importance, but COX-2 independent pathways exist as well. In addition, the efficacy of NSAID use for cancer prevention can differ significantly between individuals. Personalized medicine in this field is also greatly anticipated. Combination therapy is under extensive research in order to improve efficacy while reducing toxicity profiles. Chemoprevention of colorectal cancer is largely possible, but the ultimate drug and proper patient selection, among other elements of the cancer prevention equation, are still needed. © 2010 S. Karger AG, Basel. Source

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