Urodynamic and Frequency-Volume Chart Parameters Influencing Anticholinergic Resistance in Patients With Neurogenic Detrusor Overactivity.

PURPOSE: Neurogenic detrusor overactivity (NDOA) is characterized by involuntary detrusor muscle contractions during bladder filling in patients with neurological disorders. Anticholinergic therapy is the primary treatment; however, the reasons for treatment resistance in NDOA are not well understood. This study aimed to identify predictors of treatment failure by comparing urodynamic and frequency-volume chart data between patients with NDOA who respond and patients who do not respond to anticholinergic therapy. METHODS: We reviewed the records of 362 patients presenting with lower urinary tract symptoms and selected 85 who had NDOA and were on anticholinergic therapy. Ultimately, 67 patients were analyzed. We categorized these individuals into responders (group R) and nonresponders (group NR) based on clinical and urodynamic improvements. Three-day frequencyvolume charts and urodynamic study results were retrospectively reviewed. RESULTS: Of the 85 initial patients, 12 refused medication, and 6 were lost to follow-up. Pre- to posttreatment changes differed significantly between groups in the number of urgency urinary incontinence (UUI) episodes per 24 hours (P=0.001), maximum cystometric capacity (mL, P=0.003), NDOA frequency (P=0.004), and bladder compliance (mL/cm H2O, P=0.003). Multivariate analysis revealed that NDOA frequency (P=0.014) and UUI episodes per 24 hours (P=0.002) were significant factors associated with treatment failure. CONCLUSION: NDOA varies according to underlying neurological conditions. The frequencies of UUI episodes and NDOA in urodynamic studies can predict resistance to initial anticholinergic treatment.

The usage of anticholinergic medications in a low- and middle-income country: a longitudinal comparison of 2013-15 and 2020-22 datasets.

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.

Efficacy and safety evaluation of imidafenacin administered twice daily for continency recovery following radical prostatectomy in prostate cancer patients: Prospective open-label case-controlled randomized trial.

PURPOSE: This study aims to prospectively analyze the effects of anticholinergic therapy using imidafenacin on detrusor overactivity occurring after robot-assisted radical prostatectomy (RARP). MATERIALS AND METHODS: Patients were followed-up at outpatient visits 2-4 weeks post-surgery (visit 2) to confirm the presence of urinary incontinence. Those confirmed with urinary incontinence were randomly assigned in a 1:1 ratio to the anticholinergic medication group (imidafenacin 0.1 mg twice daily) or the control group. Patients were followed-up at 1, 3, and 6 months post-surgery for observational assessments, including the International Prostate Symptom Score (IPSS) and Overactive Bladder Symptom Score (OABSS). RESULTS: A total of 49 patients (25 in the treatment group and 24 in the control group) were randomized for the study. There were no differences observed between the groups in terms of age, comorbidities, prostate size, or pathological staging. According to the IPSS questionnaire results, there was no statistically significant difference between the medication and control groups (p=0.161). However, when comparing storage and voiding symptoms separately, there was a statistically significant improvement in storage symptom scores (p=0.012). OABSS also revealed statistically significant improvement in symptoms from 3 months post-surgery (p=0.005), which persisted until 6 months post-surgery (IPSS storage: p=0.023, OABSS: p=0.013). CONCLUSIONS: In the case of urinary incontinence that occurs after RARP, even if the function of the intrinsic sphincter is sufficiently preserved, if urinary incontinence persists due to changes in the bladder, pharmacological therapy using imidafenacin can be beneficial in managing urinary incontinence.

Clinical features and management approaches for Urinary Incontinence in Older Adults: Evidence from Three Hospitals in Qatar.

Background: Urinary incontinence (UI) is a common medical problem that seriously affects patients' physical, psychological, social, and financial well-being. To identify the most effective drug management techniques, this retrospective study aimed to describe the demographics, etiology, and medical traits of people with UI. Methods: This retrospective study was conducted at Rumailah Hospital, Ambulatory Care Centre, and Hamad General Hospital to investigate UI risk factors, causes, and management practices in people aged ≥ 65 years within the Hamad Medical Corporation (HMC) in Qatar. Results: The 272 patients enrolled in the study had a marked male preponderance, and a larger percentage of non-Qatari residents than Qataris residents. Solifenacin (24.9%), Tolterodine (4.1%), and Oxybutynin (1.1%) were the most commonly administered anticholinergic drugs, while Tamsulosin (82.9%), Alfuzosin (14.5%), and Doxazosin (1.7%) were the most frequently prescribed alpha-blockers. Conclusion: This study underscores the importance of investigating UI in institutionalized older adult populations considering the limited research available in Qatar. The identified preventable risk factors can be proactively addressed to mitigate UI. This study also highlights the need for thorough documentation of the diagnosis and reasons for improving the standards of patient care. The findings of this study provide important information that can be used to design medication management methods for enhancing patient outcomes.

Risk of falls or fall-related injuries associated with potentially inappropriate medication use among older adults with dementia.

BACKGROUND: Potentially inappropriate medications (PIMs) are prevalent in older adults with dementia and subsequent falls or fall-related injuries. The present study determined the risk of falls or fall-related injuries associated with PIM use in older adults with dementia. METHODS: The National Health Insurance Service-Elderly Cohort Database 2.0 (NHIS-ECDB 2.0) was used for this self-controlled case series (SCCS) study. This study included 1430 participants who went through exposure and non-exposure periods of PIM application among patients with dementia and experienced outcome events of falls or fall-related injuries between January 2016 and December 2019. The incidence of falls or fall-related injuries during the exposure and post-exposure periods was compared with that during the non-exposure period. Beers Criteria were used to define PIMs in patients with dementia. Negative binomial regression was conducted. The incidence rate ratio (IRR) was used to determine the risk of falls or fall-related injuries. RESULTS: During the exposure periods in which falls or fall-related injuries occurred, the mean number of PIMs among patients with dementia was 3.76 (SD = 2.99), and the most commonly used PIMs among patients with dementia were first-generation antihistamines (n = 283; 59.1%). Compared to the non-exposure period, the adjusted IRR during the exposure period was 1.57 (95% CI = 1.39-1.76). The risk of falls or fall-related injuries was increased when PIM use in patients with dementia was initiated (1-14 days: IRR = 2.76, 95% CI = 2.31-3.28; 15-28 days: IRR = 1.95, 95% CI = 1.48-2.56; ≥ 29 days: IRR = 1.17, 95% CI = 1.01-1.35). Especially, an increased risk of falls or fall-related injuries was associated with greater PIM use among patients with dementia. CONCLUSION: Among older adults with dementia, PIMs significantly increase the risk of falls and fall-related injuries. Therefore, strategies should be developed to manage PIM prescriptions in patients with dementia to prevent falls.

Application of nano- and micro-particle-based approaches for selected bronchodilators in management of asthma.

Asthma is a chronic inflammatory condition that affects the airways, posing a substantial health threat to a large number of people worldwide. Bronchodilators effectively alleviate symptoms of airway obstruction by inducing relaxation of the smooth muscles in the airways, thereby reducing breathlessness and enhancing overall quality of life. The drug targeting to lungs poses significant challenges; however, this issue can be resolved by employing nano- and micro-particles drug delivery systems. This review provides brief insights about underlying mechanisms of asthma, including the role of several inflammatory mediators that contribute to the development and progression of this disease. This article provides an overview of the physicochemical features, pharmacokinetics, and mechanism of action of particular groups of bronchodilators, including sympathomimetics, PDE-4 inhibitors (phosphodiesterase-4 inhibitors), methylxanthines, and anticholinergics. This study presents a detailed summary of the most recent developments in incorporation of bronchodilators in nano- and micro-particle-based delivery systems which include solid lipid nanoparticles, bilosomes, novasomes, liposomes, polymeric nano- and micro-particles. Specifically, it focuses on breakthroughs in the categories of sympathomimetics, methylxanthines, PDE-4 inhibitors, and anticholinergics. These medications have the ability to specifically target alveolar macrophages, leading to a higher concentration of pharmaceuticals in the lung tissues.

Effects of neuromuscular block reversal with neostigmine/glycopyrrolate versus sugammadex on bowel motility recovery after laparoscopic colorectal surgery: A randomized controlled trial.

STUDY OBJECTIVE: To compare the effects of neostigmine/glycopyrrolate (a traditional agent) and sugammadex on bowel motility recovery and the occurrence of digestive system complications after colorectal surgery. DESIGN: Prospective, randomized controlled trial. SETTING: A single tertiary center. PATIENTS: 111 patients undergoing laparoscopic colorectal surgery. INTERVENTIONS: Patients were randomized into two groups based on the block reversal agent: 1) a mixture of 50 µg.kg-1 of neostigmine and 10 µg.kg-1 of glycopyrrolate (neostigmine group) and 2) 2 mg.kg-1 of sugammadex (sugammadex group). MEASUREMENTS: The primary outcome was the time from the surgery's completion to the first flatus. The time to the first postoperative defecation, incidences of postoperative nausea or vomiting, ileus, and dry mouth, as well as postoperative length of stay, were also assessed. MAIN RESULTS: The time to the first flatus was significantly shorter in the sugammadex group than in the neostigmine group (59 [42-79] h vs 69 [53-90] h, P = 0.027). The time to the first defecation and the incidences of postoperative nausea or vomiting and ileus did not differ between the groups, nor did the postoperative length of stay. However, the incidence of postoperative dry mouth was significantly lower in the sugammadex group than in the neostigmine group (7 patients [13%] vs 39 patients [71%], P < 0.001). CONCLUSIONS: The time to the first flatus was shorter using 2 mg.kg-1 sugammadex to reverse the neuromuscular block for laparoscopic colorectal surgery compared to reversal with conventional neostigmine/glycopyrrolate.

NAD+ and Niacin Supplementation as Possible Treatments for Glaucoma and Age-Related Macular Degeneration: A Narrative Review.

Glaucoma and age-related macular degeneration (AMD) are progressive retinal diseases characterized by increased oxidative stress, inflammation, and mitochondrial dysfunction. This review investigates the potential therapeutic benefits of NAD+ and niacin supplementation in managing glaucoma and AMD. A literature search was conducted encompassing keywords such as "niacin", "NAD", "glaucoma", "AMD", and "therapeutics". NAD+ depletion is associated with increased oxidative stress and mitochondrial dysfunction in glaucoma and AMD. Niacin, a precursor to NAD+, has shown promise in replenishing NAD+ levels, improving choroidal blood flow, and reducing oxidative damage. Animal studies in glaucoma models indicate that nicotinamide (NAM) supplementation preserves RGC density and function. Large-scale population-based studies indicate an inverse correlation between niacin intake and glaucoma prevalence, suggesting a preventative role. Randomized controlled trials assessing niacin supplementation showed significant improvements in visual field sensitivity and inner retinal function, with a dose-dependent relationship. In AMD, nicotinamide supplementation may improve rod cell function and protect against oxidative stress-induced damage. Cross-sectional studies reveal that individuals with AMD have a lower dietary intake of niacin. Further studies suggest niacin's role in improving choroidal blood flow and dilating retinal arterioles, potentially mitigating ischemic damage and oxidative stress in AMD. Beyond current management strategies, NAD+ and niacin supplementation may offer novel therapeutic avenues for glaucoma and AMD. Further research is warranted to elucidate their efficacy and safety in clinical settings.

Anticholinergic burden and health-related quality of life among adult patients in a resource-limited setting: a cross-sectional study.

BACKGROUND: Anticholinergic medications are now widely acknowledged for their unfavorable risk-to-benefit profile owing to their adverse effects. Health-related quality of life (HRQoL) is commonly regarded as a crucial person-centered outcome. AIM: This study aimed to investigate the association between anticholinergic burden and HRQoL in hospitalized and ambulatory patients seen in Ethiopia. METHOD: This cross-sectional study utilized a questionnaire and medical records to collect data from a convenience sample of adult patients attending both inpatient wards and ambulatory clinic of University of Gondar Comprehensive Specialized Hospital between April and September 2022. Anticholinergic burden was measured by anticholinergic cognitive burdens scale (ACBS), while HRQoL was measured using EQ5D-index (Euroqol-5 dimensions-5-Levels index) and EQ5D-VAS (visual analogue scale). Linear regression was used to assess the influence of high anticholinergic burden (ACBS score ≥ 3) on EQ5D-index and EQ5D-VAS, with adjustments made for sociodemographic and clinical confounders. RESULTS: A total of 828 patients participated in this study (median (IQR) age was 45.0 (30, 60) and 55.9% were female). On multiple linear regression analysis, high anticholinergic burden was associated with a statistically significant decline in HRQoL, as evidenced by reductions in both EQ5D index (- 0.174 (- 0.250, - 0.098)) and EQ5D-VAS scores (- 9.4 (- 13.3, - 5.2)). CONCLUSION: A significant association between high anticholinergic burden and diminished HRQoL was found among a relatively younger cohort in a resource-limited setting, even after adjustment for important confounding variables. Clinicians should be cognizant of the cumulative impact of anticholinergic burden on HRQoL outcomes and strive to minimize anticholinergic burden.

High Anticholinergic Burden and Dental Caries: Findings from Northern Finland Birth Cohort 1966.

INTRODUCTION: Anticholinergic drugs propose a threat for oral health by causing dry mouth. The aim of this cross-sectional study was to investigate whether a high anticholinergic burden was associated with the presence of initial caries lesions, manifested caries lesions, dental fillings, or tooth loss among 46-y-old people. METHODS: The study population consisted of 1,906 participants from the Northern Finland Birth Cohort 1966 who underwent an oral health examination in 2012-2013. Socioeconomic and medical data were collected from questionnaires, medical records, and national registers. Nine previously published anticholinergic scales were combined and used to measure the high anticholinergic burden from the participants' medication data. Cariological status was determined according to the International Caries Detection and Assessment System, and the number of missing teeth (excluding third molars) was used as an indicator for tooth loss. The decayed, missing, and filled surfaces index was used to depict caries experience. Negative binominal regression models were used to estimate prevalence rate ratios (PRRs) and confidence intervals (CIs). RESULTS: Fourteen percent of the participants (n = 276) used at least 1 anticholinergic drug and about 3% had a high anticholinergic burden (n = 61). After adjusting for confounding factors, participants with a high anticholinergic burden had a higher likelihood of having manifested carious lesions needing restorative treatment (PRR, 1.60; CI, 1.11-2.29) and more missing teeth (PRR, 1.59; CI, 1.13-2.24) when compared to participants without any or with a lower anticholinergic burden. CONCLUSIONS: High anticholinergic burden was associated with a present caries experience and with tooth loss among the general middle-aged population. KNOWLEDGE TRANSFER STATEMENT: The findings of this study suggest that middle-aged patients with a high anticholinergic burden may have a heightened risk of dental caries. These patients may benefit from targeted caries preventive regimes.

Urotherapy and biofeedback resistant dysfunctional voiding: How to deal with?

OBJECTIVES: To analyze the management strategies in the children who had treatment-resistant dysfunctional voiding (DV). METHODS: Among 75 children with DV who underwent pelvic floor biofeedback therapy (BF) between 2013 and 2020, 16 patients (14 girls, 87.5%) with a mean age of 9.81 ± 2.53 years that showed incomplete clinical response following urotherapy and initial BF sessions were retrospectively reviewed. The demographic and clinical characteristics, DVSS, and uroflowmetry parameters were recorded before and after the initial BF sessions. Subsequent treatments after initial BF and clinical responses of patients were noted. RESULTS: Clinical success was observed in one patient by addition of an anticholinergic and in three patients with combination of salvage BF sessions and anticholinergics, whom had predominant overactive bladder (OAB) symptoms. The success rate of TENS alone and in combination with other treatment modalities was 88.8% (8/9 patients). In addition, salvage BF sessions (range 2 to 3) enabled clinical success in five (50%) of 10 cases as a combination with anticholinergics or TENS. In case of incomplete emptying without OAB, adequate clinical response to Botulinum-A was observed during an average follow-up of 29 months in two boys who did not respond to alpha-blockers, even though one required repeat injection after 10 months. The total clinical success rate was 87.5% (14/16 patients) after a median follow-up of 24 months. VV-EBC and Qmax increased by a mean of 30.89% and 7.13 mL/min, respectively, whereas DVSS decreased by a mean of 8.88 points and PVR-EBC decreased by a median of 19.04%. CONCLUSIONS: Our findings showed that clinical success in resistant DV was achieved by various combination treatments in the majority of children. However, a small group may still have persistent, bothersome symptoms despite multiple treatment modalities.

Efficacy of Oral Trihexyphenidyl Plus Clonazepam Versus Trihexyphenidyl for the Treatment of Dystonia in Children With Dystonic Cerebral Palsy: An Open-Label Randomized Controlled Trial.

BACKGROUND: Trihexyphenidyl and clonazepam are commonly used to treat dystonia in children with cerebral palsy (CP). However, there is a notable gap in the literature when it comes to studies that combine these first-line agents for the management of dystonia. METHODS: This open-label, randomized controlled trial aimed to compare the efficacy of adding oral clonazepam to trihexyphenidyl (THP + CLZ) versus using trihexyphenidyl alone (THP) in reducing the severity of dystonia, as measured by the Barry-Albright Dystonia (BAD) score. The study was conducted over a 12-week therapy period in children with dystonic CP aged two to 14 years. RESULTS: Each group enrolled 51 participants. The THP + CLZ group showed significantly better improvement in dystonia severity at 12 weeks compared with the THP group alone (-4.5 ± 2.9 vs -3.4 ± 1.7, P = 0.02). Furthermore, the THP + CLZ group exhibited superior improvement in the severity of choreoathetosis, upper limb function, pain perception by the child, and quality of life, with P values of 0.02, 0.009, 0.01, and 0.01, respectively. The number of participants experiencing treatment-emergent adverse events was comparable in both groups (P = 0.67). Importantly, none of the participants in any of the groups reported any serious adverse events. CONCLUSION: A combination of oral THP + CLZ proves to be more efficacious than using THP alone for the treatment of dystonic CP in children aged two to 14 years in terms of reducing the severity of dystonia.

Use of Bladder-Related Medication in Non-Muscle Invasive Bladder Cancer Patients.

Repeated transurethral bladder resections (TURBs) and instillation treatments in non-muscle invasive bladder cancer (NMIBC) might influence bladder function and, therefore, quality of life. Bladder-related medication is a surrogate marker of compromised bladder function. The objective was to investigate whether TURBs and adjuvant instillation therapy are associated with the use of anticholinergics, ß3-agonists, and cystitis-relevant antibiotics. We divided all Danish patients diagnosed with primary NMIBC during 2002-2017 registered in the Danish National Patient Registry (DNPR) based on TURB-load within the first five years from diagnosis (1 TURB, 2-4 TURBs, ≥5 TURBs). Instillation therapy with either mitomycin C (MMC) or bacillus Calmette-Guerin vaccine (BCG) was independent exposure (yes or no). We included 17,774 patients; 76% men, median age: 70 years (IQR: 63, 77). Patients exposed to ≥5 TURBs had a higher risk of using bladder-relaxing medication than patients exposed to 1 TURB, HR = 4.01 [3.33; 4.83], and higher risk of cystitis, HR = 2.27 [2.05; 2.51]. BCG-exposed patients had a higher risk of bladder-relaxing medication use compared to non-exposed, HR = 1.92 [1.69; 2.18], and a higher risk of cystitis, HR = 1.39 [1.31; 1.48]. Repeated TURBs have the highest impact on bladder function. Adjuvant instillation therapy is also associated with the use of bladder-related medication.

A comparison of changes in drug burden index between older inpatients who fell and people who have not fallen: A case-control study.

OBJECTIVE: Older inpatients who fall are often frail, with multiple co-morbidities and polypharmacy. Although the causes of falls are multifactorial, sedating and delirium-inducing drugs increase that risk. The aims were to determine whether people who fell had a change in their sedative and anticholinergic medication burden during an admission compared to people who did not fall. A secondary aim was to determine the factors associated with change in drug burden. METHODS: A retrospective, observational, case-control study of inpatients who fell. Two hundred consecutive people who fell were compared with 200 randomly selected people who had not fallen. Demographics, functional ability, frailty and cognition were recorded. For each patient, their total medications and anticholinergic and sedative burden were calculated on admission and on discharge, using the drug burden index (DBI). RESULTS: People who fell were more dependent and cognitively impaired than people who did not fallen. People who fell had a higher DBI on admission, than people who had not fall (mean: .69 vs .43, respectively, p < .001) and discharge (.66 vs .38, p < .001). For both cohorts, the DBI decreased between admission and discharge (-.03 and -.05), but neither were clinically significant. Higher total medications and a higher number DBI medications on admission were both associated with greater DBI changes (p = .003 and <.001, respectively). However, the presence (or absence) of cognitive impairment, dependency, frailty and single vs multiple falls were not significantly associated with DBI changes. CONCLUSIONS: In older people, DBI medications and falls are both common and have serious consequences, yet this study was unable to demonstrate any clinically relevant reduction in average DBI either in people who fell or people who had not fallen during a hospital admission.

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.

Efficacy and Safety of Vibegron for Persistent Symptoms of Overactive Bladder in Men Being Pharmacologically Treated for Benign Prostatic Hyperplasia: Results From the Phase 3 Randomized Controlled COURAGE Trial.

PURPOSE: The efficacy and safety of vibegron, a ß3-adrenergic receptor agonist, was assessed among men with symptoms of overactive bladder (OAB) receiving pharmacologic treatment for benign prostatic hyperplasia (BPH) in a phase 3 randomized controlled trial. MATERIALS AND METHODS: Men ≥ 45 years with OAB symptoms and BPH, treated with α-blocker with/without 5α-reductase inhibitors, were randomized 1:1 to vibegron or placebo for 24 weeks. Coprimary end points were change from baseline at week 12 in mean daily micturitions and urgency episodes. Secondary end points were change from baseline at week 12 in mean nightly nocturia and daily urge urinary incontinence episodes, International Prostate Symptom Score‒storage score, and volume voided per micturition. Safety was evaluated via adverse events (AEs). RESULTS: Of 1105 participants randomized, 965 (87.3%) completed the trial. At week 12, vibegron was associated with significant reductions vs placebo in daily micturitions (least squares mean difference [95% CI], -0.74 [-1.02, -0.46]; P < .0001) and urgency episodes (-0.95 [-1.37, -0.54]; P < .0001). Vibegron was also associated with significant improvements vs placebo at week 12 in nocturia episodes (least squares mean difference, -0.22 [-0.36, -0.09]; P = .002), urge urinary incontinence episodes (-0.80 [-1.33, -0.27]; P = .003), International Prostate Symptom Score‒storage scores (-0.9 [-1.2, -0.6]; P < .0001), and volume voided (15.07 mL [9.13-21.02]; P < .0001). AE rates were similar in vibegron (45.0%) and placebo (39.0%) arms; AEs occurring in ≥ 2% of participants were hypertension (9.0% vs 8.3%), COVID-19 (4.0% vs 3.1%), UTI (2.5% vs 2.2%), and hematuria (2.0% vs 2.5%). CONCLUSIONS: In this trial, vibegron met all primary and secondary end points and was safe and well tolerated in men with OAB symptoms and pharmacologically treated BPH.

A Mediation Analysis Examining High Risk, Anticholinergic Medication Use, Delirium, and Dementia After Major Surgery.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Treatment modalities for paediatric functional daytime lower urinary tract disorders: an updated review.

Paediatric functional bladder disorders especially those causing daytime symptoms are a common cause of significant psychosocial and/or physical morbidity and impaired quality of life. Despite the availability of many therapeutic modalities, a significant number of children appear to be refractory to treatment and continue to have symptoms. In this review, we aim to evaluate the current evidence in the use of existing and novel therapeutic options for the management of daytime lower urinary tract disorders in children. We also aim to highlight the controversies around the terminology and diagnosis of paediatric lower urinary tract dysfunction (LUTD) and specific conditions. The article will then provide a reasonable critique of the existing and emerging treatment modalities in functional daytime LUTD in children including their mode of action, efficacy, indications, and recent advances. These include standard urotherapy, specific urotherapy comprised of biofeedback, alarm therapy and electrical neural stimulation and pharmacotherapy involving selective and non-selective anticholinergics, ß3 adrenergic agonists, alpha blockers and botulinum toxin. A better understanding of this common clinical problem may help clinicians achieve better profiling of these children's diagnoses to further enable specific, targeted treatment.

A review article about new treatment options for otherwise healthy children with long-term urinary symptoms occurring during the daytime Management of paediatric functional daytime LUT disorders is complex and may benefit from a combination of treatment modalities. Urotherapy and anticholinergics appear to be effective in the majority however, non-responders warrant careful re-evaluation to characterize the specific type of LUTD to target appropriate treatment. Various novel therapies and adjuncts have been shown effective and range from smartphone apps, bladder alarms, neuromodulation systems and more effective drug delivery systems. Despite being effective, non-selective antimuscarinics are less favoured for long-term use in children due to the side-effect profile. Therefore, more selective anticholinergics, ß3 agonists and combination treatment options are being evaluated to improve compliance while maintaining/enhancing treatment efficacy. Use of alpha blockers and intravesical injection of botulinum toxin have shown promising results especially in refractory cases.

Fragility of overactive bladder medication clinical trials: A systematic review.

PURPOSE: Overactive bladder (OAB) syndrome significantly impairs quality of life, often necessitating pharmacological interventions with associated risks. The fragility of OAB trial outcomes, as measured by the fragility index (FI: smallest number of event changes to reverse statistical significance) and quotient (FQ: FI divided by total sample size expressed as a percentage), is critical yet unstudied. MATERIALS AND METHODS: We conducted a systematic search for randomized controlled trials on OAB medications published between January 2000 and August 2023. Inclusion criteria were trials with two parallel arms reporting binary outcomes related to OAB medications. We extracted trial details, outcomes, and statistical tests employed. We calculated FI and FQ, analyzing associations with trial characteristics through linear regression. RESULTS: We included 57 trials with a median sample size of 211 participants and a 12% median lost to follow-up. Most studies investigated anticholinergics (37/57, 65%). The median FI/FQ was 5/3.5%. Larger trials were less fragile (median FI 8; FQ 1.0%) compared to medium (FI: 4; FQ 2.5%) and small trials (FI: 4; FQ 8.3%). Double-blinded studies exhibited higher FQs (median 2.9%) than unblinded trials (6.7%). Primary and secondary outcomes had higher FIs (median 5 and 6, respectively) than adverse events (FI: 4). Each increase in 10 participants was associated with a +0.19 increase in FI (p < 0.001). CONCLUSIONS: A change in outcome for a median of five participants, or 3.5% of the total sample size, could reverse the direction of statistical significance in OAB trials. Studies with larger sample sizes and efficacy outcomes from blinded trials were less fragile.

Medicines Regimens Charted for Older People Living in Residential Aged Care: A Repeated Cross-Sectional Study Describing the Number of Medicines, Regimen Complexity, High-Risk Prescribing, and Potential Underprescribing.

OBJECTIVE: We aimed to explore medicines regimens charted for older people living in residential aged care facilities (RACFs). DESIGN: Repeated cross-sectional study using routinely collected data sampled in a cross-sectional manner at 11 time points (day of admission, then at 1, 3, 7, 14, and 30 days, and 3, 6, 12, 18, and 24 months post admission). SETTING AND PARTICIPANTS: The cohort is set in 34 RACFs managed by a single Australasian provider. People aged ≥65 years admitted to permanent care between January 1, 2017, and October 1, 2021, with medicines charted on the date of admission. METHODS: Medicines charted were evaluated for potentially suboptimal prescribing including number of medicines, high-risk prescribing (eg, potentially inappropriate medicines, anticholinergic burden), and potential underprescribing. RESULTS: The 3802 residents in the final cohort had a mean age of 84.9 ± 7.2 years at admission. At least 1 example of suboptimal prescribing was identified in 3479 (92%) residents at admission increasing to 1410 (97%) at 24 months. The number of medicines charted for each resident increased over time from 6.0 ± 3.8 regular and 2.8 ± 2.7 as required medicines at admission to 8.9 ± 4.1 regular and 8.1 ± 3.7 as required medicines at 24 months. Anticholinergic drug burden increased from 1.6 ± 2.4 at admission to 3.0 ± 2.8 at 24 months. Half the residents (2173; 57%) used at least 1 potentially inappropriate medicine at admission, which rose to nearly three-quarters (1060; 73%) at 24 months admission. CONCLUSION AND IMPLICATIONS: The total number of medicines charted for older adults living in RACFs increases with length of stay, with charted as required medicines nearly tripling. Effective interventions to optimize medicines use in this vulnerable population are required.