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- Beta-blockers are associated with increased risk of first cardiovascular events in non-diabetic hypertensive elderly patients. [JOURNAL ARTICLE]
- Pharmacoepidemiol Drug Saf 2014 Jul 5.
Although treatment should be considered for elderly patients with hypertension (HTN), the effectiveness of beta-blockers (BBs) compared with other medications is less clear. This study's objective is to assess the relative effectiveness of BBs in elderly primary prevention patients with uncomplicated HTN.This is a population-based nested case-control study. The cohort is composed of 94 844 elderly patients followed through 2009 and diagnosed with HTN between 2000 and 2004, without recent antecedents of diabetes, renal disease, or cardiovascular disease (CVD). Individuals with a CVD outcome were considered cases, and controls were matched to cases according to age, sex, date of cohort entry, and comorbidity index. Patients whose treatment included a BB were compared with patients on other HTN drug(s).The BB use by patients was associated with an increased risk for CVD events (odds ratio (OR) = 1.36, 95%CI: 1.31-1.40) compared with patients using antihypertensive therapies without BBs. Sensitivity analyses suggest that this increased risk is not due to differences in prescription patterns on the basis of perceived disease severity.In real-world settings, antihypertensive therapies that include BBs are associated with less effective prevention of adverse outcomes in elderly hypertensive patients in primary prevention compared with antihypertensive therapies without BBs. Pending further studies, we recommend caution when prescribing BBs in primary prevention except when otherwise indicated. Copyright © 2014 John Wiley & Sons, Ltd.
- Utilization of triptans in Sweden; analyses of over the counter and prescription sales. [JOURNAL ARTICLE]
- Pharmacoepidemiol Drug Saf 2014 Jul 18.
To enable easier access to triptans, the drug of choice for moderate to severe migraine, some countries have made triptans available without prescription, that is, over the counter (OTC). Concern has been raised about this. The aim of this study was to describe the utilization pattern of triptans in Sweden before and after the OTC switch.Wholesaler and aggregated sales data from all Swedish pharmacies 1991 to 2011 and patient identity data on dispensed prescriptions 2007 and 2011 from the Swedish National Prescribed Drug Register were used to investigate volume and expenditure of triptans. The databases contain complete data for all drugs sold in Sweden or dispensed to all Swedish inhabitants (9.5 million in 2012).Volumes of triptans have increased to 7.0 million defined daily doses (DDD) on prescriptions and 0.7 million DDDs OTC in 2011. Prescriptions were dispensed to 10.0 and 10.1 per 1000 inhabitants in 2007 and 2011, respectively. Although half of those dispensed triptans in 2007 were not in 2011, the incidence remained stable at 2.8 patients per thousand person-years. In 2011, the 10% of the heaviest users accounted for 44% and 48% of dispensed triptans in women and men, respectively.Triptans OTC and the volumes dispensed on prescription have increased as has the DDD per patient purchasing triptans on prescription. However, the number of patient's dispensed triptans on prescription has remained stable. A concern is that almost half of prescribed triptans are purchased by 10% of the users. Copyright © 2014 John Wiley & Sons, Ltd.
- How (not) to inform patients about drug use: use and effects of negations in Dutch patient information leaflets. [JOURNAL ARTICLE]
- Pharmacoepidemiol Drug Saf 2014 Jul 15.
Under EU regulations, patient information leaflets (PILs) are required to be clear and understandable. Negations (e.g., not, no) are a linguistic aspect that may impact PIL comprehension, yet go unmentioned in these regulations. We conducted two studies to determine (1) how negations are used in Dutch PILs (study 1) and (2) the effects of negations on readers (study 2).Study 1 was a content analysis of 30 PILs of different brands of pollinosis drugs, half of which were freely available in drugstores and half only by physician prescription. We mapped negation use in PIL sections on 'proper usage' and 'potential side effects'. Study 2 was an experiment in which participants (N = 80, Mage = 33.19 years, SDage = 13.66; 76.3% female) were presented with one of two PIL texts on proper drug usage. Texts were identical except for the use of negations. After reading, participants answered questions about comprehension, PIL appreciation and medical adherence intentions.Study 1 demonstrates that negations are often used in PILs as 21.0% of clauses contain at least one negation. This number is higher in sections related to potential side effects than proper usage. Study 2 demonstrates that negations decrease both actual and subjective comprehension. Negations also decrease PIL appreciation and medical adherence intentions. The reduction in medical adherence intentions is driven by the decrease of subjective and not actual comprehension.In general, participants prefer PILs that contain clear and comprehensible language. To increase comprehensibility, PIL designers should refrain from using negations as much as possible. Copyright © 2014 John Wiley & Sons, Ltd.
- Cardiovascular and mortality risks in older Medicare patients treated with varenicline or bupropion for smoking cessation: an observational cohort study. [JOURNAL ARTICLE]
- Pharmacoepidemiol Drug Saf 2014 Jul 5.
To compare cardiovascular and mortality risks in elderly patients treated with varenicline or bupropion for smoking cessation.Elderly Medicare beneficiaries were entered into new-user cohorts of varenicline or bupropion for smoking cessation and followed on therapy for primary outcomes of acute myocardial infarction (AMI), stroke, mortality, and a composite of any of these events. Secondary outcomes were unstable angina, coronary revascularization, and a composite of any primary or secondary outcome event. Propensity score stratification was used to adjust for baseline differences in potential confounding factors. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox proportional hazards, with bupropion as reference.In cohorts of 74 824 varenicline and 14 133 bupropion users, there were 164 AMI, 96 stroke, 87 death, 317 primary composite, and 814 secondary composite events while on therapy. The HRs (95%CI) were 0.79 (0.50-1.24) for AMI, 1.27 (0.63-2.55) for stroke, 0.58 (0.30-1.13) for death, 0.84 (0.58-1.23) for the primary composite, and 0.92 (0.73-1.14) for the secondary composite. The risk of AMI or the primary composite outcome did not differ in subgroups defined by age, diabetes status, or presence of underlying ischemic heart disease. Only 30% of patients remained on either study drug beyond their first prescription.Cardiovascular and mortality risks were not increased in older patients treated with varenicline compared with bupropion for smoking cessation. A potential increase in the risk of stroke with varenicline could not be excluded. Treatment persistence with either drug was low. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.
- Validity of psoriatic arthritis and capture of disease modifying antirheumatic drugs in the health improvement network. [JOURNAL ARTICLE]
- Pharmacoepidemiol Drug Saf 2014 Jul 5.
The aims of this study are to examine the validity of diagnostic codes for psoriatic arthritis in The Health Improvement Network (THIN) and to examine the agreement between General Practitioner (GP) report and prescription records for disease modifying antirheumatic drugs (DMARDs).Questionnaires were sent to the GPs of 100 randomly selected patients with at least one medical record code for psoriatic arthritis. The positive predictive value (PPV) for a GP confirmed diagnosis was calculated, and alternative algorithms were examined to determine which method resulted in the highest PPV.The PPV for a single code for psoriatic arthritis was 85% (95%CI: 75.8-91.7%). Adding a prescription for a DMARD increased the PPV to 91% but with a substantial loss in sensitivity. Agreement between GPs and prescription data for use of an oral DMARD was 69%.The diagnosis codes for psoriatic arthritis used in THIN are valid. All prescriptions for DMARDs may not be accounted for in THIN. Copyright © 2014 John Wiley & Sons, Ltd.
- Benefit-risk assessment in a post-market setting: a case study integrating real-life experience into benefit-risk methodology. [JOURNAL ARTICLE]
- Pharmacoepidemiol Drug Saf 2014 Jul 5.
Difficulties may be encountered when undertaking a benefit-risk assessment for an older product with well-established use but with a benefit-risk balance that may have changed over time. This case study investigates this specific situation by applying a formal benefit-risk framework to assess the benefit-risk balance of warfarin for primary prevention of patients with atrial fibrillation.We used the qualitative framework BRAT as the starting point of the benefit-risk analysis, bringing together the relevant available evidence. We explored the use of a quantitative method (stochastic multi-criteria acceptability analysis) to demonstrate how uncertainties and preferences on multiple criteria can be integrated into a single measure to reduce cognitive burden and increase transparency in decision making.Our benefit-risk model found that warfarin is favourable compared with placebo for the primary prevention of stroke in patients with atrial fibrillation. This favourable benefit-risk balance is fairly robust to differences in preferences. The probability of a favourable benefit-risk for warfarin against placebo is high (0.99) in our model despite the high uncertainty of randomised clinical trial data. In this case study, we identified major challenges related to the identification of relevant benefit-risk criteria and taking into account the diversity and quality of evidence available to inform the benefit-risk assessment.The main challenges in applying formal methods for medical benefit-risk assessment for a marketed drug are related to outcome definitions and data availability. Data exist from many different sources (both randomised clinical trials and observational studies), and the variability in the studies is large. Copyright © 2014 John Wiley & Sons, Ltd.
- Multiple sclerosis clinical course and cardiovascular disease risk - Swedish cohort study. [JOURNAL ARTICLE]
- Eur J Neurol 2014 Jul 17.
Cardiovascular disease (CVD) risk amongst multiple sclerosis (MS) patients appears raised, but few studies have examined CVD risk amongst an unselected MS patient group. MS course may be relevant for CVD risk. Our aim was to assess CVD risk and variation by course in MS patients.The Multiple Sclerosis Register identified 7667 patients who received an MS diagnosis between 1964 and 2005. They were matched by age, period, region and sex with 76 045 members of the general population without MS using Swedish registers. Poisson regression compared the two cohorts to estimate the relative risk for CVD, overall, as well as grouped and individual CVD diagnoses.MS patients had an increased adjusted relative risk (with 95% confidence intervals; number of MS cohort events) for CVD of 1.31 (1.22-1.41; n = 847), with some variation by course: relapsing-remitting 1.38 (1.17-1.62; n = 168); secondary progressive 1.30 (1.18-1.53; n = 405) and primary progressive 1.15 (0.93-1.41; n = 108). The association for the relapsing-remitting course was not significant after excluding the first year of follow-up. Overall incidence rates per 1000 person-years for CVD are 11.8 (11.06-12.66) for the MS cohort and 8.8 (8.60-9.05) for the non-MS cohort. The most pronounced association was for deep vein thrombosis: relapsing-remitting 2.16 (1.21-3.87; n = 14), secondary progressive 3.41 (2.45-4.75; n = 52) and primary progressive 3.57 (1.95-6.56; n = 15). MS was associated with ischaemic stroke but largely during the first year of follow-up. MS was associated with a decreased relative risk for angina pectoris and atrial fibrillation.There is a significantly increased relative risk for CVD in MS, particularly for venous thromboembolic disorders in progressive MS, suggesting immobility as a possible factor. An increased frequency of ischaemic stroke in MS is most probably due to surveillance bias resulting from diagnostic investigations for MS. There is no increased relative risk for ischaemic heart disease in MS and atrial fibrillation appears to be less common than amongst the general population.
- The burden of premature opioid-related mortality. [JOURNAL ARTICLE]
- Addiction 2014 Jul 7.
The burden of premature mortality due to opioid-related death has not been fully characterized. We calculated temporal trends in the proportion of deaths attributable to opioids and estimated years of potential life lost (YLL) due to opioid-related mortality in Ontario, Canada.Cross-sectional study.Ontario, Canada.Individuals who died of opioid-related causes between January 1991 and December 2010.We used the Registered Persons Database and data abstracted from the Office of the Chief Coroner to measure annual rates of opioid-related mortality. The proportion of all deaths related to opioids was determined by age group in each of 1992, 2001 and 2010. The YLL due to opioid-related mortality were estimated, applying the life expectancy estimates for the Ontario population.We reviewed 5935 opioid-related deaths in Ontario between 1991 and 2010. The overall rate of opioid-related mortality increased by 242% between 1991 (12.2 per 1 000 000 Ontarians) and 2010 (41.6 per 1 000 000 Ontarians; P < 0.0001). Similarly, the annual YLL due to premature opioid-related death increased threefold, from 7006 years (1.3 years per 1000 population) in 1992 to 21 927 years (3.3 years per 1000 population) in 2010. The proportion of deaths attributable to opioids increased significantly over time within each age group (P < 0.05). By 2010, nearly one of every eight deaths (12.1%) among individuals aged 25-34 years was opioid-related.Rates of opioid-related deaths are increasing rapidly in Ontario, Canada, and are concentrated among the young, leading to a substantial burden of disease.
- Metformin and the risk of head and neck cancer: a case-control analysis. [JOURNAL ARTICLE]
- Diabetes Obes Metab 2014 Jul 7.
Metformin use has been associated with a decreased risk of some cancers, though data on head and neck cancer (HNC) are scarce. We explored the relation between use of antidiabetic drugs and the risk of HNC.We conducted a case-control analysis in the UK-based Clinical Practice Research Datalink (CPRD) of people with incident HNC between 1995 and 2013 below the age of 90 years. Six controls per case were matched on age, sex, calendar time, general practice, and number of years of active history in the CPRD prior to the index date. Other potential confounders including BMI, smoking, alcohol consumption, and comorbidities were also evaluated. The final analyses were adjusted for BMI, smoking and diabetes mellitus (or diabetes duration in a sensitivity analysis). Results are presented as odds ratios (ORs) with 95% confidence intervals (CI).Use of metformin was not associated with a statistically significant altered risk of HNC overall (1-29 prescriptions: adj. OR 0.87, 95% CI 0.61-1.24 and ≥30 prescriptions adj. OR 0.80, 95% CI 0.53-1.22), nor was long-term use of sulfonylureas (adj. OR 0.87, 95% CI 0.59-1.30), or any insulin use (adj. OR 0.92, 95% CI 0.63-1.35). However, we found a (statistically non-significant) decreased risk of laryngeal cancer associated with long-term metformin use (adj. OR 0.41, 95% CI 0.17-1.03).In our population-based study, use of antidiabetic drugs was not associated with a materially altered risk of HNC. Our data suggest a protective effect of long-term metformin use for laryngeal cancer.
- [Antipsychotic drugs and their influence on the carbohydrate metabolism in patients with schizophrenia-spectrum disorders]. [English Abstract, Journal Article]
- Zh Nevrol Psikhiatr Im S S Korsakova 2014; 114(5):86-91.
The effect of antipsychotic drugs, typical and atypical neuroleptics, is described in the following sections of this paper: antipsychotic drugs and carbohydrate metabolism, prevention and risk factors, pharmacoepidemiology, treatment. It is concluded that neuroleptic treatment increases the risk of metabolic impairment. Mechanisms of this effect are not clear so far. Ethnicity, sex, age and features of the therapy may play a role. Clozapine, olanzapine, ziprasidone, sertindole and some typical neuroleptics are risk factors as well. Common glucose-reducing drugs as well as prevention of metabolic impairment and special behavioral training,including the control over the level of glycemia, are used in treatment of diabetes mellitus induced by neuroleptics.