Cara Tannenbaum

A Systematic Review of Amnestic and Non-Amnestic Mild Cognitive Impairment Induced by Anticholinergic, Antihistamine, GABAergic and Opioid Drugs

BackgroundMild cognitive deficits are experienced by 18% of community-dwelling older adults, many of whom do not progress to dementia. The effect of commonly used medication on subtle impairments in cognitive function may be under-recognized.ObjectiveThe aim of the review was to examine the evidence attributing amnestic or non-amnestic cognitive impairment to the use of medication with anticholinergic, antihistamine, GABAergic or opioid effects.MethodsMEDLINE and EMBASE were searched for randomized, doubleblind, placebo-controlled trials of adults without underlying central nervous system disorders who underwent detailed neuropsychological testing prior to and after oral administration of drugs affecting cholinergic, histaminergic, GABAergic or opioid receptor pathways. Seventy-eight studies were identified, reporting 162 trials testing medication from the four targeted drug classes. Two investigators independently appraised study quality and extracted relevant data on the occurrence of amnestic, non-amnestic or combined cognitive deficits induced by each drug class. Only trials using validated neuropsychological tests were included. Quality of the evidence for each drug class was assessed based on consistency of results across trials and the presence of a dose-response gradient.ResultsIn studies of short-, intermediate- and long-acting benzodiazepine drugs (n = 68 trials), these drugs consistently induced both amnestic and non-amnestic cognitive impairments, with evidence of a dose-response relationship. H1-antihistamine agents (n = 12) and tricyclic antidepressants (n = 15) induced non-amnestic deficits in attention and information processing. Non-benzodiazepine derivatives (n = 29) also produced combined deficits, but less consistently than benzodiazepine drugs. The evidence was inconclusive for the type of cognitive impairment induced by different bladder relaxant antimuscarinics (n = 9) as well as for narcotic agents (n = 5) and antipsychotics (n = 5). Among healthy volunteers >60 years of age, low doses of commonly used medications such as lorazepam 0.5 mg, oxybutynin immediate release 5 mg and oxycodone 10 mg produced combined deficits.ConclusionNon-amnestic mild cognitive deficits are consistently induced by first-generation antihistamines and tricyclic antidepressants, while benzodiazepines provoke combined amnestic and non-amnestic impairments. Risk-benefit considerations should be discussed with patients in order to enable an informed choice about drug discontinuation or substitution to potentially reverse cognitive adverse effects.

Trospium chloride has no effect on memory testing and is assay undetectable in the central nervous system of older patients with overactive bladder

Background:  Muscarinic receptors in the brain play an important role in cognitive function, especially memory, and there is growing awareness that specific antimuscarinic drugs for overactive bladder (OAB) may have adverse central nervous system (CNS) effects. Selection of an antimuscarinic OAB drug with reduced potential for CNS effects could be especially beneficial in the elderly people, in whom even the modest cognitive impairment may negatively affect independence.

Urinary Incontinence After Stroke Identification, Assessment, and Intervention by Rehabilitation Professionals in Canada

Background and Purpose— Urinary incontinence (UI) is a common and distressing problem after stroke. Although there is evidence of new, effective UI poststroke rehabilitation intervention, it is unknown whether occupational therapists (OTs)’ and physical therapists (PTs)’ actual practices reflect best practices. We sought to determine the extent to which OTs and PTs identify, assess, and treat UI after stroke and to identify personal and organizational predictors of UI problem identification, best-practice assessment, and intervention. Methods— Six hundred sixty-three OTs (93% participation rate) and 656 PTs (87% participation rate) working in stroke rehabilitation in Canada were randomly selected and interviewed with a telephone-administered questionnaire. Each responded to a series of open-ended questions related to a generated case (vignette) of a typical client with stroke who was experiencing UI. Results— Only 39% of OTs and 41% of PTs identified UI after stroke as a problem. Fewer than 20% of OTs and 15% of PTs used best-practice assessments, and only 2% of OTs and 3% of PTs used best-practice interventions. Working in Ontario, having allocated learning time, and doing university teaching were among the variables explaining between 6% and 9% of the variability in UI identification and assessment. Conclusions— Canadian OTs and PTs do not routinely identify poststroke UI as a problem, and best-practice assessments and interventions are underused.

Reporting Sex, Gender, or Both in Clinical Research?

Virtually every clinical research report includes basic demographic characteristics about the study participants, such as age, and how many participants were male/men or female/women. Some research articles refer to this latter variable as sex, others refer to it as gender. As one of the first pieces of data reported, the importance of including sex appears undisputed. But what does the sex-gender category really entail, and how should it be reported? With emerging evidence that both sex and gender have an effect, for instance, on how an individual selects, responds to, metabolizes, and adheres to a particular drug regimen,1 there is an ethical and scientific imperative to report to whom research results apply. This Viewpoint explains the contexts in which sex and gender are relevant and provides suggestions for improving reporting of this characteristic.

Systematic Review and Meta-Analysis:: Do Clinical Trials Testing Antimuscarinic Agents for Overactive Bladder Adequately Measure Central Nervous System Adverse Events?

Experimental studies in healthy volunteers suggest that some antimuscarinic agents confer a risk of cognitive impairment, yet clinical trials of people with overactive bladder report only rare central nervous system (CNS) side effects. A lack of systematic measurement and reporting of CNS outcomes in clinical trials may partially explain this discrepancy. The purpose of this review and meta‐analysis was to ascertain the reporting bias associated with adverse CNS events in clinical drug trials of younger and older adults with overactive bladder. Articles were identified from MEDLINE and EMBASE databases until 2010 using the search terms “clinical trial” AND (one of) “oxybutynin, tolterodine, fesoterodine, propiverine, solifenacin, darifenacin, and trospium.” Eligibility criteria included original randomized trials involving adults with overactive bladder; standard doses of medication; reports of confusion, somnolence, sedation, dizziness, drowsiness, asthenia, insomnia, and vertigo; no evidence of dementia at baseline; and trials in English. Seventy‐seven percent (242/314) of eligible trials identified in the search neither measured nor reported CNS outcomes. Of the remaining 23%, it was difficult to distinguish whether CNS adverse events were systematically measured or spontaneously reported. Only one of 72 trials that were retained objectively measured changes in cognitive performance (Mini‐Mental State Examination). Dizziness was the most frequently reported side effect, in 3% of oxybutynin, 3.2% of propiverine, and 1.8% of tolterodine users, compared with 1.6% with placebo. Confusion was reported in fewer than 1% of cases. Age‐stratified analyses of CNS outcomes from trials in adults aged 65 and older with overactive bladder were found in only eight publications. Meta‐analyses were conducted with 33 randomized, double‐blind, placebo‐controlled trials to determine the effect of each drug and dose on different CNS outcomes. Study heterogeneity, dosing inconsistency, and reporting bias limited interpretation of the findings from the meta‐analyses. More‐detailed standardized measurement of age‐stratified CNS outcomes in clinical trials is required to better inform patients and clinicians about CNS risks associated with antimuscarinic agents.

The Effect of Bleeding Risk and Frailty Status on Anticoagulation Patterns in Octogenarians With Atrial Fibrillation: The FRAIL-AF Study

BACKGROUND Older adults are at increased risk of atrial fibrillation (AF), its thromboembolic complications, and bleeding. A significant percentage of octogenarians do not receive anticoagulation therapy. The objective of this study was to investigate the effect of thromboembolic risk, bleeding risk, and frailty on the anticoagulation status of octogenarians hospitalized with AF. METHODS A cross-sectional study was conducted in 682 hospitalized patients aged 80 years and older with AF or atrial flutter in Montreal, Québec. Consumption of warfarin or a new oral anticoagulant was documented. Medical record data were used to determine each patients frailty status using the Clinical Frailty Scale (CFS) and to evaluate the risk of stroke (CHADS2 [Congestive Heart Failure, Hypertension, Age, Diabetes, Stroke/Transient Ischemic Attack]) and bleeding (HAS-BLED [Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile international normalized ratio, Elderly (> 65 years) Drugs/alcohol concomitantly]). Univariable and multivariable logistic regression analyses were used to examine the effect of frailty status and the risk of stroke and bleeding on the probability of receiving anticoagulation therapy. RESULTS Seventy percent of octogenarians with AF received anticoagulation therapy (n = 475). A high risk of stroke (CHADS2 = 3 compared with CHADS2 = 1, odds ratio [OR], 3.58; 95% confidence interval [CI], 1.09-11.77), and the absence of severe frailty (CFS < 7; OR, 3.41; 95% CI, 1.84-6.33) were independently associated with anticoagulant use in multivariable analyses. A high risk of bleeding (HAS-BLED score ≥ 3; OR, 0.33; 95% CI, 0.12-0.86) was associated with the absence of anticoagulation. CONCLUSIONS Our study suggests a higher prevalence of appropriate anticoagulation among octogenarians with AF than reported in previous studies. Further work is needed to develop and disseminate tools to optimize the use of anticoagulants in this high-risk population.

The expanding scope of pharmacists’ practice: implications for physicians

Recent legislative and regulatory changes have supported a broadening of the scope of pharmacists’ practice across Canada. Under the authority of these new regulations, hospital- and community-based pharmacists are able to renew, refuse to fill, adjust or substitute prescriptions. Pharmacists may

Masculinity and Health in Late Life Men

Masculinity is a social construction that defines itself according to context. Older men constitute an unseen minority when it comes to their health, and thus the study of masculinity as it relates to health in older men requires deeper understanding. This article offers insights into how gender, health, and ageing interact for older men and explores how men negotiate the concept of masculinity in later life. The findings from two complementary studies are presented and discussed. The first study, a qualitative analysis of focus group discussions held with 48 community-dwelling older men, indicates that the desire to uphold hegemonic ideals of independence, self-reliance, and imperviousness to pain and illness are embedded in older men’s health-related beliefs and behaviors. Ill health and help seeking are often perceived as a threat to the masculine identity, and taking action for health is considered only when health status jeopardizes independence. In the second study, more than 2,000 men aged 55 to 97 years responded to a postal survey on health behaviors and masculinity. Results of the survey indicated that age predicts health behaviors and health care seeking better than scores on a masculinity index, which tended to remain stable regardless of age. Both the qualitative and quantitative findings support the hypothesis that with age men will succeed in incorporating actions into their daily lives in a way that does not conflict with their perceived resilience to frailty and weakness, even if such actions involve seeking help for illness or adopting healthier lifestyle behaviors.

Methodological Challenges in Determining Longitudinal Associations Between Anticholinergic Drug Use and Incident Cognitive Decline

To compare the effect of using different anticholinergic drug scales and different models of cognitive decline in longitudinal studies.

Outcomes in Urinary Incontinence : Reconciling Clinical Relevance with Scientific Rigour

OBJECTIVES To aid clinicians in selecting an outcome measure for the assessment of urinary incontinence (UI), from the perspective of both scientific rigour and clinical utility. METHODS We conducted a comprehensive review of the literature on outcome measures for the assessment of UI in adults. Tools were classified by instrument type (ie, subjective measures, objective measures, clinical observations, quality of life, and combined instruments) and assessed for scientific rigour based on their psychometric properties (reliability, validity, responsiveness). The clinical relevance of each tool was considered in terms of current usage and practicality. RESULTS The most rigorous validation processes were identified for quality-of-life questionnaires, including the Incontinence Impact Questionnaire, Kings Health Questionnaire, Incontinence Quality of Life questionnaire, and Urogenital Distress Inventory. Bladder diaries, goal-attainment scales, and combined measures such as the International Consultation on Incontinence Questionnaire appear to be more practical for use in clinics. The Clinical Global Impression of Improvement is the outcome most widely used clinically, but least well validated. CONCLUSIONS To elevate the level of outcome assessment for UI to meet that of other urology specialties, it is necessary to reconcile the realities of clinical practice with the scientific rigour of UI research, and to mainstream outcome measures that are reciprocally translatable between the two settings.