Janie Coulombe

Discontinuation of Inhaled Corticosteroids in COPD and the Risk Reduction of Pneumonia

BACKGROUND The widespread use of inhaled corticosteroids (ICSs) for COPD treatment has been questioned. Recent studies of weaning some patients with COPD off ICSs found little or no adverse consequences compared with long-acting bronchodilators. It is unclear, however, whether discontinuation of ICSs reduces the elevated risk of pneumonia associated with these drugs. METHODS Using the Quebec health insurance databases, we formed a new-user cohort of patients with COPD treated with ICSs during 1990 to 2005 and followed through 2007 or until a serious pneumonia event, defined as a first hospitalization for or death from pneumonia. A nested case-control analysis of the cohort was used to estimate the rate ratio of serious pneumonia associated with discontinuation of ICS use compared with continued use, adjusted for age, sex, respiratory disease severity, and comorbidity. RESULTS The cohort included 103,386 users of ICSs, of whom 14,020 had a serious pneumonia event during 4.9 years of follow-up (incidence rate, 2.8/100/y). Discontinuation of ICSs was associated with a 37% decrease in the rate of serious pneumonia (rate ratio [RR], 0.63; 95% CI, 0.60-0.66). The risk reduction was rapidly evident, going from 20% in the first month to 50% by the fourth month after discontinuation. The risk reduction was particularly marked with fluticasone (RR, 0.58; 95% CI, 0.54-0.61) but less so with budesonide (RR, 0.87; 95% CI, 0.78-0.97). CONCLUSIONS Discontinuation of ICS use in COPD is associated with a reduction in the elevated risk of serious pneumonia, particularly so with fluticasone.

Revisiting sex differences in outcomes in non-valvular atrial fibrillation: a population-based cohort study

Aims In patients with non-valvular atrial fibrillation (NVAF), it is uncertain whether the higher risk of ischaemic stroke in women reported in some studies is due to residual confounding. We assessed this association using standard time-fixed and more accurate time-dependent adjustment for confounders. Methods and results Using the computerized databases of the Régie de l’assurance maladie du Québec (RAMQ), we identified a cohort of patients with NVAF during 2000–2009 and RAMQ medication coverage. Cox proportional hazards models were used to estimate the hazard ratio (HR) of ischaemic stroke, death, and bleeding, associated with sex, adjusting for time-fixed covariates at cohort entry. This was compared with adjustment for time-dependent covariates using an age and time-matched nested case-control analysis. The cohort included 147 622 patients. During a mean follow-up of 2.9 years 11 326 patients had a stroke (incidence rate 2.6 per 100 per year). Using time-fixed adjustment for confounders, women had a moderately higher risk of ischaemic stroke than men (HR 1.16 (Confidence interval (CI) 95% 1.11–1.21). Matching on age and using time-dependent adjustment for confounders, women were not at higher risk of stroke than men (Rate Ratio 1.01; 95% CI 0.97–1.05). Mortality and bleeding rates were lower in women compared with men in both analyses. Conclusion In NVAF, women were not at higher risk of thromboembolic events than men in our study. The small increased risk reported in previous studies may be related to residual confounding, in particular from insufficient control for age.

Long-term Use of Inhaled Corticosteroids in COPD and the Risk of Fracture

Background It is uncertain whether long‐term use of inhaled corticosteroids (ICSs), widely used to treat COPD, increases the risk of fracture, particularly in women, in view of the postmenopausal risks. We assessed whether long‐term ICS use in patients with COPD increases the risk of hip or upper extremity fractures, and examined sex‐related differences. Methods The Quebec health‐care databases were used to form a cohort of patients with COPD over 1990 to 2005, followed until 2007 for the first hip or upper extremity fracture. In a nested case‐control analysis, each case of fracture was matched with 20 control subjects on age, sex, and follow‐up time. The adjusted rate ratio (RR) of fracture with ICS use, by duration and dose, was estimated using conditional logistic regression, with an interaction term to compare the risk in men and women. Results In the cohort of 240,110 subjects, 19,396 sustained a fracture during a mean 5.3 years (rate, 15.2 per 1,000 per year). Any use of ICSs was not associated with an increased rate of fracture (RR, 1.00; 95% CI, 0.97‐1.03). The fracture rate was increased with > 4 years of ICS use at daily doses ≥ 1,000 &mgr;g in fluticasone equivalents (RR, 1.10; 95% CI, 1.02‐1.19). This risk increase did not differ between men and women. Conclusions Long‐term ICS use at high doses is associated with a modest increase in the risk of hip and upper extremity fractures in patients with COPD. This dose‐duration risk increase does not appear to be higher for women.

Temporal trends in outpatient management of incident pulmonary embolism and associated mortality

INTRODUCTION In clinical trial settings, outpatient management of pulmonary embolism (PE) is feasible and safe, but less is known on its use in routine care. We determined trends in outpatient management of PE and associated mortality in a large non-select patient population. METHODS All residents of Quebec, Canada with a first-ever work-up for suspected PE in the emergency department (ED) over 10years were included. Patients could transition to outpatient management and from unconfirmed to confirmed PE in a time-varying fashion. Comparing the years 2005-9 with 2000-4, we assessed the odds ratio (OR) for outpatient management, and relative risk (RR) for all-cause mortality, readmissions for PE, and major bleeding in 30days. We adjusted the RR for a mortality risk score. RESULTS Of 15,217 patients included, 7583 were outpatients (7.5% confirmed PE) and 7634 were inpatients (60.6% confirmed PE). In all, 10.9% of patients with confirmed PE were outpatients, but outpatient management of confirmed PE was more likely in the latter study period (OR 1.73, 95%CI 1.44-2.09). Among outpatients with confirmed PE, mortality (RR 0.84, 95%CI 0.15-4.61) and readmission (RR 1.25, 95%CI 0.45-3.48) rates were stable, and only 3 major bleeding events were noted. Inpatients with confirmed PE had stable mortality rates (RR 0.95, 95%CI 0.72-1.24). CONCLUSION Outpatient PE management increased over 10years while remaining fairly uncommon. Nevertheless, stable mortality and readmission rates indicate this practice is safe in routine care, and add to the growing evidence in support of outpatient PE management.

The Risk of Sepsis with Inhaled and Oral Corticosteroids in Patients with COPD

ABSTRACT The use of oral and inhaled corticosteroids is associated with increases in the risk of infection, especially pneumonia. The risk of sepsis with corticosteroid treatment in patients with chronic obstructive pulmonary disease (COPD) has been little studied, however. We assessed whether the use of inhaled and oral corticosteroids in COPD is associated with an increase in the risk of sepsis. We carried out a retrospective cohort study using the administrative health databases of the province of Quebec, Canada, over the period 1990–2007. The cohort of patients with COPD included patients aged 55 years or older who used respiratory medications. A quasi-cohort analysis was used to estimate the rate ratio (RR) of sepsis in current users of inhaled corticosteroids and oral corticosteroids separately, after adjusting for differences in COPD disease severity and co-morbid conditions. The cohort included 163,514 patients treated for COPD, including 1,704 who were hospitalized for or died with sepsis during follow-up (incidence rate 1.94 per 1000 per year). The RR of sepsis associated with current use of inhaled corticosteroids was 0.98 (95%confidence interval [CI] 0.84–1.14). Current oral corticosteroid use was associated with a 66% increase in the risk of sepsis (RR 1.66; 95% CI: 1.35–2.05). The increase in risk remains for around 5 months after the oral corticosteroid exposure. Among patients treated for COPD, the risk of sepsis is not increased with inhaled corticosteroids, even at high doses, while the risk is increased with oral corticosteroids. This risk should be considered when treating exacerbations of COPD.