Showing papers by "Pierre Ernst published in 2012"

Long-term natural history of chronic obstructive pulmonary disease: severe exacerbations and mortality

Abstract: Background The long-term natural history of chronic obstructive pulmonary disease (COPD) in terms of successive severe exacerbations and mortality is unknown. Methods The authors formed an inception cohort of patients from their first ever hospitalisation for COPD during 1990e2005, using the healthcare databases from the province of Quebec, Canada. Patients were followed until death or 31 March 2007, and all COPD hospitalisations occurring during follow-up were identified. The hazard functions of successive hospitalised COPD exacerbations and all-cause mortality over time were estimated, and HRs adjusted for age, sex, calendar time and comorbidity. Results The cohort included 73106 patients hospitalised for the first time for COPD, of whom 50580 died during the 17-year follow-up, with 50% and 75% mortality at 3.6 and 7.7 years respectively. The median time from the first to the second hospitalised exacerbation was around 5 years and decreased to <4 months from the 9th to the 10th. The risk of the subsequent severe exacerbation was increased threefold after the second severe exacerbation and 24-fold after the 10th, relative to the first. Mortality after a severe exacerbation peaked to 40 deaths per 10000 per day in the first week after admission, dropping gradually to 5 after 3 months. Conclusions The course of COPD involves a rapid decline in health status after the second severe exacerbation and high mortality in the weeks following every severe exacerbation. Two strategic targets for COPD management should include delaying the second severe exacerbation and improving treatment of severe exacerbations to reduce their excessive early mortality.

CNODES: the Canadian Network for Observational Drug Effect Studies.

Abstract: Although administrative health care databases have long been used to evaluate adverse drug effects, responses to drug safety signals have been slow and uncoordinated. We describe the establishment of the Canadian Network for Observational Drug Effect Studies (CNODES), a collaborating centre of the Drug Safety and Effectiveness Network (DSEN). CNODES is a distributed network of investigators and linked databases in British Columbia, Alberta, Saskatchewan, Manitoba, Ontario, Quebec and Nova Scotia. Principles of operation are as follows: (1) research questions are prioritized by the coordinating office of DSEN; (2) the linked data stay within the provinces; (3) for each question, a study team formulates a detailed protocol enabling consistent analyses in each province; (4) analyses are “blind” to results obtained elsewhere; (5) protocol deviations are permitted for technical reasons only; (6) ana­ lyses using multivariable methods are lodged centrally with a methods team, which is responsible for combining the results to provide a summary estimate of effect. These procedures are designed to achieve high internal validity of risk estimates and to eliminate the possibility of selective reporting of analyses or outcomes. The value of a coordinated multi-provincial approach is illustrated by projects studying acute renal injury with high-potency statins, community-acquired pneumonia with proton pump inhibitors, and hyperglycemic emergencies with antipsychotic drugs. CNODES is an academically based distributed network of Canadian researchers and data centres with a commitment to rapid and sophisticated analysis of emerging drug safety signals in study populations totalling over

Fluoroquinolones and the Risk of Serious Arrhythmia: A Population-Based Study

Abstract: Background Fluoroquinolones have been suspected to cause cardiac arrhythmia but data are lacking, particularly for the individual fluoroquinolones. We assessed the risk of serious arrhythmia, defined as ventricular arrhythmia or sudden/unattended death identified in hospital discharge diagnoses, related to fluoroquinolones as a class as well as for each individual molecule. Methods We used a cohort of patients treated for respiratory conditions from 1 January 1990 to 31 December 2005, identified using the healthcare databases from the province of Quebec (Canada), with follow-up until 31 March 2007. A nested case-control analysis was performed within this cohort, with all cases of serious arrhythmia occurring during follow-up identified from hospitalization records. These cases were matched with up to 20 controls. Conditional logistic regression was used to compute adjusted rate ratios (RRs) of serious arrhythmia associated with fluoroquinolone use. Results Within the cohort of 605127 subjects, 1838 cases were identified (incidence rate=4.7/10000 person-years). The rate of serious arrhythmia was elevated with current fluoroquinolone use (RR=1.76; 95% confidence interval [CI], 1.19-2.59), in particular with new current use (RR=2.23; 95% CI, 1.31-3.80). Gatifloxacin use was associated with the highest rate (RR=7.38; 95% CI, 2.30-23.70); moxifloxacin and ciprofloxacin were also associated with elevated rates of serious arrhythmia (RR=3.30; 95% CI, 1.47-7.37 and RR=2.15; 95% CI, 1.34-3.46, respectively). Conclusions The use fluoroquinolones is associated with an elevated risk of serious arrhythmia, with some differences among molecules. Given that the individual fluoroquinolones share various indications, the relative risks of serious arrhythmia could inform the choice of different molecules in high-risk patients.

β-Blockers for COPD inpatients

Abstract: For clinicians who treat patients with respiratory diseases, the use of β-blockers has, for a long time, posed a dilemma because of the potential risk of bronchospasm and neutralisation of the effectiveness of β-2 agonists. This predicament is particularly challenging for patients with chronic obstructive pulmonary disease (COPD), many of whom have substantial cardiovascular comorbidity,1 and in whom the avoidance of β-blockers might deprive them of substantial cardiovascular benefit. In the last few years, this restraint has been challenged, and rightfully so, in view of the general scarcity of data on this potential antagonism and, more importantly, its would-be effect on major outcomes. While caution is generally the sensible approach in drug safety, this is less the case here, as one would be withholding a treatment that has been demonstrated to be effective for cardiovascular disease. Several observational studies have examined the potential risks and benefits of β-blocker use in COPD. Most studies, to date, have looked at β-blocker use during the usual course of COPD without specifically examining their risk or benefit at the time of an acute exacerbation of COPD (AECOPD).2–5 Stefan et al 6 address the question of the effects of β-blockers during a serious exacerbation requiring hospitalisation. The authors specifically evaluated whether β-blockers given early to patients hospitalised for AECOPD, and who also have ischaemic heart disease or heart failure, increase the risk of mortality. They used the US Premier hospitalisation database to identify a large cohort of over 35 000 patients hospitalised for COPD, and …

Pramipexole use and the risk of pneumonia

Abstract: Patients with Parkinson's disease have an elevated risk of pneumonia and randomized trials suggest that this risk may be increased with the dopamine agonist pramipexole. It is uncertain whether pramipexole or other dopamine agonists increase the risk of pneumonia. We used the United Kingdom's General Practice Research Database (GPRD) to identify users of anti-parkinsonian drugs, 40–89 years of age, between 1997 and 2009. Using a nested case–control approach, all incident cases hospitalised for pneumonia were matched with up to ten controls selected among the cohort members. Rate ratios (RR) and 95% confidence intervals (CI) of pneumonia associated with current use of dopamine agonists were estimated using conditional logistic regression, adjusted for covariates. The cohort included 13,183 users of anti-parkinsonian drugs, with 1,835 newly diagnosed with pneumonia during follow-up (rate 40.9 per 1,000 per year). The rate of pneumonia was not increased with the current use of pramipexole (RR 0.76; 95% CI: 0.57-1.02), compared with no use. The use of pramipexole was not associated with an increased rate of pneumonia when compared with all other dopamine agonists collectively (RR 0.85; 95% CI: 0.62-1.17). The use of pramipexole does not appear to increase the risk of pneumonia.