A systematic review and meta-analysis of the clinimetric properties of the core outcome measurement instruments for clinical effectiveness trials of nutritional and metabolic interventions in critical illness (CONCISE).

BACKGROUND: CONCISE is an internationally agreed minimum set of outcomes for use in nutritional and metabolic clinical research in critically ill adults. Clinicians and researchers need to be aware of the clinimetric properties of these instruments and understand any limitations to ensure valid and reliable research. This systematic review and meta-analysis were undertaken to evaluate the clinimetric properties of the measurement instruments identified in CONCISE. METHODS: Four electronic databases were searched from inception to December 2022 (MEDLINE via Ovid, EMBASE via Ovid, CINAHL via Healthcare Databases Advanced Search, CENTRAL via Cochrane). Studies were included if they examined at least one clinimetric property of a CONCISE measurement instrument or recognised variation in adults ≥ 18 years with critical illness or recovering from critical illness in any language. The COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist for systematic reviews of Patient-Reported Outcome Measures was used. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses were used in line with COSMIN guidance. The COSMIN checklist was used to evaluate the risk of bias and the quality of clinimetric properties. Overall certainty of the evidence was rated using a modified Grading of Recommendations, Assessment, Development and Evaluation approach. Narrative synthesis was performed and where possible, meta-analysis was conducted. RESULTS: A total of 4316 studies were screened. Forty-seven were included in the review, reporting data for 12308 participants. The Short Form-36 Questionnaire (Physical Component Score and Physical Functioning), sit-to-stand test, 6-m walk test and Barthel Index had the strongest clinimetric properties and certainty of evidence. The Short Physical Performance Battery, Katz Index and handgrip strength had less favourable results. There was limited data for Lawson Instrumental Activities of Daily Living and the Global Leadership Initiative on Malnutrition criteria. The risk of bias ranged from inadequate to very good. The certainty of the evidence ranged from very low to high. CONCLUSIONS: Variable evidence exists to support the clinimetric properties of the CONCISE measurement instruments. We suggest using this review alongside CONCISE to guide outcome selection for future trials of nutrition and metabolic interventions in critical illness. TRIAL REGISTRATION: PROSPERO (CRD42023438187). Registered 21/06/2023.

The metabolic effects of intermittent versus continuous feeding in critically ill patients.

Intermittent (or bolus) feeding regimens in critically ill patients have been of increasing interest to clinicians and scientists. Changes in amino acid, fat and carbohydrate metabolites over time might yet deliver other benefits (e.g. modulation of the circadian rhythm and sleep, and impacts on ghrelin secretion, insulin resistance and autophagy). We set out to characterise these changes in metabolite concentration. The Intermittent versus Continuous Feeding in Critically Ill paitents study (NCT02358512) was an eight-centre single-blinded randomised controlled trial. Patients were randomised to received a continuous (control arm) or intermittent (6x/day, intervention arm) enteral feeding regimen. Blood samples were taken on trial days 1, 7 and 10 immediately before and 30 min after intermittent feeds, and at equivalent timepoints in the control arm. A pre-planned targeted metabolomic analysis was performend using Nuclear Resonance Spectroscopy. Five hundred and ninety four samples were analysed from 75 patients. A total of 24 amino acid-, 19 lipid based-, and 44 small molecule metabolite features. Across the main two axes of variation (40-60% and 6-8% of variance), no broad patterns distinguished between intermittent or continuous feeding arms, across intra-day sampling times or over the 10 days from initial ICU admission. Logfold decreases in abundance were seen in metabolites related to amino acids (Glutamine - 0.682; Alanine - 0.594), ketone body metabolism (Acetone - 0.64; 3-Hydroxybutyric Acid - 0.632; Acetonacetic Acid - 0.586), fatty acid (carnitine - 0.509) and carbohydrate metabolism ( Maltose - 0.510; Citric Acid - 0.485). 2-3 Butanediol, a by-product of sugar-fermenting microbial metabolism also decreased (- 0.489). No correlation was seen with change in quadriceps muscle mass for any of the 20 metabolites varying with time (all p > 0.05). Increasing severity of organ failure was related to increasing ketone body metabolism (3 Hydroxybutyric Acid-1 and - 3; p = 0.056 and p = 0.014), carnitine deficiency (p = 0.002) and alanine abundancy (p - 0.005). A 6-times a day intermittent feeding regimen did not alter metabolite patterns across time compared to continuous feeding in critically ill patients, either within a 24 h period or across 10 days of intervention. Future research on intermittent feeding regimens should focus on clinical process benefits, or extended gut rest and fasting.

Core outcome measures for clinical effectiveness trials of nutritional and metabolic interventions in critical illness: an international modified Delphi consensus study evaluation (CONCISE).

BACKGROUND: Clinical research on nutritional and metabolic interventions in critically ill patients is heterogenous regarding time points, outcomes and measurement instruments used, impeding intervention development and data syntheses, and ultimately worsening clinical outcomes. We aimed to identify and develop a set of core outcome domains and associated measurement instruments to include in all research in critically ill patients. METHODS: An updated systematic review informed a two-stage modified Delphi consensus process (domains followed by instruments). Measurement instruments for domains considered 'essential' were taken through the second stage of the Delphi and a subsequent consensus meeting. RESULTS: In total, 213 participants (41 patients/caregivers, 50 clinical researchers and 122 healthcare professionals) from 24 countries contributed. Consensus was reached on time points (30 and 90 days post-randomisation). Three domains were considered 'essential' at 30 days (survival, physical function and Infection) and five at 90 days (survival, physical function, activities of daily living, nutritional status and muscle/nerve function). Core 'essential' measurement instruments reached consensus for survival and activities of daily living, and 'recommended' measurement instruments for physical function, nutritional status and muscle/nerve function. No consensus was reached for a measurement instrument for Infection. Four further domains met criteria for 'recommended,' but not 'essential,' to measure at 30 days post-randomisation (organ dysfunction, muscle/nerve function, nutritional status and wound healing) and three at 90 days (frailty, body composition and organ dysfunction). CONCLUSION: The CONCISE core outcome set is an internationally agreed minimum set of outcomes for use at 30 and 90 days post-randomisation, in nutritional and metabolic clinical research in critically ill adults.

Ethnic disparities in hospitalisation and hospital-outcomes during the second wave of COVID-19 infection in east London.

It is unclear if changes in public behaviours, developments in COVID-19 treatments, improved patient care, and directed policy initiatives have altered outcomes for minority ethnic groups in the second pandemic wave. This was a prospective analysis of patients aged ≥ 16 years having an emergency admission with SARS-CoV-2 infection between 01/09/2020 and 17/02/2021 to acute NHS hospitals in east London. Multivariable survival analysis was used to assess associations between ethnicity and mortality accounting for predefined risk factors. Age-standardised rates of hospital admission relative to the local population were compared between ethnic groups. Of 5533 patients, the ethnic distribution was White (n = 1805, 32.6%), Asian/Asian British (n = 1983, 35.8%), Black/Black British (n = 634, 11.4%), Mixed/Other (n = 433, 7.8%), and unknown (n = 678, 12.2%). Excluding 678 patients with missing data, 4855 were included in multivariable analysis. Relative to the White population, Asian and Black populations experienced 4.1 times (3.77-4.39) and 2.1 times (1.88-2.33) higher rates of age-standardised hospital admission. After adjustment for various patient risk factors including age, sex, and socioeconomic deprivation, Asian patients were at significantly higher risk of death within 30 days (HR 1.47 [1.24-1.73]). No association with increased risk of death in hospitalised patients was observed for Black or Mixed/Other ethnicity. Asian and Black ethnic groups continue to experience poor outcomes following COVID-19. Despite higher-than-expected rates of hospital admission, Black and Asian patients also experienced similar or greater risk of death in hospital since the start of the pandemic, implying a higher overall risk of COVID-19 associated death in these communities.

Protocol for a prospective cohort study on the use of clinical nutrition and assessment of long-term clinical and functional outcomes in critically ill adult patients.

BACKGROUND AND AIMS: Limited data are available on the impact of clinical nutrition over the course of critical illness and post-discharge outcomes. The present study aims to characterize the use of nutrition support in patients admitted to European intensive care units (ICUs), and its impact on clinical outcomes. Here we present the procedures of data collection and evaluation. METHODS: Around 100 medical, surgical, or trauma ICUs in 11 countries (Austria, Belgium, Czech Republic, Germany, France, Hungary, Italy, Poland, Spain, Sweden, United Kingdom) participate in the study. In defined months between November 2019 and April 2020, approximately 1250 patients are enrolled if staying in ICU for at least five consecutive days. Data from ICU day 1-4 are collected retrospectively, followed by a prospective observation period from day 5-90 after ICU admission. Data collection includes patient characteristics, nutrition parameters, complications, ICU and hospital length of stay, discharge status, and functional outcomes. For data analysis, the target is 1000 patients with complete data. Statistical analyses will be descriptive, with multivariate analyses adjusted for potential confounders to explore associations between nutritional balance and change in functional status, time-to-weaning from invasive mechanical ventilation, time to first clinical complication, and overall 15, 30 and 90-day survival. ETHICS AND DISSEMINATION: This non-interventional study was reviewed and approved by the ethics committee of the Medical University Vienna, Vienna, Austria (approval number 1678/2019), and the respective ethical committees from participating sites at country and/or local level, as required. Results will be shared with investigators on a country level, and a publication and results presentation at the 2021 ESPEN Congress is planned. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04143503.