Association between early nutrition support and 28-day mortality in critically ill patients: the FRANS prospective nutrition cohort study.

BACKGROUND: Current guidelines suggest the introduction of early nutrition support within the first 48 h of admission to the intensive care unit (ICU) for patients who cannot eat. In that context, we aimed to describe nutrition practices in the ICU and study the association between the introduction of early nutrition support (< 48 h) in the ICU and patient mortality at day 28 (D28) using data from a multicentre prospective cohort. METHODS: The 'French-Speaking ICU Nutritional Survey' (FRANS) study was conducted in 26 ICUs in France and Belgium over 3 months in 2015. Adult patients with a predicted ICU length of stay > 3 days were consecutively included and followed for 10 days. Their mortality was assessed at D28. We investigated the association between early nutrition (< 48 h) and mortality at D28 using univariate and multivariate propensity-score-weighted logistic regression analyses. RESULTS: During the study period, 1206 patients were included. Early nutrition support was administered to 718 patients (59.5%), with 504 patients receiving enteral nutrition and 214 parenteral nutrition. Early nutrition was more frequently prescribed in the presence of multiple organ failure and less frequently in overweight and obese patients. Early nutrition was significantly associated with D28 mortality in the univariate analysis (crude odds ratio (OR) 1.69, 95% confidence interval (CI) 1.23-2.34) and propensity-weighted multivariate analysis (adjusted OR (aOR) 1.05, 95% CI 1.00-1.10). In subgroup analyses, this association was stronger in patients ≤ 65 years and with SOFA scores ≤ 8. Compared with no early nutrition, a significant association was found of D28 mortality with early enteral (aOR 1.06, 95% CI 1.01-1.11) but not early parenteral nutrition (aOR 1.04, 95% CI 0.98-1.11). CONCLUSIONS: In this prospective cohort study, early nutrition support in the ICU was significantly associated with increased mortality at D28, particularly in younger patients with less severe disease. Compared to no early nutrition, only early enteral nutrition appeared to be associated with increased mortality. Such findings are in contrast with current guidelines on the provision of early nutrition support in the ICU and may challenge our current practices, particularly concerning patients at low nutrition risk. Trial registration ClinicalTrials.gov Identifier: NCT02599948. Retrospectively registered on November 5th 2015.

Outcomes used in randomised controlled trials of nutrition in the critically ill: a systematic review.

BACKGROUND: No evidence exists to date on which to base the selection of outcome measures for assessing nutritional interventions in critically ill patients. We conducted a systematic literature review to describe the outcomes used in recent randomised controlled trials (RCTs) assessing nutritional interventions in critically ill patients. Our objective was to set the foundation for the development of a core set of outcome measures for use in future RCTs. METHODS: We searched the PubMed/MEDLINE, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases for RCTs of nutritional interventions in critically ill patients aged 18 years or older, published and/or registered between January 2000 and August 2018. Outcomes were divided into six categories (mortality, length of stay, duration of organ dysfunction, complications, functional outcomes, and others) and analysed according to the study characteristics and publication year. RESULTS: Of the 885 references retrieved, 170 were included in the review. Of these, 136 (80%) defined a primary outcome, 114 (67%) defined secondary outcomes (two per study on average), and 34 (20%) did not specify whether outcomes were primary or secondary. We identified 24 different outcomes in all, of which 19 were primary. Complications were the most widely used primary outcome (65/136, 48%). Mortality was the primary outcome in 17/136 (13%) studies, with six different timepoints. The main secondary outcomes were length of stay (90/114, 79%), mortality (82/114, 72%), and duration of organ dysfunction (75/114, 65%). CONCLUSIONS: This systematic review highlights the heterogeneity of outcomes used in recent randomized controlled trials evaluating nutritional interventions in critically ill patients. The results of our systematic review may have implications for designing future RCTs of nutritional interventions in the ICU.

Exploring how non-inferiority and equivalence are assessed in paediatrics: a systematic review.

OBJECTIVE: To review characteristics, methodology and reporting of non-inferiority and equivalence trials in the specific context of paediatrics. DESIGN: PubMed and Cochrane databases were searched (up to September 2016) for non-inferiority/equivalence randomised controlled trials conducted in children published in high-impact-factor journals (>5.0 for general/specialist medical journals; >2.2 for paediatric journals). RESULTS: We found that the statistical hypothesis was inconsistent with the objective in 12 (10%) of the 125 reports included. Non-inferiority (n=98) and equivalence trials (n=27) were mostly used to evaluate interventions with easier administration (45%, n=54/120) and/or better safety profile (34%, n=41/120). All the data needed for targeted sample size recalculation were available for 39 reports (31%). The margin-representing the largest difference between arms that would be clinically acceptable-was reported in 119 (95%), and 44/119 (37%) reported the method used for margin determination. The median sample size was 268 (IQR 125-531). Margins were wider in smaller trials (<125 randomised patients) than in larger trials (p=0.04/p<0.01 for binary/continuous outcomes, respectively). We did not agree with the authors' conclusions in 11% (11/103) of the reports that provided sufficient information. CONCLUSIONS: There is still a need to improve the quality of methodology, reporting and interpretation of non-inferiority/equivalence trials in paediatrics. In particular, the margins were often not justified and the conclusion was often not supported by the design and/or the results. As researchers have to cope with small sample size and with lack of evidence, methods for non-inferiority/equivalence trials need to be used and/or developed in this vulnerable population.

Antihypertensive pharmacotherapy for prevention of sudden cardiac death in hypertensive individuals.

BACKGROUND: High blood pressure is an important public health problem because of associated risks of stroke and cardiovascular events. Antihypertensive drugs are often used in the belief that lowering blood pressure will prevent cardiac events, including myocardial infarction and sudden death (death of unknown cause within one hour of the onset of acute symptoms or within 24 hours of observation of the patient as alive and symptom free). OBJECTIVES: To assess the effects of antihypertensive pharmacotherapy in preventing sudden death, non-fatal myocardial infarction and fatal myocardial infarction among hypertensive individuals. SEARCH METHODS: We searched the Cochrane Hypertension Specialised Register (all years to January 2016), the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online (2016, Issue 1), Ovid MEDLINE (1946 to January 2016), Ovid EMBASE (1980 to January 2016) and ClinicalTrials.gov (all years to January 2016). SELECTION CRITERIA: All randomised trials evaluating any antihypertensive drug treatment for hypertension, defined, when possible, as baseline resting systolic blood pressure of at least 140 mmHg and/or resting diastolic blood pressure of at least 90 mmHg. Comparisons included one or more antihypertensive drugs versus placebo, or versus no treatment. DATA COLLECTION AND ANALYSIS: Review authors independently extracted data. Outcomes assessed were sudden death, fatal and non-fatal myocardial infarction and change in blood pressure. MAIN RESULTS: We included 15 trials (39,908 participants) that evaluated antihypertensive pharmacotherapy for a mean duration of follow-up of 4.2 years. This review provides moderate-quality evidence to show that antihypertensive drugs do not reduce sudden death (risk ratio (RR) 0.96, 95% confidence interval (CI) 0.81 to 1.15) but do reduce both non-fatal myocardial infarction (RR 0.85, 95% CI 0.74, 0.98; absolute risk reduction (ARR) 0.3% over 4.2 years) and fatal myocardial infarction (RR 0.75, 95% CI 0.62 to 0.90; ARR 0.3% over 4.2 years). Withdrawals due to adverse effects were increased in the drug treatment group to 12.8%, as compared with 6.2% in the no treatment group. AUTHORS' CONCLUSIONS: Although antihypertensive drugs reduce the incidence of fatal and non-fatal myocardial infarction, they do not appear to reduce the incidence of sudden death. This suggests that sudden cardiac death may not be caused primarily by acute myocardial infarction. Continued research is needed to determine the causes of sudden cardiac death.