Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): study protocol for a randomized controlled trial

BACKGROUND: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). METHODS/DESIGN: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH2O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure 6430 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. DISCUSSION: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration metho

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure <= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt

Associação entre terapia hormonal e ganho de peso na transição para a menopausa e após a menopausa: uma revisão sistemática e meta-análise

Objectives: to conduct a systematic review and meta-analysis in order to assess whether hormone therapy (HT) increases weight in women in the menopausal transition and after menopause. Method: this article proposes an update to the systematic review published in 2005 by the Cochrane Library (Kongnyuy EJ et al 2005) with reference to studies assessing weight changes in women receiving HT from 1986 to 2005. Following PRISMA recommendations, we included randomized controlled trials (RCTs) ) from May 2005 onwards from Medline, Embase, and the Cochrane CENTRAL databases. Standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated. Two authors independently assessed the risk of biases in the selected studies. Results: ten RCTs were included, totaling 2,588 HT users and 764 non-users. Different regimens, dosages, and routes of administration in HT users were analyzed and compared to non-users. The results did not show statistically significant differences for most of the HT regimens evaluated. There was significant weight gain only in patients using EEC alone at dosages of 0.45 mg/day and 0.3 mg/day when compared to placebo (p 0.01); as well as in patients receiving esto-progestative combinations of 0.5 mg/day 17-beta-estradiol (E2) + 100 mg/day progesterone, with a 0.7 kg weight increase (p 0.032). On the other hand, the combinations of 1 mg/day estradiol valerate + 3 mg/day drospirenone showed a -1.0 kg reduction (p = 0.04), whereas a -0.2 kg reduction (p = 0.001) was identified in patients using 1 mg /day estradiol (E) + 0.5 mg norethisterone acetate (NETA). Tibolone therapy showed no statistically significant changes in weight. After performing a meta-analysis, the comparative results between users and non-users showed that there was a slight weight increase (+0.279 kg ; CI -1.71 to 2.27) in patients using 0.625 mg/day conjugated equine estrogen (CEE) + 2.5 mg/day medroxyprogesterone acetate (MPA). As for the patients receiving 2.5 mg/day Tibolone, weight gain (+0.670 kg; CI from -1.14 to 2.48) was also observed in them. However, these increases were not significant when compared to non-HT users. Conclusions: most regimens studied showed that patients using HT in the menopausal transition and after menopause did not show significant weight gain. The only combination that showed weight gain was 0.5 mg/day 17-beta-estradiol (E2) + 100 mg/day progesterone observed, while there was weight reduction in patients using 1 mg/day estradiol valerate + 3 mg/day drospirenone and 1 mg/day estradiol (E) + norethisterone acetate.Objetivo: realizar uma revisão sistemática e meta-análise para avaliar se a terapia hormonal (TH) aumenta o peso em mulheres na transição menopausal e após a menopausa. Métodos: este artigo propõe uma atualização da revisão sistemática publicada em 2005 pela Cochrane Library (Kongnyuy EJ et al., 2005) com referência a estudos avaliando mudanças de peso em mulheres recebendo TH de 1986 a 2005. Seguindo as recomendações do PRISMA, incluímos ensaios clínicos randomizados (RCTs) de maio de 2005 em diante do Medline, Embase e dos bancos de dados Cochrane CENTRAL. Diferenças médias padronizadas (SMD) e intervalos de confiança de 95% (IC) foram calculados. Dois autores avaliaram independentemente o risco de vieses nos estudos selecionados. Resultados: foram incluídos dez ECRs, totalizando 2.588 usuários de HT e 764 não usuários. Diferentes esquemas, dosagens e vias de administração em usuários de HT foram analisados e comparados a não usuários. Os resultados não mostraram diferenças estatisticamente significativas para a maioria dos esquemas de TH avaliados. Houve ganho de peso significativo apenas nos pacientes que usaram apenas EEC nas doses de 0,45 mg/dia e 0,3 mg/dia quando comparados ao placebo (p 0,01); assim como em pacientes recebendo combinações estoprogestativas de 0,5 mg/dia de 17-beta-estradiol (E2) + 100 mg/dia de progesterona, com aumento de peso de 0,7 kg (p 0,032). Por outro lado, as combinações de 1 mg/dia de valerato de estradiol + 3 mg/dia de drospirenona apresentaram redução de -1,0 kg (p = 0,04), enquanto foi identificada redução de -0,2 kg (p = 0,001) nas pacientes que usaram 1 mg /dia estradiol (E) + 0,5 mg de acetato de noretisterona (NETA). A terapia com tibolona não mostrou alterações estatisticamente significativas no peso. Após realizar uma meta-análise, os resultados comparativos entre usuárias e não usuárias mostraram que houve um leve aumento de peso (+0,279 kg ; IC -1,71 a 2,27) em pacientes em uso de 0,625 mg/dia de estrogênio equino conjugado (CEE) + 2,5 mg/dia de acetato de medroxiprogesterona (MPA). Quanto aos pacientes que receberam Tibolona 2,5 mg/dia, também foi observado ganho de peso (+0,670 kg; IC de -1,14 a 2,48). No entanto, esses aumentos não foram significativos quando comparados aos não usuários de HT. Conclusões: a maioria dos esquemas estudados mostrou que as pacientes em uso de TH na transição menopausal e após a menopausa não apresentaram ganho de peso significativo. A única combinação que apresentou ganho de peso foi 0,5 mg/dia de 17-beta-estradiol (E2) + 100 mg/dia de progesterona, enquanto houve redução de peso nas pacientes que usaram 1 mg/dia de valerato de estradiol + 3 mg/dia de drospirenona e 1 mg/dia estradiol (E) + acetato de noretisterona