Relevance of Protein Intake for Weaning in the Mechanically Ventilated Critically Ill: Analysis of a Large International Database.

OBJECTIVES: The association between protein intake and the need for mechanical ventilation (MV) is controversial. We aimed to investigate the associations between protein intake and outcomes in ventilated critically ill patients. DESIGN: Analysis of a subset of a large international point prevalence survey of nutritional practice in ICUs. SETTING: A total of 785 international ICUs. PATIENTS: A total of 12,930 patients had been in the ICU for at least 96 hours and required MV by the fourth day after ICU admission at the latest. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We modeled associations between the adjusted hazard rate (aHR) of death in patients requiring MV and successful weaning (competing risks), and three categories of protein intake (low: < 0.8 g/kg/d, standard: 0.8-1.2 g/kg/d, high: > 1.2 g/kg/d). We compared five different hypothetical protein diets (an exclusively low protein intake, a standard protein intake given early (days 1-4) or late (days 5-11) after ICU admission, and an early or late high protein intake). There was no evidence that the level of protein intake was associated with time to weaning. However, compared with an exclusively low protein intake, a standard protein intake was associated with a lower hazard of death in MV: minimum aHR 0.60 (95% CI, 0.45-0.80). With an early high intake, there was a trend to a higher risk of death in patients requiring MV: maximum aHR 1.35 (95% CI, 0.99-1.85) compared with a standard diet. CONCLUSIONS: The duration of MV does not appear to depend on protein intake, whereas mortality in patients requiring MV may be improved by a standard protein intake. Adverse effects of a high protein intake cannot be excluded.

Correction: A computational reproducibility study of PLOS ONE articles featuring longitudinal data analyses.

[This corrects the article DOI: 10.1371/journal.pone.0251194.].

Protein intake and outcome of critically ill patients: analysis of a large international database using piece-wise exponential additive mixed models.

BACKGROUND: Proteins are an essential part of medical nutrition therapy in critically ill patients. Guidelines almost universally recommend a high protein intake without robust evidence supporting its use. METHODS: Using a large international database, we modelled associations between the hazard rate of in-hospital death and live hospital discharge (competing risks) and three categories of protein intake (low: < 0.8 g/kg per day, standard: 0.8-1.2 g/kg per day, high: > 1.2 g/kg per day) during the first 11 days after ICU admission (acute phase). Time-varying cause-specific hazard ratios (HR) were calculated from piece-wise exponential additive mixed models. We used the estimated model to compare five different hypothetical protein diets (an exclusively low protein diet, a standard protein diet administered early (day 1 to 4) or late (day 5 to 11) after ICU admission, and an early or late high protein diet). RESULTS: Of 21,100 critically ill patients in the database, 16,489 fulfilled inclusion criteria for the analysis. By day 60, 11,360 (68.9%) patients had been discharged from hospital, 4,192 patients (25.4%) had died in hospital, and 937 patients (5.7%) were still hospitalized. Median daily low protein intake was 0.49 g/kg [IQR 0.27-0.66], standard intake 0.99 g/kg [IQR 0.89- 1.09], and high intake 1.41 g/kg [IQR 1.29-1.60]. In comparison with an exclusively low protein diet, a late standard protein diet was associated with a lower hazard of in-hospital death: minimum 0.75 (95% CI 0.64, 0.87), and a higher hazard of live hospital discharge: maximum HR 1.98 (95% CI 1.72, 2.28). Results on hospital discharge, however, were qualitatively changed by a sensitivity analysis. There was no evidence that an early standard or a high protein intake during the acute phase was associated with a further improvement of outcome. CONCLUSIONS: Provision of a standard protein intake during the late acute phase may improve outcome compared to an exclusively low protein diet. In unselected critically ill patients, clinical outcome may not be improved by a high protein intake during the acute phase. Study registration ID number ISRCTN17829198.

A computational reproducibility study of PLOS ONE articles featuring longitudinal data analyses.

Computational reproducibility is a corner stone for sound and credible research. Especially in complex statistical analyses-such as the analysis of longitudinal data-reproducing results is far from simple, especially if no source code is available. In this work we aimed to reproduce analyses of longitudinal data of 11 articles published in PLOS ONE. Inclusion criteria were the availability of data and author consent. We investigated the types of methods and software used and whether we were able to reproduce the data analysis using open source software. Most articles provided overview tables and simple visualisations. Generalised Estimating Equations (GEEs) were the most popular statistical models among the selected articles. Only one article used open source software and only one published part of the analysis code. Replication was difficult in most cases and required reverse engineering of results or contacting the authors. For three articles we were not able to reproduce the results, for another two only parts of them. For all but two articles we had to contact the authors to be able to reproduce the results. Our main learning is that reproducing papers is difficult if no code is supplied and leads to a high burden for those conducting the reproductions. Open data policies in journals are good, but to truly boost reproducibility we suggest adding open code policies.