Publications by Year: 2010

Gagne JJ, Power MC. Anti-inflammatory drugs and risk of Parkinson disease: a meta-analysis. Neurology. 2010;74 (12) :995-1002.Abstract
BACKGROUND/OBJECTIVE: Anti-inflammatory drugs may prevent Parkinson disease (PD) by inhibiting a putative underlying neuroinflammatory process. We tested the hypothesis that anti-inflammatory drugs reduce PD incidence and that there are differential effects by type of anti-inflammatory, duration of use, or intensity of use. METHODS: MEDLINE and EMBASE were searched for studies that reported risk of PD associated with anti-inflammatory medications. Random-effects meta-analyses were used to pool results across studies for each type of anti-inflammatory drug. Stratified meta-analyses were used to assess duration- and intensity-response. RESULTS: Seven studies were identified that met the inclusion criteria, all of which reported associations between nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs) and PD, 6 of which reported on aspirin, and 2 of which reported on acetaminophen. Overall, a 15% reduction in PD incidence was observed among users of nonaspirin NSAIDS (relative risk [RR] 0.85, 95% confidence interval [CI] 0.77-0.94), with a similar effect observed for ibuprofen use. The protective effect of nonaspirin NSAIDs was more pronounced among regular users (RR 0.71, 95% CI 0.58-0.89) and long-term users (RR 0.79, 95% CI 0.59-1.07). No protective effect was observed for aspirin (RR 1.08, 95% CI 0.92-1.27) or acetaminophen (RR 1.06, 95% CI 0.87-1.30). Sensitivity analyses found results to be robust. CONCLUSIONS: There may be a protective effect of nonaspirin nonsteroidal anti-inflammatory drug use on risk of Parkinson disease (PD) consistent with a possible neuroinflammatory pathway in PD pathogenesis.
Cadarette SM, Gagne JJ, Solomon DH, Katz JN, Stürmer T. Confounder summary scores when comparing the effects of multiple drug exposures. Pharmacoepidemiol Drug Saf. 2010;19 (1) :2-9.Abstract
PURPOSE: Little information is available comparing methods to adjust for confounding when considering multiple drug exposures. We compared three analytic strategies to control for confounding based on measured variables: conventional multivariable, exposure propensity score (EPS), and disease risk score (DRS). METHODS: Each method was applied to a dataset (2000-2006) recently used to examine the comparative effectiveness of four drugs. The relative effectiveness of risedronate, nasal calcitonin, and raloxifene in preventing non-vertebral fracture, were each compared to alendronate. EPSs were derived both by using multinomial logistic regression (single model EPS) and by three separate logistic regression models (separate model EPS). DRSs were derived and event rates compared using Cox proportional hazard models. DRSs derived among the entire cohort (full cohort DRS) was compared to DRSs derived only among the referent alendronate (unexposed cohort DRS). RESULTS: Less than 8% deviation from the base estimate (conventional multivariable) was observed applying single model EPS, separate model EPS or full cohort DRS. Applying the unexposed cohort DRS when background risk for fracture differed between comparison drug exposure cohorts resulted in -7 to + 13% deviation from our base estimate. CONCLUSIONS: With sufficient numbers of exposed and outcomes, either conventional multivariable, EPS or full cohort DRS may be used to adjust for confounding to compare the effects of multiple drug exposures. However, our data also suggest that unexposed cohort DRS may be problematic when background risks differ between referent and exposed groups. Further empirical and simulation studies will help to clarify the generalizability of our findings.
Maio V, Gagne JJ. Impact of ALLHAT publication on antihypertensive prescribing patterns in Regione Emilia-Romagna, Italy. J Clin Pharm Ther. 2010;35 (1) :55-61.Abstract
BACKGROUND AND OBJECTIVE: Studies from the US and Canada observed changes in antihypertensive prescribing patterns in accordance with Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) study findings immediately after the study's publication, but little is known about the impact of ALLHAT in Italy. The objective of this study was to examine antihypertensive prescribing patterns in Regione Emilia-Romagna (RER), Italy, following the publication of the ALLHAT main results. METHODS: We conducted a time series analysis using automated pharmacy data of approximately 4 million RER residents between 1 January 2000 and 31 December 2003. We computed monthly relative percentages of prescriptions for all antihypertensive medications and separately for all new antihypertensives defined as no recorded antihypertensive use in the previous year. A stepwise auto-regressive forecasting model based on data prior to the ALLHAT publication was used to estimate predicted relative percentages for the 12 months following the ALLHAT publication. Observed and predicted values were compared. RESULTS AND DISCUSSION: Use of thiazide-type diuretics showed a general increasing trend over the study period, but the difference between the observed and predicted values reached statistical significance only for new prescriptions in October 2003 (3.71% vs. 2.32%; P = 0.0170). The relative percentage of new angiotensin-converting enzyme inhibitor and angiotensin receptor blocker (ACE/ARB) prescriptions was higher than predicted for the months May to August 2003 (P < 0.05), but no significant differences were observed for total ACE/ARB prescriptions. Modest changes in patterns of prescribing of calcium channel blockers and alpha-blockers were observed. CONCLUSION: We found little evidence that the ALLHAT study had an impact on antihypertensive prescribing patterns in RER in the year following their publication.
Gagne JJ, Avorn J, Shrank WH, Schneeweiss S. Refilling and switching of antiepileptic drugs and seizure-related events. Clin Pharmacol Ther. 2010;88 (3) :347-53.Abstract
We sought to estimate the risk of seizure-related events associated with refilling prescriptions for antiepileptic drugs (AEDs) and to estimate the effect of switching between brand-name and generic drugs or between two generic versions of the same drug. We conducted a case-crossover study using health-care databases from British Columbia, Canada, among AED users who had an emergency room visit or hospitalization for seizure (index seizure-related event), defined using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9) codes 345.xx (epilepsy and recurrent seizures) and 780.3x (convulsions), between 1997 and 2005. AED prescription refilling itself was associated with 2.3-fold elevated odds of seizure-related events when the refill occurred within 21 days before the index event (odds ratio (OR) 2.31; 95% confidence interval (CI) 1.56-3.44). The OR was 2.75 (95% CI 0.88-8.64) for refills that involved switching, yielding a refill-adjusted OR for switching of 1.19 (95% CI 0.35-3.99). Refilling the same AED prescription was associated with an elevated risk of seizure-related events whether or not the refill involved switching from a brand-name to a generic product.
Kesselheim AS, Stedman MR, Bubrick EJ, Gagne JJ, Misono AS, Lee JL, Brookhart AM, Avorn J, Shrank WH. Seizure outcomes following the use of generic versus brand-name antiepileptic drugs: a systematic review and meta-analysis. Drugs. 2010;70 (5) :605-21.Abstract
The automatic substitution of bioequivalent generics for brand-name antiepileptic drugs (AEDs) has been linked by anecdotal reports to loss of seizure control. To evaluate studies comparing brand-name and generic AEDs, and determine whether evidence exists of superiority of the brand-name version in maintaining seizure control. English-language human studies identified in searches of MEDLINE, EMBASE and International Pharmaceutical Abstracts (1984 to 2009). Randomized controlled trials (RCTs) and observational studies comparing seizure events or seizure-related outcomes between one brand-name AED and at least one alternative version produced by a distinct manufacturer. We identified 16 articles (9 RCTs, 1 prospective nonrandomized trial, 6 observational studies). We assessed characteristics of the studies and, for RCTs, extracted counts for patients whose seizures were characterized as 'controlled' and 'uncontrolled'. Seven RCTs were included in the meta-analysis. The aggregate odds ratio (n = 204) was 1.1 (95% CI 0.9, 1.2), indicating no difference in the odds of uncontrolled seizure for patients on generic medications compared with patients on brand-name medications. In contrast, the observational studies identified trends in drug or health services utilization that the authors attributed to changes in seizure control. Although most RCTs were short-term evaluations, the available evidence does not suggest an association between loss of seizure control and generic substitution of at least three types of AEDs. The observational study data may be explained by factors such as undue concern from patients or physicians about the effectiveness of generic AEDs after a recent switch. In the absence of better data, physicians may want to consider more intensive monitoring of high-risk patients taking AEDs when any switch occurs.