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.

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.

O uso de fármacos anticolinérgicos e fatores associados em adultos de meia-idade e idosos / The use of anticholinergic drugs and associated factors in middle-aged adults and the elderly

Resumo O objetivo deste artigo foi descrever o uso de medicamentos anticolinérgicos e possíveis fatores associados ao seu uso em adultos de meia idade e idosos. Trata-se de um estudo transversal em que foram incluídos todos os respondentes de 44 anos ou mais entrevistados em 2015. Foi utilizada a Anticholinergic Drug Scale (ADS) para determinação da carga anticolinérgica (CAC), categorizada em elevada (≥ 3) e não-elevada (< 3). Conduziu-se regressão de Poisson com análise bruta e ajustada para investigar os fatores associados à CAC, com cálculo da razão de prevalência (RP) e intervalo de confiança 95% (IC95%). Constatou-se prevalência de 20,7% de CAC elevada entre os respondentes, maior entre adultos de meia idade (24,1%). Após análise ajustada, mantiveram-se associadas à CAC elevada na faixa etária não idosa a polifarmácia e uso esporádico de dois ou mais medicamentos. Nos idosos, continuaram associados à CAC elevada o uso esporádico de dois ou mais medicamentos e internação no último ano. Os resultados indicam maior prevalência de CAC entre adultos de meia-idade, polimedicados e em uso esporádico de medicamentos, o que sugere que a investigação do uso de anticolinérgicos nessa faixa etária demanda maior atenção.

Abstract The objective of this article was to describe the use of anticholinergic drugs and possible factors associated with their use, in middle-aged adults and in the elderly. This is a cross-sectional study, based on data from a population-based study called VIGICARDIO. All respondents aged 44 or older interviewed in 2015 were included. Anticholinergic Drug Scale (ADS) was used to determine anticholinergic burden (ACB), categorized as significant (≥3) and non-significant (< 3). Poisson regression was conducted with crude and adjusted analysis to investigate the factors associated with ACB. There was a prevalence of 20.7% of significant ACB among respondents, higher among middle-aged adults (24.1%). After adjusted analysis, significant ACB (≥ 3) remained in the non-elderly age group with polypharmacy and sporadic use of two or more drugs. In the elderly, sporadic use of two or more medications and hospitalization in the last year continued to be associated with significant ACB. The results indicate a higher prevalence of ACB among middle-aged adults, polymedicated and in sporadic use of medications, which suggests that the investigation of the use of anticholinergicsin this age group requires greater attention.

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.

[Prevalence of prescription of anticholinergic/sedative burden drugs among older people with dementia living in nursing homes]. / Prevalencia de prescripción de fármacos con carga anticolinérgica/sedante en adultos mayores institucionalizados con demencia.

BACKGROUND AND OBJECTIVE: Dementia is one of the most frequent diseases in the elderly, being its prevalence of up to 64% in institutionalized people. In this population, in addition to antidementia drugs, it is common to prescribe drugs with anticholinergic/sedative burden that, due to their adverse effects, could worsen their functionality and cognitive status. The objective is to estimate the prevalence of the use of drugs with anticholinergic/ sedative burden in institutionalized older adults with dementia and to assess the associated factors. MATERIALS AND METHODS: A cross-sectional study developed in older with dementia living in nursing homes. The prevalence of prescription of anticholinergic/sedative drugs was estimated according to the Drug Burden Index (DBI). A comparative analysis of the DBI score was performed between different types of dementia as well as among various factors and according to the anticholinergic/sedative risk, establishing as a cut-off point of DBI≥1 (high anticholinergic/sedative risk). RESULTS: 178 residents were included. 83.7% had some drug with anticholinergic/sedative burden according to DBI. 50% had a DBI≥1 score. Residents with vascular dementia had a mean DBI of 1.34 (SD 0.84), a significantly higher score than residents with Alzheimer's disease (0.41, 95% CI 0.04-0.78).). Likewise, a higher DBI was associated with more polypharmacy (3.36; 95% CI 2.64-4.08), more falls, hospital admissions and emergency room visits (P<.05). CONCLUSIONS: Polypharmacy and prescription of anticholinergic/sedative drugs is frequent among institutionalized older adults with dementia, finding an association between DBI, falls and hospital admissions or emergency department visits. Therefore, it is necessary to propose interdisciplinary pharmacotherapeutic optimization strategies.

Consistency between anticholinergic burden scales in patients with Sjögren's syndrome / Consistencia entre escalas de carga anticolinérgica en pacientes con síndrome de Sjögren

ABSTRACT Introduction: Sjögren's syndrome is the second most frequent autoimmune rheumatic disease and is characterized by exocrine gland involvement manifesting as sicca symptoms. The objective of this study was to estimate the degree of agreement between three anticholinergic burden scales related to the prescriptions of patients diagnosed with Sjögren's syndrome in Colombia. Materials and methods: An analytical concordance study was conducted. The weighted kappa coefficient with quadratic weights was used to identify consistency between the Anticholinergic Drug Scale (ADS), Anticholinergic Cognitive Burden Scale (ACB) and Anticholinergic Risk Scale (ARS), which address the prescriptions used for 3 months by patients with Sjögren s syndrome, in a population database. Results: A total of 15,696 patients with Sjögren's syndrome were identified, with a mean age of 65.4 ± 13.9 years, and 74.2% were women. A total of 94.1% of the patients received at least one topical lubricant, with carboxymethyl cellulose being the most commonly prescribed (22.9%), while oral pilocarpine was prescribed to 3.5% of patients. The ACB was the tool identified more antimuscarinic prescriptions (37.5%), followed by the ADS (35.3%) and ARS (25.2%). The greatest degree of agreement was found between the ADS and ACB (kappa 0.6520; confidence interval (CI): 0.6393-0.6648). Conclusions: Except for the ADS and ACB, little agreement was found between the three scales gauging the anticholinergic burden. Additional studies are needed to determine how these differences can impact the clinical outcomes of patients.

RESUMEN Introducción: El síndrome de Sjögren es la segunda enfermedad reumática autoinmune más frecuente, caracterizada especialmente por el compromiso de glándulas exocrinas manifestándose con síntomas sicca. El objetivo fue estimar el grado de acuerdo de 3 escalas de carga anticolinérgica en las prescripciones de pacientes con diagnóstico de síndrome de Sjögren en Colombia. Materiales y métodos: Estudio analítico de concordancia. Se empleó el coeficiente Kappa con ponderación cuadrática para identificar la consistencia entre los instrumentos Anticholin-ergic Drug Scale (ADS), Anticholinergic Cognitive Burden Scale (ACB) y Anticholinergic Risk Scale (ARS) de las prescripciones utilizadas durante 3 meses por pacientes con síndrome de Sjögren, a partir de una base de datos poblacional. Resultados: Se identificaron 15.696 pacientes con síndrome de Sjögren, con una edad media de 65,4 ±13,9 anos y el 74,2% de mujeres. El 94,1% recibieron por lo menos un lubricante tópico siendo el más prescrito la carboximetilcelulosa (22,9%), mientras que la pilocarpina oral se formuló en el 3,5% de ellos. La escala ACB fue la herramienta que más prescripciones anti-muscarínicas identificó (37,5%) seguida de la ADS (35,3%) y ARS (25,2%). El mayor grado de acuerdo se presentó entre las escalas ADS-ACB (Kappa: 0,6520; IC: 0,6393-0,6648). Conclusiones: Con excepción de las escalas ADS-ACB, hubo poco acuerdo al comparar las 3 escalas de carga anticolinérgica. Se requieren estudios adicionales para determinar cómo estas diferencias pueden impactar en la validez de los desenlaces clínicos de los pacientes.

Clinical characteristics, prevalence, and factors related to delirium in children of 5 to 14 years of age admitted to intensive care. / Características clínicas, prevalencia y factores asociados al delirium en niños de 5 a 14 años de edad ingresados en cuidados intensivos.

OBJECTIVE: To evaluate the clinical characteristics, prevalence and factors associated with delirium in critical patients from 5 to 14 years of age. DESIGN: An analytical, cross-sectional observational study was made. Delirium was assessed with the Pediatric-Confusion Assessment Method for the Intensive Care Unit (pCAM-ICU) and motor classification was established with the Delirium Rating Scale Revised-98. SETTING: A pediatric Intensive Care Unit. PATIENTS: All those admitted over a one-year period were assessed during the first 24-72h, or when possible in deeply sedated patients. EXCLUSION CRITERIA: Patients in stupor or coma, with severe communication difficulty, subjected to deep sedation throughout admission, and those with denied consent. RESULTS: Twenty-nine of the 156 assessed patients suffered delirium (18.6%) and 55.2% were hypoactive. The neurocognitive alterations evaluated by the pCAM-ICU were similar in the three motor groups. Intellectual disability (OR=17.54; 95%CI: 3.23-95.19), mechanical ventilation (OR=18.80; 95%CI: 4.29-82.28), liver failure (OR=54.88; 95%CI: 4.27-705.33), neurological disease (OR=4.41; 95%CI: 1.23-15.83), anticholinergic drug use (OR=3.23; 95%CI: 1.02-10.26), different psychotropic agents (OR=4.88; 95%CI: 1.42-16.73) and tachycardia (OR=4.74; 95%CI: 1.21-18.51) were associated to delirium according to the logistic regression analysis. CONCLUSION: The frequency of delirium and hypoactivity was high. It is therefore necessary to routinely evaluate patients with standardized instruments. All patients presented with important neurocognitive alterations. Several factors related with the physiopathology of delirium were associated to the diagnosis; some of them are modifiable through the rationalization of medical care.

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.

Anticholinergic drugs and cognitive impairment in the elderly. / Fármacos anticolinérgicos y deterioro cognitivo en el anciano.

OBJECTIVE: Describe the prevalence of the anticholinergic drugs (AD) used in patients who consult in regard to loss of memory. Assess the cognitive and functional repercussion of these drugs. PATIENTS AND METHODS: Retrospective review of the clinic history of the patients who consulted the clinic in 2015 and 2016. We used the Anticholinergic Cognitive Burden Scale. We explored cognition with the Mini Mental State Examination (MMSE) and function with the Barthel Index and the Lawton and Brody Scale. We compared the difference of scale scores between the patients exposed and not exposed to AD. RESULTS: Sample size of 610 patients (mean age=81.1years), 71% female. 37.2% of patients took AD. The mean (SD) difference between exposed and not exposed patients and the year-on-year worsening rate of the Barthel Index and the Lawton and Brody Scale and MMSE were -4 (4.5), -0.3 (0.4) and -1 (0.9), respectively. CONCLUSIONS: One third of patients who consulted for cognitive loss are taking AD. Patients exposed to AD show a greater tendency to impairment.

Efficacy and safety of tiotropium bromide in chronic obstructive pulmonary disease: a systematic review of randomized clinical trials / Eficácia e segurança do brometo de tiotrópio na doença pulmonar obstrutiva crônica. Revisão sistemática de ensaios clínicos randomizados

Chronic obstructive pulmonary disease (COPD) is among the most prevalent pulmonary diseases. This study aimed at assessing the efficacy and safety of anticholinergic tiotropium bromide (TB) in Chronic obstructive pulmonary disease patients. This is a systematic review of randomized clinical trials performed in the Brazilian Cochrane Center. Electronic database searched: Cochrane library, Medline, LILACS, Pubmed. There were no language, date or other restrictions. Participants: Patients with Chronic obstructive pulmonary disease. Intervention: tiotropium bromide. Comparison: Other bronchodilators or placebo. Outcomes: Mortality, Chronic obstructive pulmonary disease exacerbation, hospitalizations, adverse effects. Results: 14 studies were included in this systematic review. Mortality was lower in the tiotropium bromide group when compared with the salmeterol group [statistical significance: relative risk (RR) 0.16, confidence interval 95% (CI) 0.03 to 0.89, number needed to treat (NNT) of 100]. There was not a statistical difference in the mortality outcome in the comparison between tiotropium bromide and placebo groups (RR 0.88, CI 0.74 to 1.06). Chronic obstructive pulmonary disease exacerbation decreases significantly in the tiotropium bromide group when compared to placebo (statistical significance: RR 0.85, CI 0.77 to 0.93, NNT 25), but in comparison to the salmeterol group there was no statistical difference (RR 0.93, CI 0.80 to 1.08). The number of hospitalizations was lower in the tiotropium bromide group than in the placebo group (statistical significance:RR 0.77, CI 0.59 to 0.99, NNT 50). The results indicate that tiotropium bromide is an effective once-daily bronchodilator. Tiotropium bromide was associated with consistent health benefits, including reduced chronic obstructive pulmonary disease exacerbations, hospitalizations and even mortality when compared with salmeterol.(AU)

A doença pulmonar obstrutiva crônica está entre as doenças pulmonares mais prevalentes. O objetivo deste estudo foi verificar a eficácia e segurança do brometo de tiotrópio em pacientes com doença pulmonar obstrutiva crônica. Trata-se de revisão sistemática de ensaios clínicos randomizados realizada no Centro Cochrane do Brasil. A estratégia de busca eletrônica foi realizada nos nas bases LILACS, MEDLINE, Biblioteca Cochrane, PubMed. Não houve restrições à linguagem e nem à data. Participaram pacientes com doença pulmonar obstrutiva crônica. A intervenção foi o uso de brometo de tiotrópio comparado a outros broncodilatadores ou placebo. Os desfechos analisados foram mortalidade, exacerbações da doença pulmonar obstrutiva crônica, hospitalização e efeitos adversos. A mortalidade foi menor no grupo brometo de tiotrópio quando comparado com o grupo salmeterol (significância estatística: risco relativo de 0,16; intervalo de confiança de 95% de 0,03-0,89, número necessário para tratar de 100). Não houve diferença estatística no desfecho mortalidade na comparação entre os grupos brometo de tiotrópio e placebo (risco relativo de 0,88; intervalo de confiança de 95% de 0,74-1,06). As exacerbações da doença pulmonar obstrutiva crônica diminuíram significantemente no grupo brometo de tiotrópio quando comparado ao placebo (significância estatística: risco relativo de 0,85; intervalo de confiança de 95% de 0,77-0,93; número necessário para tratar de 25), porém, quando comparado ao salmeterol não obteve significância estatística (risco relativo de 0,93; intervalo de confiança de 95% 0,80-1,08). O número de hospitalizações foi menor no grupo brometo de tiotrópio do que no grupo placebo (significância estatística: risco relativo de 0,77; intervalo de confiança de 95% 0,59-0,99; número necessário para tratar de 50). Os resultados indicam que o brometo de tiotrópio é um broncodilatador eficaz em dose única diária. O brometo de tiotrópio traz benefícios à saúde com resultados consistentes, incluindo redução de exacerbações da doença pulmonar obstrutiva crônica, internações e até mesmo a mortalidade quando comparados com salmeterol.(AU)

Manejo médico de la distonía

Para el manejo médico de la distonía se han utilizado tradicionalmente varios fármacos encaminados a disminuir esta condición y a mejorar la calidad de vida. Las terapias orales solas o combinadas proporcionan control parcial de los síntomas y en la mayoría de los casos hay que recurrir a terapias invasivas.

SUMMARY During the last years, several drugs has been tried in order to try to diminish the impact of this condition and improve the quality of life of patients who suffer from dystonia. Oral therapy alone or in combination, generates only partial symptom relief and most of the cases end up requiring other more invasive therapies.

Manejo médico de la distonía / Medical management of dystonia

RESUMEN Para el manejo médico de la distonía se han utilizado tradicionalmente varios fármacos encaminados a disminuir esta condición y a mejorar la calidad de vida. Las terapias orales solas o combinadas proporcionan control parcial de los síntomas y en la mayoría de los casos hay que recurrir a terapias invasivas.

SUMMARY During the last years, several drugs has been tried in order to try to diminish the impact of this condition and improve the quality of life of patients who suffer from dystonia. Oral therapy alone or in combination, generates only partial symptom relief and most of the cases end up requiring other more invasive therapies.

Efeitos da carga anticolinérgica cognitiva em idosos ­ uma revisão integrativa / Effect of anticholinergic cognitive burden in the elderly ­ an integrative review

Idosos são mais susceptíveis aos efeitos adversos cognitivos de fármacos com atividade anticolinérgica. Isso se deve a fatores associados à velhice, como comprometimento da atividade colinérgica central, aumento da permeabilidade da barreira hematoencefálica, redução do metabolismo hepático e da excreção renal e polifarmácia. A escala de Carga Anticolinérgica Cognitiva (ACB) foi elaborada com o intuito de reduzir a ocorrência eventos adversos cognitivos à farmacoterapia, como declínio cognitivo, demência e delírio. O objetivo desta revisão integrativa foi reunir achados obtidos em estudos clínicos sobre a associação entre alterações cognitivas e ACB por meio da escala. A busca nas bases MEDLINE/PubMed e BVS-Bireme gerou 11 artigos completos em inglês. Sete são longitudinais, três transversais e um observacional. Oito foram conduzidos nos Estados Unidos. Nove de 10 evidenciaram a relação entre ACB e déficit cognitivo. O MMSE foi o teste de avaliação cognitiva mais usado. As evidências mostram a importância da revisão da farmacoterapia de todo paciente com déficit cognitivo ou delírio. Deve-se evitar assumir que o declínio cognitivo é demência até as possíveis causas farmacológicas tenham sido descartadas. (AU)

Elderly people are more susceptible to cognitive adverse effects of medications with anticholinergic activity. This is due to factors associated with aging, such as decline in central cholinergic activity, increase in blood-brain barrier permeability, decline in hepatic and renal metabolism and polypharmacy. The Anticholinergic Cognitive Burden (ACB) scale was developed reduce the risk for developing adverse cognitive outcomes such as cognitive impairment, dementia and delirium. The purpose of this integrative review is to bring together findings from clinical studies on the association between cognitive impairment and ACB scale. The search in MEDLINE/PubMed and BVS-Medicine bases generated 11 full articles in English. Seven were longitudinal, three transversal and one observational. Eight of them were conducted in the United States. Nine of 10 showed the relationship between the ACB and cognitive impairment due to at least one moderate or severe anticholinergic medication or due to concomitant use of multiple medications. MMSE was the most commonly cognitive assessment. Evidence shows the importance of the review of pharmacotherapy of all patients with cognitive impairment or delirium. It is important not to assume that cognitive decline is dementia until pharmacologic causes have been excluded. (AU)

Applicability of Anticholinergic Risk Scale in hospitalized elderly persons / Aplicabilidade da Escala de Risco Anticolinérgico em idosos hospitalizados

Abstract Objective: to define the applicability of the Anticholinergic Risk Scale (ARS) as a risk indicator of delirium in hospitalized elderly persons. Method: the medical records of elderly patients hospitalized in the medical wards of a teaching hospital were analyzed with the ARS, translated and adapted for medicines used in Brazil. The version of the Confusion Assessment Method (CAM) for the clinical diagnosis of delirium translated and validated by Fabbri et al. was used. Individuals aged ≥60 years were included in the evaluation of drug use. The sample was divided by gender and age to analyze the effect of these variables on the use of anticholinergic drugs based on the ARS, and association with delirium. Results: 123 elderly persons, 47 men and 76 women, with a mean age of 72.7(±9.2) years were included. The average consumption of drugs not listed in the ARS (some with anticholinergic action as Ipratropium and Scopolamine) was 6.1(±3.0) and the average number of drugs used listed in the ARS (Metoclopramide, Ranitidine, Atropine, Haloperidol and Risperidone) was 0.9±0.6. Four elderly persons had a score ≥3 (3.3% of total cases). Delirium was observed in 27 patients (21.9% of the total), none of whom scored more than two ARS points. There was no statistical significance regarding gender, age and delirium. Conclusion: the average score of the ARS was low among this population, and did not correlate with delirium. The ARS does not cover all anticholinergics, meaning this study should be repeated in a geriatric ward for comparison. AU

Resumo Objetivo: definir a aplicabilidade da Escala de Risco Anticolinérgico (ARS) pelo grau de risco anticolinérgico, como indicador de risco de delirium em idosos hospitalizados. Método: análise de prontuários ao término da internação de idosos hospitalizados em leitos de clínica médica de hospital de ensino pela ARS. Traduziu-se e adaptou-se a ARS aos medicamentos em uso no Brasil. Utilizou-se a versão traduzida e validada por Fabbri et al. do Confusion Assessment Method (CAM) para o diagnóstico clínico de delirium. Dividiu-se a casuística por sexo e por idade para análise dessas variáveis quanto ao uso de medicamentos anticolinérgicos pela ARS e a associação com delirium. Resultados : foram analisados os prontuários de 123 idosos com idade média de 72,7 (±9,2) anos. Consumo médio de 6,1 (±3,0) medicamentos não listados na ARS (alguns com ação anticolinérgica como Ipratrópio e Escopolamina) e de 0,9 (±0,6) listados (Metoclopramida, Ranitidina, Atropina, Haloperidol e Risperidona). Pontuação ≥3 em quatro idosos (3,3% do total de casos). Observou-se delirium em 27 pacientes (21,9% do total), nenhum deles com mais de 2 pontos na ARS. Não houve significância estatística na associação entre delirium em relação ao sexo e a idade. Conclusão: a pontuação média da ARS foi baixa na população estudada, não se correlacionando ao delirium. A ARS não abrange todos os anticolinérgicos, merecendo este estudo desdobramento em enfermaria geriátrica para efeito comparativo. AU

Patrones de prescripción de broncodilatadores y corticoides inhalados en pacientes adultos de Colombia / Prescription patterns of bronchodilators and inhaled corticosteroids in adults of Colombia

Introducción: las enfermedades pulmonares obstructivas son frecuentes en pacientes mayores de 40 años y son causa de alta morbimortalidad a nivel mundial. En el presente estudio se describen los patrones de prescripción de medicamentos para su tratamiento en pacientes de Colombia. Material y métodos: estudio descriptivo observacional con pacientes, mayores de 40 años de ambos sexos, afiliados al Sistema General de Seguridad Social en Salud, en tratamiento continuo con broncodilatadores y/o corticoides inhalados entre septiembre y diciembre del año 2013, seleccionados a partir de una base de datos de dispensación de 6.5 millones de personas. Se recolectaron variables sociodemográficas, farmacológicas (fármacos con sus dosis diarias definidas), medicamentos concomitantes y clínicas (comorbilidades). Análisis mediante SPSS 22. Resultados: se incluyeron 6856 pacientes con una edad promedio de 73.8 ± 11.3 años, 54%fueron mujeres. Del total de pacientes 17.2% recibían monoterapia y 82.8% terapia combinada. El 74.3% de sujetos recibía β2-adrenérgicos, la mayoría (81.5%) de corta duración (BDCA), mientras que 33.3% de larga acción (BDLA). El 73.1% recibía anticolinérgicos distribuidos entre ipratropio (87.1%) y tiotropio (16.9%) y 71.7% recibía corticoides inhalados. Los medicamentos prescritos concomitantemente con mayor frecuencia fueron antihipertensivos (68.9%), antiulcerosos (56.1%) e hipolipemiantes (46.2%). Tener entre 40 y 55 o más de 80 años, recibir alguna medicación concomitante, utilizar corticoides inhalados, emplear monoterapia broncodilatadora y ser tratado en Bogotá y Cali, se asociaron de manera estadísticamente significativa con menor riesgo de recibir BDLA. Conclusiones: predomina la prescripción de BDCA, pese al limitado beneficio clínico reportado. La mayoría de broncodilatadores se emplean a dosis superiores a las recomendadas. Se considera necesario establecer estrategias educativas que mejoren los hábitos de prescripción. (Acta Med Colomb 2015; 40: 218-226).

Introduction: obstructive lung diseases are common in patients older than 40 years and cause high morbidity and mortality worldwide. The patterns of drugs prescription for its treatment in Colombian patients are described in this study. Methods: descriptive observational study with patients over 40 years of both sexes, members of the General System of Social Security in Health, in continuous treatment with bronchodilators and / or inhaled steroids between September and December 2013, selected from a dispensing database of 6.5 million people. Sociodemographic and pharmacological variables (drugs with defined daily doses), concomitant medications and co-morbidities were collected. Analysis using SPSS 22. Results: A total of 6856 patients were included with a mean age of 73.8±11.3 years, 54% were women. Of the total of patients, 17.2% received monotherapy and 82.8% combined therapy. 74.3% of subjects received β2-adrenergics, most (81.5%) short-acting bronchodilators, while33.3% long acting bronchodilators. 73.1% received anticholinergics distributed between ipratropium (87.1%) and tiotropium (16.9%) and 71.7% received inhaled steroids. The medications that were most often concomitantly prescribed, were antihypertensive (68.9%), antiulcerants (56.1%) and lipid lowering drugs (46.2%). To be between 40 and 55 or over 80 years, receive any concomitant medication, inhaled corticosteroid use, bronchodilator monotherapy use and being treated in Bogota and Cali, was statistically significantly associated with lower risk of receiving long-acting bronchodilators. Conclusions: the prescription of short-acting bronchodilators predominate despite the limited clinical benefit reported. Most bronchodilators are used at higher than recommended doses. It is necessary to establish educational strategies to improve prescribing habits. (Acta Med Colomb 2015; 40: 218-226).

Prevalencia de interacciones potenciales evitables entre antidepresivos y otros medicamentos en pacientes colombianos / Prevalence of Avoidable Potential Interactions Between Antidepressants and Other Drugs in Colombian Patients

Objetivos: Determinar potenciales interacciones medicamentosas con antidepresivos y otros fármacos que pueden generar problemas relacionados con medicamentos mediante la búsqueda activa en bases de datos de pacientes afiliados al Sistema General de Seguridad Social en Salud. Métodos: Estudio descriptivo a partir de las bases de datos de dispensación de medicamentos de Audifarma S.A. a unos 4 millones de usuarios del pa ís; se hizo una revisión sistemática de potenciales interacciones de antidepresivos entre sí y con anticolinérgicos en los meses de octubre a noviembre y con tramadol durante todo el a ño 2010. Resultados: Se identificó un promedio mensual de 114.465 usuarios de antidepresivos. De estos, 5.776 (5,0 %) recibían dos antidepresivos simultáneamente y 178 (0,2 %), tres. La combinación más frecuente fue fluoxetina + trazodona (n = 3.235, el 56,9 % de los casos). A unos 1.127 (1,0 %) pacientes se les prescribió de manera simultánea un anticolinérgico. A 2.523 (2,1 %) usuarios se les dispensó al mismo tiempo tramadol, con lo que se elevaba el riesgo de aparición de síndrome serotoninérgico. Conclusiones: Las interacciones medicamentosas representan un riesgo potencial que muchas veces los médicos subestiman. La farmacovigilancia es una herramienta útil para optimizar recursos y prevenir resultados negativos relacionados con la medicación. Se recomienda considerar la búsqueda sistematizada para reforzar los programas de vigilancia de uso racional de medicamentos en el pa ís.

Objectives: To determine the possible drugs interactions with antidepressive agents in data bases of patients in the Health Insurance System of Colombia. Methods: From data bases of about 4 million users in Colombia, a systematic review of drugs dispensation statistics was made to identify drug interactions between antidepressive agents, cholinergic antagonists and tramadol in 2010. Results: We identified 114,465 monthly users of antidepressive agents. Of these, 5776 (5.0 %) received two, and 178 (0.2 %) received three antidepressive agents simultaneously. The most frequent combination was fluoxetine+trazodone (n =3235; 56.9 % of cases). About 1127 (1.0 %) patients were prescribed a cholinergic antagonist simultaneously; 2523 (2.1 %) users were dispensed tramadol at the same time, while raising the risk of serotonin syndrome. Conclusions: Drug interactions represent a potential risk that is often underestimated by physicians. Pharmacovigilance is a useful tool to optimize resources and prevent negative outcomes associated with medication. It is recommended that systematic search is made to enhance surveillance programs for the rational use of medicines in this country.

[Prevalence of Avoidable Potential Interactions Between Antidepressants and Other Drugs in Colombian Patients]. / Prevalencia de interacciones potenciales evitables entre antidepresivos y otros medicamentos en pacientes colombianos.

OBJECTIVES: To determine the possible drugs interactions with antidepressive agents in data bases of patients in the Health Insurance System of Colombia. METHODS: From data bases of about 4 million users in Colombia, a systematic review of drugs dispensation statistics was made to identify drug interactions between antidepressive agents, cholinergic antagonists and tramadol in 2010. RESULTS: We identified 114,465 monthly users of antidepressive agents. Of these, 5776 (5.0%) received two, and 178 (0.2%) received three antidepressive agents simultaneously. The most frequent combination was fluoxetine+trazodone (n=3235; 56.9% of cases). About 1127 (1.0%) patients were prescribed a cholinergic antagonist simultaneously; 2523 (2.1%) users were dispensed tramadol at the same time, while raising the risk of serotonin syndrome. CONCLUSIONS: Drug interactions represent a potential risk that is often underestimated by physicians. Pharmacovigilance is a useful tool to optimize resources and prevent negative outcomes associated with medication. It is recommended that systematic search is made to enhance surveillance programs for the rational use of medicines in this country.

Abuso de anticolinérgicos en pacientes con esquizofrenia: reportes de caso y breve revisión de la literatura / Abuse of anticholinergic drugsin schizophrenic patients: case reports and brief literature review

Introducción: El abuso de fármacos anticolinérgicos es un problema que ocasionalmente se ha reportado en la literatura médica aunque al parecer su frecuencia puede ser mayor a lo considerado usualmente; sobre todo en pacientes con esquizofrenia, donde se indica anticolinérgicos para contrarrestar los síntomas extrapiramidales secundarios al uso de antipsicóticos, es donde se detectan la mayoría de casos. Método: reportamos cuatro casos de pacientes con esquizofrenia que abusaban de anticolinérgicos y revisamos la literatura pertinente. Resultados: El uso excesivo de anticolinérgicos por pacientes con esquizofrenia ha sido atribuido a su intento de controlar síntomas depresivos o negativos o la disforia inducida por antipsicóticos sin embargo no hay usualmente correlación entre el uso de antipsicóticos y el abuso de anticolinérgicos; por tanto, es menester considerar el potencial de abuso de los anticolinérgicos. Conclusión: Se impone revisar la indiscriminada prescripción de fármacos anticolinérgicos a los usuarios de antipsicóticos de modo tal que el riesgo de abuso se detecte tempranamente.

Introduction: The abuse of anticholinergic drugs is a problem occasionally reported in the medical literature although it has been suggested that its frequency is higher than usually considered. Since the main indication of anticholinergics today is to alleviate extrapyramidal symptoms in patients using antipsychotics, several cases of excessive use of anticholinergic drugs in schizophrenic patients are detected in psychiatric practice. Method: We report four schizophrenic patients who used anticholinergic drugs in excessive doses and we review the respective bibliography. Results: The excessive use of anticholinergic drugs by schizophrenic patients has been attributed to their attempt to counteract their negative symptoms, depressive symptoms or the dysphoria induced by antipsychotics, however, there is not usually correlation between the use of neuroleptics and anticholinergics abuse; therefore it is necessary to take into account the addictive potential of antiparkinson drugs. Conclusion: We advise to review the extensive prescription of anticholinergic drugs to antipsychotic users so the risk of anticholinergic drug abuse can be detected early.