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.

Characterization and treatment of enuresis in overactive bladder patients. / Caracterización y tratamiento de la enuresis en pacientes con vejiga hiperactiva.

OBJECTIVE: To define the types of overactive bladder (OAB) patient enuresis and study daytime bladder treatment response. MATERIALS AND METHODS: A prospective, multi-center study of OAB patients with enuresis treated with anticholinergics or neuromodulation over 3 months from 2019 to 2021 was carried out. Variables achieved from the voiding calendar and PLUTSS (Pediatric Lower Urinary Tract Score System), as well as enuresis-related variables, were collected. Two study groups were created -primary enuresis (PE) and secondary enuresis (SE). Partial enuretic response (PER) was defined as a > 50% reduction in baseline enuresis, and complete enuretic response (CER) as a 100% reduction. A multivariate analysis was eventually conducted to detect CER independent predictive factors. RESULTS: 152 OAB patients were included. 109 of them (71.7%) had enuresis -29 (26.7%) SE and 80 (73.3%) PE. PLUTSS score was higher in PE patients than in SE patients (20.8 vs. 17.2; p= 0.001). PER and CER were significantly higher in the SE group (55.2% vs. 15%; p= 0.000 in PER, and 48.3% vs. 5%; p= 0.000 in CER). In the multivariate analysis, SE patients demonstrated to have a 50-fold increased probability of responding to daytime bladder treatment than PE patients (OR: 49.79; 95%CI: 6.73-36.8). CONCLUSIONS: Most OAB children have PE and not SE, which explains why enuresis does not typically respond to daytime bladder treatment. Characterizing the type of enuresis in OAB children is important to adequately approach treatment.

OBJETIVOS: Definir los tipos de enuresis de los pacientes con vejiga hiperactiva (VH) y estudiar su respuesta al tratamiento vesical diurno. MATERIAL Y METODOS: Estudio prospectivo y multicéntrico: pacientes con VH y enuresis, tratados con anticolinérgicos o neuromodulación durante 3 meses (2019-2021). Recogimos variables obtenidas del calendario miccional, cuestionario PLUTSS (Pediatric Lower Urinary Tract Score System), y relacionadas con la enuresis. Generamos 2 grupos de estudio: enuresis primaria (EP) y enuresis secundaria (ES). Consideramos respuesta parcial enurética (RPE) a la reducción del valor de enuresis inicial en más de un 50% y respuesta completa (RCE) el 100%. Finalmente realizamos un análisis multivariante para detectar factores predictivos independientes de RCE. RESULTADOS: Incluimos 152 pacientes con VH, 109 de los cuales presentaban enuresis (71,7%): 29 ES (26,7%) y 80 EP (73,3%). El valor PLUTSS fue mayor en pacientes con EP que en ES (20,8 vs. 17,2, p= 0,001.) La RPE y la RCE fueron significativamente mayores en el grupo de ES (55,2% vs. 15%, p= 0,000 en RPE y 48,3% vs. 5%, p= 0,000 en RCE). En el análisis multivariante se identificó que los pacientes con ES tienen una probabilidad de responder al tratamiento vesical diurno 50 veces superior que los pacientes con EP (OR 49,79, IC95% 6,73-36,8). CONCLUSIONES: La mayoría de niños con VH tienen una EP y no secundaria, por lo que generalmente la enuresis de estos pacientes no responde al tratamiento vesical diurno. Es importante caracterizar el tipo de enuresis de los niños con VH para plantear su tratamiento de forma adecuada.

[Polypharmacy in patients with dementia]. / Polypharmazie bei Demenzerkrankten.

The number of patients with dementia is expected to grow in the coming years due to an aging population and an increasing life-expectancy. At the same time, in an aging society there will be an increase in multimorbidity and therefore polypharmacy. This combination presents numerous challenges particularly for people with dementia, as the correct administration of the drugs can frequently no longer be guaranteed. The drug treatment of neuropsychiatric symptoms of dementia are often treated with antipsychotics with potentially severe side effects and with limited efficacy. Moreover, many drugs have an anticholinergic potential, which may worsen the cognitive function even further in patients with dementia. The use of anticholinergic drugs should be handled with care and when possible be avoided in patients with dementia.

Efficacy of sacral transcutaneous electrical nerve stimulation in patients with overactive bladder refractory to anticholinergic treatment: a prospective multi-center study. / Eficacia de la electroestimulación transcutánea sacra en pacientes con vejiga hiperactiva refractarios a fármacos anticolinérgicos. Estudio prospectivo y multicéntrico.

OBJECTIVE: To determine whether sacral transcutaneous electrical nerve stimulation (S-TENS) is an effective treatment in patients refractory to anticholinergic drugs (Achs). MATERIALS AND METHODS: A prospective multi-center study of patients with overactive bladder (OB) refractory to Achs treated with S-TENS from 2018 to 2021 was carried out. S-TENS was applied over 3 months. Symptom progression was assessed using the voiding calendar and the Pediatric Lower Urinary Tract Symptoms Score (PLUTSS), excluding questions 3 and 4 -referring to enuresis- so that progression of daytime symptoms only (LUTS variable) was analyzed. RESULTS: 66 patients -50% of whom were female- were included, with a mean age of 9.5 years (range: 5-15). S-TENS significantly lowered PLUTSS (19.1 baseline vs. 9.5 final, p< 0.001) and LUTS (13.1 baseline vs. 4.8 final, p< 0.001). It also reduced the number of mictions (8.5 baseline vs. 6.4 final, p< 0.001), while increasing urine volume in the voiding records (214 ml baseline vs. 258 ml final, p< 0.001). Enuresis was the only variable refractory to S-TENS. Complication rate was 3% (2 patients with dermatitis in the S-TENS application area). CONCLUSIONS: S-TENS is effective and safe in the short-term in patients with OB refractory to Achs. Further studies assessing long-term efficacy and potential relapses are required.

OBJETIVOS: Determinar si la electroterapia nerviosa transcutánea a nivel sacro (TENS-S) es un tratamiento efectivo en pacientes refractarios a fármacos anticolinérgicos (Ach). MATERIAL Y METODOS: Estudio prospectivo y multicéntrico: pacientes con VH refractaria a Ach tratados con TENS-S entre 2018-2021. El TENS-S se aplicó durante 3 meses. La evolución sintomática fue evaluada utilizando el calendario miccional y el cuestionario PLUTSS (Pediatric Lower Urinary Tract Symptoms Score), pero excluyendo sus preguntas 3 y 4 (referidas a la enuresis) para analizar solamente la evolución de la sintomatología diurna (variable LUTS). RESULTADOS: Fueron incluidos 66 pacientes (50% niñas), con una edad media de 9,5 años (rango: 5-15). El TENS-S disminuyó significativamente el PLUTSS (19,1 inicial vs 9,5 final, p< 0,001) y el LUTS (13,1 inicial vs 4,8 final, p< 0,001). Además, redujo el número de micciones (8,5 inicial vs 6,4 final, p< 0,001) y aumentó el volumen de orina en los registros miccionales (214 ml inicial vs 258 ml final, p< 0,001). La enuresis fue la única variable refractaria al TENS-S. La tasa de complicaciones fue del 3% (2 pacientes, dermatitis en el área de aplicación del TENS-S). CONCLUSIONES: El TENS-S es efectivo y seguro a corto plazo en pacientes con VH refractarios a los Ach. Deben realizarse estudios para evaluar la eficacia a largo plazo y posibles recaídas.

Comparative analysis of anticholinergic burden scales to explain iatrogenic cognitive impairment and self-reported side effects in the euthymic phase of bipolar disorders: Results from the FACE-BD cohort.

Bipolar disorders (BD) are characterized by cognitive impairment during the euthymic phase, to which treatments can contribute. The anticholinergic properties of medications, i.e., the ability of a treatment to inhibit cholinergic receptors, are associated with cognitive impairment in elderly patients and people with schizophrenia but this association has not been well characterized in individuals with remitted BD. Moreover, the validity of only one anticholinergic burden scale designed to assess the anticholinergic load of medications has been tested in BD. In a literature review, we identified 31 existing scales. We first measured the associations between 27 out of the 31 scales and objective cognitive impairment in bivariable regressions. We then adjusted the bivariable models with covariates: the scales significantly associated with cognitive impairment in bivariable and multiple logistic regressions were defined as having good concurrent validity to assess cognitive impairment. In a sample of 2,031 individuals with euthymic BD evaluated with a neuropsychological battery, two scales had good concurrent validity to assess cognitive impairment, whereas chlorpromazine equivalents, lorazepam equivalents, the number of antipsychotics, or the number of treatments had not. Finally, similar analyses with subjective anticholinergic side-effects as outcome variables reported 14 scales with good concurrent validity to assess self-reported peripheral anticholinergic side-effects and 13 to assess self-reported central anticholinergic side-effects. Thus, we identified valid scales to monitor the anticholinergic burden in BD, which may be useful in estimating iatrogenic cognitive impairment in studies investigating cognition in BD.

Development of the Swedish anticholinergic burden scale (Swe-ABS).

BACKGROUND: Drugs with anticholinergic properties are associated with cognitive adverse effects, especially in patients vulnerable to central muscarinic antagonism. A variety of drugs show weak, moderate or strong anticholinergic effects. Therefore, the cumulative anticholinergic burden should be considered in patients with cognitive impairment. This study aimed to develop a Swedish Anticholinergic Burden Scale (Swe-ABS) to be used in health care and research. METHODS: A systematic literature review was conducted in PubMed and Ovid Embase to identify previously published tools quantifying anticholinergic drug burden (i.e., exposure). Drugs and grading scores (0-3, no to high anticholinergic activity) were extracted from identified lists. Enteral and parenteral drugs authorized in Sweden were included. Drugs with conflicting scores in the existing lists were assessed by an expert group. Two drugs that were not previously assessed were also added to the evaluation process. RESULTS: The systematic literature search identified the following nine anticholinergic burden scales: Anticholinergic Activity Scale, Anticholinergic Burden Classification, updated Anticholinergic Cognitive Burden scale, Anticholinergic Drug Scale, Anticholinergic Load Scale, Anticholinergic Risk Scale, updated Clinician-rated Anticholinergic Scale, German Anticholinergic Burden Scale and Korean Anticholinergic Burden Scale. A list of drugs with significant anticholinergic effects provided by The Swedish National Board of Health and Welfare was included in the process. The suggested Swe-ABS consists of 104 drugs scored as having weak, moderate or strong anticholinergic effects. Two hundred and fifty-six drugs were listed as having no anticholinergic effects based on evaluation in previous scales. In total, 62 drugs were assessed by the expert group. CONCLUSIONS: Swe-ABS is a simplified method to quantify the anticholinergic burden and is easy to use in clinical practice. Publication of this scale might make clinicians more aware of drugs with anticholinergic properties and patients' total anticholinergic burden. Further research is needed to validate the Swe-ABS and evaluate anticholinergic exposure versus clinically significant outcomes.

[A multi-center observation of the therapeutic efficacy of Bencycloquidium bromide in the treatment of seasonal allergic rhinitis with predominant symptoms of rhinorrhea].

Objective:To observe the efficacy and safety of the M receptor antagonist Bencycloquidium bromide nasal spray in treatment of seasonal allergic rhinitis with runny nose as the main symptom. Methods:From August 2021 to September 2021, 134 patients with seasonal allergic rhinitis were enrolled in the otolaryngology Outpatient Department of Peking University Third Hospital, First Affiliated Hospital of Harbin Medical University and China-Japanese Friendship Hospital of Jilin University, including 71 males and 63 females, with a median age of 38 years. TNSS score and visual analogue scale（VAS） of total nasal symptoms were observed during 2 weeks of treatment with Bencycloquidium bromide nasal spray. Results:TNSS score decreased from （8.89±3.31） on day 0 to （3.71±2.51） on day 14（P<0.001）, VAS score of nasal symptoms decreased from （24.86±7.40） on day 0 to （6.84±5.94） on day 14（P<0.001）, VAS score of rhinorrhoea decreased from （6.88±2.06） on day 0 to （1.91±1.81） on day 14（P<0.001）. Rhinoconjunctivitis quality of life questionnaire（RQLQ） score decreased from （94.63±33.35） on day 0 to （44.95±32.28） on day 14（P<0.001）. The incidence of adverse reaction was low and no serious adverse events occurred during the whole experiment. Conclusion:Bencycloquidium bromide nasal spray has significant efficacy and good safety in the treatment of seasonal allergic rhinitis.

Drug burden index in people living with HIV over 50 years of age in a real clinical practice cohort.

OBJECTIVES: To determine DBI and its relationship with polypharmacy and pharmacotherapeutic complexity (PC) in a cohort of PLWH over 50 years of age at follow-up of pharmacotherapy in a tertiary hospital. METHODS: Observational and retrospective study that included PLWH in active antiretroviral treatment over 50 years of age who have been followed up in outpatient pharmacy services. Pharmacotherapeutic complexity was estimated through Medication Regimen Complexity Index (MRCI). Collected variables included comorbidities, current prescriptions and its classification according to anticholinergic and sedative activity and associated risk of falls. RESULTS: Studied population included 251 patients (85.7% men; median age: 58 years, interquartile range: 54-61). There was a high prevalence of high DBI scores (49.2%). High DBI was significantly correlated with a high PC, polypharmacy, psychiatric comorbidity and substances abuse (p<0.05). Among sedative drugs, the most prescribed were anxiolytic drugs (N05B) (n=85), antidepressant drugs (N06A) (n=41) and antiepileptic drugs (N03A) (n=29). For anticholinergic drugs, alpha-adrenergic antagonist drugs (G04C) were the most prescribed (n=18). Most frequent drugs associated with risk of falls were anxiolytics (N05B) (n=85), angiotensin-converting enzyme inhibitors (C09A) (n=61) and antidepressants (N06A) (n=41). CONCLUSION: The DBI score in older PLWH is high and it is related to PC, polypharmacy, mental diseases and substance abuse as is the prevalence of fall-related drugs. Control of these parameters as well as the reduction of the sedative and anticholinergic load should be included in the lines of work in the pharmaceutical care of people living with HIV+.

Efficacy of botulinum toxin-A injection versus oral anticholinergic medications following transurethral resection of the prostate to manage bladder outlet obstruction with overactive bladder: a prospective randomized clinical trial study.

BACKGROUND: To compare the effect of botulinum toxin-A (BoNT-A) injection versus oral anticholinergic agents following transurethral resection of the prostate (TURP) in patients with benign prostatic hyperplasia (BPH) and Overactive Bladder. MATERIALS AND METHODS: In this randomized clinical trial from February 2021 till May 2022 data of patients with obstructive urinary symptoms and urgency incontinence were analyzed. The intervention group consisted of 35 patients who were injected with 300 units of BoNT-A (Dysport®) into the detrusor muscles at the same time as TURP. 38 participants in the control group were treated with solifenacin 5 mg (Urinacin®) daily after TURP. RESULTS: In the evaluation of 73 included patients (mean age: 67.54±6.3), IPSS score change (first month, P=0.777; 6th month, P=0.761) and storage irritative symptoms change score (first month, P=0.995; 6th month, P=0.962) were decreased and Qmax was increased (first month, P=0.195; 6th month, P=0.174) similarly in 2 groups. Lower number of patients experienced urgency incontinence during follow up time in intervention group, significantly (first month, 18 versus 5, P=0.002; 6th month, 20 versus 6, P=0.002). PVR was also decreased more in first month and 6th month follow up in patients of intervention group (1th month, P=0.012; 6th month, P=0.033). CONCLUSION: Anticholinergic agents or intradetrusor BoNT-A injection would improve the storage symptoms in patients with BPH and detrusor overactivity following TURP. In contrast to IPSS score, storage irritative score and Qmax, which improve similarly in both groups, the PVR and urgency incontinence episodes will improve more in patients receive intradetrusor BoNT-A injection.

Health-related quality of life and use of medication with anticholinergic activity in patients with multiple myeloma.

PURPOSE: Verify the association between anticholinergic burden and health-related quality of life of patients with multiple myeloma. METHODS: Cross-sectional study with multiple myeloma outpatient from a state capital city in southeastern Brazil. Sociodemographic, clinical, and pharmacotherapeutic variables were collected by interview. Clinical data were complemented by medical records. Drugs with anticholinergic activity were identified with Brazilian Anticholinergic Activity Drug Scale. Health-related quality of life scores were obtained using QLQ-C30 and QLQ-MY20 instruments. Mann-Whitney was used to compare the median of the health-related quality of life scale scores and the independent variables. Multivariate linear regression was performed to verify the association between independent variables and health-related quality of life scores. RESULTS: Two hundred thirteen patients were included, 56.3% had multi-morbidities, and 71.8% used polypharmacy. In all health-related quality of life domains, there were differences between the medians of the polypharmacy variable. A significant difference was identified between the ACh burden and QLQ-C30 and QLQ-MY20 scores. Linear regression identified an association between the use of drugs with anticholinergic activity and the reduction of global status scores (QLQ-C30), functional scale (QLQ-C30), body image (QLQ-MY20), and future perspective (QLQ-MY20). Drugs with anticholinergic activity were associated with increased symptom scores (QLQ-C30 and QLQ-MY20). Polypharmacy was associated with reduction of functioning score and increase of symptom score (QLQ-C30). CONCLUSION: Anticholinergic burden in MM patients is associated with lower scores in quality of life domains: global health and symptoms (QLQ-C30) and functional (QLQ-C30 and QLQ-MY20). The presence of polypharmacy is also associated with lower scores for functional scales and symptom scales (QLQ-C30).

Cognitive effects of individual anticholinergic drugs: a systematic review and meta-analysis.

Anticholinergics (ACs) are among the most prescribed drugs. Investigating the impaired cognitive domains due to individual ACs usage is associated with controversial findings. Objective: The objective of this study was to investigate the effects of individual ACs on different aspects of cognitive function based on clinical trial studies. Methods: This systematic review was conducted following the PRISMA statement. A systematic search was performed in Embase, PubMed, Cochrane Library, Scopus, and Web of Science databases. Risk of bias (RoB) was assessed by the Joanna Briggs Institute checklists and the meta-analysis was performed using the CMA software. Results: Out of 3,026 results of searching, 138 studies were included. A total of 38 studies that assess the cognitive impacts of scopolamine were included in the meta-analysis. Included studies reported cognitive effects of scopolamine, mecamylamine, atropine, biperiden, oxybutynin, trihexyphenidyl, benzhexol, and dicyclomine; however, glycopyrrolate, trospium, tolterodine, darifenacin, fesoterodine, tiotropium, and ipratropium were not associated with cognitive decline. Based on the meta-analyses, scopolamine was associated with reduced recognition (SDM -1.84; 95%CI -2.48 to -1.21; p<0.01), immediate recall (SDM -1.82; 95%CI -2.35 to -1.30; p<0.01), matching to sample (SDM -1.76; 95%CI -2.57 to -0.96; p<0.01), delayed recall (SDM -1.54; 95%CI -1.97 to -1.10; p<0.01), complex memory tasks (SDM -1.31; 95%CI -1.78 to -0.84; p<0.01), free recall (SDM -1.18; 95%CI -1.63 to -0.73; p<0.01), cognitive function (SDM -0.95; 95%CI -1.46 to -0.44; p<0.01), attention (SDM -0.85; 95%CI -1.38 to -0.33; p<0.01), and digit span (SDM -0.65; 95%CI -1.21 to -0.10; p=0.02). There was a high RoB in our included study, especially in terms of dealing with possible cofounders. Conclusion: The limitations of this study suggest a need for more well-designed studies with a longer duration of follow-up on this topic to reach more reliable evidence.

Os anticolinérgicos (ACs) estão entre os medicamentos mais prescritos. Investigar os domínios cognitivos prejudicados devido ao uso individual de ACs está associado a achados controversos. Objetivo: Investigar os efeitos de ACs individuais em diferentes aspectos da função cognitiva, com base em estudos de ensaios clínicos. Métodos: Esta revisão sistemática foi realizada em acordo com a declaração PRISMA. Uma busca sistemática foi realizada nos bancos de dados Embase, PubMed, Cochrane Library, Scopus e Web of Science. O risco de viés (risk of bias - RoB) foi avaliado pelas listas de verificação do Joanna Briggs Institute e a meta-análise foi realizada através do software CMA. Resultados: Foram incluídos 138 estudos dos 3.026 resultados da pesquisa. Trinta e oito estudos que avaliam os impactos cognitivos da escopolamina foram incluídos na meta-análise. Os estudos incluídos relataram efeitos cognitivos de escopolamina, mecamilamina, atropina, biperideno, oxibutinina, triexifenidil, benzhexol, diciclomina; no entanto, glicopirrolato, tróspio, tolterodina, darifenacina, fesoterodina, tiotrópio e ipratrópio não foram associados ao declínio cognitivo. Com base nas meta-análises, a escopolamina foi associada a reconhecimento reduzido (DPM -1,84; IC95% -2,48 a -1,21; p<0,01), recordação imediata (DPM -1,82; IC95% -2,35 a -1,30; p<0,01), correspondência com a amostra (DPM -1,76; IC95% -2,57 a -0,96; p<0,01), recordação atrasada (DPM -1,54; IC95% -1,97 a -1,10; p <0,01), tarefas de memória complexas (DPM -1,31; IC95% -1,78 a -0,84; p<0,01), recordação livre (DPM -1,18; IC95% -1,63 a -0,73; p<0,01), função cognitiva (DPM -0,95; IC95% -1,46 a -0,44; p<0,01), atenção (DPM -0,85; IC95% -1,38 a -0,33; p<0,01) e amplitude de memória de dígitos (DPM -0,65; IC95% -1,21 a -0,10; p=0,02). Houve um alto RoB em nosso estudo, especialmente quanto aos possíveis confundidores. Conclusão: As limitações deste estudo sugerem a necessidade de estudos mais bem delineados e com maior duração de acompanhamento sobre o tema para alcançar evidências mais confiáveis.

Urinary retention and mydriasis secondary to topical glycopyrronium for axillary hyperhidrosis.

PURPOSE: Glycopyrronium, also known as glycopyrrolate, is an antimuscarinic competitive inhibitor of acetylcholine widely utilized topically for its anticholinergic properties in dermatology. A single topical glycopyrronium tosylate (GT) formulation is available on the market, and prescription of this medication has become increasingly popular among dermatologists. This medication has a relatively notable adverse effect profile and carries risks that patients need to be counseled on before initiation. SUMMARY: A 22-year-old female presented to our emergency department (ED) with a chief complaint of difficulty urinating for 48 hours and blurred vision for 2 weeks. Over the course of a week, she visited the ED once and urgent care multiple times due to complications associated with combination use of GT and cetirizine. Although these clinical effects were reversible, the patient impact in our case was profound given the time, cost, and invasive nature of these visits. CONCLUSION: The notable adverse effects of GT should be considered when prescribing this agent.

Cholinergic Antagonists and Behavioral Disturbances in Neurodegenerative Diseases.

Cholinergic antagonists interfere with synaptic transmission in the central nervous system and are involved in pathological processes in patients with neurocognitive disorders (NCD), such as behavioral and psychological symptoms of dementia (BPSD). In this commentary, we will briefly review the current knowledge on the impact of cholinergic burden on BPSD in persons with NCD, including the main pathophysiological mechanisms. Given the lack of clear consensus regarding symptomatic management of BPSD, special attention must be paid to this preventable, iatrogenic condition in patients with NCD, and de-prescription of cholinergic antagonists should be considered in patients with BPSD.

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

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

Frequency and Clinical Impact of Anticholinergic Burden in older patients: Comparing older patients with and without chronic kidney disease.

AIM: This study aimed to determine the frequency and impact of anticholinergic burden in older adults with chronic kidney disease (CKD) and compare the results to older adults without CKD. METHOD: Age- and sex-matched older adults (age ≥60) were selected from a total cohort of 1557 subjects, and grouped as CKD (n = 589) and Non-CKD (n = 589). Groups were compared for the frequency, type of anticholinergic agents, and their effects on comprehensive geriatric assessment parameters. The anticholinergic burden was assessed using the anticholinergic burden (ACB) scale. An ACB of ≥2 was categorized as high anticholinergic burden. RESULTS: The mean age of the partients was 81±6, and 66% were female. More patients in the CKD group experienced a high anticholinergic burden (45%, versus 38%, p = 0.015). Patients with CKD were more likely to receive beta blocker (25% versus 19%, p = 0.018), diuretic (19% versus 6%, p<0.001), while those who did not have CKD were more likely to be treated with dopaminergic agents (8% versus 12%, p = 0.039). A high anticholinergic burden was associated with sarcopenia (OR 1.62, 95% CI 1.10-2.38, p = 0.015), geriatric depression scale (OR 1.50, 95% CI 1.02-2.20, p = 0.037), and polypharmacy (OR 4.05, 95% CI 2.38-6.90, p<0.001), after adjustment for age, sex and comorbidities in the CKD group (p<0.05). CONCLUSION: Older patients with CKD are more likely to be exposed to drugs with anticholinergic effects, but have less clinical implications than those without CKD. A high anticholinergic burden is associated with polypharmacy, depression and sarcopenia in CKD.

Predicting delirium in older non-intensive care unit inpatients: development and validation of the DELIrium risK Tool (DELIKT).

BACKGROUND: Effective delirium prevention could benefit from automatic risk stratification of older inpatients using routinely collected clinical data. AIM: Primary aim was to develop and validate a delirium prediction model (DELIKT) suitable for implementation in hospitals. Secondary aim was to select an anticholinergic burden scale as a predictor. METHOD: We used one cohort for model development and another for validation with electronically available data collected within the first 24 h of admission. Included were patients aged ≥ 65, hospitalised ≥ 48 h with no stay > 24 h in an intensive care unit. Predictors, such as administrative and laboratory variables or an anticholinergic burden scale, were selected using a combination of feature selection filter method and forward/backward selection. The final model was based on logistic regression and the DELIKT was derived from the ß-coefficients. We report the following performance measures: area under the curve, sensitivity, specificity and odds ratio. RESULTS: Both cohorts were similar and included over 10,000 patients each (mean age 77.6 ± 7.6 years) with 11% experiencing delirium. The model included nine variables: age, medical department, dementia, hemi-/paraplegia, catheterisation, potassium, creatinine, polypharmacy and the anticholinergic burden measured with the Clinician-rated Anticholinergic Scale (CrAS). The external validation yielded an AUC of 0.795. With a cut-off at 20 points in the DELIKT, we received a sensitivity of 79.7%, specificity of 62.3% and an odds ratio of 5.9 (95% CI 5.2, 6.7). CONCLUSION: The DELIKT is a potentially automatic tool with predictors from standard care including the CrAS to identify patients at high risk for delirium.

A Universal Pharmacological-Based List of Drugs with Anticholinergic Activity.

Anticholinergic burden tools have relevant pharmacological gaps that may explain their limited predictive ability for clinical outcomes. The aim of this study was to provide a universal pharmacological-based list of drugs with their documented affinity for muscarinic receptors. A comprehensive literature review was performed to identify the anticholinergic burden tools. Drugs included in these instruments were searched in four pharmacological databases, and the investigation was supplemented with PubMed. The evidence regarding the potential antagonism of the five muscarinic receptors of each drug was assessed. The proportion of drugs included in the tools with an affinity for muscarinic receptors was evaluated. A universal list of drugs with anticholinergic activity was developed based on their documented affinity for the different subtypes of muscarinic receptors and their ability to cross the blood-brain barrier. A total of 23 tools were identified, including 304 different drugs. Only 48.68%, 47.70%, 48.03%, 43.75%, and 42.76% of the drugs had an affinity to the M1, M2, M3, M4, and M5 receptor, respectively, reported in any pharmacological database. The proportion of drugs with confirmed antagonism varied among the tools (36.8% to 100%). A universal pharmacological-based list of 133 drugs is presented. It should be further validated in different clinical settings.

A Retrospective Study of Anticholinergic Use and Later Mobilization as Risk Factors for Urinary Retention After Major Lower Extremity Joint Arthroplasty.

BACKGROUND: Postoperative urinary retention (POUR) is a common surgical complication of major joint arthroplasty and is associated with increased lengths of stay and urinary tract infections. Studies have found that certain anticholinergic medications and reduced mobility are associated with POUR. This study assessed the effect of anticholinergic burden and later postoperative ambulation on POUR. METHODS: In this retrospective cohort study, we included subjects who had undergone elective primary or revision hip or knee arthroplasty (total hip arthroplasty [THA] or total knee arthroplasty [TKA]) between March 2015 and December 2017 in a single health system. Anticholinergic burden was measured using the Anticholinergic Drug Scale (ADS). We performed bivariate and multivariable logistic regression with POUR as the dependent variable. Of the 1,397 study subjects, 622 (45%) underwent THA and 775 (55%) underwent TKA. Their mean age was 65 years (range, 21 to 98), and 841 (60%) were women. POUR developed in 183 (13%) subjects. RESULTS: In multivariable analyses, ADS was associated with POUR after THA (P < .05), but not TKA (P = .08), while later ambulation was not associated with POUR after either procedure (P > .3 for both). CONCLUSION: Anticholinergic burden after THA was independently associated with POUR. Strategies to reduce anticholinergic burden may help reduce POUR after THA.

Assessment and comparison of anticholinergic exposure in older adults at a Basic Health Unit in Porto Alegre / Avaliação e comparação da exposição anticolinérgica em idosos de uma Unidade Básica de Saúde de Porto Alegre

Objectives: To estimate the anticholinergic burden in geriatric patients using two scales and to assess the degree of agreement between them. Methods: Data from an observational study conducted in a primary health care service were used. Anticholinergic burden was assessed using the Belgian Scale Muscarinic Acetylcholinergic Receptor ANTagonist Exposure Scale and the Brazilian Scale of Medicines with Anticholinergic Activity. The cumulative anticholinergic burden score was classified using a categorical approach: Brazilian scale (0: none; 1 ­ 2: low; ≥ 3: high) and Belgian scale (0: none; 0.5 ­ 1.5: low; ≥ 2: high). The degree of agreement between the two instruments was obtained through Cohen's kappa coefficient. Results: A total of 374 older people were included, most of them female and aged between 60 and 69 years. At least one potentially inappropriate drug with anticholinergic activity was used by 60.70% of patients according to the Brazilian scale and 32.89% by the Belgian scale. On average, 20.85% were under high anticholinergic exposure. Overall, on both scales, the most commonly recurrent medications were those indicated for the treatment of psychiatric disorders. Agreement between the scales was moderate (Kappa = 0.43). Conclusions: A high percentage of older adults was exposed to drugs with an anticholinergic burden, posing risks to health and quality of life. Consensus is needed on how anticholinergic burden is calculated by these scores, as well as standardization of the list of included drugs.

Objetivos: Estimar a carga anticolinérgica em idosos com base em duas escalas e avaliar o grau de concordância entre estas. Metodologia: Foram utilizados dados de um estudo observacional realizado em um serviço de atenção primária. A carga anticolinérgica foi avaliada pela escala belga Muscarinic Acetylcholinergic Receptor ANTagonist Exposure Scale e da Escala Brasileira de Medicamentos com Atividade Anticolinérgica. A pontuação da carga anticolinérgica cumulativa foi classificada utilizando uma abordagem categórica: escala brasileira (0: nenhuma, 1 ­ 2: baixa, ≥ 3: alta) e escala belga (0: nenhuma, 0,5 ­ 1,5: baixa, ≥ 2: alta). O grau de concordância entre as duas ferramentas foi obtido por meio do coeficiente Capa de Cohen. Resultados: Foram incluídos 374 idosos, a maioria do sexo feminino e com idade entre 60 a 69 anos. O uso de pelo menos um medicamento potencialmente inapropriado com atividade anticolinérgica foi verificado em 60,70% dos idosos com a aplicação da escala brasileira e em 32,89% com a escala belga. Em média, 20.85% estavam sob alta exposição anticolinérgica. De modo geral, os medicamentos mais recorrentes, para ambas as escalas, foram os indicados para o tratamento de transtornos psiquiátricos. A concordância entre as escalas foi moderada (Capa = 0,43). Conclusão: Um percentual elevado de idosos estava exposto a medicamentos com carga anticolinérgica, representando riscos para a saúde e a qualidade de vida. É necessário um consenso sobre como calcular a carga anticolinérgica nos diferentes escores, bem como a padronização da lista de medicamentos incluídos.

Relationship between anticholinergic load and self-perceived health in a population aged 44 years or older / Relação entre carga anticolinérgica e autopercepção de saúde em população com mais de 44 anos

OBJECTIVE: To investigate the relationship between anticholinergic load (ACL) and self-perceived general health in adults in a medium-sized municipality in southern Brazil. METHODS: This cross-sectional study was based on 2015 data from a medium-sized municipality in southern Brazil. All respondents aged 44 years or older who reported using drugs in the 2 weeks before the interview were included (n = 662). The Anticholinergic Drug Scale was used to measure the ACL. Self-perceived health was categorized as positive self-perception (PSP) or negative self-perception (NSP). Crude and adjusted Poisson regression analyses were conducted to investigate the association between ACL and self-perceived health. RESULTS: NSP was found in 50.91% of 662 respondents. Significant ACL, older age, lower economic status, lower education, polypharmacy, and depression correlated with a higher frequency of NSP. Individuals with significant ACL had a prevalence of NSP of 1.27 (95% confidence interval: 1.02 ­ 1.58), and each additional ACL level represented a 6.10% higher chance of worse self-perceived health, regardless of confounding factors. CONCLUSIONS: An association was found between significant ACL and NSP, with an effect dependent on ACL level

OBJETIVO: Investigar a relação entre carga anticolinérgica (CAC) e autopercepção de saúde em adultos de um município de médio porte do sul do Brasil. METODOLOGIA: Trata-se de um estudo transversal com dados de 2015, realizado em um município de médio porte do sul do Brasil. Todos os entrevistados com 44 anos ou mais que relataram uso de drogas nas duas semanas anteriores à entrevista foram incluídos (n = 662). A Anticholinergic Drug Scale (ADS) foi utilizada para medir a CAC. A autopercepção da saúde foi categorizada em autopercepção positiva (APP) ou autopercepção negativa (APN). Análises de regressão de Poisson bruta e ajustada foram realizadas para investigar a associação entre CAC e autopercepção de saúde. RESULTADOS: Entre os 662 participantes, a CAC foi encontrada em 50,91% dos respondentes. CAC significativa, idade avançada, situação econômica mais baixa, menor escolaridade, polifarmácia e depressão foram correlacionados com maior frequência de APN. Indivíduos com CAC significativo apresentaram prevalência de APN de 1,27 (intervalo de confiança de 95%: 1,02 ­ 1,58), e cada nível adicional de CAC representou uma chance 6,10% maior de pior autopercepção de saúde, independentemente de fatores de confusão. CONCLUSÕES: Encontrou-se associação entre ACL significativo e APN, com efeito dependente do valor do CAC