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Taraneh Bahremand,1 Mahyar Etminan,2 Nardin Roshan-Moniri,1 Mary A De Vera,1 Hamid Tavakoli,1 Mohsen Sadatsafavi1 1Collaboration for Outcomes Research and Evaluation, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC, Canada; 2Department of Ophthalmology, Faculty of Medicine, The University of British Columbia, Vancouver, BC, CanadaCorrespondence: Mohsen SadatsafaviFaculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, CanadaEmail msafavi@mail.ubc.caBackground: In contemporary guidelines for the management of Chronic Obstructive Pulmonary Disease (COPD), the history of acute exacerbations plays an important role in the choice of long-term inhaled therapies. This study aimed at evaluating population-level trends of filled inhaled prescriptions over the time course of COPD and their relation to the history of exacerbations.Methods: We used administrative health databases in British Columbia, Canada (1997– 2015), to create a retrospective incident cohort of individuals with diagnosed COPD. We quantified long-acting inhaled medication prescriptions within each year of follow-up and documented their trend over the time course of COPD. Using generalized linear models, we investigated the association between the frequent exacerbator status (≥ 2 moderate or ≥ 1 severe exacerbation(s) in the previous 12 months) and filling a prescription after a physician visit.Results: 132,004 COPD patients were included (mean age 68.6, 49.2% female). The most common medication class during the first year of diagnosis was inhaled corticosteroids (ICS, used by 49.9%), followed by long-acting beta-2 adrenoreceptor agonists (LABA, 31.8%). Long-acting muscarinic receptor antagonists (LAMA) were the least commonly prescribed (10.4%). ICS remained the most common prescription throughout follow-up, being used by approximately 50% of patients during each year. 39.0% of patients received combination inhaled therapies in their first year of diagnosis, with ICS+LABA being the most common (30.7%). The association with exacerbation history was the most pronounced for triple therapy with an odds ratio (OR) of 2.68 for general practitioners and 2.02 for specialists (p< 0.001 for both). Such associations were generally stronger among GPs compared with specialists, with the exception of monotherapy with LABA or ICS.Conclusion: We documented low utilization of monotherapies (specifically LAMA) and high utilization of combination therapies (particularly ICS containing). Specialists were less likely to consider exacerbation history in the choice of inhaled therapies compared with GPs.Keywords: COPD, prescription, medication, exacerbation, time trend

Context: Fluoroquinolones are commonly prescribed classes of antibiotics. Despite numerous case reports of ocular toxicity, a pharmacoepidemiological study of their ocular safety, particularly retinal detachment, has not been performed.Objective: To examine the association between use of oral fluoroquinolones and the risk of developing a retinal detachment.Design, Setting, and Patients: Nested case-control study of a cohort of patients in British Columbia, Canada, who had visited an ophthalmologist between January 2000 and December 2007. Retinal detachment cases were defined as a procedure code for retinal repair surgery within 14 days of a physician service code. Ten controls were selected for each case using risk-set sampling, matching on age and the month and year of cohort entry.Main Outcome Measure: The association between retinal detachment and current, recent, or past use of an oral fluoroquinolone.Results: From a cohort of 989,591 patients, 4384 cases of retinal detachment and 43,840 controls were identified. Current use of fluoroquinolones was associated with a higher risk of developing a retinal detachment (3.3% of cases vs 0.6% of controls; adjusted rate ratio [ARR], 4.50 [95% CI, 3.56-5.70]). Neither recent use (0.3% of cases vs 0.2% of controls; ARR, 0.92 [95% CI, 0.45-1.87]) nor past use (6.6% of cases vs 6.1% of controls; ARR, 1.03 [95% CI, 0.89-1.19]) was associated with a retinal detachment. The absolute increase in the risk of a retinal detachment was 4 per 10,000 person-years (number needed to harm = 2500 computed for any use of fluoroquinolones). There was no evidence of an association between development of a retinal detachment and β-lactam antibiotics (ARR, 0.74 [95% CI, 0.35-1.57]) or short-acting β-agonists (ARR, 0.95 [95% CI, 0.68-1.33]).Conclusion: Patients taking oral fluoroquinolones were at a higher risk of developing a retinal detachment compared with nonusers, although the absolute risk for this condition was small. [ABSTRACT FROM AUTHOR]

BACKGROUND: Several studies have suggested that NSAID use may modify the risk of developing Parkinson's disease (PD). OBJECTIVE: Our aim was to conduct a meta-analysis of observational studies evaluating NSAID use and the risk of PD. METHODS: We systematically searched MEDLINE (1966-November 2008), EMBASE (1980-November 2008) and other databases. Data from 11 studies were included in the meta-analysis. We used the random effects model to calculate risk ratios (relative risks) and their corresponding 95% confidence intervals (CIs). RESULTS: The pooled risk ratio of PD with NSAID use was 0.95 (95% CI 0.80, 1.12). The pooled risk ratio of PD with high-dose or long-duration NSAID use was 0.91 (95% CI 0.78, 1.05). The pooled risk ratio of PD for aspirin (acetylsalicylic acid) users was 1.08 (95% CI 0.93, 1.26). The pooled risk ratio of PD among ibuprofen users was 0.76 (95% CI 0.65, 0.89). The pooled risk ratio of PD in men using NSAIDs was 0.79 (95% CI 0.69, 0.92), and in women using NSAIDs, it was 0.72 (95% CI 0.45, 1.15). CONCLUSIONS: NSAIDs as a class do not seem to modify the risk of PD. However, ibuprofen may have a slight protective effect in lowering the risk of PD. Although the risk ratios of PD in male and female NSAID users were similar, the 95% CI for men was suggestive of a slight risk reduction. [ABSTRACT FROM AUTHOR]

Background: Inhaled corticosteroids (ICS) are commonly prescribed medications for the management of asthma and chronic obstructive pulmonary disease. It is well established that long-term use of these drugs may lower bone mineral density. However, whether ICS increase the risk of fractures remains unknown. Recent studies that have attempted to explore this risk have had conflicting results. We sought to explore the risk of ICS and fractures among older adults by conducting a systematic review and meta-analysis of the literature.Methods: We systematically searched several databases, including MEDLINE, EMBASE and the Cochrane Library, to identify pertinent studies. Those studies that potentially met our inclusion criteria were identified by two reviewers. Relative risks (RRs) were pooled using the random effects model. We also explored dose-response by stratifying the analysis on high and low doses of ICS. Heterogeneity was assessed using the Q statistic and publication bias was assessed using the funnel plot.Results: Thirteen studies, including four randomized controlled trials, were included in the review. The pooled RRs for hip fractures and any fractures were 0.91 (95% CI 0.87, 0.96) and 1.02 (95% CI 0.96, 1.08), respectively. When we restricted the analysis to users of high-dose ICS, the pooled RRs for any fractures and hip fractures were 1.30 (95% CI 1.07, 1.58) and 1.32 (95% CI 0.90, 1.92), respectively. The funnel plot did not show evidence of publication bias.Conclusion: We found no association between the use of ICS and fractures in older adults. A slight increase in risk was seen in those using high-dose ICS. The significance of this association should be investigated further. [ABSTRACT FROM AUTHOR]

Background: Recently, studies have attempted to explore the interaction between ACE inhibitors and aspirin (acetylsalicylic acid) when both drugs are used concomitantly to reduce mortality in patients with coronary artery disease. Results have been conflicting due, in part, to sub-optimal methods used to explore this interaction.Methods: We reviewed systematically all studies on mortality in patients treated with ACE inhibitors and aspirin and conducted a meta-analysis in order to explore the interaction between both drugs and resolve discrepancies. To be included, each study had to provide data on mortality of patients who received both drugs, either drug and no drug. These data were necessary to calculate the synergy index (S) and its 95% confidence interval (CI) that we used to quantify the effect due to interaction between ACE inhibitors and aspirin. After testing for heterogeneity of effects, we pooled the S values from the individual studies into one summary measure. Subsequently, we compared our results with those obtained through the most common but incorrect method of evaluating interaction. This method uses significance testing of the relative risk of mortality when a 'product term' between ACE inhibitors and aspirin is entered in a logistic regression model.Results: Eight studies met the inclusion criteria. The pooled synergy index S indicates slight but precise antagonism between ACE inhibitors and aspirin (S = 0.91; 95% CI 0.80 to 1.03). In contrast, the pooled 'product term' is not significant and would have lead to the conclusion of absence of interaction (p = 0.15).Conclusion: There seems to be an antagonistic interaction between ACE inhibitors and aspirin. Former discrepancies were due to inadequate assessment of interaction. Results from the Studies on Left Ventricular Dysfunction (SOLVD) and Heart Outcome Prevention Evaluation (HOPE) trials that assessed the effect of combined administration of ACE inhibitors and aspirin were not included in this meta-analysis because those trials did not provide enough data to compute the S statistic. It is possible that results from on-going trials such as Women's Atovarstatin Trial on Cholesterol (WATCH) will shed more light on ACE inhibitor and aspirin interaction in the future. [ABSTRACT FROM AUTHOR]

Background: Recent case reports and letters have alerted practitioners to the risk of sleep attacks, usually preceded by somnolence, in patients with Parkinson's disease treated with pramipexole and ropinirole.Objective: To quantify the risk of somnolence with the new dopamine agonists pramipexole and ropinirole in patients with Parkinson's disease.Methods: We searched MEDLINE, EMBASE, International Pharmaceutical Abstracts and Cochrane Library, contacted experts and pharmaceutical manufacturers, and manually reviewed all references retrieved to identify possible articles to include. Information on randomisation, blinding, type of treatment and reporting of somnolence were abstracted by 2 independent reviewers. Disagreements were resolved by a third author.Analysis: We made 2 separate analyses. The first analysis compared the risk of somnolence in patients taking either pramipexole or ropinirole to that in patients taking placebo. The second analysis compared the risk of somnolence with these drugs (plus levodopa) versus that with levodopa alone. We calculated pooled relative risk estimates using the random effects model and when no heterogeneity was detected we used the fixed effects model.Results: Four trials were included in the analysis of patients taking pramipexole or ropinirole compared with those taking placebo. The pooled relative risk of somnolence in this analysis was 4.98 [95% confidence interval (CI) 1.79 to 13.89]. Seven trials were included in the analysis of patients taking levodopa and pramipexole or ropinirole compared with those taking levodopa alone. The pooled relative risk was 2.06 (95% CI 1.47 to 2.88).Conclusion: Patients with Parkinson's disease using pramipexole or ropinirole are at higher risk of experiencing somnolence relative to patients taking placebo. Patients taking levodopa plus either one of these dopamine agonists are at higher risk than those taking levodopa alone. Clinicians should carefully weigh this risk against the benefit of these agents when prescribing these drugs. [ABSTRACT FROM AUTHOR]

Abstract Background Despite the benefits of beta-blockers in patients with established or sub-clinical coronary artery disease, their use in patients with chronic obstructive pulmonary disease (COPD) has been controversial. Currently, no systematic review has examined the impact of beta-blockers on mortality in COPD. Methods We systematically searched electronic bibliographic databases including MEDLINE, EMBASE and Cochrane Library for clinical studies that examine the association between beta-blocker use and all cause mortality in patients with COPD. Risk ratios across studies were pooled using random effects models to estimate a pooled relative risk across studies. Publication bias was assessed using a funnel plot. Results Our search identified nine retrospective cohort studies that met the study inclusion criteria. The pooled relative risk of COPD related mortality secondary to beta-blocker use was 0.69 (95% CI: 0.62-0.78; I2=82%). Conclusion The results of this review are consistent with a protective effect of beta-blockers with respect to all cause mortality. Due to the observational nature of the included studies, the possibility of confounding that may have affected these results cannot be excluded. The hypothesis that beta blocker therapy might be of benefit in COPD needs to be evaluated in randomised controlled trials.