Tackling Brain and Muscle Dysfunction in Acute Respiratory Distress Syndrome Survivors: NHLBI Workshop Report.

Acute respiratory distress syndrome (ARDS) is associated with long-term impairments in brain and muscle function that significantly impact the quality of life of those who survive the acute illness. The mechanisms underlying these impairments are not yet well understood, and evidence-based interventions to minimize the burden on patients remain unproved. The NHLBI of the NIH assembled a workshop in April 2023 to review the state of the science regarding ARDS-associated brain and muscle dysfunction, to identify gaps in current knowledge, and to determine priorities for future investigation. The workshop included presentations by scientific leaders across the translational science spectrum and was open to the public as well as the scientific community. This report describes the themes discussed at the workshop as well as recommendations to advance the field toward the goal of improving the health and well-being of ARDS survivors.

Real-World Implications of Updated Surviving Sepsis Campaign Antibiotic Timing Recommendations.

OBJECTIVE: To evaluate real-world implications of updated Surviving Sepsis Campaign (SSC) recommendations for antibiotic timing. DESIGN: Retrospective cohort study. SETTING: Twelve hospitals in the Southeastern United States between 2017 and 2021. PATIENTS: One hundred sixty-six thousand five hundred fifty-nine adult hospitalized patients treated in the emergency department for suspected serious infection. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We determined the number and characteristics of patients affected by updated SSC recommendations for initiation of antibiotics that incorporate a risk- and probability-stratified approach. Using an infection prediction model with a cutoff of 0.5 to classify possible vs. probable infection, we found that 30% of the suspected infection cohort would be classified as shock absent, possible infection and thus eligible for the new 3-hour antibiotic recommendation. In real-world practice, this group had a conservative time to antibiotics (median, 5.5 hr; interquartile range [IQR], 3.2-9.8 hr) and low mortality (2%). Patients categorized as shock absent, probable infection had a median time to antibiotics of 3.2 hours (IQR, 2.1-5.1 hr) and mortality of 3%. Patients categorized as shock present, the probable infection had a median time to antibiotics 2.7 hours (IQR, 1.7-4.6 hr) and mortality of 17%, and patients categorized as shock present, the possible infection had a median time to antibiotics 6.9 hours (IQR, 3.5-16.3 hr) and mortality of 12%. CONCLUSIONS: These data support recently updated SSC recommendations to align antibiotic timing targets with risk and probability stratifications. Our results provide empirical support that clinicians and hospitals should not be held to 1-hour targets for patients without shock and with only possible sepsis.

Classification of Documented Goals of Care Among Hospitalized Patients with High Mortality Risk: a Mixed-Methods Feasibility Study.

BACKGROUND: The ability to classify patients' goals of care (GOC) from clinical documentation would facilitate serious illness communication quality improvement efforts and pragmatic measurement of goal-concordant care. Feasibility of this approach remains unknown. OBJECTIVE: To evaluate the feasibility of classifying patients' GOC from clinical documentation in the electronic health record (EHR), describe the frequency and patterns of changes in patients' goals over time, and identify barriers to reliable goal classification. DESIGN: Retrospective, mixed-methods chart review study. PARTICIPANTS: Adults with high (50-74%) and very high (≥ 75%) 6-month mortality risk admitted to three urban hospitals. MAIN MEASURES: Two physician coders independently reviewed EHR notes from 6 months before through 6 months after admission to identify documented GOC discussions and classify GOC. GOC were classified into one of four prespecified categories: (1) comfort-focused, (2) maintain or improve function, (3) life extension, or (4) unclear. Coder interrater reliability was assessed using kappa statistics. Barriers to classifying GOC were assessed using qualitative content analysis. KEY RESULTS: Among 85 of 109 (78%) patients, 338 GOC discussions were documented. Inter-rater reliability was substantial (75% interrater agreement; Cohen's kappa = 0.67; 95% CI, 0.60-0.73). Patients' initial documented goal was most frequently "life extension" (N = 37, 44%), followed by "maintain or improve function" (N = 28, 33%), "unclear" (N = 17, 20%), and "comfort-focused" (N = 3, 4%). Among the 66 patients whose goals' classification changed over time, most changed to "comfort-focused" goals (N = 49, 74%). Primary reasons for unclear goals were the observation of concurrently held or conditional goals, patient and family uncertainty, and limited documentation. CONCLUSIONS: Clinical notes in the EHR can be used to reliably classify patients' GOC into discrete, clinically germane categories. This work motivates future research to use natural language models to promote scalability of the approach in clinical care and serious illness research.

Protocol for a two-arm pragmatic stepped-wedge hybrid effectiveness-implementation trial evaluating Engagement and Collaborative Management to Proactively Advance Sepsis Survivorship (ENCOMPASS).

BACKGROUND: Sepsis survivors experience high morbidity and mortality, and healthcare systems lack effective strategies to address patient needs after hospital discharge. The Sepsis Transition and Recovery (STAR) program is a navigator-led, telehealth-based multicomponent strategy to provide proactive care coordination and monitoring of high-risk patients using evidence-driven, post-sepsis care tasks. The purpose of this study is to evaluate the effectiveness of STAR to improve outcomes for sepsis patients and to examine contextual factors that influence STAR implementation. METHODS: This study uses a hybrid type I effectiveness-implementation design to concurrently test clinical effectiveness and gather implementation data. The effectiveness evaluation is a two-arm, pragmatic, stepped-wedge cluster randomized controlled trial at eight hospitals in North Carolina comparing clinical outcomes between sepsis survivors who receive Usual Care versus care delivered through STAR. Each hospital begins in a Usual Care control phase and transitions to STAR in a randomly assigned sequence (one every 4 months). During months that a hospital is allocated to Usual Care, all eligible patients will receive usual care. Once a hospital transitions to STAR, all eligible patients will receive STAR during their hospitalization and extending through 90 days from discharge. STAR includes centrally located nurse navigators using telephonic counseling and electronic health record-based support to facilitate best-practice post-sepsis care strategies including post-discharge review of medications, evaluation for new impairments or symptoms, monitoring existing comorbidities, and palliative care referral when appropriate. Adults admitted with suspected sepsis, defined by clinical criteria for infection and organ failure, are included. Planned enrollment is 4032 patients during a 36-month period. The primary effectiveness outcome is the composite of all-cause hospital readmission or mortality within 90 days of discharge. A mixed-methods implementation evaluation will be conducted before, during, and after STAR implementation. DISCUSSION: This pragmatic evaluation will test the effectiveness of STAR to reduce combined hospital readmissions and mortality, while identifying key implementation factors. Results will provide practical information to advance understanding of how to integrate post-sepsis management across care settings and facilitate implementation, dissemination, and sustained utilization of best-practice post-sepsis management strategies in other heterogeneous healthcare delivery systems. TRIAL REGISTRATION: NCT04495946 . Submitted July 7, 2020; Posted August 3, 2020.

Characterizing Program Delivery for an Effective Multicomponent Sepsis Recovery Intervention.

Rationale: A recent randomized controlled trial revealed that a multicomponent sepsis transition and recovery (STAR) program delivered through specialized nurse navigators was effective in reducing a composite of 30-day readmission and mortality. Better understanding of patterns of care provided by the STAR program is needed to promote implementation and dissemination of this effective program.Objectives: This study characterizes individual care activities and distinct "packages" of care delivered by the STAR program.Methods: We performed a secondary analysis of data from the intervention arm of the IMPACTS (Improving Morbidity during Post-Acute Care Transitions for Sepsis) randomized controlled trial, conducted at three urban hospitals in the southeastern United States from January 2019 to March 2020. We used a structured data collection process to identify STAR nurse navigator care activities from electronic health record documentation. We then used latent class analysis to identify groups of patients receiving distinct combinations of intervention components. We evaluated differences in patient characteristics and outcomes between groups receiving distinct intervention packages.Results: The 317 sepsis survivors enrolled into the intervention arm of the IMPACTS trial received one or more of nine unique care activities delivered by STAR nurse navigators (care coordination, health promotion counseling, emotional listening, symptom management, medication management, chronic disease management, addressing social determinants of health, care setting advice and guidance, and primary palliative care). Patients received a median of three individual care activities (interquartile range, 2-5). Latent class analysis revealed four distinct packages of care activities delivered to patients with different observable characteristics and different frequency of 30-day readmission and mortality.Conclusions: We identified nine care activities delivered by an effective STAR program and four distinct latent classes or packages of intervention delivery. These results can be leveraged to increase widespread implementation and provide targets to augment future program delivery.

Development and validation of the HMS-Sepsis mortality model.

BACKGROUND: When comparing outcomes after sepsis, it is essential to account for patient case mix to make fair comparisons. We developed a model to assess risk-adjusted 30-day mortality in the Michigan Hospital Medicine Safety's sepsis initiative (HMS-Sepsis). QUESTION: Can HMS-Sepsis registry data adequately predict risk of 30-day mortality? Do performance assessments using adjusted vs unadjusted data differ? STUDY DESIGN AND METHODS: Retrospective cohort of community-onset sepsis hospitalizations in HMS-Sepsis registry (4/2022-9/2023), with split derivation (70%) and validation (30%) cohorts. We fit a risk-adjustment model (HMS-Sepsis mortality model) incorporating acute physiology, demographic, and baseline health data and assessed model performance using c-statistics, Brier's scores, and comparisons of predicted vs observed mortality by deciles of risk. We compared hospital performance (1st quintile, middle quintiles, 5th quintile) using observed versus adjusted mortality to understand the extent to which risk-adjustment impacted hospital performance assessment. RESULTS: Among 17,514 hospitalizations from 66 hospitals during the study period, 12,260 (70%) were used for model derivation and 5,254 (30%) for model validation. 30-day mortality for the total cohort was 19.4%. The final model included 13 physiologic variables, two physiologic interactions, and 16 demographic and chronic health variables. The most significant variables were age, metastatic solid tumor, temperature, altered mental status, and platelet count. The model c-statistic was 0.82 for the derivation cohort, 0.81 for the validation cohort, and ≥0.78 for all subgroups assessed. Overall calibration error was 0.0% and mean calibration error across deciles of risk was 1.5%. Standardized mortality ratios yielded different assessments than observed mortality for 33.9% of hospitals. CONCLUSIONS: The HMS-Sepsis mortality model had strong discrimination, adequate calibration, and reclassified one-third of hospitals to a different performance category from unadjusted mortality. Based on its strong performance, the HMS-Sepsis mortality model can aid in fair hospital benchmarking, assessment of temporal changes, and observational causal inference analysis.

Passing the SNF Test: A Secondary Analysis of a Sepsis Transition Intervention Trial Among Patients Discharged to Post-Acute Care.

OBJECTIVES: Sepsis survivors discharged to post-acute care facilities experience high rates of mortality and hospital readmission. This study compared the effects of a Sepsis Transition and Recovery (STAR) program vs usual care (UC) on 30-day mortality and hospital readmission among sepsis survivors discharged to post-acute care. DESIGN: Secondary analysis of a multisite pragmatic randomized clinical trial. SETTING AND PARTICIPANTS: Sepsis survivors discharged to post-acute care. METHODS: We conducted a secondary analysis of patients from the IMPACTS (Improving Morbidity During Post-Acute Care Transitions for Sepsis) randomized clinical trial who were discharged to post-acute care. IMPACTS evaluated the effectiveness of STAR, a nurse-navigator-led program to deliver best practice post-sepsis care. Subjects were randomized to receive either STAR or UC. The primary outcome was 30-day readmission and mortality. We also evaluated hospital-free days alive as a secondary outcome. RESULTS: Of 691 patients enrolled in IMPACTS, 175 (25%) were discharged to post-acute care [143 (82%) to skilled nursing facilities, 12 (7%) to long-term acute care hospitals, and 20 (11%) to inpatient rehabilitation]. Of these, 87 received UC and 88 received the STAR intervention. The composite 30-day all-cause mortality and readmission endpoint occurred in 26 (29.9%) patients in the UC group vs 18 (20.5%) in the STAR group [risk difference -9.4% (95% CI -22.2 to 3.4); adjusted odds ratio 0.58 (95% CI 0.28 to 1.17)]. Separately, 30-day all-cause mortality was 8.1% in the UC group compared with 5.7% in the STAR group [risk difference -2.4% (95% CI -9.9 to 5.1)] and 30-day all-cause readmission was 26.4% in the UC group compared with 17.1% in the STAR program [risk difference -9.4% (95% CI -21.5 to 2.8)]. CONCLUSIONS AND IMPLICATIONS: There are few proven interventions to reduce readmission among patients discharged to post-acute care facilities. These results suggest the STAR program may reduce 30-day mortality and readmission rates among sepsis survivors discharged to post-acute care facilities.

Older Adults' Perspectives on Screening for Cognitive Impairment Following Critical Illness: Pre-Implementation Qualitative Study.

Screening for cognitive impairment following ICU discharge is recommended but not part of routine care. We sought to understand older adults' perspectives on screening for cognitive impairment following an ICU admission to inform the design and delivery of a cognitive screening intervention. DESIGN: Qualitative study using semi-structured interviews. SUBJECTS: Adults 60 years and older within 3 months of discharge from an ICU in an academic health system. INTERVENTIONS: Interviews were conducted via telephone, audio recorded and transcribed verbatim. All transcripts were coded in duplicate. Discrepancies were resolved by consensus. Codes were organized into themes and subthemes inductively. MEASUREMENTS AND MAIN RESULTS: We completed 22 interviews. The mean age of participants was 71 ± 6 years, 14 (63.6%) were men, 16 (72.7%) were White, and 6 (27.3%) were Black. Thematic analysis was organized around four themes: 1) receptivity to screening, 2) communication preferences, 3) information needs, and 4) provider involvement. Most participants were receptive to cognitive screening; this was influenced by trust in their providers and prior experience with cognitive screening and impairment. Participants preferred simple, direct, compassionate communication. They wanted to understand the screening procedure, the rationale for screening, and expectations for recovery. Participants desired input from their primary care provider to have their cognitive screening results placed in the context of their overall health, because they had a trusted relationship, and for convenience. CONCLUSIONS: Participants demonstrated limited understanding of and exposure to cognitive screening but see it as potentially beneficial following an ICU stay. Providers should use simple, straightforward language and place emphasis on expectations. Resources may be needed to assist primary care providers with capacity to provide cognitive screening and interpret results for ICU survivors. Implementation strategies can include educational materials for clinicians and patients on rationale for screening and recovery expectations.

A Pragmatic Pilot Trial Comparing Patient-Triggered Adaptive Pressure Control to Patient-Triggered Volume Control Ventilation in Critically Ill Adults.

BACKGROUND: Patient-triggered adaptive pressure control (APC) continuous mandatory ventilation (CMV) (APC-CMV) has been widely adopted as an alternative ventilator mode to patient-triggered volume control (VC) CMV (VC-CMV). However, the comparative effectiveness of the 2 ventilator modes remains uncertain. We sought to explore clinical and implementation factors pertinent to a future definitive randomized controlled trial assessing APC-CMV versus VC-CMV as an initial ventilator mode strategy. The research objectives in our pilot trial tested clinician adherence and explored clinical outcomes. METHODS: In a single-center pragmatic sequential cluster crossover pilot trial, we enrolled all eligible adults with acute respiratory failure requiring mechanical ventilation admitted during a 9-week period to the medical ICU. Two-week time epochs were assigned a priori in which subjects received either APC-CMV or VC-CMV The primary outcome of the trial was feasibility, defined as 80% of subjects receiving the assigned mode within 1 h of initiation of ICU ventilation. The secondary outcome was proportion of the first 24 h on the assigned mode. Finally, we surveyed clinician stakeholders to understand potential facilitators and barriers to conducting a definitive randomized trial. RESULTS: We enrolled 137 subjects who received 152 discreet episodes of mechanical ventilation during time epochs assigned to APC-CMV (n = 61) and VC-CMV (n = 91). One hundred and thirty-one episodes were included in the prespecified primary outcome. One hundred and twenty-six (96%) received the assigned mode within the first hour of ICU admission (60 of 61 subjects assigned APC-CMV and 66 of 70 assigned VC-CMV). VC-CMV subjects spent a lower proportion of first 24 h (84% [95% CI 78-89]) on the assigned mode than APC-CMV recipients (95% [95% CI 91-100]). Mixed-methods analyses identified preconceived perceptions of subject comfort by clinicians and need for real-time education to address this concern. CONCLUSIONS: In this pilot pragmatic, sequential crossover trial, unit-wide allocation to a ventilator mode was feasible and acceptable to clinicians.

Systematic Review of the "Pragmatism" of Pragmatic Critical Care Trials.

To assess the pragmatism of published critical care randomized controlled trials self-described as pragmatic using a validated tool. DATA SOURCES: Medical Literature Analysis and Retrieval Online database and PubMed interface from inception to November 1, 2021. STUDY SELECTION: We performed a systematic search of randomized controlled trials evaluating interventions for critically ill adults that self-identified as pragmatic in title or abstract. DATA EXTRACTION: Reviewers independently performed study selection and data extraction in duplicate; discrepancies were resolved by consensus. Pragmatism was assessed independently in duplicate by trained reviewers using the Pragmatic-Explanatory Continuum Indicator Summary 2 (PRECIS-2), a validated tool designed to represent how explanatory/pragmatic a trial is on the pragmatic to explanatory continuum. Trials were scored in nine domains on a 5-point continuum (from 1 = very explanatory to 5 = very pragmatic). Discrepancies of greater than 2 points were adjudicated by consensus discussion. DATA SYNTHESIS: The search resulted in 284 studies; 56 met eligibility criteria. Forty-one of the trials had a discrepancy in at least one domain that required consensus discussion, most commonly in domains of eligibility and follow-up. Twelve studies (21.4%) were scored as "overall pragmatic," defined as score of greater than 4 in five domains provided the scores in the remaining domains were three. The overall PRECIS-2 score of self-identified pragmatic studies increased from 1995 to 2021 suggesting increasing pragmatism over time. Pragmatic trials were more likely to have a waiver of informed consent (p = 0.05). CONCLUSIONS: The number and pragmatism of self-identified pragmatic trials have increased, particularly in the past decade. However, less than one-quarter of these trials that use the term pragmatic in title or abstract were retrospectively rated as pragmatic. Our results support the concept that trials are designed on a spectrum of pragmatic to explanatory. Advances in the design and reporting of critical care trials are needed to ensure their real-world applicability.

Receipt of Recovery-Oriented Care Practices During Hospitalization for Sepsis.

Survivors of sepsis hospitalization are at high risk for postsepsis morbidity, readmission, and death, but these negative outcomes can be mitigated by receipt of recommended care practices. We sought to assess factors associated with the receipt of recommended recovery-oriented care practices during hospitalization for sepsis. We hypothesized that patients treated in the ICU may be more likely than ward-treated patients to receive recommended care practices given the increasing focus on survivorship in the critical care field. DESIGN: Observational cohort study. SETTING: Michigan Medicine, a tertiary academic medical center. PATIENTS: Adult patients discharged alive from a hospitalization with a primary diagnosis of sepsis or septic shock in 2019. We further limited our cohort to patients receiving longitudinal care viewable in the Michigan Medicine electronic health record to ensure ability to capture posthospital care and outcomes. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Three-hundred sixty-five sepsis hospitalizations met study inclusion criteria. Using structured chart review, we determined receipt of the following recovery-based care practices during hospitalization: medication optimization, functional status evaluation at discharge, sepsis education, and scheduled follow-up within 2 weeks. The cohort was 46.6% female, 81.1% White, with a median age of 64 years. 51.2% were treated in the ICU. Medication optimization occurred in 93.7%, functional status evaluation in 82.7%, sepsis education in 20.0%, and scheduled follow-up within 2 weeks in 54.5%. ICU-treated patients had lower receipt of medication optimization and follow-up scheduling but greater receipt of functional and mental health status evaluations. In multivariable models, ICU treatment was associated with lower odds of receiving medication optimization (adjusted odds ratio, 0.72; 95% CI, 0.03-0.69) and not associated with receipt of other care practices. CONCLUSIONS: Our study shows incomplete receipt of recommended recovery-based care practices during sepsis hospitalization in both ward and ICU-treated patients. Sepsis education and mental health evaluation were particularly uncommon.

The Effect of Outcome Selection on the Performance of Prediction Models in Patients at Risk for Sepsis.

IMPORTANCE: Risk prediction models for patients with suspected sepsis have been derived on and applied to various outcomes, including readily available outcomes such as hospital mortality and ICU admission as well as longer-term mortality outcomes that may be more important to patients. It is unknown how selecting different outcomes influences model performance in patients at risk for sepsis. OBJECTIVES: Evaluate the impact of outcome selection on risk model performance and weighting of individual predictor variables. DESIGN SETTING AND PARTICIPANTS: We retrospectively analyzed adults hospitalized with suspected infection from January 2014 to September 2017 at 12 hospitals. MAIN OUTCOMES AND MEASURES: We used routinely collected clinical data to derive logistic regression models for four outcomes: hospital mortality, composite ICU length of stay greater than 72 hours or hospital mortality, 30-day mortality, and 90-day mortality. We compared the performance of the models using area under the receiver operating characteristic curve and calibration plots. RESULTS: Among 52,184 admissions, 2,030 (4%) experienced hospital mortality, 6,659 (13%) experienced the composite of hospital mortality or ICU length of stay greater than 72 hours, 3,417 (7%) experienced 30-day mortality, and 5,655 (11%) experienced 90-day mortality. Area under the receiver operating characteristic curves decreased when hospital-based models were applied to predict 30-day (hospital mortality = 0.88-0.85; -0.03, composite ICU length of stay greater than 72 hours or hospital mortality = 0.90-0.81; -0.09) and 90-day mortality (hospital mortality = 0.88-0.81; -0.07, composite ICU length of stay greater than 72 hours or hospital mortality = 0.90-0.76; -0.14; all p < 0.01). Models were well calibrated for derived (root-mean-square error = 5-15) but not alternate outcomes (root-mean-square error = 8-35). CONCLUSIONS AND RELEVANCE: Risk models trained to predict readily available hospital-based outcomes in suspected sepsis show poorer discrimination and calibration when applied to 30- and 90-day mortality. Interpretation and application of risk models for patients at risk of sepsis should consider these findings.

Structured, proactive care coordination versus usual care for Improving Morbidity during Post-Acute Care Transitions for Sepsis (IMPACTS): a pragmatic, randomized controlled trial.

BACKGROUND: Hospital mortality for patients with sepsis has recently declined, but sepsis survivors still suffer from significant long-term mortality and morbidity. There are limited data that support effective strategies to address post-discharge management of patients hospitalized with sepsis. METHODS: The Improving Morbidity during Post-Acute Care Transitions for Sepsis (IMPACTS) study is a pragmatic, randomized controlled trial at three hospitals within a single healthcare delivery system comparing clinical outcomes between sepsis survivors who receive usual care versus care delivered through the Sepsis Transition and Recovery (STAR) program. The STAR program includes a centrally located nurse navigator using telephone counseling and electronic health record-based support to facilitate best-practice post-sepsis care strategies for patients during hospitalization and the 30 days after hospital discharge, including post-discharge review of medications, evaluation for new impairments or symptoms, monitoring existing comorbidities, and palliative care referral when appropriate. Adults admitted through the Emergency Department with suspected infection (i.e., antibiotics initiated, bacterial cultures drawn) and deemed, by previously developed risk-stratification models, high risk for readmission or death are included. Eligible patients are randomly allocated 1:1 to either Arm 1, usual care or Arm 2, STAR. Planned enrollment is 708 patients during a 6-month period. The primary outcome is the composite of all-cause hospital readmissions and mortality assessed 30 days post discharge. Secondary outcomes include 30- and 90-day hospital readmissions, mortality, emergency department visits, acute care-free days alive, and acute care and total costs. DISCUSSION: This pragmatic evaluation provides the most comprehensive assessment to date of a strategy to improve delivery of recommended post-sepsis care. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03865602. Registered retrospectively on 6 March 2019.

Rapid diagnosis of Mycobacterium abscessus endophthalmitis.

Nontuberculous mycobacteria are widely distributed in the environment and have the potential to cause a wide spectrum of infections including pulmonary, bone, soft tissue or ocular infections. They are a rare cause of endophthalmitis, a potentially devastating condition, which may be acquired through contamination of water or antiseptic solutions. Diagnosis is often delayed due to low clinical suspicion, resulting in poor clinical outcomes. Newer laboratory techniques such as real-time PCR can be used for rapid detection, identification and speciation of mycobacteria and allow for initiation of focused antibiotic therapy. We describe a case of Mycobacterium abscessus endophthalmitis that developed 30 years after traumatic loss of cornea in a patient with diabetes mellitus.