Geoeconomic variations in epidemiology, ventilation management, and outcomes in invasively ventilated intensive care unit patients without acute respiratory distress syndrome: a pooled analysis of four observational studies

Background: Geoeconomic variations in epidemiology, the practice of ventilation, and outcome in invasively ventilated intensive care unit (ICU) patients without acute respiratory distress syndrome (ARDS) remain unexplored. In this analysis we aim to address these gaps using individual patient data of four large observational studies. Methods: In this pooled analysis we harmonised individual patient data from the ERICC, LUNG SAFE, PRoVENT, and PRoVENT-iMiC prospective observational studies, which were conducted from June, 2011, to December, 2018, in 534 ICUs in 54 countries. We used the 2016 World Bank classification to define two geoeconomic regions: middle-income countries (MICs) and high-income countries (HICs). ARDS was defined according to the Berlin criteria. Descriptive statistics were used to compare patients in MICs versus HICs. The primary outcome was the use of low tidal volume ventilation (LTVV) for the first 3 days of mechanical ventilation. Secondary outcomes were key ventilation parameters (tidal volume size, positive end-expiratory pressure, fraction of inspired oxygen, peak pressure, plateau pressure, driving pressure, and respiratory rate), patient characteristics, the risk for and actual development of acute respiratory distress syndrome after the first day of ventilation, duration of ventilation, ICU length of stay, and ICU mortality. Findings: Of the 7608 patients included in the original studies, this analysis included 3852 patients without ARDS, of whom 2345 were from MICs and 1507 were from HICs. Patients in MICs were younger, shorter and with a slightly lower body-mass index, more often had diabetes and active cancer, but less often chronic obstructive pulmonary disease and heart failure than patients from HICs. Sequential organ failure assessment scores were similar in MICs and HICs. Use of LTVV in MICs and HICs was comparable (42\ub74% vs 44\ub72%; absolute difference \u20131\ub769 [\u20139\ub758 to 6\ub711] p=0\ub767; data available in 3174 [82%] of 3852 patients). The median applied positive end expiratory pressure was lower in MICs than in HICs (5 [IQR 5\u20138] vs 6 [5\u20138] cm H2O; p=0\ub70011). ICU mortality was higher in MICs than in HICs (30\ub75% vs 19\ub79%; p=0\ub70004; adjusted effect 16\ub741% [95% CI 9\ub752\u201323\ub752]; p<0\ub70001) and was inversely associated with gross domestic product (adjusted odds ratio for a US$10 000 increase per capita 0\ub780 [95% CI 0\ub775\u20130\ub786]; p<0\ub70001). Interpretation: Despite similar disease severity and ventilation management, ICU mortality in patients without ARDS is higher in MICs than in HICs, with a strong association with country-level economic status. Funding: No funding

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Níveis de suplementação de vitamina C na ração sobre a ocorrência de ectoparasitas, sobrevivência e biomassa em alevinos de tilápia do Nilo (Oreochromis niloticus L.)

Different vitamin levels C in the ration on the ectoparasitas occurrence, survival and total biomass in fingerlings of Nile tilápia Oreochromis. Niloticus L. (Perciformes, Cichlidae) were evaluated after sexual reversion, for 57 days. Fingerlings began the experiment with approximately 0,30g and 24mm and were submitted to four diets with 300-mg (T1), 600-mg (T2), and 900mg-(T3) e 1200-mg (T4) of vitamin C/kg of ration. In the beginning the ectoparasites occurrence was of 100%, 38,0% of Trichodina and 62,0% of mixed infection (Trichodina and monogenetics). At the end, there was not significant difference for total occurrence, for Trichodina and mixed infection. Considering the occurrence of the monogeneas there were significant differences between T1 and the others. In relation to the schedules of collection, a significant difference was found in the occurrence among the schedule of the 15:00 compared to the other schedules. No significant differences were observed in relation to weigh, total and standard medium length, biomass and survival, though. Results indicated that it is unnecessary to use vitamin C in superior levels to the 300-ration mg/Kg, enough to reach the tilápias fingerlings' nutritional needs, bred in controlled system.Avaliou-se diferentes níveis de vitamina C na ração sobre a ocorrência de ectoparasitas, sobrevivência e biomassa total em alevinos de tilápia do Nilo, Oreochromis. Niloticus L. (Perciformes, Cichlidae) pós-revertidos, durante 57 dias. Alevinos com aproximadamente 0,30g e 24mm foram submetidos a 4 dietas contendo: 300 mg (T1), 600 mg (T2), 900 mg (T3) e 1200 mg (T4) de vitamina C por kg de ração. Inicialmente, a ocorrência de ectoparasitas foi de 100%, 38% de Trichodina e 62% de infecção mista (Trichodina + monogenéticos). Ao final não houve diferença significativa para ocorrência acumulada total, para Trichodina e infecção mista. Considerando a ocorrência dos monogenéticos, houve diferenças significativas entre o T1 e os demais. Em relação aos horários de coleta, foi encontrada uma diferença significativa na ocorrência entre o horário das 15h em relação aos demais horários. Em relação ao peso, comprimento médio total e padrão, biomassa e sobrevivência, não houve diferenças significativas. Conclui-se, então, que é desnecessário o uso de vitamina C em níveis superiores a 300mg/Kg de ração, sendo suficiente para atingir as exigências nutricionais a alevinos de tilápias criados em regime de manejo controlado