Small longitudinal study of serum anticholinergic activity and cognitive change in community-dwelling older adults.

OBJECTIVE: The discriminative ability of serum anticholinergic activity (SAA) to differentiate between older individuals with stable versus deteriorating cognition remains undetermined. We examined the relationship between SAA changes, the presence or absence of a mild neurocognitive disorder, age and anticholinergic medication over a one-year time period. METHODS: SAA at baseline and one-year follow-up was measured for 121 older adults without dementia. Participants were classified at both timepoints as being cognitively intact or meeting the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for a mild neurocognitive disorder. Medications were assessed according to the Anticholinergic Cognitive Burden (ACB) scale. RESULTS: SAA changes did not discriminate between individuals whose cognition remained stable versus those with improvement or decline (H[3]=0.725, p=0.867). SAA change did not vary between age groups, and could not reliably differentiate between individuals on ACB medication or not. CONCLUSION: While SAA does not appear to be a valid biomarker for cognitive decline, longitudinal studies with a larger sample size and longer duration are required to confirm this finding.

Pathophysiology of idiopathic overactive bladder and the success of treatment: a systematic review from ICI-RS 2013.

AIMS: To investigate the frequency of phenotype profiling of patients with idiopathic overactive bladder (OAB) syndrome, and to determine the effectiveness of treatment among individuals with different pathophysiologic profiles. METHODS: The electronic databases MEDLINE, EMBASE, Cochrane CENTRAL, Cochrane Database of Systematic Reviews, and CINAHL were searched from January 1, 1980 to August 12, 2013 for interventional randomized controlled treatment trials (RCTs) of idiopathic OAB. Phenotying for pathophysiologies originating in the urothelial/mucosal layer of the bladder, the detrusor muscle cell layer, and the central nervous system were sought. Articles that analyzed urgency outcomes based on pathophysiologic profiling were selected. Due to the heterogeneity of the included interventions and outcome assessment measures, meta-analysis was not appropriate and a qualitative synthesis was undertaken. RESULTS: Of 239 original RCTs of idiopathic OAB, 48 (20%) profiled participants on underlying pathophysiology. Less than half of these (n = 20) reported treatment efficacy for urgency symptoms by pathophysiological sub-type. One examined the effect of botulinum A toxin on interstitial cell protein expression. Four compared treatment efficacy in OAB patients with and without involuntary detrusor contractions. Fifteen compared the effect of treatment on urgency reduction in patients with detrusor overactivity. There were no consistent trends in treatment efficacy according to pathophysiologic sub-type. No studies examined urothelial dysfunction or abnormal central processing of bladder afferent signaling in response to treatment. CONCLUSIONS: In order to advance the field of idiopathic OAB, more trials are needed that profile and test urgency outcomes in participants according to suspected underlying pathophysiology. Neurourol. Urodynam. 33:611-617, 2014. © 2014 Wiley Periodicals, Inc.

Prevalence of commonly prescribed medications potentially contributing to urinary symptoms in a cohort of older patients seeking care for incontinence.

BACKGROUND: Several medication classes may contribute to urinary symptoms in older adults. The purpose of this study was to determine the prevalence of use of these medications in a clinical cohort of incontinent patients. METHODS: A cross-sectional study was conducted among 390 new patients aged 60 years and older seeking care for incontinence in specialized outpatient geriatric incontinence clinics in Quebec, Canada. The use of oral estrogens, alpha-blocking agents, benzodiazepines, antidepressants, antipsychotics, ACE inhibitors, loop diuretics, NSAIDs, narcotics and calcium channel blockers was recorded from each patient's medication profile. Lower urinary tract symptoms and the severity of incontinence were measured using standardized questionnaires including the International Consultation on Incontinence Questionnaire. The type of incontinence was determined clinically by a physician specialized in incontinence. Co-morbidities were ascertained by self-report. Logistic regression analyses were used to detect factors associated with medication use, as well as relationships between specific medication classes and the type and severity of urinary symptoms. RESULTS: The prevalence of medications potentially contributing to lower urinary tract symptoms was 60.5%. Calcium channel blockers (21.8%), benzodiazepines (17.4%), other centrally active agents (16.4%), ACE inhibitors (14.4%) and estrogens (12.8%) were most frequently consumed. Only polypharmacy (OR = 4.9, 95% CI = 3.1-7.9), was associated with medication use contributing to incontinence in analyses adjusted for age, sex, and multimorbidity. No associations were detected between specific medication classes and the type or severity of urinary symptoms in this cohort. CONCLUSION: The prevalence of use of medications potentially causing urinary symptoms is high among incontinent older adults. More research is needed to determine whether de-prescribing these medications results in improved urinary symptoms.

Evidence-based information leads to reduction in inappropriate drug prescribing: Results from Indian older inpatients.

BACKGROUND: Although several guidelines for appropriate prescribing are available, inappropriate drug prescription remains noteworthy problem among older adults. Indian older patients are also not spare from this issue and existing literature indicates a fair level of inappropriate drug use (IDU). OBJECTIVES: Identified potentially IDU and documented their reduction based on provided evidence-based information and also identified possible predictors of IDU in older inpatients. SETTING: Three years prospective study included 1510 inpatients aged 60 years or over, of both sexes. IDU identified using the Modified Updated AGS Beers Criteria 2012. RESULTS: The patients had an average age of 67.10 ± 0.23 years and on an average were prescribed 9.29 ± 0.11 medications. Using AGS Beers Criteria 2012, total IDU was found to be 21% (n = 325). Of total 287 patients received only one inappropriate drug whereas 38 patients received two or more inappropriate drug(s). According to first list of criteria long acting benzodiazepines, anticholinergics, nitrofurantoin and digoxin were most common IDU. Prescription of theophylline in insomnia followed by aspirin in gastric ulcer and calcium channel blocker in constipation were listed from second list of criteria. 31% reductions in IDU were observed based on evidence-based information regarding each identified inappropriate drugs. CONCLUSIONS: The findings of this study provide evidence that provision of unbiased evidenced based information is the best possible means for improvement of pharmacotherapy in older patients.

Methodological challenges in determining longitudinal associations between anticholinergic drug use and incident cognitive decline.

OBJECTIVES: To compare the effect of using different anticholinergic drug scales and different models of cognitive decline in longitudinal studies. DESIGN: Longitudinal cohort study. SETTING: Outpatient clinics, Quebec, Canada. PARTICIPANTS: Individuals aged 60 and older without dementia or depression (n = 102). MEASUREMENTS: Using baseline and 1-year follow-up data, four measures of anticholinergic burden (anticholinergic component of the Drug Burden Index (DBI-Ach), Anticholinergic Cognitive Burden (ACB), Anticholinergic Drug Scale (ADS), and Anticholinergic Risk Scale (ARS)) were applied. Three models of cognitive decline (worsening of raw neuropsychological test scores, Reliable Change Index (RCI), and a standardized regression based measure (SRB)) were compared in relation to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) criteria for the onset of a new mild neurocognitive disorder. The consistency of associations was examined using logistic regression. RESULTS: The frequency of identifying individuals with an increase in anticholinergic burden over 1 year varied from 18% with the DBI-Ach to 23% with the ACB. The frequency of identifying cognitive decline ranged from 8% to 86% using different models. The raw change score had the highest sensitivity (0.91), and the RCI the highest specificity (0.93) against DSM-V criteria. Memory decline using the SRB method was associated with an increase in ACB (odds ratio (OR) = 5.3, 95% confidence interval (CI) = 1.1-25.8), ADS (OR = 5.7, 95% CI = 1.1-27.7), and ARS (OR = 6.5, 95% CI = 1.34-32.3). An increase in the DBI-Ach was associated with a decline on memory testing using the raw change score method (OR = 4.2, 95% CI = 1.8-15.4) and on the Trail-Making Test Part B using SRB (OR = 2.9, 95% CI = 1.1-8.0). No associations were observed using the DSM-V criteria or RCI method. CONCLUSION: The choice of different methods for defining drug exposure and cognitive decline will have a significant effect on the results of pharmacoepidemiological studies.

Drug-drug interactions and their predictors: Results from Indian elderly inpatients.

BACKGROUND: In view of the multiple co-morbidities, the elderly patients receiving drugs are prone to suffer with drug interactions since they receive a greater number of drugs. OBJECTIVE: The study was undertaken to determine the prevalence of drug interactions, as well as their predictors. METHODS: The prescriptions of a total of 1510 inpatients were collected prospectively for 1.5 years from inpatients wards of public tertiary care teaching hospital. All the prescriptions were checked for drug interactions using the Micromedex® Drug-Reax database-2010 and Stockley's Drug Interactions. Regression analyses sought to determine predictors for the drug interaction. RESULTS: The patients, with the average age of 67.2 ±0.2 years, were prescribed an average of 9.15 ±0.03 medications. It was found that out of 1510 prescriptions of inpatients, 126 (8.3%) prescriptions had one or more than one drug interaction. All the identified interactions were severe in nature. The top most interacting drugs were acetylsalicylic acid and anticoagulant (n=59). The second top most interacting drug combination was clopidogrel and proton pump inhibitors (n=51). The most commonly involved drugs in interactions were C (cardiovascular system) and A (alimentary tract and metabolism). Using multivariate binary logistic regression, multiple drugs (Odds Ratio=4.5; 95% Confidence Interval: - 2.38 -9.47) and multiple diagnoses (Odds Ratio=2.6; 95%CI: -1.40 -5.57) were found to be significant predictors for drug interaction. CONCLUSIONS: The results of this study substantiate the occurrence of severe drug interactions among Indian elderly inpatients. In order to provide safer pharmaceutical care, the active involvement of clinical pharmacists is a potential option.