Exploratory analyses of treatment subgroup interaction by PD-L1 status and according to PD-L1 expression in the JAVELIN Bladder 100 trial.

PURPOSE: Post hoc analysis of the JAVELIN Bladder 100 trial of avelumab maintenance in locally advanced/metastatic urothelial carcinoma (la/mUC) to determine the interaction by programmed death ligand 1 (PD-L1) status for overall survival (OS), and additional analyses of survival per a different PD-L1 expression cutoff of ≥ 1% in tumor cells or immune cells (TC/IC). METHODS: JAVELIN Bladder 100 data were used for the analysis of the interaction by PD-L1 status (per cutoff used in the trial) for OS and, additionally, OS and progression-free survival (PFS) analyses per a different ≥ 1% TC/IC PD-L1 expression cutoff (Ventana SP263 assay). RESULTS: No significant interaction between treatment and PD-L1 status was observed for OS. Clinically meaningful and robust survival data were observed in favor of avelumab using the different ≥ 1% TC/IC PD-L1 expression cutoff. CONCLUSIONS: These results demonstrate the benefit of avelumab maintenance in la/mUC regardless of PD-L1 expression, consistent with approved labels.

Tuberculosis treatment intermittency in the continuation phase and mortality in HIV-positive persons receiving antiretroviral therapy.

BACKGROUND: Some tuberculosis (TB) treatment guidelines recommend daily TB treatment in both the intensive and continuation phases of treatment in HIV-positive persons to decrease the risk of relapse and acquired drug resistance. However, guidelines vary across countries, and treatment is given 7, 5, 3, or 2 days/week. The effect of TB treatment intermittency in the continuation phase on mortality in HIV-positive persons on antiretroviral therapy (ART), is not well-described. METHODS: We conducted an observational cohort study among HIV-positive adults treated for TB between 2000 and 2018 and after enrollment into the Caribbean, Central, and South America network for HIV epidemiology (CCASAnet; Brazil, Chile, Haiti, Honduras, Mexico and Peru). All received standard TB therapy (2-month initiation phase of daily isoniazid, rifampin or rifabutin, pyrazinamide ± ethambutol) and continuation phase of isoniazid and rifampin or rifabutin, administered concomitantly with ART. Known timing of ART and TB treatment were also inclusion criteria. Kaplan-Meier and Cox proportional hazards methods compared time to death between groups. Missing model covariates were imputed via multiple imputation. RESULTS: 2303 patients met inclusion criteria: 2003(87%) received TB treatment 5-7 days/week and 300(13%) 2-3 days/week in the continuation phase. Intermittency varied by site: 100% of patients from Brazil and Haiti received continuation phase treatment 5-7 days/week, followed by Honduras (91%), Peru (42%), Mexico (7%), and Chile (0%). The crude risk of death was lower among those receiving treatment 5-7 vs. 2-3 days/week (HR = 0.68; 95% CI = 0.51-0.91; P = 0.008). After adjusting for age, sex, CD4, ART use at TB diagnosis, site of TB disease (pulmonary vs. extrapulmonary), and year of TB diagnosis, mortality risk was lower, but not significantly, among those treated 5-7 days/week vs. 2-3 days/week (HR 0.75, 95%CI 0.55-1.01; P = 0.06). After also stratifying by study site, there was no longer a protective effect (HR 1.42, 95%CI 0.83-2.45; P = 0.20). CONCLUSIONS: TB treatment 5-7 days/week was associated with a marginally decreased risk of death compared to TB treatment 2-3 days/week in the continuation phase in multivariable, unstratified analyses. However, little variation in TB treatment intermittency within country meant the results could have been driven by other differences between study sites. Therefore, randomized trials are needed, especially in heterogenous regions such as Latin America.

Maintenance treatment in advanced HER2-negative gastric cancer.

Survival for patients with advanced gastric cancer (GC) remains poor. Systemic chemotherapy which has reached a plateau stays the standard first-line (1L) treatment for advanced human epidermal growth-factor receptor 2 (HER2)-negative GC. To maximize the benefit of 1L treatment, the concept of maintenance treatment is constantly being explored. In advanced HER2-negative GC, current clinical guidelines do not recommend a standard maintenance therapy strategy. In addition to the monotherapy maintenance with fluorouracil after 4-6 cycles of 1L chemotherapy, some agents that are active against novel targets have been evaluated in clinical trials for maintenance treatment. Whereas most of these trials do not reach their primary endpoints, they open new horizons for the 1L treatment of advanced HER2-negative GC. Therefore, we reviewed the clinical trials in the field of maintenance treatment in advanced HER2-negative GC and discussed some of the problems in clinical trials.

Intervenções para tratamento da obesidade: revisão sistemática / Interventions in obesity treatments: a systematic review / Intervenciones para el tratamiento de la obesidad: una revisión sistemática

Objetivo: fazer uma revisão sistemática para avaliar a efetividade e segurança dos métodos para redução de peso, sendo eles: cirúrgico, farmacológico e mudanças do estilo de vida (MEV), que incluem exercícios físicos e dietas. Os resultados clínicos de interesse foram a perda de peso e sua manutenção pelo prazo mínimo de 1 ano. Método: foi feita uma busca de artigos nas bases de dados PUBMED, Scielo e Biblioteca do Cochrane, com as palavras-chave weight loss maintenance e obesity treatment. A busca incluiu artigos em português, inglês e espanhol publicados até outubro de 2011. Foram incluídos revisões sistemáticas, metanálises e ensaios clínicos randomizados que tivessem um período de seguimento maior ou igual a um ano. Os estudos deveriam ter como participantes: adultos obesos (maior que 18 anos e com índice de massa corpórea ­ IMC maior que 30) e que comparassem intervenções distintas para o tratamento da obesidade. Resultados: foram selecionados 5 artigos que contemplaram os critérios de inclusão, sendo que cada um desses estudaram isoladamente, comparados com MEV, a eficácia do Orlistat, Sibutramina, Pramlintide e gastroplastia. A gastroplastia teve um resultado significativo (p < 0,05) para evitar o total reganho de peso. O Orlistat produziu uma perda de peso significativa durante o primeiro ano de tratamento e o ganho de peso foi diminuído com seu uso no segundo ano de tratamento (p < 0,001). A Sibutramina se mostrou eficaz na manutenção do peso após um período de perda com dieta de grande restrição calórica. O Pramlintide mostrou efetividade na perda de peso e redução da circunferência abdominal. Conclusões: As intervenções farmacológicas e cirúrgicas se mostraram mais efetivas quando comparadas à MEV em relação à perda de peso e a sua manutenção a longo prazo, porém é necessária a realização de mais estudos que analisem a comparação entre as diferentes intervenções disponíveis para o tratamento da obesidade.

Objective: to make a systematic review to evaluate the effectiveness and safety of methods to reduce weight, as follows: surgical, pharmacological and changes in lifestyle, which include exercise and diet. Clinical outcomes of interest were weight loss and long-term loss maintenance. Methods: a search for the keywords "weight loss maintenance" and "obesity treatment" in articles from PubMed, Scielo and Cochrane Library database was performed. The search included articles in English, Portuguese and Spanish published until October 2011. Systematic reviews, meta-analysis and randomized clinical trials that had a follow-up period greater or equal to one year were included. The studies should have obese adults (over 18 years with body mass index greater than 30) as participants and compare different interventions to the treatment of obesity. Results: five articles that fulfill the inclusion criteria were selected, and each of these articles separately studied the effectiveness of Orlistat, Sibutramine, Pramlintide and gastroplasty, in comparison to changes in lifestyle. Gastroplasty presented significant results (p < 0.05) to avoid the total weight regain. Orlistat produced significant weight loss during the first year of treatment and weight gain was reduced with its use in the second year of treatment (p < 0.001). Sibutramine was effective in maintaining weight loss after a weight loss diet with high caloric restriction. Pramlintide showed effectiveness in weight loss and reduction in waist circumference. Conclusions: Pharmacological and surgical interventions were more effective compared to changes in lifestyle regarding weight loss and maintenance in the long term, but further studies need to be carried out to examine the comparison between the different interventions available for the treatment of obesity.

Objetivo: Realizar una revisión sistemática para evaluar la eficacia y la seguridad de los siguientes métodos para reducción de peso: cirugía, medicación y cambio de estilo de vida (CEV), incluyendo el ejercicio y la dieta. Los resultados clínicos evaluados fueron la pérdida de peso y su manutención por el plazo mínimo de un año. Métodos: Se buscaron artículos en las base de datos PubMed, Scielo y en la Biblioteca Cochrane con las palabras-clave "mantenimiento de la pérdida de peso" y "tratamiento de la obesidad". La búsqueda incluyó artículos en Inglés, Portugués y Español publicados hasta octubre de 2011. Se incluyeron revisiones sistemáticas, meta-análisis y ensayos clínicos aleatorizados que tuviesen un período de seguimiento mayor o igual a un año. Los estudios debían tener como participantes: adultos obesos (mayores de 18 años y con índice de masa corporal mayor que 30) y que comparasen diferentes intervenciones para el tratamiento de la obesidad. Resultados: Se seleccionaron cinco artículos que contemplaron los criterios de inclusión, cada uno de ellos fue estudiado por separado con relación al CEV, la eficacia del Orlistat, la Sibutramina, la Pramlintida, y la gastroplastia. La gastroplastia tuvo un resultado significativo (p < 0,05) para evitar la recuperación del peso total. El Orlistat produjo una pérdida significativa de peso durante el primer año de tratamiento y su uso disminuyó el aumento de peso en el segundo año de tratamiento (p < 0,001). La Sibutramina fue eficaz en el mantenimiento de peso después de un período de pérdida con una dieta de gran restricción calórica. La Pramlintida mostró eficacia en la pérdida de peso y reducción de la circunferencia abdominal. Conclusiones: Las intervenciones farmacológicas y quirúrgicas fueron más efectivas en comparación con el CEV en relación con la pérdida de peso y su mantenimiento a largo plazo, pero es necesario llevar a cabo más estudios que analicen la comparación entre las diferentes intervenciones disponibles para el tratamiento de la obesidad.

Diretrizes da World Federation of Societies of Biological Psychiatry (WFSBP) para tratamento biológico de transtornos depressivos unipolares, 2ª parte: tratamento de manutenção do transtorno depressivo maior e tratamento dos transtornos depressivos crônicos e das depressões subliminares / World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for biological treatment of unipolar depressive disorders, part 2: maintenance treatment of major depressive disorder and treatment of chronic depressive disorders and subthreshold depressions

Estas diretrizes práticas para o tratamento biológico de transtornos depressivos unipolares foram desenvolvidas por uma Força-Tarefa internacional da Federação Mundial de Sociedades de Psiquiatria Biológica (WFSBP). O objetivo ao desenvolver tais diretrizes foi rever sistematicamente todas as evidências existentes referentes ao tratamento de transtornos depressivos unipolares e produzir uma série de recomendações práticas com significado clínico e científico, baseadas nas evidências existentes. Têm como objetivo seu uso por todos os médicos que atendam e tratem pacientes com essas afecções. Os dados usados para o desenvolvimento das diretrizes foram extraídos primariamente de várias diretrizes e painéis nacionais de tratamento para transtornos depressivos, bem como de metanálises e revisões sobre a eficácia dos antidepressivos e outras intervenções de tratamento biológico identificadas por uma busca no banco de dados MEDLINE e Cochrane Library. A literatura identificada foi avaliada quanto à força das evidências sobre sua eficácia e, então, categorizada em quatro níveis de evidências (A a D). Esta primeira parte das diretrizes abrange definição, classificação, epidemiologia e evolução dos transtornos depressivos unipolares, bem como tratamento das fases aguda e de manutenção. As diretrizes se referem primariamente ao tratamento biológico (incluindo antidepressivos, outros medicamentos psicofarmacológicos e hormonais, eletroconvulsoterapia, fototerapia, estratégias terapêuticas complementares e novas) de adultos jovens e também, embora em menor grau, de crianças, adolescentes e adultos idosos.

These practice guidelines for the biological treatment of unipolar depressive disorders were developed by an international Task Force of the World Federation of Societies of Biological Psychiatry (WFSBP). The goal for developing these guidelines was to systematically review all available evidence pertaining to the treatment of the complete spectrum of unipolar depressive disorders, and to produce a series of practice recommendations that are clinically and scientifically meaningful based on the available evidence. These guidelines are intended for use by all physicians seeing and treating patients with these conditions. The data used for developing these guidelines have been extracted primarily from various national treatment guidelines and panels for depressive disorders, as well as from meta-analyses and reviews on the efficacy of antidepressant medications and other biological treatment interventions identified by a search of the MEDLINE database and Cochrane Library. The identified literature was evaluated with respect to the strength of evidence for its efficacy and was then categorized into four levels of evidence (A-D). The first part of these WFSBP guidelines on unipolar depressive disorders covered the acute and continuation treatment of major depressive disorder (Bauer et al., 2002). This second part of the guidelines covers the management of the maintenance-phase treatment of major depressive disorder, as well as the treatment of chronic and subthreshold depressive disorders (dysthymic disorder, double depression, minor depressive disorder and recurrent brief depression). These guidelines are primarily concerned with thebiological treatment (including antidepressants, lithium, other psychopharmacological and hormonal medications, and electroconvulsive therapy) of young adults and also, albeit to a lesser extent, children, adolescents and older adults.

Evaluación farmacoeconómica del tratamiento de la depresión bipolar / Pharmacotherapy for bipolar depression: an economic assessment

Los trastornos bipolares I y II (TB) son trastornos del estado de ánimo frecuentes, graves y recurrentes asociados con tasas elevadas de comorbilidades, suicidio, disfunción y una carga socioeconómica considerable. Aunque tradicionalmente el tratamiento de los TB se ha concentrado en la terapia inmediata de la manía, la naturaleza crónica de estos trastornos exige un tratamiento de mantenimiento prolongado. La depresión bipolar es el trastorno del estado de ánimo predominante en los TB y produce mayor discapacidad y carga económica que la manía. La farmacoterapia de mantenimiento puede reducir las tasas de episodios futuros y, en consecuencia, los riesgos asociados, la discapacidad funcional y la carga económicade la enfermedad bipolar.

Bipolar disorders I and II (BPD) is a common, severe and recurrent mood disorder associated with high rates of comorbidities, suicide, dysfunction and a high socioeconomic burden. Although the management of BPD hastraditionally focused on the acute treatment of mania,the chronic nature of BPD necessitates long-term maintenance treatment. Bipolar depression is the predominant mood state in BPD and causes greaterdisability and economic burden than mania. Maintenance pharmacotherapy can reduce rates of future episodes,and subsequently, the associated risks, functional disability and economic burden of bipolar illness.