Anticholinergic Medication Use Research Articles

Associations Between Midlife Anticholinergic Medication Use and Subsequent Cognitive Decline: A British Birth Cohort Study.

Anticholinergic medication use is associated with cognitive decline and incident dementia. Our study, a prospective birthcohortanalysis, aimed to determine if repeated exposure to anticholinergic medicationswas associated with greater decline, and whether decline was reversed with medication reduction. From the Medical Research Council (MRC) National Survey of Health and Development, a British birth cohort with all participants born in a single week of March 1946, we quantified anticholinergic exposure between ages 53 and 69 years using the Anticholinergic Cognitive Burden Scale (ACBS). We used multinomial regression to estimate associations with global cognition, quantified bythe Addenbrooke's Cognitive Examination, 3rd Edition (ACE-III). Longitudinal associations between ACBS and cognitive test results (Verbal memory quantifiedby theWord Learning Test [WLT], and processing speed quantified by theTimed Letter Search Task [TLST]) at three time points (age 53, 60-64 and 69) were assessed using mixed and fixed effects linear regression models. Analyses were adjusted for sex, childhood cognition, education, chronic disease count and severity, and mental health symptoms. Anticholinergic exposure was associated cross-sectionally with lower ACE-III scores at age 69, with the greatest effects in those with high exposure at ages 60-64 (mean difference - 2.34, 95% confidence interval [CI] - 3.51 to - 1.17). Longitudinally, both mild-moderate and high ACBS scores were linked to lower WLT scores, again with high exposure showing larger effects (mean difference with contemporaneous exposure - 0.90, 95% CI - 1.63 to - 0.17; mean difference with lagged exposure - 1.53, 95% CI - 2.43 to - 0.64). Associations remained in fixed effects models (mean difference with contemporaneous exposure -1.78, 95% CI -2.85 to - 0.71; mean difference with lagged exposure - 2.23, 95% CI - 3.33 to - 1.13). Associations with TLST were noted only in isolated contemporaneous exposure (mean difference - 13.14, 95% CI - 19.04 to - 7.23; p<0.01). Anticholinergic exposure throughout mid and later life was associated with lower cognitive function. Reduced processing speed was associated only with contemporaneous anticholinergic medication use, and not historical use. Associations with lower verbal recall were evident with both historical and contemporaneous use of anticholinergic medication, and associations with historical use persisted in individuals even when their anticholinergic medication use decreased over the course of the study.

Assessing the Impact of Overactive Bladder Medications on Cognition.

Emerging literature has associated the use of anticholinergic medications to cognitive decline. The aim of this study was to evaluate the association of overactive bladder medications on cognitive function with prospective longitudinal cognitive assessments. A population-based cohort of individuals 50 years and older who had serial validated cognitive assessment, in accordance with the Mayo Clinic Study of Aging, was evaluated from October 2004 through December 2021. Anticholinergic overactive bladder medications were grouped by traditional anticholinergic medications and central nervous system (CNS)- sparing anticholinergic medications and compared to no medication exposure. A linear mixed effects model with time-dependent exposures evaluated the association between overactive bladder anticholinergic medication exposure and subsequent trajectories of cognitive z-scores. We included 5,872 participants with a median follow-up of 6.4 years. Four hundred forty-three were exposed to traditional anticholinergic medications, 60 to CNS-sparing medications, and 5,369 had no exposure. On multivariable analyses, exposure to any anticholinergic overactive bladder medication was significantly associated with deterioration in longitudinal cognitive scores in the language and attention assessments compared to the control cohort. Traditional anticholinergic medication exposure was associated with worse attention scores than nonexposed participants. Exposure to CNS-sparing anticholinergic medications was associated with a deterioration in the language domain compared to those unexposed. Among women, traditional anticholinergic medication exposure was associated with worse global and visuospatial scores than nonexposed participants, but this association was not identified in the CNS-sparing group. Exposure to anticholinergic overactive bladder medications was associated with small but significantly worse decline in cognitive scoring in the language and attention domains when compared to nonexposed individuals.

Anticholinergic Burden in Patients Treated for Overactive Bladder: Second-Line Therapy with Tibial Nerve Stimulation as a Solution.

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.

Anticholinergic and sedative medication use in older patients with cognitive concerns.

Anticholinergic (AC) and sedative medications are a risk factor for cognitive impairment. This study sought to characterize AC and sedative use in older patients seen for outpatient neuropsychological evaluation and evaluate their associations with different cognitive domains. We hypothesized that AC and sedative use would be associated with worse attention/processing speed (AP), executive functioning (EF), and memory. We conducted a cross-sectional chart review of 392 patients (mean [M] age = 72 ± 7.7 years, range = 54-91). Medications were characterized by number of AC medications (≥1 on the Anticholinergic Cognitive Burden Scale [ACB]), number of sedative medications, and polypharmacy (≥5 daily medications). Demographically adjusted composites were calculated for AP, EF, and memory. Bivariate Pearson correlations assessed relationships between medication use and cognition. Multivariate linear regressions evaluated significant medication-cognition associations, controlling for total medications, medical comorbidities, and estimated premorbid cognitive functioning. Polypharmacy was common (80%; n = 314). Most patients (70%; n = 275) used ≥1 sedative medications (range = 0-9). Over half (63%; n = 248) used ≥1 AC drugs (range = 0-7), yet ACB scores were ≤2 in 74% of patients. Sedative use was negatively correlated with AP (r = -0.134, p = 0.008) and EF (r = -0.105, p = 0.04). ACB scores were negatively correlated with AP (r = -0.106, p = 0.037). Sedatives and a priori covariates significantly predicted AP performance (R2 = 0.127, p < 0.001); using more sedative medications was uniquely associated with worse AP (β = -0.426, p = 0.049). No significant associations were found with memory. AC and sedative medications and polypharmacy were prevalent in this sample of older patients. Though both drug classes had negative relationships with AP and EF, sedatives had a particularly negative association with AP. Contrary to our hypotheses, memory was not associated with medication use; however, anticholinergic burden was low within the sample, and AP and EF deficits may masquerade as memory problems.

Association of systemic anticholinergic medication use and accelerated decrease in lung function in older adults

Older adults are frequently exposed to medicines with systemic anticholinergic properties, which are linked to increased risk of negative health outcomes. The association between systemic anticholinergics and lung function has not been reported. The aim of this study was to investigate if exposure to systemic anticholinergics influences lung function in older adults. Participants of the southernmost centres of the Swedish National study on Aging and Care (SNAC) were followed from 2001 to 2021. In total, 2936 subjects (2253 from Good Aging in Skåne and 683 from SNAC-B) were included. An extensive medical examination including spirometry assessments was performed during the study visits. The systemic anticholinergic burden was described using the anticholinergic cognitive burden scale. The effect of new use of systemic anticholinergics on the annual change in forced expiratory volume (FEV1s) was estimated using mixed models. During follow-up, 802 (27.3%) participants were exposed to at least one systemic anticholinergic medicine. On average, the FEV1s of participants without systemic anticholinergic exposure decreased 37.2 ml/year (95% CI [33.8; 40.6]) while participants with low and high exposure lose 47.2 ml/year (95% CI [42.4; 52.0]) and 43.7 ml/year (95% CI [25.4; 62.0]). A novel association between new use of medicines with systemic anticholinergic properties and accelerated decrease in lung function in older adults was found. The accelerated decrease is comparable to that observed in smokers. Studies are needed to further explore this potential side effect of systemic anticholinergics.

Development of an individualized risk calculator of treatment resistance in patients with first-episode psychosis (TRipCal) using automated machine learning: a 12-year follow-up study with clozapine prescription as a proxy indicator.

About 15-40% of patients with schizophrenia are treatment resistance (TR) and require clozapine. Identifying individuals who have higher risk of development of TR early in the course of illness is important to provide personalized intervention. A total of 1400 patients with FEP enrolled in the early intervention for psychosis service or receiving the standard psychiatric service between July 1, 1998, and June 30, 2003, for the first time were included. Clozapine prescriptions until June 2015, as a proxy of TR, were obtained. Premorbid information, baseline characteristics, and monthly clinical information were retrieved systematically from the electronic clinical management system (CMS). Training and testing samples were established with random subsampling. An automated machine learning (autoML) approach was used to optimize the ML algorithm and hyperparameters selection to establish four probabilistic classification models (baseline, 12-month, 24-month, and 36-month information) of TR development. This study found 191 FEP patients (13.7%) who had ever been prescribed clozapine over the follow-up periods. The ML pipelines identified with autoML had an area under the receiver operating characteristic curve ranging from 0.676 (baseline information) to 0.774 (36-month information) in predicting future TR. Features of baseline information, including schizophrenia diagnosis and age of onset, and longitudinal clinical information including symptoms variability, relapse, and use of antipsychotics and anticholinergic medications were important predictors and were included in the risk calculator. The risk calculator for future TR development in FEP patients (TRipCal) developed in this study could support the continuous development of data-driven clinical tools to assist personalized interventions to prevent or postpone TR development in the early course of illness and reduce delay in clozapine initiation.

Efficacy of Long-Acting Injectable Antipsychotics Versus Oral Antipsychotics in Preventing Psychiatric Rehospitalizations.

Schizophrenia is a chronic, debilitating mental illness that incurs a large economic burden. Decreasing hospital readmissions is a priority in health care to improve patient quality of life and decrease health care costs. Determining ways to prevent readmissions such as improving access to long-acting injectable (LAI) antipsychotics is important to assess. A single-center retrospective review was conducted comparing readmission rates of patients diagnosed with schizophrenia or schizoaffective disorder discharged on LAI or oral antipsychotics between August 1, 2019, and June 30, 2022. The primary outcome was the 30-day psychiatric readmission rate. Secondary outcomes included chlorpromazine equivalent doses and use of anticholinergic medications. The 30-day readmission rate was 1.9% for the LAI antipsychotic group and 8.3% for the oral antipsychotic group ( P = 0.03; 95% confidence interval, 1.05-20.02). The average chlorpromazine equivalent antipsychotic dose of patients discharged on LAI versus oral antipsychotic medications was 477.3 and 278.6 mg/d, respectively ( P < 0.001). In addition, the prevalence of medications used to treat extrapyramidal symptom was 22.3% (n = 23) for the LAI antipsychotic group and 30.8% (n = 74) for the oral antipsychotic group ( P = 0.12). Sixty-four percent of LAI antipsychotics utilized were obtained from pharmaceutical company hospital inpatient free trial programs. Long-acting injectable antipsychotics showed a statistically significant reduction in 30-day rehospitalizations as compared with oral antipsychotics and hospital inpatient free trial programs aided in LAI antipsychotic acquisition.

Carers' experiences and perspectives of the use of anticholinergic medications in people living with dementia: Analysis of an online discussion forum

AbstractIntroductionThere is concern about the use of anticholinergic medications in people living with dementia (PLWD). Such medicines may increase cognitive decline and may be associated with higher mortality in PLWD who take these medicines. The aim of this study was to analyse data from an online dementia discussion forum to explore the experiences and perspectives of PLWD and carers about the use of anticholinergic medicines in this population.MethodsFollowing receipt of ethical approval, archived discussions (posts) from Dementia Talking Point, a fully public online forum for anyone affected by dementia, created and maintained by the Alzheimer's Society, were searched from the date of inception to January 2022 using a range of search terms including commonly used anticholinergic medicines. Posts, including any of the search terms, were assessed for relevance and analysed using inductive thematic analysis.ResultsFive hundred and fifty unique posts were analysed, all of which had been provided by carers, with no posts attributed to PLWD. The themes that encompassed carers' experiences were (1) motivators of prescribing, (2) perspectives on the process of prescribing and (3) the outcomes of prescribing. The dominant motivator of prescribing was the management of noncognitive symptoms, pre‐ and postdiagnosis of dementia. Carers' perspectives on the process of prescribing were informed by an assessment of the risk‐benefit of starting a medication and shared decision‐making between the carer and healthcare professional to a greater or lesser degree. The outcomes of prescribing were observing the effects of the medicines, which in turn influenced whether prescribing was reviewed and continued unchanged, continued but amended, reinitiated if the medicine had been previously stopped or discontinued (the process of deprescribing).ConclusionThis study has provided unique insights into carers' experiences and perspectives about the use of anticholinergic medications in PLWD, highlighting how commonly these medications are prescribed for PLWD and carers' concerns about their use. There is a clear need for carers and PLWD to receive information about these medicines and healthcare professionals to consider how to optimise the use of these medicines to avoid adverse effects.Patient or Public ContributionThis work was informed by findings from previous research studies focusing on optimising medicine use for people with dementia in primary care, in which interviews were conducted with PLWD, their carers and primary healthcare professionals. Although not strictly patient and public involvement, we utilised the feedback provided by key stakeholders to inform the research questions and aim/objectives of this study.

Increased anticholinergic medication use in middle-aged and older autistic adults and its associations with self-reported memory difficulties and cognitive decline.

Many commonly used prescription and over-the-counter medicines have potent anticholinergic (AC) effects. Among older adults, AC medications are associated with cognitive impairment and risk for cognitive disorders, including Alzheimer's disease. Collectively, the impact of AC medications is known as anticholinergic cognitive burden (ACB). Because of the high rates of co-occurring medical and psychiatric conditions, autistic adults may have high AC exposure and, thus, may experience elevated ACB. However, no research has characterized AC exposure or examined its associations with cognitive outcomes in autistic adults. Autistic adults (40-83 years) recruited via Simons Powering Autism Research's (SPARK) Research Match service self-reported their medication use (N = 415) and memory complaints (N = 382) at Time (T)1. At T2, 2 years later, a subset of T1 participants (N = 197) self-reported on decline in cognition. Medications were coded using two scales of AC potency. A high proportion (48.2%-62.9%, depending upon the AC potency scale) of autistic adults reported taking at least one medication with AC effects, and 20.5% to 26.5% of autistic adults reported clinically-relevant levels of AC medication (potency ≥3). After controlling for birth-sex, and age, hierarchical linear regression models showed total ACB scores and AC potency values of ≥3 predicted greater memory complaints. Logistic regression models showed that AC medicines at T1 were associated with self-reported cognitive decline at follow-up 2 years later. Understanding AC medications-including potentially earlier AC polypharmacy-and their impacts on cognition (e.g., dementia risk) in autistic adults is warranted.

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

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.

Changes in the Use of Long-Term Medications Following Incident Dementia Diagnosis

Dementia is a life-altering diagnosis that may affect medication safety and goals for chronic disease management. To examine changes in medication use following an incident dementia diagnosis among community-dwelling older adults. In this cohort study of adults aged 67 years or older enrolled in traditional Medicare and Medicare Part D, patients with incident dementia diagnosed between January 2012 and December 2018 were matched to control patients based on demographics, geographic location, and baseline medication count. The index date was defined as the date of first dementia diagnosis or, for controls, the date of the closest office visit. Data were analyzed from August 2021 to June 2023. Incident dementia diagnosis. The main outcomes were overall medication counts and use of cardiometabolic, central nervous system (CNS)-active, and anticholinergic medications. A comparative time-series analysis was conducted to examine quarterly changes in medication use in the year before through the year following the index date. The study included 266 675 adults with incident dementia and 266 675 control adults; in both groups, 65.1% were aged 80 years or older (mean [SD] age, 82.2 [7.1] years) and 67.8% were female. At baseline, patients with incident dementia were more likely than controls to use CNS-active medications (54.32% vs 48.39%) and anticholinergic medications (17.79% vs 15.96%) and less likely to use most cardiometabolic medications (eg, diabetes medications, 31.19% vs 36.45%). Immediately following the index date, the cohort with dementia had a greater increase in mean number of medications used (0.41 vs -0.06; difference, 0.46 [95% CI, 0.27-0.66]) and in the proportion of patients using CNS-active medications (absolute change, 3.44% vs 0.79%; difference, 2.65% [95% CI, 0.85%-4.45%]) owing to an increased use of antipsychotics, antidepressants, and antiepileptics. The cohort with dementia also had a modestly greater decline in use of anticholinergic medications (quarterly change in use, -0.53% vs -0.21%; difference, -0.32% [95% CI, -0.55% to -0.08%]) and most cardiometabolic medications (eg, quarterly change in antihypertensive use: -0.84% vs -0.40%; difference, -0.44% [95% CI, -0.64% to -0.25%]). One year after diagnosis, 75.2% of the cohort with dementia were using 5 or more medications (2.8% increase). In this cohort study of Medicare Part D beneficiaries, following an incident dementia diagnosis, patients were more likely to initiate CNS-active medications and modestly more likely to discontinue cardiometabolic and anticholinergic medications compared with the control group. These findings suggest missed opportunities to reduce burdensome polypharmacy by deprescribing long-term medications with high safety risks or limited likelihood of benefit or that may be associated with impaired cognition.

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.

Cost analysis for mirabegron use in the treatment of children with neurogenic bladder

Mirabegron is a beta-3 adrenergic receptor agonist that received FDA approval in 2021 to treat neurogenic detrusor overactivity (NDO) in children ages three years and older. Despite its safety and efficacy, access to mirabegron frequently remains restricted by payor coverage policies. This cost minimization study sought to determine the cost implications from a payor perspective of mirabegron use at different points in the treatment pathway for pediatric NDO. A Markov decision analytic model was constructed to assess the costs for eight treatment strategies over a 10-year period, using six-month cycles (Table). Five strategies involve mirabegron use as first-, second-, third-, or fourth-line therapy. Two strategies, including the "base case," entail use of anticholinergic medications followed by onabotulinum toxin type A (Botox) injection and augmentation cystoplasty. A strategy involving first-line Botox was also modeled. The effectiveness, adverse event rates, attrition rates, and costs associated with each treatment option were obtained from the clinical literature and adjusted to a six-month cycle. Costs were adjusted to 2021-dollar value. A discount rate of 3% was used. To quantify uncertainty, costs and treatment transition probabilities were modeled as gamma and PERT distributions, respectively. One-way sensitivity analyses were performed. Probabilistic sensitivity analysis (PSA) was conducted using a Monte Carlo simulation with 100,000 iterations. Analyses were performed using Treeage Pro (Healthcare Version). The least costly strategy involved first-line mirabegron (expected cost $37,954). All strategies involving mirabegron were less costly than the base case ($56,417). On PSA, first-line mirabegron was the least costly strategy in 88.9% of cases (mean $37,604, 95% CI: $37,579-37,628); in 100% of cases, the least costly strategy involved mirabegron use. Cost savings associated with mirabegron use were attributable to decreased use of augmentation cystoplasty and Botox injections. This is the first study to compare costs across multiple strategies involving mirabegron to treat pediatric NDO. Mirabegron use likely yields cost savings for the payor: the least costly strategy involved first-line mirabegron, and all pathways incorporating mirabegron were less costly than those without mirabegron use. These findings provide an updated cost analysis for the treatment of NDO by investigating mirabegron use alongside more established treatment options. Use of mirabegron for the treatment of pediatric NDO is likely associated with cost savings as compared to treatment pathways without mirabegron. Expansion of payor coverage for mirabegron, as well as clinical studies to study first-line mirabegron use, should be considered.

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.

Design and validation of neuronal exocytosis blocking peptides as potential novel antiperspirants.

Thermoregulation and heat dissipation by sweat production and evaporation are vital for human survival. However, hyperhidrosis or excessive perspiration might affect people's quality of life by causing discomfort and stress. The prolonged use of classical antiperspirants, anticholinergic medications or botulinum toxin injections for persistent hyperhidrosis might produce diverse side effects that limit their clinical use. Inspired by botox molecular mode of action, we used an in silico molecular modelling approach to design novel peptides to target neuronal acetylcholine exocytosis by interfering with the Snapin-SNARE complex formation. Our exhaustive design rendered the selection of 11 peptides that decreased calcium-dependent vesicle exocytosis in rat DRG neurons, reducing αCGRP release and TRPV1 inflammatory sensitization. The most potent peptides were palmitoylated peptides SPSR38-4.1 and SPSR98-9.1 that significantly suppressed acetylcholine release in vitro in human LAN-2 neuroblastoma cells. Noteworthy, local acute and chronic administration of SPSR38-4.1 peptide significantly decreased, in a dose-dependent manner, pilocarpine-induced sweating in an in vivo mouse model. Taken together, our in silico approach lead to the identification of active peptides able to attenuate excessive sweating by modulating neuronal acetylcholine exocytosis, and identified peptide SPSR38-4.1 as a promising new antihyperhidrosis candidate for clinical development.

MP37-14 CHOICE OF FIRST MEDICATION PRESCRIBED FOR OVERACTIVE BLADDER CHANGES WITH TIME: TRENDS FROM THE AUA AQUA REGISTRY

You have accessJournal of UrologyCME1 Apr 2023MP37-14 CHOICE OF FIRST MEDICATION PRESCRIBED FOR OVERACTIVE BLADDER CHANGES WITH TIME: TRENDS FROM THE AUA AQUA REGISTRY Camille Vélez, Max Bowman, Katherine Shapiro, Rachel Mbassa, Raymond Fang, Benjamin Brucker, and Michelle van Kuiken Camille VélezCamille Vélez More articles by this author , Max BowmanMax Bowman More articles by this author , Katherine ShapiroKatherine Shapiro More articles by this author , Rachel MbassaRachel Mbassa More articles by this author , Raymond FangRaymond Fang More articles by this author , Benjamin BruckerBenjamin Brucker More articles by this author , and Michelle van KuikenMichelle van Kuiken More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003275.14AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Overactive bladder (OAB) is a clinical condition that can greatly affect quality of life. Pharmacological management of OAB may involve use of anticholinergic (ACH) or beta-3 agonists (B3) medications; however, there is increasing evidence of cognitive side-effects associated with the long-term use of ACH medications. Using the AUA AQUA Registry, we aim to evaluate how prescription trends between ACH and B3 agonists has changed over time. METHODS: We queried the AUA Quality (AQUA) Registry database, a national Qualified Clinical Data Registry, for patients >18 years with a new diagnosis of OAB including urinary urgency, frequency, and urgency urinary incontinence (UUI) from 2014-2020 using ICD-9 and ICD-10 codes. Patients with a diagnosis of neurogenic bladder or neurologic diagnosis associated with neurogenic bladder were excluded. The choice of first medication prescribed for OAB was assessed and these trends were observed and analyzed. RESULTS: A total of 641,112 patients were diagnosed with OAB over the study period, 17.5% of whom received a medication prescription. In 2014, ACH comprised 76.3% of OAB treatment prescriptions, while B3 agonists made up 22.1%; Over time, ACH use steadily declined to only 60.3% of first prescriptions, while B3 agonist prescriptions nearly doubled to a peak of 41.4% in 2019, leveling off to 38% in 2020. (Figure 1a). When comparing individual ACH medications, a sharp decrease was observed in solifenacin prescriptions, which went from the most prescribed ACH at 34.8% in 2014 to third most prescribed at 7.7% in 2020. As solifenacin use declined, oxybutynin ER use increased from 11.9% in 2014 to a peak of 26.4% in 2020 to become the most prescribed ACH (Figure 1b). CONCLUSIONS: These prescription trends illustrate that ACH medications remain the most common class of medications first prescribed for OAB, however B3 agonist use has steadily increased with time. Further investigation leveraging the AUA AQUA Registry will help understand what drives OAB medication prescription trends by urologists in the US. Source of Funding: This study was supported by AUA statistical services © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e519 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Camille Vélez More articles by this author Max Bowman More articles by this author Katherine Shapiro More articles by this author Rachel Mbassa More articles by this author Raymond Fang More articles by this author Benjamin Brucker More articles by this author Michelle van Kuiken More articles by this author Expand All Advertisement PDF downloadLoading ...

Anticholinergic Medication and Caries Status Predict Xerostomia under 65.

The use of anticholinergic medications is increasing in younger ages, yet information about xerostomia, the most common anticholinergic side effect, is limited. This case-control retrospective study examines the relationship between anticholinergic medication-induced xerostomia and caries status among adults between 18 and 65 years of age. The study sample comprised 649 cases with xerostomia and 649 age- and gender-matched controls. The anticholinergic burden was estimated using the anticholinergic drug scale (ADS). Caries experience was recorded by calculating the Decayed, Missing, Filled Tooth (DMFT) index. Individuals with xerostomia had a higher mean DMFT index (16.02 ± 9.50), which corresponded with a higher level of anticholinergic exposure from medications (3.26 ± 2.81) compared to their age and gender-matched controls without xerostomia (13.83 + 8.83 and 1.89 ± 2.45, respectively). Logistic regression analysis verified the effects of DMFT, the total number of AC medications, and the ADS burden on xerostomia status. Comparing adults with or without xerostomia revealed statistical differences in several risk factors, such as smoking, diabetes, sleep apnea, and the utilization of anticholinergic medications. A personalized dental care plan should include the evaluation of the anticholinergic burden from medications regardless of the patient's age to prevent increased caries severity.

Effect of topical anticholinergic medication on clinical manifestations control among patients with vasomotor rhinitis versus allergic rhinitis: as comparative clinical trials

BackgroundThe use of a topical anticholinergic medication, ipratropium bromide, and its ability to inhibit methacholine and rhinitis-induced hypersecretion is emphasized. Ipratropium bromide appears to be both safe and effective in reducing this troublesome symptom. This study is designed to show the therapeutic effect of anticholinergic local treatment on nasal mucosa in patients with vasomotor rhinitis.ObjectiveTo assess the therapeutic effect of local anticholinergic treatment on nasal mucosa in patients with vasomotor rhinitis compared to non-vasomotor (allergic) patients and normal individuals, and if there any down regulation of the muscarinic receptors or not.Patients and methodsThis prospective intervention study was conducted in Otorhinolaryngology Department, Faculty of Medicine, Ain Shams University. This study was conducted on 60 cases. All patients were divided into 3 groups: study group (1) includes 20 patients diagnosed clinically non-allergic rhinitis suggestive to be vasomotor rhinitis. Study group (2) includes 20 patients diagnosed as allergic rhinitis. Study group (3) includes 20 patients performing surgery for non-vasomotor rhinitis non-allergic causes (as septoplasty or rhinoplasty).ResultsComparison between the pre- and post-SNOT questionnaire of symptoms among vasomotor group showed that there was a significant difference between the pre- and post-treatment SNOT questionnaire symptoms; nasal obstruction, runny nose, post-nasal drip, thick nasal discharge and Lack of good night sleep. Among allergic cases group, there was a significant difference between the pre- and post-treatment IHC (immunohistochemistry) findings considering Epithelium, Glands, arteries and veins. 20% of cases had grade 3 epithelium before treatment while after treatment, this was dropped to 0%. Comparison between the pre- and post-SNOT questionnaire of symptoms among allergic group showed that there was a significant difference between the pre- and post-treatment SNOT questionnaire symptoms; runny nose, post-nasal drip, and thick nasal discharge. Among non-vasomotor rhinitis non-allergic causes (as septoplasty or rhinoplasty) group, there was a significant difference between the pre- and post-treatment IHC findings considering epithelium, glands, and arteries; however, no significant difference between the pre- and post-IHC veins grade. Also, there was no significant difference between the pre- and post-treatment SNOT questionnaire symptoms.ConclusionTopical anticholinergics such as ipratropium bromide nasal spray are effective in treating rhinorrhea symptoms in allergic and non-allergic rhinitis. Further controlled studies with larger sample size and longer follow-up are needed to confirm our results and to identify risk factors of adverse events.

Drug Burden Index in Older Adults with Psychiatric Illnesses: A Cross-Sectional Study.

Medications with anticholinergic and/or sedative properties are commonly used in the management of psychiatric illnesses. The burden of anticholinergic and sedative medication use has been measured by the Drug Burden Index (DBI) score tool. A higher DBI score has been associated with increased risk of falls, bone and hip fractures, and functional and cognitive impairment, among other serious health outcomes, especially in older adults. We aimed to describe the drug burden in older adults with psychiatric illnesses using DBI, determine the factors that are associated with the drug burden measured by DBI, and examine the association between DBI score and Katz for activities of daily living (ADL) index. A cross-sectional study was conducted in the psychogeriatric division of an aged-care home. The study sample comprised all inpatients, aged ≥ 65 years, diagnosed with psychiatric illness. The data obtained included demographic characteristics, duration of hospital stay, primary psychiatric diagnosis and comorbidities, functional status using the Katz ADL index, and cognitive status using the Mini-Mental State Examination (MMSE) score. DBI score was calculated for each anticholinergic and sedative medication used. Of the 200 patients eligible for analysis, 106 (53.1%) were females and the mean age was 76 ± 9 years. The most commonly encountered chronic disorders were hypertension 102 (51%) and schizophrenia 94 (47%). The use of drugs with anticholinergic and/or sedative effects was seen in 163 (81.5%) patients; the mean DBI score was 1.25 ± 1. The results of the multinomial logistic regression showed that schizophrenia (odds ratio (OR) = 2.1 (95% confidence interval (CI) 1.57-4.45), p = 0.01), level of dependency (OR = 3.50 (95% CI 1.38-5.70), p = 0.001), and polypharmacy (OR = 2.99 (95% CI 2.15-4.29), p = 0.003) were significantly associated with DBI score ≥ 1 compared to DBI score 0. The study showed that anticholinergic and sedative medication exposure measured by DBI was associated with higher levels of dependency on the Katz ADL index in a sample of older adults with psychiatric illnesses from an aged-care home.