Dream of the Endless: Updates in Agents for Procedural Sedation.

Procedural sedation and analgesia is an essential activity in the emergency department for managing pain and anxiety during a variety of medical procedures. Various pharmacotherapy options, including opioid analgesics, antiemetics, anticholinergics, sedatives, and ketamine have been utilized, all with their unique efficacy and safety profiles. This review highlights the challenges associated with using certain agents and discusses emerging trends such as the use of newer synthetic opioids and the expanding use of dexmedetomidine. Overall, the selection of the optimal agents for procedural sedation and analgesia should be guided based on the unique characteristics of each agent tailored to the needs of the specific procedure, along with consideration for individual patient characteristics.

Differences of anticholinergic drug burden between older hospitalized patients with and without delirium: a systematic review and meta-analysis based on prospective cohort studies.

OBJECTIVES: This review aims to comprehensively summarize the differences in anticholinergic drug burden (ADB) scores between older hospitalized patients with and without delirium. METHODS: We searched PubMed, Embase, Web of Science, Cochrane Library and CINAHL EBSCOhost databases to identify prospective cohort studies exploring the relationship between ADB and the occurrence of delirium in older hospitalized patients. The primary outcome of the review was the mean ADB scores for the delirium and non-delirium groups, and the secondary outcome was the scores for the subsyndromal and non-delirium groups. The standardized mean difference (SMD) and corresponding 95% confidence intervals (95% CI) were incorporated using a fixed-effect method. Moreover, we performed subgroup analysis according to the admission type, age, the ADB scale type and the ADB classification. RESULTS: Nine prospective cohort studies involving 3791 older patients with a median age of 75.1 (71.6-83.9) were included. The ADB score was significantly higher in the delirium group than in the non-delirium group (SMD = 0.21, 95%CI 0.13-0.28). In subgroup analysis, the age subgroup was split into < 75 and ≥ 75 according to the median age of the older people. There were significant differences in ADB scores between older people with delirium and those without delirium in various subgroups: surgical (SMD = 0.20, 95%CI 0.12-0.28), internal medicine (SMD = 0.64, 95%CI 0.25-1.02), age < 75 (SMD = 0.17, 95%CI 0.08-0.26), age ≥ 75 (SMD = 0.27, 95%CI 0.15-0.39), ADS scale (SMD = 0.13, 95%CI 0.13-0.40), ARS scale (SMD = 0.15, 95%CI 0.03-0.26), ACB scale (SMD = 0.13, 95%CI 0.01-0.25), pre-admission ADB (SMD = 0.24, 95%CI 0.05-0.43) and ADB during hospitalization (SMD = 0.20, 95%CI 0.12-0.27). CONCLUSIONS: We found a quantitative relationship between ADB and delirium in older patients admitted for internal medicine and surgery. And this relationship remained significant in different age, ADB scale type and ADB classification subgroups. However, the actual difference in ADB scores between patients with delirium and without delirium was small. More high-quality observational studies should be conducted to explore the impact of ADB on delirium and subsyndromal delirium. CLINICAL TRIAL REGISTRATION: The protocol was published in the International Prospective Register of Systematic Reviews (PROSPERO) [Ref: CRD42022353649].

Medication burden and anticholinergic use are associated with overt HE in individuals with cirrhosis.

BACKGROUND: Polypharmacy and anticholinergic medications are associated with cognitive decline in elderly populations. Although several medications have been associated with HE, associations between medication burden, anticholinergics, and HE have not been explored. We examined medication burden and anticholinergics in patients with cirrhosis and their associations with HE-related hospitalization. METHODS: We conducted a retrospective cohort study of patients aged 18-80 with cirrhosis seen in hepatology clinics during 2019. The number of chronic medications (medication burden) and anticholinergic use were recorded. The primary outcome was HE-related hospitalization. RESULTS: A total of 1039 patients were followed for a median of 840 days. Thirty-seven percent had a history of HE, and 9.8% had an HE-related hospitalization during follow-up. The mean number of chronic medications was 6.1 ± 4.3. Increasing medication burden was associated with HE-related hospitalizations in univariable (HR: 1.09, 95% CI: 1.05-1.12) and multivariable (HR: 1.07, 95% CI: 1.03-1.11) models. This relationship was maintained in those with baseline HE but not in those without baseline HE. Twenty-one percent were taking an anticholinergic medication. Anticholinergic exposure was associated with increased HE-related hospitalizations in both univariable (HR: 1.68, 95% CI: 1.09-2.57) and multivariable (HR: 1.71, 95% CI: 1.11-2.63) models. This relationship was maintained in those with baseline HE but not in those without baseline HE. CONCLUSIONS: Anticholinergic use and medication burden are both associated with HE-related hospitalizations, particularly in those with a history of HE. Special considerations to limit anticholinergics and minimize overall medication burden should be tested for potential benefit in this population.

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.

The impact of pharmacotherapy on sexual function in female patients being treated for idiopathic overactive bladder: a systematic review.

BACKGROUND: Overactive bladder (OAB) is a condition defined by urgency with or without incontinence which disproportionately affects female patients and has a negative impact on sexual enjoyment and avoidance behaviour. Pharmacotherapy can be considered one of the main options for treating OAB. This research set out to determine the impact of pharmacotherapy on sexual function in females with OAB. METHODS: This research used the robust methodology of a systematic review. The clinical question was formulated using the PICO (population, intervention, control, and outcomes) format to include females being treated with pharmacotherapy (anticholinergics or beta-3 adrenergic agonists) for idiopathic OAB with the use of a validated questionnaire assessing self-reported sexual function at baseline and post-treatment. The review incorporated the MEDLINE, PubMed and EMBASE databases. The AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews) appraisal tool was used to guide the review process. Two reviewers worked independently in screening abstracts, deciding on the inclusion of full-texts, data extraction and risk of bias assessment. RESULTS: In female patients with OAB, pharmacotherapy does seem to offer at least partial improvement in self-reported sexual function outcomes after 12 weeks of therapy. Still, the value of this finding is limited by an overall poor quality of evidence. Patients with a higher degree of bother at baseline stand to benefit the most from treatment when an improvement within this health-related quality of life domain is sought. CONCLUSION: This research should form the basis for a well-conducted randomized controlled study to accurately assess sexual function improvements in females being treated with pharmacotherapy for OAB.

[New clinical guidelines for COPD - a paradigm shift: A review].

Chronic obstructive pulmonary disease is now one of the most common noncommunicable diseases and the main causes of morbidity, disability and mortality in the world. In recent years, new approaches to epidemiology, diagnosis, classification (categorization), evaluation of phenotypes, as well as characterization and assessment of the severity of сhronic obstructive pulmonary disease exacerbations have emerged. Modern approaches to starting and subsequent drug therapy have changed significantly. This is largely due to the results of recently conducted major clinical trials, demonstrated high efficacy of triple fixed combinations, including inhaled glucocorticosteroids, long-acting beta-agonists and long-acting anticholinergic drugs. The use of non-medication methods (smoking cessation, physical activity and respiratory rehabilitation) and modern approaches to the treatment of respiratory failure and antibiotic therapy remain important. In terms of their significance, all these updates have a significant impact on real clinical practice and can be considered as a novel paradigm of the approaches to the diagnosis and management of this disease.

Critical reappraisal of short-acting bronchodilators for pediatric respiratory diseases.

Short-acting bronchodilators are a class of medications commonly used to treat asthma, chronic obstructive pulmonary disease, and other respiratory conditions. The use of these medications has evolved over time as we have gained a better understanding of their effectiveness and safety in the pediatric population. This comprehensive review synthesizes the current understanding of short-acting ß2-agonists and short-acting anticholinergics in children. It addresses indications, contraindications, safety considerations, and highlights areas where further research is needed to guide the most effective use of short-acting bronchodilators.

Treatment of Anticholinergic Delirium with Oral Rivastigmine: A Case Report.

BACKGROUND: Anticholinergic toxicity is commonly encountered in the emergency department. However, the availability of physostigmine, a central acetylcholinesterase inhibitor used to reverse anticholinergic delirium, has been significantly limited due to national drug shortages in the United States. Several articles have explored the viability of rivastigmine as an alternative treatment in these patients. CASE REPORT: A 33-year-old man presented to the emergency department after a suspected suicide attempt. The patient was found with an empty bottle of diphenhydramine at the scene. On arrival, he was tachycardic and delirious, with dilated and nonreactive pupils and dry skin. As the clinical picture was highly suggestive of anticholinergic toxicity, the patient was treated with oral rivastigmine at a starting dose of 4.5 mg to reverse his anticholinergic delirium. Although a repeat dose was required, his delirium resolved without recurrence. Why Should an Emergency Physician Be Aware of This? Oral rivastigmine has been applied successfully here and in other case reports to reverse anticholinergic delirium with the benefit of prolonged agitation control. Emergency physicians may consider this medication in consultation with a specialist, with initial doses starting at 4.5-6 mg, if encountering anticholinergic delirium when physostigmine is not available.

Exploring the impact of anticholinergic burden on urinary independence: insights from a post-stroke cohort of older adults.

BACKGROUND: Anticholinergic burden is associated with adverse events in the older adults. However, there is a lack of evidence regarding its effect on urinary independence in stroke patients. AIM: This study examined the association between increased anticholinergic burden during hospitalization and urinary independence in post-stroke patients undergoing rehabilitation. METHOD: This observational cross-sectional study included stroke patients admitted to a post-acute rehabilitation hospital between 2020 and 2022 who were not independently urinating. The degree of urinary independence was assessed using the Functional Independence Measure-Bladder (FIM-Bladder), a subscale of the motor domain of the FIM, and urinary independence was defined as FIM-Bladder ≥ 6. Anticholinergic burden was assessed using the anticholinergic risk scale (ARS), and changes in ARS during hospitalization were calculated by subtracting the value at admission from the value at discharge. The study outcome was urinary independence at discharge. Logistic regression analysis was used to examine whether change in ARS score was independently associated with the outcome. Statistical significance was set at P < 0.05. RESULTS: Of the 573 patients enrolled, 312 patients (mean age 77.5 years, 51.9% male) were included in the analysis. ARS increased during hospitalization in 57 patients (18.3%). Change in ARS score was independently associated with urinary independence (odds ratio: 0.432, 95% confidence interval: 0.247-0.756, P = 0.003). CONCLUSION: Increased anticholinergic burden in post-stroke patients who require assistance with urination is significantly associated with less independent urination. Anticholinergic agents may need to be introduced cautiously in patients who require assistance with urination.

A Comparison of U.S. Individual and Family Plan Medication Coverage for Overactive Bladder.

IMPORTANCE: There is strong evidence for long-term cognitive effects with anticholinergic use. Differences in insurance coverage of anticholinergics and beta-3 agonists hinder individualization of overactive bladder (OAB) treatment. OBJECTIVES: The aims of the study were to assess individual and family health insurance plan coverage for select OAB medications and to compare coverage of preferred medications to those with a greater risk of cognitive dysfunction. STUDY DESIGN: This cross-sectional study analyzed formularies for the top 7 U.S. medical insurers. Coverage tiers were assessed for the following 7 OAB medications: (1) oxybutynin instant-release 5 mg, (2) oxybutynin extended-release 5 mg, (3) solifenacin 5 mg, (4) trospium instant-release 20 mg, (5) trospium extended-release 60 mg, (6) mirabegron 25 mg, and (7) vibegron 75 mg. Coverage was compared between nonpreferred (oxybutynin, solifenacin) and preferred medications (trospium, mirabegron, vibegron). Coverage scores, representing a weighted average based on coverage tier frequency relative to the number of plans investigated for each state or insurer, were generated with a lower coverage score indicating better coverage (range, 0.2-1.0). RESULTS: A total of 2,780 insurance plans from 41 states representing a 47% market share for the individual and family marketplace were evaluated. Oxybutynin IR had the best coverage score across insurers (0.2) while vibegron had the worst (0.92). Preferred medications were more often designated to higher tiers with worse coverage compared with nonpreferred medications (P < 0.001). Less concordance in coverage between insurers was noted for anticholinergics with greater bladder specificity and for extended-release formulations. CONCLUSIONS: Despite risks with anticholinergics, beta-3 agonists were more expensive across all insurers highlighting the need for expanded coverage of preferred medications to avoid cognitive dysfunction when undergoing treatment for OAB.

Rivastigmine for the management of anticholinergic delirium.

INTRODUCTION: Anticholinergic agents are commonly taken in overdose, often causing delirium. The spectrum of anticholinergic delirium ranges from mild agitation to severe behavioural disturbance. Physostigmine is an effective treatment for anticholinergic delirium, but its availability is limited. As rivastigmine is readily available, it has been used to manage anticholinergic delirium; however, there is limited research investigating its use. METHOD: This was a retrospective review of patients with anticholinergic delirium treated in two toxicology units with rivastigmine (oral capsule or transdermal patch) from January 2019 to June 2023. The primary outcome was the use of further parenteral treatment (sedation or physostigmine) for delirium post rivastigmine administration. RESULTS: Fifty patients were administered rivastigmine for the management of anticholinergic delirium. The median age was 36 years (interquartile range: 25-49 years) and 27 (54 per cent) were females. Features consistent with anticholinergic toxicity included tachycardia in 44 (88 per cent) and urinary retention requiring catheterisation in 40 (80 per cent). Forty-three patients (86 per cent) were treated with physostigmine before rivastigmine administration. Twenty-two were managed with transdermal rivastigmine (most commonly 9.5 mg/24 hour patch), and 28 with oral rivastigmine 6 mg. Further parenteral sedation and/or physostigmine treatment were required more often in patients given transdermal than oral rivastigmine [16/22 (73 per cent) versus 9/28 (32 per cent), P = 0.010)]. No patients had bradycardia or gastrointestinal symptoms following rivastigmine administration. One patient with a history of epilepsy had a seizure, 1.5 hours post physostigmine administration and 7 hours post transdermal rivastigmine. DISCUSSION: Rivastigmine has been increasingly used for the management of patients with anticholinergic delirium, due to the lack of availability of physostigmine. In this case series, rivastigmine transdermal patch appeared to be less effective than oral rivastigmine capsules, likely due to its slow onset of action and/or insufficient dose. CONCLUSION: Rivastigmine can be used to treat anticholinergic delirium. In our case series oral rivastigmine appeared more effective than transdermal rivastigmine.

Risks of Dementia After Treatment with an Anticholinergic, Beta-3 Agonist, or Combination of Both for an Overactive Bladder: A Korean National Cohort Study.

BACKGROUND AND OBJECTIVE: An overactive bladder (OAB) is primarily managed with behavioural therapy and using anticholinergics and beta-3 agonists. Reports have shown that the use of anticholinergics by OAB patients was associated with an increased risk of new-onset dementia compared with those using beta-3 agonists. This study compares the risks of dementia among patients with an OAB starting on a beta-3 agonist alone, an anticholinergic alone, or a combination treatment. METHODS: Using data from the Korean National Health Insurance Service database, we studied a nationwide population cohort comprising patients newly diagnosed with an OAB who initiated their OAB medications between 2015 and 2020. The treatment types were categorised as anticholinergics (oxybutynin, solifenacin, tolterodine, trospium, fesoterodine, flavoxate, and propiverine) alone, a beta-3 agonist (mirabegron) alone, and combination therapy (an anticholinergic plus the beta-3 agonist). To evaluate the impact of cumulative drug exposure, we quantified the cumulative exposure to solifenacin and mirabegron as cumulative defined daily doses (cDDDs) using proportional hazards regression analyses, adjusted for factors known to be associated with dementia. KEY FINDINGS AND LIMITATIONS: Among the study's 3 452 705 patients, 671 974 were new users of a beta-3 agonist alone (19.5%), 1 943 414 new users of anticholinergics alone (56.3%), and 837 317 receiving combination therapy (24.3%). The most common anticholinergic used both alone and as part of a combination treatment was solifenacin (42.9% and 56.3%, respectively). There was an increased risk of dementia between the users of an anticholinergic alone (adjusted hazard ratio [aHR] = 1.213; 95% confidence interval [CI], 1.195-1.232) and those taking a combination treatment (aHR = 1.345; 95% CI, 1.323-1.366) compared with the users of beta-3 agonists alone after the adjustment of covariates. However, the incidence of dementia was also significantly higher, with an increase in the cumulative dose of mirabegron (aHR = 1.062 [1.021-1.106] for 28-120 cDDDs and aHR = 1.044 [1.004-1.084)] for patients who received >121 cDDDs compared with those who received <27 cDDDs). A marked increased risk of dementia was associated with the use of solifenacin, tolterodine, fesoterodine, and propiverine, both separately and in combination with mirabegron. CONCLUSIONS AND CLINICAL IMPLICATIONS: In this large Korean cohort, the use of anticholinergics with or without a beta-3 agonist increased the risk of new-onset dementia compared with the use of a beta-3 agonist alone. Given that the risk of dementia was most significantly elevated with combination treatments, care should be taken when considering combination treatment for OAB patients with risk factors for dementia. Furthermore, there could be a possible association between beta-3 agonists and dementia, although future studies are needed. PATIENT SUMMARY: This study investigated the risk of dementia induced by overactive bladder (OAB) treatment in a large Korean cohort. Two representative OAB treatment drugs, anticholinergics and beta-3 agonists, both increased the risk of new-onset dementia. Clinicians should be cautious in using OAB treatment drugs since no drugs could be concluded as safe.

Urological Outcomes in Post-Pubertal Patients With Myelomeningocele: A Single-Center Retrospective Study.

BACKGROUND: Recent decades have seen changes in the urological treatment of myelomeningocele (MMC). We aimed to evaluate the urological outcomes in post-pubertal patients and to clarify associations with walking status, hydrocephalus, and sex. METHODS: A retrospective study of 103 MMC patients at their final pediatric urological control. Urological procedures, the necessity for Clean Intermittent Catheterization (CIC) and anticholinergic medication, the state of continence, renal ultrasound findings, and serum creatinine values were assessed. RESULTS: The median age of the patients was 18 years (IQR 16.7-19.6), with 51 (49.5%) being female. Renal function was preserved in all but of one, who presented with mild hydronephrosis. 38 patients walked without assistance, 46 used wheelchairs. Most patients (93%) utilized CIC, and 83% had interventions for overactive or poorly compliant bladder, including anticholinergic medication (47%), Botox treatments (35%), or bladder augmentation (36%). Nearly half (45%) had undergone bladder neck procedures. Continence status revealed 55% fully continent, 18% were rarely incontinent, and 26% were incontinent daily, with most episodes limited to droplet leakage. Incontinence was not associated with the ambulatory status, hydrocephalus, or sex (p = 0.08, >0.99, and 0.07 respectively). CONCLUSIONS: Renal function was effectively maintained with our treatment strategy; however, daily incontinence episodes occurred in one out of four patients, with an additional 18% experiencing occasional rare incontinence episodes. Incontinence, when present, was mostly mild. We found no association between patient characteristics, treatment approach, and continence. Emphasizing incontinence treatment becomes a mainstay in future studies. LEVEL OF EVIDENCE: IV.

Reducing the drug burden of sedative and anticholinergic medications in older adults: a scoping review of explicit decision criteria.

OBJECTIVES: To describe the extent, characteristics, and knowledge gaps regarding explicit decision criteria for deprescribing drugs with anticholinergic or sedative properties (Ach/Sed) in older adults. DESIGN: Scoping review. SETTING AND PARTICIPANTS: Original studies, clinical trial protocols, grey literature, and Summaries of Product Characteristics. METHODS: Searches targeting explicit decision criteria for deprescribing Ach/Sed were performed across MEDLINE, EMBASE, CINAHL, and Web of Science, including trial registries (clinicaltrials.gov, ICTRP, EU-CTR, ANZCTR) for pertinent articles, study protocols. Additionally, to encompass non-traditional or 'grey literature' sources, Google searches and relevant agency websites were explored, alongside the summary of product characteristics for Ach/Sed. RESULTS: The initial literature search identified 8,192 unique data sources. After review, 188 original articles or books, 79 internet sources, and 127 SmPCs were included. Examining these sources for explicit criteria for 154 Ach/Sed, overall, 1,271 explicit criteria guidance for identifying clinical scenarios warranting deprescription of Ach/Sed across 145/154 Ach/Sed were identified. These criteria were identified mainly from qualitative research and Summaries of Product Characteristics. Additionally, 455 criteria-based recommendations suggesting approaches for tapering implementation across 76/154 Ach/Sed were identified, mostly from sources classified as expert opinions. Significant heterogeneity was found across the approaches for tapering Ach/Sed. CONCLUSIONS: This scoping review provides a comprehensive overview of the literature providing guidance for clinical scenarios where Ach/Sed should be deprescribed and highlights the existing knowledge gaps regarding comprehensive guidance on tapering these drugs which warranties future research and development.

Addressing Comorbidities in People with Parkinson's Disease: Considerations From An Expert Panel.

In the UK, guidance exists to aid clinicians and patients deciding when treatment for Parkinson's disease (PD) should be initiated and which therapies to consider. National Institute for Health and Care Excellence (NICE) guidance recommends that before starting PD treatment clinicians should discuss the following: the patient's individual clinical circumstances; lifestyle; preferences; needs and goals; as well as the potential benefits and harms of the different drug classes. Individualization of medicines and management in PD significantly improves patients' outcomes and quality of life. This article aims to provide simple and practical guidance to help clinicians address common, but often overlooked, co-morbidities. A multi-disciplinary group of PD experts discussed areas where clinical care can be improved by addressing commonly found co-morbidities in people with Parkinson's (PwP) based on clinical experience and existing literature, in a roundtable meeting organized and funded by Bial Pharma UK Ltd. The experts identified four core areas (bone health, cardiovascular risk, anticholinergic burden, and sleep quality) that, if further standardized may improve treatment outcomes for PwP patients. Focusing on anticholinergic burden, cardiac risk, sleep, and bone health could offer a significant contribution to personalizing regimes for PwP and improving overall patient outcomes. Within this opinion-based paper, the experts offer a list of guiding factors to help practitioners in the management of PwP.

Who Progresses to Third-Line Therapies for Overactive Bladder? Trends From the AQUA Registry.

INTRODUCTION: Overactive bladder (OAB) patients who do not achieve satisfactory results with second-line OAB medications should be offered third-line therapies (percutaneous tibial nerve stimulation, sacral neuromodulation, onabotulinumtoxinA bladder injection [BTX-A]). We aimed to determine which clinical factors affect progression from second- to third-line OAB therapy. METHODS: Between 2014 and 2020, the AUA Quality Registry was queried for adult patients with idiopathic OAB. For the primary outcome, patient and provider factors associated with increased odds of progression from second- to third-line therapy were assessed. Secondary outcomes included median time for progression to third-line therapy and third-line therapy utilization across subgroups. RESULTS: A total of 641,122 patients met inclusion criteria and were included in analysis. Of these, only 7487 (1.2%) received third-line therapy after receiving second-line therapy. On multivariate analysis, patients aged 65 to 79, women, White race, history of dual anticholinergic and ß3 agonist therapy, metropolitan area, government insurance, and single specialty practice had the greatest odds of progressing to third-line therapy. Black and Asian race, male gender, and rural setting had lower odds of progressing to third-line therapy. BTX-A was the most common therapy overall (40% BTX-A, 32% sacral neuromodulation, 28% percutaneous tibial nerve stimulation). The median time of progression from second- to third-line therapy was 15.4 months (IQR 5.9, 32.4). Patients < 50 years old and women progressed fastest to third-line therapy. CONCLUSIONS: Very few patients received third-line therapies, and the time to progression from second- to third-line therapies is > 1 year. The study findings highlight a potential need to improve third-line therapy implementation.

Prevalence and Appropriateness of Polypharmacy in Older Adults with Inflammatory Bowel Diseases.

BACKGROUND: Despite the growing prevalence of older adults with inflammatory bowel diseases (IBD), polypharmacy, an important geriatric construct, is poorly understood. We described polypharmacy and its implications in older adults with IBD. METHODS: In a cross sectional study of adults ≥ 60 years with IBD, we obtained medication lists from the medical record and patients. We assessed medications by the Beer's criteria, anti-cholinergic burden and drug-drug interactions. We constructed multi-variate logistic regression models to assess association between polypharmacy with low quality-of-life, controlling for age, sex, IBD-type, number of comorbidities and depression. RESULTS: In 100 adults ≥ 60 years with IBD, with a median age of 68 years, 56% met criteria for remission by a validated disease activity index. Polypharmacy, defined as ≥ 5 concomitant medications, was noted in 86% of the cohort and 45% had severe polypharmacy, defined as ≥ 10 concomitant medications. In this cohort, 48% were on ≥ 1 medication that met Beer's criteria for potentially inappropriate in older adults and 24% had a cumulative anti-cholinergic drug burden score of ≥ 3, the threshold for serious adverse events attributed to anti-cholinergic burden. Serious drug-drug interactions were found in 26% with 7% involving an IBD medication. Controlling for potential confounders, polypharmacy, defined both numerically (OR 22.79, p < 0.01) and by medication appropriateness (OR 1.95, p < 0.01), was significantly associated with low quality of life. CONCLUSION: Polypharmacy is prevalent in older adults with IBD and independently associated with low quality of life. Describing polypharmacy can guide de-prescription strategies tailored to GI clinic for older adults with IBD.

The Drug Burden Index and Level of Frailty as Determinants of Healthcare Costs in a Cohort of Older Frail Adults in New Zealand.

OBJECTIVES: Frailty is common in older people and is associated with increased use of healthcare services and ongoing use of multiple medications. This study provides insights into the healthcare cost structure of a frail group of older adults in Aotearoa, New Zealand. Furthermore, we investigated the relationship between participants' anticholinergic and sedative medication burden and their total healthcare costs to explore the viability of deprescribing interventions within this cohort. METHODS: Healthcare cost analysis was conducted using data collected during a randomized controlled trial within a frail, older cohort. The collected information included participant demographics, medications used, frailty, cost of service use of aged residential care and outpatient hospital services, hospital admissions, and dispensed medications. RESULTS: Data from 338 study participants recruited between 25 September 2018 and 30 October 2020 with a mean age of 80 years were analyzed. The total cost of healthcare per participant ranged from New Zealand $15 (US dollar $10) to New Zealand $270 681 (US dollar $175 943) over 6 months postrecruitment into the study. Four individuals accounted for 26% of this cohort's total healthcare cost. We found frailty to be associated with increased healthcare costs, whereas the drug burden was only associated with increased pharmaceutical costs, not overall healthcare costs. CONCLUSIONS: With no relationship found between a patient's anticholinergic and sedative medication burden and their total healthcare costs, more research is required to understand how and where to unlock healthcare cost savings within frail, older populations.

Topical Anticholinergics in the Management of Focal Hyperhidrosis in Adults and Children. A Narrative Review. / Anticolinérgicos tópicos en el manejo de la hiperhidrosis focal en adultos y niños. Una revisión narrativa.

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

An Improved Statistical Modeling Approach to Individual Anticholinergic Drug Use Trend Analysis.

Anticholinergic (AC) drugs are commonly prescribed to older adults for treating diseases and chronic conditions, such as chronic obstructive pulmonary disease, urinary incontinence, gastrointestinal disorder, or simply pain and allergy. The high prevalence of AC drug use can have a detrimental effect on the mental health of older adults. We aim to improve the prediction of future trends of AC drug use at the individual level, with pharmacy refill data. The individual drug use data presents challenges in the modeling, such as data being discrete-valued with excess zeros and having significant unobserved heterogeneity in the trend pattern. To address these challenges, we propose a statistical model of hierarchical structure and an EM scheme for the model parameter estimation. We evaluate the proposed modeling approach through a numerical study with synthetic data and a case study with real-world pharmacy refill data. The simulation study show that our analysis method outperforms the existing ones (e.g., reducing MSE significantly), particularly in terms of accurately predicting the trend pattern. The real-world case study further verifies the out-performance and demonstrate the advantageous features of our method. We expect the prediction tool developed based on our study can assist pharmacists' decision on initiating or strengthening behavioral interventions with the hope of discontinuing AC drug misuse.