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Background Huntington's disease (HD) is a rare neurodegenerative disorder with protean clinical manifestations. Its management is challenging, consisting mainly of off-label treatments. Objectives The International Parkinson and Movement Disorder Society commissioned a task force to review and evaluate the evidence of available therapies for HD gene expansion carriers. Methods We followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Eligible randomized controlled trials were identified via an electronic search of the CENTRAL, MEDLINE, and EMBASE databases. All eligible trials that evaluated one or more of 33 predetermined clinical questions were included. Risk of bias was evaluated using the Cochrane Risk of Bias tool. A framework was adapted to allow for efficacy and safety conclusions to be drawn from the balance between the GRADE level of evidence and the importance of the benefit/harm of the intervention. Results Twenty-two eligible studies involving 17 interventions were included, providing data to address 8 clinical questions. These data supported a likely effect of deutetrabenazine on motor impairment, chorea, and dystonia and of tetrabenazine on chorea. The data did not support a disease-modifying effect for premanifest and manifest HD. There was no eligible evidence to support the use of specific treatments for depression, psychosis, irritability, apathy, or suicidality. Similarly, no evidence was eligible to support the use of physiotherapy, occupational therapy, exercise, dietary, or surgical treatments. Conclusions Data for therapeutic interventions in HD are limited and support only the use of VMAT2 inhibitors for specific motor symptoms. (c) 2021 International Parkinson and Movement Disorder Society

RESUMO A nutrição parentérica (NP) desempenha um papel vital em doentes críticos, sendo muitas vezes necessária a sua preparação personalizada, ajustada às necessidades de doentes com carências específicas. A manipulação de NP poderá ser realizada de forma manual ou automatizada, requerendo sempre condições asséticas e pessoal treinado. A implementação de um sistema automatizado requer uma análise cuidada da sua necessidade/justificação, de forma a que, baseado em fundamentação adequada, se estruture um plano exequível. A monitorização do desempenho do sistema automatizado é um processo fundamental de validação farmacêutica. Nos Serviços Farmacêuticos (SF) do Centro Hospitalar e Universitário de São João (CHUSJ), elaborou-se um estudo de controlo de qualidade gravimétrico antes e após implementação do sistema automatizado, no sentido de monitorizar a precisão dos resultados obtidos para este ensaio de verificação. Como resultados estatísticos, o método de enchimento automatizado relacionou-se com a menor média para o desvio ao peso teórico, assim como menor desvio padrão, corroborando uma menor percentagem de erro e também uma menor dispersão dos resultados. Da análise dos resultados obtidos concluiu-se que a implementação da automatização se traduziu em melhorias a nível de precisão de resultados para o controlo gravimétrico das bolsas nutritivas, aumentando a segurança das misturas produzidas e, consequentemente, a qualidade dos cuidados prestados ao doente. É de elevada importância que se implementem procedimentos de validação do desempenho do sistema automatizado, como foi o caso, sendo que deverão ser complementados com outro tipo de avaliações, preferencialmente realizadas por entidades externas à instituição em causa.

Background Changes in phosphodiesterase 10A enzyme levels may be a suitable biomarker of disease progression in Huntington's disease. Objectives To evaluate phosphodiesterase 10A PET imaging as a biomarker of HD progression using the radioligand, [18 F]MNI-659. Methods The cross-sectional study (NCT02061722) included 45 Huntington's disease gene-expansion carriers stratified into four disease stages (early and late premanifest and Huntington's disease stages 1 and 2) and 45 age- and sex-matched healthy controls. The primary analysis compared striatal and pallidal phosphodiesterase 10A availability between Huntington's disease gene-expansion carriers and healthy controls as assessed by [18 F]MNI-659 binding. We assessed changes in phosphodiesterase 10A expression using several PET methodologies and compared with previously proposed measures of Huntington's disease progression (PET imaging of D2/3 receptors and anatomical volume loss on MRI). The longitudinal follow-up study (NCT02956148) continued evaluation of phosphodiesterase 10A availability in 35 Huntington's disease gene-expansion carriers at a mean of 18 months from baseline of the cross-sectional study. Results Primary analyses revealed that phosphodiesterase 10A availability in caudate, putamen, and globus pallidus was significantly lower in Huntington's disease gene-expansion carriers versus healthy controls across all stages. Striatal and pallidal phosphodiesterase 10A availability progressively declined in the premanifest stages and appeared to plateau between stages 1 and 2. The percentage decline of phosphodiesterase 10A availability measured cross-sectionally between Huntington's disease gene-expansion carriers and healthy controls was greater than that demonstrated by D2/3 receptor availability or volumetric changes. Annualized rates of phosphodiesterase 10A change showed a statistically significant decline between the cross-sectional study and follow-up. Conclusions [18 F]MNI-659 PET imaging is a biologically plausible biomarker of Huntington's disease progression that is more sensitive than the dopamine-receptor and volumetric methods currently used. © 2020 International Parkinson and Movement Disorder Society.

PURPOSE Operable triple-negative breast cancers (TNBCs) have a higher risk of relapse than non-TNBCs with standard therapy. The GEICAM/2003-11_CIBOMA/2004-01 trial explored extended adjuvant capecitabine after completion of standard chemotherapy in patients with early TNBC. PATIENTS AND METHODS Eligible patients were those with operable, node-positive-or node negative with tumor 1 cm or greater-TNBC, with prior anthracycline- and/or taxane-containing chemotherapy. After central confirmation of TNBC status by immunohistochemistry, patients were randomly assigned to either capecitabine or observation. Stratification factors included institution, prior taxane-based therapy, involved axillary lymph nodes, and centrally determined phenotype (basal v nonbasal, according to cytokeratins 5/6 and/or epidermal growth factor receptor positivity by immunohistochemistry). The primary objective was to compare disease-free survival (DFS) between both arms. RESULTS Eight hundred seventy-six patients were randomly assigned to capecitabine (n = 448) or observation (n = 428). Median age was 49 years, 55.9% were lymph node negative, 73.9% had a basal phenotype, and 67.5% received previous anthracyclines plus taxanes. Median length of follow-up was 7.3 years. DFS was not significantly prolonged with capecitabine versus observation [hazard ratio (HR), 0.82; 95% CI, 0.63 to 1.06; P = .136]. In a preplanned subgroup analysis, nonbasal patients seemed to derive benefit from the addition of capecitabine with a DFS HR of 0.53 versus 0.94 in those with basal phenotype (interaction test P = .0694) and an HR for overall survival of 0.42 versus 1.23 in basal phenotype (interaction test P = .0052). Tolerance of capecitabine was as expected, with 75.2% of patients completing the planned 8 cycles. CONCLUSION This study failed to show a statistically significant increase in DFS by adding extended capecitabine to standard chemotherapy in patients with early TNBC. In a preplanned subset analysis, patients with nonbasal phenotype seemed to obtain benefit with capecitabine, although this will require additional validation. (C) 2019 by American Society of Clinical Oncology