Yola Moride

Benzodiazepine use and risk of Alzheimer’s disease: case-control study

Objectives To investigate the relation between the risk of Alzheimer’s disease and exposure to benzodiazepines started at least five years before, considering both the dose-response relation and prodromes (anxiety, depression, insomnia) possibly linked with treatment. Design Case-control study. Setting The Quebec health insurance program database (RAMQ). Participants 1796 people with a first diagnosis of Alzheimer’s disease and followed up for at least six years before were matched with 7184 controls on sex, age group, and duration of follow-up. Both groups were randomly sampled from older people (age >66) living in the community in 2000-09. Main outcome measure The association between Alzheimer’s disease and benzodiazepine use started at least five years before diagnosis was assessed by using multivariable conditional logistic regression. Ever exposure to benzodiazepines was first considered and then categorised according to the cumulative dose expressed as prescribed daily doses (1-90, 91-180, >180) and the drug elimination half life. Results Benzodiazepine ever use was associated with an increased risk of Alzheimer’s disease (adjusted odds ratio 1.51, 95% confidence interval 1.36 to 1.69; further adjustment on anxiety, depression, and insomnia did not markedly alter this result: 1.43, 1.28 to 1.60). No association was found for a cumulative dose <91 prescribed daily doses. The strength of association increased with exposure density (1.32 (1.01 to 1.74) for 91-180 prescribed daily doses and 1.84 (1.62 to 2.08) for >180 prescribed daily doses) and with the drug half life (1.43 (1.27 to 1.61) for short acting drugs and 1.70 (1.46 to 1.98) for long acting ones). Conclusion Benzodiazepine use is associated with an increased risk of Alzheimer’s disease. The stronger association observed for long term exposures reinforces the suspicion of a possible direct association, even if benzodiazepine use might also be an early marker of a condition associated with an increased risk of dementia. Unwarranted long term use of these drugs should be considered as a public health concern.

Delirium in older emergency department patients discharged home: effect on survival

OBJECTIVES: To determine whether prevalent delirium is an independent predictor of mortality in older patients seen in emergency departments (EDs) and discharged home without admission.

Long-Term Continuous Use of Benzodiazepines by Older Adults in Quebec: Prevalence, Incidence and Risk Factors

OBJECTIVE: To determine the prevalence and incidence of long‐term use of benzodiazepines and to assess patient‐, prescriber‐, and drug‐related risk factors.

Benzodiazepine use and risk of dementia: a nested case-control study.

The objective of this article was to examine the possible association between benzodiazepine use and the risk of dementia in the elderly. This was a nested case--control study set in community settings in Bordeaux area, France. The participants were a representative sample of 3,777 elderly persons (65 years of age and older) followed from 1989 to 1997. The main outcome measures were the use of benzodiazepines in incident cases of dementia versus nondemented controls. On the basis of medical and psychological data, 150 patients were diagnosed with dementia according to the criteria of the third revision of the Diagnostic and Statistical Manual of Mental Disorders. Information on benzodiazepine use was obtained by face-to-face interview and visual assessment of patients medicine chest by a trained neuropsychologist. After controlling for age, gender, education level, living alone, wine consumption, psychiatric history, and depressive symptomatology, ever use of benzodiazepines was associated with a significantly increased risk of dementia [adjusted odds ratio (OR), 1.7; 95% confidence interval, 1.2-2.4]. Former use was associated with a significantly increased risk of dementia (adjusted OR, 2.3; 95% CI,1.2-4.5). No association was found between dementia and the current use of benzodiazepines (adjusted OR, 1.0; 95% CI, 0.6-1.6). Our finding suggest that former use of benzodiazepines could be a risk factor for dementia, but more detailed investigation are needed.

Evaluation of the confusion assessment method (CAM) as a screening tool for delirium in the emergency room

The objective of this study was to compare the results of the Confusion Assessment Method (CAM) obtained by a trained non-physician interviewer to those obtained by a geriatrician, among a sample of elderly patients seen in an emergency room. A group of 110 elderly patients (> or =66 years) were evaluated in the emergency room by a lay interviewer. The geriatrician conducted an interview in the presence of the lay interviewer. Subsequently, the geriatrician and the lay interviewer completed a CAM checklist independently. Kappa statistics, sensitivity, specificity, positivity predictive value (PPV), and negative predictive value (NPV) for the geriatricians and lay interviewers results with the CAM diagnostic algorithm were compared. The kappa coefficient was 0.91, the sensitivity 0.86, the specificity 1.00, the PPV 1.00, and the NPV 0.97. In conclusion, the CAM used by a trained lay interviewer in the emergency room is sensitive, specific, reliable and easy to use for the identification of patients with delirium. The under-recognition and under-treatment of delirium is a major health issue and has important clinical and financial implications. The implementation of systematic screening in populations at risk could increase the rate of early detection and lead to the appropriate management of delirious patients.

Does long-acting injectable risperidone make a difference to the real-life treatment of schizophrenia? Results of the Cohort for the General study of Schizophrenia (CGS)

OBJECTIVE The primary aim of this study was to compare the impact of risperidone long-acting injectable (R-LAI) to other antipsychotics on rates of hospitalisation in real-life settings. METHOD The Cohort for the General study of Schizophrenia (CGS) followed 1859 patients diagnosed with schizophrenia (DSM-IV) from 177 psychiatric wards of public and private hospitals across France over a mean period of 12months. These patients were ambulatory or had been hospitalised for less than 93days at study entry. Recruitment was stratified for long-acting second-generation antipsychotic use. A multivariate Poisson regression adjusted for confounding with propensity scores and allowing for autocorrelation was used for the calculation of relative rates of hospitalisation with 95% confidence intervals. RESULTS The mean age of participants was 37.65years, 68.3% were male and 36.7% were hospitalised for less than 93days at study entry. Altogether, participants accumulated 796 hospital stays (53.4 per 100 person-years). R-LAI patients were slightly younger and had been hospitalised more often in the past 12months compared to non-R-LAI users. The adjusted Poisson regression analysis showed R-LAI use to be associated with a lower rate of future hospitalisation: 0.66 [0.46-0.96] compared to non-R-LAI use, and 0.53 [0.32-0.88] compared to use of other LAIs. CONCLUSION Use of R-LAI was associated with lower rates of hospitalisation compared to non-use of R-LAI.

Donepezil and rivastigmine in the treatment of Alzheimer's disease: a best-evidence synthesis of the published data on their efficacy and cost-effectiveness

BACKGROUND Various drugs have been approved for the treatment of Alzheimers disease (AD) in the United States and Canada, including donepezil and rivastigmine, although questions remain as to their efficacy, effectiveness, and long-term benefits. OBJECTIVE The goal of this study was to conduct a best-evidence synthesis of data on the efficacy and cost-effectiveness of donepezil and rivastigmine in the treatment of AD. METHODS Relevant published randomized controlled trials (RCTs) and Phase IV open-label extension studies (excluding abstracts) were identified through searches of MEDLINE, HealthSTAR, and PsycINFO for the period January 1984 to October 2001. The bibliographies of retrieved articles were searched for additional publications. For inclusion in the best-evidence synthesis, clinical trials had to pass a blinded quality assessment (score > or =5 on the Jadad scale) and use National Institute of Neurological and Communicative Disease and Stroke-Alzheimers Disease and Related Disorders Association diagnostic criteria. Economic studies were selected using National Health Service Centre for Reviews and Dissemination criteria for reporting critical summaries of economic evaluations. RESULTS Nine RCTs of donepezil and 2 of rivastigmine were identified and met inclusion criteria for the best-evidence synthesis. Eight donepezil trials and both rivastigmine trials included patients with mild AD (Mini-Mental State Examination [MMSE] score, 15-27) or moderate AD (MMSE score, 8-14); 1 donepezil trial included patients with moderate or severe AD (MMSE score, 0-7). In the RCTs of donepezil, the mean decrease in scores on the Alzheimers Disease Assessment Scale-cognitive subscale (ADAS-cog) was greater with active treatment than with placebo (lower scores indicate less cognitive deterioration). In the RCTs of rivastigmine, ADAS-cog scores decreased over the follow-up period with both active treatment and placebo; however, scores decreased more with active treatment. Three Phase IV studies of donepezil and I Phase IV study of rivastigmine were identified. Their results were consistent with those of the RCTs. Ten economic studies (7 donepezil, 3 rivastigmine) were identified and reviewed. In 4 of the donepezil studies and all 3 rivastigmine studies, use of the drug cost less than a no-drug strategy. CONCLUSIONS The efficacy data indicate that both donepezil and rivastigmine can delay cognitive impairment and deterioration in global health for at least 6 months in patients with mild to moderate AD. Patients receiving active treatment will have more favorable ADAS-cog scores for at least 6 months, after which their scores will begin to converge with those of patients receiving placebo. Differences in methodology, types of direct or indirect costs included, and sources of cost data made it difficult to compare and synthesize findings of the economic studies; therefore, the cost-effectiveness data are inconclusive.

Antipsychotic Use and Myocardial Infarction in Older Patients With Treated Dementia

BACKGROUND Antipsychotic agents (APs) are commonly prescribed to older patients with dementia. Antipsychotic use is associated with an increased risk of ischemic stroke in this population. Our study aimed to investigate the association of AP use with the risk of acute myocardial infarction (MI). METHODS A retrospective cohort of community-dwelling older patients who initiated cholinesterase inhibitor treatment was identified between January 1, 2000, and December 31, 2009, using the Quebec, Canada, prescription claims database. From this source cohort, all new AP users during the study period were matched with a random sample of AP nonusers. The risk of MI was evaluated using Cox proportional hazards models, adjusting for age, sex, cardiovascular risk factors, psychotropic drug use, and propensity scores. In addition, a self-controlled case series study using conditional Poisson regression modeling was conducted. RESULTS Among the source cohort of 37,138 cholinesterase inhibitor users, 10,969 (29.5%) initiated AP treatment. Within 1 year of initiating AP treatment, 1.3% of them had an incident MI. Hazard ratios for the risk of MI after initiation of AP treatment were 2.19 (95% CI, 1.11-4.32) for the first 30 days, 1.62 (95% CI, 0.99-2.65) for the first 60 days, 1.36 (95% CI, 0.89-2.08) for the first 90 days, and 1.15 (95% CI, 0.89-1.47) for the first 365 days. The self-controlled case series study conducted among 804 incident cases of MI among new AP users yielded incidence rate ratios of 1.78 (95% CI, 1.26-2.52) for the 1- to 30-day period, 1.67 (95% CI, 1.09-2.56) for the 31- to 60-day period, and 1.37 (95% CI, 0.82-2.28) for the 61- to 90-day period. CONCLUSION Antipsychotic use is associated with a modest and time-limited increase in the risk of MI among community-dwelling older patients treated with cholinesterase inhibitors.

Impact of noncompliance with alendronate and risedronate on the incidence of nonvertebral osteoporotic fractures in elderly women.

AIMS To evaluate the association between noncompliance with alendronate and risedronate and the risk of nonvertebral osteoporotic fracture in community-dwelling elderly women. METHODS A nested case-control study was conducted using the Quebec administrative health databases. To be included in the cohort, women needed to be aged > or = 68 years and to have initiated treatment with alendronate or risedronate between 1 January 2002 and 31 March 2005. Cases consisted of all women with an incident nonvertebral osteoporotic fracture occurring > or = 1 year after initiation of therapy. Each case was matched with up to 20 controls using incidence density sampling, according to age (+/- 1 year) and follow-up duration. A woman was noncompliant if she had a medication possession ratio (MPR) <80% for total follow-up duration. Rate ratios (RR) for fracture were estimated through conditional logistic regression analysis, adjusting for potential confounders. RESULTS Among the 30 259 women included in the cohort, 1036 nonvertebral fracture cases were identified and were matched to 20 069 controls. Compared with women with a MPR > or = 80%, those with a MPR < 80% had a greater risk of nonvertebral fracture [adjusted RR 1.27, 95% confidence interval (CI) 1.12, 1.44]. Considering hip fracture only, the multivariate model yielded similar results, (adjusted RR 1.28, 95% CI 1.02, 1.61). CONCLUSIONS Among community-dwelling elderly women, noncompliance with alendronate or risedronate is associated with an increased risk of nonvertebral fracture.

Suboptimal Duration of Antidepressant Treatments in the Older Ambulatory Population of Quebec: Association with Selected Physician Characteristics

OBJECTIVES: To assess the association between selected physician characteristics and suboptimal duration of antidepressant use in the older outpatient population.