Search

Background: While the effects of anticholinergic drug use have been increasingly highlighted, trends in anticholinergic use remain poorly understood. Aim: To determine the changes in frequency and pattern of anticholinergic drug use within a low- and middle-income country. Method: Comparisons were made between population-based datasets collected from Malaysian residents aged 55 years and older in 2013–15 and 2020–22. Anticholinergic exposure was determined using the anticholinergic cognitive burden (ACB) tool. Drugs with ACB were categorised according to the Anatomical Therapeutic Chemical (ATC) classification. Results: A total number of 5707 medications were recorded from the 1616 participants included in the 2013–15 dataset. A total number of 6175 medications were recorded from 2733 participants in 2020–22. Two hundred and ninety-three (18.1%) and 280 (10.2%) participants consumed ≥ 1 medication with ACB ≥ 1 in 2013–15 and 2020–22 respectively. The use of nervous system drugs with ACB had increased (27 (0.47%) versus 39 (0.63%). The use of ACB drugs in the cardiovascular (224 (3.9%) versus 215 (3.4%)) and alimentary tract and metabolism (30 (0.52%) versus 4 (0.06%)) classes had reduced over time. Participants in 2020–22 were significantly less likely than those in 2013–15 to have total ACB = 1 − 2 (odds ratio [95% confidence interval] = 0.473[0.385–0.581]) and ACB ≥ 3 (0.251[0.137 − 0.460]) compared to ACB = 0 after adjustment for potential confounders (p < 0.001). Conclusion: Although anticholinergic exposure has decreased over time, the use of medications with anticholinergic effects in the nervous system class has risen. This increase is attributable to antipsychotic use, which is of concern due to potential cardiovascular complications, and deserves further evaluation. [ABSTRACT FROM AUTHOR]

Overactive bladder (OAB) is a highly prevalent condition with significant associated comorbidities. Current management guidelines suggest the utilization of anticholinergic medication as a second line after nonpharmacological treatment. Tibial nerve stimulation (TNS), which has previously been thought to have been expensive and inaccessible, was relegated to a third-line therapy. However, given the recently discovered association between anticholinergic medication use and dementia as well as the recent FDA approval of transcutaneous tibial nerve stimulation (TTNS), there may be a need to revisit management guidelines. In this commentary, we identify the two types of TNS, percutaneous tibial nerve stimulation (PTNS) and TTNS and compare them with anticholinergics. By considering their respective efficacies, side-effects profiles, and associated costs, we make the case in this commentary for an update to guidelines that includes TNS as second-line OAB management ahead of anticholinergic medication. [ABSTRACT FROM AUTHOR]

Anticholinergic medications are known to cause adverse cognitive effects in community-dwelling older adults and medical inpatients, including dementia. The prevalence with which such medications are prescribed in older adults undergoing major surgery is not well described nor is their mediating relationship with delirium and dementia. We sought to determine the prevalence of high-risk medication use in major surgery patients and their relationship with the subsequent development of dementia. This was a retrospective cohort study which used data between January 2013 and December 2019, in a large midwestern health system, including sixteen hospitals. All patients over age 50 undergoing surgery requiring an inpatient stay were included. The primary exposure was the number of doses of anticholinergic medications delivered during the hospital stay. The primary outcome was a new diagnosis of Alzheimer's disease and related dementias at 1-y postsurgery. Regression methods and a mediation analysis were used to explore relationships between anticholinergic medication usage, delirium, and dementia. There were 39,665 patients included, with a median age of 66. Most patients were exposed to anticholinergic medications (35,957/39,665; 91%), and 7588/39,665 (19.1%) patients received six or more doses during their hospital stay. Patients with at least six doses of these medications were more likely to be female, black, and with a lower American Society of Anesthesiologists class. Upon adjusted analysis, high doses of anticholinergic medications were associated with increased odds of dementia at 1 y relative to those with no exposure (odds ratio 2.7; 95% confidence interval 2.2-3.3). On mediation analysis, postoperative delirium mediated the effect of anticholinergic medications on dementia, explaining an estimated 57.6% of their association. High doses of anticholinergic medications are common in major surgery patients and, in part via a mediating relationship with postoperative delirium, are associated with the development of dementia 1 y following surgery. Strategies to decrease the use of these medications and encourage the use of alternatives may improve long-term cognitive recovery. [ABSTRACT FROM AUTHOR]

Introduction and hypothesis: Studies within the past decade have suggested associations among composition of the urinary microbiota, local immune responses, and urinary incontinence symptoms. To investigate these relationships, we evaluated the structure of the urinary microbiome, local inflammatory markers, and patient responses prior to and at 6-weeks after treatment with anticholinergic medication for urgency urinary incontinence (UUI). Methods: Using a prospective pilot study, we enrolled women who presented with UUI symptoms and were prescribed treatment with anticholinergics. Catheterized urine samples were collected from participants at their baseline and 6-week follow-up visits for microbiological (standard and 16S rRNA gene phylotyping analyses) and cytokine analysis along with the UDI-6 questionnaire and 2-day bladder diary. Results: Patients were Caucasian, post- menopausal, with a median age of 64 and median BMI of 30.1 kg/m2. Among the patients, 75% had UUI symptoms for less than 2 years, but with a frequency of at least a few times a week or every day. Most women were prescribed 10 mg oxybutynin ER daily at enrollment. Patients had varied urinary microbiota by culture and 16S phylotyping, with species of Lactobacillus being the most common, in six samples, in addition to taxa associated with Enterococcus, Staphylococcus, and mixed flora. Cytokine levels showed no differences before and after treatment with anticholinergics, nor correlation with urinary bacteria or microbiome composition. Conclusions: Our pilot study suggests factors in addition to the urinary microbiome and local immune responses may be involved in patients' response to anticholinergics for UUI. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: Sparse published reports exist nowadays on vibegron and pediatric overactive bladder, so its usefulness of this agent remains unclear. The purpose of this study was to clarify the effectiveness of vibegron for pediatric cases of daytime urinary incontinence (DUI), including refractory cases. Methods: Participants comprised 57 patients treated with vibegron for DUI from March 2019 to April 2022. To investigate treatment outcomes and risk factors for pediatric patients with refractory DUI, the following factors were evaluated: age at initiatial administration; frequency of DUI; duration of vibegron treatment; presence of neurodevelopmental disorders (NDDs); presence of constipation; and anticholinergic medications before and after initiation of treatment. Results: Patients included 38 boys and 19 girls with a median age at initial administration of 111 months (range: 64–202 months) and a median administration term of 6 months (range: 1–33 months). With treatment for 6 months, the response rate (complete response + partial response) was 68.3%. A total of 24 cases with NDD showed a 72.0% response rate at 6 months. As for the relationship between anticholinergic agents and vibegron, 15 cases were treated with vibegron as the first choice without anticholinergics (First‐choice cases), and 33 cases were treated with vibegron alone after switching from anticholinergics (Switch cases). Vibegron was used in combination with anticholinergic agents in 9 cases (Add‐on cases). Response rates at 6 months were 85.0% in First‐choice cases, 66.3% in Switch cases, and 40.7% in Add‐on cases. Univariate analyses failed to identify any significant risk factors for refractory cases. Conclusions: Vibegron was effective in pediatric cases of DUI, with efficacy demonstrated within a short time in many cases. Vibegron is expected to play a significant role in the treatment of DUI in pediatric cases. [ABSTRACT FROM AUTHOR]

Background: Female sexual function has been shown to improve with overactive bladder (OAB) treatment. Aim: The objective of this study was to evaluate the effects of anticholinergics (ACHs) or a beta-agonist (BAG) on female sexual function. Methods: This was a prospective multicenter cohort study. Sexually active women with OAB completed the Overactive Bladder questionnaire (OAB-q) and Female Sexual Function Index (FSFI) prior to and after 12 weeks of therapy. Sample sizes of 63 per group were calculated to detect a clinically relevant difference in the FSFI. Outcomes: The primary outcome was FSFI change from baseline at 12 weeks. Results: A total of 157 patients were recruited, and 91 completed follow-up (58/108, ACH; 31/49, BAG). There were within-group FSFI differences from pre- to posttreatment: a worsening of arousal in the ACH group (P = .046) and an improvement in overall FSFI (P = .04) and pain (P = .04) in the BAG group. After treatment, postmenopausal women in the BAG group had significantly better overall FSFI (P = .01), desire (P = .003), arousal (P = .009), and orgasm (P = .01). Clinical Implications: While further research is necessary, this study provides information about the comparative effects of OAB treatments on female sexual function, which may ultimately lead to better patient selection and outcomes. Strengths and Limitations: While there was no difference between the subjects who completed the study and those who did not, the study remained underpowered after the loss to follow-up. The multicenter cohort design allows for generalizability of results. Conclusion: Although this study was underpowered, an improvement in overall sexual function was seen with BAGs, while ACHs were associated with worsening aspects of sexual function. [ABSTRACT FROM AUTHOR]

Background: Higher medication anticholinergic burden is associated with increased risk of cardiovascular disease and cognitive decline. A mechanistic pathway has not been established. We aimed to determine whether inflammation may mediate these associations. Methods: Participants were drawn from the European Prospective Investigation into Cancer, Norfolk cohort (40‐79 years at baseline). Anticholinergic burden score (ACB) was calculated at first (1HC) (1993/97) and second (2HC) (1998/2000) health checks. Fibrinogen and C‐reactive protein (CRP) were measured during 1HC and tumour necrosis factor alpha (TNF‐α) and interleukin 6 (IL‐6) during 2HC. Cross‐sectional associations between ACB and inflammatory markers were examined for both health checks. Prospective associations were also examined between 1HC ACB and 2HC inflammatory markers. Models were adjusted for age, sex, lifestyle factors, comorbidities and medications. Results: In total, 17 678 and 22 051 participants were included in cross‐sectional analyses for CRP, and fibrinogen, respectively. Furthermore, 5101 participants with data on TNF‐α and IL‐6 were included in the prospective analyses. Cross‐sectionally, compared to ACB = 0, ACB ≥ 4 was associated with higher fibrinogen, beta (95% confidence interval) = 0.134 g/L (0.070, 0.199), CRP 1.175 mg/L (0.715, 1.634), IL‐6 0.593 pg/mL (0.254, 0.932) and TNF‐α 0.137 pg/mL (0.033, 0.241). In addition, a point increase in ACB was associated with higher levels of all markers. Prospectively, compared to ACB = 0, ACB ≥ 4 was associated with higher IL‐6(pg/mL) of 0.019 (−0.323, 0.361) and TNF‐α (pg/mL) of 0.202% (0.81, 0.323). A unit increase in ACB was associated with a significantly higher TNF‐α and IL‐6. Conclusion: Higher ACB was associated with higher inflammatory markers. Inflammation may mediate the relationship between anticholinergic medications and adverse outcomes. [ABSTRACT FROM AUTHOR]

Purpose: A growing literature points to an association between overactive bladder (OAB) medications and dementia. Given differences in side effects for extended‐release (ER) and immediate‐release (IR) anticholinergic formulations and beta‐3 agonists, we examined prescription utilization patterns in a national dataset of older adults from 2014 to 2018. Methods: We performed a retrospective study using the Medicare Part D Drug Spending Dashboard, a publicly available database that includes data from outpatient pharmacy claims from 2014 to 2018 in the United States. We identified total claims and total spending on common OAB medications, and further assessed trends by anticholinergic burden by medication, and immediate and ER formulations. Results: There were 54.1 million claims for OAB medications, accounting for $10.1 billion (2018 United States dollars) in spending from 2014 to 2018. When considering beta‐agonist, mirabegron accounted for 13.1% of total claims and 29.0% of total spending. Mirabegron accounted for a greater proportion of OAB medication claims and spending during the 5 years from 5.7% to 20.1% and 11.3% to 44%, respectively. IR anticholinergics accounted for fewer total claims over this period, from 58.5% to 42.6%. ER formulations increased in proportion of all OAB medication total claims from 35.8% to 37.5% from 2014 to 2016, and decreased to 37.3% by 2018. Conclusion: OAB medications and expenditures increased from 2014 to 2018. Mirabegron accounted for higher proportions and IR‐formulations for decreased proportions of each from 2014 to 2018. The impact on clinical outcomes is a key area for future investigation considering our findings. [ABSTRACT FROM AUTHOR]

Objective: To determine if OAB anticholinergics have an increased risk of delirium or falls/fractures relative to OAB beta‐3 agonist medications. Methods: This was a retrospective, cohort study using linked administrative data from the universal healthcare system of Ontario, Canada. Participants were all residents >66 years of age who newly initiated an OAB medication between January 2016 and March 2020. Coprimary outcomes were evidence of a hospital visit with delirium, or for a fall/fracture. We used matching weights to make the three exposure groups (beta‐3 agonist, oxybutynin, or newer OAB anticholinergics) comparable across 82 baseline characteristics. We examined both the risk during the first 30 days (logistic regression) and the risk during continuous usage (proportional hazards). Results: We identified 103 024 older adults who started OAB medications. With matching weights, all measured variables were similar. The 30‐day incidence of delirium was 0.31%, and fall/fracture was 1.07%; there was no significantly increased risk of either delirium (oxybutynin users OR 1.28 [95% CI 0.84–1.96], newer OAB anticholinergic users OR 0.92 [95% CI 0.58–1.46]) or falls/fractures (oxybutynin users OR 1.19 [95% CI 0.95–1.49], newer OAB anticholinergic users OR 1.14 [95% CI 0.91–1.43]) compared to beta‐3 agonist users. With continuous usage, there was an increased HR of delirium among users of newer anticholinergics (HR 1.13, 95% CI 1.02–1.26) and an increased HR for fall/fracture among oxybutynin users (HR 1.13, 95% CI 1.02–1.24). Conclusions: Compared to beta‐3 agonists, the continuous use of oxybutynin is associated with a significantly increased risk of fall/fracture, and newer OAB anticholinergics are associated with a significantly increased risk of delirium. [ABSTRACT FROM AUTHOR]

Background Despite common use, anticholinergic medications have been associated with serious health risks. Interventions to reduce their use are being developed and there is a need to understand their implementation into clinical care. Aim of review This systematic review aims to identify and analyse qualitative research studies exploring the barriers and facilitators to reducing anticholinergic burden. Methods Medline (OVID), EMBASE (OVID), CINAHL (EMBSCO) and PsycINFO (OVID) were searched using comprehensive search terms. Peer reviewed studies published in English presenting qualitative research in relation to the barriers and facilitators of deprescribing anticholinergic medications, involving patients, carers or health professionals were eligible. Normalization Process Theory was used to explore and explain the data. Results Of 1764 identified studies, two were eligible and both involved healthcare professionals (23 general practitioners, 13 specialist clinicians and 12 pharmacists). No studies were identified that involved patients or carers. Barriers to collaborative working often resulted in poor motivation to reduce anticholinergic use. Low confidence, system resources and organisation of care also hindered anticholinergic burden reduction. Good communication and relationships with patients, carers and other healthcare professionals were reported as important for successful anticholinergic burden reduction. Having a named person for prescribing decisions, and clear role boundaries, were also important facilitators. Conclusions This review identified important barriers and facilitators to anticholinergic burden reduction from healthcare provider perspectives which can inform implementation of such deprescribing interventions. Studies exploring patient and carer perspectives are presently absent but are required to ensure person-centeredness and feasibility of future interventions. [ABSTRACT FROM AUTHOR]

Objectives: The present study aimed to investigate the effect of use of calcium channel blockers and non-steroid anti-inflammatory drugs as alternative to the anticholinergics therapy in cases of urge urinary incontinence in women. Methods: A total of 63 women with urge incontinence were included in the study after inclusion and exclusion criteria and randomized into three treatment groups and their clinical and urodynamic parameters were recorded and analyzed comparatively. Results: Significant differences were found in the means of patients' urinary incontinence parameters including numbers of voidings and of leakage episodes per day as well as their urodynamic parameters including maximum bladder capacity, volume at 1st contraction and residual volume after using Solifenacine, calcium channel blocker (Nifidipine) or Non-steroid anti-inflammatory (Ponstan) drugs (P<0.05). Furthermore, significant differences were found among study's groups regarding their response for treatment indicated by improvement in clinical and urodynamic parameters (P<0.05). Conclusion: The study demonstrated that CCBs seem to be having some beneficial effects, with a different adverse effect profile and so may be used to complement a lower dose of anticholinergic drug. [ABSTRACT FROM AUTHOR]

Background: Harmine is a β-carboline alkaloid that displays antidepressant, antitumor and other pharmacological effects. However, the strong toxic effects limit its clinical application, and should be first considered. Purpose: To evaluate the in vivo toxicity of harmine and explore intervention strategies against its toxicity. Methods: The in vivo toxicity of harmine was assessed from the symptoms, biochemical indices, and cardiovascular effects in mice. The intervention experiments were performed by using anesthetics, central drugs, and peripheral anticholinergics. Results: The acute toxicity of harmine is significantly dose-dependent and the median lethal dose is 26.9 mg/kg in vivo. The typical symptoms include convulsion, tremor, jumping, restlessness, ataxia, opisthotonos, and death; it also changes cardiovascular function. The anesthetics improved the survival rate and abolished the symptoms after harmine poisoning. Two central inhibitors, benzhexol and phenytoin sodium, uniformly improved the survival rates of mice poisoned with harmine. The peripheral anticholinergics didn't show any effects. Conclusion: Harmine exposure leads to central neurological symptoms, cardiovascular effects and even death through direct inhibition of the central AChE activity, where the death primarily comes from central neurological symptoms and is cooperated by the secondary cardiovascular collapse. Central inhibition prevents the acute toxicity of harmine, and especially rapid gaseous anesthetics such as isoflurane, might have potential application in the treatment of harmine poisoning. [ABSTRACT FROM AUTHOR]

Evidence suggests that the prescription of bladder anticholinergics is increasing. Recent studies have accentuated concerns about whether certain prescribed medications could increase risk of dementia, including anticholinergic drugs, and specifically anticholinergics used for bladder symptoms. Nevertheless, it can be difficult to draw together the evidence to review the case for possible causation. Recognising this issue in 1965, Bradford‐Hill set out nine criteria to help assess whether evidence of a causal relationship could be inferred between a presumed cause and an observed effect. In this commentary, we explore the extent to which associations between anticholinergics and dementia satisfy the Bradford‐Hill criteria and examine the potential implications. First, we look at studies that have examined the relationship between anticholinergic drugs with urological properties (bladder drugs) and the onset of dementia, and then present those studies which specifically focus on the cognitive effects of bladder drugs that affect muscarinic receptors in the brain versus the bladder on older people along with suggestions for future research. We also discuss the risks and benefits of these drugs for treating overactive bladder. If it can be shown that certain medications carry a specific risk of dementia, it is possible that initiatives to change prescribing could become a key tool in reducing the risk of dementia and may be easier to implement than some lifestyle changes. [ABSTRACT FROM AUTHOR]

Objective: Age-associated decline in central cholinergic activity makes older adults susceptible to harmful effects of anticholinergics (ACs). Evidence exists of an association between effects of AC medications on cognition. This retrospective cohort study examines how ACs affect cognition among older adults with Alzheimer's disease (AD) who received acetylcholine esterase inhibitors (AChEIs) over the course of 12 months. Results: A total of 133 (80% women, mean age 78.38 years, SD 7.4) were recruited. No difference in sex, age and comorbid diseases was observed between participants who took ACs, benzodiazepines (BZDs) and AChEIs. The most common prescribed ACs was quetiapine, being used for behavioral and psychological symptoms (BPSD). Multilevel analysis showed that the change of mental state examination scores were significantly predicted in the group using ACs (t (169), − 2.52, p =.020) but not with the groups using BZD (t (162), 0.84, p =.440). Evidence showed that older adults with Alzheimer's disease and exposed to ACs exhibited lower global cognitive scores than those without AC exposure. Using ACs could be a trade-off between controlling BPSD and aggravating cognitive impairment. Highlighting the awareness of the potential anticholinergic effect is important and may be the best policy. [ABSTRACT FROM AUTHOR]

Background: Studies have shown an association between lower urinary tract symptoms (LUTS) and an increased risk of dementia. Whether anticholinergic use contributes to the development of dementia in patients with LUTS remains unknown, especially in Asian populations. This study aims to investigate the association between anticholinergic use and dementia in patients with LUTS.Methods: This study included patients aged 50 years and over with newly diagnosed LUTS (January 2001 to December 2005), divided into four groups according to their cumulative defined daily doses (cDDDs) of anticholinergics: < 28 cDDDs, 28-84 cDDDs, 85-336 cDDDs, ≥337 cDDDs. Patients were followed up until dementia developed or until the end of 2012.Results: We recruited a total of 16,412 patients. The incidence of dementia was 10% in the < 28 cDDD group, 8.9% in the 28-84 cDDD group, 11.5% in the 85-336 cDDD group, and 14.4% in the ≥337 cDDD group (p = .005). In a Cox proportional hazards analysis, the adjusted hazard ratio of dementia was 1.15 (95% CI = 0.97-1.37) in the 85-336 cDDD group, and 1.40 (95% CI = 1.12-1.75) in the ≥337 cDDD group after adjusting for covariates.Conclusions: Our study indicates that higher cumulative anticholinergic exposure is associated with an increase in the risk of incident dementia in patients with LUTS aged 50 years of age and over. Either using one anticholinergic agent or switching anticholinergic agents cumulatively increases this risk. Therapeutic risks and benefits of using anticholinergics in LUTS treatment should be clinically reviewed and weighed. [ABSTRACT FROM AUTHOR]

Aims: We investigated anticholinergic medicines use among older adults initiating dementia medicines. Methods: We used Pharmaceutical Benefits Scheme dispensing claims to identify patients who initiated donepezil, rivastigmine, galantamine or memantine between 1 January 2013 and 30 June 2017 (after a period of ≥180 days with no dispensing of these medicines) and remained on therapy for ≥180 days (n = 4393), and dispensed anticholinergic medicines in the 180 days before and after initiating dementia medicines. We further examined anticholinergic medicines prescribed by a prescriber other than the one initiating dementia medicines. Results: One‐third of the study cohort (1439/4393) was exposed to anticholinergic medicines up to 180 days before or after initiating dementia medicines. Among patients exposed to anticholinergic medicines, 46% (659/1439) had the same medicine dispensed before and after initiating dementia medicines. The proportion of patients dispensed anticholinergic medicines increased by 2.5% (95% confidence interval [CI]: 1.3–3.7) after initiating dementia medicines. Antipsychotics use increased by 10.1% (95% CI: 7.6–12.7) after initiating dementia medicines; driven by increased risperidone use (7.3%, 95% CI: 5.3–9.3). Nearly half of patients dispensed anticholinergic medicines in the 180 days after (537/1133), were prescribed anticholinergic medicines by a prescriber other than the one initiating dementia medicines. Conclusion: Use of anticholinergic medicines is common among patients initiating dementia medicines and this occurs against a backdrop of widespread campaigns to reduce irrational medicine combinations in this vulnerable population. Decisions about deprescribing medicines with questionable benefit among patients with dementia may be complicated by conflicting recommendations in prescribing guidelines. [ABSTRACT FROM AUTHOR]

Few studies have evaluated the association between anticholinergic burden and treatment modification after starting a cholinesterase inhibitor in clinical practice. We aimed to evaluate the effect of anticholinergic burden on anti‐dementia treatment modification, delirium and mortality. We retrospectively analysed older adults (n = 25 825) who started a cholinesterase inhibitor during 2003–2011 from Korean National Health Insurance Service Senior Cohort Database. High anticholinergic burden was defined as an average daily Anticholinergic Cognitive Burden (ACB) score of >3 during the first 3 months. We investigated the impact of high anticholinergic burden on the rate of treatment modification, delirium and mortality in comparison with minimal ACB (ACB score ≤1) in propensity‐matched cohorts (N = 7438). Approximately 6.0% of patients with dementia were exposed to a high anticholinergic burden within the first three months of treatment. In high anticholinergic burden cohorts, significantly more patients experienced treatment modification (34.9% vs. 32.1%) or delirium (5.6% vs. 3.6%) and the mortality rate was also higher (16.8% vs. 14.1%) than controls. A multivariate Cox proportional hazard regression analysis showed that an average ACB score >3 within the first three months significantly increased the risk of treatment modification (hazard ratio (HR): 1.12, 95% confidence interval (CI): 1.02‐1.24), delirium (HR: 1.52, CI: 1.17‐1.96) and mortality (HR: 1.23, CI: 1.06‐1.41). This study showed that high anticholinergic burden negatively affected the treatment response to cholinesterase inhibitors and that an average ACB score >3 was an independent prognostic factor for delirium or mortality in dementia patients. [ABSTRACT FROM AUTHOR]

Abstract The present study sought to determine the pharmacological effects of penehyclidine, an anticholinergic agent, on the angiogenic capacity of pulmonary microvascular endothelial cells (PMVECs). In vitro Matrigel network formation assay, cell proliferation assay, cell-matrix adhesion assay, and wound-healing assay were performed in PMVECs with or without exposure to penehyclidine or, in some cases, glycopyrrolate or acetylcholine, over a concentration range. In addition, the phosphorylation state of Akt and ERK, as well as the endogenous level of mTOR and RICTOR were examined in PMVECs by Western blot following the cells exposure to penehyclidine or, for some proteins, glycopyrrolate or acetylcholine. Finally, Western blot for Akt phosphorylation and in vitro Matrigel network formation assay were performed in PMVECs following their exposure to penehyclidine with or without phosphoinositide 3-kinase (PI3K) inhibitor LY294002 or mTOR inhibitor torin-1. We found that, in PMVECs, penehyclidine affected the network formation and cell migration, but not proliferation or cell-matrix adhesion, in a concentration-specific manner, i.e., penehyclidine increased the network formation and cell migration at lower concentrations but increased these processes at higher concentrations. Coincidentally, we observed that penehyclidine concentration-specifically affected the phosphorylation state of Akt in PMVECs, i.e., increased Akt phosphorylation at lower concentrations and decreased it at higher concentrations. In contrast, glycopyrrolate was found straightly to decrease network formation and Akt phosphorylation in a concentration-dependent manner. Further, we demonstrated that PI3K or mTOR blockade abolished both the enhanced network formation and the increased Akt phosphorylation by penehyclidine. Hence, penehyclidine may differentially alter the angiogenic capacity of PMVECs through affecting the Akt signaling pathway downstream of PI3K and mTOR. Findings from this study suggest a unique pharmacological feature of penehyclidine, which may imply its clinical and therapeutic value in modulating angiogenesis. [ABSTRACT FROM AUTHOR]

Antipsychotics specifically the first-generation line of drugs is closely associated with the development of extrapyramidal side effects. Ever since its alleviating sequel was known, anticholinergic agents such as Artane and Procyclydine has been the mainstay therapeutic agent in combating the unwanted outcomes of antipsychotics use. Anticholinergics itself however has uninvited adverse effects of its own. Other than the uncontrollable central and peripheral side effects, there are studies to date which discovered the euphoric sensation experienced by anticholinergic consumers. As the attending physician, one must be aware of the benefits and risks of anticholinergics when prescribing such drugs to a mentally unwell patient. [ABSTRACT FROM AUTHOR]

Context: Death rattle (DR) is a dramatic sign in the dying patient. Existing studies with anticholinergic agents are controversial, as this class of drugs has been commonly administered without considering the rationale of the mechanism of action. A meaningful use of these drugs may provide a better outcome.Objectives: The aim of this study was to assess the efficacy of hyoscine butylbromide (HB), given prophylactically in comparison with HB administered once DR occurs.Methods: Dying patients having a score of ≥3 in the Richmond Agitation-Sedation Scale-palliative version were included in the study. HB (60 mg/day) was given when DR occurred (Group 1) or as pre-emptive treatment (Group 2). The onset of DR (death rattle free time) and intensity of DR were recorded at intervals until death.Results: Eighty-one and 51 patients were randomized to Group 1 and 2, respectively. Patients in Group 2 survived longer than those in Group 1 (P < 0.05). DR occurred in 49 (60.5%) and three patients (5.9%) in Group 1 and 2, respectively (P = 0.001). A significant difference in the number of patients reporting DR was found at intervals examined (30 minutes, one hour, and then every six hours until death [P = 0.001]). In Group 1 and 2, DR free time was 20.4 (20.5) and 27.3 hours (25.2), respectively (P = 0.001). In Group 1, the treatment was considered effective in 10 patients (20.4%) only, after a mean of 14.4 hours (SD 8.57).Conclusion: The prophylactic use of HB is an efficient method to prevent DR, whereas the late administration produces a limited response, confirming data from traditional studies performed with anticholinergics. This could be considered a new paradigm to manage a difficult and dramatic sign, such as DR. [ABSTRACT FROM AUTHOR]

Objectives: To assess anticholinergic use, especially the use of antimuscarinics, in the elderly (aged ≥65 years) Japanese overactive bladder and non‐overactive bladder populations. Methods: Patient records were sourced from a large, nationwide Japanese pharmacy claims database. Anticholinergic use on a random day in 2016 (index date) was investigated through the Anticholinergic Cognitive Burden scale (primary scale), the Anticholinergic Drug Scale, the Anticholinergic Risk Scale and Beers criteria. The prevalence of anticholinergic use and anticholinergic scores at the index date were summarized descriptively. The overactive bladder population was defined as patients who had at least one prescription record for any antimuscarinic (fesoterodine, imidafenacin, oxybutynin, propiverine, solifenacin or tolterodine) or the β3‐adrenoreceptor agonist, mirabegron, within the 1‐year pre‐index period. Results: Among 1 216 126 outpatients, 35 138 (2.9%) were included in the overactive bladder group. In total, 112 (68.7%) of the anticholinergics listed in the scales were identified. In those who received any Anticholinergic Cognitive Burden scale‐listed anticholinergic, the mean scores were higher in overactive bladder patients versus non‐overactive bladder patients (3.2 ± 1.3 and 1.6 ± 1.1, respectively). Similarly, overactive bladder patients who received antimuscarinics had higher Anticholinergic Cognitive Burden scores (3.3 ± 1.2) than patients who received mirabegron only (1.7 ± 1.1). In 58.8% of the overactive bladder patients, ≥80% of the total Anticholinergic Cognitive Burden score was exclusively attributable to antimuscarinics. Conclusions: Anticholinergic use was higher in overactive bladder patients versus non‐overactive bladder patients. This increased use was largely attributable to antimuscarinics. The alternative use of mirabegron could therefore be considered to reduce the burden experienced by patients in Japan. [ABSTRACT FROM AUTHOR]

Background: Anticholinergic burden is associated with poorer cognitive and functional outcomes in people with dementia. However, the impact of anticholinergics on significant adverse outcomes such as stroke has not been studied previously.Objective: To investigate the association between total anticholinergic cognitive burden (ACB) and risk of stroke and death in people with different dementia subtypes.Methods: This was a cohort study of 39,107 people with dementia and no prior history of stroke registered in the Swedish Dementia Registry (SveDem) from 2008-2014. Data were extracted from the Swedish Prescribed Drug Register, the Swedish National Patient Register, and the Swedish Total Population Register. Competing risk regression models were used to compute hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between time-varying ACB score and risk of stroke and all-cause mortality.Results: During a mean follow-up period of 2.31 (standard deviation 1.66) years, 11,224 (28.7%) individuals had a stroke or died. Compared with non-users of anticholinergic medications, ACB score of 1 (HR 1.09, 95% CI 1.04-1.14) and ACB score of ≥2 (HR 1.20, 95% CI 1.14-1.26) increased the risk of developing the composite outcome of stroke and death. When stratifying by dementia disorder, the association remained significant in Alzheimer's disease, mixed dementia, and vascular dementia.Conclusions: The use of anticholinergic medicines may be associated with an increased risk of stroke and death in people with dementia. A dose-response relationship was observed. Careful consideration should be made when prescribing medications with anticholinergic properties to people with dementia. [ABSTRACT FROM AUTHOR]

Objectives: To estimate prescribing tends of and correlates independently associated with high‐risk anticholinergic prescriptions in adults aged 65 and older in office‐based outpatient visits. Design: Repeated cross‐sectional analysis. Setting: National Ambulatory Medical Care Survey (NAMCS). Participants: A national sample of office‐based physician visits by adults aged 65 and older from 2006 to 2015 (n=96,996 unweighted). Measurements: Prescriptions of high‐risk anticholinergics, regardless of indication, were identified, and overall prescribing trends were estimated from 2006 to 2015. Stratified analyses of prescribing trends according to physician specialty and anticholinergic drug class were also performed. We used a multivariable logistic regression analysis to estimate the odds of high‐risk anticholinergic prescription. Results: Between 2006 and 2015, a high‐risk anticholinergic prescription was listed for 5,876 (6.2%) 96,996 visits of older adults, representative of 14.6 million total visits nationally. The most common drug classes were antidepressants, antimuscarinics, and antihistamines, which accounted for more than 70% of prescribed anticholinergics. Correlates independently associated with greater odds of receiving a high‐risk anticholinergic prescription were female sex, the Southern geographic region, specific physician specialties (e.g., psychiatry, urology), receipt of 6 or more concomitantly prescribed medications, and related clinical diagnoses (e.g., urinary continence) (p<.01 for all). Conclusion: The prevalence of high‐risk anticholinergic prescriptions was stable over time but varied according to physician specialty and drug class. Quality prescribing should be promoted because safer alternatives are available. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effect of trospium chloride, which has an anticholinergic effect, used in overactive bladder (OAB) treatment on the intraocular pressure (IOP) and tear secretion after 12 weeks of treatment. Materials and methods: This prospective study was performed at a single center between October 2014 and January 2016. A detailed history was obtained from the female OAB patients at the eye outpatient department. After checking the exclusion criteria, oral trospium chloride 30 mg bd was started. The patients were followed-up in terms of drug effectiveness and ophthalmic and other side effects at the 4th and 12th weeks. All procedures were repeated at both of these time-points. Results: The mean age of the patients was 48.98 ± 11.98 years (range 19–75). The data of 80 OAB patients were evaluated in the study. Trospium chloride did not cause any significant change in the OAB patients regarding their 4th week and 12th week IOP measurements (p = 0.251,p = 0.340, respectively). It was found to decrease tear secretion significantly at both time-points (p = 0.020,p = 0.001, respectively). Trospium chloride treatment of one patient (1.25%) was discontinued due to dry eye. Conclusions: Trospium chloride decreases the symptoms in female OAB patients. Trospium chloride can be safely used in female OAB patients with normal IOP and no comorbidity as regards IOP changes as it did not cause a significant change in IOP in these patients. Pre-treatment and post-treatment dry eye symptoms of OAB patients about to start using trospium chloride should be queried beforehand as it can cause a statistically significant decrease in tear secretion. We concluded that it would be appropriate to refer the patients to an ophthalmologist before starting the drug if relevant symptoms are present. [ABSTRACT FROM PUBLISHER]