Diagnostic accuracy of community optometrists for age-related macular degeneration using colour fundus photographs: A pilot evaluation.

PURPOSE: The accurate diagnosis of age-related macular degeneration (AMD) represents an important step in delaying and preventing vision loss and achieving optimal patient care. Therefore, this pilot study aimed to estimate the diagnostic accuracy of community optometrists for identifying AMD using colour fundus photographs (CFPs) to support sample size calculations for subsequent definitive studies. METHODS: Five practising community optometrists were invited to classify a total of 1023 CFPs for the (1) presence of AMD, and, if applicable, (2) stage of AMD (early/intermediate/late geographic atrophy/late neovascular AMD). Diagnosis by referral centre clinicians formed the reference standard. Diagnostic accuracy was assessed by the area under the receiver operating characteristic curve (aROC). Sensitivity, specificity, positive and negative predictive values were also calculated. RESULTS: Of the 1023 CFPs included in the study, 226 images were of AMD and 797 images were of other ocular conditions or no abnormal findings. Participating community optometrists had a mean (SD) age of 30.2 (8.9) years, 60.0% (3/5) were female and the mean number of years practising in primary eye care was 5.4 (5.4) years. Community optometrists demonstrated excellent performance for diagnosing AMD, with an aROC of 0.86 (95% CI 0.83 to 0.89), sensitivity of 84.5% (95% CI 79.1 to 89.0) and specificity of 88.0% (95% CI 85.5 to 90.1). The aROC (95% CI) for diagnosing early, intermediate, late geographic atrophy and late neovascular AMD was 0.82 (0.73 to 0.91), 0.76 (0.72 to 0.81), 0.69 (0.49 to 0.90) and 0.55 (0.34 to 0.75), respectively. CONCLUSIONS: These results justify the need for an appropriately powered definitive study to assess community clinicians' diagnostic accuracy for AMD.

Modifiable risk factors for ventilator associated diaphragmatic dysfunction: a multicenter observational study.

BACKGROUND: Diaphragmatic dysfunction is known to be associated with difficulties weaning from invasive mechanical ventilation and is related to worse patient outcomes yet our understanding of how to prevent diaphragmatic dysfunction remains incomplete. We examined potentially modifiable risk factors for diaphragmatic dysfunction and attempted to estimate benefits attributable to altering these modifiable risk factors. METHODS: This prospective multicenter observational study was undertaken in the general ICUs of two tertiary care teaching hospitals. Critically ill adults expected to receive invasive mechanical ventilation for at least 48 h were enrolled. Diaphragm function was assessed by ultrasound each study day, with dysfunction defined as thickening fraction less than 20%. RESULTS: From January to December 2019, 856 patients were screened and 126 patients were enrolled. Overall, 40.5% (51/126) of patients experienced diaphragmatic dysfunction during invasive mechanical ventilation. Patients with diaphragmatic dysfunction were more likely to develop ventilator associated pneumonia (risk difference [RD] + 12.9%, 95% Confidence Interval [CI] 1.4 to 24.4%, P = 0.028), were more likely to experience extubation failure (RD + 8.5%, 95% CI 0.4 to 16.6%, P = 0.039) and required a longer duration of invasive mechanical ventilation (RD + 1.3 days, 95% CI 0.1 to 2.5 days, P = 0.035). They also required a longer hospital stay (RD + 1.2 days, 95% CI 0.04 to 2.4 days, P = 0.041) and were more likely to die before hospital discharge (RD + 18.1%, 95% CI 3.7 to 32.5%, P = 0.014). Multivariable analysis considered the impact of age, sex, pre-existing nutritional status, caloric intake, amino acid intake, acute disease severity, modes of mechanical ventilation, measures of respiratory status, sedation, pain control and baseline diaphragm thickness. Only SOFA score (P = 0.008) and early amino acid intake (P = 0.001) remained significant independent risk factors for the onset of diaphragmatic dysfunction. Causal path modeling suggested early amino acid intake may significantly reduce diaphragmatic dysfunction (RRR 29%, 95% CI 10% to 48%, P = 0.003) and may also reduce mortality (RRR 49%, 95% CI 25% to 73%, P < 0.0001). CONCLUSIONS: Amino acid intake during the first 24 h of ICU stay may represent an important, modifiable risk factor for diaphragmatic dysfunction and may have a direct causal effect on mortality. We recommend additional research on this topic.

Diagnostic accuracy of OCTA and OCT for myopic choroidal neovascularisation: a systematic review and meta-analysis.

BACKGROUND/OBJECTIVES: The purpose of this project was to systematically review and meta-analyse studies assessing the diagnostic accuracy of optical coherence tomography angiography (OCTA) and optical coherence tomography (OCT) for myopic choroidal neovascularisation (mCNV). Fluorescein angiography (FA) was accepted as the reference standard. METHODS: PUBMED and EMBASE were searched from inception to March 2021 for studies evaluating the test accuracy of OCTA and/or OCT for diagnosing mCNV. The Preferred Reporting Items for Systematic Reviews and Meta-analyses of Diagnostic Test Accuracy Studies guideline was followed, and the Grading of Recommendations, Assessment, Development and Evaluation approach was used to frame clinical recommendations. Pooled estimates of test accuracy were obtained using a bivariate model. RESULTS: Of 410 studies assessed for eligibility, 3 studies were identified that compared OCTA to FA and 3 studies were identified that compared spectral domain (SD) OCT to FA. All studies had at least one major methodological flaw leading to an overall high risk of bias. On meta-analysis, the pooled sensitivity of OCTA was 0.89 (95% CI 0.78-0.94) and pooled specificity was 0.93 (95% CI 0.79-0.98). The pooled sensitivity of SD-OCT was 0.99 (95% CI 0.91-1.00). Due to uncertainty in individual studies, the pooled specificity of SD-OCT could not be estimated. CONCLUSIONS: OCTA can reliably diagnose mCNV in clinically suspected patients, however, SD-OCT may not reliably establish a positive diagnosis of mCNV. Future large, prospective studies with improvements in conduct and reporting are needed to strengthen these clinical recommendations.

Attitudes of optometrists towards artificial intelligence for the diagnosis of retinal disease: A cross-sectional mail-out survey.

PURPOSE: Artificial intelligence (AI)-based systems have demonstrated great potential in improving the diagnostic accuracy of retinal disease but are yet to achieve widespread acceptance in routine clinical practice. Clinician attitudes are known to influence implementation. Therefore, this study aimed to identify optometrists' attitudes towards the use of AI to assist in diagnosing retinal disease. METHODS: A paper-based survey was designed to assess general attitudes towards AI in diagnosing retinal disease and motivators/barriers for future use. Two clinical scenarios for using AI were evaluated: (1) at the point of care to obtain a diagnostic recommendation, versus (2) after the consultation to provide a second opinion. Relationships between participant characteristics and attitudes towards AI were explored. The survey was mailed to 252 randomly selected practising optometrists across Australia, with repeat mail-outs to non-respondents. RESULTS: The response rate was 53% (133/252). Respondents' mean (SD) age was 42.7 (13.3) years, and 44.4% (59/133) identified as female, whilst 1.5% (2/133) identified as gender diverse. The mean number of years practising in primary eye care was 18.8 (13.2) years with 64.7% (86/133) working in an independently owned practice. On average, responding optometrists reported positive attitudes (mean score 4.0 out of 5, SD 0.8) towards using AI as a tool to aid the diagnosis of retinal disease, and would be more likely to use AI if it is proven to increase patient access to healthcare (mean score 4.4 out of 5, SD 0.6). Furthermore, optometrists expressed a statistically significant preference for using AI after the consultation to provide a second opinion rather than during the consultation, at the point-of-care (+0.12, p = 0.01). CONCLUSIONS: Optometrists have positive attitudes towards the future use of AI as an aid to diagnose retinal disease. Understanding clinician attitudes and preferences for using AI may help maximise its clinical potential and ensure its successful translation into practice.

Actively implementing an evidence-based feeding guideline for critically ill patients (NEED): a multicenter, cluster-randomized, controlled trial.

BACKGROUND: Previous cluster-randomized controlled trials evaluating the impact of implementing evidence-based guidelines for nutrition therapy in critical illness do not consistently demonstrate patient benefits. A large-scale, sufficiently powered study is therefore warranted to ascertain the effects of guideline implementation on patient-centered outcomes. METHODS: We conducted a multicenter, cluster-randomized, parallel-controlled trial in intensive care units (ICUs) across China. We developed an evidence-based feeding guideline. ICUs randomly allocated to the guideline group formed a local "intervention team", which actively implemented the guideline using standardized educational materials, a graphical feeding protocol, and live online education outreach meetings conducted by members of the study management committee. ICUs assigned to the control group remained unaware of the guideline content. All ICUs enrolled patients who were expected to stay in the ICU longer than seven days. The primary outcome was all-cause mortality within 28 days of enrollment. RESULTS: Forty-eight ICUs were randomized to the guideline group and 49 to the control group. From March 2018 to July 2019, the guideline ICUs enrolled 1399 patients, and the control ICUs enrolled 1373 patients. Implementation of the guideline resulted in significantly earlier EN initiation (1.20 vs. 1.55 mean days to initiation of EN; difference - 0.40 [95% CI - 0.71 to - 0.09]; P = 0.01) and delayed PN initiation (1.29 vs. 0.80 mean days to start of PN; difference 1.06 [95% CI 0.44 to 1.67]; P = 0.001). There was no significant difference in 28-day mortality (14.2% vs. 15.2%; difference - 1.6% [95% CI - 4.3% to 1.2%]; P = 0.42) between groups. CONCLUSIONS: In this large-scale, multicenter trial, active implementation of an evidence-based feeding guideline reduced the time to commencement of EN and overall PN use but did not translate to a reduction in mortality from critical illness. TRIAL REGISTRATION: ISRCTN, ISRCTN12233792 . Registered November 20th, 2017.

Early oral protein-containing diets following elective lower gastrointestinal tract surgery in adults: a meta-analysis of randomized clinical trials.

BACKGROUND: Although current guidelines make consensus recommendations for the early resumption of oral intake after surgery, a recent comprehensive meta-analysis failed to identify any patient-centered benefits. We hypothesized this finding was attributable to pooling studies providing effective protein-containing diets with ineffective non-protein liquid diets. Therefore, the aim of this paper was to investigate the safety and efficacy of early oral protein-containing diets versus later (traditional) feeding after elective lower gastrointestinal tract surgery in adults. METHODS: PubMed, Embase, and the China National Knowledge Infrastructure databases were searched from inception until 1 August 2019. Reference lists of retrieved studies were hand searched to identify randomized clinical trials reporting mortality. No language restrictions were applied. Study selection, risk of bias appraisal and data abstraction were undertaken independently by two authors. Disagreements were settled by obtaining an opinion of a third author. Majority decisions prevailed. After assessment of underlying assumptions, a fixed-effects method was used for analysis. The primary outcome was mortality. Secondary outcomes included surgical site infections, postoperative nausea and vomiting, serious postoperative complications and other key measures of safety and efficacy. RESULTS: Eight randomized clinical trials recruiting 657 patients were included. Compared with later (traditional) feeding, commencing an early oral protein-containing diet resulted in a statistically significant reduction in mortality (odds ratio [OR] 0.31, P = 0.02, I2 = 0%). An early oral protein-containing diet also significantly reduced surgical site infections (OR 0.39, P = 0.002, I2 = 32%), postoperative nausea and vomiting (OR 0.62, P = 0.04, I2 = 37%), serious postoperative complications (OR 0.60, P = 0.01, I2 = 25%), and significantly improved other major outcomes. No harms attributable to an early oral protein-containing diet were identified. CONCLUSIONS: The results of this systematic review can be used to upgrade current guideline statements to a grade A recommendation supporting an oral protein-containing diet commenced before the end of postoperative day 1 after elective lower gastrointestinal surgery in adults.

Nutritional practice in critically ill COVID-19 patients: A multicenter ambidirectional cohort study in Wuhan and Jingzhou.

BACKGROUND AND OBJECTIVES: The novel coronavirus disease (COVID-19) epidemic is spreading all over the world. With the number of cases increasing rapidly, the epidemiological data on the nutritional practice is scarce. In this study, we aim to describe the clinical characteristics and nutritional practice in a cohort of critically ill COVID-19 patients. METHODS AND STUDY DESIGN: This is a multicenter, ambidirectional cohort study conducted at 11 hospitals in Hubei Province, China. All eligible critical COVID-19 patients in the study hospital intensive care units at 00:00, March 6th, 2020, were included. Data collection was performed via written case report forms. RESULTS: A total of 44 patients were identified and enrolled, of whom eight died during the 28-day outcome follow- up period. The median interval between hospital admission and the study day was 24 (interquartile range, 13- 26) days and 52.2% (23 of 44) of patients were on invasive mechanical ventilation. The median nutrition risk in critically ill (mNUTRIC) score was 3 (interquartile range, 2-5) on the study day. During the enrolment day, 68.2% (30 of 44) of patients received enteral nutrition (EN), while 6.8% (3 of 44) received parenteral nutrition (PN) alone. Nausea and aspiration were uncommon, with a prevalence of 11.4% (5 of 44) and 6.8% (3 of 44), respectively. As for energy delivery, 69.7% (23 of 33) of patients receiving EN and/or PN were achieving their prescribed targets. CONCLUSIONS: The study showed that EN was frequently applied in critical COVID-19 patients. Energy delivery may be suboptimal in this study requiring more attention.

Early on-demand drainage or standard management for acute pancreatitis patients with acute necrotic collections and persistent organ failure: A pilot randomized controlled trial.

BACKGROUND/PURPOSE: The current standard care for acute pancreatitis with acute necrotic collections (ANC) is to postpone invasive intervention for 4 weeks when indicated. However, in patients with persistent organ failure (POF), this delayed approach may prolong organ failure. In this study, we aimed to assess the feasibility and safety of earlier drainage for acute pancreatitis patients with ANC and POF. METHODS: A single-center, randomized controlled trial was conducted. Eligible patients were randomly assigned to either the early on-demand (EOD) group or the standard management (SM) group. Within 21 days of randomization, early drainage was triggered by unremitted or worsening organ failure in the EOD group. The primary endpoint was a composite of major complications/death during 90-days follow-up. RESULTS: Thirty patients were randomized. Within 21 days of randomization, eight of the 15 patients (53%) in the EOD group underwent percutaneous drainage compared to four of the 15 patients (27%) in the SM group (P = 0.26). The primary outcome occurred in three of the 15 (20%) patients in the EOD group and seven of the 15(46.7%) in the controls (P = 0.25, relative risk 0.43, 95%CI 0.14 to 1.35). CONCLUSIONS: Although the EOD approach did not result in significant differences between groups, the primary outcome assessed in this trial demonstrated the potential for clinical benefits favoring early drainage.

Nebulised heparin for patients with or at risk of acute respiratory distress syndrome: a multicentre, randomised, double-blind, placebo-controlled phase 3 trial.

BACKGROUND: Mechanical ventilation in intensive care for 48 h or longer is associated with the acute respiratory distress syndrome (ARDS), which might be present at the time ventilatory support is instituted or develop afterwards, predominantly during the first 5 days. Survivors of prolonged mechanical ventilation and ARDS are at risk of considerably impaired physical function that can persist for years. An early pathogenic mechanism of lung injury in mechanically ventilated, critically ill patients is inflammation-induced pulmonary fibrin deposition, leading to thrombosis of the microvasculature and hyaline membrane formation in the air sacs. The main aim of this study was to determine if nebulised heparin, which targets fibrin deposition, would limit lung injury and thereby accelerate recovery of physical function in patients with or at risk of ARDS. METHODS: The Can Heparin Administration Reduce Lung Injury (CHARLI) study was an investigator-initiated, multicentre, double-blind, randomised phase 3 trial across nine hospitals in Australia. Adult intensive care patients on invasive ventilation, with impaired oxygenation defined by a PaO2/FiO2 ratio of less than 300, and with the expectation of invasive ventilation beyond the next calendar day were recruited. Key exclusion criteria were heparin allergy, pulmonary bleeding, and platelet count less than 50 X 109/L. Patients were randomly assigned 1:1, with stratification by site and using blocks of variable size and random seed, via a web-based system, to either unfractionated heparin sodium 25 000 IU in 5 mL or identical placebo (sodium chloride 0·9% 5 mL), administered using a vibrating mesh membrane nebuliser every 6 h to day 10 while invasively ventilated. Patients, clinicians, and investigators were masked to treatment allocation. The primary outcome was the Short Form 36 Health Survey Physical Function Score (out of 100) of survivors at day 60. Prespecified secondary outcomes, which are exploratory, included development of ARDS to day 5 among at-risk patients, deterioration of the Murray Lung Injury Score (MLIS) to day 5, mortality at day 60, residence of survivors at day 60, and serious adverse events. Analyses followed the intention-to-treat principle. There was no imputation of missing data. The trial is registered with the Australian and New Zealand Clinical Trials Register, number ACTRN12612000418875 . FINDINGS: Between Sept 4, 2012, and Aug 23, 2018, 256 patients were randomised. Final follow-up was on Feb 25, 2019. We excluded three patients who revoked consent and one ineligible participant who received no intervention. Of 252 patients included in data analysis, the mean age was 58 years (SD 15), 157 (62%) were men, and 118 (47%) had ARDS. 128 (51%) patients were assigned to the heparin group and 124 (49%) to the placebo group, all of whom received their assigned intervention. Survivors in the heparin group (n=97) had similar SF-36 Physical Function Scores at day 60 compared to the placebo group (n=94; mean 53·6 [SD 31·6] vs 48·7 [35·7]; difference 4·9 [95% CI -4·8 to 14·5]; p=0·32). Compared with the placebo group, the heparin group had fewer cases of ARDS develop to day 5 among the at-risk patients (nine [15%] of 62 patients vs 21 [30%] of 71 patients; hazard ratio 0·46 [95% CI 0·22 to 0·98]; p=0·0431), less deterioration of the MLIS to day 5 (difference -0·14 [-0·26 to -0·02]; p=0·0215), similar day 60 mortality (23 [18%] of 127 patients vs 18 [15%] of 123 patients; odds ratio [OR] 1·29 [95% CI 0·66 to 2·53]; p=0·46), and more day 60 survivors at home (86 [87%] of 99 patients vs 73 [73%] of 100 patients; OR 2·45 [1·18 to 5·08]; p=0·0165). A similar number of serious adverse events occurred in each group (seven [5%] of 128 patients in the heparin group vs three [2%] of 124 patients in the placebo group; OR 2·33 [0·59 to 9·24]; p=0·23), which were a transient increase in airway pressure during nebulisation (n=3 in the heparin group), major non-pulmonary bleeding (n=2 in each group), haemoptysis (n=1 in the heparin group), tracheotomy site bleeding (n=1 in the heparin group), and hypoxaemia during nebulisation (n=1 in the placebo group). INTERPRETATION: In patients with or at risk of ARDS, nebulised heparin did not improve self-reported performance of daily physical activities, but was well tolerated and exploratory outcomes suggest less progression of lung injury and earlier return home. Further research is justified to establish if nebulised heparin accelerates recovery in those who have or are at risk of ARDS. FUNDING: Rowe Family Foundation, TR and RB Ditchfield Medical Research Endowment Fund, Patricia Madigan Charitable Trust, and The J and R McGauran Trust Fund.

Evidence summary resources may influence clinical decision making: A case-based scenario evaluation of an evidence summary tool.

PURPOSE: Evidence summary resources are popular with clinicians but it is unknown whether they can influence clinical decision making. We evaluated whether an extremely condensed and explicit evidence summary tool could influence clinical decision making. MATERIALS AND METHODS: An evidence summary tool was developed using a formal mapping exercise and graphic design principles. An invitation to participate was sent to subscribers of a critical care e-mail discussion list. Participants received a study package (evidence summary tool précising prone positioning in severe ARDS; case-based scenario describing a patient with severe ARDS plus evaluation questionnaire). Influence on clinical decisions was captured regarding six competing interventions, with Belief in benefit measured before and after reading the summary tool. RESULTS: Among 93 participants, 87% were male with a mean age of 49.6(SD9.3) years. Mean ICU experience was 20.0(SD9.9) years. The evidence summary tool significantly influenced clinical decision making: belief in benefit of prone positioning increased (P < .001), belief in benefit of higher PEEP decreased (P = .002) and belief in benefit in ECMO decreased (P = .07). CONCLUSIONS: Using a before-after evaluation, we demonstrated an extremely condensed and explicit information format can influence clinical decision making. Evidence summary tools may be a useful adjunct to support closing evidence-practice gaps.

Intravenous amino acid therapy for kidney protection in cardiac surgery patients: A pilot randomized controlled trial.

OBJECTIVE: To determine whether a continuous intravenous infusion of standard amino acids could preserve kidney function after on-pump cardiac surgery. METHODS: Adult patients scheduled to receive cardiac surgery lasting longer than 1 hour on-pump were randomized to standard care (n = 36) or an infusion of amino acids initiated immediately after induction of anesthesia (n = 33). The study's primary outcome measurements assessed renal function. These assessments included duration of renal dysfunction, duration and severity of acute kidney injury (AKI), estimated glomerular filtration rate (eGFR) over time, urine output, and use of renal-replacement therapy. Complications and other measures of morbidity were also assessed. RESULTS: Sixty-nine patients (mean age 71.5 [standard deviation 9.2] years; 19 of 69 women) were enrolled and randomized. Patients received coronary artery bypass graft surgery (37/69), valve surgery (24/69), coronary artery bypass graft and valve surgery (6/69), or other procedures (2/69). Mean on-pump time was 268 [standard deviation 136] minutes. Duration of renal dysfunction did not differ between the groups (relative risk, 0.86; 95% confidence interval [CI], 0.19-3.79, P = .84). However, patients who received the amino acid infusion had a reduced duration of AKI (relative risk, 0.02; 95% CI, 0.005-0.11, P < .0001) and greater eGFR (+10.8%; 95% CI, 1.0%-20.8%, P = .033). Daily mean urine output was also significantly greater in patients who received the amino acid infusion (1.4 ± 0.5 vs 1.7 ± 0.9 L/d; P = .046). CONCLUSIONS: Commencing an infusion of standard amino acids immediately after the induction of anesthesia did not alter duration of renal dysfunction; however, other key measures of renal function (duration of AKI, eGFR and urine output) were significantly improved. These results warrant replication in multicenter clinical trials.

Early Enteral Nutrition Reduces Mortality and Improves Other Key Outcomes in Patients With Major Burn Injury: A Meta-Analysis of Randomized Controlled Trials.

OBJECTIVES: To identify, appraise, and synthesize current evidence to determine whether early enteral nutrition alters patient outcomes from major burn injury. DATA SOURCES: Medline, Embase, and the China National Knowledge Infrastructure were searched. The close out date was May 1, 2018. STUDY SELECTION: Early enteral nutrition was defined as a standard formula commenced within 24 hours of injury or admission to ICU or burn unit. Comparators included any form of nutrition support "except" early enteral nutrition. Only randomized controlled trials reporting patient-centered outcomes were eligible for inclusion. DATA EXTRACTION: The primary outcome was mortality. Gastrointestinal hemorrhage, sepsis, pneumonia, renal failure, and hospital stay were evaluated as secondary outcomes. DATA SYNTHESIS: Nine-hundred fifty-eight full-text articles were retrieved and screened. Seven randomized controlled trials enrolling 527 participants with major burn injury were included. Compared with all other types of nutrition support, early enteral nutrition significantly reduced mortality (odds ratio, 0.36; 95% CI, 0.18-0.72; p = 0.003; I = 0%). Early enteral nutrition also significantly reduced gastrointestinal hemorrhage (odds ratio, 0.21; 95% CI, 0.09-0.51; p = 0.0005; I = 0%), sepsis (odds ratio, 0.23; 95% CI, 0.11-0.48; p < 0.0001; I = 0%), pneumonia (odds ratio, 0.41; 95% CI, 0.21-0.81; p = 0.01; I = 63%), renal failure (odds ratio, 0.27; 95% CI, 0.09-0.82; p = 0.02; I = 32%), and duration of hospital stay (-15.31 d; 95% CI, -20.43 to -10.20; p < 0.00001; I = 0%). CONCLUSIONS: The improvements in clinical outcomes demonstrated in this meta-analysis are consistent with the physiologic rationale cited to support clinical recommendations for early enteral nutrition made by major clinical practice guidelines: gut integrity is preserved leading to fewer gastrointestinal hemorrhages, less infectious complications, a reduction in consequent organ failures, and a reduction in the onset of sepsis. The cumulative benefit of these effects improves patient survival and reduces hospital length of stay.

The Effect of IV Amino Acid Supplementation on Mortality in ICU Patients May Be Dependent on Kidney Function: Post Hoc Subgroup Analyses of a Multicenter Randomized Trial.

OBJECTIVES: We investigated whether preexisting kidney function determines if ICU patients may benefit from increased (2.0 g/kg/d) protein intake. DESIGN: Post hoc, hypothesis-generating, subgroup analysis of a multicenter, phase 2, randomized clinical trial. All analyses were conducted by intention to treat and maintained group allocation. Ninety-day mortality was the primary outcome. SETTING: ICUs of 16 hospitals throughout Australia and New Zealand. PATIENTS: Adult critically ill patients expected to remain in the study ICU for longer than 2 days. INTERVENTIONS: Random allocation to receive a daily supplement of up to 100 g of IV amino acids to achieve a total protein intake of 2.0 g/kg/d or standard nutrition care. MEASUREMENTS AND MAIN RESULTS: A total of 474 patients were randomized: 235 to standard care and 239 to IV amino acid supplementation. There was a statistically significant interaction between baseline kidney function and supplementation with study amino acids (p value for interaction = 0.026). Within the subgroup of patients with normal kidney function at randomization, patients who were allocated to receive the study amino acid supplement were less likely to die before study day 90 (covariate-adjusted risk difference, -7.9%; 95% CI, -15.1 to -0.7; p = 0.034). Furthermore, amino acid supplementation significantly increased estimated glomerular filtration rate in these patients (repeated-measures treatment × time interaction p = 0.009). Within the subgroup of patients with baseline kidney dysfunction and/or risk of progression of acute kidney injury, a significant effect of the study intervention on mortality was not found (covariate-adjusted risk difference, -0.6%; 95% CI, -16.2 to 15.2; p = 0.95). CONCLUSIONS: In this post hoc, hypothesis-generating, subgroup analysis, we observed reduced mortality and improved estimated glomerular filtration rate in ICU patients with normal kidney function who were randomly allocated to receive increased protein intake (up to 2.0 g/kg/d). We strongly recommend confirmation of these results in trials with low risk of bias before this treatment is recommended for routine care.