Early Discontinuation of Metformin in Individuals Treated with Inhibitors of Transporters of Metformin

The aim of this study was to examine the risk of early discontinuation of metformin as a proxy for intolerance, associated with use of drugs known to inhibit transporters involved in metformin distribution. We analysed all incident users of metformin in Denmark between 2000 and 2012 (n = 132,221) and in a cohort of US patients (n = 296,903). Risk of early discontinuation of metformin was assessed using adjusted logistic regression for 28 drugs putatively inhibiting metformin transporters and four negative controls. Increased odds ratio of early discontinuation of metformin was only associated with codeine, an inhibitor of organic cation transporter 1 in both cohorts [adjusted odds ratio (OR) in Danish cohort (95% CI): 1.13 (1.02–1.26), adjusted OR in American cohort (95% CI): 1.32 (1.19–1.47)]. The remaining drugs were not associated with increased odds ratio of early discontinuation and, surprisingly, four drugs were associated with a decreased risk. These findings indicate that codeine use may be associated with risk of early discontinuation of metformin and could be used as a basis for further investigation.     

Smokeless tobacco use among United States Air Force trainees

Background: The prevalence of smokeless tobacco use in the United States Air Force (USAF) exceeds civilian use rates. The prevalence and correlates of smokeless tobacco use were assessed and evaluated in a sample of USAF trainees. Methods: We conducted a cross-sectional survey of USAF technical training school personnel at Joint Base San Antonio-Lackland and Fort Sam Houston (N = 14,810). Survey completion rate was 78%. Logistic regression was used to analyze the associations between demographic variables, tobacco use, and social factors for both regular and infrequent smokeless tobacco (e.g., chewing tobacco, snuff) users. Results: Overall, 16% of Airmen had ever used smokeless tobacco and 10% regularly used smokeless tobacco. In multivariate analyses, men had greater odds than women of regular smokeless tobacco use (adjusted odds ratio [OR] = 15.2; 95% confidence interval [CI]: 10.8–21.5) and infrequent smokeless tobacco use (adjusted OR = 4.2; 95% CI: 3.1–5.7). Smokeless tobacco use was associated with participation in high school sports (adjusted OR = 1.9; 95% CI: 1.6–2.3 for regular users; adjusted OR = 1.4; 95% CI: 1.1–1.7 for infrequent users), smoking cigarettes (adjusted OR = 4.3; 95% CI: 3.6–5.1 for regular users; adjusted OR = 4.0; 95% CI: 3.2–5.0 for infrequent users), or living with someone who used smokeless tobacco (adjusted OR = 2.2; 95% CI: 1.9–2.6 for regular users; adjusted OR = 1.4; 95% CI: 1.1–1.7 for infrequent users). Black or African Americans were less likely than whites to be regular (adjusted OR = 0.3; 95% CI: 0.1–0.4) or infrequent (adjusted OR = 0.3; 95% CI: 0.2–0.4) users of smokeless tobacco. Conclusions: Smokeless tobacco use among incoming Air Force recruits is common and negatively impacts the Air Force's goal to be tobacco-free. Understanding sociodemographic characteristics perpetuating smokeless tobacco use in the Air Force population can inform the development of health promotion interventions.     

Initial non-compliance with antihypertensive monotherapy is followed by complete discontinuation of antihypertensive therapy

PURPOSE: Discontinuation with treatment is a major problem in the treatment of hypertension. The objective of our study was to assess the association between non-compliance and discontinuation in patients who started using antihypertensive monotherapy. METHODS: A nested case-control study within a cohort of new users of antihypertensive drugs between 1st January 1999 and 31st December 2002 was performed. We used data from the PHARMO database, a record linkage system containing drug-dispensing records from community pharmacies and linked hospital discharge records of approximately 950,000 subjects. Cases discontinued their use of antihypertensive monotherapy and were not switched to other antihypertensive treatment, controls stayed on their initially prescribed monotherapy. Conditional logistic regression was used to calculate odds ratios (OR) and their 95% confidence intervals (CI). RESULTS: In a cohort of 39,714 new users of antihypertensive drugs, we identified 9111 cases and 9111 matched controls. The percentage of non-compliant patients (compliance < 80%) among cases and controls was 14.0% and 5.8%, respectively [OR 2.86 (95%CI: 2.52-3.24)]. Patients who used less than 90 days had a higher risk on discontinuation [OR 3.10 (95%CI: 2.67-3.59)] than patients who used more than 90 days [OR 2.28 (95%CI: 1.79-2.92)]. The association was generally similar among males and females, among the different types of antihypertensives and among the different age groups. CONCLUSION: In patients who start antihypertensive monotherapy, non-compliance is often followed by discontinuation of this antihypertensive treatment. The pharmacy medication history is a valuable tool for physicians to identify patients who have a high risk on discontinuation with antihypertensive treatment.     

Risk of upper gastrointestinal bleeding with oral bisphosphonates and non steroidal anti-inflammatory drugs: a case-control study

Background Gastrointestinal injuries including gastric ulcers have been reported with oral bisphosphonate therapy. However, the risk of the more serious upper gastrointestinal bleeding (UGB) especially in the community setting with these drugs remains unknown. Similarly, the risk of UGB among users of both bisphosphonates and non steroidal anti‐inflammatory drugs (NSAIDs) in the community is also unknown. Aim To explore the risk of more serious UGB among users of bisphosphonates and the risk of UGB among users of both bisphosphonates and NSAIDs in the community. Methods We conducted a case‐control study within a cohort of Quebec residents who had received a revascularization procedure from 1995 to 2004. Cohort members were followed up from the date of their first procedure until the earliest of: (1) study outcome, (2) date of death or (3) end of health care coverage. Cases were defined as those with the first diagnosis of a UGB. For each case, 20 controls were selected and matched to the cases by index date, age and cohort entry. Adjusted odds ratios for current use of bisphosphonates, NSAIDs and co‐therapy of both drugs were computed. Results Within the initial cohort, 3253 incident cases of UGBs and corresponding 65 060 matched controls were identified. The adjusted odds ratio (OR) for UGB by current users of bisphosphonates was 1.01 (95% CI, 0.72–1.43). Current NSAID use was associated with an increased risk of UGB OR = 1.75; 95% CI, 1.53–1.99. The OR for use of bisphosphonates and NSAIDs was elevated OR = 2.00; 95% CI, 1.12–3.57. This risk was still elevated for users of bisphosphonates and COX‐2 inhibitors [OR = 2.38 (95% CI, 1.26–4.50)]. Conclusion We found no evidence of an increase in the risk of UGB among current users of bisphosphonates. The risk of combined NSAID and bisphosphonate therapy was increased, but this risk was not higher than the risk for NSAID users alone.     

The impact of infliximab infusion reactions on long-term outcomes in patients with Crohn's disease

Background Little is known about long‐term outcomes in patients who experience infusion reactions while receiving infliximab. Aim To investigate long‐term outcomes in patients who experience infusion reactions while receiving infliximab. Methods Retrospective electronic chart review of long‐term clinical outcomes. Results Clinical data on 287 patients who received infliximab infusions for Crohn’s disease were reviewed, of whom 51 developed at least one infusion reaction (18%). Ileo‐colonic disease (OR 2.2, 95% CI 1.1–4.4) and episodic infliximab (OR 2.4, 95% CI 1.2–4.7) were associated with a higher risk of infusion reactions in univariate analysis, but concomitant azathioprine/mercaptopurine therapy at the initiation of infliximab was associated with a reduced risk (OR 0.4, 95% CI 0.2–0.8). Only the effect of concomitant immunomodulators persisted on multivariate analysis. Patients who experienced infusion reactions were less likely to be in remission at 1 year (OR 0.6, 95% CI 0.3–1.2), 2 years (OR 0.4, 95% CI 0.2–0.8, P = 0.01), or 5 years (OR 0.4, 95% CI 0.1–1.3) and more likely to require surgery (OR 2.2, 95% CI 1.1–4.1, P = 0.01) than those who did not experience such reactions. Conclusions Patients who experienced infusion reactions to infliximab had a high rate of discontinuation of therapy in this cohort. Concomitant immunomodulators and maintenance therapy reduced the risk of infusion reactions.     

Use of beta-2 agonists and risk of hip/femur fracture: a population-based case-control study

INTRODUCTION: Administration of beta-2 agonists decreased bone mineral density in rats. But the association between bronchodilators and fracture risk has not been studied in humans. OBJECTIVES: To examine the association between use of beta-2 agonists and risk of hip/femur fracture. METHODS: We conducted a population-based case-control study (6763 cases) in the Dutch PHARMO database. Current beta-2 agonist use was compared to never use. We adjusted for severity of the underlying respiratory disease and disease and drug history. RESULTS: A hospitalisation for asthma/COPD in the year before index date increased risk of hip/femur fracture: crude OR 2.17 (95% CI, 1.41-3.34). Patients using higher doses of beta-2 agonists had increased risk of hip/femur fracture: crude OR 1.94 (95% CI, 1.41-2.66) for daily dosages of >or=1600 microg albuterol equivalent. The excess fracture risk reduced after adjustment for disease severity (1.46; 95% CI, 1.02-2.08) and after exclusion of oral glucocorticoid users (1.31; 95% CI, 0.80-2.15). Risk of hip/femur fracture was similar between users of beta-2 agonists, inhaled glucocorticoids and anticholinergics. CONCLUSION: We found increases in the risk of hip/femur fracture in patients using higher doses of beta-2 agonists. However, the excess risk of hip/femur fracture substantially reduced after exclusion of oral glucocorticoid users and after adjustment for the underlying disease. Risk of hip/femur fracture was similar between users of beta-2 agonists, inhaled glucocorticoids and anticholinergics. The severity of the underlying disease, rather than the use of beta-2 agonists, may play an important role in the aetiology of hip/femur fractures in patients using beta-2 agonists.     

Benzodiazepine therapy in psychiatric outpatients is associated with deliberate self-poisoning events at emergency departments—a population-based nested case–control study

Rationale

Deliberate self-poisoning (DSP), the most common form of deliberate self-harm, is closely associated with suicide. Identifying risk factors of DSP is necessary for implementing prevention strategies.

Objectives

This study aimed to evaluate the relationship between benzodiazepine (BZD) treatment in psychiatric outpatients and DSP cases at emergency departments (EDs).

Methods

We performed a retrospective nested case–control study of psychiatric patients receiving BZD therapy to evaluate the relationship between BZD use and the diagnosis of DSP at EDs using data from the nationwide Taiwan National Health Insurance Research Database.

Results

Regression analysis yielded an odds ratio (OR) and 95 % confidence interval (95 % CI) indicating that the use of BZDs in psychiatric outpatients was significantly associated with DSP cases at EDs (OR?=?4.46, 95 % CI?=?3.59–5.53). Having a history of DSP, sleep disorders, anxiety disorders, schizophrenia, depression, or bipolar disorder was associated with a DSP diagnosis at EDs (OR?=?13.27, 95 % CI?=?8.28–21.29; OR?=?5.04, 95 % CI?=?4.25–5.98; OR?=?3.95, 95 % CI?=?3.32–4.70; OR?=?7.80, 95 % CI?=?5.28–11.52; OR?=?15.20, 95 % CI?=?12.22–18.91; and OR?=?18.48, 95 % CI?=?10.13–33.7, respectively). After adjusting for potential confounders, BZD use remained significantly associated with a subsequent DSP diagnosis (adjusted OR?=?2.47, 95 % CI?=?1.93–3.17). Patients taking higher average cumulative BZD doses were at greater risk of DSP.

Conclusion

Vigilant evaluation of the psychiatric status of patients prescribed with BZD therapy is critical for the prevention of DSP events at EDs.