A retrospective propensity-score-matched cohort study of the impact of procalcitonin testing on antibiotic use in hospitalized patients during the first wave of COVID-19.

BACKGROUND: Procalcitonin (PCT) is a blood marker used to help diagnose bacterial infections and guide antibiotic treatment. PCT testing was widely used/adopted during the COVID-19 pandemic in the UK. OBJECTIVES: Primary: to measure the difference in length of early (during first 7 days) antibiotic prescribing between patients with COVID-19 who did/did not have baseline PCT testing during the first wave of the pandemic. Secondary: to measure differences in length of hospital/ICU stay, mortality, total days of antibiotic prescribing and resistant bacterial infections between these groups. METHODS: Multi-centre, retrospective, observational, cohort study using patient-level clinical data from acute hospital Trusts/Health Boards in England/Wales. Inclusion: patients ≥16 years, admitted to participating Trusts/Health Boards and with a confirmed positive COVID-19 test between 1 February 2020 and 30 June 2020. RESULTS: Data from 5960 patients were analysed: 1548 (26.0%) had a baseline PCT test and 4412 (74.0%) did not. Using propensity-score matching, baseline PCT testing was associated with an average reduction in early antibiotic prescribing of 0.43 days [95% confidence interval (CI): 0.22-0.64 days, P < 0.001) and of 0.72 days (95% CI: 0.06-1.38 days, P = 0.03] in total antibiotic prescribing. Baseline PCT testing was not associated with increased mortality or hospital/ICU length of stay or with the rate of antimicrobial-resistant secondary bacterial infections. CONCLUSIONS: Baseline PCT testing appears to have been an effective antimicrobial stewardship tool early in the pandemic: it reduced antibiotic prescribing without evidence of harm. Our study highlights the need for embedded, rapid evaluations of infection diagnostics in the National Health Service so that even in challenging circumstances, introduction into clinical practice is supported by evidence for clinical utility. STUDY REGISTRATION NUMBER: ISRCTN66682918.

The cost-effectiveness of procalcitonin for guiding antibiotic prescribing in individuals hospitalized with COVID-19: part of the PEACH study.

BACKGROUND: Many hospitals introduced procalcitonin (PCT) testing to help diagnose bacterial coinfection in individuals with COVID-19, and guide antibiotic decision-making during the COVID-19 pandemic in the UK. OBJECTIVES: Evaluating cost-effectiveness of using PCT to guide antibiotic decisions in individuals hospitalized with COVID-19, as part of a wider research programme. METHODS: Retrospective individual-level data on patients hospitalized with COVID-19 were collected from 11 NHS acute hospital Trusts and Health Boards from England and Wales, which varied in their use of baseline PCT testing during the first COVID-19 pandemic wave. A matched analysis (part of a wider analysis reported elsewhere) created groups of patients whose PCT was/was not tested at baseline. A model was created with combined decision tree/Markov phases, parameterized with quality-of-life/unit cost estimates from the literature, and used to estimate costs and quality-adjusted life years (QALYs). Cost-effectiveness was judged at a £20 000/QALY threshold. Uncertainty was characterized using bootstrapping. RESULTS: People who had baseline PCT testing had shorter general ward/ICU stays and spent less time on antibiotics, though with overlap between the groups' 95% CIs. Those with baseline PCT testing accrued more QALYs (8.76 versus 8.62) and lower costs (£9830 versus £10 700). The point estimate was baseline PCT testing being dominant over no baseline testing, though with uncertainty: the probability of cost-effectiveness was 0.579 with a 1 year horizon and 0.872 with a lifetime horizon. CONCLUSIONS: Using PCT to guide antibiotic therapy in individuals hospitalized with COVID-19 is more likely to be cost-effective than not, albeit with uncertainty.

Nurses' decision-making around gastric residual volume measurement in UK adult intensive care: A four-centre survey.

BACKGROUND: Despite increasing evidence of the potential inaccuracy and unwarranted practice of regular GRV measurement in critically in adults, this practice persists within the United Kingdom. AIM: To explore adult intensive care nurses' decision-making around the practice of GRV measurement to guide enteral feeding. STUDY DESIGN: A cross-sectional 16 item electronic survey in four adult intensive care units (ICUs) in England and Wales. RESULTS: Two hundred and seventy-three responses were obtained across four ICUs with acceptable response rates for most [Unit 1 74 /127 = 58.2%; Unit 2 87/129 = 67.4%; Unit 3 77/120 = 64.1%; Unit 4 35/168 = 20.8%]. Most (243/273 (89%) reported measuring GRV 4-6 hourly, with most (223/273 82%) reporting that the main reason was to assess feed tolerance or intolerance and 37/273 (13.5%) saying their unit protocol required it. In terms of factors affecting decision-making, volume obtained was the most important factor, followed by the condition of the patient, with aspirate colour and appearance less important. When asked how they would feel about not measuring GRV routinely, the majority (78.2%) of nurses felt worried (140/273 = 51.2%) or very worried (74/273 = 27%). CONCLUSIONS: Factors affecting the nurses' decision-making around GRV were based largely on fear of risk (around vomiting and pulmonary aspiration) and compliance with unit protocols. RELEVANCE TO CLINICAL PRACTICE: Despite increasing evidence suggesting it is unnecessary, nurses' beliefs around the value of this practice persist and it continues to be embedded into unit protocols around feeding.

Predicting ICU Mortality in Acute Respiratory Distress Syndrome Patients Using Machine Learning: The Predicting Outcome and STratifiCation of severity in ARDS (POSTCARDS) Study.

OBJECTIVES: To assess the value of machine learning approaches in the development of a multivariable model for early prediction of ICU death in patients with acute respiratory distress syndrome (ARDS). DESIGN: A development, testing, and external validation study using clinical data from four prospective, multicenter, observational cohorts. SETTING: A network of multidisciplinary ICUs. PATIENTS: A total of 1,303 patients with moderate-to-severe ARDS managed with lung-protective ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We developed and tested prediction models in 1,000 ARDS patients. We performed logistic regression analysis following variable selection by a genetic algorithm, random forest and extreme gradient boosting machine learning techniques. Potential predictors included demographics, comorbidities, ventilatory and oxygenation descriptors, and extrapulmonary organ failures. Risk modeling identified some major prognostic factors for ICU mortality, including age, cancer, immunosuppression, Pa o2 /F io2 , inspiratory plateau pressure, and number of extrapulmonary organ failures. Together, these characteristics contained most of the prognostic information in the first 24 hours to predict ICU mortality. Performance with machine learning methods was similar to logistic regression (area under the receiver operating characteristic curve [AUC], 0.87; 95% CI, 0.82-0.91). External validation in an independent cohort of 303 ARDS patients confirmed that the performance of the model was similar to a logistic regression model (AUC, 0.91; 95% CI, 0.87-0.94). CONCLUSIONS: Both machine learning and traditional methods lead to promising models to predict ICU death in moderate/severe ARDS patients. More research is needed to identify markers for severity beyond clinical determinants, such as demographics, comorbidities, lung mechanics, oxygenation, and extrapulmonary organ failure to guide patient management.

Patient diversity and author representation in clinical studies supporting the Surviving Sepsis Campaign guidelines for management of sepsis and septic shock 2021: a systematic review of citations.

BACKGROUND: The generalizability of the Surviving Sepsis Campaign (SSC) guidelines to various patient populations and hospital settings has been debated. A quantitative assessment of the diversity and representation in the clinical evidence supporting the guidelines would help evaluate the generalizability of the recommendations and identify strategic research goals and priorities. In this study, we evaluated the diversity of patients in the original studies, in terms of sex, race/ethnicity, and geographical location. We also assessed diversity in sex and geographical representation among study first and last authors. METHODS: All clinical studies cited in support of the 2021 SSC adult guideline recommendations were identified. Original clinical studies were included, while editorials, reviews, non-clinical studies, and meta-analyses were excluded. For eligible studies, we recorded the proportion of male patients, percentage of each represented racial/ethnic subgroup (when available), and countries in which they were conducted. We also recorded the sex and location of the first and last authors. The World Bank classification was used to categorize countries. RESULTS: The SSC guidelines included six sections, with 85 recommendations based on 351 clinical studies. The proportion of male patients ranged from 47 to 62%. Most studies did not report the racial/ ethnic distribution of the included patients; when they did so, most were White patients (68-77%). Most studies were conducted in high-income countries (77-99%), which included Europe/Central Asia (33-66%) and North America (36-55%). Moreover, most first/last authors were males (55-93%) and from high-income countries (77-99%). CONCLUSIONS: To enhance the generalizability of the SCC guidelines, stakeholders should define strategies to enhance the diversity and representation in clinical studies. Though there was reasonable representation in sex among patients included in clinical studies, the evidence did not reflect diversity in the race/ethnicity and geographical locations. There was also lack of diversity among the first and last authors contributing to the evidence.

Redefining ARDS: a paradigm shift.

Although the defining elements of "acute respiratory distress syndrome" (ARDS) have been known for over a century, the syndrome was first described in 1967. Since then, despite several revisions of its conceptual definition, it remains a matter of debate whether ARDS is a discrete nosological entity. After almost 60 years, it is appropriate to examine how critical care has modeled this fascinating syndrome and affected patient's outcome. Given that the diagnostic criteria of ARDS (e.g., increased pulmonary vascular permeability and diffuse alveolar damage) are difficult to ascertain in clinical practice, we believe that a step forward would be to standardize the assessment of pulmonary and extrapulmonary involvement in ARDS to ensure that each patient can receive the most appropriate and effective treatment. The selection of treatments based on arbitrary ranges of PaO2/FiO2 lacks sufficient sensitivity to individualize patient care.

Quality of the discussion of asthma on twitter.

IntroductionPatients obtain a large amount of medical information online. Much of this information may not be reliable or of high quality. We investigated what influences the discussion of asthma on Twitter by evaluating the most popular tweets and the quality of the links shared.MethodsWe used Symplur Signals to extract data from Twitter examining characteristics of the top 100 most shared tweets and the 50 most shared links that included the hashtag #asthma. Information on each site was assessed using an Asthma Content score, and validated DISCERN scores and HONCode criteria.ResultsThe top 100 asthma-related tweets were shared 10,169 times and had 16,044 likes. Healthcare organizations posted 49 of the top 100 tweets, non-healthcare individuals posted 20, non-healthcare organizations posted 16 and clinicians posted 14. Of the top 100 tweets, 62 were educational, 11 research-related, 10 political and 15 promotional. The top 50 links were shared 6009 times (median number of shares 92 per link (range 60-710)). Links most commonly (42%) led to educational content while 24% of links led to research articles, 22% to promotional websites, and 12% to political websites. Educational links had higher Asthma Content scores than other links (p < 0.005). Overall, all three scores were low for all types of links. Only 34% of sites met HONCode criteria, and 14% were assessed as high quality by DISCERN score.ConclusionThe top tweets using the hashtag #asthma were commonly educational. The majority of top links on Twitter scored poorly on asthma content, quality, and reliability.

Effect of Lower Tidal Volume Ventilation Facilitated by Extracorporeal Carbon Dioxide Removal vs Standard Care Ventilation on 90-Day Mortality in Patients With Acute Hypoxemic Respiratory Failure: The REST Randomized Clinical Trial.

Importance: In patients who require mechanical ventilation for acute hypoxemic respiratory failure, further reduction in tidal volumes, compared with conventional low tidal volume ventilation, may improve outcomes. Objective: To determine whether lower tidal volume mechanical ventilation using extracorporeal carbon dioxide removal improves outcomes in patients with acute hypoxemic respiratory failure. Design, Setting, and Participants: This multicenter, randomized, allocation-concealed, open-label, pragmatic clinical trial enrolled 412 adult patients receiving mechanical ventilation for acute hypoxemic respiratory failure, of a planned sample size of 1120, between May 2016 and December 2019 from 51 intensive care units in the UK. Follow-up ended on March 11, 2020. Interventions: Participants were randomized to receive lower tidal volume ventilation facilitated by extracorporeal carbon dioxide removal for at least 48 hours (n = 202) or standard care with conventional low tidal volume ventilation (n = 210). Main Outcomes and Measures: The primary outcome was all-cause mortality 90 days after randomization. Prespecified secondary outcomes included ventilator-free days at day 28 and adverse event rates. Results: Among 412 patients who were randomized (mean age, 59 years; 143 [35%] women), 405 (98%) completed the trial. The trial was stopped early because of futility and feasibility following recommendations from the data monitoring and ethics committee. The 90-day mortality rate was 41.5% in the lower tidal volume ventilation with extracorporeal carbon dioxide removal group vs 39.5% in the standard care group (risk ratio, 1.05 [95% CI, 0.83-1.33]; difference, 2.0% [95% CI, -7.6% to 11.5%]; P = .68). There were significantly fewer mean ventilator-free days in the extracorporeal carbon dioxide removal group compared with the standard care group (7.1 [95% CI, 5.9-8.3] vs 9.2 [95% CI, 7.9-10.4] days; mean difference, -2.1 [95% CI, -3.8 to -0.3]; P = .02). Serious adverse events were reported for 62 patients (31%) in the extracorporeal carbon dioxide removal group and 18 (9%) in the standard care group, including intracranial hemorrhage in 9 patients (4.5%) vs 0 (0%) and bleeding at other sites in 6 (3.0%) vs 1 (0.5%) in the extracorporeal carbon dioxide removal group vs the control group. Overall, 21 patients experienced 22 serious adverse events related to the study device. Conclusions and Relevance: Among patients with acute hypoxemic respiratory failure, the use of extracorporeal carbon dioxide removal to facilitate lower tidal volume mechanical ventilation, compared with conventional low tidal volume mechanical ventilation, did not significantly reduce 90-day mortality. However, due to early termination, the study may have been underpowered to detect a clinically important difference. Trial Registration: ClinicalTrials.gov Identifier: NCT02654327.

Risk Factors for 1-Year Mortality and Hospital Utilization Patterns in Critical Care Survivors: A Retrospective, Observational, Population-Based Data Linkage Study.

OBJECTIVES: Clear understanding of the long-term consequences of critical care survivorship is essential. We investigated the care process and individual factors associated with long-term mortality among ICU survivors and explored hospital use in this group. DESIGN: Population-based data linkage study using the Secure Anonymised Information Linkage databank. SETTING: All ICUs between 2006 and 2013 in Wales, United Kingdom. PATIENTS: We identified 40,631 patients discharged alive from Welsh adult ICUs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Primary outcome was 365-day survival. The secondary outcomes were 30- and 90-day survival and hospital utilization in the 365 days following ICU discharge. Kaplan-Meier curves were plotted to compare survival rates. Cox proportional hazards regression models were used to determine risk factors of mortality. Seven-thousand eight-hundred eighty-three patients (19.4%) died during the 1-year follow-up period. In the multivariable Cox regression analysis, advanced age and comorbidities were significant determinants of long-term mortality. Expedited discharge due to ICU bed shortage was associated with higher risk. The rate of hospitalization in the year prior to the critical care admission was 28 hospitalized days/1,000 d; post critical care was 88 hospitalized days/1,000 d for those who were still alive; and 57 hospitalized days/1,000 d and 412 hospitalized days/1,000 d for those who died by the end of the study, respectively. CONCLUSIONS: One in five ICU survivors die within 1 year, with advanced age and comorbidity being significant predictors of outcome, leading to high resource use. Care process factors indicating high system stress were associated with increased risk. More detailed understanding is needed on the effects of the potentially modifiable factors to optimize service delivery and improve long-term outcomes of the critically ill.

Improving outcome of sepsis on the ward: introducing the 'Sepsis Six' bundle.

BACKGROUND: The Sepsis Six bundle is designed to facilitate early intervention with three diagnostic and three therapeutic steps to be delivered within 1 h to patients with suspected sepsis. AIMS AND OBJECTIVES: To investigate the effects of delivering the 'Sepsis Six' bundle by the Critical Care Outreach team on patient outcomes. DESIGN: In a prospective observational study, all adult patients on the general wards from June 2012 to January 2014 with sepsis who were screened and treated by the Critical Care Outreach team were included. METHODS: The main outcome measure was the change in National Early Warning Score following the delivery of the Sepsis Six bundle within 24 h. Secondary outcomes were 90-day mortality and overall bundle compliance. RESULTS: A total of 207 patients were included in the analysis. Overall bundle compliance was 84%. National Early Warning Scores decreased significantly 24 h after administering the Sepsis Six, from 7·4 ± 2·6 to 3·1 ± 2·4 (p < 0·001). The distribution of the National Early Warning Score changed significantly. Mortality was lower at 90 days when patients who presented with signs of sepsis within 48 h of hospital admission were compared with those who presented with signs of sepsis after 48 h of hospital admission (14·5% versus 35·4% p < 0·03) despite similar baseline physiological variables. CONCLUSIONS: We found better outcomes after the administration of Sepsis Six. Reliable delivery of the bundle, defined as 80% of patients receiving the standard of care, is achievable, and our quality improvement data suggest that it is likely to be sustainable in our environment. RELEVANCE TO CLINICAL PRACTICE: Sepsis Six can reduce physiological impairment, monitored by the National Early Warning Scores. Consistent delivery of the bundle can lead to better patient outcomes.

A Snapshot of Compliance with the Sepsis Six Care Bundle in Two Acute Hospitals in the West Midlands, UK.

BACKGROUND: The sepsis six care bundle has been adopted by hospitals in England and Wales for the management of patients with sepsis, with the aim of increasing survival when all elements of the bundle are achieved. AIM: To assess compliance with the Sepsis Six Care Bundle in two acute NHS hospitals in the West Midlands. MATERIALS AND METHODS: Adults admitted to hospital over a 24-hour period were screened for sepsis. Sepsis was identified using the Systemic Inflammatory Response (SIRS) criteria and the quick sequential organ failure assessment (qSOFA) score. Adherence to the Sepsis Six Care Bundle was assessed. RESULTS: 249 patients were screened and 24 patients were identified as having sepsis (9.6%). One patient received all six elements of the bundle. Compliance was highest for giving intravenous fluids (58.3%) and antibiotics (58.3%), and lowest for measuring urine output (16.7%). CONCLUSIONS: Further research is needed to establish the reasons for low compliance. HOW TO CITE THIS ARTICLE: Frankling C, Patel J, Sharif B, Melody T, Yeung J, Gao F, et al. A Snapshot of Compliance with the Sepsis Six Care Bundle in Two Acute Hospitals in the West Midlands, UK. Indian J Crit Care Med 2019;23(7):310-315.

Microbe-specific unconventional T cells induce human neutrophil differentiation into antigen cross-presenting cells.

The early immune response to microbes is dominated by the recruitment of neutrophils whose primary function is to clear invading pathogens. However, there is emerging evidence that neutrophils play additional effector and regulatory roles. The present study demonstrates that human neutrophils assume Ag cross-presenting functions and suggests a plausible scenario for the local generation of APC-like neutrophils through the mobilization of unconventional T cells in response to microbial metabolites. Vγ9/Vδ2 T cells and mucosal-associated invariant T cells are abundant in blood, inflamed tissues, and mucosal barriers. In this study, both human cell types responded rapidly to neutrophils after phagocytosis of Gram-positive and Gram-negative bacteria producing the corresponding ligands, and in turn mediated the differentiation of neutrophils into APCs for both CD4(+) and CD8(+) T cells through secretion of GM-CSF, IFN-γ, and TNF-α. In patients with acute sepsis, circulating neutrophils displayed a similar APC-like phenotype and readily processed soluble proteins for cross-presentation of antigenic peptides to CD8(+) T cells, at a time when peripheral Vγ9/Vδ2 T cells were highly activated. Our findings indicate that unconventional T cells represent key controllers of neutrophil-driven innate and adaptive responses to a broad range of pathogens.

The impact of extracerebral organ failure on outcome of patients after cardiac arrest: an observational study from the ICON database.

BACKGROUND: We used data from a large international database to assess the incidence and impact of extracerebral organ dysfunction on prognosis of patients admitted after cardiac arrest (CA). METHODS: This was a sub-analysis of the Intensive Care Over Nations (ICON) database, which contains data from all adult patients admitted to one of 730 participating intensive care units (ICUs) in 84 countries from 8-18 May 2012, except admissions for routine postoperative surveillance. For this analysis, patients admitted after CA (defined as those with "post-anoxic coma" or "cardiac arrest" as the reason for ICU admission) were included. Data were collected daily in the ICU for a maximum of 28 days; patients were followed up for outcome data until death, hospital discharge, or a maximum of 60 days in-hospital. Favorable neurological outcome was defined as alive at hospital discharge with a last available neurological Sequential Organ Failure Assessment (SOFA) subscore of 0-2. RESULTS: Among the 469 patients admitted after CA, 250 (53 %) had had out-of-hospital CA; 210 (45 %) patients died in the ICU and 357 (76 %) had an unfavorable neurological outcome. Non-survivors had a higher incidence of renal (43 vs. 16 %), cardiovascular (56 vs. 45 %), and respiratory (62 vs. 48 %) failure on admission and during the ICU stay than survivors (all p < 0.05). Similar results were found for patients with unfavorable vs. favorable neurological outcomes. In multivariable analysis, independent predictors of ICU mortality were renal failure on admission, high admission Simplified Acute Physiology Score (SAPS) II, high maximum serum lactate levels within the first 24 h after ICU admission, and development of sepsis. Independent predictors of unfavorable neurological outcome were mechanical ventilation on admission, high admission SAPS II score, and neurological dysfunction on admission. CONCLUSIONS: In this multicenter cohort, extracerebral organ dysfunction was common in CA patients. Renal failure on admission was the only extracerebral organ dysfunction independently associated with higher ICU mortality.

Improving compliance with central venous catheter care bundles using electronic records.

BACKGROUND: Health care associated infections are a major contributor to avoidable harm experienced by patients in modern health care settings. Recent reports suggest that electronic checklists for the documentation of a central line bundle may significantly enhance documented process compliance and help to reduce catheter-related bloodstream infection rates. AIMS: This paper describes the use of our electronic tool to monitor and feedback process compliance in conjunction of introducing bespoke central line insertion packs to tackle catheter-related bloodstream infections in our intensive care unit in a medium-sized district general hospital. DESIGN AND METHODS: Continuous quality improvement programme with 'Plan-Do-Study-Act' cycles was implemented. The central venous catheter insertion and maintenance bundle was rolled out in 2007. To monitor compliance with the bundle elements, an electronic tool was designed as part of our bedside Clinical Information System. From 2009, regular quarterly feedback was provided on the number of central venous catheter lines inserted, compliance with the insertion and maintenance bundle and catheter-related bloodstream infection rate using the data collected through the Clinical Information System. We have also introduced dedicated line insertion trolleys and factory-prepared insertion packs. We used segmented regression analysis to assess the changes in the catheter-related bloodstream infection rate before and after implementation of the central venous catheter bundle. RESULTS: Bundle compliance increased during the implementation period and reached over 95% within 6 months. We observed a significant reduction in the catheter-related bloodstream infection rate from 15.6/1000 days to 0.4/1000 days. Regression analysis showed that only the compliance had significant effect on the number and prevalence of catheter-related bloodstream infections. CONCLUSION/IMPLICATIONS: Implementation of evidence-based care bundles reinforced by real-time feedback on the performance of caregivers can significantly reduce the rate of catheter-related bloodstream infection in the intensive care unit. Ensuring that change processes are seamlessly integrated in the workflow with minimal administrative burden is crucial to the quality improvement process.

Standards for research in NHS Wales critical care units: A modified Delphi study.

Introduction: The importance of research and development in all aspects of healthcare is well acknowledged. Within critical care, national guidelines provide a limited number of standards and series of recommendations on Research and Development (R&D) activity. The aim of this study was to create a broader set of standards in support of R&D activity in critical care departments. Methods: A modified Delphi study was undertaken across NHS Wales critical care units. Proposed standards were developed by a group of experts, which across three rounds, majority agreement was sought. Additional standards were added based on participant's responses. Results: This study identified 49 standards for R&D activity within critical care units in NHS Wales. All these standards reached majority agreement, as determined by >70% of multi-disciplinary participants determine each standard as essential. Conclusions: The results of this study will be utilised within Wales to inform wider service specification with regard workforce requirements, responsibilities, reporting and collaboration.

Efficacy and safety of corticosteroids for the treatment of community-acquired pneumonia: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The role of corticosteroids in the treatment of community-acquired pneumonia (CAP) remains uncertain. We conducted an updated meta-analysis to investigate the effectiveness and potential effect modifiers of adjunctive corticosteroids in patients with CAP. METHODS: The protocol of this meta-analysis was registered with PROSPERO (CRD42022354920). We searched MEDLINE, Embase, the Cochrane Library and trial registers from inception till March 2023 to identify randomized controlled trials (RCTs) investigating corticosteroids in adult patients with CAP. Our primary outcome was the risk of all-cause mortality within 30 days after randomization (if not reported at day 30, we extracted the outcome closest to 30 days). Risk ratios (RR) and mean differences (MDs) were pooled under a random-effects model. RESULTS: Fifteen RCTs (n = 3252 patients) were included in this review. Corticosteroids reduced the risk of all-cause mortality in CAP patients (RR: 0.69, 95% CI: 0.53-0.89; high certainty). This significant result was restricted to hydrocortisone therapy and patients with severe CAP. Additionally, younger patients demonstrated a greater reduction in mortality. Corticosteroids reduced the incidence of shock and the need for mechanical ventilation (MV), and decreased the length of hospital and ICU stay (moderate certainty). CONCLUSIONS: Corticosteroids reduce the risk of all-cause mortality, especially in younger patients receiving hydrocortisone, and probably decrease the need for MV, the incidence of shock, and the length of hospital and ICU stay in patients with CAP. Our findings indicate that patients with CAP, especially severe CAP, will benefit from adjunctive corticosteroid therapy.

Evaluating the clinical and cost-effectiveness of a conservative approach to oxygen therapy for invasively ventilated adults in intensive care: Protocol for the UK-ROX trial.

Background: In the United Kingdom, around 184,000 adults are admitted to an intensive care unit (ICU) each year with over 30% receiving mechanical ventilation. Oxygen is the commonest therapeutic intervention provided to these patients but it is unclear how much oxygen should be administered for the best clinical outcomes. Methods: The UK-ROX trial will evaluate the clinical and cost-effectiveness of conservative oxygen therapy (the minimum oxygen concentration required to maintain an oxygen saturation of 90% ± 2%) versus usual oxygen therapy in critically ill adults receiving supplemental oxygen when invasively mechanically ventilated in ICUs in England, Wales and Northern Ireland. The trial will recruit 16,500 patients from approximately 100 UK adult ICUs. Using a deferred consent model, enrolled participants will be randomly allocated (1:1) to conservative or usual oxygen therapy until ICU discharge or 90 days after randomisation. Objectives: The primary clinical outcome is all cause mortality at 90 days following randomisation. Discussion: The UK-ROX trial has received ethical approval from the South Central - Oxford C Research Ethics Committee (Reference: 20/SC/0423) and the Confidentiality Advisory Group (Reference: 22/CAG/0154). The trial commenced in May 2021 and, at the time of publication, 95 sites had opened to recruitment.