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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.
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Imidazoles , Prostatectomía , Neoplasias de la Próstata , Incontinencia Urinaria , Humanos , Masculino , Prostatectomía/efectos adversos , Prostatectomía/métodos , Imidazoles/uso terapéutico , Imidazoles/administración & dosificación , Imidazoles/efectos adversos , Incontinencia Urinaria/etiología , Estudios Prospectivos , Anciano , Neoplasias de la Próstata/cirugía , Persona de Mediana Edad , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Vejiga Urinaria Hiperactiva/etiología , Recuperación de la Función , Complicaciones Posoperatorias/tratamiento farmacológico , Resultado del Tratamiento , Esquema de Medicación , Antagonistas Colinérgicos/uso terapéutico , Antagonistas Colinérgicos/administración & dosificación , Antagonistas Colinérgicos/efectos adversos , Agentes Urológicos/uso terapéutico , Agentes Urológicos/administración & dosificación , Procedimientos Quirúrgicos Robotizados/efectos adversosRESUMEN
BACKGROUND AND OBJECTIVES: Data on the population-based epidemiology of hyperhidrosis (HH) are scarce. This study investigated the epidemiology and healthcare of HH in Germany. DESIGN AND SETTING: Claims data of adult persons insured by a German statutory health insurance (DAK-Gesundheit) between 2016 and 2020 were analysed. Included were persons aged 18 years and older with a diagnosis of HH (confirmed inpatient or outpatient diagnosis in the observation year) who were continuously insured. Following outcomes were measured: prevalence and incidence rates, severity of hyperhidrosis and inpatient and outpatient care by a group of specialists. RESULTS: In 2020, 0.70% of insured adults were confirmed to have HH (mean age 59.5 years, SD 18.9, 61.6% female), with 9.24% having a 'localised' form, 8.65% a 'generalised' form and 84.80% an 'unspecified' form. 0.04% of the total population had a severe form. The incidence was 0.35%. Localised HH was more common in younger age groups (18 to <30 years), while older age groups (70 to <80 years) were significantly more likely to suffer from generalised HH. Systemic anticholinergics were used in 4.55%, and botulinum toxin injection therapy in 0.81%. General practitioners were most frequently involved in care. Inpatient stays due to HH were very rare, with 0.14% in 2019 and 0.04% in 2020. CONCLUSION: Multisource data analysis connecting primary and secondary data will be needed for a complete picture of the healthcare and epidemiology of HH.
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Hiperhidrosis , Revisión de Utilización de Seguros , Humanos , Hiperhidrosis/epidemiología , Alemania/epidemiología , Femenino , Persona de Mediana Edad , Masculino , Adulto , Anciano , Adulto Joven , Adolescente , Incidencia , Prevalencia , Anciano de 80 o más Años , Antagonistas Colinérgicos/uso terapéutico , Atención Ambulatoria/estadística & datos numéricos , Hospitalización/estadística & datos numéricosRESUMEN
INTRODUCTION: There is concern about the use of anticholinergic medications in people living with dementia (PLWD). Such medicines may increase cognitive decline and may be associated with higher mortality in PLWD who take these medicines. The aim of this study was to analyse data from an online dementia discussion forum to explore the experiences and perspectives of PLWD and carers about the use of anticholinergic medicines in this population. METHODS: Following receipt of ethical approval, archived discussions (posts) from Dementia Talking Point, a fully public online forum for anyone affected by dementia, created and maintained by the Alzheimer's Society, were searched from the date of inception to January 2022 using a range of search terms including commonly used anticholinergic medicines. Posts, including any of the search terms, were assessed for relevance and analysed using inductive thematic analysis. RESULTS: Five hundred and fifty unique posts were analysed, all of which had been provided by carers, with no posts attributed to PLWD. The themes that encompassed carers' experiences were (1) motivators of prescribing, (2) perspectives on the process of prescribing and (3) the outcomes of prescribing. The dominant motivator of prescribing was the management of noncognitive symptoms, pre- and postdiagnosis of dementia. Carers' perspectives on the process of prescribing were informed by an assessment of the risk-benefit of starting a medication and shared decision-making between the carer and healthcare professional to a greater or lesser degree. The outcomes of prescribing were observing the effects of the medicines, which in turn influenced whether prescribing was reviewed and continued unchanged, continued but amended, reinitiated if the medicine had been previously stopped or discontinued (the process of deprescribing). CONCLUSION: This study has provided unique insights into carers' experiences and perspectives about the use of anticholinergic medications in PLWD, highlighting how commonly these medications are prescribed for PLWD and carers' concerns about their use. There is a clear need for carers and PLWD to receive information about these medicines and healthcare professionals to consider how to optimise the use of these medicines to avoid adverse effects. PATIENT OR PUBLIC CONTRIBUTION: This work was informed by findings from previous research studies focusing on optimising medicine use for people with dementia in primary care, in which interviews were conducted with PLWD, their carers and primary healthcare professionals. Although not strictly patient and public involvement, we utilised the feedback provided by key stakeholders to inform the research questions and aim/objectives of this study.
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Cuidadores , Antagonistas Colinérgicos , Demencia , Humanos , Cuidadores/psicología , Demencia/tratamiento farmacológico , Antagonistas Colinérgicos/uso terapéutico , Femenino , Masculino , MotivaciónRESUMEN
Chronic sialorrhea is a condition characterized by excessive drooling, often associated with neurological and neuromuscular disorders such as Parkinson's disease, cerebral palsy, and stroke. Despite its prevalence, it remains underdiagnosed and poorly understood, leading to a lack of comprehensive data on patient demographics, clinical characteristics, and treatment patterns. This study aimed to help fill these existing gaps by analyzing real-world data using Optum's de-identified Clinformatics® Data Mart Database. Patients were required to have a diagnosis indicative of sialorrhea plus evidence of sialorrhea treatment between 1/1/2007 and 5/31/2022. Two cohorts were analyzed: patients with evidence of newly diagnosed sialorrhea and associated treatment, and sialorrhea patients initiating incobotulinumtoxinA. Clinical characteristics, comorbidities, symptoms, and treatment utilization were described before and after diagnosis and incobotulinumtoxinA initiation. No formal statistical comparisons were performed. Patients were predominantly aged 65 or older, male, and non-Hispanic white. Parkinson's disease and cerebral palsy were the most common comorbidities among adults and children, respectively. Treatment patterns suggest that anticholinergics are more commonly used than botulinum toxin therapy. The findings offer valuable information for improving diagnosis and treatment approaches and suggest a need for further research into treatment effectiveness, safety, and disease burden.
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Toxinas Botulínicas Tipo A , Sialorrea , Humanos , Masculino , Sialorrea/tratamiento farmacológico , Femenino , Anciano , Toxinas Botulínicas Tipo A/uso terapéutico , Persona de Mediana Edad , Adulto , Enfermedad Crónica , Niño , Adolescente , Antagonistas Colinérgicos/uso terapéutico , Adulto Joven , Anciano de 80 o más Años , Preescolar , Enfermedad de Parkinson/tratamiento farmacológico , ComorbilidadRESUMEN
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.
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Analgésicos Opioides , Hipnóticos y Sedantes , Humanos , Hipnóticos y Sedantes/uso terapéutico , Analgésicos Opioides/uso terapéutico , Dexmedetomidina/uso terapéutico , Sedación Consciente/métodos , Ketamina/uso terapéutico , Servicio de Urgencia en Hospital , Antieméticos/uso terapéutico , Manejo del Dolor/métodos , Antagonistas Colinérgicos/uso terapéuticoRESUMEN
BACKGROUND: Long-term exposure to anticholinergic and sedative drugs could be a modifiable risk factor for cognitive decline. The objective of this study was to measure the association between previous cumulative anticholinergic and sedative drug exposure (Drug Burden Index) and cognitive decline. METHODS: A cohort study (MEMORA cohort) was conducted in a French memory clinic for patients attending a consultation between November 2014 and December 2020, with at least 2 Mini-Mental State Examination (MMSE) measurements (≥ 6 months apart) and available medication data from the local Primary Health Insurance Fund database (n = 1,970). Drug Burden Index was linearly cumulated until each MMSE measurement and was used to categorise patients according to their level of exposure (no exposure, moderate, or high). The longitudinal association between Drug Burden Index and MMSE was assessed using a multivariate linear mixed model, adjusted for age, education level, anxiety disorders, depressive disorders, functional autonomy, and behavioural disorders. RESULTS: Overall, 1,970 patients were included with a mean follow-up duration of 2.78 years (± 1.54) and 2.99 visits per patients (5,900 MMSE + Drug Burden Index measurements collected). At baseline, 68.0% of patients had moderate cumulative anticholinergic and sedative drug exposure and a mean MMSE of 21.1. MMSE decrease was steeper in patients with moderate and high Drug Burden Index ( -1.74 and -1.70/year, respectively) than in patients with no exposure (-1.26/year) after adjusting for age, education, anxiety and depressive disorders, functional autonomy, and behavioural disorders (p < 0.01). CONCLUSIONS: Long-term exposure to anticholinergic and sedative drugs is associated with steeper cognitive decline. Medication review focusing on de-prescribing these drugs could be implemented early to reduce cognitive impairment.
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Antagonistas Colinérgicos , Disfunción Cognitiva , Hipnóticos y Sedantes , Humanos , Masculino , Femenino , Hipnóticos y Sedantes/efectos adversos , Anciano , Antagonistas Colinérgicos/efectos adversos , Estudios de Cohortes , Disfunción Cognitiva/inducido químicamente , Disfunción Cognitiva/epidemiología , Anciano de 80 o más Años , Cognición/efectos de los fármacos , Pruebas de Estado Mental y Demencia , Estudios Longitudinales , Francia/epidemiologíaRESUMEN
OBJECTIVE: This review summarizes the approaches to pediatric sialorrhea management from least-to-most invasive: non-pharmacological management, anticholinergic medications, botulinum neurotoxin, non-invasive surgery, and invasive surgical intervention. REVIEW METHODS: An electronic literature review identified English-language articles on sialorrhea management in pediatric patients. Publications between 1982 and 2022 were used, with a focus on articles published from 2012 to 2022. Additional augmentation of pharmacologic information was obtained from the latest editions of medical textbooks supplemented with official package inserts of investigated medications. CONCLUSIONS: Sialorrhea is abnormal in patients greater than four years of age. Severe cases warrant intervention to improve patient quality of life and reduce caregiver burden. Management starts with conservative approaches. Viable candidates begin with non-pharmacological management options. Anticholinergic medications can decrease saliva production, but adverse side effects may outweigh benefits. Botulinum neurotoxin injection of the salivary glands decreases salivary flow rate; however, relief is transient and thus multiple treatments are required. Non-invasive sclerotherapy is an emerging treatment option showing promising results for sialorrhea. In contrast, surgical intervention is reserved as a last-resort treatment for patients with severe symptoms, due to its higher risk for adverse consequences. IMPLICATIONS FOR PRACTICE: Physicians should be familiar with the different pediatric sialorrhea management options, including advantages and disadvantages, to adequately facilitate shared decision making with caretakers of pediatric patients who require treatment.
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Antagonistas Colinérgicos , Sialorrea , Humanos , Sialorrea/terapia , Sialorrea/etiología , Niño , Antagonistas Colinérgicos/uso terapéutico , Preescolar , Calidad de Vida , Glándulas Salivales , Femenino , Adolescente , Toxinas Botulínicas/uso terapéutico , Toxinas Botulínicas/administración & dosificación , MasculinoRESUMEN
OBJECTIVE: To describe the prevalence of frailty among Medicare beneficiaries with overactive bladder (OAB), analyze oral therapy patterns, and examine potential disparities in treatment. METHODS: This retrospective cohort study utilized the 20% Research Identifiable File Medicare Part D prescription claims dataset (2013-2018). Using the Claims-Based Frailty Index (CFI), Medicare beneficiaries ≥65 years old with OAB were categorized as not frail (CFI <0.15), prefrail (0.15 ≤CFI<0.25), and frail (CFI >0.25). Logistic regression models assessed associations between frailty and pharmacotherapy utilization. RESULTS: Among 111,761 patients (15.8% of the OAB cohort) receiving oral pharmacotherapy (anticholinergic oral medications or mirabegron), 71% were women, 83% were White, and 11.9% were frail. After controlling for age, copayments and dual eligibility status, frail status (OR 1.16; 95% CI [1.09-1.24]), urology (OR 2.05; 95% CI [1.94-2.16]) or gynecology (OR 1.74; 95% CI [1.6-1.9]) prescribers and residing in the Southern United States (OR 1.53; CI [1.49-1.61]) were associated with higher likelihood of mirabegron utilization. Black (OR 0.79; 95% CI [0.74-0.85]) and American Indian/Alaska Native (OR 0.54; 95% CI [0.39-0.74]) patients were less likely to utilize Mirabegron than White beneficiaries. CONCLUSION: Frail beneficiaries and those with urology and gynecology prescribers showed higher likelihoods of beta-3 agonist utilization. Despite adjustments, Black and American Indian/Alaskan Native patients were less likely to fill mirabegron prescriptions, suggesting disparities in treatment. Our findings highlight the need for policies, interventions, and initiatives to promote equitable OAB oral therapy utilization in vulnerable populations.
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Acetanilidas , Disparidades en Atención de Salud , Medicare Part D , Vejiga Urinaria Hiperactiva , Humanos , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Estados Unidos , Femenino , Anciano , Masculino , Estudios Retrospectivos , Medicare Part D/estadística & datos numéricos , Disparidades en Atención de Salud/estadística & datos numéricos , Administración Oral , Anciano de 80 o más Años , Acetanilidas/uso terapéutico , Tiazoles/uso terapéutico , Antagonistas Colinérgicos/uso terapéutico , Fragilidad , Factores Sociodemográficos , Estudios de CohortesRESUMEN
OBJECTIVES: To evaluate polypharmacy, anticholinergic burden (ACB) and drug-drug interactions (DDIs) in people with four-class-resistant HIV (4DR-PWH). METHODS: We performed a cross-sectional study, including 4DR-PWH from the PRESTIGIO Registry taking at least one non-antiretroviral drug. Polypharmacy was defined as taking five or more non-antiretroviral drugs. ACB was calculated using the ACB scale: 0â=âno AC effect, 1-2â=âlow/moderate risk, ≥3â=âhigh AC risk. Participants' characteristics by ACB score were compared using the Kruskal-Wallis test, and Spearman's correlation coefficient was used to assess linear relationships. DDIs were evaluated using the Liverpool database. RESULTS: Overall, 172 4DR-PLWH were evaluated: 75.6% males, median age 49.9â years (IQRâ=â45.6-56), 62 (27.1%) on polypharmacy, 124 (72.1%) using a boosting agent and 72 (41.8%) with four or more antiretrovirals. Based on ACB, 128 (74.45%), 33 (19.2%) and 11 (6.4%) had a no, low/moderate and high AC risk, respectively. The most common AC drugs were ß-blockers (12.2%), diuretics (8.7%) and antidepressants (8.7%). The high ACB was significantly related to the number of drugs/person (râ=â0.33, Pâ<â0.0001) and the number of clinical events (râ=â0.222, Pâ=â0.004). Overall, 258 DDIs were found between antiretrovirals and co-medications in 115 (66.8%) PWH, and 14 (8.1%) PWH received contraindicated drug combinations. CONCLUSIONS: In 4DR-PWH, polypharmacy, DDIs and the proportion of people with moderate/high AC burden were high. In 4DR-PWH undetectability achievement and maintenance is the priority and use of boosted PIs is common. A strict collaboration (infectious diseases specialists, virologists, pharmacologists) is needed to limit the risk of ACB and DDIs and to explore the advantages of new antiretrovirals.
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Fármacos Anti-VIH , Antagonistas Colinérgicos , Interacciones Farmacológicas , Infecciones por VIH , Polifarmacia , Sistema de Registros , Humanos , Masculino , Infecciones por VIH/tratamiento farmacológico , Femenino , Persona de Mediana Edad , Estudios Transversales , Fármacos Anti-VIH/uso terapéutico , Antagonistas Colinérgicos/administración & dosificación , Farmacorresistencia Viral , AdultoRESUMEN
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.
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Antagonistas Colinérgicos , Encefalopatía Hepática , Hospitalización , Cirrosis Hepática , Polifarmacia , Humanos , Antagonistas Colinérgicos/efectos adversos , Antagonistas Colinérgicos/uso terapéutico , Masculino , Cirrosis Hepática/tratamiento farmacológico , Estudios Retrospectivos , Femenino , Persona de Mediana Edad , Anciano , Hospitalización/estadística & datos numéricos , Encefalopatía Hepática/tratamiento farmacológico , Adulto , Anciano de 80 o más Años , Adolescente , Adulto JovenRESUMEN
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].
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Antagonistas Colinérgicos , Delirio , Hospitalización , Humanos , Delirio/epidemiología , Antagonistas Colinérgicos/efectos adversos , Antagonistas Colinérgicos/uso terapéutico , Anciano , Estudios Prospectivos , Anciano de 80 o más Años , Estudios de CohortesRESUMEN
BACKGROUND: Recent studies have shown that anticholinergic medications are associated with cardiovascular disease. Little is known about how discontinuation of anticholinergic medication affects this association. We investigated how baseline anticholinergic load and change in anticholinergic load associates with major adverse cardiovascular events (MACE) on four different scales. METHODS: We included all geriatric outpatients aged 65 and older in Denmark between January 2011 and December 2018. Data were sourced from Danish national registries. Anticholinergic drug exposure was assessed at first contact to the outpatient clinic (baseline) and changes were assessed at 180 days after outpatient contact. Anticholinergic scales were the CRIDECO Anticholinergic Load Scale, Anticholinergic Drugs Scale, Anticholinergic Cognitive Burden and a scale by the Danish Institute of Rational Pharmacotherapy. Multivariate analyses were conducted to investigate the 1- and 5-year risk of MACE by baseline anticholinergic load and changes in anticholinergic load after 180 days. RESULTS: We included a total of 64 378 patients in the analysis of baseline anticholinergic load and 54 010 patients remained after 180 days for inclusion in the analysis of change in anticholinergic load. At baseline the mean age was 81.7 year (SD 7.5) and 68% were women. Higher level of anticholinergic load on any scale associated with greater risk of MACE in a dose response pattern. There were no association between reduction in anticholinergic load and risk of MACE. CONCLUSION: While anticholinergic load at baseline was associated with MACE, reducing anticholinergic load did not lower the risk of MACE indicating the association may not be causal.
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Enfermedades Cardiovasculares , Antagonistas Colinérgicos , Sistema de Registros , Humanos , Antagonistas Colinérgicos/efectos adversos , Femenino , Masculino , Anciano de 80 o más Años , Dinamarca/epidemiología , Anciano , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/inducido químicamente , Factores de Riesgo de Enfermedad Cardiaca , Medición de Riesgo , Pacientes Ambulatorios/estadística & datos numéricos , Evaluación Geriátrica/métodos , Estudios de CohortesRESUMEN
AIMS: This study evaluated the use of machine learning to leverage drug absorption, distribution, metabolism and excretion (ADME) data together with physicochemical and pharmacological data to develop a novel anticholinergic burden scale and compare its performance to previously published scales. METHODS: Experimental and in silico ADME, physicochemical and pharmacological data were collected for antimuscarinic activity, blood-brain barrier penetration, bioavailability, chemical structure and P-glycoprotein (P-gp) substrate profile. These five drug properties were used to train an unsupervised model to assign anticholinergic burden scores to drugs. The model performance was evaluated through 10-fold cross-validation and compared with the clinical Anticholinergic Cognitive Burden (ACB) scale and nonclinical Anticholinergic Toxicity Scores (ATS) scale, which is based primarily on muscarinic binding affinity. RESULTS: In silico software (ADMET Predictor) used for screening drugs for their blood-brain barrier (BBB) penetration correctly identified some drugs that do not cross the BBB. The mean area under the curve for the unsupervised and ACB scale based on the five selected variables was 0.76 and 0.64, respectively. The unsupervised model agreed with the ACB scale on the classification of more than half of the drugs (49 of 88) agreed on the classification of less than half the drugs in the ATS scale (12 of 25). CONCLUSIONS: Our findings suggest that the commonly used ACB scale may misclassify certain drugs due to their inability to cross the BBB. By contrast, the ATS scale would misclassify drugs solely depending on muscarinic binding affinity without considering other drug properties. Machine learning models can be trained on these features to build classification models that are easy to update and have greater generalizability.
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Barrera Hematoencefálica , Antagonistas Colinérgicos , Simulación por Computador , Aprendizaje Automático , Humanos , Barrera Hematoencefálica/efectos de los fármacos , Barrera Hematoencefálica/metabolismo , Antagonistas Colinérgicos/efectos adversos , Antagonistas Colinérgicos/farmacocinética , Cognición/efectos de los fármacos , Disponibilidad Biológica , Antagonistas Muscarínicos/farmacocinética , Antagonistas Muscarínicos/efectos adversos , Modelos Biológicos , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismoRESUMEN
Green and white chemistry are vital to revolutionizing the chemical industry through their unparalleled potential to enhance sustainability and efficiency. In this study, nine sustainability tools of both green and white metrics, including green analytical procedure index (GAPI), ComplexGAPI, analytical greenness, analytical greenness metric for sample preparation, Analytical Eco-Scale (ESA), analytical method greenness score, high-performance liquid chromatography- environmental assessment tool (HPLC-EAT), analytical method volume intensity, and blue applicability grade index (BAGI), have been developed for appraising environmental friendliness for both innovative and straightforward mean centering of ratio spectra (MCR) and reversed-phase high-performance liquid chromatography (RP-HPLC) strategies utilized for concurrent analysis and separation of cyclopentolate (CYC) and C12 and C14 homologs of benzalkonium chloride (BNZ) in pure and ophthalmic solution. The mobile phase, formed of buffer phosphate and acetonitrile (35:65, v/v), was adjusted to pH 6.3, and 215-nm UV detection was used. The experimental flow rate was 2.0 mL min-1, and the analytical column was L11 Inertsil Ph-3 (150 mm × 4.6 mm, 5 µm). All sequences were run at 25°C in the column oven. The MCR approach effectively resolved the drug's spectral overlapping. CYC and BNZ employed this approach at 227.5 and 220.4 nm, respectively. As part of the HPLC analysis, an isocratic method was employed with phosphate buffer and acetonitrile in the mobile phase at 35:65. A correlation coefficient greater than 0.999 was observed between the calibration curves for the HPLC and MCR methods in the ranges of 20-320 µg mL-1 and 5-30 µg mL-1 for all drugs. The technique yields excellent primary recovery rates, ranging from 97.2% to 100.5%. The recommended approach has been validated according to International Council for Harmonization guidelines.
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Antagonistas Colinérgicos , Cromatografía Líquida de Alta Presión , Antagonistas Colinérgicos/análisis , Antagonistas Colinérgicos/química , Cromatografía de Fase Inversa/métodos , Tecnología Química Verde , Soluciones Oftálmicas/química , Estructura MolecularRESUMEN
Background In older inpatients, anticholinergic medications can increase the risk of complications that may increase length of stay (LOS). Cyclobenzaprine is an anticholinergic medication associated with mental status changes, falls, and injuries in older patients. Objective The purpose of this study is to determine whether use of a lower cyclobenzaprine dose (5 mg) compared with higher dosing (10 mg) will affect LOS, 30-day readmission rates, and need for injectable psychotropic agents in inpatients 65 years of age and older. Methods This was a retrospective cohort analysis comparing outcomes in patients 65 years of age and older who received either a 5 mg or 10 mg cyclobenzaprine dose during their inpatient admission over a 2.5-year period. The primary outcome was hospital LOS, adjusted using multivariate linear regression. Secondary outcomes included 30-day readmission rate adjusted using logistic regression and use of injectable antipsychotics or benzodiazepines. A sub-analysis evaluated the impact of the institution's implementation of a geriatric prescribing context (GEM-CON) on cyclobenzaprine dose selection. Results The adjusted LOS was 32.7% longer (95% CI 25.9%-39.9%) for patients exposed to higher-dose cyclobenzaprine. Use of injectable antipsychotics or benzodiazepines was also significantly greater in the higher-dose group (P < 0.001; P = 0.025). Cyclobenzaprine dose was not significantly associated with readmission on multivariate analysis (OR = 0.93, 95% CI 0.45-1.93). After GEM-CON implementation, there was a significant increase in use of the recommended lower cyclobenzaprine dose (P < 0.001). Conclusion Use of lower cyclobenzaprine dosing in older inpatients is associated with reduced hospital LOS and need for injectable antipsychotics and benzodiazepines.
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Amitriptilina , Relación Dosis-Respuesta a Droga , Tiempo de Internación , Readmisión del Paciente , Humanos , Anciano , Estudios Retrospectivos , Masculino , Femenino , Anciano de 80 o más Años , Readmisión del Paciente/estadística & datos numéricos , Amitriptilina/administración & dosificación , Amitriptilina/análogos & derivados , Amitriptilina/efectos adversos , Pacientes Internos , Antagonistas Colinérgicos/administración & dosificación , Antagonistas Colinérgicos/efectos adversos , Estudios de Cohortes , Antipsicóticos/administración & dosificación , Antipsicóticos/efectos adversosRESUMEN
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.
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Biorretroalimentación Psicológica , Humanos , Femenino , Masculino , Biorretroalimentación Psicológica/métodos , Niño , Estudios Retrospectivos , Vejiga Urinaria Hiperactiva/terapia , Trastornos Urinarios/terapia , Antagonistas Colinérgicos/uso terapéutico , Resultado del Tratamiento , Diafragma Pélvico/fisiopatología , Terapia Combinada , Estimulación Eléctrica Transcutánea del Nervio/métodosRESUMEN
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.
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Antagonistas Colinérgicos , Nervio Tibial , Estimulación Eléctrica Transcutánea del Nervio , Vejiga Urinaria Hiperactiva , Vejiga Urinaria Hiperactiva/terapia , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Humanos , Antagonistas Colinérgicos/efectos adversos , Antagonistas Colinérgicos/uso terapéutico , Femenino , Guías de Práctica Clínica como AsuntoRESUMEN
INTRODUCTION: Vibegron is a selective ß3-adrenergic receptor agonist that was approved by the US Food and Drug Administration in December 2020 for the treatment of overactive bladder in adults. This retrospective study assessed US pharmacy claims data to evaluate the real-world adherence and persistence of vibegron compared with mirabegron and with anticholinergics. MATERIALS AND METHODS: This analysis used the Optum Research Database to identify adults with ≥1 pharmacy claim for vibegron, mirabegron, or an anticholinergic from April 1, 2021, to August 31, 2022. Patients had ≥ 90 days of continuous commercial or Medicare medical and pharmacy coverage preindex and ≥ 60 days of continuous pharmacy coverage postindex. Two independent propensity-score models matched patients treated with (1) vibegron versus mirabegron and (2) vibegron versus anticholinergics on key variables such as demographics and clinical characteristics, index copay, days' supply, and time of entry into analysis (index quarter). Adherence was measured by proportion of days covered (PDC) from index to the end of follow-up and was defined as PDC ≥ 80%. Persistence was defined as days to discontinuation of index medication (first 30-day gap) or end of follow-up. RESULTS: The matched vibegron and mirabegron cohorts included 4921 and 9842 patients, respectively, and the matched vibegron and anticholinergic cohorts included 4676 and 9352 patients, respectively. Patients receiving vibegron had greater mean PDC versus patients receiving mirabegron (0.67 vs. 0.64, respectively; p < 0.001) or anticholinergics (0.67 vs. 0.58; p < 0.001). A greater percentage of patients receiving vibegron were adherent versus those receiving mirabegron (49.0% vs. 45.1%, respectively; p < 0.001) or anticholinergics (49.1% vs. 38.5%; p < 0.001). Persistence was longer with vibegron compared with both mirabegron (median [95% CI], 171 [159-182] vs. 128 [122-137] days, respectively; p < 0.001) and anticholinergics (172 [159-183] vs. 91 [91] days; p < 0.001). CONCLUSION: In this retrospective analysis of pharmacy claims data, patients receiving vibegron exhibited significantly higher adherence and demonstrated longer persistence in comparison to matched patient cohorts receiving either mirabegron or anticholinergics.
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Acetanilidas , Agonistas de Receptores Adrenérgicos beta 3 , Antagonistas Colinérgicos , Cumplimiento de la Medicación , Tiazoles , Vejiga Urinaria Hiperactiva , Humanos , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Vejiga Urinaria Hiperactiva/diagnóstico , Vejiga Urinaria Hiperactiva/fisiopatología , Estudios Retrospectivos , Masculino , Femenino , Antagonistas Colinérgicos/uso terapéutico , Persona de Mediana Edad , Anciano , Acetanilidas/uso terapéutico , Agonistas de Receptores Adrenérgicos beta 3/uso terapéutico , Tiazoles/uso terapéutico , Adulto , Pirrolidinas , Tiazidas/uso terapéutico , Estados Unidos , Agentes Urológicos/uso terapéutico , PirimidinonasRESUMEN
BACKGROUND: Cognitive dysfunction is a non-motor manifestation of Parkinson's disease (PD). We aimed to determine the frequency and patterns of cognitive dysfunction in treated patients with PD and their predictors. RESEARCH DESIGN AND METHODS: This study included 80 patients (male = 48; female = 32) and 30 healthy individuals. They underwent neuropsychiatric evaluations. Measurements included Beck's depression inventory - II (BDI-II), mini-mental state examination (MMSE) and Montreal cognitive assessment (MoCA). RESULTS: Patients had mean age of 55.56 ± 9.06 yrs, duration of PD of 4.86 ± 2.71 yrs and Hoehn and Yahr Scoring of 2.19 ± 0.89. They were on levodopa/carbidopa therapy and adjuvant therapy with benztropine mesylate, an anticholinergic drug, (n = 51) or amantadine sulfate, a dopaminergic drug, (n = 29). Sixteen (20%) had moderate depressive symptoms. Mild and moderate cognitive impairments were reported in 38.8% and 28.8% (by MMSE) and 46.3% and 31.3% (by MoCA). Patients had lower global cognitive scoring (p = 0.0001) and scorings of different cognitive functions (naming, attention, language, abstraction, memory and orientation) than controls. Patients treated with benztropine had lower cognition than with amantadine. Correlation analyses showed that lower cognition was only associated with chronic PD and its treatment (p = 0.0001). CONCLUSIONS: Cognitive dysfunction is common with PD (77.5%) particularly with anticholinergic drugs. De-prescription of anticholinergics is recommended for patients with PD.