Nutritional supplementation in children with severe pneumonia in Uganda and Kenya (COAST-Nutrition): a phase 2 randomised controlled trial.

Background: Severe pneumonia in African children results in poor long-term outcomes (deaths/readmissions) with undernutrition as a key risk factor. We hypothesised additional energy/protein-rich Ready-to-Use Therapeutic Foods (RUTF) would meet additional nutritional requirements and improve outcomes. Methods: COAST-Nutrition was an open-label Phase 2 randomised controlled trial in children (aged 6 months-12 years) hospitalised with severe pneumonia (and hypoxaemia, SpO2 <92%) in Mbale, Soroti, Jinja, Masaka Regional Referral Hospitals, Uganda and Kilifi County Hospital, Kenya (ISRCTN10829073 (registered 6th June 2018) PACTR202106635355751 (registered 2nd June 2021)). Children were randomised (ratio 1:1) to enhanced nutritional supplementation with RUTF (plus usual diet) for 56 days vs usual diet (control). The primary outcome was change in mid-upper arm circumference (MUAC) at 90 days as a composite with mortality. Secondary outcomes include anthropometric status, mortality, and readmissions at Days 28, 90 and 180. Findings: Between 12 August 2018 and 22 April 2022, 846 eligible children were randomised, 424 to RUTF and 422 to usual diet, and followed for 180-days [12 (1%) lost-to-follow-up]. RUTF supplement was initiated in 417/419 (>99%). By Day 90, there was no significant difference in the composite endpoint (probabilistic index 0.49, 95% CI 0.45-0.53, p = 0.74). Respective 90-day mortality (13/420 3.1% vs 14/421 3.3%) and MUAC increment (0.54 (SD 0.85) vs 0.55 (SD 0.81)) were similar between arms. There was no difference in any anthropometric secondary endpoints to Day 28, 90 or 180 except skinfold thickness at Day 28 and Day 90 was greater in the RUTF arm. Serious adverse events were higher in the RUTF arm (n = 164 vs 108), mainly due to hospital readmission for acute illness (54/387 (14%) vs 37/375 (10%). Interpretation: Our study suggested that nutritional supplementation with RUTF did not improve outcomes to 180 days in children with severe pneumonia. Funding: This trial is part of the EDCTP2 programme (grant number RIA-2016S-1636-COAST-Nutrition) supported by the European Union, and UK Joint Global Health Trials scheme: Medical Research Council, Department for International Development, Wellcome Trust (grant number MR/L004364/1, UK).

Protocol for a Randomized Controlled Trial to Evaluate a Permissive Blood Pressure Target Versus Usual Care in Critically Ill Children with Hypotension (PRESSURE).

OBJECTIVES: Management of hypotension is a fundamental part of pediatric critical care, with cardiovascular support in the form of fluids or vasoactive drugs offered to every hypotensive child. However, optimal blood pressure (BP) targets are unknown. The PRotocolised Evaluation of PermiSSive BP Targets Versus Usual CaRE (PRESSURE) trial aims to evaluate the clinical and cost-effectiveness of a permissive mean arterial pressure (MAP) target of greater than a fifth centile for age compared with usual care. DESIGN: Pragmatic, open, multicenter, parallel-group randomized control trial (RCT) with integrated economic evaluation. SETTING: Eighteen PICUs across the United Kingdom. PATIENTS: Infants and children older than 37 weeks corrected gestational age to 16 years accepted to a participating PICU, on mechanical ventilation and receiving vasoactive drugs for hypotension. INTERVENTIONS: Adjustment of hemodynamic support to achieve a permissive MAP target greater than fifth centile for age during invasive mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: Randomization is 1:1 to a permissive MAP target or usual care, stratified by site and age group. Due to the emergency nature of the treatment, approaching patients for written informed consent will be deferred until after randomization. The primary clinical outcome is a composite of death and days of ventilatory support at 30 days. Baseline demographics and clinical status will be recorded as well as daily measures of BP and organ support, and discharge outcomes. This RCT received Health Research Authority approval (reference 289545), and a favorable ethical opinion from the East of England-Cambridge South Research Ethics Committee on May 10, 2021 (reference number 21/EE/0084). The trial is registered and has an International Standard RCT Number (reference 20609635). CONCLUSIONS: Trial findings will be disseminated in U.K. national and international conferences and in peer-reviewed journals.

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.

Evaluation of pragmatic oxygenation measurement as a proxy for Covid-19 severity.

Choosing optimal outcome measures maximizes statistical power, accelerates discovery and improves reliability in early-phase trials. We devised and evaluated a modification to a pragmatic measure of oxygenation function, the [Formula: see text] ratio. Because of the ceiling effect in oxyhaemoglobin saturation, [Formula: see text] ratio ceases to reflect pulmonary oxygenation function at high [Formula: see text] values. We found that the correlation of [Formula: see text] with the reference standard ([Formula: see text]/[Formula: see text] ratio) improves substantially when excluding [Formula: see text] and refer to this measure as [Formula: see text]. Using observational data from 39,765 hospitalised COVID-19 patients, we demonstrate that [Formula: see text] is predictive of mortality, and compare the sample sizes required for trials using four different outcome measures. We show that a significant difference in outcome could be detected with the smallest sample size using [Formula: see text]. We demonstrate that [Formula: see text] is an effective intermediate outcome measure in COVID-19. It is a non-invasive measurement, representative of disease severity and provides greater statistical power.

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.

GWAS and meta-analysis identifies 49 genetic variants underlying critical COVID-19.

Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown1 to be highly efficient for discovery of genetic associations2. Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group3. Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We identify potentially druggable targets in multiple systems, including inflammatory signalling (JAK1), monocyte-macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Mortality As a Measure of Treatment Effect in Clinical Trials Recruiting Critically Ill Patients.

OBJECTIVES: All-cause mortality is a common measure of treatment effect in ICU-based randomized clinical trials (RCTs). We sought to understand the performance characteristics of a mortality endpoint by evaluating its temporal course, responsiveness to differential treatment effects, and impact when used as an outcome measure in trials of acute illness. DATA SOURCES: We searched OVID Medline for RCTs published from 1990 to 2018. STUDY SELECTION: We reviewed RCTs that had randomized greater than or equal to 100 patients, were published in one of five high-impact general medical or eight critical care journals, and reported mortality at two or more distinct time points. We excluded trials recruiting pediatric or neonatal patients and cluster RCTs. DATA EXTRACTION: Mortality by randomization group was recorded from the article or estimated from survival curves. Trial impact was assessed by inclusion of results in clinical practice guidelines. DATA SYNTHESIS: From 2,592 potentially eligible trials, we included 343 RCTs (228,784 adult patients). While one third of all deaths by 180 days had occurred by day 7, the risk difference between study arms continued to increase until day 60 (p = 0.01) and possibly day 90 (p = 0.07) and remained stable thereafter. The number of deaths at ICU discharge approximated those at 28-30 days (95% [interquartile range [IQR], 86-106%]), and deaths at hospital discharge approximated those at 60 days (99% [IQR, 94-104%]). Only 13 of 43 interventions (30.2%) showing a mortality benefit have been adopted into widespread clinical practice. CONCLUSIONS: Our findings provide a conceptual framework for choosing a time horizon and interpreting mortality outcome in trials of acute illness. Differential mortality effects persist for 60 to 90 days following recruitment. Location-based measures approximate time-based measures for trials conducted outside the United States. The documentation of a mortality reduction has had a modest impact on practice.

Ethnic differences in SARS-CoV-2 infection and COVID-19-related hospitalisation, intensive care unit admission, and death in 17 million adults in England: an observational cohort study using the OpenSAFELY platform.

BACKGROUND: COVID-19 has disproportionately affected minority ethnic populations in the UK. Our aim was to quantify ethnic differences in SARS-CoV-2 infection and COVID-19 outcomes during the first and second waves of the COVID-19 pandemic in England. METHODS: We conducted an observational cohort study of adults (aged ≥18 years) registered with primary care practices in England for whom electronic health records were available through the OpenSAFELY platform, and who had at least 1 year of continuous registration at the start of each study period (Feb 1 to Aug 3, 2020 [wave 1], and Sept 1 to Dec 31, 2020 [wave 2]). Individual-level primary care data were linked to data from other sources on the outcomes of interest: SARS-CoV-2 testing and positive test results and COVID-19-related hospital admissions, intensive care unit (ICU) admissions, and death. The exposure was self-reported ethnicity as captured on the primary care record, grouped into five high-level census categories (White, South Asian, Black, other, and mixed) and 16 subcategories across these five categories, as well as an unknown ethnicity category. We used multivariable Cox regression to examine ethnic differences in the outcomes of interest. Models were adjusted for age, sex, deprivation, clinical factors and comorbidities, and household size, with stratification by geographical region. FINDINGS: Of 17 288 532 adults included in the study (excluding care home residents), 10 877 978 (62·9%) were White, 1 025 319 (5·9%) were South Asian, 340 912 (2·0%) were Black, 170 484 (1·0%) were of mixed ethnicity, 320 788 (1·9%) were of other ethnicity, and 4 553 051 (26·3%) were of unknown ethnicity. In wave 1, the likelihood of being tested for SARS-CoV-2 infection was slightly higher in the South Asian group (adjusted hazard ratio 1·08 [95% CI 1·07-1·09]), Black group (1·08 [1·06-1·09]), and mixed ethnicity group (1·04 [1·02-1·05]) and was decreased in the other ethnicity group (0·77 [0·76-0·78]) relative to the White group. The risk of testing positive for SARS-CoV-2 infection was higher in the South Asian group (1·99 [1·94-2·04]), Black group (1·69 [1·62-1·77]), mixed ethnicity group (1·49 [1·39-1·59]), and other ethnicity group (1·20 [1·14-1·28]). Compared with the White group, the four remaining high-level ethnic groups had an increased risk of COVID-19-related hospitalisation (South Asian group 1·48 [1·41-1·55], Black group 1·78 [1·67-1·90], mixed ethnicity group 1·63 [1·45-1·83], other ethnicity group 1·54 [1·41-1·69]), COVID-19-related ICU admission (2·18 [1·92-2·48], 3·12 [2·65-3·67], 2·96 [2·26-3·87], 3·18 [2·58-3·93]), and death (1·26 [1·15-1·37], 1·51 [1·31-1·71], 1·41 [1·11-1·81], 1·22 [1·00-1·48]). In wave 2, the risks of hospitalisation, ICU admission, and death relative to the White group were increased in the South Asian group but attenuated for the Black group compared with these risks in wave 1. Disaggregation into 16 ethnicity groups showed important heterogeneity within the five broader categories. INTERPRETATION: Some minority ethnic populations in England have excess risks of testing positive for SARS-CoV-2 and of adverse COVID-19 outcomes compared with the White population, even after accounting for differences in sociodemographic, clinical, and household characteristics. Causes are likely to be multifactorial, and delineating the exact mechanisms is crucial. Tackling ethnic inequalities will require action across many fronts, including reducing structural inequalities, addressing barriers to equitable care, and improving uptake of testing and vaccination. FUNDING: Medical Research Council.

Mechanical Ventilation for Acute Respiratory Distress Syndrome during Extracorporeal Life Support. Research and Practice.

Ventilator-induced lung injury remains a key contributor to the morbidity and mortality of acute respiratory distress syndrome (ARDS). Efforts to minimize this injury are typically limited by the need to preserve adequate gas exchange. In the most severe forms of the syndrome, extracorporeal life support is increasingly being deployed for severe hypoxemia or hypercapnic acidosis refractory to conventional ventilator management strategies. Data from a recent randomized controlled trial, a post hoc analysis of that trial, a meta-analysis, and a large international multicenter observational study suggest that extracorporeal life support, when combined with lower Vt and airway pressures than the current standard of care, may improve outcomes compared with conventional management in patients with the most severe forms of ARDS. These findings raise important questions not only about the optimal ventilation strategies for patients receiving extracorporeal support but also regarding how various mechanisms of lung injury in ARDS may potentially be mitigated by ultra-lung-protective ventilation strategies when gas exchange is sufficiently managed with the extracorporeal circuit. Additional studies are needed to more precisely delineate the best strategies for optimizing invasive mechanical ventilation in this patient population.

Conservative vs liberal fluid therapy in septic shock (CLASSIC) trial-Protocol and statistical analysis plan.

INTRODUCTION: Intravenous (IV) fluid is a key intervention in the management of septic shock. The benefits and harms of lower versus higher fluid volumes are unknown and thus clinical equipoise exists. We describe the protocol and detailed statistical analysis plan for the conservative versus liberal approach to fluid therapy of septic shock in the Intensive Care (CLASSIC) trial. The aim of the CLASSIC trial is to assess benefits and harms of IV fluid restriction versus standard care in adult intensive care unit (ICU) patients with septic shock. METHODS: CLASSIC trial is an investigator-initiated, international, randomised, stratified, and analyst-blinded trial. We will allocate 1554 adult patients with septic shock, who are planned to be or are admitted to an ICU, to IV fluid restriction versus standard care. The primary outcome is mortality at day 90. Secondary outcomes are serious adverse events (SAEs), serious adverse reactions (SARs), days alive at day 90 without life support, days alive and out of the hospital at day 90 and mortality, health-related quality of life (HRQoL), and cognitive function at 1 year. We will conduct the statistical analyses according to a pre-defined statistical analysis plan, including three interim analyses. For the primary analysis, we will use logistic regression adjusted for the stratification variables comparing the two interventions in the intention-to-treat (ITT) population. DISCUSSION: The CLASSIC trial results will provide important evidence to guide clinicians' choice regarding the IV fluid therapy in adults with septic shock.

Perioperative administration of buffered versus non-buffered crystalloid intravenous fluid to improve outcomes following adult surgical procedures: a Cochrane systematic review.

BACKGROUND: Buffered intravenous fluid preparations contain substrates to maintain acid-base status. The objective of this systematic review was to compare the effects of buffered and non-buffered fluids administered during the perioperative period on clinical and biochemical outcomes. METHODS: We searched MEDLINE, EMBASE, CINAHL and the Cochrane Library until May 2017 and included all randomised controlled trials that evaluated buffered versus non-buffered fluids, whether crystalloid or colloid, administered to surgical patients. We assessed the selected studies for risk of bias and graded the level of evidence in accordance with Cochrane recommendations. RESULTS: We identified 19 publications of 18 randomised controlled trials, totalling 1096 participants. Mean difference (MD) in postoperative pH was 0.05 units lower immediately following surgery in the non-buffered group (12 studies of 720 participants; 95% confidence interval (CI) 0.04 to 0.07; I 2 = 61%). This difference did not persist on postoperative day 1. Serum chloride concentration was higher in the non-buffered group at the end of surgery (10 trials of 530 participants; MD 6.77 mmol/L, 95% CI 3.38 to 10.17). This effect persisted until postoperative day 1 (5 trials of 258 participants; MD 8.48 mmol/L, 95% CI 1.08 to 15.88). Quality of this evidence was moderate. We identified variable protocols for fluid administration and total volumes of fluid administered to patients intraoperatively. Outcome data was variably reported at disparate time points and with heterogeneous patient groups. Consequently, the effect size and overall confidence interval was reduced, despite the relatively low inherent risk of bias. There was insufficient evidence on the effect of fluid composition on mortality and organ dysfunction. Confidence intervals of this outcome were wide and the quality of evidence was low (3 trials of 276 participants for mortality; odds ratio (OR) 1.85, 95% CI 0.37 to 9.33; I 2 = 0%). CONCLUSIONS: Small effect sizes for biochemical outcomes and lack of correlated clinical follow-up data mean that robust conclusions on major morbidity and mortality associated with buffered versus non-buffered perioperative fluid choices are still lacking. Buffered fluid may have biochemical benefits, including a significant reduction in postoperative hyperchloraemia and metabolic acidosis.

Randomized Study of Early Continuous Positive Airways Pressure in Acute Respiratory Failure in Children With Impaired Immunity (SCARF) ISRCTN82853500.

OBJECTIVES: Previous trials in adults with impaired immunity and respiratory failure suggest that early noninvasive ventilation avoids endotracheal intubation and improves survival. No randomized clinical trials have addressed this question in children. DESIGN: We undertook an open, parallel-group randomized trial in three pediatric hospitals. SUBJECTS: Children with impaired immunity and acute respiratory failure defined as tachypnoea (> 90th centile); a new requirement for supplemental oxygen; and new chest radiograph infiltrates. INTERVENTIONS: Children were randomly assigned to early PICU admission for continuous positive airways pressure (early continuous positive airways pressure) or to standard care. The primary outcome was endotracheal intubation by 30 days. MEASUREMENTS AND MAIN RESULTS: One-hundred fourteen children met inclusion criteria of whom 42 were randomized between January 2013 and January 2016. There was no significant difference in endotracheal intubation by 30 days with early continuous positive airways pressure (10/21; 48%) compared with standard care (5/21; 24%), odds ratio 2.9 (0.8-10.9), p value equals to 0.11. However, 30-day mortality was significantly higher with early continuous positive airways pressure (7/21; 33%) compared with standard care (1/21; 5%), odds ratio 10.0 (1.1-90.6), p value equals to 0.041. Mortality at 90 days was early continuous positive airways pressure (11/21; 52%) versus standard care (4/21; 19%), odds ratio 4.7 (1.2-18.6), p value equals to 0.029, whereas mortality at 1 year was similar early continuous positive airways pressure (13/21; 61.9%) versus standard care (9/21; 42.7%), odds ratio 2.2 (0.6-7.4), p value equals to 0.22. There were two serious adverse events: early continuous positive airways pressure (pneumothorax) and standard care (hemothorax). CONCLUSIONS: This study provided no evidence to support early PICU admission for continuous positive airways pressure in children with acute respiratory failure and impaired immunity. There was a trend toward increased endotracheal intubation and a higher early mortality in the early continuous positive airways pressure group.

Incidence and Outcomes for Patients With Cirrhosis Admitted to the United Kingdom Critical Care Units.

OBJECTIVE: To assess the epidemiology and outcome of patients with cirrhosis following critical care unit admission. DESIGN: Retrospective cohort study. SETTING: Critical care units in England, Wales, and Northern Ireland participating in the U.K. Intensive Care National Audit and Research Centre Case Mix Programme. PATIENTS: Thirty-one thousand three hundred sixty-three patients with cirrhosis identified of 1,168,650 total critical care unit admissions (2.7%) admitted to U.K. critical care units between 1998 and 2012. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Ten thousand nine hundred thirty-six patients had alcohol-related liver disease (35%). In total, 1.6% of critical care unit admissions in 1998 had cirrhosis rising to 3.1% in 2012. The crude critical care unit mortality of patients with cirrhosis was 41% in 1998 falling to 31% in 2012 (p < 0.001). Crude hospital mortality fell from 58% to 46% over the study period (p < 0.001). Mean(SD) Acute Physiology and Chronic Health Evaluation II score in 1998 was 20.3 (8.5) and 19.5 (7.1) in 2012. Mean Acute Physiology and Chronic Health Evaluation II score for patients with alcohol-related liver disease in 2012 was 20.6 (7.0) and 19.0 (7.2) for non-alcohol-related liver disease (p < 0.001). In adjusted analysis, alcohol-related liver disease was associated with increased risk of death (odds ratio, 1.51 [95% CI, 1.42-1.62; p < 0.001]) with a year-on-year reduction in hospital mortality (adjusted odds ratio, 0.95/yr, [0.94-0.96, p < 0.001]). CONCLUSIONS: More patients with cirrhosis are being admitted to critical care units but with increasing survival rates. Patients with alcohol-related liver disease have reduced survival rates partly explained by higher levels of organ failure at admission. Patients with cirrhosis and organ failure warrant a trial of organ support and universal prognostic pessimism is not justified.

Association of a Care Coordination Model With Health Care Costs and Utilization: The Johns Hopkins Community Health Partnership (J-CHiP).

Importance: The Johns Hopkins Community Health Partnership was created to improve care coordination across the continuum in East Baltimore, Maryland. Objective: To determine whether the Johns Hopkins Community Health Partnership (J-CHiP) was associated with improved outcomes and lower spending. Design, Setting, and Participants: Nonrandomized acute care intervention (ACI) and community intervention (CI) Medicare and Medicaid participants were analyzed in a quality improvement study using difference-in-differences designs with propensity score-weighted and matched comparison groups. The study spanned 2012 to 2016 and took place in acute care hospitals, primary care clinics, skilled nursing facilities, and community-based organizations. The ACI analysis compared outcomes of participants in Medicare and Medicaid during their 90-day postacute episode with those of a propensity score-weighted preintervention group at Johns Hopkins Community Health Partnership hospitals and a concurrent comparison group drawn from similar Maryland hospitals. The CI analysis compared changes in outcomes of Medicare and Medicaid participants with those of a propensity score-matched comparison group of local residents. Interventions: The ACI bundle aimed to improve transition planning following discharge. The CI included enhanced care coordination and integrated behavioral support from local primary care sites in collaboration with community-based organizations. Main Outcomes and Measures: Utilization measures of hospital admissions, 30-day readmissions, and emergency department visits; quality of care measures of potentially avoidable hospitalizations, practitioner follow-up visits; and total cost of care (TCOC) for Medicare and Medicaid participants. Results: The CI group had 2154 Medicare beneficiaries (1320 [61.3%] female; mean age, 69.3 years) and 2532 Medicaid beneficiaries (1483 [67.3%] female; mean age, 55.1 years). For the CI group's Medicaid participants, aggregate TCOC reduction was $24.4 million, and reductions of hospitalizations, emergency department visits, 30-day readmissions, and avoidable hospitalizations were 33, 51, 36, and 7 per 1000 beneficiaries, respectively. The ACI group had 26 144 beneficiary-episodes for Medicare (13 726 [52.5%] female patients; mean patient age, 68.4 years) and 13 921 beneficiary-episodes for Medicaid (7392 [53.1%] female patients; mean patient age, 52.2 years). For the ACI group's Medicare participants, there was a significant reduction in aggregate TCOC of $29.2 million with increases in 90-day hospitalizations and 30-day readmissions of 11 and 14 per 1000 beneficiary-episodes, respectively, and reduction in practitioner follow-up visits of 41 and 29 per 1000 beneficiary-episodes for 7-day and 30-day visits, respectively. For the ACI group's Medicaid participants, there was a significant reduction in aggregate TCOC of $59.8 million and the 90-day emergency department visit rate decreased by 133 per 1000 episodes, but hospitalizations increased by 49 per 1000 episodes and practitioner follow-up visits decreased by 70 and 182 per 1000 episodes for 7-day and 30-day visits, respectively. In total, the CI and ACI were associated with $113.3 million in cost savings. Conclusions and Relevance: A care coordination model consisting of complementary bundled interventions in an urban academic environment was associated with lower spending and improved health outcomes.

Recovery after critical illness: putting the puzzle together-a consensus of 29.

In this review, we seek to highlight how critical illness and critical care affect longer-term outcomes, to underline the contribution of ICU delirium to cognitive dysfunction several months after ICU discharge, to give new insights into ICU acquired weakness, to emphasize the importance of value-based healthcare, and to delineate the elements of family-centered care. This consensus of 29 also provides a perspective and a research agenda about post-ICU recovery.

Perioperative administration of buffered versus non-buffered crystalloid intravenous fluid to improve outcomes following adult surgical procedures.

BACKGROUND: Perioperative fluid strategies influence clinical outcomes following major surgery. Many intravenous fluid preparations are based on simple solutions, such as normal saline, that feature an electrolyte composition that differs from that of physiological plasma. Buffered fluids have a theoretical advantage of containing a substrate that acts to maintain the body's acid-base status - typically a bicarbonate or a bicarbonate precursor such as maleate, gluconate, lactate, or acetate. Buffered fluids also provide additional electrolytes, including potassium, magnesium, and calcium, more closely matching the electrolyte balance of plasma. The putative benefits of buffered fluids have been compared with those of non-buffered fluids in the context of clinical studies conducted during the perioperative period. This review was published in 2012, and was updated in 2017. OBJECTIVES: To review effects of perioperative intravenous administration of buffered versus non-buffered fluids for plasma volume expansion or maintenance, or both, on clinical outcomes in adults undergoing all types of surgery. SEARCH METHODS: We electronically searched the Clinicaltrials.gov major trials registry, the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 6) in the Cochrane Library, MEDLINE (1966 to June 2016), Embase (1980 to June 2016), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to June 2016). We handsearched conference abstracts and, when possible, contacted leaders in the field. We reran the search in May 2017. We added one potential new study of interest to the list of 'Studies awaiting classification' and will incorporate this trial into formal review findings when we prepare the review update. SELECTION CRITERIA: Only randomized controlled trials that compared buffered versus non-buffered intravenous fluids for surgical patients were eligible for inclusion. We excluded other forms of comparison such as crystalloids versus colloids and colloids versus different colloids. DATA COLLECTION AND ANALYSIS: Two review authors screened references for eligibility, extracted data, and assessed risks of bias. We resolved disagreements by discussion and consensus, in collaboration with a third review author. We contacted trial authors to request additional information when appropriate. We presented pooled estimates for dichotomous outcomes as odds ratios (ORs) and for continuous outcomes as mean differences (MDs), with 95% confidence intervals (CIs). We analysed data via Review Manager 5.3 using fixed-effect models, and when heterogeneity was high (I² > 40%), we used random-effects models. MAIN RESULTS: This review includes, in total, 19 publications of 18 randomized controlled trials with a total of 1096 participants. We incorporated five of those 19 studies (330 participants) after the June 2016 update. Outcome measures in the included studies were thematically similar, covering perioperative electrolyte status, renal function, and acid-base status; however, we found significant clinical and statistical heterogeneity among the included studies. We identified variable protocols for fluid administration and total volumes of fluid administered to patients intraoperatively. Trial authors variably reported outcome data at disparate time points and with heterogeneous patient groups. Consequently, many outcome measures are reported in small group sizes, reducing overall confidence in effect size, despite relatively low inherent bias in the included studies. Several studies reported orphan outcome measures. We did not include in the results of this review one large, ongoing study of saline versus Ringer's solution.We found insufficient evidence on effects of fluid therapies on mortality and postoperative organ dysfunction (defined as renal insufficiency leading to renal replacement therapy); confidence intervals were wide and included both clinically relevant benefit and harm: mortality (Peto OR 1.85, 95% CI 0.37 to 9.33; I² = 0%; 3 trials, 6 deaths, 276 participants; low-quality evidence); renal insufficiency (OR 0.82, 95% CI 0.34 to 1.98; I² = 0%; 4 trials, 22 events, 276 participants; low-quality evidence).We noted several metabolic differences, including a difference in postoperative pH measured at end of surgery of 0.05 units - lower in the non-buffered fluid group (12 studies with a total of 720 participants; 95% CI 0.04 to 0.07; I² = 61%). However, this difference was not maintained on postoperative day one. We rated the quality of evidence for this outcome as moderate. We observed a higher postoperative serum chloride level immediately after operation, with use of non-buffered fluids reported in 10 studies with a total of 530 participants (MD 6.77 mmol/L, 95% CI 3.38 to 10.17), and this difference persisted until day one postoperatively (five studies with a total of 258 participants; MD 8.48 mmol/L, 95% CI 1.08 to 15.88). We rated the quality of evidence for this outcome as moderate. AUTHORS' CONCLUSIONS: Current evidence is insufficient to show effects of perioperative administration of buffered versus non-buffered crystalloid fluids on mortality and organ system function in adult patients following surgery. Benefits of buffered fluid were measurable in biochemical terms, particularly a significant reduction in postoperative hyperchloraemia and metabolic acidosis. Small effect sizes for biochemical outcomes and lack of correlated clinical follow-up data mean that robust conclusions on major morbidity and mortality associated with buffered versus non-buffered perioperative fluid choices are still lacking. Larger studies are needed to assess these relevant clinical outcomes.