RESUMO
PI3K-δ inhibitors have shown impressive activity in lymphoid malignancies but have been hampered by autoimmune and infectious toxicities, leading to market withdrawals. We previously demonstrated activity of the PI3K-δγ inhibitor duvelisib in T cell lymphomas (TCLs) that was associated with inflammatory adverse events. As reported here, we conducted a phase 1b/2a study of duvelisib in combination with either romidepsin (n = 66) or bortezomib (n = 32) in patients with relapsed/refractory TCL and found that the addition of romidepsin, but not bortezomib, appeared to increase efficacy while attenuating PI3K inhibitor-driven toxicity. The primary endpoint of the study was to determine the safety and maximum tolerated dose of duvelisib, which was 75 mg twice daily when combined with romidepsin versus 25 mg twice daily when combined with bortezomib. The most common adverse events were neutropenia (42%, 25/59) and fatigue (37%, 22/59) in patients treated with duvelisib and romidepsin and diarrhea (48%, 11/23) and neutropenia (30%, 7/23) in patients treated with duvelisib and bortezomib. Duvelisib and romidepsin resulted in less grade 3/4 hepatotoxicity (14%, 8/59) compared to 40% (14/35) in our previous study with duvelisib monotherapy. This was associated with reductions in circulating inflammatory mediators and myeloid cell inflammatory gene expression. Secondary endpoints of overall and complete response rates were 55% (35/64) and 34% (22/64) for patients treated with duvelisib and romidepsin and 34% (11/32) and 13% (4/32) for patients treated with duvelisib and bortezomib. Among patients with peripheral T cell lymphomas (PTCLs), overall and complete response rates of duvelisib and romidepsin were 56% (27/48) and 44% (21/48), respectively, with exploratory analyses showing increased response rates in patients with a follicular helper T cell subtype. These findings support further development of combined PI3K and histone deacetylase (HDAC) inhibition in TCLs and suggest a unique strategy to enable PI3K inhibitor-based combinations for additional patient populations. ClinicalTrials.gov identifier: NCT02783625 .
RESUMO
Evaluar las conductas auto protectoras en el hogar que aplican las trabajadoras domésticasremuneradas.MetodologíaEstudio de tipo cuantitativo descriptivo. Se seleccionaron 30 trabajadoras domésticaspor conveniencia, residentes en las ciudades de Pereira, Armenia y Manizales. Se aplicóuna encuesta elaborada por los investigadores con base en los objetivos planteados queindagó sobre: a) perfil sociodemográfico b) condiciones de contratación y c) conductas yprácticas de salud/protección en las labores desempeñadas por estas trabajadoras.ResultadosEl 50,0% eran madres cabeza de familia, de las cuales 37,0% tenían a su cargo 3 o máspersonas. 76,7% refirió tener un contrato de forma verbal; sólo 10,0% informaron estaraseguradas al régimen contributivo y 20,0% a una administradora de riesgos laboralesy administradora de fondo de pensiones, por parte de su patrón. 23,3% había recibidocapacitación relacionada con su trabajo y 71,4% de éstas lo habían hecho por iniciativapropia. Más del 30,0% de estas trabajadoras tenían conductas y prácticas inseguras ypresentaban desconocimiento frente a este tema.ConclusionesLa ausencia de conductas auto-protectoras en estas trabajadoras podría estar relacionadacon la falta de capacitación por parte de sus empleadores, producto de la informalidadque se maneja en este tipo de trabajo...
To evaluate self-protective behaviors that paid domestic workers apply.MethodologyQuantitative descriptive study. 30 domestic workers were selected by convenience, residentsin the cities of Pereira, Armenia and Manizales. A survey designed by researchers, basedon the objectives that inquired about socio-demographic profile, conditions of employmentand behavior and health practices / protection in the work performed by these workers,was applied.Results50,0% were single mothers, of which 37,0% were over 3 or more people. 76,7% reportedhaving a verbal contract; only 10,0% reported being secured to the contributory schemeand 20,0% to occupational risks insurer and pension fund by their employer. 23,3% hadreceived training related to their work and 71,4% of them had done so on their owninitiative. More than 30,0% of these workers were unsafe behaviors and practices andshowed ignorance regarding this issue.ConclusionsThe absence of self-protective behaviors in these workers could be related to the lack oftraining by their employers as a result of informality that is handled in this kind of work...