Machine-learning model for the prediction of acute orthostatic hypotension after levodopa administration.

BACKGROUND: Levodopa could induce orthostatic hypotension (OH) in Parkinson's disease (PD) patients. Accurate prediction of acute OH post levodopa (AOHPL) is important for rational drug use in PD patients. Here, we develop and validate a prediction model of AOHPL to facilitate physicians in identifying patients at higher probability of developing AOHPL. METHODS: The study involved 497 PD inpatients who underwent a levodopa challenge test (LCT) and the supine-to-standing test (STS) four times during LCT. Patients were divided into two groups based on whether OH occurred during levodopa effectiveness (AOHPL) or not (non-AOHPL). The dataset was randomly split into training (80%) and independent test data (20%). Several models were trained and compared for discrimination between AOHPL and non-AOHPL. Final model was evaluated on independent test data. Shapley additive explanations (SHAP) values were employed to reveal how variables explain specific predictions for given observations in the independent test data. RESULTS: We included 180 PD patients without AOHPL and 194 PD patients with AOHPL to develop and validate predictive models. Random Forest was selected as our final model as its leave-one-out cross validation performance [AUC_ROC 0.776, accuracy 73.6%, sensitivity 71.6%, specificity 75.7%] outperformed other models. The most crucial features in this predictive model were the maximal SBP drop and DBP drop of STS before medication (ΔSBP/ΔDBP). We achieved a prediction accuracy of 72% on independent test data. ΔSBP, ΔDBP, and standing mean artery pressure were the top three variables that contributed most to the predictions across all individual observations in the independent test data. CONCLUSIONS: The validated classifier could serve as a valuable tool for clinicians, offering the probability of a patient developing AOHPL at an early stage. This supports clinical decision-making, potentially enhancing the quality of life for PD patients.

Adverse reactions after large-scale treatment of onchocerciasis with ivermectin: combined results from eight community trials

Eight community trials were carried out by the Onchocerciasis Control Programme in West Africa to determine the safety of the new microfilaricide ivermectin during large-scale treatment of onchocersiasis. The trial areas were located in eight different countries and varied greatly in endemicity level; a total of 50,929 persons were treated and monitored for 72 hours. Overall treatment coverage was 60 percent of the census population, the main reasons for non-treatment being the exclusion criteria. Of those treated, 9 percent reported with adverse reactions, 2.4 percent with moderate reactions, and 0.24 percent with severe reactions. Most reactions were reported during the first day of follow-up, the most frequent severe reaction being severe symptomatic postural hypotension (in 49 cases). Three cases of severe dyspnoea were life-threatening but their relationship with ivermectin treatment is uncertain. The incidence of adverse reactions was directly related to skin microfilarial load and was highest in the foci with the highest endemicity levels. Treatment resulted in 98 percent reductions in mean microfilarial loads at all endemicity levels. The benefit of treatment largely compensated for the discomfort due to adverse reactions, which were all transient and managed successfully. Ivermectin thus appears to be ...(AU)

Diagnóstico e tratamento da depressäo no paciente de risco-idoso e cardiopata / Diagnosis and treatment of depression in the elderly and heart disease patients

Este artigo revê o diagnóstico e tratamento da depressäo no paciente de risco-idoso e cardiopata. O diagnóstico segue as orientaçöes do DSM-III-R. Entretanto, maiores dificuldades säo encontradas no reconhecimento da depressäo, particularmente nos idosos hospitalizados, devido a vários fatores tais cmo múltiplas doenças e polifarmácia associadas. Isto faz com que muitos pacientes näo sejam diagnosticados e, consequentemente, näo tratados. Os antidepressivos, particularmente os tricíclicos, constituem a terapêutica de escolha nos quadros depressivos maiores; sendo a eletroconvulsoterapia reservada para casos de necessidade de resposta mais rápida, de näo-resposta, ou de intolerância aos Ads. Os IMAO e os AD de 2º geraçäo näo foram ainda adequadamente estudados no deprimido cardiopata, näo se conhecendo ainda a sua segurança neste grupo de risco. Há evidências de que os ADTs em doses terapêuticas diminuem o risco de mortalidade cardiovascular em pacientes portadores de depressäo maior. Näo obstante, muitos pacientes de risco näo säo adequadamente tratados por preconceitos, em geral infundados, acerca da possível cardiotoxidade destes fármacos. Os efeitos cardiovasculares destes medicamentos, em doses terapêuticas e tóxicas, säo revistos. Pretendemos com esta revisäo desmistificar os efeitos cardiovasculares dos ADTs em doses terapêuticas assim como a aplicaçäo da ECT em deprimidos de risco (idosos e cardiopatas)

Programa de Ansiedade e Depressäo-UFRJ. Série Psicofarmacologia. 11: IMAOs no tratamento da depressäo do paciente idoso refratário / MAOIs in the treatment of depression of refractory geriatric patient

Os inibidores da monoaminoxidase (IMAOs), nos últimos 15 anos, vêm sendo reabilitados dentro da psiquiatria. Por exemplo, considera-se, atualmente, que sejam agentes de primeira linha na depressäo atípica, fobia social e nos pacientes resistentes ou refratários aos antidepressivos tricíclicos (ADTs). Há indicaçöes ainda controvertidas, tal como sua utilizaçäo no idoso, onde o próprio fabricante da tranilcipromina contra-indica seu uso. Contudo, a depressäo no idoso muitas vezes cursa com elevada morbidade-mortalidade, existindo também um grupo significativo de pacientes apresentando refratariedade ou intolerância aos efeitos indesejáveis de antidepressivos como os tricíclicos, o que justifica alternativas como os IMAOs. Fez-se revisäo da literatura sobre a eficácia e segurança dos IMAOs no paciente geriátrico deprimido, ilustrando com quatro casos tratados no Programa de Ansiedade e Depressäo - UFRJ. Localizaram-se quatro ensaios abertos e três duplos-cegos, controlados, todos com resultados favoráveis em termos de eficácia, constituindo a hipotensäo ortostática o efeito indesejável mais comum e mais trabalhoso. Conclui-se que os IMAOs podem ser tratamento seguro e eficaz nessa faixa etária, na medida em que os doentes sigam dieta com baixa concentraçäo de tiramina e evitem drogas simpaticomiméticas