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- Potential increased risk of cancer from commonly used medications: an umbrella review of meta-analyses. [JOURNAL ARTICLE]
- Ann Oncol 2013 Dec 4.
Several commonly used medications have been associated with increased cancer risk in the literature. Here, we evaluated the strength and consistency of these claims in published meta-analyses. We carried out an umbrella review of 74 meta-analysis articles addressing the association of commonly used medications (antidiabetics, antihyperlipidemics, antihypertensives, antirheumatics, drugs for osteoporosis, and others) with cancer risk where at least one meta-analysis in the medication class included some data from randomized trials. Overall, 51 articles found no statistically significant differences, 13 found some decreased cancer risk, and 11 found some increased risk (one reported both increased and decreased risks). The 11 meta-analyses that found some increased risks reported 16 increased risk estimates, of which 5 pertained to overall cancer and 11 to site-specific cancer. Six of the 16 estimates were derived from randomized trials and 10 from observational data. Estimates of increased risk were strongly inversely correlated with the amount of evidence (number of cancer cases) (Spearman's correlation coefficient = -0.77, P < 0.001). In 4 of the 16 topics, another meta-analysis existed that was larger (n = 2) or included better controlled data (n = 2) and in all 4 cases there was no statistically significantly increased risk of malignancy. No medication or class had substantial and consistent evidence for increased risk of malignancy. However, for most medications we cannot exclude small risks or risks in population subsets. Such risks are unlikely to be possible to document robustly unless very large, collaborative studies with standardized analyses and no selective reporting are carried out.
- Utilization patterns of Antihyperuricemic Agents Following Safety Announcement on Allopurinol and Benzbromarone by Taiwan Food and Drug Administration. [JOURNAL ARTICLE]
- Pharmacoepidemiol Drug Saf 2013 Dec 5.
The purpose of this study is to evaluate the utilization of four approved antihyperuricemic agents in Taiwan before and after two safety announcements rescinded an indication for allopurinol and added a warning on benzbromarone-induced hepatotoxicity in the year 2005.An interrupted time series design and segmented regression models were used to examine impacts of the safety announcements on the utilization of allopurinol, benzbromarone, probenecid, or sulfinpyrazone. All outpatient prescriptions of the four antihyperuricemic agents were extracted from a longitudinal cohort dataset with 1 000 000 individuals randomly sampled from the National Health Insurance Research Database. We examined utilization patterns of antihyperuricemic agents before and after the policy intervention (i.e., safety announcements and labeling changes of allopurinol and benzbromarone) in the year 2005.Following the safety announcements, there was a reduction in the number of allopurinol users in the first year of intervention (-95.82 users per 100 000 persons, 95%CI, [-166.84, -24.80]) and a continuous reduction afterward at a rate of -53.17 per 100 000 persons per year. The utilization of benzbromarone grew steadily before 2005 but decreased drastically after the intervention, with a 30.12% reduction in the number of users by the end of year 2008. There was no commensurate change in the number of probenecid or sulfinpyrazone users after the intervention.Further research is required to evaluate the direct impacts of the safety announcements on clinical outcomes, treatment costs, and patient's quality of life. Copyright © 2013 John Wiley & Sons, Ltd.
- Performance of instrumental variable methods in cohort and nested case-control studies: a simulation study. [JOURNAL ARTICLE]
- Pharmacoepidemiol Drug Saf 2013 Dec 5.
Instrumental variable (IV) analysis is becoming increasingly popular to adjust for confounding in observational pharmacoepidemiologic research. One of the prerequisites of an IV is that it is strongly associated with exposure; if it is weakly associated with exposure, IV estimates are reported to be biased. We aimed to assess the performance of IV estimates in various (pharmaco-)epidemiologic settings.Data were simulated for continuous/binary exposure, outcome and IV in cohort and nested case-control (NCC) designs with different incidences of the outcome. Pearson's correlation, point bi-serial correlation, odds ratio (OR), and F-statistic were used to assess the IV-exposure association. Two-stage analysis was performed to estimate the exposure effect.For all types of IV and exposure in the cohort and NCC designs, IV estimates were extremely unstable and biased when the IV was very weakly associated with exposure (e.g. Pearson's correlation < 0.15 for continuous or OR < 2.0 for binary IV and exposure; although specific cut-off values depend on simulation settings). For stronger IVs, estimates were unbiased and become less variable compared with weaker IVs in the case of continuous and binary (risk difference scale) outcomes. For a similar IV-exposure association (e.g. OR = 1.4 and 5% incidence of the outcome), the variability of the estimates was more pronounced in the NCC (standard deviation = 2.37, case : control = 1:5) compared with the cohort design (standard deviation = 1.14). The variability was even more pronounced for rare (≤1%) outcomes. However, IV estimates from the NCC design became less variable with an increasing number of controls per case. Moreover, estimates were biased when the IV was related to confounders even with strong IVs.Instrumental variable analysis performs poorly when the IV-exposure association is extremely weak, especially in the NCC design. IV estimates in the NCC design become less variable when the number of control increases. As NCC does not use the entire cohort, in order to achieve stable estimates, this design requires a stronger IV-exposure association than the cohort design. Copyright © 2013 John Wiley & Sons, Ltd.
- Same song, different audience: pharmaceutical promotion targeting non-physician health care providers. [Journal Article]
- PLoS Med 2013 Nov; 10(11):e1001560.
- Are high-care nursing home residents at greater risk of unplanned hospital admission than other elderly patients when exposed to Beers potentially inappropriate medications? [JOURNAL ARTICLE]
- Geriatr Gerontol Int 2013 Dec 3.
To compare the risk of unplanned hospitalization in high-care nursing home residents taking Beers potentially inappropriate medications (PIM) against that of other elderly.Using an enhanced case-time-control design and conditional logistic regression applied to the pharmaceutical claims and other linked data of 245 436 Western Australians aged ≥65 years (1993-2005), the study derived odds ratios for unplanned hospitalization in each group, from which attributable fractions, numbers, proportions and rates of PIM-related admissions were derived.Overall, 383 150 unplanned hospitalizations were identified. PIM exposure was associated with a similar proportional increase in unplanned hospitalizations in high-care nursing home residents as in other older people; adjusted OR 1.21 (95% CI 1.10-1.34; attributable fraction 17.5%) versus OR 1.19 (95% CI 1.16-1.21; attributable fraction 15.7%). However, high-care nursing home residents had much higher estimated rates of hospitalizations attributed to Beers medications than other elderly (3951 vs 115 per 100 000 person-years). The relative risk of unplanned hospitalization rose similarly in both groups with increasing numbers of different PIM taken (OR 5.1 for 10 vs 0 PIM), but was affected more markedly by 3-month PIM consumption in nursing home residents (OR 4.85, 95% CI 2.40-9.83 for 900 vs 0 PIM daily doses) than in other older adults (OR 2.10, 95% CI 1.73-2.55).High-care nursing home residents do not appear to have a greater relative risk of unplanned hospitalization when given PIM, but do incur a higher absolute burden than other older adults. Physicians should exert caution with Beers medications in all older patients, restricting the number of different PIM and PIM quantity prescribed whenever possible. Geriatr Gerontol Int 2013; ●●: ●●-●●.
- Restoring trust in the pharmaceutical sector on the basis of the SSRI case. [JOURNAL ARTICLE]
- Drug Discov Today 2013 Nov 29.
Teaser: The present article demonstrates that the restoration of public trust should rely on reinforcing the competence of the industry and authorities instead of increasing or intensifying regulations. The lack of public trust in the pharmaceutical sector (i.e. industry, authorities and doctors) could compromise the future of drug development and the regulatory system. Public trust integrates two important components, namely the vulnerability of the truster and the competence of the trustee. Because trust appears to have eroded as a result of drug safety controversies, this paper analyzes the role of public trust during the selective serotonin reuptake inhibitor (SSRI) and suicidality controversy focusing on the aforementioned trust components. Because the competence component of trust is argued to be paramount in determining and maintaining public trust, the SSRI case shows that this component is a part of public trust where these institutions can build on, and might therefore be better used to substantiate and reinforce, public trust. Efforts to build trust should rely on the ethical, professional (competence) and societal commitment of institutions and individuals to protect the vulnerability of the public during controversies. Because shared values can create trust or increase its levels within a specific environment, industry, authorities and physicians ought to develop novel and cooperative strategies to highlight their shared values and motivations. Rules, regulations and settlements are indispensable tools but undue regulation is costly and can backfire on the rather sensitive trust relationships in the pharmaceutical sector.
- Comparative effectiveness of rosuvastatin versus simvastatin in primary prevention among new users: a cohort study in the French national health insurance database. [JOURNAL ARTICLE]
- Pharmacoepidemiol Drug Saf 2013 Dec 2.
Using the French claims database (Système National d'Information Inter-Régimes de l'Assurance Maladie) linked to the hospital discharge database (Programme de Médicalisation des Systèmes d'Information), this observational study compared the effectiveness of rosuvastatin and simvastatin prescribed at doses with close LDL-cholesterol-lowering potency on all-cause mortality and cardiovascular and cerebrovascular diseases (CCDs) in primary prevention.This historical cohort included patients with no prior CCD, aged 40-79 years, who initiated statin therapy with rosuvastatin 5 mg or simvastatin 20 mg in 2008-2009 in general practice. Follow-up started after a 1-year period used to select patients who regularly received the initial treatment. In an intention-to-treat analysis, patients were followed up to December 2011. In a per-protocol analysis, they were censored prematurely when they discontinued their initial treatment. Adjustment for baseline covariates (age, deprivation index, comedications, comorbidities, prior hospital admissions) was carried out by a Cox proportional hazards model. In the per-protocol analysis, estimation was done by "inverse probability of censoring weighting" using additional time-dependent covariates. Analyses were gender-specific.A total of 106 941 patients initiated statin therapy with rosuvastatin 5 mg and 56 860 with simvastatin 20 mg. Mean follow-up was 35.8 months. For both genders and both types of analyses, the difference in incidence rates of mortality and/or CCD between rosuvastatin 5 mg and simvastatin 20 mg users was not statistically significant after adjustment (e.g., for CCD and/or mortality in men, in intention-to-treat analysis HR = 0.94 [95% CI = 0.85-1.04], in per-protocol analysis HR = 0.98 [0.87-1.10]).The results of this real-life study based on medico-administrative databases do not support preferential prescription of rosuvastatin compared to simvastatin for primary prevention of CCD. © 2013 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.
- Is combined use of SSRIs and NSAIDs associated with an increased risk of starting peptic ulcer treatment? [JOURNAL ARTICLE]
- Br J Clin Pharmacol 2013 Dec 2.
- Risk of acute myocardial infarction, stroke, or death in patients initiating olmesartan or other angiotensin receptor blockers - a cohort study using the Clinical Practice Research Datalink. [JOURNAL ARTICLE]
- Pharmacoepidemiol Drug Saf 2013 Nov 28.
Results of two randomized trials (ROADMAP and ORIENT) suggest that high-dose (40 mg/day) olmesartan (Olm) is associated with increased cardiovascular mortality compared to placebo in diabetic patients. We evaluated the risks of acute myocardial infarction (AMI) and death in patients initiating Olm compared with an active comparator group, other angiotensin receptor blockers (ARBs), with a focus on high-dose and diabetic subgroups.We conducted a cohort study with patients who initiated Olm or another ARB between 2003 and 2011, using the UK Clinical Practice Research Datalink GOLD. We included patients who had no prior ARB or angiotensin converting enzyme inhibitor exposure during the preceding 6 months. Hazard ratios (HRs) were estimated using Cox regression models with both multivariable adjustment and propensity score matching.There were 3964 Olm and 54 653 other-ARB initiators, respectively. Adjusted HRs comparing Olm and other-ARBs were 1.04 (95% CI: 0.75-1.42) for AMI and 1.16 (0.95-1.42) for death, using multivariable adjustment. Comparing patients initiated with a high-dose Olm and a high-dose other-ARB, HRs were 3.09 (0.94-10.13) for AMI and 2.03 (0.74-5.61) for death, using multivariable adjustment; and 4.38 (0.97-19.66) and 1.99 (0.63-6.32) for AMI and death, using propensity score matching.Overall, no differences in risk were observed in the main cohort analyses comparing Olm initiators with patients initiating therapy with other ARBs; however, HRs were marginally increased for all study endpoints which compared high-dose subgroups, suggesting potential increased risk may be associated with high-dose Olm. Published 2013. This article is a U. S. Government work and is in the public domain in the USA.
- Acetaminophen receipt among HIV-infected patients with advanced hepatic fibrosis. [Journal Article]
- Pharmacoepidemiol Drug Saf 2013 Dec; 22(12):1352-6.
HIV-infected patients may be at particular risk for acetaminophen-induced hepatotoxicity, but acetaminophen use in the context of liver injury has been incompletely examined among HIV-infected patients. Among a sample of HIV-infected patients, we aimed to determine acetaminophen exposure, assess the cross-sectional association between acetaminophen exposure and advanced hepatic fibrosis, and determine whether factors associated with acetaminophen exposure varied by HCV status.We conducted a cross-sectional analysis of the Veterans Aging Cohort Study. Advanced hepatic fibrosis was defined as a FIB-4 > 3.25, a composite score calculated based on age, alanine aminotransferase, aspartate aminotransferase, and platelet count. Multivariable ordered polytomous logistic regression was used to determine the association between FIB-4 status and acetaminophen exposure stratified by HCV status.Among HIV-infected patients (n = 14 885), 31% received at least one acetaminophen prescription. Among those receiving acetaminophen, acetaminophen overuse was common among both HIV-monoinfected and HIV/HCV-coinfected patients (846 [31%] vs 596[32%], p = 0.79). After stratifying by HCV status, those with evidence of advanced liver fibrosis were equally likely to be exposed to acetaminophen. Furthermore, HIV-monoinfected patients with an alcohol use disorder were more likely to have acetaminophen overuse (OR [95%CI] = 1.56 [1.21-2.02]).Strategies to minimize acetaminophen exposure, especially for HIV-monoinfected patients, are warranted. Copyright © 2013 John Wiley & Sons, Ltd.