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.

Health Resource Utilisation and Disparities: an Ecological Study of Admission Patterns Across Ethnicity in England Between 2017 and 2020.

BACKGROUND AND AIM: The COVID-19 pandemic highlighted adverse outcomes in Asian, Black, and ethnic minority groups. More research is required to explore underlying ethnic health inequalities. In this study, we aim to examine pre-COVID ethnic inequalities more generally through healthcare utilisation to contextualise underlying inequalities that were present before the pandemic. DESIGN: This was an ecological study exploring all admissions to NHS hospitals in England from 2017 to 2020. METHODS: The primary outcomes were admission rates within ethnic groups. Secondary outcomes included age-specific and age-standardised admission rates. Sub-analysis of admission rates across an index of multiple deprivation (IMD) deciles was also performed to contextualise the impact of socioeconomic differences amongst ethnic categories. Results were presented as a relative ratio (RR) with 95% confidence intervals. RESULTS: Age-standardised admission rates were higher in Asian (RR 1.40 [1.38-1.41] in 2019) and Black (RR 1.37 [1.37-1.38]) and lower in Mixed groups (RR 0.91 [0.90-0.91]) relative to White. There was significant missingness or misassignment of ethnicity in NHS admissions: with 11.7% of admissions having an unknown/not-stated ethnicity assignment and 'other' ethnicity being significantly over-represented. Admission rates did not mirror the degree of deprivation across all ethnic categories. CONCLUSIONS: This study shows Black and Asian ethnic groups have higher admission rates compared to White across all age groups and when standardised for age. There is evidence of incomplete and misidentification of ethnicity assignment in NHS admission records, which may introduce bias to work on these datasets. Differences in admission rates across individual ethnic categories cannot solely be explained by socioeconomic status. Further work is needed to identify ethnicity-specific factors of these inequalities to allow targeted interventions at the local level.

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.

The Barts Health NHS Trust COVID-19 cohort: characteristics, outcomes and risk scoring of patients in East London.

BACKGROUND: Barts Health National Health Service Trust (BHNHST) serves a diverse population of 2.5 million people in London, UK. We undertook a health services assessment of factors used to evaluate the risk of severe acute respiratory coronavirus 2 (SARS-CoV-2) infection.METHODS: Patients with confirmed polymerase chain reaction (PCR) test results admitted between 1 March and 1 August 2020 were included, alongwith clinician-diagnosed suspected cases. Prognostic factors from the 4C Mortality score and 4C Deterioration scores were extracted from electronic health records and logistic regression was used to quantify the strength of association with 28-day mortality and clinical deterioration using national death registry linkage.RESULTS: Of 2783 patients, 1621 had a confirmed diagnosis, of whom 61% were male and 54% were from Black and Minority Ethnic groups; 26% died within 28 days of admission. Mortality was strongly associated with older age. The 4C mortality score had good stratification of risk with a calibration slope of 1.14 (95% CI 1.01-1.27). It may have under-estimated mortality risk in those with a high respiratory rate or requiring oxygen.CONCLUSION: Patients in this diverse patient cohort had similar mortality associated with prognostic factors to the 4C score derivation sample, but survival might be poorer in those with respiratory failure.

Correction to: Serum sodium and intracranial pressure changes after desmopressin therapy in severe traumatic brain injury patients: a multi-centre cohort study.

Following publication of the original article [1], we were notified that the collaborators' names part of the "The TBI Collaborative" group has not been indexed in Pubmed. Below the collaborators names full list.

Report of the first AKI Round Table meeting: an initiative of the ESICM AKI Section.

PURPOSE: Critical Care Nephrology is an emerging sub-specialty of Critical Care. Despite increasing awareness about the serious impact of acute kidney injury (AKI) and renal replacement therapy (RRT), important knowledge gaps persist. This report represents a summary of a 1-day meeting of the AKI section of the European Society of Intensive Care Medicine (ESICM) identifying priorities for future AKI research. METHODS: International Members of the AKI section of the ESICM were selected and allocated to one of three subgroups: "AKI diagnosis and evaluation", "Medical management of AKI" and "Renal Replacement Therapy for AKI." Using a modified Delphi methodology, each group identified knowledge gaps and developed potential proposals for future collaborative research. RESULTS: The following key research projects were developed: Systematic reviews: (a) epidemiology of AKI with stratification by patient cohorts and diagnostic criteria; (b) role of higher blood pressure targets in patients with hypertension admitted to the Intensive Care Unit, and (c) specific clearance characteristics of different modalities of continuous renal replacement therapy (CRRT). Observational studies: (a) epidemiology of critically ill patients according to AKI duration, and (b) current clinical practice of CRRT. Intervention studies:( a) Comparison of different blood pressure targets in critically ill patients with hypertension, and (b) comparison of clearance of solutes with various molecular weights between different CRRT modalities. CONCLUSION: Consensus was reached on a future research agenda for the AKI section of the ESICM.

Serum sodium and intracranial pressure changes after desmopressin therapy in severe traumatic brain injury patients: a multi-centre cohort study.

BACKGROUND: In traumatic brain injury (TBI) patients desmopressin administration may induce rapid decreases in serum sodium and increase intracranial pressure (ICP). AIM: In an international multi-centre study, we aimed to report changes in serum sodium and ICP after desmopressin administration in TBI patients. METHODS: We obtained data from 14 neurotrauma ICUs in Europe, Australia and UK for severe TBI patients (GCS ≤ 8) requiring ICP monitoring. We identified patients who received any desmopressin and recorded daily dose, 6-hourly serum sodium, and 6-hourly ICP. RESULTS: We studied 262 severe TBI patients. Of these, 39 patients (14.9%) received desmopressin. Median length of treatment with desmopressin was 1 [1-3] day and daily intravenous dose varied between centres from 0.125 to 10 mcg. The median hourly rate of decrease in serum sodium was low (- 0.1 [- 0.2 to 0.0] mmol/L/h) with a median period of decrease of 36 h. The proportion of 6-h periods in which the rate of natremia correction exceeded 0.5 mmol/L/h or 1 mmol/L/h was low, at 8% and 3%, respectively, and ICPs remained stable. After adjusting for IMPACT score and injury severity score, desmopressin administration was independently associated with increased 60-day mortality [HR of 1.83 (1.05-3.24) (p = 0.03)]. CONCLUSIONS: In severe TBI, desmopressin administration, potentially representing instances of diabetes insipidus is common and is independently associated with increased mortality. Desmopressin doses vary markedly among ICUs; however, the associated decrease in natremia rarely exceeds recommended rates and median ICP values remain unchanged. These findings support the notion that desmopressin therapy is safe.

Age of patients undergoing surgery.

BACKGROUND: Advancing age is independently associated with poor postoperative outcomes. The ageing of the general population is a major concern for healthcare providers. Trends in age were studied among patients undergoing surgery in the National Health Service in England. METHODS: Time trend ecological analysis was undertaken of Hospital Episode Statistics and Office for National Statistics data for England from 1999 to 2015. The proportion of patients undergoing surgery in different age groupings, their pooled mean age, and change in age profile over time were calculated. Growth in the surgical population was estimated, with associated costs, to the year 2030 by use of linear regression modelling. RESULTS: Some 68 205 695 surgical patient episodes (31 220 341 men, 45·8 per cent) were identified. The mean duration of hospital stay was 5·3 days. The surgical population was older than the general population of England; this gap increased over time (1999: 47·5 versus 38·3 years; 2015: 54·2 versus 39·7 years). The number of people aged 75 years or more undergoing surgery increased from 544 998 (14·9 per cent of that age group) in 1999 to 1 012 517 (22·9 per cent) in 2015. By 2030, it is estimated that one-fifth of the 75 years and older age category will undergo surgery each year (1·49 (95 per cent c.i. 1·43 to 1·55) million people), at a cost of €3·2 (3·1 to 3·5) billion. CONCLUSION: The population having surgery in England is ageing at a faster rate than the general population. Healthcare policies must adapt to ensure that provision of surgical treatments remains safe and sustainable.

Systematic review and consensus definitions for the Standardised Endpoints in Perioperative Medicine (StEP) initiative: renal endpoints.

BACKGROUND: Renal injury is a common perioperative complication. The adoption of renal endpoints, standardised and valid for use in perioperative clinical trials, would enhance the quality of perioperative clinical research. The Standardised Endpoints in Perioperative Medicine (StEP) initiative was established to derive standardised endpoints for use in perioperative clinical trials. METHODS: A systematic review was conducted to identify renal endpoints currently reported in perioperative clinical trials. In parallel, an initial list of candidate endpoints was developed based on renal theme group expertise. A multi-round Delphi consensus process was used to refine this list and produce a suite of recommended perioperative renal outcome measures. RESULTS: Based on our systematic review, 63 studies were included for analysis. Marked heterogeneity and imprecision of endpoint definitions were observed. Our initial list of candidate endpoints included 10 endpoints for consideration. The response rates for Delphi rounds 1, 2, and 3 were 89% (n=16), 90% (n=75), and 100% (n=6), respectively. A final list of four renal endpoints was identified: acute kidney injury defined by the Kidney Disease: Improving Global Outcomes (KDIGO) consensus criteria, acute kidney disease defined by ≥30% decline in estimated glomerular filtration rate from baseline at 30 days after operation in patients meeting the acute-kidney-injury criteria within 7 days of surgery, the composite of death or renal replacement therapy, and the Major Adverse Kidney Events (MAKE) composite. CONCLUSIONS: We identified four key renal outcome measures that should be considered for use in perioperative clinical trials. Using standardised definitions to capture and report these endpoints will facilitate improved benchmarking and meta-analysis of future trials.

In-hospital clinical outcomes after upper gastrointestinal surgery: Data from an international observational study.

AIMS: Previous research suggests that patients undergoing upper gastrointestinal surgery are at high risk of poor postoperative outcomes. The aim of our study was to describe patient outcomes after elective upper gastrointestinal surgery at a global level. METHODS: Prospective analysis of data collected during an international seven-day cohort study of 474 hospitals in 27 countries. Patients undergoing elective upper gastrointestinal surgery were recruited. Outcome measures were in-hospital complications and mortality at 30-days. Results are presented as n(%) and odds ratios with 95% confidence intervals. RESULTS: 2139 patients were included, of whom 498 (23.2%) developed one or more postoperative complications, with 30 deaths (1.4%). Patients with complications had longer median hospital stay 11 (6-18) days vs. 5 (2-10) days. Infectious complications were most frequent, affecting 368 (17.2%) patients. 328 (15.3%) patients were admitted to critical care postoperatively, of whom 161 (49.1%) developed a complication with 14 deaths (4.3%). In a multivariable logistic regression model we identified age (OR 1.02 [1.01-1.03]), American Society of Anesthesiologists physical status III (OR 2.12 [1.44-3.16]) and IV (OR 3.23 [1.72-6.09]), surgery for cancer (OR 1.63 [1.27-2.11]), open procedure (OR 1.40 [1.10-1.78]), intermediate surgery (OR 1.75 [1.12-2.81]) and major surgery (OR 2.65 [1.72-4.23]) as independent risk factors for postoperative complications. Patients undergoing major surgery for upper gastrointestinal cancer experienced twice the rate of complications compared to those undergoing other procedures (224/578 patients [38.8%] versus 274/1561 patients [17.6%]). CONCLUSIONS: Complications and death are common after upper gastrointestinal surgery. Patients undergoing major surgery for cancer are at greatest risk.

Renal recovery after acute kidney injury.

Acute kidney injury (AKI) is a frequent complication of critical illness and carries a significant risk of short- and long-term mortality, chronic kidney disease (CKD) and cardiovascular events. The degree of renal recovery from AKI may substantially affect these long-term endpoints. Therefore maximising recovery of renal function should be the goal of any AKI prevention and treatment strategy. Defining renal recovery is far from straightforward due in part to the limitations of the tests available to assess renal function. Here, we discuss common pitfalls in the evaluation of renal recovery and provide suggestions for improved assessment in the future. We review the epidemiology of renal recovery and of the association between AKI and the development of CKD. Finally, we stress the importance of post-discharge follow-up of AKI patients and make suggestions for its incorporation into clinical practice. Summary key points are that risk factors for non-recovery of AKI are age, CKD, comorbidity, higher severity of AKI and acute disease scores. Second, AKI and CKD are mutually related and seem to have a common denominator. Third, despite its limitations full recovery of AKI may best be defined as the absence of AKI criteria, and partial recovery as a fall in AKI stage. Fourth, after an episode of AKI, serial follow-up measurements of serum creatinine and proteinuria are warranted to diagnose renal impairment and prevent further progression. Measures to promote recovery are similar to those preventing renal harm. Specific interventions promoting repair are still experimental.

Acute kidney injury and mortality 1 year after major non-cardiac surgery.

BACKGROUND: Even mild and transient acute kidney injury (AKI), defined by increases in serum creatinine level, has been associated with adverse outcomes after major surgery. However, characteristic decreases in creatinine concentration during major illness could confound accurate assessment of postoperative AKI. METHODS: In a single-hospital, retrospective cohort study of non-cardiac surgery, the association between postoperative AKI, defined using the Kidney Disease: Improving Global Outcomes criteria, and 1-year survival was modelled using a multivariable Cox proportional hazards analysis. Factors associated with development of AKI were examined by means of multivariable logistic regression. Temporal changes in serum creatinine during and after the surgical admission in patients with and without AKI were compared. RESULTS: Some 1869 patients were included in the study, of whom 128 (6·8 per cent) sustained AKI (101 stage 1, 27 stage 2-3). Seventeen of the 128 patients with AKI (13·3 per cent) died in hospital compared with 16 of 1741 (0·9 per cent) without AKI (P < 0·001). By 1 year, 34 patients with AKI (26·6 per cent) had died compared with 106 (6·1 per cent) without AKI (P < 0·001). Over the 8-365 days after surgery, AKI was associated with an adjusted hazard ratio for death of 2·96 (95 per cent c.i. 1·86 to 4·71; P < 0·001). Among hospital survivors without AKI, the creatinine level fell consistently (median difference at discharge versus baseline -7 (i.q.r. -15 to 0) µmol/l), but not in those with AKI (0 (-16 to 26) µmol/l) (P < 0·001). CONCLUSION: Although the majority of postoperative AKI was mild, there was a strong association with risk of death in the year after surgery. Underlying decreases in serum creatinine concentration after major surgery could lead to underestimation of AKI severity and overestimation of recovery.

Preoperative renal dysfunction and mortality after non-cardiac surgery.

BACKGROUND: Chronic kidney disease is an important preoperative risk factor. However, the association between renal dysfunction and risk of death has not been well explored in non-cardiac surgery. METHODS: Two prospective observational studies in non-cardiac surgery were analysed: the European Surgical Outcomes Study (EuSOS) and the UK National Confidential Enquiry into Patient Outcome and Death (NCEPOD). The relationship between preoperative estimated glomerular filtration rate (eGFR) and postoperative mortality was examined using multivariable Cox proportional hazards models. RESULTS: In EuSOS, 1580 (4·3 per cent) of 36 779 patients died in hospital; in NCEPOD, 298 (2·8 per cent) of 10 466 patients had died by 60 days after surgery. Chronic kidney disease (eGFR below 60·0 ml per min per 1·73 m(2) ) was present in 6415 patients (17·4 per cent) in EuSOS and 2262 (21·6 per cent) in NCEPOD. Preoperative chronic kidney disease was associated with older age, men, diagnosis of diabetes, cardiovascular or respiratory disease, and non-elective surgery. Preoperative eGFR categories below 60·0 ml per min per 1·73 m(2) were associated with increasing adjusted hazard ratios (HRs) for death compared with a value of 90·0 ml per min per 1·73 m(2) and above. In EuSOS, the risk of death increased with lower eGFR category, to a maximum with eGFR 15·0-29·9 ml per min per 1·73 m(2) (HR 3·37, 95 per cent c.i. 2·70 to 4·22). In NCEPOD, the risk of death also increased with declining eGFR and was maximal for eGFR below 15·0 ml per min per 1·73 m(2) (HR 3·40, 1·78 to 6·50). CONCLUSION: Renal dysfunction is an important risk factor for death after non-cardiac surgery and the risk increases steeply for patients with moderate to severe kidney dysfunction.

Incidence and associations of acute kidney injury after major abdominal surgery.

PURPOSE: Acute kidney injury (AKI) is a recognised risk factor for adverse outcomes in critical illness and hospitalised patients in general. To understand the incidence and associations of AKI as a peri-operative complication of major abdominal surgery, we conducted a systematic literature review and meta-analysis. METHODS: Using a systematic strategy, we searched the electronic reference databases for articles describing post-operative renal outcomes using consensus criteria for AKI diagnosis (RIFLE, AKIN or KDIGO) in the setting of major abdominal surgery. Pooled incidence of AKI and, where reported, pooled relative risk of death after post-operative AKI were estimated using random effects models. RESULTS: From 4287 screened titles, 19 articles met our inclusion criteria describing AKI outcomes in 82,514 patients undergoing abdominal surgery. Pooled incidence of AKI was 13.4% (95% CI 10.9-16.4%). In eight studies that reported the short-term mortality, relative risk of death in the presence of post-operative AKI was 12.6 fold (95% CI, 6.8-23.4). Where reported, length of stay was greater and non-renal post-operative complications were also more frequent in patients experiencing AKI. CONCLUSIONS: Using modern consensus definitions, AKI is a common complication of major abdominal surgery that is associated with adverse patient outcomes including death. While a causative role for AKI cannot be concluded from this analysis, as an important signal of peri-operative harm, AKI should be regarded as an important surgical outcome measure and potential target for clinical interventions.

Indications and management of mechanical fluid removal in critical illness.

BACKGROUND: The Acute Dialysis Quality Initiative (ADQI) dedicated its Twelfth Consensus Conference (2013) to all aspects of fluid therapy, including the management of fluid overload (FO). The aim of the working subgroup 'Mechanical fluid removal' was to review the indications, prescription, and management of mechanical fluid removal within the broad context of fluid management of critically ill patients. METHODS: The working group developed a list of preliminary questions and objectives and performed a modified Delphi analysis of the existing literature. Relevant studies were identified through a literature search using the MEDLINE database and bibliographies of relevant research and review articles. RESULTS: After review of the existing literature, the group agreed the following consensus statements: (i) in critically ill patients with FO and with failure of or inadequate response to pharmacological therapy, mechanical fluid removal should be considered as a therapy to optimize fluid balance. (ii) When using mechanical fluid removal or management, targets for rate of fluid removal and net fluid removal should be based upon the overall fluid balance of the patient and also physiological variables, individualized, and reassessed frequently. (iii) More research on the role and practice of mechanical fluid removal in critically ill patients not meeting fluid balance goals (including in children) is necessary. CONCLUSION: Mechanical fluid removal should be considered as a therapy for FO, but more research is necessary to determine its exact role and clinical application.