Anticholinergic Use Research Articles

Epidemiology and clinical impact of chronic obstructive pulmonary disease in patients with atrial fibrillation: findings from an european prospective observational registry

Abstract Background The interplay between atrial fibrillation (AF) and chronic obstructive pulmonary disease (COPD) has been poorly investigated and understood, with previous studies reporting unsatisfactory management and poor prognosis of patients with AF and COPD. Purpose To describe the epidemiology, management and natural history of AF patients with COPD using a contemporary European prospective cohort. Methods From a European-wide prospective observational AF registry, we identified patients with COPD as reported by the investigators. We analysed the association between COPD and the odds of receiving oral anticoagulants (OAC) and other pharmacological treatments using multivariable logistic regression models. We also assessed the associations between COPD and risk of major outcomes using multivariable Cox-regression models. Our primary outcome was all-cause mortality; secondary outcome was the risk of major adverse cardiovascular events (MACE). We finally evaluated the interaction between disease-specific treatments for COPD and the risk of major outcomes in AF-COPD patients. Results A total of 10,219 AF patients were included in this analysis (mean age 69.2 ± 11.4 years; 40.3% females); COPD was found in 909 patients (8.9%). Patients with COPD were older, more likely males, and had a higher burden of thromboembolic and bleeding risk factors. No differences were observed in the likelihood of receiving OAC or non-vitamin K antagonist oral anticoagulants (NOAC) in COPD vs. no COPD patients (OR: 1.00, 95%CI: 0.81-1.24, and OR: 0.91, 95%CI: 0.77-1.06, respectively for OAC vs. non OAC and NOAC vs. VKA prescription). Patients with COPD were less likely treated with ACE inhibitors, beta-blockers, amiodarone and class IC antiarrhythmics, while they showed higher odds of receiving diuretic, digoxin, and non-dihydropyridinic calcium channel blockers (Figure 1). Over a median follow-up of 24.3 [IQR: 23.0-25.0] months, the risk of all-cause death was higher among COPD patients (HR: 1.52, 95%CI: 1.28-1.80), as well as the risk of MACE (HR: 1.49, 95%CI: 1.22-1.83) and the composite outcome of ‘all-cause death and MACE’ (HR: 1.50, 95%CI: 1.29-1.74) (Figure 2). No statistically significant interactions were observed between the use of beta-blockers, beta-2 agonists and anticholinergic drugs, and the risk of death in COPD patients. Conclusions COPD was common in AF patients and was associated with higher prescription of rate-control (except for beta-blockers) and lower prescription of rhythm control drugs, with no differences in OAC treatment. COPD was associated with worse prognosis, without significant interaction observed for beta-blockers or other COPD-specific treatment.Figure 1Figure 2

5 Anticholinergic Medications, Cognition, and Parkinson’s Disease. Do Medications matter?

Objective:While Parkinson’s disease (PD) is traditionally known as a movement disorder, cognitive decline is one of the most debilitating and common non-motor symptoms. Cognitive profiles of individuals with PD are notably heterogeneous (Goldman et al., 2018). While this variability may arise from the disease itself, other factors might play a role. Greater anticholinergic medication use has been linked to worse cognition in those with PD (Fox et al., 2011, Shah et al., 2013). However, past studies on this topic had small sample sizes, limited ranges of disease duration, and only used cognitive screeners. Thus, this study aimed to examine this question within a large, clinical sample, using a more comprehensive neuropsychological battery. We hypothesized that higher anticholinergic medication usage would relate to worse cognitive performance, particularly memory.Participants and Methods:Participants included 491 nondemented individuals with PD (m=64.7, SD=9.04 years old; education m=15.01, SD=2.79; 71.9% male; 94.3% non-Hispanics white) who underwent a comprehensive neuropsychological assessment at the UF Fixel Institute’s movement disorders program. Medications at the time of the neuropsychological evaluation were identified from chart review and scored based on anticholinergic properties using the Magellan Anticholinergic Risk Scale (Rudolph J.L., et al, 2008); each medication was scored from 0 (no load) to 3 (high load). The neuropsychological battery included measures across 5 cognitive domains: (1) executive function (Trails B, Stroop Interference, Letter Fluency), (2) verbal delayed memory (WMS-III Logical Memory and Hopkin’s Verbal Learning Test-Revised delayed recalls), (3) language (Boston Naming Test-II, Animal Fluency), (4) visuospatial skills (Judgment of Line Orientation, Face Recognition Test), and (5) attention/working memory (WAIS-III Digit Span Forward and Backward). The published normative scores for each task were converted into z-scores and averaged into a domain composite. Due to non-normality of Magellan scores, Spearman correlations examined the relationship between each cognitive domain composite score and Magellan scores.Results:As predicted, higher Magellan scores were significantly associated with worse memory (r=-0.11, p=0.016), with a small effect size. There were no significant relationships between Magellan scores and the remaining cognitive domains (EF, language, visuospatial, attention).Conclusions:We found that greater anticholinergic burden was associated with worse performance on memory, but not other neuropsychological domains, in a large cohort of nondemented individuals with PD who underwent comprehensive assessment. This finding corresponds to previous literature in smaller PD cohorts. Though the effect size was low, this finding highlights the importance of monitoring anticholinergic burden in PD patients in order to minimize detrimental effects of medications on memory function. Future work should examine whether greater anticholinergic burden predicts future progression of memory decline.Acknowledgement: Supported in part by the NIH, T32-NS082168

Airway Clearance Strategies and Secretion Management in Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a rare, neurodegenerative motor neuron disease that affects voluntary muscle movement. Often, difficulty in coughing, breathing, and swallowing are sequela associated with the condition, and the presence of bulbar muscle predominant weakness results in deleterious effects on airway clearance and secretion management. This narrative review will provide practical guidance for clinicians treating this population. Cough insufficiency in this population typically manifests as a prolonged, slow, weak cough effort that impedes the clearability of secretions and airway protection. Dystussia and dysphagia frequently occur simultaneously in bulbar dysfunction, subsequently impacting respiratory health. Measures of respiratory strength should be obtained and monitored every 3-6 months, preferably in a multidisciplinary clinic setting. Cough augmentation, whether manual or mechanical techniques, should be sought as early in the disease progression as possible to adequately control secretions in the proximal airways. This airway clearance strategy can aid in the prevention and treatment of respiratory tract infections (RTIs), which can pose a significant clinical hurdle to those with ALS. The use of mechanical insufflation-exsufflation may be complicated by severe bulbar dysfunction rendering this technique ineffective. Though peripheral airway clearance strategies, such as high-frequency chest-wall compression, have the advantage of being less impacted by bulbar dysfunction, it is only recommended this modality be used in conjunction with, versus in lieu of, proximal strategies. Salivary secretion management includes the use of anticholinergics, botulinum toxin, and radiation therapy depending on severity and desire for relief.

A - 97 Anticholinergic Burden Scales Are Not Created Equal: Differential Relationships to Cognition in Parkinson's Disease.

Cognitive changes are common in Parkinson's disease (PD). While previous research suggests greater anticholinergic medication use relates to worse broad cognition in PD, its domain-specific relationships remain unknown. This study compared three anticholinergic scales to examine their relationship to worse memory and executive function in individuals with PD. Participants included 493 non-demented individuals with PD (mean age = 65.74, SD = 9.04; mean education = 15.0, SD = 2.79; 72% male; 94% White (non-Hispanic)) from a movement disorders specialty clinic. Medications were identified via chart review. Each medication was scored (0-3) and summed using three scales: Anticholinergic Risk Scale (ARS), Anticholinergic Drug Scale (ADS), Anticholinergic Cognitive Burden Scale (ACBS). Cognitive composites averaged normative z-scores: Executive Function (EF; Trails B, Stroop Color-Word, Letter Fluency) and Memory (HVLT-R and WMS-III Logical Memory delayed recalls). Analyses included Bonferroni-adjusted, bootstrapped Spearman correlations. The three scales were significantly related, but with only fair agreement (Kendall's W(2) = 0.37, p < 0.001). Worse memory related to higher cholinergic burden on only the ACBS (r = -0.10, p = 0.02). Exploratory analyses indicated sex differences in the relationship between cognition and anticholinergic burden. For men, worse memory related to higher scores on both the ACBS (r = -0.11, p = 0.04) and ARS (r = -0.11, p = 0.045). For women, higher ACBS scores related to worse EF (r = -0.18, p = 0.03), whereas higher ADS scores related to worse memory and EF (r = -0.18, p = 0.04; r = -0.26, p = 0.002). Anticholinergic burden scales differentially related to cognitive performance in PD, with only ACBS showing a significant relationship to memory. Exploratory analyses suggest that scales may have differential relationships to memory and EF in men and women.

Patient and Clinician Challenges with Anticholinergic Step Therapy in the Treatment of Overactive Bladder: A Narrative Review.

Anticholinergics have been used in the treatment of overactive bladder (OAB), but their use is limited by poor tolerability and anticholinergic-related side effects. Increasingly, providers are discontinuing anticholinergic prescribing because of growing evidence of the association of anticholinergic use with increased risk of cognitive decline and other adverse effects. Newer medications for OAB, the β3-adrenergic receptor agonists mirabegron and vibegron, do not have anticholinergic properties and are typically well tolerated; however, many insurance plans have limited patient access to these newer OAB medications by requiring step therapy, meaning less expensive anticholinergic medications must be trialed and/or failed before a β3-agonist will be covered and dispensed. Thus, many patients are unable to easily access these medications. Step therapy and other drug utilization strategies (e.g., prior authorization) are often used to manage the growing costs of pharmaceuticals, but these policies do not always follow treatment guidelines and may harm patients as a result of treatment delays, discontinuations, or related increases in adverse events. Medical professionals have called for reform of drug utilization strategies through partnerships that include clinicians and policymakers. This narrative review discusses prescribing patterns for OAB treatment and the effect of switching between drugs, as well as the costs of step therapy and prior authorization on patients and prescribers.

Association of silodosin, tamsulosin, and naftopidil with delirium: analysis of the pharmacovigilance database in Japan.

An association between adrenergic alpha-1 receptor antagonists and delirium has been suggested, but the details are unclear. This study investigated the association between adrenergic alpha-1 receptor antagonists and delirium in patients with benign prostatic hyperplasia using the Japanese Adverse Drug Event Report database. First, disproportionality analysis compared the frequency of delirium in the adrenergic alpha-1 receptor antagonists silodosin, tamsulosin, and naftopidil. Next, multivariate logistic analysis was performed to examine the association between delirium and adrenergic alpha-1 receptor antagonists where disproportionality was detected. A disproportionality in delirium was observed in patients receiving tamsulosin (reporting odds ratio [ROR] 1.85, 95% confidence interval [CI] 1.38-2.44, P < 0.01) compared with those who did not, and also in patients receiving naftopidil (ROR 2.23, 95% CI 1.45-3.28, P < 0.01) compared with those who did not. Multivariate logistic analysis revealed that in addition to previously reported risk factors for delirium, delirium in patients receiving tamsulosin was significantly increased with concomitant use of anticholinergics (odds ratio 2.73, 95% CI 1.41-5.29, P < 0.01) and delirium in patients receiving naftopidil was significantly increased with concomitant use of beta3-adrenergic receptor agonists (odds ratio 4.19, 95% CI 1.66-10.6, P < 0.01). Anticholinergics or beta3-adrenergic receptor agonists to treat overactive bladder in patients receiving tamsulosin and naftopidil was strongly associated with delirium. Confirming the medical history and concomitant medications of patients receiving tamsulosin or naftopidil may contribute to preventing delirium in patients with benign prostatic hyperplasia and to improving their outcomes.

Anticolinérgicos tópicos en el manejo de la hiperhidrosis focal en adultos y niños. Una revisión narrativa

Hyperhidrosis, or excessive sweating, is characterized by overactivity of the eccrine sweat glands, usually associated with dysfunction of the autonomic nervous system. Primary focal hyperhidrosis is the most common form and can affect the axillae, palms, soles, and/or face, often leading to significantly impaired quality of life and social functioning. Treatment is complex. Topical antiperspirants are normally recommended as the first-line treatment for mild hyperhidrosis. Multiple clinical trials and prospective studies support the efficacy and tolerability of oral and topical anticholinergics in the management of hyperhidrosis. Topical glycopyrronium, which has been investigated in at least 8 clinical trials enrolling more than 2000 patients, is probably the first-line pharmacological treatment for axillary hyperhidrosis in patients with moderate to severe disease poorly controlled with topical antiperspirants. Second-line treatments include botulinum toxin injections, microwave treatment, and oral anticholinergics. We review the use of topical anticholinergics in the management of focal hyperhidrosis in adults and children.

Exploring Concomitant Acetylcholinesterase Inhibitor and Overactive Bladder Anticholinergic Use and Risk of Hospitalization in Medicare and Dual-Eligible Medicare-Medicaid Populations in a Historic Database.

Overactive bladder prevalence increases in older adults often complicating the management of other comorbidities. The theoretical antagonism between the parasympathetic-blocking anticholinergic agent and the parasympathetic stimulatory agents concomitantly used by patients is only recently being explored. The primary aim was to determine the frequency of the annual use of acetylcholinesterase inhibitors, overactive bladder anticholinergics, and the use of both agents in the same year. The secondary aim was measurement of the association between annual hospitalization and same-year use of both acetylcholinesterase inhibitors and anticholinergics. The US nationally representative MarketScan® Medicare databases were analyzed. In the Medicare enrollees, there were 122 020, 141 920, and 15 639 users of acetylcholinesterase inhibitors, anticholinergics, and both agents, respectively. The percentage of acetylcholinesterase inhibitor users who also used anticholinergics was 12.8%. Comparing users of both acetylcholinesterase inhibitors and anticholinergics to those using AChEI alone, 5 608 of the former experienced a hospitalization (35.9%) compared to 33 182 of the latter (31.2%). There was an increased risk of hospitalization for those using both acetylcholinesterase inhibitors and anticholinergics in the same year, with an odds ratio (OR) of 1.23 (95% CI, 1.19, 1.28). Clinicians should consider improved monitoring of the usage of both medications and clarify alternative regimens that avoid anticholinergics in at-risk older adults.

Extrapyramidal adverse events and anticholinergics use after the long-term treatment of patients with schizophrenia with the new long-acting antipsychotic Risperidone ISM®: results from matching-adjusted indirect comparisons versus once-monthly formulations of Paliperidone palmitate and Aripiprazole monohydrate in 52-week studies

BackgroundRisperidone ISM® is a newly developed long-acting injectable (LAI) treatment for schizophrenia in adults. In the absence of head-to-head comparisons with other similar antipsychotics, the objective of this study was to generate indirect evidence of some aspects of the safety and tolerability of Risperidone ISM compared to other LAI antipsychotics for treatment of patients with schizophrenia in the maintenance treatment setting.MethodsA literature review was conducted systematically to identify maintenance treatment studies reporting safety and tolerability outcomes for LAI antipsychotic therapies. Following an assessment of between-trial heterogeneity, a matching-adjusted indirect comparison (MAIC) was performed to account for between-trial imbalances in patient characteristics and to generate comparative evidence for safety and tolerability endpoints.ResultsThe analysis showed that incidence of extrapyramidal symptoms (EPS) was found to be numerically, but not statistically significantly, lower in patients receiving Risperidone ISM than in those receiving Paliperidone palmitate (PP) (OR [95% CI] 0.63 [0.29, 1.38], p = 0.253) and statistically significantly lower than with Aripiprazole monohydrate once-monthly (AOM) (OR [95% CI] 0.25 [0.12, 0.53], p < 0.001). Use of anticholinergic agents for the alleviation of EPS was also shown to be significantly lower in Risperidone ISM patients than in those receiving PP (OR [95% CI] 0.29 [0.10, 0.83], p = 0.021) or AOM (OR [95% CI] 0.01 [0.003, 0.06], p < 0.001), suggesting a superior tolerability profile for clinically relevant EPS. Results from the sensitivity analyses comparing stabilized and stable patients receiving Risperidone ISM to those receiving AOM yielded similarly favorable conclusions in line with the base case analyses.ConclusionsThis MAIC is consistent with the safety and tolerability results obtained during the PRISMA-3 clinical trial in the long-term treatment of schizophrenia and suggests a favorable safety and tolerability profile in terms of EPS incidence and anticholinergic agent use, relative to other antipsychotic therapies used for treatment of patients with schizophrenia in the maintenance setting.

Anesthetic Considerations in a Patient with Large Cavernous Carotid Aneurysm

AbstractCavernous carotid aneurysms (CCA) are a rare form of intracranial aneurysms. Patients undergoing clipping of a large unruptured CCA pose multiple anesthetic concerns including intraoperative trigeminocardiac reflex (TCR). The anesthetist's role is paramount, specifically, preprocedure anesthetic preparation, close vital monitoring, familiarity with surgical steps, provision of a relaxed brain, and meticulous control of hemodynamics. Closed-loop communication with the surgeons throughout the surgical procedure is paramount. When TCR occurs, unnecessary use of anticholinergics should be discouraged as the hemodynamic perturbations resolve with cessation of the surgical stimulus.

Effects of Opioids, Steroids, Benzodiazepines, Anticholinergics, and Antihistamines on the Efficacy of Antipsychotics for Treating Delirium in End-of-Life Adult Patients Undergoing Palliative Care

The purpose of the study was to determine the effect of combination therapy involving opioids, steroids, benzodiazepines, anticholinergics, and antihistamines on antipsychotics efficacy for delirium. The study included adult inpatients receiving end-of-life palliative care and diagnosed with hyperactive delirium. Changes in delirium symptoms were assessed using the Intensive Care Delirium Screening Checklist (ICDSC). A retrospective analysis was conducted on 97 patients with ICDSC scores of ≥4, comparing the scores before and after antipsychotic administration. A mean score <4 sustained for 3 days after antipsychotics administration was considered effective. The mean days with ICDSC <4 within a 3-day period were evaluated as well. The efficacy of antipsychotics was compared between cases with and without the use of opioids, steroids, benzodiazepines, anticholinergics, and antihistamines. The results revealed no significant differences in the efficacy of antipsychotics for delirium when used in conjunction with opioids (odds ratio 0.614, 95% CI [0.179-2.105]), benzodiazepines (0.387, [0.108-1.390]), steroids (1.258, [0.276-5.746]), or anticholinergics (2.085, [0. 148-29.458]). Additionally, no significant differences were observed in the mean days with ICDSC <4 within 3-day period. Although opioids, benzodiazepines, steroids, anticholinergics, and antihistamines are recognized as delirium risk factors, their use for symptom relief in patients with delirium may not affect antipsychotic efficacy.

Assessing the Utility of Tamsulosin in Delaying Progression to Clean Intermittent Catheterization and End-stage Renal Disease in Patients With Posterior Urethral Valves: Are We Postponing the Inevitable?

To assess whether tamsulosin may aid emptying of the lower urinary tract in posterior urethral valves patients, mitigating the likelihood of progressing to clean intermittent catheterization (CIC) or need for renal replacement therapy. We reviewed a prospective institutional database containing posterior urethral valves patients treated between January 2000 and January 2022. After assessing baseline characteristics, Kaplan-Meier survival curves and log-rank tests were generated to assess differences in clinically significant outcomes (progression to CIC, dialysis, or kidney transplantation) between those prescribed tamsulosin and those who were not. A total of 179 patients were included. Fifty-nine patients received tamsulosin prior to initiation of CIC (group 1), and 120 did not (group 2). The baseline characteristics were similar between the two groups, except for anticholinergic use (tamsulosin group - 35/59 vs no tamsulosin - 32/120, P<.001). The median age at tamsulosin initiation was 26.0 months (IQR 15.5-48.6) and the median time from initiation of tamsulosin to progression to CIC was 52.6 months (IQR 10.1-69.3). Kaplan-Meier survival curves showed that patients on tamsulosin were less likely to progress to CIC (P=.021), however, there was no difference in progression to dialysis or kidney transplantation. A Cox-regression analysis controlling for baseline characteristics, including age, anticholinergic use, vesicoureteral reflux severity, and CKD stage at 1-year of life, showed a consistent effect of tamsulosin in delaying progression to CIC (HR 0.444 95%CI 0.218-0.902, P=.025). While tamsulosin may delay CIC, it does not appear to delay progression to end-stage renal disease. Additional studies exploring specific patient factors are required to determine the timing and subset who may benefit the most from tamsulosin.

Association of medication use with falls and mortality among long-term care residents: a longitudinal cohort study

BackgroundFalls in long-term care are common. The aim of our study was to explore how medication use is associated with incidence of falls, related consequences, and all-cause mortality among long-term care residents.MethodsFive hundred thirty two long-term care residents aged 65 years or older participated in this longitudinal cohort study in 2018–2021. Data on medication use were retrieved from medical records. Polypharmacy was defined as use of 5–10 medications and excessive polypharmacy as use of > 10 medications. The numbers of falls, injuries, fractures, and hospitalizations were collected from medical records over 12 months following baseline assessment. Participants were followed for three years for mortality. All analysis were adjusted for age, sex, Charlson Comorbidity Index, Clinical dementia rating, and mobility.ResultsA total of 606 falls occurred during the follow-up. Falls increased significantly with the number of medications used. Fall rate was 0.84/person-years (pyrs) (95% CI 0.56 to 1.13) for the non-polypharmacy group, 1.13/pyrs (95% CI 1.01 to 1.26) for the polypharmacy group, and 1.84/pyrs (95% CI 1.60 to 2.09) for the excessive polypharmacy group. Incidence rate ratio for falls was 1.73 (95% CI 1.44 to 2.10) for opioids, 1.48 (95% CI 1.23 to 1.78) for anticholinergic medication, 0.93 (95% CI 0.70 to 1.25) for psychotropics, and 0.91 (95% CI 0.77 to 1.08) for Alzheimer medication. The three-year follow-up showed significant differences in mortality between the groups, the lowest survival rate (25%) being in the excessive polypharmacy group.ConclusionPolypharmacy, opioid and anticholinergic medication use predicted incidence of falls in long-term care. The use of more than 10 medications predicted all-cause mortality. Special attention should be paid to both number and type of medications when prescribing in long-term care.

Characteristics of providers who prescribed only anticholinergic medications for overactive bladder in 2020

Pharmacologic therapy for overactive bladder typically includes either an anticholinergic or a beta-3 agonist. Based on research that has demonstrated increased risks of cognitive impairment and dementia associated with anticholinergic use, current guidelines support the use of beta-3 agonists rather than anticholinergics in older patients. This study aimed to describe the characteristics of providers prescribing only anticholinergics to treat overactive bladder in patients aged ≥65 years. The US Centers for Medicare and Medicaid Services publishes data on medications dispensed to Medicare beneficiaries. Data include the National Provider Identifier of the prescriber and the number of pills prescribed and dispensed for any given medication for beneficiaries aged ≥65 years. We obtained each provider's National Provider Identifier, gender, degree, and primary specialty. National Provider Identifiers were linked to an additional Medicare database that includes graduation year. We included providers who prescribed pharmacologic therapy for overactive bladder in 2020 for patients aged ≥65 years. We calculated the percentage of providers who prescribed only anticholinergics (and did not prescribe beta-3 agonists) for overactive bladder and stratified by provider characteristics. Data are reported as adjusted risk ratios. In 2020, 131,605 providers prescribed overactive bladder medications. Of those identified, 110,874 (84.2%) had complete demographic information available. Although only 7% of providers who prescribed medications for overactive bladder were urologists, prescriptions from urologists accounted for 29% of total prescriptions. Among providers prescribing medications for overactive bladder, 73% of female providers prescribed only anticholinergics, whereas 66% of male providers prescribed only anticholinergics (P<.001). The percentage of providers that prescribed only anticholinergics also varied by specialty (P<.001), with providers specialized in geriatric medicine being least likely to prescribe only anticholinergics (40%), followed by urologists (44%). Nurse practitioners (75%) and family medicine physicians (73%) were more likely to prescribe only anticholinergics. The percentage of providers who prescribed only anticholinergics was the highest for recent medical school graduates and decreased with time since graduation. Overall, 75% of providers within 10 years of graduation prescribed only anticholinergics, whereas only 64% of providers who were >40 years of age from graduation prescribed only anticholinergics (P<.001). This study identified considerable differences in prescribing practices based on provider characteristics. Female physicians, nurse practitioners, physicians trained in family medicine, and those who recently graduated from medical school were the most likely to prescribe only anticholinergic medications and not prescribe any beta-3 agonist for the treatment of overactive bladder. This study identified differences in prescribing practices based on provider demographics that may guide educational outreach programs.

Oral anticholinergic drugs versus placebo or no treatment for managing overactive bladder syndrome in adults.

Around 16% of adults have symptoms of overactive bladder (OAB; urgency with frequency and/or urge incontinence), with prevalence increasing with age. Anticholinergic drugs are commonly used to treat this condition. This is an update of a Cochrane Review first published in 2002 and last updated in 2006. To assess the effects of anticholinergic drugs compared with placebo or no treatment for treating overactive bladder syndrome in adults. We searched the Cochrane Incontinence Specialised Register, which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE In-Process,MEDLINE Epub Ahead of Print, ClinicalTrials.gov, WHO ICTRP and handsearching of journals and conference proceedings (searched 14 January 2020), and the reference lists of relevant articles. We updated this search on 3 May 2022, but these results have not yet been fully incorporated. We included randomised or quasi-randomised trials in adults with overactive bladder syndrome that compared an anticholinergic drug alone with placebo treatment. Two review authors independently assessed eligibility and extracted data from the included studies, including an assessment of the risk of bias. We assessed the certainty of the body of evidence using the GRADE approach. We processed data as described in the Cochrane Handbook for Systematic Reviews of Interventions. We included 104 studies, 71 of which were new or updated for this version of the review. Although 12 studies did not report the number of participants, there were 47,106 people in the remainder of the included studies.The majority of the studies had insufficient information to allow judgement of risk of bias and we judged them to be unclear for all domains. Nine anticholinergic drugs were included in these studies: darifenacin; fesoterodine; imidafenacin; oxybutynin; propantheline; propiverine; solifenacin; tolterodine and trospium.No studies were found that compared anticholinergic drugs to no treatment. At the end of the treatment period, anticholinergics may slightly increase condition-specific quality of life (mean difference (MD) 4.41 lower, 95% confidence interval (CI) 5.28 lower to 3.54 lower (scale range -100 to 0); 12 studies, 6804 participants; low-certainty evidence). Anticholinergics are probably better than placebo in terms of patient perception of cure or improvement (risk ratio (RR) 1.38, 95% CI 1.15 to 1.66; 9 studies, 8457 participants; moderate-certainty evidence), and the mean number of urgency episodes per 24-hour period (MD 0.85 lower, 95% CI 1.03 lower to 0.67 lower; 23 studies, 16,875 participants; moderate-certainty evidence). Compared to placebo, anticholinergics may result in an increase in dry mouth adverse events (RR 3.50, 95% CI 3.26 to 3.75; 66 studies, 38,368 participants; low-certainty evidence), and may result in an increased risk of urinary retention (RR 3.52, 95% CI 2.04 to 6.08; 17 studies, 7862 participants; low-certainty evidence). Taking anticholinergics may be more likely to lead to participants withdrawing from the studies due to adverse events (RR 1.37, 95% CI 1.21 to 1.56; 61 studies, 36,943 participants; low-certainty evidence). However, taking anticholinergics probably reduces the mean number of micturitions per 24-hour period compared to placebo (MD 0.85 lower, 95% CI 0.98 lower to 0.73 lower; 30 studies, 19,395 participants; moderate-certainty evidence). The use of anticholinergic drugs by people with overactive bladder syndrome results in important but modest improvements in symptoms compared with placebo treatment. In addition, recent studies suggest that this is generally associated with only modest improvement in quality of life. Adverse effects were higher with all anticholinergics compared with placebo. Withdrawals due to adverse effects were also higher for all anticholinergics except tolterodine. It is not known whether any benefits of anticholinergics are sustained during long-term treatment or after treatment stops.

Classifying Polypharmacy According to Pharmacotherapeutic and Clinical Risks in Older Adults: A Latent Class Analysis in Quebec, Canada.

The simplistic definition of polypharmacy, often designated as the concomitant use of five medications or more, does not distinguish appropriate from inappropriate polypharmacy. Classifying polypharmacy according to varying levels of health risk would help optimise medication use. We aimed to characterise different types of polypharmacy among older adults and evaluate their association with mortality and institutionalisation. Using healthcare databases from the Quebec Integrated Chronic Disease Surveillance System, we selected a community-based random sample of the population ≥ 66 years old covered by the public drug plan. Categorical indicators used to describe polypharmacy included number of medications, potentially inappropriate medications (PIMs), drug-drug interactions, enhanced surveillance medications, complex route of administration medications, anticholinergic cognitive burden (ACB) score and use of blister cards. We used a latent class analysis to subdivide participants into distinct groups of polypharmacy. Their association with 3-year mortality and institutionalisation was assessed with adjusted Cox models. In total, 93,516 individuals were included. A four-class model was selected with groups described as (1) no polypharmacy (46% of our sample), (2) high-medium number of medications, low risk (33%), (3) medium number of medications, PIM use with or without high ACB score (8%) and (4) hyperpolypharmacy, complex use, high risk (13%). Using the class without polypharmacy as the reference, all polypharmacy classes were associated with 3-year mortality and institutionalisation, with the most complex/inappropriate classes denoting the highest risk (hazard ratio [HR] [95% confidence interval]: class 3, 70-year-old point estimate for mortality 1.52 [1.30-1.78] and institutionalisation 1.86 [1.52-2.29]; class 4, 70-year-old point estimate for mortality 2.74 [2.44-3.08] and institutionalisation 3.11 [2.60-3.70]). We distinguished three types of polypharmacy with varying pharmacotherapeutic and clinical appropriateness. Our results highlight the value of looking beyond the number of medications to assess polypharmacy.

Predictors of Surgical Failure of Open Burch Colposuspension Versus Retropubic Midurethral Sling for Stress Urinary Incontinence

To identify and compare long-term predictors for 'surgical failures' in matched groups of Midurethral sling (MUS) and Burch colposuspension (BC). A secondary analysis of patients with urodynamic stress incontinence who were treated either by open BC or retropubic MUS. The study had a cohort of 1344 women with a ratio of 1:3 (BC: MUS). We defined surgical success or failure by combining Patient Reported Outcome Measures and the need for repeat surgery. Risk factors for failure identified by multivariate analysis. Of the 1344 women included, 336 had BC, and 1008 had MUS. Patients were followed-up for 13.1 and 10.1 years, and the rate of failure was 22% and 20%, for BC and MUS, respectively (P=0.35). Significant predictors for MUS failure were Body mass index (BMI)>30, preoperative anticholinergic medication use, smoking, diabetes, and previous surgery for incontinence (Hazard ratio 3.6, 2.6, 2.5, 1.8, 2.3, respectively). BMI>25, preoperative use of anticholinergic medication, age>60, previous surgery for incontinence, and loss of follow-up>5 years (Hazard ratio: 3.2, 2.8, 2.6, 2.5, 2.1, respectively), were significant predictors of BC failure. This study shows similar predictors for surgical failure for BC and MUS, with high BMI, mixed urinary incontinence, and previous continence procedures being the most important.

Delirium: The Next Vital Sign in the PICU?*

Delirium: The Next Vital Sign in the PICU?*

Clozapine use at a specialised psychiatric hospital in Johannesburg.

Clozapine is the gold standard medication for treatment-resistant psychosis, with robust evidence supporting its efficacy in multiple symptom domains. However, clozapine's side effect profile contributes to its underutilisation and discontinuation. This study aimed to explore the magnitude of clozapine use and describe factors that impact on its effective use among in-patients. Tara Hospital, a specialised psychiatric hospital in Johannesburg. This was a retrospective, cross-sectional file review of clozapine-treated patients admitted over the 2-year study period. Data variables included: demographics, clinical information, discharge prescription, clozapine-related side effects and details of clozapine discontinuation, where applicable. A cohort of 33.2% of patients from Tara's biological wards received a trial of clozapine. Participants experienced anti-cholinergic clozapine-related side effects that included weight gain (79.5%), tachycardia (35.2%) and constipation (35.2%). Clozapine was discontinued in 13.7% of participants, and no life-threatening side effects or deaths occurred. Significantly more use of flupenthixol decanoate (64.3% vs. 30.7%; p = 0.0322) and anticholinergics (35.7% vs. 11.4%; p = 0.0474) occurred in the clozapine-discontinued group. Polypharmacy rates were high for psychiatric and non-psychiatric medications. One-third of patients received clozapine trials, most of whom continued at discharge. Although side effects occurred frequently, life-threatening side effects did not. Clozapine monitoring protocols, side effect rating scales, pre-emptive management of side effects, lifestyle interventions and clinician education may improve outcomes of clozapine use. The use of plasma clozapine levels may be beneficial. This study expands our limited knowledge regarding current clozapine prescribing trends in South Africa.

Association of anticholinergic drug use with postoperative mortality among patients with hip fracture. A nationwide cohort study

PurposeAnticholinergic (AC) drugs are associated with various determinantal outcomes. Data regarding the effect of AC drugs on mortality among geriatric hip fracture patients are limited and inconsistent. MethodsUsing Danish health registries, we identified 31,443 patients aged ≥65 years undergoing hip fracture surgery. AC burden was assessed 90 days before surgery by the Anticholinergic Cognitive Burden (ACB) score and number of AC drugs. Logistic and Cox regression producing odds ratios (OR) and hazard ratios (HR) for 30- and 365- day mortality, adjusting for age, sex, and comorbidities were computed. ResultsAC drugs were redeemed by 42% of patients. The 30-day mortality increased from 7% for patients with ACB score of 0 to 16% for patients with ACB score of ≥5, corresponding to an adjusted OR 2.5 (CI: 2.0–3.1). The equivalent adjusted HR for 365-mortality was 1.9 (CI: 1.6–2.1). Using count of AC drugs as exposure we found a stepwise increase in ORs and HRs with increased number of AC drugs; Compared to non-users, adjusted ORs for 30-days mortality were 1.6 (CI: 1.4–1.7), 1.9 (CI: 1.7–2.1), and 2.3 (CI: 1.9–2.7) for users of 1, 2 and 3+ AC drugs. HRs for 365-day mortality were 1.4 (CI: 1.3–1.5), 1.6 (CI: 1.5–1.7) and 1.8 (CI: 1.7–2.0). ConclusionUse of AC drugs was associated with increased 30-day and 365-day mortality among older adults with hip fracture. Simply counting the number of AC drugs may be a clinically relevant and easy AC risk assessment tool. Continued effort to reduce AC drug-use is relevant.