Proton pump inhibitors and the risk of colorectal cancer

INTRODUCTION: Proton pump inhibitor (PPI) use is associated with increased serum gastrin levels and bacterial overgrowth, resulting in more toxic bile salt formation. Concern has risen that these factors may increase the risk of developing colorectal neoplasia. AIM: To investigate the association between the use of PPIs and the risk of colorectal cancer. METHODS: A population-based case-control study was conducted within the Dutch Primary Care Information (IPCI) database over the period 1996-2005. Cases with colorectal cancer were matched with up to 20 controls on age, gender, calendar time, and duration of follow-up prior to diagnosis. Cumulative exposure to PPIs was assessed in the 5 yr prior to diagnosis with a 1-yr lag time analysis. We calculated adjusted odds ratios (OR) with 95% confidence intervals (95% CI) using multivariate, conditional logistic regression analysis. RESULTS: Within the source population of 457,024 persons, we identified 595 colorectal cancer cases. The odds of colorectal cancer were not increased among patients ever using PPIs compared with patients who never used PPIs (OR 0.85, 95% CI 0.63-1.16). Also, the use of PPIs for > 365 days was not associated with a greater risk of colorectal cancer (OR 0.79, 95% CI 0.44-1.41) compared with nonusers. The odds of colorectal cancer in neither the right nor the left hemicolon were significantly increased in patients using PPIs. CONCLUSION: The present study indicates no association between PPI use and the risk of colorectal cancer. Larger numbers of long-term PPI users are needed to confirm the absence of a risk-increasing effect of long-term PPI exposur

Adherence to Gastroprotective Agents and the Risk of Upper Gastrointestinal Complications in Coxib Users

Thionyl chloride (SOCl2) acts as halogenation reagent in its reaction with 1-[phenyl(hydroxy)methyl]-2-R-1,2-dicarba-closo-dodecaborane 1a,b but unexpectedly behaves as an oxidant for 1-[2'-pyridyl(hydroxy)methyl]-2-R-1,2-dicarba-closo-dodecaboranes 2a,b. The synthesis and characterization of all new compounds, including structure determinations of 1a, 2a, 1-[phenyl(chloro)methyl]-2-methyl-1,2-dicarba-closo-dodecaborane 3a, and 1-[2'-pyridyl(oxo)methyl]-2-methyl- 1,2-dicarba-closo-dodecaboranes 4a are reported and the possible pathways are discussed

Risk of cardiac valve regurgitation with dopamine agonist use in Parkinson's disease and hyperprolactinaemia: a multi-country, nested case-control study

Background: There is growing evidence that ergot dopamine agonists may induce cardiac valve regurgitation (CVR) in persons with Parkinson's disease. It is unclear whether the CVR risk is increased with ergot-dopamine agonist use in persons with hyperprolactinaemia, in whom the dose is much lower. Objective: The aim of the study was to explore the association between different dopamine agonists and CVR in patients with Parkinson's disease or hyperprolactinaemia. Design: Nested case-control studies conducted separately in cohorts of Parkinson's disease and hyperprolactinaemia patients. Cases were patients who developed newly diagnosed CVR. Controls were CVR-free patients from the same cohorts and were matched to cases by age, sex, database and calendar year. Setting and Patients: Study patients were identified from over 4.5 million persons in The Health Improvement Network (THIN; UK), Health Search (Italy), and Integrated Primary Care Information (IPCI; the Netherlands) general practice databases in the years 1996-2007. The Parkinson's disease cohort included new users of dopamine agonists or levodopa, while the hyperprolactinaemia cohort included new users or non-users of dopamine agonists. Main Outcome Measure: Risk of newly diagnosed CVR with dopamine agonist use compared with levodopa use in the Parkinson's disease cohort, and dopamine agonist-naive patients in the hyperprolactinaemia cohort. Results: In the Parkinson's disease cohort (7893 dopamine agonist users, 11 766 levodopa users), 85 incident CVR cases were identified. Increased CVR risk was observed for ergot dopamine agonists (adjusted OR [ORadj] 3.82; 95% CI 2.14, 6.81), but not for non-ergot dopamine agonists (ORadj 1.20; 95% CI 0.63, 2.29). In the hyperprolactinaemia cohort (6740 dopamine agonist users and 14 299 dopamine agonist-naive patients), 37 CVR cases were identified during a mean follow-up of 4.5 years and 3.5 years for new users and non-users of dopamine agonists, respectively. However, no association with ever use of ergot dopamine agonists was observed (ORadj 0.47; 95% CI 0.20, 1.19). Conclusion: Ergot-derived dopamine agonists are associated with an increased risk of CVR in Parkinson's disease but not in hyperprolactinaemia patients