Cognitive effects of individual anticholinergic drugs: a systematic review and meta-analysis / Efeitos cognitivos de drogas anticolinérgicas individuais: uma revisão sistemática e meta-análise

ABSTRACT. 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.

RESUMO. 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.

Evaluation of anticholinergic burden in elderly outpatients and the risk factors / 中南大学学报(医学版)

OBJECTIVES@#The use of anticholinergic drugs in the elderly may lead to negative events such as falls, delirium, urinary retention and cognitive decline, and the higher the number of anticholinergic drugs use, the more such negative events occur. This study aims to analyze the risk factors associated with the prescription of total anticholinergic drugs in elderly outpatients and evaluate the rationality of anticholinergic drugs, and to provide a reference for reducing the adverse effects of anticholinergic drugs.@*METHODS@#A list of drugs with anticholinergic activity based on the Beers criteria was established. The basic information (such as age and gender), clinical diagnosis, and medications of elderly outpatient were extracted from hospital electronic medical records, and the Anticholinergic Cognitive Burden (ACB) Scale was used to calculate the anticholinergic burden for each patient. Logistic regression analysis was used to identify the potential risk factors for the occurrence of problems such as multiple medication and insomnia.@*RESULTS@#A total of 1 840 prescriptions for elderly patients were reviewed. Of these patients, ACB score was more than or equal to 1 in 648 (35.22%) patients. Number of prescription medication (95% CI: 1.221 to 1.336) and insomnia (95% CI: 3.538 to 6.089) were independent factors affecting ACB scores (both P<0.01). Medications for patients of ACB scores were most commonly treated with the central nervous system drugs (such as alprazolam and eszopiclone) and for the cardiovascular system drugs (such as metoprolol and nifedipine).@*CONCLUSIONS@#There is a high rate of ACB drugs use in geriatric patients, and the clinical focus should be on multiple medication prescriptions, especially on the central nervous system drugs (such as alprazolam and eszopiclone) and cardiovascular system drugs (such as metoprolol and nifedipine). The prescription review should be emphasized to reduce adverse reactions to anticholinergic drugs in elderly patients.

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

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.

Uso de emulsiones lipídicas en el tratamiento exitoso de un caso de intoxicación por difenhidramina / Use of lipid emulsions in the successful treatment of a case of diphenhydramine poisoning / Uso de emulsões lipídicas no sucesso do tratamento de um caso de intoxicação por difenidramina

La difenhidramina tiene efectos antihistamínico anti-H1 específico y antimuscarínico que pueden ocasionar un desenlace fatal según la dosis total ingerida. Se reporta un caso de intoxicación por difenhidramina tratado de forma exitosa con emulsiones lipídicas a pesar de ingesta de dosis letal. Se presenta el caso de un paciente de 19 años que ingresó por intoxicación por difenhidramina a dosis de 25 mg/kg (1.5 g) después del tiempo de descontaminación, con toxidrome anticolinérgico, con neurotoxicidad, cardiotoxicidad (QRS y QT prolongados) y sin respuesta al enfoque inicial, se iniciaron emulsiones lipídicas y, a su vez, se logró alta temprana por evolución clínica favorable y resolución de la prolongación del intervalo QTc y del cuadro anticolinérgico. La emulsión lipídica es una opción terapéutica para disminuir la morbimortalidad y la estancia hospitalaria por contrarrestar la cardiotoxicidad y neurotoxicidad producidas por moléculas lipofílicas como la difenhidramina.

Diphenhydramine has specific anti-H1 antihistamine and antimuscarinic effects that can be fatal depending on the total dose ingested. A case of diphenhydramine poisoning successfully treated with lipid emulsions despite ingesting a lethal dose is presented. We present the case of a 19-year-old patient who was admitted for diphenhydramine intoxication at a dose of 25 mg/kg (1.5 g) after the decontamination time, with anticholinergic toxidrome, with neurotoxicity, cardiotoxicity (prolonged QRS and QT) and without response to initial approach. Lipid emulsions were started and, in turn, early discharge was achieved due to favorable clinical evolution and resolution of the prolongation of the QTc interval and the anticholinergic symptoms. Lipid emulsion is a therapeutic option to reduce morbidity and mortality and hospital stay by counteracting cardiotoxicity and neurotoxicity produced by lipophilic molecules such as diphenhydramine.

A difenidramina tem efeitos anti-histamínicos e antimuscarínicos anti-H1 específicos que podem ser fatais dependendo da dose total ingerida. Relata-se um caso de intoxicação por difenidramina tratada com sucesso com emulsões lipídicas apesar da ingestão de uma dose letal. Apresentamos o caso de uma paciente de 19 anos que foi internada por intoxicação por difenidramina na dose de 25 mg/kg (1,5 g) após o tempo de des-contaminação, com toxina anticolinérgica, neurotoxicidade, cardiotoxicidade (QS e QT prolongados) e sem resposta na abordagem inicial, iniciaram-se emulsões lipídicas e, por sua vez, obteve-se alta precoce devido à evolução clínica favorável e resolução do prolongamento do intervalo QTc e dos sintomas anticolinérgicos. A emulsão lipídica é uma opção terapêutica para reduzir a morbimortalidade e o tempo de internação por neutralizar a cardiotoxicidade e a neurotoxicidade produzidas por moléculas lipofílicas como a difenidramina.

Uso de medicamentos com ação anticolinérgica em idosos e comparação entre escalas de risco: estudo de base populacional / Use of anticholinergic drugs among the elderly and a comparison between risk scales: a population-based study

Resumo O padrão de morbimortalidade tem-se modificado nos últimos anos com aumento das doenças crônicas não-transmissíveis levando a múltiplas comorbidades e ao uso de muitos medicamentos. O objetivo foi avaliar o uso de medicamentos com ação anticolinérgica por idosos. Estudo transversal de base populacional, com indivíduos de 60 anos ou mais. Foram investigados fatores socioeconômicos, problemas de saúde e utilização de medicamentos nos últimos 15 dias. Para a classificação dos medicamentos com atividade anticolinérgica foram utilizadas as escalas: Anticholinergic Drug Scale (ADS), Anticholinergic Risc Scale (ARS), Anticolinergic Cognitive Burden Scale (ACB). Entrevistados 1.451 idosos, destes, 1.305 utilizaram medicamentos, sendo que 60,7% usaram fármacos com ação anticolinérgica, sobretudo aqueles com mais de 80 anos e os menos escolarizados. No total, 5.703 medicamentos foram usados, 1.282 (22,5%) com ação anticolinérgica. Observou-se concordância kappa de 0,63 quando se avaliou as escalas de risco ACB e ADS. A prevalência de uso de fármacos com ação anticolinérgica foi alta, deve-se estar atento às consequências relativas ao seu uso, tendo em vista a tomada de decisão mais racional na prática clínica.

Abstract The pattern of morbidity and mortality has changed in recent years due to the increase in chronic noncommunicable diseases, leading to multiple comorbidities and the use of several medications. The scope of the study was to evaluate the anticholinergic drugs used by elderly people, according to risk scales. It involved a population-based cross-sectional study with elderly people. Socioeconomic factors, health problems, and medication use were investigated in the previous 15 days. The Anticholinergic Drug Scale (ADS), the Anticholinergic Risk Scale (ARS) and the Anticholinergic Cognitive Burden Scale (ACB) were used for risk classification according to anticholinergic activity of the drugs. A total of 1451 elderly people were interviewed and 1305 used medications, 60.7% of which with anticholinergic action, especially among the 80-year-old age bracket and the less educated. In total, 5703 drugs were used, 1282 (22.5%) of which with anticholinergic action. Kappa agreement of 0.63 was observed when assessing the ACB and ADS risk scales. The prevalence of the use of drugs with anticholinergic action was high, and attention should be paid to the consequences related to their use, with a view to more rational decision-making in clinical practice.

Development of monolithic matrix type transdermal patches containing cinnarizine: Physical characterization and permeation studies

To overcome the problems associated with bioavailability and systemic side effects of the drug by oral administration, monolithic matrix type transdermal patches containing cinnarizine (CNZ) were developed. For this purpose, films based on hydroxypropyl methylcellulose and polyvinylpyrrolidone as matrix-forming polymers were designed. Physical characteristics of transdermal films and drug-excipient compatibility were investigated. Factors affecting in vitro drug release and ex vivo skin penetration and permeation of the drug were studied. It was confirmed that films displayed sufficient flexibility and mechanical strength for application onto the skin for a long time period. Ex vivo penetration experiments gave satisfactory results for transdermal drug delivery through rat skin. The parameters determining good skin penetration were also evaluated. The highest drug permeation rate was obtained with incorporation of Transcutol® (0.102 mg/cm2/h) into the base CNZ formulation, followed by propylene glycol (0.063 mg/cm2/h), menthol (0.045 mg/cm2/h), and glycerin (0.021 mg/cm2/h) as penetration enhancers (p < 0.05). As a result, the developed transdermal patches of CNZ may introduce an alternative treatment for various conditions and diseases such as idiopathic urticarial vasculitis, Ménière's disease, motion sickness, nausea, and vertigo. Thus, the risk of systemic side effects caused by the drug can be reduced or eliminated

Experiencia con el uso de toxina botulínica en niños con vejiga hiperactiva neurogénica: Una serie de casos / Experience with Botulinum Toxin in Children with Neurogenic Overactive Bladder: A Case Series

Objetivo Describir la experiencia con la administración de inyección de toxina botulínica en niños con vejiga hiperactiva neurogénica refractaria a manejo de primera línea. Materiales y Métodos Estudio observacional descriptivo (serie de casos) que incluyó a 14 niños con diagnóstico de vejiga hiperactiva neurogénica refractarios a tratamiento de primera línea sometidos a administración intravesical de toxina botulínica entre 2015 y 2021; se realizó el seguimiento teniendo en cuenta las variables clínicas, con evaluación de la respuesta y de los eventos adversos. Se reportaron frecuencias absolutas y porcentajes para las variables cualitativas; para las variables cuantitativas, se reportaron medidas de tendencia central y dispersión. Resultados Se incluyeron 6 niños y 8 niñas, con una media de edad 10,1 (desviación estándar [DE]: ± 4,4) años. Todos los pacientes fueron tratados previamente con anticolinérgico y cateterismos limpios intermitentes, con una media de uso de 2,8 (DE: ± 1.0) pañales al día; 11 (78,5%) pacientes tenían antecedente de infección urinaria, 13 (92,8%), estreñimiento, y 2 (15,3%), incontinencia fecal. En la ecografía, 7 (50,0%) pacientes presentaban engrosamiento de las paredes vesicales, y 6 (42,8%), hidronefrosis. Tras el procedimiento, 1 paciente presentó infección urinaria como complicación, 6 presentaron una respuesta completa, 7, respuesta parcial, y 1 paciente no obtuvo respuesta con la primera inyección, con un tiempo promedio efectivo de la terapia 8 (DE: ± 6,3) meses. Una segunda inyección fue necesaria en 6 (42.8%) pacientes, y, de estos, 3 (50%) requirieron una tercera inyección. Conclusión La inyección de toxina botulinica intravesical como terapia de segunda línea de manejo para vejiga hiperactiva neurogénica tiene buenos resultados, con bajas tasas de complicaciones.

Objective To describe the experience with the administration of botulinum toxin injection in children with neurogenic overactive bladder who were refractory to the first-line management. Materials and Methods A descriptive observational study (case series) which included 14 children with a diagnosis of neurogenic overactive bladder who were refractory to the first-line treatment and were aubmitted to the intravesical administration of botulinum toxin between 2015 and 2021. Follow-up was performed taking into account the clinical variables, wth an evaluation of the response and the adverse events. Absolute frequencies and percentages were reported for the qualitative variables; for the quantitative variables, measures of central tendency and dispersion were reported. Results We included 6 boys and 8 girls with a mean age of 10.1 (standard deviation [SD]: ± 4.4) years. All patients were previously treated with anticholinergics and clean intermittent catheterizations, with a mean use of 2.8 (SD: ± 1.0) diapers per day; 11 (78.5%) had a history of urinary tract infection, 13 (92.8%), constipation, and 2 (15.3%), fecal incontinence. On ultrasound, 7 (50.0%) patients presented bladder wall thickening, and 6 (42.8%), hydronephrosis. After the procedure, 1 patient presented urinary tract infection as a complication, 6 presented complete response, 7, partial response, and 1 patient did not obtain a response with the first injection, with an effective mean time of therapy of 8 (SD: ± 6.3) months. A second injection was required by 6 (42.8%) patients, and of these, 3 (50%) required a third injection. Conclusion Intravesical botulinum toxin injection as a second-line management therapy for neurogenic overactive bladder yileds good results, with low rates of complications.

A comparison of the efficacy and tolerability of treating primary nocturnal enuresis with Solifenacin Plus Desmopressin, Tolterodine Plus Desmopressin, and Desmopressin alone: a randomized controlled clinical trial

ABSTRACT Introduction: Nocturnal enuresis (enuresis) is one of the most common developmental problems of childhood, which has often a familial basis, causes mental and psychological damage to the child and disrupts family solace. Objectives: In this study, we compared therapeutic efficacy and tolerability of treating primary nocturnal enuresis (PNE) with solifenacin plus desmopressin, tolterodine plus desmopressin, and desmopressin alone. Because we don't have enough information about this comparison especially about solifenacin plus desmopressin. Patients and Methods: This clinical trial study was performed on 62 patients with enuresis aged 5-15 years who referred to the urology clinic of Imam Khomeini Hospital in Ahwaz in 2017-2018. Patients were randomly assigned to one of the three different therapeutic protocols and any participants were given a specific code. After that, we compared the therapeutic response and the level of satisfaction of each therapeutic group in different months. Data were analyzed using SPSS 22 software and descriptive and analytical statistics. Results: The mean age of patients was 8.70±66 years. In the therapeutic group with desmopressin and solifenacin, 19 of 20 patients (95%) achieved complete remission (1) after a 3-month treatment in comparison with monotherapy group in which 14 of 22 patients (63.63%) achieved complete remission; and in the combination therapy group of desmopressin and tolterodine, in the study and the evaluation of the consequences of 3-month treatment of this group, it was found that 17 of 20 patients (85%) had complete remission. Overall, the therapeutic response in combination therapy groups of desmopressin plus anticholinergic was higher than the monotherapy group of desmopressin alone. Conclusion: Our results demonstrate that the combination of desmopressin and an anticholinergic agent is highly effective in treatment of children with PMNE. Although desmopressin has long been a first - line treatment for PMNE, desmopressin monotherapy often fails to achieve a successful response in patients with PMNE.

Uso de testosterona en mujeres: un comentario sobre el consenso global sobre el uso de la terapia de testosterona para mujeres / Global consensus position statement on the use of testosterone therapy for women

Las mujeres han sido tratadas por décadas con testosterona intentando aliviar una gran variedad de síntomas con riesgos y beneficios inciertos. En la mayoría de los países, la testosterona se prescribe "off-label", de modo que las mujeres están utilizando compuestos y dosis ideadas para tratamientos en hombres. En este sentido, varias sociedades médicas de distintos continentes adoptaron recientemente por consenso una toma de posición sobre los beneficios y potenciales riesgos de la terapia con testosterona en la mujer, explorar las áreas de incertidumbre e identificar prácticas de prescripción con potencial de causar daño. Las recomendaciones con respecto a los beneficios y riesgos de la terapia con testosterona se basan en los resultados de ensayos clínicos controlados con placebo de al menos 12 semanas de duración. A continuación se comentan las recomendaciones. (AU)

There are currently no clear established indications for testosterone replacement therapy for women. Nonetheless, clinicians have been treating women with testosterone to alleviate a variety of symptoms for decades with uncertainty regarding its benefits and risks. In most countries, testosterone therapy is prescribed off-label, which means that women are using testosterone formulations or compounds approved for men with a modified dose for women. Due to these issues, there was a need for a global Consensus Position Statement on testosterone therapy for women based on the available evidence from placebo randomized controlled trials (RCTs). This Position Statement was developed to inform health care professionals about the benefits and potential risks of testosterone therapy intended for women. The aim of the Consensus was to provide clear guidance as to which women might benefit from testosterone therapy; to identify symptoms, signs, and certain conditions for which the evidence does not support the prescription of testosterone; to explore areas of uncertainty, and to identify any prescribing practices that have the potential to cause harm. (AU)

Current treatment options for craniofacial hyperhidrosis / Opções atuais de tratamento para hiperidrose craniofacial

Abstract Hyperhidrosis (HH) is characterized by sweating exceeding the amount necessary to meet the thermal regulation and physiological needs of the body. Approximately 9.41% of individuals with HH have craniofacial hyperhidrosis (FH). The present study aims to review the most current data in the literature regarding craniofacial hyperhidrosis, including pathophysiology, diagnosis and clinical presentation, treatment options (clinical and surgical), and outcomes. VATS (videothoracoscopy sympathectomy) is considered the gold standard for definitive treatment of axillary or palmar hyperhidrosis. Recently, several studies have shown the usefulness of clinical treatment with oxybutynin hydrochloride, leading to clinical improvement of HH in more than 70% of users. Both clinical and surgical treatment of craniofacial hyperhidrosis have good results. However, surgical treatment of FH is associated with more complications. Clinical treatment with oxybutynin hydrochloride yields good results and can be the first therapeutic option. When the patient is not satisfied with this treatment and has good clinical conditions, surgical treatment can be used safely.

Resumo A hiperidrose (HH) é caracterizada por transpiração além da quantidade necessária para manter a regulação térmica e as necessidades fisiológicas do corpo. Aproximadamente 9,41% dos indivíduos com HH apresentam hiperidrose craniofacial (FH). Este estudo tem como objetivo revisar os dados mais atuais da literatura sobre FH, incluindo fisiopatologia, diagnóstico e apresentação clínica, opções de tratamento (clínico e cirúrgico) e desfechos. A simpatectomia por videotoracoscopia (VATS) é considerada o padrão-ouro para o tratamento definitivo da hiperidrose axilar ou palmar. Recentemente, vários estudos demonstraram a utilidade do tratamento clínico com cloridrato de oxibutinina, que leva à melhora clínica da HH em mais de 70% dos pacientes. O tratamento clínico e o cirúrgico apresentam bons resultados no tratamento da FH. No entanto, o tratamento cirúrgico da FH apresenta mais complicações. O tratamento clínico com cloridrato de oxibutinina fornece bons resultados e pode ser a primeira opção terapêutica. Quando o paciente não está satisfeito com esse tratamento e mostra boas condições clínicas, o tratamento cirúrgico pode ser usado com segurança.

La depresión: un desafío en la práctica médica general / La depresión: un desafío en la práctica médica general

Asociada o no a una enfermedad orgánica, la depresión tiene gran prevalencia en la práctica médica pero es subdiagnosticada. El trastorno del ánimo suele coexistir con variadas quejas somáticas y dolores crónicos, configurando síndromes mixtos con un diagnóstico diferencial complejo. En este artículo se describen distintas presentaciones clínicas de la depresión en medicina general, con énfasis en los estados depresivos atípicos, depresiones enmascaradas muy relevantes por su frecuencia y consecuencias: depresión posquirúrgica, cuadros dolorosos crónicos como cefaleas o lumbago, la fatiga crónica y la fibromialgia. Solo el reconocimiento y diagnóstico de la depresión subyacente posibilitará la implementación de las adecuadas intervenciones terapéuticas. Se revisan también algunas recomendaciones para el uso de antidepresivos en atención primaria y la eventual consulta psiquiátrica. (AU)

Associated or not with an organic disease, depression has a high prevalence in medical practice but is underdiagnosed. The mood disorder usually coexists with varied somatic complaints and chronic pain, forming mixed syndromes with a complex differential diagnosis. This article describes different clinical presentations of depression in general medicine, with emphasis on atypical depressive states, masked depressions very relevant for their frequency and consequences: post-surgical depression, chronic painful conditions such as headaches or lumbago, chronic fatigue and fibromyalgia. Only the recognition and diagnosis of the underlying depression will enable the implementation of appropriate therapeutic interventions. Some recommendations for the use of antidepressant drugs in primary care and the eventual psychiatric consultation are also reviewed. (AU)

Brazilian consensus in enuresis-recomendations for clinical practice

ABSTRACT Introduction Enuresis, defined as an intermittent urinary incontinence that occurs during sleep, is a frequent condition, occurring in about 10% of children at 7 years of age. However, it is frequently neglected by the family and by the primary care provider, leaving many of those children without treatment. Despite of many studies in Enuresis and recent advances in scientific and technological knowledge there is still considerable heterogeneity in evaluation methods and therapeutic approaches. Materials and Methods The board of Pediatric Urology of the Brazilian Society of Urology joined a group of experts and reviewed all important issues on Enuresis and elaborated a draft of the document. On September 2018 the panel met to review, discuss and write a consensus document. Results and Discussion Enuresis is a multifactorial disease that can lead to a diversity of problems for the child and family. Children presenting with Enuresis require careful evaluation and treatment to avoid future psychological and behavioral problems. The panel addressed recommendations on up to date choice of diagnosis evaluation and therapies.

Comparação entre oxibutinina, eletroestimulação do nervo tibial posterior e exercícios perineais no tratamento da síndrome da bexiga hiperativa / Comparación entre oxibutinina, electroestimulación del nervio tibial posterior y ejercicios perineales en el tratamiento del síndrome de la vejiga hiperactiva / Comparison of oxybutynin, electrostimulation of the posterior tibial nerve and perineal exercises in the treatment of overactive bladder syndrome

RESUMO Objetivou-se avaliar a eficácia dos exercícios perineais, da eletroestimulação transcutânea do nervo tibial posterior (ETNTP) e da oxibutinina em mulheres com síndrome da bexiga hiperativa, que é a segunda causa mais comum de incontinência urinária, com sintomas urinários extremamente incômodos que prejudicam a qualidade de vida. Foram randomizadas 65 mulheres, das quais 57 completaram o tratamento. Formaram-se três grupos: o de exercícios perineais, ETNTP e o grupo controle, que utilizou oxibutinina. Os exercícios foram realizados em grupo, nas posições em pé, supino e sentado, duas vezes por semana, com duração de 30 minutos cada sessão, totalizando 12 sessões. Na ETNTP utilizou-se eletrodo transcutâneo posicionado em maléolo medial e outro 10cm acima, com frequência de 10Hz e largura de pulso de 200 microssegundos, por 30 minutos, duas vezes por semana, totalizando 12 sessões. Na medicação as pacientes receberam oxibutinina de 10mg/dia de liberação imediata divididos e duas doses de 5mg/dia, durante 12 semanas consecutivas. Antes e depois dos tratamentos, as pacientes passaram por uma avaliação composta pela análise do diário miccional, avaliação funcional do assoalho pélvico e aplicação de questionário de qualidade de vida OAB-V8. Houve redução da incontinência de urgência em 50%, 70,5% e 41% nos grupos de exercício, ETNTP e oxibutinina, respectivamente, com significância estatística somente da eletroestimulação. As três modalidades de tratamento foram eficazes na melhora da qualidade de vida para a terapêutica em curto prazo, estatisticamente semelhantes entre si.

RESUMEN Se evaluó la eficacia de los ejercicios perineales, de la electroestimulación transcutánea del nervio tibial posterior (ETNTP) y de la oxibutinina en mujeres con síndrome de la vejiga hiperactiva, la segunda causa más común de incontinencia urinaria, con síntomas muy incómodos, que perjudican la calidad de vida. Sesenta y cinco mujeres, de las cuales 57 completaron el tratamiento, formaron tres grupos: el de ejercicios perineales, ETNTP y el grupo de control, que utilizó oxibutinina. Los ejercicios se realizaron en grupo, en las posiciones en pie, supino y sentado, dos veces por semana, con duración de 30 minutos cada sesión, totalizando 12 sesiones. En la ETNTP se utilizó electrodo transcutáneo posicionado en el maléolo medial y otro 10 cm arriba, con frecuencia de 10Hz y ancho de pulso de 200 microsegundos, por 30 minutos, dos veces por semana, totalizando 12 sesiones. En la medicación las pacientes recibieron oxibutinina de 10 mg/día de liberación inmediata, divididos en dos dosis de 5mg/día, durante 12 semanas consecutivas. Antes y después de los tratamientos, las pacientes pasaron por una evaluación compuesta por el análisis del diario miccional, la evaluación funcional del piso pélvico y la aplicación del cuestionario de calidad de vida OAB-V8. Se observó una reducción de la incontinencia de urgencia en un 50%, 70,5% y 41% en los grupos de ejercicio, ETNTP y oxibutinina, respectivamente, con significancia estadística solamente de la electroestimulación. Las tres modalidades de tratamiento fueron eficaces en la mejora de la calidad de vida para la terapéutica a corto plazo y estadísticamente similares.

ABSTRACT The objective of this study was to evaluate the efficacy of perineal exercises, transcutaneous electrostimulation of the posterior tibial nerve (TPTNS) and oxybutynin in women with overactive bladder syndrome, which is the second most common cause of urinary incontinence, with extremely uncomfortable urinary symptoms which impair their quality of life. A total of 65 women were randomized, of whom 57 completed treatment. Three groups were formed: the perineal exercises group, the TPTNS group and the control group, which used oxybutynin. The exercises were performed in groups, in the standing, supine and sitting positions, twice a week in 30-minute sessions, totaling 12 sessions. In the TPTNS group, carried out with 10Hz frequency and 200 microsecond pulse width, a transcutaneous electrode was positioned on the patients' medial malleolus, and another was positioned 10cm above it. The patients of the control group received 10 mg/day doses of immediate release oxybutynin, divided into two 5mg/day doses for 12 consecutive weeks. Before and after the treatments, the patients' voiding diary was analyzed, their pelvic floor was functionally evaluated and they were asked to fill in an OAB-V8 quality of life questionnaire. Urge incontinence was reduced by 50%, 70.5% and 41% in the exercises, TPTNS and oxybutynin groups, respectively, and statistical significance was detected for stimulation only. The three treatment modalities were effective for improving quality of life in the short-term therapy, and were statistically similar to each other.

Development of a Brazilian anticholinergic activity drug scale / Desenvolvimento de uma escala brasileira de medicamentos com atividade anticolinérgica

ABSTRACT Objective To develop a scale of anticholinergic activity drugs used in Brazil, to be applied in health care and pharmacoepidemiology research. Methods We performed a literature review on PubMed/MEDLINE® to identify previously published scales of anticholinergic drugs. This scale started with anticholinergic drugs, and those with known anticholinergic activity as per the 4th level, chemical-therapeutic subgroup, of the Anatomical Therapeutic Chemical classification. We also included drugs with high anticholinergic activity, as described in a list of potentially inappropriate medications for use in older adults, according to the 2015 American Geriatrics Society Beers Criteria. Drugs listed in at least two anticholinergic scales were added. Then we verified which drugs in the previous steps were marketed in Brazil. We assigned a score of 1, 2 and 3, based on their anticholinergic action. Results A total of 273 anticholinergic drugs were identified, of which 125 were included in the scale. We identified 45 (36.0%) drugs with a score of 3, 13 (10.4%) with a score of 2, and 67 (53.6%) with a score of 1. Drugs for the nervous and respiratory systems were the most frequent in the scale. Eight drugs were not present in previous scales. Conclusion The methodology used for development of the Brazilian anticholinergic activity scale is simple, systematized, reproducible and easy to update. The scale allows evaluating the impact of anticholinergic burden on health outcomes, and can potentially contribute to pharmacoepidemiology research, leading to more accurate measurements of anticholinergic activity.

RESUMO Objetivo Desenvolver uma escala de atividade anticolinérgica abrangendo os medicamentos utilizados no Brasil, para aplicação no cuidado em saúde e em pesquisas farmacoepidemiológicas. Métodos Realizou-se revisão da literatura no PubMed/MEDLINE®para identificação das escalas de mensuração da atividade anticolinérgica. Iniciou-se a escala com os fármacos anticolinérgicos e aqueles com atividade anticolinérgica conhecida, relacionados segundo o nível 4, subgrupo químico, na classificação da Anatomical Therapeutic Chemical . Incluíram-se os fármacos com atividade anticolinérgica alta, descritos na lista de medicamentos potencialmente inapropriados para idosos, segundo o 2015 American Geriatrics Society Beers Criteria . Adicionaram-se os medicamentos que constavam em, no mínimo, duas escalas anticolinérgicas. Em seguida, verificaram-se os medicamentos constantes nas etapas anteriores comercializados no Brasil. A magnitude da atividade anticolinérgica foi estabelecida em escores com os valores de 1, 2 e 3. Resultados Foram identificados 273 medicamentos com atividade anticolinérgica, sendo 125 incluídos na escala. Destes, 45 (36,0%) receberam pontuação 3, 13 (10,4%) tiveram pontuação 2, e 67 (53,6%) pontuação 1. A maioria dos medicamentos da escala atuava nos sistemas nervoso e respiratório. Oito fármacos não constavam em escalas prévias. Conclusão A metodologia de desenvolvimento da escala brasileira de atividade anticolinérgica é simples, sistematizada, reprodutível e de fácil atualização. A escala permite avaliar o impacto da carga anticolinérgica nos resultados em saúde e pode contribuir com as pesquisas farmacoepidemiológicas, propiciando mensurações mais exatas da atividade anticolinérgica.

A Report of Rabbit Syndrome Who Benefited from Sigma 1 Agonist Fluvoxamine

Rabbit Syndrome is an uncommon side effect of antipsychotic treatment. Although it is usually associated with typical antipsychotics, it can also be related to atypical antipsychotics. Anticholinergics are the most accepted treatment approach in treating Rabbit Syndrome. Fluvoxamine is a member of selective serotonin reuptake inhibitors and it is a potent agonist of sigma 1 receptors. In this article, we report a Rabbit Syndrome case who has benefited from fluvoxamine, in terms of both depressive disorder and Rabbit Syndrome; and present the data on the effects of sigma 1 agonist fluvoxamine on numerous movement disorders.

Pharmacotherapy for chronic obstructive pulmonary disease

Appropriate pharmacologic therapy can reduce symptoms and risk and severity of exacerbations, as well as improve the health status and exercise tolerance of patients with chronic obstructive pulmonary disease. The most important medications for treating chronic obstructive pulmonary disease are inhaled bronchodilators including beta2-agonist and anticholinergics. Inhaled corticosteroids as anti-inflammatory drug should be considered in certain patients with caution considering risk and benefit. The choice within each class depends on the availability of medication and the patient's responses and preferences. Each treatment regimen needs to be individualized as the relationship between severity of symptoms, airflow limitation and severity of exacerbation can differ between patients.

A Korean Postmarketing Study Assessing the Effectiveness of OnabotulinumtoxinA for the Treatment of Neurogenic Detrusor Overactivity or Idiopathic Overactive Bladder Using a Validated Patient-Reported Outcome Measure / 대한배뇨장애요실금학회지

PURPOSE: OnabotulinumtoxinA has demonstrated efficacy and safety in the treatment of urinary incontinence (UI) associated with neurogenic detrusor overactivity (NDO) and idiopathic overactive bladder (OAB); however, real-world evidence is limited. This postmarketing surveillance study aimed to assess the effectiveness and safety of onabotulinumtoxinA in Korean patients with UI associated with NDO or OAB with an inadequate response or intolerance to anticholinergics. METHODS: Patients received 200 U (NDO) or 100 U (OAB) of onabotulinumtoxinA. Effectiveness (assessed using the validated International Consultation on Incontinence Questionnaire-Short Form [ICIQ-SF]) and safety were assessed for 1–4 months after onabotulinumtoxinA administration. RESULTS: Overall, 686 patients (NDO, 161; OAB, 525) comprised the safety population; of these, 612 patients were analyzed for effectiveness. There was a significant decrease (P5 points from baseline in the ICIQ-SF score was observed in 64.9% and 47.3% of patients in the NDO and OAB groups, respectively. Following treatment, 59.9% in the NDO group and 43.0% in the OAB group were dry. There was no effect of age on effectiveness in either group. Only 10 adverse drug reactions (ADRs) were reported in 5.6% of NDO patients and 20 ADRs in 3.2% of OAB patients. Most ADRs in both groups were related to the lower urinary tract such as dysuria (NDO, 1.2%; OAB, 0.6%) and urinary retention (NDO, 0.6%; OAB, 1.5%). CONCLUSIONS: Effectiveness and safety of onabotulinumtoxinA in Korea in a real-world setting was demonstrated.