Adherence to key recommendations for design and analysis of stepped-wedge cluster randomized trials: A review of trials published 2016-2022.

BACKGROUND/AIMS: The stepped-wedge cluster randomized trial (SW-CRT), in which clusters are randomized to a time at which they will transition to the intervention condition - rather than a trial arm - is a relatively new design. SW-CRTs have additional design and analytical considerations compared to conventional parallel arm trials. To inform future methodological development, including guidance for trialists and the selection of parameters for statistical simulation studies, we conducted a review of recently published SW-CRTs. Specific objectives were to describe (1) the types of designs used in practice, (2) adherence to key requirements for statistical analysis, and (3) practices around covariate adjustment. We also examined changes in adherence over time and by journal impact factor. METHODS: We used electronic searches to identify primary reports of SW-CRTs published 2016-2022. Two reviewers extracted information from each trial report and its protocol, if available, and resolved disagreements through discussion. RESULTS: We identified 160 eligible trials, randomizing a median (Q1-Q3) of 11 (8-18) clusters to 5 (4-7) sequences. The majority (122, 76%) were cross-sectional (almost all with continuous recruitment), 23 (14%) were closed cohorts and 15 (9%) open cohorts. Many trials had complex design features such as multiple or multivariate primary outcomes (50, 31%) or time-dependent repeated measures (27, 22%). The most common type of primary outcome was binary (51%); continuous outcomes were less common (26%). The most frequently used method of analysis was a generalized linear mixed model (112, 70%); generalized estimating equations were used less frequently (12, 8%). Among 142 trials with fewer than 40 clusters, only 9 (6%) reported using methods appropriate for a small number of clusters. Statistical analyses clearly adjusted for time effects in 119 (74%), for within-cluster correlations in 132 (83%), and for distinct between-period correlations in 13 (8%). Covariates were included in the primary analysis of the primary outcome in 82 (51%) and were most often individual-level covariates; however, clear and complete pre-specification of covariates was uncommon. Adherence to some key methodological requirements (adjusting for time effects, accounting for within-period correlation) was higher among trials published in higher versus lower impact factor journals. Substantial improvements over time were not observed although a slight improvement was observed in the proportion accounting for a distinct between-period correlation. CONCLUSIONS: Future methods development should prioritize methods for SW-CRTs with binary or time-to-event outcomes, small numbers of clusters, continuous recruitment designs, multivariate outcomes, or time-dependent repeated measures. Trialists, journal editors, and peer reviewers should be aware that SW-CRTs have additional methodological requirements over parallel arm designs including the need to account for period effects as well as complex intracluster correlations.

A Comparison of High and Usual Protein Dosing in Critically Ill Patients With Obesity: A Post Hoc Analysis of an International, Pragmatic, Single-Blinded, Randomized Clinical Trial.

OBJECTIVES: Across guidelines, protein dosing for critically ill patients with obesity varies considerably. The objective of this analysis was to evaluate whether this population would benefit from higher doses of protein. DESIGN: A post hoc subgroup analysis of the effect of higher protein dosing in critically ill patients with high nutritional risk (EFFORT Protein): an international, multicenter, pragmatic, registry-based randomized trial. SETTING: Eighty-five adult ICUs across 16 countries. PATIENTS: Patients with obesity defined as a body mass index (BMI) greater than or equal to 30 kg/m 2 ( n = 425). INTERVENTIONS: In the primary study, patients were randomized into a high-dose (≥ 2.2 g/kg/d) or usual-dose protein group (≤ 1.2 g/kg/d). MEASUREMENTS AND MAIN RESULTS: Protein intake was monitored for up to 28 days, and outcomes (time to discharge alive [TTDA], 60-d mortality, days of mechanical ventilation [MV], hospital, and ICU length of stay [LOS]) were recorded until 60 days post-randomization. Of the 1301 patients in the primary study, 425 had a BMI greater than or equal to 30 kg/m 2 . After adjusting for sites and covariates, we observed a nonsignificant slower rate of TTDA with higher protein that ruled out a clinically important benefit (hazard ratio, 0.78; 95% CI, 0.58-1.05; p = 0.10). We found no evidence of difference in TTDA between protein groups when subgroups with different classes of obesity or patients with and without various nutritional and frailty risk variables were examined, even after the removal of patients with baseline acute kidney injury. Overall, 60-day mortality rates were 31.5% and 28.2% in the high protein and usual protein groups, respectively (risk difference, 3.3%; 95% CI, -5.4 to 12.1; p = 0.46). Duration of MV and LOS in hospital and ICU were not significantly different between groups. CONCLUSIONS: In critically ill patients with obesity, higher protein doses did not improve clinical outcomes, including those with higher nutritional and frailty risk.

The impact of higher protein dosing on outcomes in critically ill patients with acute kidney injury: a post hoc analysis of the EFFORT protein trial.

BACKGROUND: Based on low-quality evidence, current nutrition guidelines recommend the delivery of high-dose protein in critically ill patients. The EFFORT Protein trial showed that higher protein dose is not associated with improved outcomes, whereas the effects in critically ill patients who developed acute kidney injury (AKI) need further evaluation. The overall aim is to evaluate the effects of high-dose protein in critically ill patients who developed different stages of AKI. METHODS: In this post hoc analysis of the EFFORT Protein trial, we investigated the effect of high versus usual protein dose (≥ 2.2 vs. ≤ 1.2 g/kg body weight/day) on time-to-discharge alive from the hospital (TTDA) and 60-day mortality and in different subgroups in critically ill patients with AKI as defined by the Kidney Disease Improving Global Outcomes (KDIGO) criteria within 7 days of ICU admission. The associations of protein dose with incidence and duration of kidney replacement therapy (KRT) were also investigated. RESULTS: Of the 1329 randomized patients, 312 developed AKI and were included in this analysis (163 in the high and 149 in the usual protein dose group). High protein was associated with a slower time-to-discharge alive from the hospital (TTDA) (hazard ratio 0.5, 95% CI 0.4-0.8) and higher 60-day mortality (relative risk 1.4 (95% CI 1.1-1.8). Effect modification was not statistically significant for any subgroup, and no subgroups suggested a beneficial effect of higher protein, although the harmful effect of higher protein target appeared to disappear in patients who received kidney replacement therapy (KRT). Protein dose was not significantly associated with the incidence of AKI and KRT or duration of KRT. CONCLUSIONS: In critically ill patients with AKI, high protein may be associated with worse outcomes in all AKI stages. Recommendation of higher protein dosing in AKI patients should be carefully re-evaluated to avoid potential harmful effects especially in patients who were not treated with KRT. TRIAL REGISTRATION: This study is registered at ClinicalTrials.gov (NCT03160547) on May 17th 2017.

The Efficacy of Glutamine Supplementation in Severe Adult Burn Patients: A Systematic Review With Trial Sequential Meta-Analysis.

OBJECTIVES: Evidence supporting glutamine supplementation in severe adult burn patients has created a state of uncertainty due to the variability in the treatment effect reported across small and large randomized controlled trials (RCTs). We aimed to systematically review the effect of glutamine supplementation on mortality in severe adult burn patients. DATA SOURCES: MEDLINE, Embase, CINAHL, and Cochrane Central were searched from inception to February 10, 2023. STUDY SELECTION: RCTs evaluating the effect of enteral or IV glutamine supplementation alone in severe adult burn patients were included. DATA EXTRACTION: Two reviewers independently extracted data on study characteristics, burn injury characteristics, description of the intervention between groups, adverse events, and clinical outcomes. DATA SYNTHESIS: Random effects meta-analyses were performed to estimate the pooled risk ratio (RR). Trial sequential analyses (TSA) for mortality and infectious complications were performed. Ten RCTs (1,577 patients) were included. We observed no significant effect of glutamine supplementation on overall mortality (RR, 0.65, 95% CI, 0.33-1.28; p = 0.21), infectious complications (RR, 0.83; 95% CI, 0.63-1.09; p = 0.18), or other secondary outcomes. In subgroup analyses, we observed no significant effects based on administration route or burn severity. We did observe a significant subgroup effect between single and multicenter RCTs in which glutamine significantly reduced mortality and infectious complications in singe-center RCTs but not in multicenter RCTs. However, TSA showed that the pooled results of single-center RCTs were type 1 errors and further trials would be futile. CONCLUSIONS: Glutamine supplementation, regardless of administration, does not appear to improve clinical outcomes in severely adult burned patients.

Intravenous vitamin C monotherapy in critically ill patients: a systematic review and meta-analysis of randomized controlled trials with trial sequential analysis.

BACKGROUND: A recent landmark randomized controlled trial (RCT) in septic patients demonstrated an increased risk of death and persistent organ dysfunction with intravenous Vitamin C (IVVC) monotherapy, which represents a disparate result from previous systematic reviews and meta-analyses (SRMA). We performed an updated SRMA of IVVC monotherapy to summarize and explore heterogeneity across current trials and conduct trial sequential analysis (TSA) to guard against type-I or type-II statistical errors. METHODS: RCTs evaluating IVVC in adult critically ill patients were included. Four databases were searched from inception to 22 June 2022 without language restrictions. The primary outcome was overall mortality. Random effect meta-analysis was performed to estimate the pooled risk ratio. TSA for mortality was performed using the DerSimonian-Laird random effect model, alpha 5%, beta 10%, and relative risk reduction (RRR) of 30%, 25%, and 20%. RESULTS: We included 16 RCTs (n = 2130). IVVC monotherapy is associated with significant reduction in overall mortality [risk ratio (RR) 0.73, 95% confidence interval (CI) 0.60-0.89; p = 0.002; I2 = 42%]. This finding is supported by TSA using RRR of 30% and 25%, and sensitivity analysis using fixed-effect meta-analysis. However, the certainty of our mortality finding was rated low using GRADE due to the serious risk of bias and inconsistency. In a priori subgroup analyses, we found no differences between single vs multicenter, higher (≥ 10,000 mg/day) vs lower dose and sepsis vs non-sepsis trials. Post-hoc, we found no differences in subgroup analysis of earlier (< 24 h) vs delayed treatment, longer (> 4 days) vs shorter treatment duration, and low vs other risk of bias studies. IVVC may have the greatest benefit in trials that enrolled patients above (i.e., > 37.5%; RR 0.65, 95% CI 0.54-0.79) vs below (i.e., ≤ 37.5%; RR 0.89, 95% CI 0.68-1.16) median control group mortality (test for subgroup differences: p = 0.06), and TSA supported this. CONCLUSIONS: IVVC monotherapy may be associated with mortality benefits in critically ill patients, particularly in patients with a high risk of dying. Given the low certainty of evidence, this potentially life-saving therapy warrants further studies to identify the optimal timing, dosage, treatment duration, and patient population that will benefit most from IVVC monotherapy. PROSPERO Registration ID: CRD42022323880. Registered 7th May 2022.

A scoping review described diversity in methods of randomization and reporting of baseline balance in stepped-wedge cluster randomized trials.

OBJECTIVES: In stepped-wedge cluster randomized trials (SW-CRTs), clusters are randomized not to treatment and control arms but to sequences dictating the times of crossing from control to intervention conditions. Randomization is an essential feature of this design but application of standard methods to promote and report on balance at baseline is not straightforward. We aimed to describe current methods of randomization and reporting of balance at baseline in SW-CRTs. STUDY DESIGN AND SETTING: We used electronic searches to identify primary reports of SW-CRTs published between 2016 and 2022. RESULTS: Across 160 identified trials, the median number of clusters randomized was 11 (Q1-Q3: 8-18). Sixty-three (39%) used restricted randomization-most often stratification based on a single cluster-level covariate; 12 (19%) of these adjusted for the covariate(s) in the primary analysis. Overall, 50 (31%) and 134 (84%) reported on balance at baseline on cluster- and individual-level characteristics, respectively. Balance on individual-level characteristics was most often reported by condition in cross-sectional designs and by sequence in cohort designs. Authors reported baseline imbalances in 72 (45%) trials. CONCLUSION: SW-CRTs often randomize a small number of clusters using unrestricted allocation. Investigators need guidance on appropriate methods of randomization and assessment and reporting of balance at baseline.

The effect of higher protein dosing in critically ill patients with high nutritional risk (EFFORT Protein): an international, multicentre, pragmatic, registry-based randomised trial.

BACKGROUND: On the basis of low-quality evidence, international critical care nutrition guidelines recommend a wide range of protein doses. The effect of delivering high-dose protein during critical illness is unknown. We aimed to test the hypothesis that a higher dose of protein provided to critically ill patients would improve their clinical outcomes. METHODS: This international, investigator-initiated, pragmatic, registry-based, single-blinded, randomised trial was undertaken in 85 intensive care units (ICUs) across 16 countries. We enrolled nutritionally high-risk adults (≥18 years) undergoing mechanical ventilation to compare prescribing high-dose protein (≥2·2 g/kg per day) with usual dose protein (≤1·2 g/kg per day) started within 96 h of ICU admission and continued for up to 28 days or death or transition to oral feeding. Participants were randomly allocated (1:1) to high-dose protein or usual dose protein, stratified by site. As site personnel were involved in both prescribing and delivering protein dose, it was not possible to blind clinicians, but patients were not made aware of the treatment assignment. The primary efficacy outcome was time-to-discharge-alive from hospital up to 60 days after ICU admission and the secondary outcome was 60-day morality. Patients were analysed in the group to which they were randomly assigned regardless of study compliance, although patients who dropped out of the study before receiving the study intervention were excluded. This study is registered with ClinicalTrials.gov, NCT03160547. FINDINGS: Between Jan 17, 2018, and Dec 3, 2021, 1329 patients were randomised and 1301 (97·9%) were included in the analysis (645 in the high-dose protein group and 656 in usual dose group). By 60 days after randomisation, the cumulative incidence of alive hospital discharge was 46·1% (95 CI 42·0%-50·1%) in the high-dose compared with 50·2% (46·0%-54·3%) in the usual dose protein group (hazard ratio 0·91, 95% CI 0·77-1·07; p=0·27). The 60-day mortality rate was 34·6% (222 of 642) in the high dose protein group compared with 32·1% (208 of 648) in the usual dose protein group (relative risk 1·08, 95% CI 0·92-1·26). There appeared to be a subgroup effect with higher protein provision being particularly harmful in patients with acute kidney injury and higher organ failure scores at baseline. INTERPRETATION: Delivery of higher doses of protein to mechanically ventilated critically ill patients did not improve the time-to-discharge-alive from hospital and might have worsened outcomes for patients with acute kidney injury and high organ failure scores. FUNDING: None.

A Randomized Trial of Enteral Glutamine for Treatment of Burn Injuries.

BACKGROUND: Glutamine is thought to have beneficial effects on the metabolic and stress response to severe injury. Clinical trials involving patients with burns and other critically ill patients have shown conflicting results regarding the benefits and risks of glutamine supplementation. METHODS: In a double-blind, randomized, placebo-controlled trial, we assigned patients with deep second- or third-degree burns (affecting ≥10% to ≥20% of total body-surface area, depending on age) within 72 hours after hospital admission to receive 0.5 g per kilogram of body weight per day of enterally delivered glutamine or placebo. Trial agents were given every 4 hours through a feeding tube or three or four times a day by mouth until 7 days after the last skin grafting procedure, discharge from the acute care unit, or 3 months after admission, whichever came first. The primary outcome was the time to discharge alive from the hospital, with data censored at 90 days. We calculated subdistribution hazard ratios for discharge alive, which took into account death as a competing risk. RESULTS: A total of 1209 patients with severe burns (mean burn size, 33% of total body-surface area) underwent randomization, and 1200 were included in the analysis (596 patients in the glutamine group and 604 in the placebo group). The median time to discharge alive from the hospital was 40 days (interquartile range, 24 to 87) in the glutamine group and 38 days (interquartile range, 22 to 75) in the placebo group (subdistribution hazard ratio for discharge alive, 0.91; 95% confidence interval [CI], 0.80 to 1.04; P = 0.17). Mortality at 6 months was 17.2% in the glutamine group and 16.2% in the placebo group (hazard ratio for death, 1.06; 95% CI, 0.80 to 1.41). No substantial between-group differences in serious adverse events were observed. CONCLUSIONS: In patients with severe burns, supplemental glutamine did not reduce the time to discharge alive from the hospital. (Funded by the U.S. Department of Defense and the Canadian Institutes of Health Research; RE-ENERGIZE ClinicalTrials.gov number, NCT00985205.).

Early versus delayed enteral nutrition in mechanically ventilated patients with circulatory shock: a nested cohort analysis of an international multicenter, pragmatic clinical trial.

INTRODUCTION: Real-world evidence on the timing and efficacy of enteral nutrition (EN) practices in intensive care unit (ICU) patients with circulatory shock is limited. We hypothesized early EN (EEN), as compared to delayed EN (DEN), is associated with improved clinical outcomes in mechanically ventilated (MV) patients with circulatory shock. METHODS: We analyzed a dataset from an international, multicenter, pragmatic randomized clinical trial (RCT) evaluating protein dose in ICU patients. Data were collected from ICU admission, and EEN was defined as initiating < 48 h from ICU admission and DEN > 48 h. We identified MV patients in circulatory shock to evaluate the association between the timing of EN initiation and clinical outcomes. The regression analysis model controlled for age, mNUTRIC score, APACHE II score, sepsis, and Site. RESULTS: We included 626 patients, from 52 ICUs in 14 countries. Median age was 60 years [18-93], 55% had septic shock, 99% received norepinephrine alone, 91% received EN alone, and 50.3% were randomized to a usual protein dose. Forty-two percent of EEN patients had persistent organ dysfunction syndrome plus death at day 28, compared to 53% in the DEN group (p = 0.04). EEN was associated with more ICU-free days (9.3 ± 9.2 vs. 5.7 ± 7.9, p = 0.0002), more days alive and free of vasopressors (7.1 ± 3.1 vs. 6.3 ± 3.2, p = 0.007), and shorter duration of MV among survivors (9.8 ± 10.9 vs. 13.8 ± 14.5, p = 0.0002). This trend was no longer observed in the adjusted analysis. There were no differences in ICU/60-day mortality or feeding intolerance rates between groups. CONCLUSION: In MV patients with circulatory shock, EEN, as compared to DEN, was associated with improved clinical outcomes, but no longer when adjusting for illness severity. RCTs comparing the efficacy of EEN to DEN in MV patients with circulatory shock are warranted.

Impact of nationwide essential trace element shortages: A before-after, single-center analysis of hospitalized adults receiving home parenteral nutrition therapy.

BACKGROUND: Recent data on the prevalence of essential trace element (ETE) deficiencies in home parenteral nutrition (HPN) patients are scarce. We investigated whether ETE deficiencies are still an important issue for HPN patients and whether the prevalence of such deficiencies may be influenced by nationwide drug shortages. METHODS: We conducted a single-institution, retrospective analysis from 2006 to 2015 of hospitalized HPN patients who continued PN during and in between hospitalizations. In subgroup analysis, patients were dichotomized as those with HPN duration <1 vs ≥1 year. Zinc (Zn), copper (Cu), and selenium (Se) levels were abstracted for patients over the study period. Prevalence of ETE deficiency was compared using chi-squared test for patients hospitalized during nonshortage vs shortage (2011-2014) periods. RESULTS: Ninety-six patients were included in the analysis. Prevalence of ETE deficiency during nonshortage vs shortage periods was 48% vs 54% (Zn), 15% vs 21% (Cu), and 24% vs 48% (Se; P = .01), respectively. When comparing patients who received HPN <1 year vs ≥1 year, the prevalence of Se deficiency doubled during shortage in both subgroups (24% to 42% vs 26% to 49%); and Cu deficiency tripled during shortage period in the group receiving HPN ≥1 year (5% to 16%). CONCLUSION: ETE deficiency is prevalent in hospitalized HPN patients and was exacerbated during nationwide shortages of parenteral supplements. Statistical significance may be limited by small sample size. Future studies are needed to determine optimal ETE supplementation strategies for minimizing the impacts of nationwide drug shortages on HPN patients.

Combination of enteral and parenteral nutrition in the acute phase of critical illness: An updated systematic review and meta-analysis.

BACKGROUND: Uncertainty remains about the best route and timing of medical nutrition therapy in the acute phase of critical illness. Early combined enteral nutrition (EN) and parenteral nutrition (PN) may represent an attractive option to achieve recommended energy and protein goals in select patient groups. This meta-analysis aims to update and summarize the current evidence. METHODS: This systematic review and meta-analysis includes randomized controlled trials (RCTs) targeting the effect of EN alone vs a combination of EN with PN in the acute phase of critical illness in adult patients. Assessed outcomes include mortality, intensive care unit (ICU) and hospital length of stay (LOS), ventilation days, infectious complications, physical recovery, and quality-of-life outcomes. RESULTS: Twelve RCTs with 5543 patients were included. Treatment with a combination of EN with PN led to increased delivery of macronutrients. No statistically significant effect of a combination of EN with PN vs EN alone on any of the parameters was observed: mortality (risk ratio = 1.0; 95% CI, 0.79-1.28; P = .99), hospital LOS (mean difference, -1.44; CI, -5.59 to 2.71; P = .50), ICU LOS, and ventilation days. Trends toward improved physical outcomes were observed in two of four trials. CONCLUSION: A combination of EN with PN improved nutrition intake in the acute phase of critical illness in adults and was not inferior regarding the patients' outcomes. Large, adequately designed trials in select patient groups are needed to answer the question of whether this nutrition strategy has a clinically relevant treatment effect.

Early Enteral Nutrition Adequacy Mitigates the Neutrophil-Lymphocyte Ratio Improving Clinical Outcomes in Critically Ill Surgical Patients.

BACKGROUND: Neutrophil-lymphocyte ratio (NLR) is a measure of host inflammatory response; a higher NLR is associated with worse clinical outcomes. Enteral nutrition (EN) may mitigate inflammation through interaction with gut-associated lymphoid tissue. We hypothesized that early EN adequacy in critically ill surgical patients is associated with lower NLR and better clinical outcomes. METHODS: In this retrospective study, we analyzed data from adult surgical intensive care unit (ICU) patients receiving EN. NLR at baseline ICU admission (NLR-B), NLR after 3-5 days of EN (F-NLR), nutrition adequacy, caloric deficit (CD), protein deficit (PD), hospital length of stay (LOS), ICU LOS, 28-day ventilator-free days (28-VFD), and in-hospital mortality were collected. Tertiles groups were created for NLR, F-NLR, CD, and PD; the highest (H) and lowest (L) tertiles were compared. Regression analyses were performed to control for effect of age, gender, APACHE II, and NLR. RESULTS: Subjects in the L-CD group had lower median F-NLR (7 [range, 5-11] vs 10 [7-22], P = 0.005) and shorter ICU LOS (9 [6-16]) vs 16 [9-32] days; P = 0.006). The L-NLR group had shorter hospital LOS (18 [10-31] vs 22 [15-38] days, P = 0.023), greater 28-VFD (23 [18-25] vs 19 [11-22] days, P = 0.005), and lower in-hospital mortality (13% vs 41%, P = 0.002). CONCLUSION: In critically ill surgical patients, early enteral caloric adequacy is associated with less inflammation and improved clinical outcomes.

Early nutritional inadequacy is associated with psoas muscle deterioration and worse clinical outcomes in critically ill surgical patients.

PURPOSE: To explore whether psoas cross sectional area (CSA) and density (Hounsfield Units, HU) are associated with nutritional adequacy and clinical outcomes in surgical intensive care unit patients. MATERIALS AND METHODS: Subjects with at least one CT scan within 72h of ICU admission were included. Demographic, nutritional, radiographic, and outcomes data were collected. Psoas muscle CSA and HU were assessed at the L4-L5 intervertebral disk level. Change (Δ) in CSA and HU overall and per day were calculated. RESULTS: 140 patients were included. There was no significant correlation between baseline CSA and HU and clinical outcomes. Patients with at least two CT scans (n=65), had a median decrease in CSA of -15% [IQR: -20%, -8%] and decrease in HU of -2% [IQR: -30%, +24%]. Patients with the greatest daily %HU decline received significantly fewer calories/kg and proteins/kg and accumulated greater protein deficits at day 7 and overall. Patients with daily %HU increase had the shortest ICU and hospital LOS and more ventilator-free days in univariate and multivariable analyses. CONCLUSIONS: In this exploratory study, early nutritional deficits were correlated with muscle quality deterioration. Inpatient gain in psoas density, compared to maintenance or loss, is associated with shorter hospital stay.

Increased Efficacy and Safety of Enteral Nutrition Support with a Protocol (ASNET) in Noncritical Patients: A Randomized Controlled Trial.

BACKGROUND: Unintentional underfeeding is common in patients receiving enteral nutrition (EN), and is associated with increased risk of malnutrition complications. Protocols for EN in critically ill patients have been shown to enhance adequacy, resulting in better clinical outcomes; however, outside of intensive care unit (ICU) settings, the influence of a protocol for EN is unknown. OBJECTIVE: To evaluate the efficacy and safety of implementing an EN protocol in a noncritical setting. DESIGN: Randomized controlled clinical trial. PARTICIPANTS AND SETTINGS: This trial was conducted from 2014 to 2016 in 90 adult hospitalized patients (non-ICU) receiving exclusively EN. Patients with carcinomatosis, ICU admission, or <72 hours of EN were excluded. INTERVENTION: The intervention group received EN according to a protocol, whereas the control group was fed according to standard practice. MAIN OUTCOME MEASURES: The proportion of patients receiving ≥80% of their caloric target at Day 4 after EN initiation. STATISTICAL ANALYSES PERFORMED: Student t test or Wilcoxon rank-sum test were used for continuous variables and the difference between the groups in the time to receipt of the optimal amount of nutrition was analyzed using Kaplan-Meier curves. RESULTS: Forty-five patients were randomized to each group. At Day 4 after EN initiation, 61% of patients in the intervention arm had achieved the primary end point compared with 23% in the control group (P=0.001). In malnourished patients, 63% achieved the primary end point in the intervention group compared with 16% in the control group (P=0.003). The cumulative deficit on Day 4 was lower in the intervention arm compared with the control arm: 2,507 kcal (interquartile range [IQR]=1,262 to 2,908 kcal) vs 3,844 kcal (IQR=2,620 to 4,808 kcal) (P<0.001) and 116 g (IQR=69 to 151 g) vs 191 g (IQR=147 to 244 g) protein (P<0.001), respectively. The rates of gastrointestinal complications were not significantly different between groups. CONCLUSIONS: Implementation of an EN protocol outside the ICU significantly improved the delivery of calories and protein when compared with current standard practice without increasing gastrointestinal complications.

Enteral nutritional support in non-ICU hospitalized patients: current practice in Mexico.

BACKGROUND AND OBJECTIVES: Patients receiving >=80% of their energy requirements by enteral nutrition (EN) have better clinical outcomes; unfortunately, there are discrepancies between the amount prescribed and amount received. The aim of this study was to explore the nutritional clinical practice, determine the adequacy and identify reasons for underfeeding. METHODS AND STUDY DESIGN: A retrospective study was conducted in hospitalized, non-intensive care unit, adult patients receiving EN for >=72 h. The following data were recorded: the prescribed target of energy and protein per day, daily energy intake, and the percentage of adequacy of the energy and protein requirement up to hospital day seven. Complications during administration or reasons for interruption and the proportion of patients who received >=80% of the energy goals on days four and seven were also recorded. RESULTS: In total, 52 patients were included (61.5% women), with a median age of 57.5 years; 20.4% and 6.1% of the patients received >=80% of their energy and protein goals, respectively, on day four, which improved to 28% (p<0.005) and 19% (p<0.001), respectively, on day seven. During the first seven days, a statistically significant (p<0.001) difference was observed between the amount of prescribed and administered energy over 24 h. The patients who received <80% of their total energy requirement remained hospitalized for 29 days (IQR 16.5-45.5), while those who received >=80% were hospitalized for 18 days (IQR 13.3-28.8) (p<0.05). CONCLUSIONS: Significant energy and protein deficits were documented. Furthermore, it is necessary to use strategies such as the implementation of an algorithm to optimize EN.