Methods: This non-randomised controlled study was conducted for 16 weeks at 17 government health clinics in Selangor, Malaysia. Eligible patients attending the outpatient pharmacies of intervention clinics were recruited consecutively and their consent was obtained. A structured review of PPIs was performed in which pharmacists identified patient demographics, indications and the length of PPI therapy using a PPI intervention form. Recommendations were discussed with physicians before prescription changes were made and documented. Moreover, standard management was conducted in the control clinics.

Results: A total of 568 patients with prescriptions containing PPIs were sampled, with a total of 284 patients being placed into the control and intervention groups, respectively. Compared to the control group, inappropriate PPI utilisation in the intervention group significantly decreased from 79.9 to 30.4% (p<0.05). The changes to PPI prescriptions observed in the intervention group included: stop PPI therapy (30.8%), step-down therapy (22.9%), start substitution therapy (15.9%) and no change (30.4%). The physicians' acceptance rate for pharmacist intervention was 67.8%. A 66.1% reduction in monthly PPI pill count and a 72.0% reduction in monthly medication expenditure (RM44.85/patient/year) were observed.

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.

DESIGN: This was a single-center prospective observational study that compared resting energy expenditure estimated by 15 commonly used predictive equations against resting energy expenditure measured by indirect calorimetry at different phases. Degree of agreement between resting energy expenditure calculated by predictive equations and resting energy expenditure measured by indirect calorimetry was analyzed using intraclass correlation coefficient and Bland-Altman analyses. Resting energy expenditure values calculated from predictive equations differing by ± 10% from resting energy expenditure measured by indirect calorimetry was used to assess accuracy. A score ranking method was developed to determine the best predictive equations.

SETTING: General Intensive Care Unit, University of Malaya Medical Centre.

PATIENTS: Mechanically ventilated critically ill patients.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: Indirect calorimetry was measured thrice during acute, late, and chronic phases among 305, 180, and 91 ICU patients, respectively. There were significant differences (F= 3.447; p = 0.034) in mean resting energy expenditure measured by indirect calorimetry among the three phases. Pairwise comparison showed mean resting energy expenditure measured by indirect calorimetry in late phase (1,878 ± 517 kcal) was significantly higher than during acute phase (1,765 ± 456 kcal) (p = 0.037). The predictive equations with the best agreement and accuracy for acute phase was Swinamer (1990), for late phase was Brandi (1999) and Swinamer (1990), and for chronic phase was Swinamer (1990). None of the resting energy expenditure calculated from predictive equations showed very good agreement or accuracy.

METHODS: Using indirect calorimetry, REE was measured at acute (≤5 days; n = 294) and late (≥6 days; n = 180) phases of intensive care unit admission. PEs were developed by multiple linear regression. A multi-fold cross-validation approach was used to validate the PEs. The best PEs were selected based on the highest coefficient of determination (R2), the lowest root mean square error (RMSE) and the lowest standard error of estimate (SEE). Two PEs developed from paired 168-patient data were compared with measured REE using mean absolute percentage difference.

RESULTS: Mean absolute percentage difference between predicted and measured REE was <20%, which is not clinically significant. Thus, a single PE was developed and validated from data of the larger sample size measured in the acute phase. The best PE for REE (kcal/day) was 891.6(Height) + 9.0(Weight) + 39.7(Minute Ventilation)-5.6(Age) - 354, with R2 = 0.442, RMSE = 348.3, SEE = 325.6 and mean absolute percentage difference with measured REE was: 15.1 ± 14.2% [acute], 15.0 ± 13.1% [late].

CONCLUSIONS: Separate PEs for acute and late phases may not be necessary. Thus, we have developed and validated a PE from acute phase data and demonstrated that it can provide optimal estimates of REE for patients in both acute and late phases.

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.

DATA SOURCES: Systematic search of MEDLINE, EMBASE, CINAHL, and the Cochrane Register of Controlled Trials.

STUDY SELECTION: Randomized controlled trials testing IV vitamin C in critically ill patients.

DATA ABSTRACTION: Two independent reviewers abstracted patient characteristics, treatment details, and clinical outcomes.

DATA SYNTHESIS: Fifteen studies involving 2,490 patients were identified. Compared with placebo, IV vitamin C administration is associated with a trend toward reduced overall mortality (relative risk, 0.87; 95% CI, 0.75-1.00; p = 0.06; test for heterogeneity I2 = 6%). High-dose IV vitamin C was associated with a significant reduction in overall mortality (relative risk, 0.70; 95% CI, 0.52-0.96; p = 0.03), whereas low-dose IV vitamin C had no effect (relative risk, 0.94; 95% CI, 0.79-1.07; p = 0.46; test for subgroup differences, p = 0.14). IV vitamin C monotherapy was associated with a significant reduction in overall mortality (relative risk, 0.64; 95% CI, 0.49-0.83; p = 0.006), whereas there was no effect with IV vitamin C combined therapy. No trial reported an increase in adverse events related to IV vitamin C.

DATA SOURCES: None.

STUDY SELECTION: Current literature describing the conduct, reporting, and appraisal of systematic reviews and meta-analyses.

DATA EXTRACTION: Best practices for conducting, reporting, and appraising systematic review were summarized.

DATA SYNTHESIS: A systematic review is a review of a clearly formulated question that uses systematic and explicit methods to identify, select, and critically appraise relevant original research, and to collect and analyze data from the studies that are included in the review. Critical appraisal methods address both the credibility (quality of conduct) and rate the confidence in the quality of summarized evidence from a systematic review. The A Measurement Tool to Assess Systematic Reviews-2 tool is a widely used practical tool to appraise the conduct of a systematic review. Confidence in estimates of effect is determined by assessing for risk of bias, inconsistency of results, imprecision, indirectness of evidence, and publication bias.

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.

METHODS: A systematic search of MEDLINE, EMBASE, CINAHL and CENTRAL was conducted to identify all randomized controlled trials in critically ill patients published from inception to June 2021, which investigated clinical omega-6 sparing effects. Two independent reviewers extracted bias risk, treatment details, patient characteristics and clinical outcomes. Random effect meta-analysis was performed.

RESULTS: 1054 studies were identified in our electronic search, 136 trials were assessed for eligibility and 26 trials with 1733 critically ill patients were included. The median methodologic score was 9 out of 14 points (95% confidence interval [CI] 7, 10). Omega-6 FA sparing PN in comparison with traditional lipid emulsions did not decrease overall mortality (20 studies; risk ratio [RR] 0.91; 95% CI 0.76, 1.10; p = 0.34) but hospital length of stay was substantially reduced (6 studies; weighted mean difference [WMD] - 6.88; 95% CI - 11.27, - 2.49; p = 0.002). Among the different lipid emulsions, fish oil (FO) containing PN reduced the length of intensive care (8 studies; WMD - 3.53; 95% CI - 6.16, - 0.90; p = 0.009) and rate of infectious complications (4 studies; RR 0.65; 95% CI 0.44, 0.95; p = 0.03). When FO was administered as a stand-alone medication outside PN, potential mortality benefits were observed compared to standard care.

METHODS: Patients were selected based on the availability of selenium biomarker information. Four subgroups were defined according to the patient's baseline status, including those with normal kidney function, reduced kidney function, selenium deficiency, and submaximal GPx3 activity.

RESULTS: Two hundred and forty-four patients were included in this analysis. Overall, higher serum concentrations of selenium, selenoprotein P (SELENOP) and GPx3 were correlated with less organ injury. GPx3 activity at baseline was predictive of 6-month survival (AUC 0.73; p = 0.03). While selenium treatment elevated serum selenium and SELENOP concentrations but not GPx3 activity in the full patient cohort, subgroup analyses revealed that GPx3 activity increased in patients with reduced kidney function, selenium deficiency and low to moderate GPx3 activity. Clinical outcomes did not vary between selenium treatment and placebo in any of these subgroups, though the study was not powered to conclusively detect differences in outcomes.

METHODS: This single-center, retrospective, observational study included patients aged ≥18 years with an abdominal CT conducted within 72 hours of admission to the intensive care unit. SMI generated from CT images at the level of the mid-third lumbar vertebra were extracted from the medical records. Area under the receiver operating characteristic curves (AUC) was generated to determine the SMI cutoff values for hospital mortality. Association between LM (defined by SMI cutoff value) and hospital mortality was further evaluated by multivariable logistic regression.

RESULTS: In a sample of 228 patients, the overall SMI cutoff value (cm2 /m2 ) for hospital mortality was 42.0 (AUC: 0.637; sensitivity: 66.7%, specificity: 56.8%), whereas it was 46.5 in males and 35.3 in females. More males than females had LM (51.4% vs 37.5%), and >40% of overweight/obese patients had LM. Patients with LM were older and had a longer duration of mechanical ventilation and hospitalization. After adjusting for known confounders, LM independently predicted hospital mortality in the overall sample (adjusted odds ratio: 2.42; 95% CI 1.16-5.03; P = 0.003) and in both sexes.