Ruxolitinib for Glucocorticoid-Refractory Acute Graft-versus-Host Disease

BACKGROUND: Acute graft-versus-host disease (GVHD) remains a major limitation of allogeneic stem-cell transplantation; not all patients have a response to standard glucocorticoid treatment. In a phase 2 trial, ruxolitinib, a selective Janus kinase (JAK1 and JAK2) inhibitor, showed potential efficacy in patients with glucocorticoid-refractory acute GVHD. METHODS: We conducted a multicenter, randomized, open-label, phase 3 trial comparing the efficacy and safety of oral ruxolitinib (10 mg twice daily) with the investigator's choice of therapy from a list of nine commonly used options (control) in patients 12 years of age or older who had glucocorticoid-refractory acute GVHD after allogeneic stem-cell transplantation. The primary end point was overall response (complete response or partial response) at day 28. The key secondary end point was durable overall response at day 56. RESULTS: A total of 309 patients underwent randomization; 154 patients were assigned to the ruxolitinib group and 155 to the control group. Overall response at day 28 was higher in the ruxolitinib group than in the control group (62% [96 patients] vs. 39% [61]; odds ratio, 2.64; 95% confidence interval [CI], 1.65 to 4.22; P<0.001). Durable overall response at day 56 was higher in the ruxolitinib group than in the control group (40% [61 patients] vs. 22% [34]; odds ratio, 2.38; 95% CI, 1.43 to 3.94; P<0.001). The estimated cumulative incidence of loss of response at 6 months was 10% in the ruxolitinib group and 39% in the control group. The median failure-free survival was considerably longer with ruxolitinib than with control (5.0 months vs. 1.0 month; hazard ratio for relapse or progression of hematologic disease, non-relapse-related death, or addition of new systemic therapy for acute GVHD, 0.46; 95% CI, 0.35 to 0.60). The median overall survival was 11.1 months in the ruxolitinib group and 6.5 months in the control group (hazard ratio for death, 0.83; 95% CI, 0.60 to 1.15). The most common adverse events up to day 28 were thrombocytopenia (in 50 of 152 patients [33%] in the ruxolitinib group and 27 of 150 [18%] in the control group), anemia (in 46 [30%] and 42 [28%], respectively), and cytomegalovirus infection (in 39 [26%] and 31 [21%]). CONCLUSIONS: Ruxolitinib therapy led to significant improvements in efficacy outcomes, with a higher incidence of thrombocytopenia, the most frequent toxic effect, than that observed with control therapy

A importância de cuidados paliativos em Pediatria

Ultimamente muito se tem falado da necessidade de implementar programas de cuidados paliativos e continuados no nosso país. O mais recente plano da Direcção Geral de Saúde, através da Unidade de Missão para os Cuidados Continuados Integrados, refere pela primeira vez a necessidade de “elaborar e desenvolver um Programa de Formação para suporte à prestação de cuidados a colectivos específicos (ex. doenças neurológicas, SIDA e crianças)”1.Esta é uma realidade a que a Pediatria não pode fugir. Mas quando se fala em “cuidados paliativos”, são quase sempre confundidos com um dos seus componentes, os “cuidados terminais” ou “cuidados de fim de vida”, quando na realidade são muito mais do que isso - “cuidados holísticos e proactivos a crianças e adolescentes que não vão melhorar da sua doença”2.E embora mais raras que nos adultos, são muitas as situações passíveis de paliação (Quadro)3. O exemplo habitual são as doenças oncológicas, mas não podemos esquecer, por exemplo, as neurodegenerativas, as respiratórias, as malformações cardíacas graves, nem a Neonatologia ou os Cuidados Intensivos.Em 2000 a Academia Americana de Pediatria4 considerou que “Program development in pediatric palliative care, along with community outreach and public education, must be a priority of tertiary care centers serving children”. (pág. 355).Por sua vez, o grupo de trabalho pediátrico (IMPaCCT) da Associação Europeia de Cuidados Paliativos (EAPC) elaborou em 2007 as suas recomendações5, de onde destacamos: “Effective palliative care requires a broad multidisciplinary approach that includes the family and makes use of available community resources; it can be successfully implemented even if resources are limited.” (pág. 109)

A classificação de Kennedy e o tipo de reabilitação protética removível realizada em doentes da Clínica de Medicina Dentária Egas Moniz

Dissertação para obtenção do grau de Mestre no Instituto Superior de Ciências da Saúde Egas MonizObjetivos: Determinar a prevalência dos desdentados parciais segundo a classificação de Kennedy, avaliar qual a Reabilitação proposta, a realizada e se são coincidentes, identificar as causas para as suas alterações, de uma amostra de doentes da Clínica de Medicina Dentária Egas Moniz. Materiais e Métodos: Foram analisadas as Histórias clínicas dos processos de todos os doentes que frequentaram as consultas da Unidade Curricular Clínica de Reabilitação Oral I e II entre os meses de Setembro de 2014 e Junho de 2015, tendo sido caracterizados pelas seguintes variáveis: idade, sexo, Classificação de Kennedy para a maxila e mandíbula, tipo de reabilitação proposta realizada. Efectuou-se uma análise estatística descritiva com recurso a tabelas de dupla entrada, através do Software SPSS Statistics 20.0. Resultados: Foram recolhidos 240 processos, que depois de aplicados os critérios de inclusão e exclusão, obtivemos 73 processos para os quais foram planeadas 95 próteses. 68,4% pertenciam ao sexo feminino. A média de idades rondou os 59 anos, sendo as mulheres mais novas. A classe III de Kennedy foi a classe mais frequente (43%) e a IV a menos frequente (3,2%) sendo o maior grupo de desdentados mandibulares (52,6%). A prótese parcial removível em cromo-cobalto foi a reabilitação mais frequentemente utilizada (55,8%). A maioria das próteses em Cromo-cobalto foram realizadas nas classes III de Kennedy, independentemente das arcadas. Na mandíbula a reabilitação mais utilizada foi prótese parcial em Cromo-cobalto, enquanto na maxila foi prótese parcial Acrílica. Conclusões: A classe de Kennedy mais frequente é a classe II (43%) e classe de Kennedy menos frequente é a classe IV (3,2%). As próteses Acrílicas apresentam maior número de dentes protéticos. O tipo de Reabilitação protética proposto foi o realizado

Trends in cause and place of death for children in Portugal (a European country with no Paediatric palliative care) during 1987–2011: a population-based study

Abstract Background Children and adolescents dying from complex chronic conditions require paediatric palliative care. One aim of palliative care is to enable a home death if desired and well supported. However, there is little data to inform care, particularly from countries without paediatric palliative care, which constitute the majority worldwide. Methods This is an epidemiological study analysing death certificate data of decedents aged between 0 and 17 years in Portugal, a developed Western European country without recognised provision of paediatric palliative care, from 1987 to 2011. We analysed death certificate data on cause and place of death; the main outcome measure was home death. Complex chronic conditions included cancer, cardiovascular, neuromuscular, congenital/genetic, respiratory, metabolic, gastro-intestinal, renal, and haematology/immunodeficiency conditions. Multivariate analysis determined factors associated with home death in these conditions. Results Annual deaths decreased from 3268 to 572. Of 38,870 deaths, 10,571 were caused by complex chronic conditions, their overall proportion increasing from 23.7% to 33.4% (22.4% to 45.4% above age 1-year). For these children, median age of death increased from 0.5 to 4.32-years; 19.4% of deaths occurred at home, declining from 35.6% to 11.5%; factors associated with home death were year of death (adjusted odds ratio 0.89, 95% confidence interval 0.89–0.90), age of death (6–10 year-olds 21.46, 16.42–28.04, reference neonates), semester of death (October–March 1.18, 1.05–1.32, reference April–September), and cause of death (neuromuscular diseases 1.59, 1.37–1.84, reference cancer), with wide regional variation. Conclusions This first trend analysis of paediatric deaths in Portugal (an European country without paediatric palliative care) shows that palliative care needs are increasing. Children are surviving longer and, in contrast with countries where paediatric palliative care is thriving, there is a long-term trend of dying in hospital instead of at home. Age, diagnosis, season and region are associated with home death, and should be considered when planning services to support families choosing this option. Priorities should address needs of the youngest children, those with cancer, neuromuscular and cardiovascular conditions, as well as inequities related to place of residence

Le Peuple : organe quotidien du syndicalisme

30 août 19371937/08/30 (A17,N6065)-1937/08/30

Additional file 6: Figure S4. of Trends in cause and place of death for children in Portugal (a European country with no Paediatric palliative care) during 1987–2011: a population-based study

Trend for home death in 0–17 year-old decedents from cancer and non-cancer CCCs in Portugal (1987–2011, N = 10,571). (DOCX 101 kb

Additional file 3: Table S2. of Trends in cause and place of death for children in Portugal (a European country with no Paediatric palliative care) during 1987–2011: a population-based study

Annual trend for home death in 0–17 year-old decedents from complex chronic conditions in Portugal (1987–2011). (DOCX 65 kb

Additional file 8: Figure S5. of Trends in cause and place of death for children in Portugal (a European country with no Paediatric palliative care) during 1987–2011: a population-based study

Percentage of deaths occurring at home, by subregion NUTS III, in 0–17 year-old decedents from CCCs in Portugal (1987–2011, N = 10,440). (DOCX 502 kb

Os cuidados paliativos em Portugal

info:eu-repo/semantics/publishedVersio