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1.  Cardiac glycosides use and the risk of lung cancer: a nested case–control study 
BMC Cancer  2014;14:573.
Two studies have reported statistically significant associations between the use of cardiac glycosides (CGs) and an increased risk of lung cancer. However, these studies had a number of methodological limitations. Thus, the objective of this study was to assess this association in a large population-based cohort of patients.
We used the United Kingdom Clinical Practice Research Datalink (CPRD) to identify a cohort of patients, at least 40 years of age, newly-diagnosed with heart failure, or supra-ventricular arrhythmia. A nested case–control analysis was conducted where each incident case of lung cancer identified during follow-up was randomly matched with up to 10 controls. Exposure to CGs was assessed in terms of ever use, cumulative duration of use and cumulative dose. Rate ratios (RRs) with 95% confidence intervals (CIs) were estimated using conditional logistic regression after adjusting for potential confounders.
A total of 129,002 patients were included, and followed for a mean (SD) of 4.7 (3.8) years. During follow-up, 1237 patients were newly-diagnosed with lung cancer. Overall, ever use of CGs was not associated with an increased risk of lung cancer when compared to never use (RR = 1.09, 95% CI: 0.94-1.26). In addition, no dose–response relationship was observed in terms of cumulative duration of use and cumulative dose with all RRs around the null value across quartile categories.
The results of this large population-based study indicate that the use of CGs is not associated with an increased risk of lung cancer.
PMCID: PMC4132915  PMID: 25104329
Lung cancer; Cardiac glycoside; Digoxin; Case–control study; Risk factor
2.  Pramipexole use and the risk of pneumonia 
BMC Neurology  2012;12:113.
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.
PMCID: PMC3522019  PMID: 23020246
Anti-parkinsonian drugs; Drug safety; Parkinson's disease; Restless leg syndrome; Observational study
3.  A net clinical benefit analysis of warfarin and aspirin on stroke in patients with atrial fibrillation: a nested case–control study 
As the management of patients treated with anticoagulants and antiplatelet drugs entails balancing coagulation levels, we evaluated the net clinical benefit of warfarin and aspirin on stroke in a large cohort of patients with atrial fibrillation (AF).
A population-based cohort study of all patients at least 18 years of age with a first-ever diagnosis of chronic AF during the period 1993–2008 was conducted within the United Kingdom General Practice Research Database. A nested case–control analysis was conducted to estimate the risk of ischemic stroke and intracranial hemorrhage associated with the use of warfarin and aspirin. Cases were matched up to 10 controls on age, sex, and date of cohort entry. The adjusted net clinical benefit of warfarin and aspirin (expressed as the number of strokes prevented per 100 persons per year) was calculated by subtracting the ischemic stroke rate (prevented by therapy) from the intracranial hemorrhage (ICH) rate (increased by therapy).
The cohort included 70,766 patients newly-diagnosed with chronic AF, of whom 5519 experienced an ischemic stroke and 689 an ICH during follow-up. The adjusted net clinical benefit of warfarin was 0.59 (95% CI: 0.45, 0.73). However, the benefit was not seen for patients below (0.08, 95%: -0.38, 0.54) and above (−0.49, 95% CI: -1.13, 0.15) therapeutic range. The net clinical benefit of warfarin, apparent after 3 months of continuous use, increased as a function of CHADS2 score. The net clinical benefit was not significant with aspirin (−0.07, 95% CI: -0.22, 0.08), though it was seen in certain subgroups.
Warfarin provides a net clinical benefit in patients with atrial fibrillation, which is maintained with longer duration of use, particularly when used within therapeutic range. A similar net effect is not as clear with aspirin.
PMCID: PMC3444325  PMID: 22734842
Atrial fibrillation; stroke; intracranial hemorrhage; warfarin; aspirin; net clinical benefit
4.  Risk of herpes zoster in patients prescribed inhaled corticosteroids: a cohort study 
Little is known concerning risk factors for herpes zoster in the general population. We hypothesised that inhaled corticosteroids (ICS) are a risk factor for herpes zoster especially among users of inhibitors of cytochrome P450 enzymes involved in their metabolism.
We identified a cohort of adult users of respiratory medications in the General Practice Research Database and carried out a nested case control analysis of inhaled corticosteroid use among 8900 new cases of herpes zoster and 88032 controls matching on age and calendar time.
The adjusted odds ratio for the relationship between current use of ICS and the occurrence of herpes zoster was 1.00 (95% confidence interval (CI), 0.94-1.07). There was no increase in risk of herpes zoster even at higher ICS doses; odds ratio 1.05 (95% CI, 0.96-1.14). Among subjects with concomitant prescriptions for an ICS and an inhibitor of cytochrome P450 3A4, the point estimate for the association between herpes zoster and the use of higher doses of inhaled corticosteroids was 1.23 (95% CI, 0.81-1.88).
The use of inhaled corticosteroids, even at high doses and in conjunction with inhibitors of their metabolism, was not a significant risk factor for the occurrence of herpes zoster in adults.
PMCID: PMC3267692  PMID: 22177425
herpes zoster; inhaled corticosteroids; adverse drug effects; observational studies; cytochrome P450
5.  Use of venlafaxine compared with other antidepressants and the risk of sudden cardiac death or near death: a nested case-control study 
Objective To assess whether use of the antidepressant venlafaxine is associated with an increased risk of sudden cardiac death or near death compared with other commonly used antidepressants.
Design Population based observational study.
Setting We did a nested case-control analysis within a new user cohort formed using the United Kingdom General Practice Research Database.
Participants New users of venlafaxine, fluoxetine, citalopram, or dosulepin on or after 1 January 1995, aged 18 to 89 years, with a diagnosis of depression or anxiety. Participants were followed-up until February 2005, or the occurrence of sudden cardiac death or near death, identified from medical records indicating non-fatal acute ventricular tachyarrhythmia, sudden death due to cardiac causes, or out of hospital deaths from acute ischaemic cardiac events. For each case, 30 controls were selected matched for age, sex, calendar time, and indication. We used conditional logistic regression to calculate the adjusted odds ratio of sudden cardiac death or near death associated with current use of venlafaxine compared with current use of fluoxetine, citalopram or dosulepin.
Results 207 384 participants were followed-up for an average of 3.3 years. There were 568 cases of sudden cardiac death or near death, which were matched to 14 812 controls. The adjusted odds ratio of sudden cardiac death or near death associated with venlafaxine use was 0.66 (95% confidence interval 0.38 to 1.14) relative to fluoxetine use, whereas compared with citalopram it was 0.89 (0.50 to 1.60) and with dosulepin 0.83 (0.46 to 1.52).
Conclusions In this large, population based study, the use of venlafaxine was not associated with an excess risk of sudden cardiac death or near death compared with fluoxetine, dosulepin, or citalopram, in patients with depression or anxiety.
PMCID: PMC2817047  PMID: 20139216
6.  Long-term natural history of chronic obstructive pulmonary disease: severe exacerbations and mortality 
Thorax  2012;67(11):957-963.
The long-term natural history of chronic obstructive pulmonary disease (COPD) in terms of successive severe exacerbations and mortality is unknown.
The authors formed an inception cohort of patients from their first ever hospitalisation for COPD during 1990–2005, 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.
The cohort included 73 106 patients hospitalised for the first time for COPD, of whom 50 580 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 10 000 per day in the first week after admission, dropping gradually to 5 after 3 months.
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.
PMCID: PMC3505864  PMID: 22684094
Asthma epidemiology; clinical epidemiology; COPD epidemiology; asthma; pulmonary embolism

Results 1-6 (6)