Use of selective gut decontamination in critically ill children: PICnIC a pilot RCT and mixed-methods study.

Background: Healthcare-associated infections are a major cause of morbidity and mortality in critically ill children. In adults, data suggest the use of selective decontamination of the digestive tract may reduce the incidence of healthcare-associated infections. Selective decontamination of the digestive tract has not been evaluated in the paediatric intensive care unit population. Objectives: To determine the feasibility of conducting a multicentre, cluster-randomised controlled trial in critically ill children comparing selective decontamination of the digestive tract with standard infection control. Design: Parallel-group pilot cluster-randomised controlled trial with an integrated mixed-methods study. Setting: Six paediatric intensive care units in England. Participants: Children (> 37 weeks corrected gestational age, up to 16 years) requiring mechanical ventilation expected to last for at least 48 hours were eligible for the PICnIC pilot cluster-randomised controlled trial. During the ecology periods, all children admitted to the paediatric intensive care units were eligible. Parents/legal guardians of recruited patients and healthcare professionals working in paediatric intensive care units were eligible for inclusion in the mixed-methods study. Interventions: The interventions in the PICnIC pilot cluster-randomised controlled trial included administration of selective decontamination of the digestive tract as oro-pharyngeal paste and as a suspension given by enteric tube during the period of mechanical ventilation. Main outcome measures: The decision as to whether a definitive cluster-randomised controlled trial is feasible is based on multiple outcomes, including (but not limited to): (1) willingness and ability to recruit eligible patients; (2) adherence to the selective decontamination of the digestive tract intervention; (3) acceptability of the definitive cluster-randomised controlled trial; (4) estimation of recruitment rate; and (5) understanding of potential clinical and ecological outcome measures. Results: A total of 368 children (85% of all those who were eligible) were enrolled in the PICnIC pilot cluster-randomised controlled trial across six paediatric intensive care units: 207 in the baseline phase (Period One) and 161 in the intervention period (Period Two). In sites delivering selective decontamination of the digestive tract, the majority (98%) of children received at least one dose of selective decontamination of the digestive tract, and of these, 68% commenced within the first 6 hours. Consent for the collection of additional swabs was low (44%), though data completeness for potential outcomes, including microbiology data from routine clinical swab testing, was excellent. Recruited children were representative of the wider paediatric intensive care unit population. Overall, 3.6 children/site/week were recruited compared with the potential recruitment rate for a definitive cluster-randomised controlled trial of 3 children/site/week, based on data from all UK paediatric intensive care units. The proposed trial, including consent and selective decontamination of the digestive tract, was acceptable to parents and staff with adaptations, including training to improve consent and communication, and adaptations to the administration protocol for the paste and ecology monitoring. Clinical outcomes that were considered important included duration of organ failure and hospital stay, healthcare-acquired infections and survival. Limitations: The delivery of the pilot cluster-randomised controlled trial was disrupted by the COVID-19 pandemic, which led to slow set-up of sites, and a lack of face-to face training. Conclusions: PICnIC's findings indicate that a definitive cluster-randomised controlled trial in selective decontamination of the digestive tract in paediatric intensive care units is feasible with the inclusion modifications, which would need to be included in a definitive cluster-randomised controlled trial to ensure that the efficiency of trial processes is maximised. Future work: A definitive trial that incorporates the protocol adaptations and outcomes arising from this study is feasible and should be conducted. Trial registration: This trial is registered as ISRCTN40310490. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 16/152/01) and is published in full in Health Technology Assessment; Vol. 28, No. 8. See the NIHR Funding and Awards website for further award information.

Each year, around 20,000 critically ill children are admitted to paediatric intensive care units in the UK. These children are at a higher risk of healthcare-associated infections, one of the main sources of which is the large number of bacteria in the digestive tract. Spread of bacteria from the digestive tract into other organs, such as the lung (causing ventilator-associated pneumonia) or bloodstream (causing sepsis), can be life-threatening. The risk is highest in those children whose illness is so severe that they require prolonged mechanical ventilation. Stopping the growth of bacteria in the digestive tract (called selective decontamination of the digestive tract) has been shown in adults to reduce the number of hospital-acquired infections. However, there have been no trials in children. We wanted to assess how practical and acceptable such a trial would be comparing standard infection control to selective decontamination of the digestive tract-enhanced infection control and monitoring how each intervention affected antimicrobial resistance. We undertook a pilot study to examine whether clinicians could identify eligible children, enrol them in the study and follow study procedures during the course of paediatric intensive care unit admission. Alongside this, we interviewed parents and clinicians to get their views on the proposed trial. Six hospitals recruited 559 patients over a period of roughly 7 months. Hospitals were randomly allocated to continue with the standard infection control procedure or to give selective decontamination of the digestive tract. Overall, recruitment was higher than expected. Alongside this, we examined the views of patients, caregivers and healthcare professionals to assess their views on whether a trial should be carried out to see if selective decontamination of the digestive tract should become part of the infection control regime for children most at risk of hospital-acquired infection in the paediatric intensive care unit. Overall results suggest that a larger PICnIC trial incorporating patient stakeholder and clinical staff feedback on design and outcomes is feasible and that it is appropriate to conduct a trial into the effectiveness of selective decontamination of the digestive tract administration to minimise hospital-acquired infections.

Short-duration selective decontamination of the digestive tract infection control does not contribute to increased antimicrobial resistance burden in a pilot cluster randomised trial (the ARCTIC Study).

OBJECTIVE: Selective decontamination of the digestive tract (SDD) is a well-studied but hotly contested medical intervention of enhanced infection control. Here, we aim to characterise the changes to the microbiome and antimicrobial resistance (AMR) gene profiles in critically ill children treated with SDD-enhanced infection control compared with conventional infection control. DESIGN: We conducted shotgun metagenomic microbiome and resistome analysis on serial oropharyngeal and faecal samples collected from critically ill, mechanically ventilated patients in a pilot multicentre cluster randomised trial of SDD. The microbiome and AMR profiles were compared for longitudinal and intergroup changes. Of consented patients, faecal microbiome baseline samples were obtained in 89 critically ill children. Additionally, samples collected during and after critical illness were collected in 17 children treated with SDD-enhanced infection control and 19 children who received standard care. RESULTS: SDD affected the alpha and beta diversity of critically ill children to a greater degree than standard care. At cessation of treatment, the microbiome of SDD patients was dominated by Actinomycetota, specifically Bifidobacterium, at the end of mechanical ventilation. Altered gut microbiota was evident in a subset of SDD-treated children who returned late longitudinal samples compared with children receiving standard care. Clinically relevant AMR gene burden was unaffected by the administration of SDD-enhanced infection control compared with standard care. SDD did not affect the composition of the oral microbiome compared with standard treatment. CONCLUSION: Short interventions of SDD caused a shift in the microbiome but not of the AMR gene pool in critically ill children at the end mechanical ventilation, compared with standard antimicrobial therapy.

Selective digestive tract decontamination to prevent healthcare associated infections in critically ill children: the PICNIC multicentre randomised pilot clinical trial.

Healthcare-associated infections (HCAIs) are a major cause of morbidity and mortality in critically ill children. Data from adult studies suggest Selective Decontamination of the Digestive tract (SDD) may reduce the incidence of HCAIs and improve survival. There are no data from randomised clinical trials in the paediatric setting. An open label, parallel group pilot cRCT and mixed-methods perspectives study was conducted in six paediatric intensive care units (PICUs) in England. Participants were children (> 37 weeks corrected gestational age, up to 16 years) requiring mechanical ventilation expected to last for at least 48 h. Sites undertook standard care for a period of 9 weeks and were randomised into 3 sites which continued standard care and 3 where SDD was incorporated into infection control practice for eligible children. Interviews and focus groups were conducted for parents and staff working in PICU. 434 children fulfilled eligibility criteria, of whom 368 (85%) were enrolled. This included 207 in the baseline phase (Period One) and 161 in the intervention period (Period Two). In sites delivering SDD, the majority (98%) of children received at least one dose of SDD and of these, 68% commenced within the first 6 h. Whilst admission swabs were collected in 91% of enrolled children, consent for the collection of additional swabs was low (44%). Recruited children were representative of the wider PICU population. Overall, 3.6 children/site/week were recruited compared with the potential recruitment rate for a definitive cRCT of 3 children/site/week, based on data from all UK PICUs. Parents (n = 65) and staff (n = 44) were supportive of the aims of the study, suggesting adaptations for a larger definitive trial including formulation and administration of SDD paste, approaches to consent and ecology monitoring. Stakeholders identified preferred clinical outcomes, focusing on complications of critical illness and quality-of-life. A definitive cRCT in SDD to prevent HCAIs in critically ill children is feasible but should include adaptations to ecology monitoring along with the dosing schedule and packaging into a paediatric specific format. A definitive study is supported by the findings with adaptations to ecology monitoring and SDD administration.Trial Registration: ISRCTN40310490 Registered 30/10/2020.

Use of Mechanical Ventilation Across 3 Countries.

Importance: The ability to provide invasive mechanical ventilation (IMV) is a mainstay of modern intensive care; however, whether rates of IMV vary among countries is unclear. Objective: To estimate the per capita rates of IMV in adults across 3 high-income countries with large variation in per capita intensive care unit (ICU) bed availability. Design, Setting, and Participants: This cohort study examined 2018 data of patients aged 20 years or older who received IMV in England, Canada, and the US. Exposure: The country in which IMV was received. Main Outcomes and Measures: The main outcome was the age-standardized rate of IMV and ICU admissions in each country. Rates were stratified by age, specific diagnoses (acute myocardial infarction, pulmonary embolus, upper gastrointestinal bleed), and comorbidities (dementia, dialysis dependence). Data analyses were conducted between January 1, 2021, and December 1, 2022. Results: The study included 59 873 hospital admissions with IMV in England (median [IQR] patient age, 61 [47-72] years; 59% men, 41% women), 70 250 in Canada (median [IQR] patient age, 65 [54-74] years; 64% men, 36% women), and 1 614 768 in the US (median [IQR] patient age, 65 [54-74] years; 57% men, 43% women). The age-standardized rate per 100 000 population of IMV was the lowest in England (131; 95% CI, 130-132) compared with Canada (290; 95% CI, 288-292) and the US (614; 95% CI, 614-615). Stratified by age, per capita rates of IMV were more similar across countries among younger patients and diverged markedly in older patients. Among patients aged 80 years or older, the crude rate of IMV per 100 000 population was highest in the US (1788; 95% CI, 1781-1796) compared with Canada (694; 95% CI, 679-709) and England (209; 95% CI, 203-214). Concerning measured comorbidities, 6.3% of admitted patients who received IMV in the US had a diagnosis of dementia (vs 1.4% in England and 1.3% in Canada). Similarly, 5.6% of admitted patients in the US were dependent on dialysis prior to receiving IMV (vs 1.3% in England and 0.3% in Canada). Conclusions and Relevance: This cohort study found that patients in the US received IMV at a rate 4 times higher than in England and twice that in Canada in 2018. The greatest divergence was in the use of IMV among older adults, and patient characteristics among those who received IMV varied markedly. The differences in overall use of IMV among these countries highlight the need to better understand patient-, clinician-, and systems-level choices associated with the varied use of a limited and expensive resource.

New-onset atrial fibrillation in intensive care: epidemiology and outcomes.

AIMS: New-onset atrial fibrillation (NOAF) is common in patients treated on an intensive care unit (ICU), but the long-term impacts on patient outcomes are unclear. We compared national hospital and long-term outcomes of patients who developed NOAF in ICU with those who did not, before and after adjusting for comorbidities and ICU admission factors. METHODS AND RESULTS: Using the RISK-II database (Case Mix Programme national clinical audit of adult intensive care linked with Hospital Episode Statistics and mortality data), we conducted a retrospective cohort study of 4615 patients with NOAF and 27 690 matched controls admitted to 248 adult ICUs in England, from April 2009 to March 2016. We examined in-hospital mortality; hospital readmission with atrial fibrillation (AF), heart failure, and stroke up to 6 years post discharge; and mortality up to 8 years post discharge. Compared with controls, patients who developed NOAF in the ICU were at a higher risk of in-hospital mortality [unadjusted odds ratio (OR) 3.22, 95% confidence interval (CI) 3.02-3.44], only partially explained by patient demographics, comorbidities, and ICU admission factors (adjusted OR 1.50, 95% CI 1.38-1.63). They were also at a higher risk of subsequent hospitalization with AF [adjusted cause-specific hazard ratio (aCHR) 5.86, 95% CI 5.33-6.44], stroke (aCHR 1.47, 95% CI 1.12-1.93), and heart failure (aCHR 1.28, 95% CI 1.14-1.44) independent of pre-existing comorbidities. CONCLUSION: Patients who develop NOAF during an ICU admission are at a higher risk of in-hospital death and readmissions to hospital with AF, heart failure, and stroke than those who do not.

Pharmacological and non-pharmacological treatments and outcomes for new-onset atrial fibrillation in ICU patients: the CAFE scoping review and database analyses.

BACKGROUND: New-onset atrial fibrillation occurs in around 10% of adults treated in an intensive care unit. New-onset atrial fibrillation may lead to cardiovascular instability and thromboembolism, and has been independently associated with increased length of hospital stay and mortality. The long-term consequences are unclear. Current practice guidance is based on patients outside the intensive care unit; however, new-onset atrial fibrillation that develops while in an intensive care unit differs in its causes and the risks and clinical effectiveness of treatments. The lack of evidence on new-onset atrial fibrillation treatment or long-term outcomes in intensive care units means that practice varies. Identifying optimal treatment strategies and defining long-term outcomes are critical to improving care. OBJECTIVES: In patients treated in an intensive care unit, the objectives were to (1) evaluate existing evidence for the clinical effectiveness and safety of pharmacological and non-pharmacological new-onset atrial fibrillation treatments, (2) compare the use and clinical effectiveness of pharmacological and non-pharmacological new-onset atrial fibrillation treatments, and (3) determine outcomes associated with new-onset atrial fibrillation. METHODS: We undertook a scoping review that included studies of interventions for treatment or prevention of new-onset atrial fibrillation involving adults in general intensive care units. To investigate the long-term outcomes associated with new-onset atrial fibrillation, we carried out a retrospective cohort study using English national intensive care audit data linked to national hospital episode and outcome data. To analyse the clinical effectiveness of different new-onset atrial fibrillation treatments, we undertook a retrospective cohort study of two large intensive care unit databases in the USA and the UK. RESULTS: Existing evidence was generally of low quality, with limited data suggesting that beta-blockers might be more effective than amiodarone for converting new-onset atrial fibrillation to sinus rhythm and for reducing mortality. Using linked audit data, we showed that patients developing new-onset atrial fibrillation have more comorbidities than those who do not. After controlling for these differences, patients with new-onset atrial fibrillation had substantially higher mortality in hospital and during the first 90 days after discharge (adjusted odds ratio 2.32, 95% confidence interval 2.16 to 2.48; adjusted hazard ratio 1.46, 95% confidence interval 1.26 to 1.70, respectively), and higher rates of subsequent hospitalisation with atrial fibrillation, stroke and heart failure (adjusted cause-specific hazard ratio 5.86, 95% confidence interval 5.33 to 6.44; adjusted cause-specific hazard ratio 1.47, 95% confidence interval 1.12 to 1.93; and adjusted cause-specific hazard ratio 1.28, 95% confidence interval 1.14 to 1.44, respectively), than patients who did not have new-onset atrial fibrillation. From intensive care unit data, we found that new-onset atrial fibrillation occurred in 952 out of 8367 (11.4%) UK and 1065 out of 18,559 (5.7%) US intensive care unit patients in our study. The median time to onset of new-onset atrial fibrillation in patients who received treatment was 40 hours, with a median duration of 14.4 hours. The clinical characteristics of patients developing new-onset atrial fibrillation were similar in both databases. New-onset atrial fibrillation was associated with significant average reductions in systolic blood pressure of 5 mmHg, despite significant increases in vasoactive medication (vasoactive-inotropic score increase of 2.3; p < 0.001). After adjustment, intravenous beta-blockers were not more effective than amiodarone in achieving rate control (adjusted hazard ratio 1.14, 95% confidence interval 0.91 to 1.44) or rhythm control (adjusted hazard ratio 0.86, 95% confidence interval 0.67 to 1.11). Digoxin therapy was associated with a lower probability of achieving rate control (adjusted hazard ratio 0.52, 95% confidence interval 0.32 to 0.86) and calcium channel blocker therapy was associated with a lower probability of achieving rhythm control (adjusted hazard ratio 0.56, 95% confidence interval 0.39 to 0.79) than amiodarone. Findings were consistent across both the combined and the individual database analyses. CONCLUSIONS: Existing evidence for new-onset atrial fibrillation management in intensive care unit patients is limited. New-onset atrial fibrillation in these patients is common and is associated with significant short- and long-term complications. Beta-blockers and amiodarone appear to be similarly effective in achieving cardiovascular control, but digoxin and calcium channel blockers appear to be inferior. FUTURE WORK: Our findings suggest that a randomised controlled trial of amiodarone and beta-blockers for management of new-onset atrial fibrillation in critically ill patients should be undertaken. Studies should also be undertaken to provide evidence for or against anticoagulation for patients who develop new-onset atrial fibrillation in intensive care units. Finally, given that readmission with heart failure and thromboembolism increases following an episode of new-onset atrial fibrillation while in an intensive care unit, a prospective cohort study to demonstrate the incidence of atrial fibrillation and/or left ventricular dysfunction at hospital discharge and at 3 months following the development of new-onset atrial fibrillation should be undertaken. TRIAL REGISTRATION: Current Controlled Trials ISRCTN13252515. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 71. See the NIHR Journals Library website for further project information.

BACKGROUND: Atrial fibrillation can cause heart failure and stroke. It can also affect heart rate in different ways. It is common for patients admitted to intensive care units to develop atrial fibrillation. When patients have never had atrial fibrillation before, this is called 'new-onset atrial fibrillation'. We do not know how new-onset atrial fibrillation in patients treated in an intensive care unit affects heart rate and blood pressure, what the best treatments are or how treatments affect how people recover. METHODS: We looked at studies of new-onset atrial fibrillation treatments in intensive care units to see if some treatments have been shown to work better. We used a national database to see what happens to intensive care unit patients in the UK who develop new-onset atrial fibrillation. We also used two databases from intensive care units in the UK and the USA to see how many patients in the intensive care units have new-onset atrial fibrillation, how atrial fibrillation affects heart rate and blood pressure, and whether or not some treatments work better than others. RESULTS: Between 6% and 11% of intensive care unit patients develop new-onset atrial fibrillation. These patients are more likely to die in hospital and in the first 90 days after discharge than those who do not. They are also more likely to be readmitted to hospital with atrial fibrillation, stroke and heart failure. The evidence for new-onset atrial fibrillation treatments is limited, but suggests that beta-blockers or amiodarone may work better than calcium channel blockers or digoxin. CONCLUSIONS: New-onset atrial fibrillation in intensive care units is common, and outcomes are worse in patients who develop new-onset atrial fibrillation than in those who do not. Our research shows that some new-onset atrial fibrillation treatments work better than others. This information will help us to plan a study to improve health after new-onset atrial fibrillation.

Trends in Intensive Care for Patients with COVID-19 in England, Wales, and Northern Ireland.

Rationale: By describing trends in intensive care for patients with coronavirus disease (COVID-19) we aim to support clinical learning, service planning, and hypothesis generation.Objectives: To describe variation in ICU admission rates over time and by geography during the first wave of the epidemic in England, Wales, and Northern Ireland; to describe trends in patient characteristics on admission to ICU, first-24-hours physiology in ICU, processes of care in ICU and patient outcomes; and to explore deviations in trends during the peak period.Methods: A cohort of 10,741 patients with COVID-19 in the Case Mix Program national clinical audit from February 1 to July 31, 2020, was used. Analyses were stratified by time period (prepeak, peak, and postpeak periods) and geographical region. Logistic regression was used to estimate adjusted differences in 28-day in-hospital mortality between periods.Measurements and Main Results: Admissions to ICUs peaked almost simultaneously across regions but varied 4.6-fold in magnitude. Compared with patients admitted in the prepeak period, patients admitted in the postpeak period were slightly younger but with higher degrees of dependency and comorbidity on admission to ICUs and more deranged first-24-hours physiology. Despite this, receipt of invasive ventilation and renal replacement therapy decreased, and adjusted 28-day in-hospital mortality was reduced by 11.8% (95% confidence interval, 8.7%-15.0%). Many variables exhibited u-shaped or n-shaped curves during the peak.Conclusions: The population of patients with COVID-19 admitted to ICUs, and the processes of care in ICUs, changed over the first wave of the epidemic. After adjustment for important risk factors, there was a substantial improvement in patient outcomes.

Prognostic Factors for 30-Day Mortality in Critically Ill Patients With Coronavirus Disease 2019: An Observational Cohort Study.

OBJECTIVES: To identify characteristics that predict 30-day mortality among patients critically ill with coronavirus disease 2019 in England, Wales, and Northern Ireland. DESIGN: Observational cohort study. SETTING: A total of 258 adult critical care units. PATIENTS: A total of 10,362 patients with confirmed coronavirus disease 2019 with a start of critical care between March 1, 2020, and June 22, 2020, of whom 9,990 were eligible (excluding patients with a duration of critical care less than 24 hr or missing core variables). MEASUREMENTS AND MAIN RESULTS: The main outcome measure was time to death within 30 days of the start of critical care. Of 9,990 eligible patients (median age 60 yr, 70% male), 3,933 died within 30 days of the start of critical care. As of July 22, 2020, 189 patients were still receiving critical care and a further 446 were still in acute hospital. Data were missing for between 0.1% and 7.2% of patients across prognostic factors. We imputed missing data ten-fold, using fully conditional specification and continuous variables were modeled using restricted cubic splines. Associations between the candidate prognostic factors and time to death within 30 days of the start of critical care were determined after adjustment for multiple variables with Cox proportional hazards modeling. Significant associations were identified for age, ethnicity, deprivation, body mass index, prior dependency, immunocompromise, lowest systolic blood pressure, highest heart rate, highest respiratory rate, Pao2/Fio2 ratio (and interaction with mechanical ventilation), highest blood lactate concentration, highest serum urea, and lowest platelet count over the first 24 hours of critical care. Nonsignificant associations were found for sex, sedation, highest temperature, and lowest hemoglobin concentration. CONCLUSIONS: We identified patient characteristics that predict an increased likelihood of death within 30 days of the start of critical care for patients with coronavirus disease 2019. These findings may support development of a prediction model for benchmarking critical care providers.

Development, Validation, and Clinical Utility Assessment of a Prognostic Score for 1-Year Unplanned Rehospitalization or Death of Adult Sepsis Survivors.

Importance: The longer-term risk of rehospitalizations and death of adult sepsis survivors is associated with index sepsis illness characteristics. Objective: To derive and validate a parsimonious prognostic score for unplanned rehospitalizations or death in the first year after hospital discharge of adult sepsis survivors. Design, Setting, and Participants: This cohort study used data from the Intensive Care National Audit & Research Centre Case Mix Programme database on adult sepsis survivors identified from consecutive critical care admissions to 192 adult general critical care units in England, United Kingdom, between April 1, 2009, and March 31, 2014 (94 748 patients in the derivation cohort), and between April 1, 2014, and March 31, 2015 (24 669 patients in the validation cohort). Statistical analysis was performed from July 5 to October 31, 2019. Generic characteristics (age, sex, race/ethnicity, 2015 Index of Multiple Deprivation [IMD2015] in England quintiles, preadmission dependence, previous hospitalizations in the year preceding index sepsis admission, comorbidity, admission type, Acute Physiology and Chronic Health Evaluation II physiology score, hospital length of stay, worst blood lactate and blood hemoglobin concentrations, and type of hospital) and sepsis-specific characteristics (site of infection, numbers of organ dysfunctions, and organ support) at the index sepsis admission were used as predictors. Main Outcomes and Measures: Prognostic score derived and validated using multivariable logistic regression for the outcome of unplanned rehospitalization or death in the first year after hospital discharge of adult sepsis survivors, as well as clinical usefulness assessed using decision curve analysis. Prognostic score validation was performed for internal validation with bootstrapping and temporal cohort external validation. Results: This cohort study included 94 748 patients (51 164 men [54.0%]; mean [SD] age, 61.3 [17.0] years) in the derivation cohort and 24 669 patients (13 255 men [53.7%]; mean [SD] age, 62.1 [16.8%]) in the validation cohort. Unplanned rehospitalization or death in the first year after hospital discharge occurred for 48 594 patients (51.3%) in the derivation cohort and 13 129 patients (53.2%) in the validation cohort. Eight independent predictors were identified and weighted to generate a prognostic score for every patient: previous hospitalizations, age in 10-year increments, IMD2015 in England quintiles, preadmission dependence, comorbidities, admission type, blood hemoglobin level, and site of infection. The total prognostic score ranged from 0 to 22 points, with lower scores indicating a lower risk of the outcome. The derivation and validation cohorts had similar rates of prognostic scores of 0 to 4 points (5088 of 16 684 patients [30.5%] and 471 of 1725 patients [27.3%]) and prognostic scores of 11 points or more (15 732 of 21 641 patients [72.7%] and 5753 of 7952 patients [72.3%]). The area under the receiver operating characteristic curve for the prognostic score was 0.675 (95% CI, 0.672-0.679). The decision curve analysis highlighted an optimal score cutoff of 7 points or more. Conclusions and Relevance: The prognostic score reported in this study uses 8 internationally feasible predictors measured during the index sepsis admission and provides clinically useful information on sepsis survivors' risk of unplanned rehospitalization or death in the first year after hospital discharge.

Risk Factors at Index Hospitalization Associated With Longer-term Mortality in Adult Sepsis Survivors.

Importance: Sepsis survivors, defined as adult patients who survived to hospital discharge following a critical care unit admission for sepsis, are at increased risk of long-term mortality. Identifying factors independently associated with long-term mortality, known during critical care admission for sepsis, could inform targeted strategies to reduce this risk. Objective: To assess, in adult sepsis survivors, factors independently associated with long-term mortality, known during their index critical care admission for sepsis, meeting Third International Consensus Definitions for Sepsis and Septic Shock criteria. Design, Setting, and Participants: This cohort study included a nationally representative sample of 94 748 adult sepsis survivors from 192 critical care units in England. Participants were identified from consecutive critical care admissions between April 1, 2009, and March 31, 2014, with survival status ascertained as of March 31, 2015. Statistical analyses were completed in June 2017. Exposures: Generic patient characteristics (age, sex, ethnicity, severe comorbidities [defined using the Acute Physiology and Chronic Health Evaluation II method], dependency, surgical status, and acute illness severity [scored using the Acute Physiology and Chronic Health Evaluation II acute physiology component]) and sepsis-specific patient characteristics (site of infection, number of organ dysfunctions, and septic shock status) known during index critical care admission for sepsis. Main Outcomes and Measures: Long-term mortality in adult sepsis survivors with maximum follow-up of 6 years. Adjusted hazard ratios (HRs) were estimated using Cox regression for both generic and sepsis-specific patient characteristics. Results: Sepsis survivors had a mean (SD) age of 61.3 (17.0) years, 43 584 (46.0%) were female, and 86 056 (90.8%) were white. A total of 46.3% had respiratory site of infection. By 1 year from hospital discharge, 15% of sepsis survivors had died, with 6% to 8% dying per year over the subsequent 5 years. Age, sex, race/ethnicity, severe comorbidities, dependency, nonsurgical status, and site of infection were independently associated with long-term mortality. Compared with single-organ dysfunction, having 2 or 3 organ dysfunctions was associated with increased risk of long-term mortality (adjusted HR, 1.07; 95% CI, 1.01-1.13; and adjusted HR, 1.18; 95% CI, 1.03-1.14, respectively), while having 4 organ dysfunctions or more was not associated with increased risk. Unexpectedly, the Acute Physiology and Chronic Health Evaluation acute physiology component score had an incremental association with long-term mortality (adjusted HR, 1.11 for every 5-point increase; 95% CI, 1.08-1.13). The adjusted HR for septic shock was 0.89 (95% CI, 0.85-0.92). Conclusions and Relevance: This study suggests that generic and sepsis-specific risk factors, known during index critical care admission for sepsis, could identify a high-risk sepsis survivor population for biological characterization and designing interventions to reduce long-term mortality.

Characteristics and Outcome of Cancer Patients Admitted to the ICU in England, Wales, and Northern Ireland and National Trends Between 1997 and 2013.

OBJECTIVE: To describe trends in outcomes of cancer patients with an unplanned admission to the ICU between 1997 and 2013 and to identify risk factors for mortality of those admitted between 2009 and 2013. DESIGN: Retrospective analysis. SETTING: Intensive Care National Audit & Research Centre Case Mix Programme Database including data of ICUs in England, Wales, and Northern Ireland. PATIENTS: Patients (99,590) with a solid tumor and 13,538 patients with a hematological malignancy with an unplanned ICU admission between 1997 and 2013; 39,734 solid tumor patients and 6,652 patients with a hematological malignancy who were admitted between 2009 and 2013 were analyzed in depth. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In solid tumor patients admitted between 2009 and 2013, hospital mortality was 26.4%. Independent risk factors for hospital mortality were metastatic disease (odds ratio, 1.99), cardiopulmonary resuscitation before ICU admission (odds ratio, 1.63), Intensive Care National Audit & Research Centre Physiology score (odds ratio, 1.14), admission for gastrointestinal (odds ratio, 1.12), respiratory (odds ratio, 1.48) or neurological (odds ratio, 1.65) reasons, and previous ICU admission (odds ratio, 1.18). In patients with a hematological malignancy admitted between 2009 and 2013, hospital mortality was 53.6%. Independent risk factors for hospital mortality were age (odds ratio, 1.02), cardiopulmonary resuscitation before ICU admission (odds ratio, 1.90), Intensive Care National Audit & Research Centre Physiology Score (odds ratio, 1.12), admission for hematological (odds ratio, 1.48) or respiratory (odds ratio, 1.56) reasons, bone marrow transplant (odds ratio, 1.53), previous ICU admission (odds ratio, 1.43), and mechanical ventilation within 24 hours of admission (odds ratio, 1.33). Trend analysis showed a significant decrease in ICU and hospital mortality and length of stay between 1997 and 2013 despite little change in severity of illness during this time. CONCLUSIONS: Between 1997 and 2013, the outcome of cancer patients with an unplanned admission to ICU improved significantly. Among those admitted between 2009 and 2013, independent risk factors for hospital mortality were age, severity of illness, previous cardiopulmonary resuscitation, previous ICU admission, metastatic disease, and admission for respiratory reasons.

Psychometric assessment of the Family Satisfaction in the Intensive Care Unit questionnaire in the United Kingdom.

PURPOSE: To establish the psychometric properties of the Family Satisfaction in the Intensive Care Unit 24-item (FS-ICU-24) questionnaire in the United Kingdom. MATERIALS AND METHODS: The Family-Reported Experiences Evaluation study recruited family members of patients staying at least 24 hours in 20 participating intensive care units. Questionnaires were evaluated for nonresponse, floor/ceiling effects, redundancy, and construct validity. Internal consistency was evaluated with item-to-own scale correlations and Cronbach α. Confirmatory and exploratory factor analyses were used to explore the underlying structure. RESULTS: Twelve thousand three hundred forty-six family members of 6380 patients were recruited and 7173 (58%) family members of 4615 patients returned a completed questionnaire. One family member per patient was included in the psychometric assessment. Six items had greater than 10% nonresponse; 1 item had a ceiling effect; and 11 items had potential redundancy. Internal consistency was high (Cronbach α, overall .96; satisfaction with care, .94; satisfaction with decision making, .93). The 2-factor solution was not a good fit. Exploratory factor analysis indicated that satisfaction with decision making encompassed 2 constructs-satisfaction with information and satisfaction with the decision-making process. CONCLUSIONS: The Family Satisfaction in the Intensive Care Unit 24-item questionnaire demonstrated good psychometric properties in the United Kingdom setting. Construct validity could be improved by use of 3 domains and some scope for further improvement was identified.

Development and validation of the new ICNARC model for prediction of acute hospital mortality in adult critical care.

PURPOSE: To develop and validate an improved risk model to predict acute hospital mortality for admissions to adult critical care units in the UK. MATERIALS AND METHODS: 155,239 admissions to 232 adult critical care units in England, Wales and Northern Ireland between January and December 2012 were used to develop a risk model from a set of 38 candidate predictors. The model was validated using 90,017 admissions between January and September 2013. RESULTS: The final model incorporated 15 physiological predictors (modelled with continuous nonlinear models), age, dependency prior to hospital admission, chronic liver disease, metastatic disease, haematological malignancy, CPR prior to admission, location prior to admission/urgency of admission, primary reason for admission and interaction terms. The model was well calibrated and outperformed the current ICNARC model on measures of discrimination (area under the receiver operating characteristic curve 0.885 versus 0.869) and model fit (Brier's score 0.108 versus 0.115). On average, the new model reclassified patients into more appropriate risk categories (net reclassification improvement 19.9; P<0.0001). The model performed well across patient subgroups and in specialist critical care units. CONCLUSIONS: The risk model developed in this study showed excellent discrimination and calibration and when validated on a different period of time and across different types of critical care unit. This in turn allows improved accuracy of comparisons between UK critical care providers.

Relationship Between Peak Lactate and Patient Outcome Following High-Risk Gastrointestinal Surgery: Influence of the Nature of Their Surgery: Elective Versus Emergency.

OBJECTIVES: The association between hyperlactatemia and adverse outcome in patients admitted to ICUs following gastrointestinal surgery has not been reported. To explore the hypothesis that in a large cohort of gastrointestinal surgical patients, the peak serum lactate (in the first 24 hr) observed in patients admitted to ICU following surgery is associated with unadjusted and severity-adjusted acute hospital mortality and that the strength of association is greater in patients admitted following "emergency" surgery than in patients admitted following "elective" surgery. DESIGN: A retrospective cohort study of all patients who had gastrointestinal surgery and were admitted directly to the ICU between 2008 and 2012. SETTING: Two hundred forty-nine hospitals in the United Kingdom. PATIENTS: One hundred twenty-one thousand nine hundred ninety patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Peak blood lactate in the first 24 hours of admission to critical care, acute hospital mortality, length of stay, and other variables routinely collected within the U.K. Intensive Care National Audit and Research Centre Case Mix Programme database. Elevated blood lactate was associated with increased risk of death and prolonged duration of stay, and the relationship was maintained once adjusted for confounding variables. The positive association between mortality and levels of blood lactate continued down into the "normal range," without evidence of a plateau. There was no difference in the extent to which hyperlactatemia was related to mortality between patients admitted following elective and emergency surgery. CONCLUSIONS: These findings have implications for our understanding of the role of lactate in critically ill patients.

[Prevalence of cardiovascular risk factors in a cohort of affected by the toxic oil syndrome]. / Prevalencia de factores de riesgo cardiovascular en una cohorte de afectados por el síndrome del aceite tóxico.

BACKGROUND AND OBJECTIVE: During the first stages of the toxic oil syndrome (TOS), elevations of the blood pressure as well as increases in the cholesterol, glucose and triglycerides levels were reported. Here we analyze these cardiovascular risk factors in the chronic phase of the illness and their distribution according to the severity of the illness. We also compare them with those found in the general population. PATIENTS AND METHOD: We studied a sample of 1,862 individuals aged between 35 and 65 years. A medical examination was performed in each and blood pressure, weight, height, tobacco consumption, cholesterol, glucose and triglycerides levels were measured. RESULTS: The prevalence of high blood pressure (>140/90 mmHg) was 46.1% and the prevalence of diabetes mellitus (>126 mg/dl) was 9.1%. The prevalence of obesity (BMI>30) was 24.9%. 11.8% of patients had hypertriglyceridemia (>200 mg/dl) and 19.8% had hypercholesterolemia (>250 mg/dl). 37.9% were smokers. The standardized prevalence rate (SPR) of high blood pressure was 1.35 (95% CI, 1.28-1.44); tobacco consumption SPR=1.27 (95% CI, 1.20-1.36); hypercholesterolemia SPR=1.10 (95% CI, 1.01-1.21). The prevalence of risk factors was higher among the most seriously affected subjects. CONCLUSIONS: The chronic phase of TOS is characterized by a high prevalence of cardiovascular risk factors, which was significantly higher than that expected in the general population.