Desafios na profilaxia do tromboembolismo venoso: abordagem do paciente crítico

JUSTIFICATIVA E OBJETIVOS: O tromboembolismo venoso (TEV), que inclui a trombose venosa profunda (TVP) e o tromboembolismo pulmonar (TEP) são complicações comuns em pacientes críticos. A ocorrência de TEV acarreta um substancial aumento da morbimortalidade dos pacientes internados em unidades de terapia intensiva (UTI). CONTEÚDO: A maioria dos pacientes críticos apresenta alto risco para ocorrência de complicações tromboembólicas, entretanto, a prevenção do TEV muitas vezes não é realizada de maneira adequada para este grupo de pacientes. A heparina de baixo peso molecular (HBPM) parece ser o método mais eficiente para a prevenção do TEV em pacientes de UTI. Entretanto, é patente a escassez de estudos voltados para esta população, cujas particularidades levam a recomendações específicas em relação ao diagnóstico e tratamento. CONCLUSÕES: Esta revisão faz uma análise do risco, discute os principais trabalhos publicados a respeito da profilaxia e sugere estratégias para a diminuição da ocorrência de TEV nos pacientes críticos

Safety and immunogenicity of one versus two doses of Takeda\u27s tetravalent dengue vaccine in children in Asia and Latin America: Interim results from a phase 2, randomised, placebo-controlled study

© 2017 Elsevier Ltd Background Dengue is the most common mosquito-borne viral disease in human beings, and vector control has not halted its spread worldwide. A dengue vaccine for individuals aged 9 years and older has been licensed, but there remains urgent medical need for a vaccine that is safe and effective against all four dengue virus serotypes (DENV-1–4) in recipients of all ages. Here, we present the preplanned interim analyses at 6 months of a tetravalent dengue vaccine candidate (TDV), which is comprised of an attenuated DENV-2 virus strain (TDV-2) and three chimeric viruses containing the premembrane and envelope protein genes of DENV-1, DENV-3, and DENV-4 genetically engineered into the attenuated TDV-2 genome backbone (TDV-1, TDV-3, and TDV-4). Methods An ongoing phase 2, randomised, double-blind, placebo-controlled trial of a TDV is being done at three sites in dengue-endemic countries (Dominican Republic, Panama, and the Philippines) to determine its safety and immunogenicity over 48 months in healthy participants aged 2–17 years who were randomly assigned (1:2:5:1) using an interactive web response system (stratified by age) to subcutaneous TDV injection (one 0·5 mL dose containing 2·5 × 104 plaque-forming units [PFU] of TDV-1; 6·3 × 103 PFU of TDV-2; 3·2 × 104 PFU of TDV-3; and 4·0 × 105 PFU of TDV-4) in different dose schedules (two-dose regimen at 0 and 3 months, one dose at 0 months, or one dose at 0 months and a booster at 12 months) or placebo. The primary endpoint of this 6 month interim analysis was geometric mean titres (GMTs) of neutralising antibodies against DENV-1–4 in the per-protocol immunogenicity subset at 1 month, 3 months, and 6 months after the first injection. Safety was assessed as a secondary outcome as percentage of participants with serious adverse events in all participants who were injected (safety set), and solicited and unsolicited adverse events (immunogenicity subset). This trial is registered with ClinicalTrials.gov, number NCT02302066. Findings 1800 participants were enrolled between Dec 5, 2014, and Feb 13, 2015. 1794 participants were given study injection as follows: 200 participants were given two-dose regimen at 0 and 3 months (group 1), 398 were given one dose at 0 months (group 2), 998 were given one dose at 0 months and will be given (trial ongoing) a booster at 12 months (group 3), and 198 were given placebo (group 4). These 1794 participants were included in the safety set; 562 participants were randomly assigned to the immunogenicity subset, of which 503 were included in the per-protocol set. TDV elicited neutralising antibodies against all DENV serotypes, which peaked at 1 month and remained elevated above baseline at 6 months. At 6 months, GMTs of neutralising antibodies against DENV-1 were 489 (95% CI 321–746) for group 1, 434 (306–615) for group 2, 532 (384–738) for group 3, and 62 (32–120) for group 4; GMTs of neutralising antibodies against DENV-2 were 1565 (1145–2140) for group 1, 1639 (1286–2088) for group 2, 1288 (1031–1610) for group 3, and 86 (44–169) for group 4; GMTs of neutralising antibodies against DENV-3 were 160 (104–248) for group 1, 151 (106–214) for group 2, 173 (124–240) for group 3, and 40 (23–71) for group 4; and GMTs of neutralising antibodies against DENV-4 were 117 (79–175) for group 1, 110 (80–149) for group 2, 93 (69–125) for group 3, and 24 (15–38) for group 4. No vaccine-related serious adverse events occurred; 15 (3%) of 562 participants in the immunogenicity subset reported vaccine-related unsolicited adverse events. The reactogenicity profile of TDV was acceptable, and similar to previous findings with TDV. Interpretation TDV is safe and immunogenic in individuals aged 2–17 years, irrespective of previous dengue exposure. A second TDV dose induced enhanced immunogenicity against DENV-3 and DENV-4 in children who were seronegative before vaccination. These data supported the initiation of phase 3 evaluation of the efficacy and safety of TDV given in a two-dose schedule 3 months apart, with analyses that take into account baseline age and dengue serostatus. Funding Takeda Vaccines

GRT-R910: a self-amplifying mRNA SARS-CoV-2 vaccine boosts immunity for ≥6 months in previously-vaccinated older adults

Abstract SARS-CoV-2 has resulted in high levels of morbidity and mortality world-wide, and severe complications can occur in older populations. Humoral immunity induced by authorized vaccines wanes within 6 months, and frequent boosts may only offer transient protection. GRT-R910 is an investigational self-amplifying mRNA (samRNA)-based SARS-CoV-2 vaccine delivering full-length Spike and selected conserved non-Spike T cell epitopes. This study reports interim analyses for a phase I open-label dose-escalation trial evaluating GRT-R910 in previously vaccinated healthy older adults (NCT05148962). Primary endpoints of safety and tolerability were assessed. Most solicited local and systemic adverse events (AEs) following GRT-R910 dosing were mild to moderate and transient, and no treatment-related serious AEs were observed. The secondary endpoint of immunogenicity was assessed via IgG binding assays, neutralization assays, interferon-gamma ELISpot, and intracellular cytokine staining. Neutralizing antibody titers against ancestral Spike and variants of concern were boosted or induced by GRT-R910 and, contrasting to authorized vaccines, persisted through at least 6 months after the booster dose. GRT-R910 increased and/or broadened functional Spike-specific T cell responses and primed functional T cell responses to conserved non-Spike epitopes. This study is limited due to small sample size, and additional data from ongoing studies will be required to corroborate these interim findings