Search

BACKGROUND: Pulmonary vascular microthrombi are a proposed mechanism of COVID-19 respiratory failure. We hypothesized that early administration of tissue plasminogen activator (tPA) followed by therapeutic heparin would improve pulmonary function in these patients. RESEARCH QUESTION: Does tPA improve pulmonary function in severe COVID-19 respiratory failure, and is it safe? STUDY DESIGN AND METHODS: Adults with COVID-19-induced respiratory failure were randomized from May14, 2020 through March 3, 2021, in two phases. Phase 1 (n = 36) comprised a control group (standard-of-care treatment) vs a tPA bolus (50-mg tPA IV bolus followed by 7 days of heparin; goal activated partial thromboplastin time [aPTT], 60-80 s) group. Phase 2 (n = 14) comprised a control group vs a tPA drip (50-mg tPA IV bolus, followed by tPA drip 2 mg/h plus heparin 500 units/h over 24 h, then heparin to maintain aPTT of 60-80 s for 7 days) group. Patients were excluded from enrollment if they had not undergone a neurologic examination or cross-sectional brain imaging within the previous 4.5 h to rule out stroke and potential for hemorrhagic conversion. The primary outcome was Pao2 to Fio2 ratio improvement from baseline at 48 h after randomization. Secondary outcomes included Pao2 to Fio2 ratio improvement of > 50% or Pao2 to Fio2 ratio of ≥ 200 at 48 h (composite outcome), ventilator-free days (VFD), and mortality. RESULTS: Fifty patients were randomized: 17 in the control group and 19 in the tPA bolus group in phase 1 and eight in the control group and six in the tPA drip group in phase 2. No severe bleeding events occurred. In the tPA bolus group, the Pao2 to Fio2 ratio was significantly (P < .017) higher than baseline at 6 through 168 h after randomization; the control group showed no significant improvements. Among patients receiving a tPA bolus, the Pao2 to Fio2 ratio at 48 h (16.9% [interquartile range (IQR), -8.3% to 36.8%] vs 29.8% [IQR, 4.5%-88.7%]; P = .11), the composite outcome (11.8% vs 47.4%; P = .03), VFD (0.0 [IQR, 0.0-9.0] vs 12.0 [IQR, 0.0-19.0]; P = .11), and in-hospital mortality (41.2% vs 21.1%; P = .19) did not reach statistically significant differences when compared with those of control participants. The patients who received a tPA drip did not experience benefit. INTERPRETATION: The combination of tPA bolus plus heparin is safe in severe COVID-19 respiratory failure. A phase 3 study is warranted given the improvements in oxygenation and promising observations in VFD and mortality. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT04357730; URL: www.clinicaltrials.gov.

OBJECTIVES Availability of long-term acute care hospitals has been associated with hospital discharge practices. It is unclear if long-term acute care hospital availability can influence patient care decisions. We sought to determine the association of long-term acute care hospital availability at different hospitals with the likelihood of tracheostomy. DESIGN Retrospective cohort study. SETTING California Patient Discharge Database, 2016-2018. PATIENTS Adult patients receiving mechanical ventilation for respiratory failure. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Using the California Patient Discharge Database 2016-2018, we identified all mechanically ventilated patients and those who received tracheostomy. We determine the association between tracheostomy and the distance between each hospital and the nearest long-term acute care hospital and the number of long-term acute care hospital beds within 20 miles of each hospital. Among 281,502 hospitalizations where a patient received mechanical ventilation, 22,899 (8.1%) received a tracheostomy. Patients admitted to a hospital closer to a long-term acute care hospital compared with those furthest from a long-term acute care hospital had 38.9% (95% CI, 33.3-44.6%) higher odds of tracheostomy (closest hospitals 8.7% vs furthest hospitals 6.3%, adjusted odds ratio = 1.65; 95% CI, 1.40-1.95). Patients had a 32.4% (95% CI, 27.6-37.3%) higher risk of tracheostomy when admitted to a hospital with more long-term acute care hospital beds in the immediate vicinity (most long-term acute care hospital beds within 20 miles 8.9% vs fewest long-term acute care hospital beds 6.7%, adjusted odds ratio = 1.54; 95% CI, 1.31-1.80). Distance to the nearest long-term acute care hospital was inversely correlated with hospital risk-adjusted tracheostomy rates (ρ = -0.25; p < 0.0001). The number of long-term acute care hospital beds within 20 miles was positively correlated with hospital risk-adjusted tracheostomy rates (ρ = 0.22; p < 0.0001). CONCLUSIONS Proximity and availability of long-term acute care hospital beds were associated with patient odds of tracheostomy and hospital tracheostomy practices. These findings suggest a hospital effect on tracheostomy decision-making over and above patient case-mix. Future studies focusing on shared decision-making for tracheostomy are needed to ensure goal-concordant care for prolonged mechanical ventilation.

Supplemental Digital Content is available in the text., OBJECTIVES: Respiratory failure, multiple organ failure, shortness of breath, recovery, and mortality have been identified as critically important core outcomes by more than 9300 patients, health professionals, and the public from 111 countries in the global coronavirus disease 2019 core outcome set initiative. The aim of this project was to establish the core outcome measures for these domains for trials in coronavirus disease 2019. DESIGN: Three online consensus workshops were convened to establish outcome measures for the four core domains of respiratory failure, multiple organ failure, shortness of breath, and recovery. SETTING: International. PATIENTS: About 130 participants (patients, public, and health professionals) from 17 countries attended the three workshops. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Respiratory failure, assessed by the need for respiratory support based on the World Health Organization Clinical Progression Scale, was considered pragmatic, objective, and with broad applicability to various clinical scenarios. The Sequential Organ Failure Assessment was recommended for multiple organ failure, because it was routinely used in trials and clinical care, well validated, and feasible. The Modified Medical Research Council measure for shortness of breath, with minor adaptations (recall period of 24 hr to capture daily fluctuations and inclusion of activities to ensure relevance and to capture the extreme severity of shortness of breath in people with coronavirus disease 2019), was regarded as fit for purpose for this indication. The recovery measure was developed de novo and defined as the absence of symptoms, resumption of usual daily activities, and return to the previous state of health prior to the illness, using a 5-point Likert scale, and was endorsed. CONCLUSIONS: The coronavirus disease 2019 core outcome set recommended core outcome measures have content validity and are considered the most feasible and acceptable among existing measures. Implementation of the core outcome measures in trials in coronavirus disease 2019 will ensure consistency and relevance of the evidence to inform decision-making and care of patients with coronavirus disease 2019.

Prior work has shown substantial between-hospital variation in do-not-resuscitate orders, but stability of do-not-resuscitate preferences between hospitalizations and the institutional influence on do-not-resuscitate reversals are unclear. We determined the extent of do-not-resuscitate reversals between hospitalizations and the association of the readmission hospital with do-not-resuscitate reversal.Retrospective cohort study.California Patient Discharge Database, 2016-2018.Nonsurgical patients admitted to an acute care hospital with an early do-not-resuscitate order (within 24 hr of admission).None.We identified nonsurgical adult patients who survived an initial hospitalization with an early-do-not-resuscitate order and were readmitted within 30 days. The primary outcome was the association of do-not-resuscitate reversal with readmission to the same or different hospital from the initial hospital. Secondary outcomes included association of readmission to a low versus high do-not-resuscitate-rate hospital with do-not-resuscitate reversal. Among 49,336 patients readmitted within 30 days following a first do-not-resuscitate hospitalization, 22,251 (45.1%) experienced do-not-resuscitate reversal upon readmission. Patients readmitted to a different hospital versus the same hospital were at higher risk of do-not-resuscitate reversal (59.5% vs 38.5%; p0.001; adjusted odds ratio = 2.4; 95% CI, 2.3-2.5). Patients readmitted to low versus high do-not-resuscitate-rate hospitals were more likely to have do-not-resuscitate reversals (do-not-resuscitate-rate quartile 1 77.0% vs quartile 4 27.2%; p0.001; adjusted odds ratio = 11.9; 95% CI, 10.7-13.2). When readmitted to a different versus the same hospital, patients with do-not-resuscitate reversal had higher rates of mechanical ventilation (adjusted odds ratio = 1.9; 95% CI, 1.6-2.1) and hospital death (adjusted odds ratio = 1.2; 95% CI, 1.1-1.3).Do-not-resuscitate reversals at the time of readmission are more common than previously reported. Although changes in patient preferences may partially explain between-hospital differences, we observed a strong hospital effect contributing to high do-not-resuscitate-reversal rates with significant implications for patient outcomes and resource.

Background: Fluid and vasopressor management in septic shock remains controversial. In this randomized controlled trial, we evaluated the efficacy of dynamic measures (stroke volume change during passive leg raise) to guide resuscitation and improve patient outcome. Research Question: Will resuscitation guided by dynamic assessments of fluid responsiveness in patients with septic shock improve patient outcomes? Study Design and Methods: Prospective, multicenter, randomized clinical trial at 13 hospitals in the United States and United Kingdom. Patients presented to Emergency Rooms with sepsis associated hypotension and anticipated Intensive Care Unit (ICU) admission. Intervention arm patients were assessed for fluid responsiveness before clinically driven fluid bolus or increase in vasopressors. The protocol included reassessment and therapy as indicated by the PLR result. The control arm received Usual Care. Primary clinical outcome was positive fluid balance at 72 hours or ICU discharge, whichever occurred first. Results: In modified-ITT (mITT) analysis including 83 Intervention and 41 Usual Care eligible patients, fluid balance at 72 hours or ICU discharge was significantly lower (-1.37L favoring Intervention arm, 0.65 ± 2.85L Intervention arm vs. 2.02 ± 3.44L Usual Care arm, p=0.021. Fewer patients required renal replacement therapy (5.1% vs 17.5%, p=0.04) or mechanical ventilation (17.7% vs 34.1%, p=0.04) in the Intervention arm compared to Usual Care. In the allrandomized Intent to Treat (ITT) population (102 Intervention, 48 Usual Care) there were no significant differences in safety signals. Interpretation: Physiologically informed fluid and vasopressor resuscitation using passive leg raise-induced stroke volume change to guide management of septic shock is safe and demonstrated lower net fluid balance and reductions in the risk of renal and respiratory failure. Dynamic assessments to guide fluid administration may improve outcomes for septic shock patients compared with Usual Care. Trial Registration clinicaltrials.gov identifier: NCT02837731

BACKGROUND: The coronavirus (COVID-19) pandemic has seen a global surge in anxiety, depression, post-traumatic stress disorder (PTSD), and stress. AIMS: This study aimed to describe the perspectives of patients with COVID-19, their family, health professionals, and the general public on the impact of COVID-19 on mental health. METHODS: A secondary thematic analysis was conducted using data from the COVID-19 COS project. We extracted data on the perceived causes and impact of COVID-19 on mental health from an international survey and seven online consensus workshops. RESULTS: We identified four themes (with subthemes in parenthesis): anxiety amidst uncertainty (always on high alert, ebb and flow of recovery); anguish of a threatened future (intense frustration of a changed normality, facing loss of livelihood, trauma of ventilation, a troubling prognosis, confronting death); bearing responsibility for transmission (fear of spreading COVID-19 in public; overwhelming guilt of infecting a loved one); and suffering in isolation (severe solitude of quarantine, sick and alone, separation exacerbating grief). CONCLUSION: We found that the unpredictability of COVID-19, the fear of long-term health consequences, burden of guilt, and suffering in isolation profoundly impacted mental health. Clinical and public health interventions are needed to manage the psychological consequences arising from this pandemic.

IntroductionAmong critically ill patients undergoing orotracheal intubation in the emergency department (ED) or intensive care unit (ICU), failure to visualise the vocal cords and intubate the trachea on the first attempt is associated with an increased risk of complications. Two types of laryngoscopes are commonly available: direct laryngoscopes and video laryngoscopes. For critically ill adults undergoing emergency tracheal intubation, it remains uncertain whether the use of a video laryngoscope increases the incidence of successful intubation on the first attempt compared with the use of a direct laryngoscope.Methods and analysisTheDirEct versusVIdeo LaryngosCopE(DEVICE) trial is a prospective, multicentre, non-blinded, randomised trial being conducted in 7 EDs and 10 ICUs in the USA. The trial plans to enrol up to 2000 critically ill adults undergoing orotracheal intubation with a laryngoscope. Eligible patients are randomised 1:1 to the use of a video laryngoscope or a direct laryngoscope for the first intubation attempt. The primary outcome is successful intubation on the first attempt. The secondary outcome is the incidence of severe complications between induction and 2 min after intubation, defined as the occurrence of one or more of the following: severe hypoxaemia (lowest oxygen saturation Ethics and disseminationThe trial protocol was approved with waiver of informed consent by the single institutional review board at Vanderbilt University Medical Center and the Human Research Protection Office of the Department of Defense. The results will be presented at scientific conferences and submitted for publication in a peer-reviewed journal.Trial registration numberClinicalTrials.gov Registry (NCT05239195).

Background: \ud In COVACTA, a randomised, placebo-controlled trial in patients hospitalised with coronavirus disease-19 (COVID-19), tocilizumab did not improve 28-day mortality, but shortened hospital and intensive care unit stay. Longer-term effects of tocilizumab in patients with COVID-19 are unknown. Therefore, the efficacy and safety of tocilizumab in COVID-19 beyond day 28 and its impact on Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) clearance and antibody response in COVACTA were investigated.\ud \ud Methods: \ud Adults in Europe and North America hospitalised with COVID-19 (N = 452) between April 3, 2020 and May 28, 2020 were randomly assigned (2:1) to double-blind intravenous tocilizumab or placebo and assessed for efficacy and safety through day 60. Assessments included mortality, time to hospital discharge, SARS-CoV-2 viral load in nasopharyngeal swab and serum samples, and neutralising anti-SARS-CoV-2 antibodies in serum. ClinicalTrials.gov registration: NCT04320615.\ud \ud Findings: \ud By day 60, 24·5% (72/294) of patients in the tocilizumab arm and 25·0% (36/144) in the placebo arm died (weighted difference –0·5% [95% CI –9·1 to 8·0]), and 67·0% (197/294) in the tocilizumab arm and 63·9% (92/144) in the placebo arm were discharged from the hospital. Serious infections occurred in 24·1% (71/295) of patients in the tocilizumab arm and 29·4% (42/143) in the placebo arm. Median time to negative reverse transcriptase–quantitative polymerase chain reaction result in nasopharyngeal/oropharyngeal samples was 15·0 days (95% CI 14·0 to 21·0) in the tocilizumab arm and 21·0 days (95% CI 14·0 to 28·0) in the placebo arm. All tested patients had positive test results for neutralising anti–SARS-CoV-2 antibodies at day 60.\ud \ud Interpretation: \ud There was no mortality benefit with tocilizumab through day 60. Tocilizumab did not impair viral clearance or host immune response, and no new safety signals were observed. Future investigations may explore potential biomarkers to optimize patient selection for tocilizumab treatment and combination therapy with other treatments.\ud \ud Funding: \ud F. Hoffmann-La Roche Ltd and the US Department of Health and Human Services, Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority, under OT number HHSO100201800036C.

Background: Severe alcohol withdrawal syndrome (SAWS) is highly morbid, costly, and common among hospitalized patients, yet minimal evidence exists to guide inpatient management. Research needs in this field are broad, spanning the translational science spectrum. Goals: This research statement aims to describe what is known about SAWS, identify knowledge gaps, and offer recommendations for research in each domain of the Institute of Medicine T0-T4 continuum to advance the care of hospitalized patients who experience SAWS. Methods: Clinicians and researchers with unique and complementary expertise in basic, clinical, and implementation research related to unhealthy alcohol consumption and alcohol withdrawal were invited to participate in a workshop at the American Thoracic Society 2019 International Conference. The committee was subdivided into four groups on the basis of interest and expertise: T0-T1 (basic science research with translation to humans), T2 (research translating to patients), T3 (research translating to clinical practice), and T4 (research translating to communities). A medical librarian conducted a pragmatic literature search to facilitate this work, and committee members reviewed and supplemented the resulting evidence, identifying key knowledge gaps. Results: The committee identified several investigative opportunities to advance the care of patients with SAWS in each domain of the translational science spectrum. Major themes included 1) the need to investigate non-γ-aminobutyric acid pathways for alcohol withdrawal syndrome treatment; 2) harnessing retrospective and electronic health record data to identify risk factors and create objective severity scoring systems, particularly for acutely ill patients with SAWS; 3) the need for more robust comparative-effectiveness data to identify optimal SAWS treatment strategies; and 4) recommendations to accelerate implementation of effective treatments into practice. Conclusions: The dearth of evidence supporting management decisions for hospitalized patients with SAWS, many of whom require critical care, represents both a call to action and an opportunity for the American Thoracic Society and larger scientific communities to improve care for a vulnerable patient population. This report highlights basic, clinical, and implementation research that diverse experts agree will have the greatest impact on improving care for hospitalized patients with SAWS.

Critical care practitioners have some of the highest levels of burnout in health care.What are key drivers of burnout across the multidisciplinary ICU team?We conducted a multicenter mixed-methods cohort study in ICUs at three diverse hospitals. We recruited physicians, nurses, respiratory therapists, and other staff members who worked primarily in an ICU. Participants completed the Maslach Burnout Inventory for Human Services Survey for Medical Personnel (MBI) and a qualitative focus group or interview using a phenomenologic approach. MBI subscales for emotional exhaustion, depersonalization, and lack of personal accomplishment were calculated. Emergent shared themes contributing to burnout were identified from qualitative interviews.Fifty-eight providers (26 physicians, 22 nurses, six respiratory therapists, three pharmacists, and one case manager) participated. Ten participants (17.9%) described their burnout as moderate to high. However, participants scored moderate or high levels across the three MBI subscales (emotional exhaustion, 71.4%; depersonalization, 53.6%; and lack of personal achievement, 53.6%). Drivers of burnout aligned with three core themes: patient factors, team dynamics, and hospital culture. Individual drivers included medically futile cases, difficult families, contagiousness of burnout, lack of respect between team members, the increasing burden of administrative or regulatory requirements at the cost of time with patients, lack of recognition from hospital leadership, and technology. All were highly interconnected across the three larger domains. Despite differences in MBI scores, most provider types described very similar drivers of burnout.High levels of burnout were identified through the MBI, but participants did not self-report high levels of burnout, suggesting a lack of awareness. Drivers of burnout were highly interconnected, but factors related to team dynamics and hospital culture were most prominent and shared across provider types. The shared drivers of burnout across multiple provider types highlights the need for interventions focused on team- and system-level drivers.

Tracheostomy utilization has dramatically increased recently. Large gaps exist between expected and actual outcomes resulting in significant decisional conflict and regret. We determined 1-year patient outcomes and healthcare utilization following tracheostomy to aid in decision-making and resource allocation.Retrospective cohort study.All California hospital discharges from 2012 to 2013 with follow-up through 2014.Nonsurgical patients who received a tracheostomy for acute respiratory failure.None.Our primary outcome was 30-day, 90-day, and 1-year mortality. We also determined hospitals readmissions rates and healthcare utilization in the first year following tracheostomy. We identified 8,343 tracheostomies during the study period. One-year mortality following tracheostomy was high, 46.5%. Older adults (≥ 65 yr) had significantly higher mortality compared with younger patients (65 yr) (54.7% vs 36.5%; p0.0001). Median survival for older adults was 175 days (95% CI, 150-202 d) compared with greater than 1 year for younger adults (adjusted hazard ratio, 1.25; 95% CI, 1.14-1.36). Within 1 year of tracheostomy, 60.3% of patients required hospital readmission. Older adults were more likely to be readmitted in the first year after tracheostomy compared with younger adults (66.1% vs 55.2%; adjusted hazard ratio, 1.19; 95% CI, 1.09-1.29). Total short-term acute care hospital costs (index and readmissions) in the first year after tracheostomy were high (mean, $215,369; SD, $160,874).Long-term outcomes following tracheostomy are extremely poor with high mortality, morbidity, and healthcare resource utilization especially among older patients. Some subsets of younger patients may have better outcomes compared with the general tracheostomy population. Short-term acute care costs were extremely high in the first year following tracheostomy. If extended to the entire U.S. population, total short-term acute care hospital costs approach $11 billion dollars per year for tracheostomy-related to acute respiratory failure. These findings may aid families and surrogates in the decision-making process.

Objectives Prior studies investigating hospital mechanical ventilation volume-outcome associations have had conflicting findings. Volume-outcome relationships within contemporary mechanical ventilation practices are unclear. We sought to determine associations between hospital mechanical ventilation volume and patient outcomes. Design Retrospective cohort study. Setting The California Patient Discharge Database 2016. Patients Adult nonsurgical patients receiving mechanical ventilation. Interventions The primary outcome was hospital death with secondary outcomes of tracheostomy and 30-day readmission. We used multivariable generalized estimating equations to determine the association between patient outcomes and hospital mechanical ventilation volume quartile. Measurements and main results We identified 51,689 patients across 274 hospitals who required mechanical ventilation in California in 2016. 38.2% of patients died in the hospital with 4.4% receiving a tracheostomy. Among survivors, 29.5% required readmission within 30 days of discharge. Patients admitted to high versus low volume hospitals had higher odds of death (quartile 4 vs quartile 1 adjusted odds ratio, 1.40; 95% CI, 1.17-1.68) and tracheostomy (quartile 4 vs quartile 1 adjusted odds ratio, 1.58; 95% CI, 1.21-2.06). However, odds of 30-day readmission among survivors was lower at high versus low volume hospitals (quartile 4 vs quartile 1 adjusted odds ratio, 0.77; 95% CI, 0.67-0.89). Higher hospital mechanical ventilation volume was weakly correlated with higher hospital risk-adjusted mortality rates (ρ = 0.16; p = 0.008). These moderately strong observations were supported by multiple sensitivity analyses. Conclusions Contrary to previous studies, we observed worse patient outcomes at higher mechanical ventilation volume hospitals. In the setting of increasing use of mechanical ventilation and changes in mechanical ventilation practices, multiple mechanisms of worse outcomes including resource strain are possible. Future studies investigating differences in processes of care between high and low volume hospitals are necessary.

Interventions designed to improve care and reduce costs for patients with the highest rates of hospital utilization (super-utilizers) continue to proliferate, despite conflicting evidence of cost savings.We evaluated a practice transformation intervention that implemented team-based care and risk-stratification to match specific primary care resources based on need. This included an intensive outpatient clinic for super-utilizers. We used multivariate regression and a difference-in-differences approach to compare changes in mortality, utilization, and charges between the intervention group and a historical control. Sensitivity analyses tested the robustness of findings and revealed the inherent challenges associated with quasi-experimental designs.Observed charges for the intervention group were significantly lower than expected charges as derived by the trend of the historical control (p0.04) resulting in total charge avoidance of approximately $26 million. While inpatient admissions were significantly higher (p0.01), charges associated with total inpatient (p=0.01), intensive-care unit (p0.05, not robust to sensitivity analyses), and surgery (p0.01) were significantly lower than expected in the intervention group. One year mortality was significantly less in the intervention group (12.6% vs 11.5%, p0.01).The use of tailored services, including a dedicated intensive outpatient clinic, for super-utilizers within a larger primary care practice transformation reduced mortality and provided significant savings, even while total hospitalizations increased. These savings were achieved through a reduction in the intensity of inpatient services. The unexpected finding of a reduction in ICU charges deserves further exploration.These findings suggest that intensity of inpatient service, and not merely volume of services, should be considered a focus for future intervention design and evaluated as an outcome.Level III (Quasi-Experimental Design).

Rationale: Deficiencies exist in the communication of prognosis for patients requiring prolonged mechanical ventilation (PMV) from COVID-19 pneumonia, in part because of clinician uncertainty about the natural history of disease and observational cohort studies with variable outcomes. In order to address this gap for PMV patients, we developed a modified clinical prediction model based on the ProVent-14 model to predict in-hospital mortality for patients receiving at least 14 days of mechanical ventilation for acute respiratory distress syndrome (ARDS) from COVID-19. Methods: We evaluated 107 patients with COVID-19 requiring PMV (at least 14 days of mechanical ventilation (MV)) at 2 tertiary care medical centers in the US in a retrospective observational cohort study. On day 14 of MV, we collected data for the original ProVent-14 variables (age, platelet count, requirement for vasopressors, non-trauma admission, and dialysis requirement). We also collected data for 2 other potential predictor variables (extra-corporeal membrane oxygenation (ECMO) on day 14 and neutrophil to lymphocyte ratio). Model Development: Logistic regression models were used to evaluate the performance of the ProVent-14 variables with the outcome inhospital mortality. We then assessed successive models adding variable combinations including requirement of ECMO and neutrophil to lymphocyte ratio on day 14 to predict inhospital mortality. We assessed discrimination of the models by measuring the area under the receiver operating characteristic curve (AUC). We assessed calibration by the Hosmer-Lemeshow goodness of fit statistic. Results: The AUC for the model using original Provent-14 variables was 0.78 (trauma omitted for N=1). The most parsimonious model using the additional variables includes risk factors age 50-64 and ≥65;platelet count 15) improves the model slightly AUC=0.83, Goodness-of-fit p=0.61, though this variable was available for only 60% of the cohort. Conclusion: A modified clinical prediction model based on the previously validated ProVent-14 model is a simple method to accurately identify patients with ARDS from COVID-19 requiring PMV who are at high risk of in-hospital mortality. Further validation of model performance in a larger population and including long-term survival is warranted.

Background Coronavirus disease 2019 (Covid-19) is associated with immune dysregulation and hyperinflammation, including elevated interleukin-6 levels. The use of tocilizumab, a monoclonal antibody against the interleukin-6 receptor, has resulted in better outcomes in patients with severe Covid-19 pneumonia in case reports and retrospective observational cohort studies. Data are needed from randomized, placebo-controlled trials. Methods In this phase 3 trial, we randomly assigned patients who were hospitalized with severe Covid-19 pneumonia in a 2:1 ratio receive a single intravenous infusion of tocilizumab (at a dose of 8 mg per kilogram of body weight) or placebo. Approximately one quarter of the participants received a second dose of tocilizumab or placebo 8 to 24 hours after the first dose. The primary outcome was clinical status at day 28 on an ordinal scale ranging from 1 (discharged or ready for discharge) to 7 (death) in the modified intention-to-treat population, which included all the patients who had received at least one dose of tocilizumab or placebo. Results Of the 452 patients who underwent randomization, 438 (294 in the tocilizumab group and 144 in the placebo group) were included in the primary and secondary analyses. The median value for clinical status on the ordinal scale at day 28 was 1.0 (95% confidence interval [CI], 1.0 to 1.0) in the tocilizumab group and 2.0 (non-ICU hospitalization without supplemental oxygen) (95% CI, 1.0 to 4.0) in the placebo group (between-group difference, -1.0; 95% CI, -2.5 to 0; P = 0.31 by the van Elteren test). In the safety population, serious adverse events occurred in 103 of 295 patients (34.9%) in the tocilizumab group and in 55 of 143 patients (38.5%) in the placebo group. Mortality at day 28 was 19.7% in the tocilizumab group and 19.4% in the placebo group (weighted difference, 0.3 percentage points (95% CI, -7.6 to 8.2; nominal P = 0.94). Conclusions In this randomized trial involving hospitalized patients with severe Covid-19 pneumonia, the use of tocilizumab did not result in significantly better clinical status or lower mortality than placebo at 28 days. (Funded by F. Hoffmann-La Roche and the Department of Health and Human Services; COVACTA ClinicalTrials.gov number, NCT04320615.).

OBJECTIVES: Prone position ventilation is a potentially life-saving ancillary intervention but is not widely adopted for coronavirus disease 2019 or acute respiratory distress syndrome from other causes. Implementation of lung-protective ventilation including prone positioning for coronavirus disease 2019 acute respiratory distress syndrome is limited by isolation precautions and personal protective equipment scarcity. We sought to determine the safety and associated clinical outcomes for coronavirus disease 2019 acute respiratory distress syndrome treated with prolonged prone position ventilation without daily repositioning. DESIGN: Retrospective single-center study. SETTING: Community academic medical ICU. PATIENTS: Sequential mechanically ventilated patients with coronavirus disease 2019 acute respiratory distress syndrome. INTERVENTIONS: Lung-protective ventilation and prolonged protocolized prone position ventilation without daily supine repositioning. Supine repositioning was performed only when Fio2 less than 60% with positive end-expiratory pressure less than 10 cm H2O for greater than or equal to 4 hours. MEASUREMENTS AND MAIN RESULTS: Primary safety outcome: proportion with pressure wounds by Grades (0-4). Secondary outcomes: hospital survival, length of stay, rates of facial and limb edema, hospital-acquired infections, device displacement, and measures of lung mechanics and oxygenation. Eighty-seven coronavirus disease 2019 patients were mechanically ventilated. Sixty-one were treated with prone position ventilation, whereas 26 did not meet criteria. Forty-two survived (68.9%). Median (interquartile range) time from intubation to prone position ventilation was 0.28 d (0.11-0.80 d). Total prone position ventilation duration was 4.87 d (2.08-9.97 d). Prone position ventilation was applied for 30.3% (18.2-42.2%) of the first 28 days. Pao2:Fio2 diverged significantly by day 3 between survivors 147 (108-164) and nonsurvivors 107 (85-146), mean difference -9.632 (95% CI, -48.3 to 0.0; p = 0·05). Age, driving pressure, day 1, and day 3 Pao2:Fio2 were predictive of time to death. Thirty-eight (71.7%) developed ventral pressure wounds that were associated with prone position ventilation duration and day 3 Sequential Organ Failure Assessment. Limb weakness occurred in 58 (95.1%) with brachial plexus palsies in five (8.2%). Hospital-acquired infections other than central line-associated blood stream infections were infrequent. CONCLUSIONS: Prolonged prone position ventilation was feasible and relatively safe with implications for wider adoption in treating critically ill coronavirus disease 2019 patients and acute respiratory distress syndrome of other etiologies.

On September 22nd the US officially recorded 200,000 COVID-19 deaths. It is unclear how many deaths might have been expected in the case of an early and effective response to the pandemic. We aim to provide a best-case estimate of COVID-19 deaths in the US by September 22nd using the experience of Germany as a benchmark. Our methods accommodate the differences in demographics between Germany and the US. We match cumulative incidence of COVID-19 deaths by age group in Germany to non-Hispanic whites in the US and project the implied number of deaths in this population and among the black and Hispanic populations under observed racial/ethnic disparities in cumulative COVID-19 mortality in the US. We estimate that if the US had been as successful as Germany in managing the pandemic we would have expected 22% of the deaths actually recorded. The number of deaths would have been lower by a further one-third if we could have eliminated racial/ethnic disparites in COVID-19 outcomes. We conclude that almost 80 percent of the COVID-19 deaths in the US by September 22nd could have been avoided with an early and effective response producing similar age-specific death rates among non-Hispanic whites as in Germany.

BACKGROUNDCOVID-19 is associated with immune dysregulation and hyperinflammation. Tocilizumab is an anti–interleukin-6 receptor antibody.METHODSPatients hospitalized with severe COVID-19 pneumonia receiving standard care were randomized (2:1) to double-blinded intravenous tocilizumab 8 mg/kg or placebo. The primary outcome measure was clinical status on a 7-category ordinal scale at day 28 (1, discharged/ready for discharge; 7, death).RESULTSOverall, 452 patients were randomized; the modified-intention-to-treat population included 294 tocilizumab-treated and 144 placebo-treated patients. Clinical status at day 28 was not statistically significantly improved for tocilizumab versus placebo (P=0.36). Median (95% CI) ordinal scale values at day 28: 1.0 (1.0 to 1.0) for tocilizumab and 2.0 (1.0 to 4.0) for placebo (odds ratio, 1.19 [0.81 to 1.76]). There was no difference in mortality at day 28 between tocilizumab (19.7%) and placebo (19.4%) (difference, 0.3% [95% CI, –7.6 to 8.2]; nominal P=0.94). Median time to hospital discharge was 8 days shorter with tocilizumab than placebo (20.0 and 28.0, respectively; nominal P=0.037; hazard ratio 1.35 [95% CI 1.02 to 1.79]). Median duration of ICU stay was 5.8 days shorter with tocilizumab than placebo (9.8 and 15.5, respectively; nominal P=0.045). In the safety population, serious adverse events occurred in 34.9% of 295 patients in the tocilizumab arm and 38.5% of 143 in the placebo arm.CONCLUSIONSIn this randomized placebo-controlled trial in hospitalized COVID-19 pneumonia patients, tocilizumab did not improve clinical status or mortality. Potential benefits in time to hospital discharge and duration of ICU stay are being investigated in ongoing clinical trials.Trial registrationClinicalTrials.gov NCTG432G615

Supplemental Digital Content is available in the text., Objectives: There are over 4,000 trials conducted in people with coronavirus disease 2019. However, the variability of outcomes and the omission of patient-centered outcomes may diminish the impact of these trials on decision-making. The aim of this study was to generate a consensus-based, prioritized list of outcomes for coronavirus disease 2019 trials. Design: In an online survey conducted in English, Chinese, Italian, Portuguese, and Spanish languages, adults with coronavirus disease 2019, their family members, health professionals, and the general public rated the importance of outcomes using a 9-point Likert scale (7–9, critical importance) and completed a Best-Worst Scale to estimate relative importance. Participant comments were analyzed thematically. Setting: International. Subjects: Adults 18 years old and over with confirmed or suspected coronavirus disease 2019, their family members, members of the general public, and health professionals (including clinicians, policy makers, regulators, funders, and researchers). Interventions: None. Measurements: None. Main Results: In total, 9,289 participants from 111 countries (776 people with coronavirus disease 2019 or family members, 4,882 health professionals, and 3,631 members of the public) completed the survey. The four outcomes of highest priority for all three groups were: mortality, respiratory failure, pneumonia, and organ failure. Lung function, lung scarring, sepsis, shortness of breath, and oxygen level in the blood were common to the top 10 outcomes across all three groups (mean > 7.5, median ≥ 8, and > 70% of respondents rated the outcome as critically important). Patients/family members rated fatigue, anxiety, chest pain, muscle pain, gastrointestinal problems, and cardiovascular disease higher than health professionals. Four themes underpinned prioritization: fear of life-threatening, debilitating, and permanent consequences; addressing knowledge gaps; enabling preparedness and planning; and tolerable or infrequent outcomes. Conclusions: Life-threatening respiratory and other organ outcomes were consistently highly prioritized by all stakeholder groups. Patients/family members gave higher priority to many patient-reported outcomes compared with health professionals.

Current procedural terminology (CPT) codes for surgical stabilization of rib fractures (SSRF) are based solely on the number of ribs fixed, tricotomized at 1-3, 4-6, and ≥ 7. Our objective was to validate CPT codes against operative time at our institution, as well as further stratify complexity by rib fracture location and surgical approach. The purpose of this study is to validate the current CPT coding schema for SSRF, and to identify potential modifiers that are associated with increased case complexity. We hypothesized that operative time is associated with CPT code, number of fractures repaired, exposure technique, and fracture location.Retrospective review of SSRF cases from October 2010 to March 2020. The primary outcome was the length of the operation (minutes). Predictor variables were CPT code, number of fractures repaired (grouped similarly to CPT codes), fractures repaired:ribs repaired ratio1, fracture location (sub-scapular vs. other), and positioning/exposure (supine, lateral, prone, and multiple). Kaplan-Meier time-to-event analyses were used to assess relationship with operative time.188 patients underwent repair of 904 fractures. Operative time was significantly associated with both number of ribs repaired and number of fractures repaired (p0.01). Although operative time varied significantly by CPT group (p0.01), there was no significant difference between the 4-6 rib and the ≥ 7 rib groups (p = 0.33). By contrast, each group was significantly different from the others when organized by number of fractures repaired (p = 0.04). Operative time was significantly longer when the fractures repaired:ribs repaired ratio was1 (p0.01), even after stratifying by number of ribs repaired. Both multiple positions/exposures (p0.01), and repair of ≥ 1 sub-scapular fracture (p0.01) were significantly associated with operative time.Number of fractures repaired provided a more accurate estimation of operative time as compared to number of ribs repaired. Based on these data, we recommend altering the CPT schema for SSRF to involve number of fractures repaired, with modifiers for both multiple positions/exposures and repair of sub-scapular fractures.

Background: Despite improved survival and increasing hospital mandates, discordance with sepsis resuscitation guidelines is common. We sought to determine whether choice architecture can promote faster or slower decision-making among physicians and the associated risk of guideline-discordance in sepsis.Methods: We conducted an electronic, survey-based time-to-event analysis using a sepsis clinical vignette and multivariable Cox proportional hazards regression. Respondents included physicians from multiple specialties and levels of training at an academic tertiary-care hospital and academic safety-net hospital. Respondents were randomized to one of three distinct answer sets: control (6 options with no time limit), time constraint (10 seconds, intended to promote faster thinking) or choice overload (24 options, intended to promote slower thinking). The primary outcomes were response time and discordance with Surviving Sepsis Campaign 2016 fluid resuscitation guidelines, adjusting for physician characteristics. Physician risk tolerance and predisposition towards intuitive or analytical thinking were assessed for effect modification.Results: 189 of 624 (30.3%) physicians completed the survey. Total response time was lower in time constraint (45.8s, IQR 38.3s-56.6s, PConclusions: Choice architecture may impact clinical decisions and guideline discordance in sepsis, warranting further investigation in real-world contexts.

Intensive care units (ICUs) are an appropriate focus of antibiotic stewardship program efforts because a large proportion of any hospital's use of parenteral antibiotics, especially broad-spectrum, occurs in the ICU. Given the importance of antibiotic stewardship for critically ill patients and the importance of critical care practitioners as the front line for antibiotic stewardship, a workshop was convened to specifically address barriers to antibiotic stewardship in the ICU and discuss tactics to overcome these. The working definition of antibiotic stewardship is "the right drug at the right time and the right dose for the right bug for the right duration." A major emphasis was that antibiotic stewardship should be a core competency of critical care clinicians. Fear of pathogens that are not covered by empirical antibiotics is a major driver of excessively broad-spectrum therapy in critically ill patients. Better diagnostics and outcome data can address this fear and expand efforts to narrow or shorten therapy. Greater awareness of the substantial adverse effects of antibiotics should be emphasized and is an important counterargument to broad-spectrum therapy in individual low-risk patients. Optimal antibiotic stewardship should not focus solely on reducing antibiotic use or ensuring compliance with guidelines. Instead, it should enhance care both for individual patients (by improving and individualizing their choice of antibiotic) and for the ICU population as a whole. Opportunities for antibiotic stewardship in common ICU infections, including community- and hospital-acquired pneumonia and sepsis, are discussed. Intensivists can partner with antibiotic stewardship programs to address barriers and improve patient care.

Fluid and vasopressor management in septic shock remains controversial. In this randomized controlled trial, we evaluated the efficacy of dynamic measures (stroke volume change during passive leg raise) to guide resuscitation and improve patient outcome.Will resuscitation that is guided by dynamic assessments of fluid responsiveness in patients with septic shock improve patient outcomes?We conducted a prospective, multicenter, randomized clinical trial at 13 hospitals in the United States and United Kingdom. Patients presented to EDs with sepsis that was associated hypotension and anticipated ICU admission. Intervention arm patients were assessed for fluid responsiveness before clinically driven fluid bolus or increase in vasopressors occurred. The protocol included reassessment and therapy as indicated by the passive leg raise result. The control arm received usual care. The primary clinical outcome was positive fluid balance at 72 hours or ICU discharge, whichever occurred first.In modified intent-to-treat analysis that included 83 intervention and 41 usual care eligible patients, fluid balance at 72 hours or ICU discharge was significantly lower (-1.37 L favoring the intervention arm; 0.65 ± 2.85 L intervention arm vs 2.02 ± 3.44 L usual care arm; P = .021. Fewer patients required renal replacement therapy (5.1% vs 17.5%; P = .04) or mechanical ventilation (17.7% vs 34.1%; P = .04) in the intervention arm compared with usual care. In the all-randomized intent-to-treat population (102 intervention, 48 usual care), there were no significant differences in safety signals.Physiologically informed fluid and vasopressor resuscitation with the use of the passive leg raise-induced stroke volume change to guide management of septic shock is safe and demonstrated lower net fluid balance and reductions in the risk of renal and respiratory failure. Dynamic assessments to guide fluid administration may improve outcomes for patients with septic shock compared with usual care.NCT02837731.

Objectives: The outcomes reported in trials in coronavirus disease 2019 are extremely heterogeneous and of uncertain patient relevance, limiting their applicability for clinical decision-making. The aim of this workshop was to establish a core outcomes set for trials in people with suspected or confirmed coronavirus disease 2019. Design: Four international online multistakeholder consensus workshops were convened to discuss proposed core outcomes for trials in people with suspected or confirmed coronavirus disease 2019, informed by a survey involving 9,289 respondents from 111 countries. The transcripts were analyzed thematically. The workshop recommendations were used to finalize the core outcomes set. Setting: International. Subjects: Adults 18 years old and over with confirmed or suspected coronavirus disease 2019, their family members, members of the general public and health professionals (including clinicians, policy makers, regulators, funders, researchers). Interventions: None. Measurements: None. Main Results: Six themes were identified. “Responding to the critical and acute health crisis” reflected the immediate focus on saving lives and preventing life-threatening complications that underpinned the high prioritization of mortality, respiratory failure, and multiple organ failure. “Capturing different settings of care” highlighted the need to minimize the burden on hospitals and to acknowledge outcomes in community settings. “Encompassing the full trajectory and severity of disease” was addressing longer term impacts and the full spectrum of illness (e.g. shortness of breath and recovery). “Distinguishing overlap, correlation and collinearity” meant recognizing that symptoms such as shortness of breath had distinct value and minimizing overlap (e.g. lung function and pneumonia were on the continuum toward respiratory failure). “Recognizing adverse events” refers to the potential harms of new and evolving interventions. “Being cognizant of family and psychosocial wellbeing” reflected the pervasive impacts of coronavirus disease 2019. Conclusions: Mortality, respiratory failure, multiple organ failure, shortness of breath, and recovery are critically important outcomes to be consistently reported in coronavirus disease 2019 trials.

Strong evidence supports use of noninvasive ventilation (NIV) for patients with respiratory distress from chronic obstructive pulmonary disease and heart failure (strong evidence conditions [SECs]). Despite unclear benefits of NIV for other causes of acute respiratory failure, utilization for conditions with weaker evidence is increasing, despite evidence demonstrating higher mortality for patients who suffer NIV failure (progression from NIV to invasive mechanical ventilation [IMV])) compared with being treated initially with IMV.To determine the association of hospital variation in evidence-based utilization of NIV with patient outcomes.Using the California State Inpatient Database 2011, we identified adult patients who received NIV. Patients were considered to have an SEC for NIV if they had an acute exacerbation of chronic obstructive pulmonary disease or heart failure. We used multivariable hierarchical logistic regression to determine the association between hospital rates of NIV use for SECs and patient risk of NIV failure (need for IMV after NIV).Among 22,706 hospitalizations with NIV as the initial ventilatory strategy, 6,820 (30.0%) had SECs. Patients with SECs had lower risk of NIV failure than patients with weak evidence conditions (8.1 vs. 18.2%, P 0.0001). Regardless of underlying diagnosis, patients admitted to hospitals with greater use of NIV for SECs had lower risk of NIV failure (Quartile 4 vs. Quartile 1 adjusted odds ratio = 0.62; 95% CI = 0.49-0.80). Even patients without an SEC benefited from admission to hospitals that used NIV more often for patients with SECs (Quartile 4 vs. Quartile 1 adjusted odds ratio for NIV failure = 0.68; 95% CI = 0.52-0.88).Most patients who received NIV did not have conditions with strong supporting evidence for its use with wide institutional variation in patient selection for NIV. Surprisingly, we found that all patients, even those without an SEC, benefited from admission to hospitals with greater evidence-based utilization of NIV, suggesting a "hospital effect" that is synergistic with patient selection.

Purpose of review Diagnosis of pulmonary infection, including hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) in the critically ill patient remains a common and therapeutically challenging diagnosis with significant attributable morbidity, mortality, and cost. Current clinical approaches to surveillance, early detection and, conventional culture-based microbiology are inadequate for optimal targeted antibiotic treatment and stewardship. Efforts to enhance diagnosis of HAP and VAP and the impact of these novel approaches on rational antimicrobial selection and stewardship are the focus of recent studies reviewed here. Recent findings Recent consensus guidelines for diagnosis and management of HAP and VAP are relatively silent on the potential role of novel rapid microbiological techniques and reply heavily on conventional culture strategies of noninvasively obtained (including endotracheal aspirate samples). Novel rapid microbiological diagnostics, including nucleic acid amplification, mass spectrometry, and fluorescence microscopy-based technologies are promising approaches for the future. Exhaled breath biomarkers, including measurement of VOC represent a future approach. Summary Further validation of novel diagnostic technology platforms will be required to evaluate their utility for enhancing diagnosis and guiding treatment of pulmonary infections in the critically ill. However, the integration of novel diagnostics for rapid microbial identification, resistance phenotyping, and antibiotic sensitivity testing into usual care practice could significantly transform the care of patients and potentially inform improved targeted antimicrobial selection, de-escalation, and stewardship.

Purpose: Sepsis stimulates pro- and anti-inflammatory immune responses. The innate immune response is critical to organ injury repair. We tested for an association between innate immune function and organ function recovery in a prospective cohort of immune-competent adults with sepsis. Methods: We conducted a prospective observational cohort study enrolling immune-competent adults with sepsis. We tested innate immune function by quantification of lipopolysaccharide (LPS)-stimulated tumor necrosis factor (TNF) α production capacity in whole blood samples on hospital days 1, 4, and 6. The primary outcome was organ function recovery on day 4 defined as a 4-point decrease in the composite cardiovascular and respiratory Sequential Organ Failure Assessment (SOFA) score components or a SOFA score ≤2. Results: Patients with sepsis who recovered organ function by day 4 (n = 11) had similar baseline characteristics when compared to those with ongoing organ failure (n = 13). Tumor necrosis factor α production capacity was similar between the 2 groups on hospital days 1 and 4 but significantly different on day 6. Patients who regained organ function recovery had significantly higher TNF-α production capacity on day 6 ( P = .01), which persisted after adjustment for age, Acute Physiology and Chronic Health Evaluation III score, and steroid administration ( P = .03). There was no difference in TNF-α production capacity over time in those who survived to hospital discharge versus nonsurvivors. Conclusion: Increasing TNF-α production capacity is associated with improved organ failure recovery. Further studies are needed to evaluate a causal association between innate immune suppression and organ failure recovery as well as predictive accuracy for hospital survival. Impaired TNF-α production as a marker of sepsis-associated innate immune dysfunction may be a feasible target for immune stimulation to decrease time to organ failure recovery.

The crisis in the Middle East has raised awareness about the challenges encountered by migrant populations, in particular, health-care access and delivery. Similar challenges are encountered by migrant populations around the world, including those entering the United States as refugees and/or survivors of torture as well as Mexicans and other Latin Americans crossing the border. During the 2016 International American Thoracic Society Meeting held in San Francisco, California, a group of researchers and health-care providers discussed these challenges at a minisymposium devoted to the respiratory health of migrants. The discussion focused on the increased incidence of airway diseases among individuals migrating to more developed countries, the problems created by sleep disorders and their implications for cardiovascular and mental health, the challenges inherent in the control of infections in refugee populations, and the problems resulting from deportation. The group also discussed the potential impact of novel strategies made available by Internet-based technologies and how these strategies could be deployed to support worldwide efforts in assisting migrants and refugees, even in countries that find themselves in the direst circumstances. These presentations are summarized in this document, which is not meant to be exhaustive, but to improve awareness about the challenges confronted by migrants and their host nations regarding respiratory health-care access and delivery, and about the need for adequate investment of resources to better define these challenges through research and for the development of efficient strategies for intervention.

Rationale There remains significant controversy regarding the optimal approach to fluid resuscitation for patients in shock. The magnitude of care variability in shock resuscitation, the confounding effects of disease severity and comorbidity, and the relative impact on sepsis survival are poorly understood. Objective To evaluate usual care variability and determine the differential effect of observed and predicted fluid resuscitation volumes on risk-adjusted hospital mortality for mechanically ventilated patients in shock. Methods We performed a retrospective outcome analysis of mechanically ventilated patients admitted to intensive care units using the 2013 Premier Hospital Database (Premier, Inc.). Observed and predicted hospital mortality were evaluated by observed and predicted day 1 fluid administration, using the difference in predicted and observed outcomes to adjust for disease severity between groups. Both predictive models were validated using a second large administrative database (Truven Health Analytics Inc.). Secondary outcomes included duration of mechanical ventilation, hospital and ICU length of stay, and cost. Results Among 33,831 patients, observed hospital mortality was incrementally higher than predicted for each additional liter of day 1 fluid beginning at 7 L (40.9% vs. 37.2%, p = 0.008). Compared to patients that received expected (± 1.5 L predicted) day 1 fluid volumes, greater-than-expected fluid resuscitation was associated with increased risk-adjusted hospital mortality (52.3% vs. 45.0%, p p p p = 0.037) day 1 fluid resuscitation were associated with increased risk-adjusted hospital mortality. Conclusions Highly variable day 1 fluid resuscitation was associated with a non-uniform impact on risk-adjusted hospital mortality among distinct subgroups of mechanically ventilated patients with shock. These findings support closer evaluation of fluid resuscitation strategies that include broadly applied fluid volume targets in the early phase of shock resuscitation.

BackgroundHospitalised patients whose inpatient teams rotate off service experience increased mortality related to end-of-rotation care transitions, yet standardised handoff practices are lacking.ObjectiveDevelop and implement a multidisciplinary patient-centred handoff intervention to improve outcomes for patients who are critically ill during end-of-rotation transitions.Design, setting and participantsSingle-centre, controlled pilot study of medical intensive care unit (ICU) patients whose resident team was undergoing end-of-rotation transition at a university hospital from June 2017 to February 2018.InterventionA 4-item intervention was implemented over two study periods. Intervention 1 included: (1) in-person bedside handoff between teams rotating off and on service, (2) handoff checklist, (3) nursing involvement in handoff, and (4) 30 min education session. Intervention 2 included the additional option to conduct bedside handoff via videoconferencing.Main outcome measuresImplementation was measured by repeated clinician surveys and direct observation. Patient outcomes included length of stay (LOS; ICU and hospital) and mortality (ICU, hospital and 30 days). Clinician perceptions were modelled over time using per cent positive responses in logistic regression. Patient outcomes were compared with matched control ‘transition’ patients from 1 year prior to implementation of the intervention.ResultsAmong 270 transition patients, 46.3% were female with a mean age of 55.9 years. Mechanical ventilation (64.1%) and in-hospital death (27.6%) rates were prevalent. Despite high implementation rates—handoff participation (93.8%), checklist utilisation (75.0%), videoconferencing (62.5%), nursing involvement (75.0%)—the intervention did not significantly improve LOS or mortality. Multidisciplinary survey data revealed significant improvement in acceptability by nursing staff, while satisfaction significantly declined for resident physicians.ConclusionsIn this controlled pilot study, a structured ICU end-of-rotation care transition strategy was feasible to implement with high fidelity. While mortality and LOS were not affected in a pilot study with limited power, the pragmatic strategy of this intervention holds promise for future trials.

Purpose Patients with alcohol misuse are less likely to receive preventive health services but more likely to utilize emergency health services. However, the association between alcohol misuse and outpatient follow-up after hospitalization is unknown and may depend on whether a patient experiences a critical illness. We sought to determine whether alcohol misuse was associated with lower rates of outpatient follow-up after hospital discharge and whether the magnitude of this association differed in patients who experienced a critical illness. Materials and methods This was a retrospective cohort study using administrative data from an urban safety net hospital. Patients were included if they were admitted between 2011 and 2015, were between the ages of 18 and 89, resided within the safety net county, were discharged home, and were at moderate to high risk for hospital readmission within the subsequent 30 days. Alcohol misuse was identified using a combination of ICD-9 codes and response to a single screening question. The primary outcome was a combined measure of follow-up with a primary care physician or specialist provider in the 30 days following hospital discharge. Multivariable logistic regression was used to adjust for factors known to be associated with healthcare utilization. Results Overall, 17,575 patients were included in the analysis; 4984 (28%) had alcohol misuse. In the 30 days following hospital discharge, 46% of patients saw any outpatient provider. In an unadjusted analysis, the association between alcohol misuse and attending any outpatient follow-up was dependent on whether patients had a critical illness (p value