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We sought to determine if the difference between PThis was a retrospective cohort study of adult patients who achieved return of spontaneous circulation (ROSC) after OHCA over 3 years. The primary exposure was the POf 698 OHCA patients transported to the hospitals, 381 had sustained ROSC and qualifying ENeither P

BackgroundTest-negative design (TND) studies have produced validated estimates of vaccine effectiveness (VE) for influenza vaccine studies. However, syndrome-negative controls have been proposed for differentiating bias and true estimates in VE evaluations for COVID-19. To understand the use of alternative control groups, we compared characteristics and VE estimates of syndrome-negative and test-negative VE controls.MethodsAdults hospitalized at 21 medical centers in 18 states March 11-August 31, 2021 were eligible for analysis. Case patients had symptomatic acute respiratory infection (ARI) and tested positive for SARS-CoV-2. Control groups were test-negative patients with ARI but negative SARS-CoV-2 testing, and syndrome-negative controls were without ARI and negative SARS-CoV-2 testing. Chi square and Wilcoxon rank sum tests were used to detect differences in baseline characteristics. VE against COVID-19 hospitalization was calculated using logistic regression comparing adjusted odds of prior mRNA vaccination between cases hospitalized with COVID-19 and each control group.Results5811 adults (2726 cases, 1696 test-negative controls, and 1389 syndrome-negative controls) were included. Control groups differed across characteristics including age, race/ethnicity, employment, previous hospitalizations, medical conditions, and immunosuppression. However, control-group-specific VE estimates were very similar. Among immunocompetent patients aged 18-64years, VE was 93% (95% CI: 90-94) using syndrome-negative controls and 91% (95% CI: 88-93) using test-negative controls.ConclusionsDespite demographic and clinical differences between control groups, the use of either control group produced similar VE estimates across age groups and immunosuppression status. These findings support the use of test-negative controls and increase confidence in COVID-19 VE estimates produced by test-negative design studies.

The SARS-CoV-2 Omicron variant (B.1.1.529 or BA.1) became predominant in the United States by late December 2021 (1). BA.1 has since been replaced by emerging lineages BA.2 (including BA.2.12.1) in March 2022, followed by BA.4 and BA.5, which have accounted for a majority of SARS-CoV-2 infections since late June 2022 (1). Data on the effectiveness of monovalent mRNA COVID-19 vaccines against BA.4/BA.5-associated hospitalizations are limited, and their interpretation is complicated by waning of vaccine-induced immunity (2-5). Further, infections with earlier Omicron lineages, including BA.1 and BA.2, reduce vaccine effectiveness (VE) estimates because certain persons in the referent unvaccinated group have protection from infection-induced immunity. The IVY Network

Background . Adults in the United States (US) began receiving the adenovirus vector coronavirus disease 2019 (COVID-19) vaccine, Ad26.COV2.S (Johnson & Johnson [Janssen]), in February 2021. We evaluated Ad26.COV2.S vaccine effectiveness (VE) against COVID-19 hospitalization and high disease severity during the first 10 months of its use. Methods . In a multicenter case-control analysis of US adults (≥18 years) hospitalized 11 March to 15 December 2021, we estimated VE against susceptibility to COVID-19 hospitalization (VEs), comparing odds of prior vaccination with a single dose Ad26.COV2.S vaccine between hospitalized cases with COVID-19 and controls without COVID-19. Among hospitalized patients with COVID-19, we estimated VE against disease progression (VEp) to death or invasive mechanical ventilation (IMV), comparing odds of prior vaccination between patients with and without progression. Results . After excluding patients receiving mRNA vaccines, among 3979 COVID-19 case-patients (5% vaccinated with Ad26.COV2.S) and 2229 controls (13% vaccinated with Ad26.COV2.S), VEs of Ad26.COV2.S against COVID-19 hospitalization was 70% (95% confidence interval [CI]: 63–75%) overall, including 55% (29–72%) among immunocompromised patients, and 72% (64–77%) among immunocompetent patients, for whom VEs was similar at 14–90 days (73% [59–82%]), 91–180 days (71% [60–80%]), and 181–274 days (70% [54–81%]) postvaccination. Among hospitalized COVID-19 case-patients, VEp was 46% (18–65%) among immunocompetent patients. Conclusions . The Ad26.COV2.S COVID-19 vaccine reduced the risk of COVID-19 hospitalization by 72% among immunocompetent adults without waning through 6 months postvaccination. After hospitalization for COVID-19, vaccinated immunocompetent patients were less likely to require IMV or die compared to unvaccinated immunocompetent patients.

Background Understanding COVID-19 epidemiology is crucial to clinical care and to clinical trial design and interpretation. Objective To describe characteristics, treatment, and outcomes among patients hospitalized with COVID-19 early in the pandemic. Methods A retrospective cohort study of consecutive adult patients with laboratory-confirmed, symptomatic SARS-CoV-2 infection admitted to 57 US hospitals from March 1 to April 1, 2020. Results Of 1480 inpatients with COVID-19, median (IQR) age was 62.0 (49.4-72.9) years, 649 (43.9%) were female, and 822 of 1338 (61.4%) were non-White or Hispanic/Latino. Intensive care unit admission occurred in 575 patients (38.9%), mostly within 4 days of hospital presentation. Respiratory failure affected 583 patients (39.4%), including 284 (19.2%) within 24 hours of hospital presentation and 413 (27.9%) who received invasive mechanical ventilation. Median (IQR) hospital stay was 8 (5-15) days overall and 15 (9-24) days among intensive care unit patients. Hospital mortality was 17.7% (n = 262). Risk factors for hospital death identified by penalized multivariable regression included older age; male sex; comorbidity burden; symptoms-to-admission interval; hypotension; hypoxemia; and higher white blood cell count, creatinine level, respiratory rate, and heart rate. Of 1218 survivors, 221 (18.1%) required new respiratory support at discharge and 259 of 1153 (22.5%) admitted from home required new health care services. Conclusions In a geographically diverse early-pandemic COVID-19 cohort with complete hospital folllow-up, hospital mortality was associated with older age, comorbidity burden, and male sex. Intensive care unit admissions occurred early and were associated with protracted hospital stays. Survivors often required new health care services or respiratory support at discharge.

Considering the COVID-19 pandemic where concomitant occurrence of ARDS and severe acute brain injury (sABI) has increasingly coemerged, we synthesize existing data regarding the simultaneous management of both conditions. Our aim is to provide readers with fundamental principles and concepts for the management of sABI and ARDS, and highlight challenges and conflicts encountered while managing concurrent disease. Up to 40% of patients with sABI can develop ARDS. Although there are trials and guidelines to support the mainstays of treatment for ARDS and sABI independently, guidance on concomitant management is limited. Treatment strategies aimed at managing severe ARDS may at times conflict with the management of sABI. In this narrative review, we discuss the physiological basis and risks involved during simultaneous management of ARDS and sABI, summarize evidence for treatment decisions, and demonstrate these principles using hypothetical case scenarios. Use of invasive or noninvasive monitoring to assess brain and lung physiology may facilitate goal-directed treatment strategies with the potential to improve outcome. Understanding the pathophysiology and key treatment concepts for comanagement of these conditions is critical to optimizing care in this high-acuity patient population.

Background/Objective Cardiac arrest is a leading cause of death and disability in the United States. Current consensus guidelines recommend obtaining a non-contrast CT head as part of standard post-arrest care. We aimed to correlate early CT findings of hypoxic-ischemic encephalopathy (HIE) with specific arrest characteristics in a pragmatic and generalizable fashion. Methods This is a retrospective multi-center cohort of patients with out-of-hospital cardiac arrest (OHCA) who underwent whole-body imaging within 6 hours of hospital arrival. Head CT reports were systematically analyzed with an emphasis on findings suggestive of HIE, including cerebral edema, sulcal effacement, and blurred grey-white junction. The primary exposure was the duration of cardiac arrest. Secondary exposures included bystander cardiopulmonary resuscitation (CPR), initial cardiac rhythm, and cause of arrest. The primary outcome was the presence of CT findings consistent with HIE. Results A total of 227 patients (average age 55 years, 32% female, 65% White, 56% witnessed arrest, 31% shockable rhythm) were included in the final analysis. CT findings of HIE were seen in 47 (48.3%) patients. Univariable analysis showed an association between HIE and CPR duration (OR 1.05, 95% CI 1.02–1.09, p = 0.002), age (OR 0.97, 95% CI 0.95–0.99, p = 0.004), and shockable rhythm (OR 0.34, 95% CI 0.14–0.81, p = 0.015). Multivariate analysis demonstrated a correlation between CT findings of HIE and age under 55 (OR 2.6, 95% CI 1.2 -5 .6, p = 0.02) and CPR duration (OR 1.1, 95% CI 1.02–1.1, p

his is the sixth annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. This summary addresses the most recently published resuscitation evidence reviewed by International Liaison Committee on Resuscitation Task Force science experts. Topics covered by systematic reviews include cardiopulmonary resuscitation during transport; approach to resuscitation after drowning; passive ventilation; minimizing pauses during cardiopulmonary resuscitation; temperature management after cardiac arrest; use of diagnostic point-of-care ultrasound during cardiac arrest; use of vasopressin and corticosteroids during cardiac arrest; coronary angiography after cardiac arrest; public-access defibrillation devices for children; pediatric early warning systems; maintaining normal temperature immediately after birth; suctioning of amniotic fluid at birth; tactile stimulation for resuscitation immediately after birth; use of continuous positive airway pressure for respiratory distress at term birth; respiratory and heart rate monitoring in the delivery room; supraglottic airway use in neonates; prearrest prediction of in-hospital cardiac arrest mortality; basic life support training for likely rescuers of high-risk populations; effect of resuscitation team training; blended learning for life support training; training and recertification for resuscitation instructors; and recovery position for maintenance of breathing and prevention of cardiac arrest. Members from 6 task forces have assessed, discussed, and debated the quality of the evidence using Grading of Recommendations Assessment, Development, and Evaluation criteria and generated consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence-to-Decision Framework Highlights sections, and priority knowledge gaps for future research are listed. This is the sixth annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. This summary addresses the most recently published resuscitation evidence reviewed by International Liaison Committee on Resuscitation Task Force science experts. Topics covered by systematic reviews include cardiopulmonary resuscitation during transport; approach to resuscitation after drowning; passive ventilation; minimizing pauses during cardiopulmonary resuscitation; temperature management after cardiac arrest; use of diagnostic point-of-care ultrasound during cardiac arrest; use of vasopressin and corticosteroids during cardiac arrest; coronary angiography after cardiac arrest; public-access defibrillation devices for children; pediatric early warning systems; maintaining normal temperature immediately after birth; suctioning of amniotic fluid at birth; tactile stimulation for resuscitation immediately after birth; use of continuous positive airway pressure for respiratory distress at term birth; respiratory and heart rate monitoring in the delivery room; supraglottic airway use in neonates; prearrest prediction of in-hospital cardiac arrest mortality; basic life support training for likely rescuers of high-risk populations; effect of resuscitation team training; blended learning for life support training; training and recertification for resuscitation instructors; and recovery position for maintenance of breathing and prevention of cardiac arrest. Members from 6 task forces have assessed, discussed, and debated the quality of the evidence using Grading of Recommendations Assessment, Development, and Evaluation criteria and generated consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence-to-Decision Framework Highlights sections, and priority knowledge gaps for future research are listed.

The objective of this study is to describe incidence and factors associated with early withdrawal of life-sustaining therapies based on presumed poor neurologic prognosis (WLST-N) and practices around multimodal prognostication after out-of-hospital cardiac arrest (OHCA).We performed a subanalysis of a randomized controlled trial assessing prehospital therapeutic hypothermia in adult patients admitted to nine hospitals in King County with nontraumatic OHCA between 2007 and 2012. Patients who underwent tracheal intubation and were unconscious following return of spontaneous circulation were included. Our outcomes were (1) incidence of early WLST-N (WLST-N within 72 h from return of spontaneous circulation), (2) factors associated with early WLST-N compared with patients who remained comatose at 72 h without WLST-N, (3) institutional variation in early WLST-N, (4) use of multimodal prognostication, and (5) use of sedative medications in patients with early WLST-N. Analysis included descriptive statistics and multivariable logistic regression.We included 1,040 patients (mean age was 65 years, 37% were female, 41% were White, and 44% presented with arrest due to ventricular fibrillation) admitted to nine hospitals. Early WLST-N accounted for 24% (n = 154) of patient deaths and occurred in half (51%) of patients with WLST-N. Factors associated with early WLST-N in multivariate regressions were older age (odds ratio [OR] 1.02, 95% confidence interval [CI]: 1.01-1.03), preexisting do-not-attempt-resuscitation orders (OR 4.67, 95% CI: 1.55-14.01), bilateral absent pupillary reflexes (OR 2.4, 95% CI: 1.42-4.10), and lack of neurological consultation (OR 2.60, 95% CI: 1.52-4.46). The proportion of patients with early WLST-N among all OHCA admissions ranged from 19-60% between institutions. A head computed tomography scan was obtained in 54% (n = 84) of patients with early WLST-N; 22% (n = 34) and 5% (n = 8) underwent ≥ 1 and ≥ 2 additional prognostic tests, respectively. Prognostic tests were more frequently performed when neurological consultation occurred. Most patients received sedating medications (90%) within 24 h before early WLST-N; the median time from last sedation to early WLST-N was 4.2 h (interquartile range 0.4-15).Nearly one quarter of deaths after OHCA were due to early WLST-N. The presence of concerning neurological examination findings appeared to impact early WLST-N decisions, even though these are not fully reliable in this time frame. Lack of neurological consultation was associated with early WLST-N and resulted in underuse of guideline-concordant multimodal prognostication. Sedating medications were often coadministered prior to early WLST-N and may have further confounded the neurological examination. Standardizing prognostication, restricting early WLST-N, and a multidisciplinary approach including neurological consultation might improve outcomes after OHCA.

ImportanceEpinephrine improves return of spontaneous circulation after out-of-hospital cardiac arrest (OHCA). These beneficial cardiac effects do not directly translate to better neurologic outcomes, possibly because of epinephrine-induced microvascular effects that produce critical brain ischemia.ObjectiveTo examine whether targeted temperature management (TTM) modifies the adverse association between increasing prehospital epinephrine dose and neurologically favorable survival.Design, Setting, and ParticipantsThis retrospective cohort study assessed 14 612 adults from Seattle and King County, Washington, with nontraumatic OHCA between January 1, 2008, and December 31, 2018, and included those who achieved return of spontaneous circulation and were unconscious at hospital admission. Data analysis was performed from April 2021 to May 2022.ExposuresEpinephrine dose and TTM during prehospital resuscitation.Main Outcomes and MeasuresFavorable neurologic survival (Cerebral Performance Category [CPC] 1 or 2) and survival to hospital discharge.ResultsOf the 14 612 assessed adults, 5253 (median age, 63 years; IQR, 51-74 years; 3460 [65.8%] male) were eligible for the study. The median epinephrine dose was 2.0 mg (IQR, 1.0-3.0 mg); 3052 patients (58.1%) received TTM. In all, 1889 patients (36.0%) survived with CPC 1 to 2, and 2177 (41.4%) survived to discharge. Increasing doses of epinephrine were associated with a decreasing likelihood of CPC 1 to 2 (odds ratio [OR], 0.46; 95% CI 0.42-0.50 for each additional milligram of epinephrine) and survival (OR, 0.47; 95% CI, 0.43-0.51). The dose-dependent epinephrine association was modified by TTM. After adjusting for Utstein covariates, TTM was associated with a relative stepwise improvement in odds of CPC 1 to 2 (interaction OR, 1.36; 95% CI, 1.22-1.51) and survival (interaction OR, 1.37; 95% CI, 1.24-1.51). A significant interaction was also observed when the analysis was stratified according to initial rhythm among shockable OHCA and nonshockable OHCA (shockable interaction OR, 1.20; 95% CI, 1.04-1.39; and nonshockable interaction OR, 1.24, 95% CI, 1.07-1.45).Conclusions and RelevanceThis cohort study found an interaction between TTM and epinephrine dose such that the beneficial association of TTM increased with increasing epinephrine dose, suggesting that TTM may attenuate the adverse effects of higher-dose epinephrine.

Guidelines recommend monitoring end-tidal carbon dioxide (EThis retrospective, observational cohort analysis included adult OHCA patients who received a defibrillation shock during treatment by an urban EMS agency from 2015 to 2021. Peak EOf 518 eligible patients, mean age was 61, 72% were male, 50% had a bystander-witnessed arrest, and 62% had at least one episode of ROSC. The most common arrest etiology was medical (92%). Among all patients, peak EE

OBJECTIVES: In mechanically ventilated patients, awareness with paralysis (AWP) can have devastating consequences, including post-traumatic stress disorder (PTSD), depression, and thoughts of suicide. Single-center data from the emergency department (ED) demonstrate an event rate for AWP factors higher than that reported from the operating room. However, there remains a lack of data on AWP among critically ill, mechanically ventilated patients. The objective was to assess the proportion of ED patients experiencing AWP and investigate modifiable variables associated with its occurrence. DESIGN: An a priori planned secondary analysis of a multicenter, prospective, before-and-after clinical trial. SETTING: The ED of three academic medical centers. PATIENTS: Mechanically ventilated adult patients that received neuromuscular blockers. INTERVENTIONS: None MEASUREMENTS AND MAIN RESULTS: All data related to sedation and analgesia were collected. AWP was the primary outcome, assessed with the modified Brice questionnaire, and was independently adjudicated by three expert reviewers. Perceived threat, in the causal pathway for PTSD, was the secondary outcome. A total of 388 patients were studied. The proportion of patients experiencing AWP was 3.4% (n= 13), the majority of whom received rocuronium (n= 12/13; 92.3%). Among patients who received rocuronium, 5.5% (n= 12/230) experienced AWP, compared to 0.6% (n= 1/158) among patients who did not receive rocuronium in the ED [odds ratio, 8.64; 95% confidence interval (CI) 1.11 to 67.15]. Patients experiencing AWP had a higher mean (standard deviation) threat perception scale score, compared to patients without AWP [15.6 (5.8) vs. 7.7 (6.0), p < 0.01]. CONCLUSIONS: AWP was present in a concerning proportion of mechanically ventilated ED patients, was associated with rocuronium exposure in the ED, and led to increased levels of perceived threat, placing patients at greater risk for PTSD. Studies that aim to further quantify AWP in this vulnerable population and eliminate its occurrence are urgently needed.

To summarize pathophysiology, key conflicts, and therapeutic approaches in managing concomitant severe acute brain injury (SABI) and acute respiratory distress syndrome (ARDS).ARDS is common in SABI and independently associated with worse outcomes in all SABI subtypes. Most landmark ARDS trials excluded patients with SABI, and evidence to guide decisions is limited in this population. Potential areas of conflict in the management of patients with both SABI and ARDS are (1) risk of intracranial pressure (ICP) elevation with high levels of positive end-expiratory pressure (PEEP), permissive hypercapnia due to lung protective ventilation (LPV), or prone ventilation; (2) balancing a conservative fluid management strategy with ensuring adequate cerebral perfusion, particularly in patients with symptomatic vasospasm or impaired cerebrovascular blood flow; and (3) uncertainty about the benefit and harm of corticosteroids in this population, with a mortality benefit in ARDS, increased mortality shown in TBI, and conflicting data in other SABI subtypes. Also, the widely adapted partial pressure of oxygen (PThe management of SABI with ARDS is highly complex, and conventional ARDS management strategies may result in increased ICP and decreased cerebral perfusion. A crucial aspect of concurrent management is to recognize the risk of secondary brain injury in the individual patient, monitor with vigilance, and adjust management during critical time windows. The care of these patients requires meticulous attention to oxygenation and ventilation, hemodynamics, temperature management, and the neurological exam. LPV and prone ventilation should be utilized, and supplemented with invasive ICP monitoring if there is concern for cerebral edema and increased ICP. PEEP titration should be deliberate, involving measures of hemodynamic, pulmonary, and brain physiology. Serial volume status assessments should be performed in SABI and ARDS, and fluid management should be individualized based on measures of brain perfusion, the neurological exam, and cardiopulmonary status. More research is needed to define risks and benefits in corticosteroids in this population.

To compare the effectiveness of a primary covid-19 vaccine series plus booster doses with a primary series alone for the prevention of hospital admission with omicron related covid-19 in the United States.Multicenter observational case-control study with a test negative design.Hospitals in 18 US states.4760 adults admitted to one of 21 hospitals with acute respiratory symptoms between 26 December 2021 and 30 June 2022, a period when the omicron variant was dominant. Participants included 2385 (50.1%) patients with laboratory confirmed covid-19 (cases) and 2375 (49.9%) patients who tested negative for SARS-CoV-2 (controls).The main outcome was vaccine effectiveness against hospital admission with covid-19 for a primary series plus booster doses and a primary series alone by comparing the odds of being vaccinated with each of these regimens versus being unvaccinated among cases versus controls. Vaccine effectiveness analyses were stratified by immunosuppression status (immunocompetent, immunocompromised). The primary analysis evaluated all covid-19 vaccine types combined, and secondary analyses evaluated specific vaccine products.Overall, median age of participants was 64 years (interquartile range 52-75 years), 994 (20.8%) were immunocompromised, 85 (1.8%) were vaccinated with a primary series plus two boosters, 1367 (28.7%) with a primary series plus one booster, and 1875 (39.3%) with a primary series alone, and 1433 (30.1%) were unvaccinated. Among immunocompetent participants, vaccine effectiveness for prevention of hospital admission with omicron related covid-19 for a primary series plus two boosters was 63% (95% confidence interval 37% to 78%), a primary series plus one booster was 65% (58% to 71%), and for a primary series alone was 37% (25% to 47%) (P0.001 for the pooled boosted regimens compared with a primary series alone). Vaccine effectiveness was higher for a boosted regimen than for a primary series alone for both mRNA vaccines (BNT162b2 (Pfizer-BioNTech): 73% (44% to 87%) for primary series plus two boosters, 64% (55% to 72%) for primary series plus one booster, and 36% (21% to 48%) for primary series alone (P0.001); mRNA-1273 (Moderna): 68% (17% to 88%) for primary series plus two boosters, 65% (55% to 73%) for primary series plus one booster, and 41% (25% to 54%) for primary series alone (P=0.001)). Among immunocompromised patients, vaccine effectiveness for a primary series plus one booster was 69% (31% to 86%) and for a primary series alone was 49% (30% to 63%) (P=0.04).During the first six months of 2022 in the US, booster doses of a covid-19 vaccine provided additional benefit beyond a primary vaccine series alone for preventing hospital admissions with omicron related covid-19.This article is a living test negative design study that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication.

Background Coronavirus Disease 2019 (COVID-19) has caused over 1 200 000 deaths worldwide as of November 2020. However, little is known about the clinical outcomes among hospitalized patients with active COVID-19 after in-hospital cardiac arrest (IHCA). Aim We aimed to characterize outcomes from IHCA in patients with COVID-19 and to identify patient- and hospital-level variables associated with 30-day survival. Methods We conducted a multicentre retrospective cohort study across 11 academic medical centres in the U.S. Adult patients who received cardiopulmonary resuscitation and/or defibrillation for IHCA between March 1, 2020 and May 31, 2020 who had a documented positive test for Severe Acute Respiratory Syndrome Coronavirus 2 were included. The primary outcome was 30-day survival after IHCA. Results There were 260 IHCAs among COVID-19 patients during the study period. The median age was 69 years (interquartile range 60–77), 71.5% were male, 49.6% were White, 16.9% were Black, and 16.2% were Hispanic. The most common presenting rhythms were pulseless electrical activity (45.0%) and asystole (44.6%). ROSC occurred in 58 patients (22.3%), 31 (11.9%) survived to hospital discharge, and 32 (12.3%) survived to 30 days. Rates of ROSC and 30-day survival in the two hospitals with the highest volume of IHCA over the study period compared to the remaining hospitals were considerably lower (10.8% vs. 64.3% and 5.9% vs. 35.7% respectively, p Conclusions We found rates of ROSC and 30-day survival of 22.3% and 12.3% respectively. There were large variations in centre-level outcomes, which may explain the poor survival in prior studies.

Introduction Extracorporeal cardiopulmonary resuscitation (ECPR) is an emerging invasive rescue therapy for treatment of refractory out-of-hospital cardiac arrests (OHCA). We aim to describe the incidence of traumatic and hemorrhagic complications among patients undergoing ECPR for OHCA and examine the association between CPR duration and ECPR-related injuries or bleeding. Methods We examined prospectively collected data from the Extracorporeal Resuscitation Outcomes Database (EROD), which includes ECPR-treated OHCAs from participating hospitals (October 2014 to August 2019). The primary outcome was traumatic or hemorrhagic complications, defined any of the following: pneumothorax, pulmonary hemorrhage, major bleeding, cannula site bleeding, gastrointestinal bleeding, thoracotomy, cardiac tamponade, aortic dissection, or vascular injury during hospitalization. The primary exposure was the cardiac arrest to ECPR initiation interval (CA-ECPR interval), measured as the time from arrest to initiation of ECPR. Descriptive statistics were used to compare demographic, cardiac arrest, and ECPR characteristics among patients with and without CPR-related traumatic or bleeding complications. Multivariable logistic regression was used to examine the association between CA-ECPR interval and traumatic or bleeding complications. Results A total of 68 patients from 4 hospitals receiving ECPR for OHCA were entered into EROD and met inclusion criteria. Median age was 51 (interquartile range 38–58), 81% were male, 40% had body mass index > 30, and 70% had pre-existing medical comorbidities. A total of 65% had an initial shockable cardiac rhythm, mechanical CPR was utilized in at least 29% of patients, and 27% were discharged alive. The median time from arrest to ECPR initiation was 73 min (IQR 60–104). A total of 37% experienced a traumatic or bleeding complication, with major bleeding (32%), vascular injury (18%), and cannula site bleeding (15%) being the most common. Compared to patients with shorter CPR times, patients with a longer CA-ECPR interval had 18% (95% confidence interval — 2–42%) higher odds of suffering a mechanical or bleeding complication, but this did not reach statistical significance (p = 0.08). Conclusions Traumatic injuries and bleeding complications are common among patients undergoing ECPR. Further study is needed to investigate the relation between arrest duration and complications. Clinicians performing ECPR should anticipate and assess for injuries and bleeding in this high-risk population.

Chest compressions during CPR induce oscillations in capnography (EWe conducted a retrospective study of 307 out-of-hospital cardiac arrest (OHCA) cases in Seattle, WA during 2019. EMedian [interquartile range] AOI across all cases using Methods 1-4 was 28.0 % [17.9-45.5 %], 20.6 % [13.0-36.6 %], 18.3 % [11.4-30.4 %], and 22.4 % [12.8-38.5 %], respectively (p 0.001). Cases with ROSC had a higher median AOI than those without ROSC across all methods, though not statistically significant. Cases with ROSC had a significantly higher median [interquartile range] ΔEWe calculated AOI using four proposed methods resulting in significantly different AOI. Additionally, AOI and ΔE

The ORCHID (Outcomes Related to COVID-19 treated with Hydroxychloroquine among In-patients with symptomatic Disease) trial is a multicenter, blinded, randomized trial of hydroxychloroquine versus placebo for the treatment of adults hospitalized with coronavirus disease (COVID-19). This document provides the rationale and background for the trial and highlights key design features. We discuss five novel challenges to the design and conduct of a large, multicenter, randomized trial during a pandemic, including 1) widespread, off-label use of the study drug before the availability of safety and efficacy data; 2) the need to adapt traditional procedures for documentation of informed consent during an infectious pandemic; 3) developing a flexible and robust Bayesian analysis incorporating significant uncertainty about the disease, outcomes, and treatment; 4) obtaining indistinguishable drug and placebo without delaying enrollment; and 5) rapidly obtaining administrative and regulatory approvals. Our goals in describing how the ORCHID trial progressed from study conception to enrollment of the first patient in 15 days are to inform the development of other high-quality, multicenter trials targeting COVID-19. We describe lessons learned to improve the efficiency of future clinical trials, particularly in the setting of pandemics. The ORCHID trial will provide high-quality, clinically relevant data on the safety and efficacy of hydroxychloroquine for the treatment of COVID-19 among hospitalized adults.Clinical trial registered with www.clinicaltrials.gov (NCT04332991).

Purpose We sought to understand current POCUS practices and comfort as well as assess opinions about POCUS across our medical system via a survey to guide program development. Methods This study was conducted as a 19 question RedCap survey with multiple parts. Respondents were queried for demographics as well as experience with, attitudes toward, and clinical use of POCUS in common critical care scenarios. Results The survey was completed by 343 individuals, a response rate of 30%. Most respondents "agreed" that POCUS is a needed skill and helped them provide safer care (78% and 86% agreement). Most faculty and trainees reported some POCUS training (62% and 88%) and at least weekly use. Trainees rated themselves more comfortable than faculty for most exam types. The majority of faculty rated their POCUS education as inadequate while trainees had mixed responses. Conclusions POCUS is a frequently used tool, yet users are less confident in their skills than expected. POCUS applications are viewed as needed for future practice but there is a substantial need for improved education among faculty and trainees. Pooling resources and sharing educational initiatives across multiple specialties may help improve POCUS implementation.

Background: Leadership and teamwork are critical to the performance of a multidisciplinary team responding to emergencies in the intensive care unit; yet, these skills are variably taught to pulmonary and critical care trainees. Currently, there is no standardized leadership curriculum in critical care training. Objective: We developed a longitudinal crisis leadership curriculum for first-year pulmonary and critical care fellows using high-fidelity simulation as a medium to practice and solidify skills. The goal was to improve leadership skills and trainee confidence when leading a team during life-threatening emergencies. Methods: Guided by a needs assessment of current and recently graduated fellows, we developed a leadership curriculum from a review of the available literature and local expert opinion. Four sessions were conducted over the academic years of 2016 to 2017 and 2017 to 2018, each including small-group teaching on effective leadership behaviors, followed by simulation with postsession leadership debriefing to review performance. Fellows were surveyed regarding their experiences with the curriculum. Results: Over two academic years, 100% of targeted fellows (N = 13) completed every session. Participants reported improved understanding of key elements of effective leadership, greater confidence in leading a multidisciplinary team, and increased preparedness to lead during a crisis. Simulation with debriefing was viewed as an effective medium for learning leadership skills, and fellows provided positive feedback regarding the experience. Conclusion: Implementation of a longitudinal crisis leadership curriculum within the first year of pulmonary and critical care fellowship was feasible and highly valued by learners. More research is needed to determine effective methods for teaching and assessing leadership skills.

We sought to assess whether persistent COVID-19 symptoms beyond 6 months (Long-COVID) among patients with mild COVID-19 is associated with poorer health status, quality of life, and psychological distress.This was a multicenter prospective cohort study that included adult outpatients with acute COVID-19 from eight sites during 2-week sampling periods from April 1 and July 28, 2020. Participants were contacted 6-11 months after their first positive SARS-CoV-2 to complete a survey, which collected information on the severity of eight COVID-19 symptoms using a 4-point scale ranging from 0 (not present) to 3 (severe) at 1 month before COVID-19 (pre-illness) and at follow-up; the difference for each was calculated as an attributable persistent symptom severity score. A total attributable persistent COVID-19 symptom burden score was calculated by summing the attributable persistent severity scores for all eight symptoms. Outcomes measured at long-term follow-up comprised overall health status (EuroQol visual analogue scale), quality of life (EQ-5D-5L), and psychological distress (Patient Health Questionnaire-4). The association between the total attributable persistent COVID-19 burden score and each outcome was analyzed using multivariable proportional odds regression.Of the 2092 outpatients with COVID-19, 436 (21%) responded to the survey. The median (IQR) attributable persistent COVID-19 symptom burden score was 2 (0, 4); higher scores were associated with lower overall health status (aOR 0.63; 95% CI: 0.57-0.69), lower quality of life (aOR: 0.65; 95%CI: 0.59-0.72), and higher psychological distress (aOR: 1.40; 95%CI, 1.28-1.54) after adjusting for age, race, ethnicity, education, and income.In participants with mild acute COVID-19, the burden of persistent symptoms was significantly associated with poorer long-term health status, poorer quality of life, and psychological distress.

COVID-19 mRNA vaccines were authorized in the United States in December 2020. Although vaccine effectiveness (VE) against mild infection declines markedly after several months, limited understanding exists on the long-term durability of protection against COVID-19-associated hospitalization.Case control analysis of adults (≥18 years) hospitalized at 21 hospitals in 18 states March 11 - December 15, 2021, including COVID-19 case patients and RT-PCR-negative controls. We included adults who were unvaccinated or vaccinated with two doses of a mRNA vaccine before the date of illness onset. VE over time was assessed using logistic regression comparing odds of vaccination in cases versus controls, adjusting for confounders. Models included dichotomous time (180 vs ≥180 days since dose two) and continuous time modeled using restricted cubic splines.10,078 patients were included, 4906 cases (23% vaccinated) and 5172 controls (62% vaccinated). Median age was 60 years (IQR 46-70), 56% were non-Hispanic White, and 81% had ≥1 medical condition. Among immunocompetent adults, VE180 days was 90% (95%CI: 88-91) vs 82% (95%CI: 79-85) at ≥180 days (p 0.001). VE declined for Pfizer-BioNTech (88% to 79%, p 0.001) and Moderna (93% to 87%, p 0.001) products, for younger adults (18-64 years) [91% to 87%, p = 0.005], and for adults ≥65 years of age (87% to 78%, p 0.001). In models using restricted cubic splines, similar changes were observed.In a period largely pre-dating Omicron variant circulation, effectiveness of two mRNA doses against COVID-19-associated hospitalization was largely sustained through 9 months.

Background The study objective was to evaluate 2- and 3-dose coronavirus disease 2019 (COVID-19) mRNA vaccine effectiveness (VE) in preventing COVID-19 hospitalization among adult solid organ transplant (SOT) recipients. Methods We conducted a 21-site case-control analysis of 10 425 adults hospitalized in March to December 2021. Cases were hospitalized with COVID-19; controls were hospitalized for an alternative diagnosis (severe acute respiratory syndrome coronavirus 2-negative). Participants were classified as follows: SOT recipient (n = 440), other immunocompromising condition (n = 1684), or immunocompetent (n = 8301). The VE against COVID-19-associated hospitalization was calculated as 1-adjusted odds ratio of prior vaccination among cases compared with controls. Results Among SOT recipients, VE was 29% (95% confidence interval [CI], −19% to 58%) for 2 doses and 77% (95% CI, 48% to 90%) for 3 doses. Among patients with other immunocompromising conditions, VE was 72% (95% CI, 64% to 79%) for 2 doses and 92% (95% CI, 85% to 95%) for 3 doses. Among immunocompetent patients, VE was 88% (95% CI, 87% to 90%) for 2 doses and 96% (95% CI, 83% to 99%) for 3 doses. Conclusions Effectiveness of COVID-19 mRNA vaccines was lower for SOT recipients than immunocompetent adults and those with other immunocompromising conditions. Among SOT recipients, vaccination with 3 doses of an mRNA vaccine led to substantially greater protection than 2 doses.

Respiratory mechanics, such as tidal volume (VIn this prospective, pilot investigation of patients receiving prehospital advanced airway placement, paramedics applied a device to measure respiratory mechanics. We evaluated tidal volume (VOver 16-months, 7371 post-intubation breaths were measured in 54 patients, 32 patients with cardiac arrest and 22 with other conditions. Paramedics ventilated 19 patients with a small bag and 35 patients with a large bag. Overall, mean VWe observed that measuring respiratory mechanics in the prehospital setting was feasible. Tidal volumes were generally delivered within a safe range. Respiratory mechanics varied most significantly with active CPR with lower V

BACKGROUND: Patients with coronavirus disease 2019 (COVID-19) often develop acute hypoxemic respiratory failure and receive invasive mechanical ventilation. Much remains unknown about their respiratory mechanics, including the trajectories of pulmonary compliance and [Formula: see text] / [Formula: see text] , the prognostic value of these parameters, and the effects of prone positioning. We described respiratory mechanics among subjects with COVID-19 who were intubated during the first month of hospitalization. METHODS: We included patients with COVID-19 who were mechanically ventilated between February and May 2020. Daily values of pulmonary compliance, [Formula: see text] , [Formula: see text] , and the use of prone positioning were abstracted from electronic medical records. The trends were analyzed separately over days 1–10 and days 1–35 of intubation, stratified by prone positioning use, survival, and initial [Formula: see text] / [Formula: see text]. RESULTS: Among 49 subjects on mechanical ventilation day 1, the mean compliance was 41 mL/cm H(2)O, decreasing to 25 mL/cm H(2)O by day 14, the median duration of mechanical ventilation. In contrast, the [Formula: see text] / [Formula: see text] on day 1 was similar to day 14. The overall mean compliance was greater among the non-survivors versus the survivors (27 mL/cm H(2)O vs 24 mL/cm H(2)O; P = .005), whereas [Formula: see text] / [Formula: see text] was higher among the survivors versus the non-survivors over days 1–10 (159 mm Hg vs 138 mm Hg; P = .002) and days 1–35 (175 mm Hg vs 153 mm Hg; P < .001). The subjects who underwent early prone positioning had lower compliance during days 1–10 (27 mL/cm H(2)O vs 33 mL/cm H(2)O; P < .001) and lower [Formula: see text] / [Formula: see text] values over days 1–10 (139.9 mm Hg vs 167.4 mm Hg; P < .001) versus those who did not undergo prone positioning. After day 21 of hospitalization, the average compliance of the subjects who had early prone positioning surpassed that of the subjects who did not have prone positioning. CONCLUSIONS: Respiratory mechanics of the subjects with COVID-19 who were on mechanical ventilation were characterized by persistently low respiratory system compliance and [Formula: see text] / [Formula: see text] , similar to ARDS due to other etiologies. The [Formula: see text] / [Formula: see text] was more tightly associated with mortality than with compliance.

Objective To compare the effectiveness of a primary covid-19 vaccine series plus booster doses with a primary series alone for the prevention of hospital admission with omicron related covid-19 in the United States. Design Multicenter observational case-control study with a test negative design. Setting Hospitals in 18 US states. Participants 4760 adults admitted to one of 21 hospitals with acute respiratory symptoms between 26 December 2021 and 30 June 2022, a period when the omicron variant was dominant. Participants included 2385 (50.1%) patients with laboratory confirmed covid-19 (cases) and 2375 (49.9%) patients who tested negative for SARS-CoV-2 (controls). Main outcome measures The main outcome was vaccine effectiveness against hospital admission with covid-19 for a primary series plus booster doses and a primary series alone by comparing the odds of being vaccinated with each of these regimens versus being unvaccinated among cases versus controls. Vaccine effectiveness analyses were stratified by immunosuppression status (immunocompetent, immunocompromised). The primary analysis evaluated all covid-19 vaccine types combined, and secondary analyses evaluated specific vaccine products. Results Overall, median age of participants was 64 years (interquartile range 52-75 years), 994 (20.8%) were immunocompromised, 85 (1.8%) were vaccinated with a primary series plus two boosters, 1367 (28.7%) with a primary series plus one booster, and 1875 (39.3%) with a primary series alone, and 1433 (30.1%) were unvaccinated. Among immunocompetent participants, vaccine effectiveness for prevention of hospital admission with omicron related covid-19 for a primary series plus two boosters was 63% (95% confidence interval 37% to 78%), a primary series plus one booster was 65% (58% to 71%), and for a primary series alone was 37% (25% to 47%) (P Conclusion During the first six months of 2022 in the US, booster doses of a covid-19 vaccine provided additional benefit beyond a primary vaccine series alone for preventing hospital admissions with omicron related covid-19. Readers’ note This article is a living test negative design study that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication.

Background: COVID-19 has a widely variable clinical syndrome that is difficult to distinguish from bacterial sepsis, leading to high rates of antibiotic use. Early studies indicate low rates of secondary bacterial infections (SBIs) but have included heterogeneous patient populations. Here, we catalogue all SBIs and antibiotic prescription practices in a population of mechanically ventilated patients with COVID-19 induced acute respiratory distress syndrome (ARDS). Methods: This was a retrospective cohort study of all patients with COVID-19 ARDS requiring mechanical ventilation from 3 Seattle, Washington hospitals in 2020. Data were obtained via electronic and manual review of the electronic medical record. We report the incidence and site of SBIs, mortality, and antibiotics per day using descriptive statistics. Results: We identified 126 patients with COVID-19 induced ARDS during the study period. Of these patients, 61% developed clinical infection confirmed by bacterial culture. Ventilator associated pneumonia was confirmed in 55% of patients, bacteremia in 20%, and urinary tract infection (UTI) in 17%. Staphylococcus aureus was the most commonly isolated bacterial species. A total of 97% of patients received antibiotics during their hospitalization, and patients received nearly one antibiotic per day during their hospital stay. Conclusions: Mechanically ventilated patients with COVID-19 induced ARDS are at high risk for secondary bacterial infections and have extensive antibiotic exposure.

• Background:Antiretroviral therapy (ART) has led to dramatic improvements in survival for people living with HIV, but is unable to cure infection, or induce viral control off therapy. Designing intervention trials with novel agents with the potential to confer a period of HIV remission without ART, remains a key scientific and community goal. We detail the rationale, design, and outcomes of a randomised, placebo-controlled trial of two HIV-specific long-acting broadly neutralising antibodies (bNAbs); 3BNC117-LS and 10-1074-LS, which target CD4 binding site and V3 loop respectively, on post-treatment viral control.• Methods:RIO is a randomised, placebo-controlled, double-blinded prospective phase II study. Eligible individuals will have started ART within 3 months of primary HIV infection and have viral sequences that appear to be sensitive to both bNAbs. It will randomise 72 eligible participants 1:1 to the following arms via a two-stage design. In stage 1, arm A participants are given dual long-acting (LS-variants) bNAbs infusions, followed by intensively monitored Analytical Treatment Interruption (ATI) (n=36); in arm B, participants receive placebo infusions followed by ATI. The primary endpoint will be time to viral rebound within 36 weeks after ATI. Upon viral rebound, the participant and researcher are unblinded. Participants in arm A recommence ART and complete the study. Participants in arm B are invited to restart ART and enroll into stage 2 where they will receive open-label LS bNAbs, followed by a second ATI 24 weeks after. Secondary and exploratory endpoints include adverse events, time to undetectable viraemia after re-starting ART, immunological markers, HIV proviral DNA, serum bNAb concentrations in blood, bNAb resistance at viral rebound, and quality of life measures.• Discussion:The two-stage design was determined in collaboration with community involvement. This design allows all participants the option to receive bNAbs. It also tests the hypothesis that bNAbs may drive sustained HIV-control beyond the duration of detectable bNAb concentrations. Community representatives were involved at all stages. This included the two-stage design, discussion on the criteria to restart ART, frequency of monitoring visits off ART and reducing the risk of onward transmission to HIV-negative partners. It also included responding to the challenges of COVID-19.Trial registration: The protocol is registered on Clinical.trials.gov and EudraCT and has approval from UK Ethics and MHRA.