Operationalizing Equity, Inclusion, and Access in Research Practice at a Large Academic Institution.

INTRODUCTION: Healthcare advances are hindered by underrepresentation in prospective research; sociodemographic, data, and measurement infidelity in retrospective research; and a paucity of guidelines surrounding equitable research practices. OBJECTIVE: The Joint Research Practices Working Group was created in 2021 to develop and disseminate guidelines for the conduct of inclusive and equitable research. METHODS: Volunteer faculty and staff from two research centers at the University of Pennsylvania initiated a multi-pronged approach to guideline development, including literature searches, center-level feedback, and mutual learning with local experts. RESULTS: We developed guidelines for (1) participant payment and incentives; (2) language interpretation and translation; (3) plain language in research communications; (4) readability of study materials; and (5) inclusive language for scientific communications. Key recommendations include (1) offer cash payments and multiple payment options to participants when required actions are completed; (2) identify top languages of your target population, map points of contact, and determine available interpretation and translation resources; (3) assess reading levels of materials and simplify language, targeting 6th- to 8th-grade reading levels; (4) improve readability through text formatting and style, symbols, and visuals; and (5) use specific, humanizing terms as adjectives rather than nouns. CONCLUSIONS: Diversity, inclusion, and access are critical values for research conduct that promotes justice and equity. These values can be operationalized through organizational commitment that combines bottom-up and top-down approaches and through partnerships across organizations that promote mutual learning and synergy. While our guidelines represent best practices at one time, we recognize that practices evolve and need to be evaluated continuously for accuracy and relevance. Our intention is to bring awareness to these critical topics and form a foundation for important conversations surrounding equitable and inclusive research practices.

Prediction of In-hospital Mortality Among Intensive Care Unit Patients Using Modified Daily Laboratory-based Acute Physiology Score, Version 2.

BACKGROUND: Mortality prediction for intensive care unit (ICU) patients frequently relies on single ICU admission acuity measures without accounting for subsequent clinical changes. OBJECTIVE: Evaluate novel models incorporating modified admission and daily, time-updating Laboratory-based Acute Physiology Score, version 2 (LAPS2) to predict in-hospital mortality among ICU patients. RESEARCH DESIGN: Retrospective cohort study. PATIENTS: ICU patients in 5 hospitals from October 2017 through September 2019. MEASURES: We used logistic regression, penalized logistic regression, and random forest models to predict in-hospital mortality within 30 days of ICU admission using admission LAPS2 alone in patient-level and patient-day-level models, or admission and daily LAPS2 at the patient-day level. Multivariable models included patient and admission characteristics. We performed internal-external validation using 4 hospitals for training and the fifth for validation, repeating analyses for each hospital as the validation set. We assessed performance using scaled Brier scores (SBS), c -statistics, and calibration plots. RESULTS: The cohort included 13,993 patients and 107,699 ICU days. Across validation hospitals, patient-day-level models including daily LAPS2 (SBS: 0.119-0.235; c -statistic: 0.772-0.878) consistently outperformed models with admission LAPS2 alone in patient-level (SBS: 0.109-0.175; c -statistic: 0.768-0.867) and patient-day-level (SBS: 0.064-0.153; c -statistic: 0.714-0.861) models. Across all predicted mortalities, daily models were better calibrated than models with admission LAPS2 alone. CONCLUSIONS: Patient-day-level models incorporating daily, time-updating LAPS2 to predict mortality among an ICU population performs as well or better than models incorporating modified admission LAPS2 alone. The use of daily LAPS2 may offer an improved tool for clinical prognostication and risk adjustment in research in this population.

Patients' Perspectives on Life and Recovery 1 Year After COVID-19 Hospitalization.

BACKGROUND: Many patients hospitalized for COVID-19 experience prolonged symptoms months after discharge. Little is known abou t patients' personal experiences recovering from COVID-19 in the United States (US), where medically underserved populations are at particular risk of adverse outcomes. OBJECTIVE: To explore patients' perspectives on the impact of COVID-19 hospitalization and barriers to and facilitators of recovery 1 year after hospital discharge in a predominantly Black American study population with high neighborhood-level socioeconomic disadvantage. DESIGN: Qualitative study utilizing individual, semi-structured interviews. PARTICIPANTS: Adult patients hospitalized for COVID-19 approximately 1 year after discharge home who were engaged in a COVID-19 longitudinal cohort study. APPROACH: The interview guide was developed and piloted by a multidisciplinary team. Interviews were audio-recorded and transcribed. Data were coded and organized into discrete themes using qualitative content analysis with constant comparison techniques. KEY RESULTS: Of 24 participants, 17 (71%) self-identified as Black, and 13 (54%) resided in neighborhoods with the most severe neighborhood-level socioeconomic disadvantage. One year after discharge, participants described persistent deficits in physical, cognitive, or psychological health that impacted their current lives. Repercussions included financial suffering and a loss of identity. Participants reported that clinicians often focused on physical health over cognitive and psychological health, an emphasis that posed a barrier to recovering holistically. Facilitators of recovery included robust financial or social support systems and personal agency in health maintenance. Spirituality and gratitude were common coping mechanisms. CONCLUSIONS: Persistent health deficits after COVID-19 resulted in downstream consequences in participants' lives. Though participants received adequate care to address physical needs, many described persistent unmet cognitive and psychological needs. A more comprehensive understanding of barriers and facilitators for COVID-19 recovery, contextualized by specific healthcare and socioeconomic needs related to socioeconomic disadvantage, is needed to better inform intervention delivery to patients that experience long-term sequelae of COVID-19 hospitalization.

A Data-Driven Analysis of Ward Capacity Strain Metrics That Predict Clinical Outcomes Among Survivors of Acute Respiratory Failure.

Supply-demand mismatch of ward resources ("ward capacity strain") alters care and outcomes. Narrow strain definitions and heterogeneous populations limit strain literature. Evaluate the predictive utility of a large set of candidate strain variables for in-hospital mortality and discharge destination among acute respiratory failure (ARF) survivors. In a retrospective cohort of ARF survivors transferred from intensive care units (ICUs) to wards in five hospitals from 4/2017-12/2019, we applied 11 machine learning (ML) models to identify ward strain measures during the first 24 hours after transfer most predictive of outcomes. Measures spanned patient volume (census, admissions, discharges), staff workload (medications administered, off-ward transports, transfusions, isolation precautions, patients per respiratory therapist and nurse), and average patient acuity (Laboratory Acute Physiology Score version 2, ICU transfers) domains. The cohort included 5,052 visits in 43 wards. Median age was 65 years (IQR 56-73); 2,865 (57%) were male; and 2,865 (57%) were white. 770 (15%) patients died in the hospital or had hospice discharges, and 2,628 (61%) were discharged home and 964 (23%) to skilled nursing facilities (SNFs). Ward admissions, isolation precautions, and hospital admissions most consistently predicted in-hospital mortality across ML models. Patients per nurse most consistently predicted discharge to home and SNF, and medications administered predicted SNF discharge. In this hypothesis-generating analysis of candidate ward strain variables' prediction of outcomes among ARF survivors, several variables emerged as consistently predictive of key outcomes across ML models. These findings suggest targets for future inferential studies to elucidate mechanisms of ward strain's adverse effects.

Wellness and Coping of Physicians Who Worked in ICUs During the Pandemic: A Multicenter Cross-Sectional North American Survey.

OBJECTIVES: Few surveys have focused on physician moral distress, burnout, and professional fulfilment. We assessed physician wellness and coping during the COVID-19 pandemic. DESIGN: Cross-sectional survey using four validated instruments. SETTING: Sixty-two sites in Canada and the United States. SUBJECTS: Attending physicians (adult, pediatric; intensivist, nonintensivist) who worked in North American ICUs. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: We analysed 431 questionnaires (43.3% response rate) from 25 states and eight provinces. Respondents were predominantly male (229 [55.6%]) and in practice for 11.8 ± 9.8 years. Compared with prepandemic, respondents reported significant intrapandemic increases in days worked/mo, ICU bed occupancy, and self-reported moral distress (240 [56.9%]) and burnout (259 [63.8%]). Of the 10 top-ranked items that incited moral distress, most pertained to regulatory/organizational ( n = 6) or local/institutional ( n = 2) issues or both ( n = 2). Average moral distress (95.6 ± 66.9), professional fulfilment (6.5 ± 2.1), and burnout scores (3.6 ± 2.0) were moderate with 227 physicians (54.6%) meeting burnout criteria. A significant dose-response existed between COVID-19 patient volume and moral distress scores. Physicians who worked more days/mo and more scheduled in-house nightshifts, especially combined with more unscheduled in-house nightshifts, experienced significantly more moral distress. One in five physicians used at least one maladaptive coping strategy. We identified four coping profiles (active/social, avoidant, mixed/ambivalent, infrequent) that were associated with significant differences across all wellness measures. CONCLUSIONS: Despite moderate intrapandemic moral distress and burnout, physicians experienced moderate professional fulfilment. However, one in five physicians used at least one maladaptive coping strategy. We highlight potentially modifiable factors at individual, institutional, and regulatory levels to enhance physician wellness.

Intensive Care Unit Capacity Strain and Outcomes of Critical Illness in a Resource-Limited Setting: A 2-Hospital Study in South Africa.

OBJECTIVE: To measure the association of intensive care unit (ICU) capacity strain with processes of care and outcomes of critical illness in a resource-limited setting. METHODS: We performed a retrospective cohort study of 5332 patients referred to the ICUs at 2 public hospitals in South Africa using the country's first published multicenter electronic critical care database. We assessed the association between multiple ICU capacity strain metrics (ICU occupancy, turnover, census acuity, and referral burden) at different exposure time points (ICU referral, admission, and/or discharge) with clinical and process of care outcomes. The association of ICU capacity strain at the time of ICU admission with ICU length of stay (LOS), the primary outcome, was analyzed with a multivariable Cox proportional hazard model. Secondary outcomes of ICU triage decision (with strain at ICU referral), ICU mortality (with strain at ICU admission), and ICU LOS (with strain at ICU discharge), were analyzed with linear and logistic multivariable regression. RESULTS: No measure of ICU capacity strain at the time of ICU admission was associated with ICU LOS, the primary outcome. The ICU occupancy at the time of ICU admission was associated with increased odds of ICU mortality (odds ratio = 1.07, 95% confidence interval: 1.02-1.11; P = .004), a secondary outcome, such that a 10% increase in ICU occupancy would be associated with a 7% increase in the odds of ICU mortality. CONCLUSIONS: In a resource-limited setting in South Africa, ICU capacity strain at the time of ICU admission was not associated with ICU LOS. In secondary analyses, higher ICU occupancy at the time of ICU admission, but not other measures of capacity strain, was associated with increased odds of ICU mortality.

Early Oseltamivir After Hospital Admission Is Associated With Shortened Hospitalization: A 5-Year Analysis of Oseltamivir Timing and Clinical Outcomes.

BACKGROUND: Neuraminidase inhibitors (NAIs) are the only effective therapy for influenza, but few studies have assessed the impact of early NAI therapy on clinical outcomes or the patient-level factors that determine early NAI delivery in hospitalized patients. METHODS: We conducted a retrospective cohort study of all adults hospitalized in a metropolitan tertiary care hospital with confirmed influenza from April 2009 to March 2014. We performed logistic regression to determine patient-level factors that were associated with early NAI therapy. We analyzed the association of early NAI therapy with hospital lengths of stay (LOS) and in-hospital mortality rates using linear and logistic regression, respectively. RESULTS: In total, 699 patients were admitted with influenza during the 5 influenza seasons. Of those, 582 (83.4%) received NAI therapy; however, only 26.0% received the first dose within 6 hours of hospitalization (early NAI). Patients with diabetes mellitus or pregnancy were more likely to receive early NAI (P = .01, vs. P < .001 in those without these conditions), as were those reporting fever or myalgias at presentation (P = .002, vs. P = .005 without). Immunosuppressed patients were less likely to receive early NAI (P = .04). Early NAI was associated with shorter hospital LOS (P < .001). No patients died in the early NAI group, compared to 18 deaths in the 399 patients receiving NAI after 6 hours (4.5%) and 4 deaths in the 116 patients not receiving NAI (3.4%). CONCLUSIONS: Over multiple influenza seasons, early NAI therapy was associated with shorter LOS in patients admitted with influenza. This suggests that efforts should focus on facilitating earlier therapy in patients with suspected influenza.

Determining the Association Between End-of-Life Care Resources and Patient Outcomes in Pennsylvania ICUs.

OBJECTIVES: As ICUs are increasingly a site of end-of-life care, many have adopted end-of-life care resources. We sought to determine the association of such resources with outcomes of ICU patients. DESIGN: Retrospective cohort study. SETTING: Pennsylvania ICUs. PATIENTS: Medicare fee-for-service beneficiaries. INTERVENTIONS: Availability of any of one hospital-based resource (palliative care consultants) or four ICU-based resources (protocol for withdrawal of life-sustaining therapy, triggers for automated palliative care consultation, protocol for family meetings, and palliative care clinicians embedded in ICU rounds). MEASUREMENTS AND MAIN RESULTS: In mixed-effects regression analyses, admission to a hospital with end-of-life resources was not associated with mortality, length of stay, or treatment intensity (mechanical ventilation, hemodialysis, tracheostomy, gastrostomy, artificial nutrition, or cardiopulmonary resuscitation); however, it was associated with a higher likelihood of discharge to hospice (odds ratio, 1.58; 95% CI, 1.11-2.24), an effect that was driven by ICU-based resources (odds ratio, 1.37; 95% CI, 1.04-1.81) rather than hospital-based resources (odds ratio, 1.19; 95% CI, 0.83-1.71). Instrumental variable analysis using differential distance (defined as the additional travel distance beyond the hospital closest to a patient's home needed to reach a hospital with end-of-life resources) demonstrated that among those for whom differential distance would influence receipt of end-of-life resources, admission to a hospital with such resources was not associated with any outcome. CONCLUSIONS: ICU-based end-of-life care resources do not appear to change mortality but are associated with increased hospice utilization. Given that this finding was not confirmed by the instrumental variable analysis, future studies should attempt to verify this finding, and identify specific resources or processes of care that impact the care of ICU patients at the end of life.

Validation of an Administrative Definition of ICU Admission Using Revenue Center Codes.

OBJECTIVES: Describe the operating characteristics of a proposed set of revenue center codes to correctly identify ICU stays among hospitalized patients. DESIGN: Retrospective cohort study. We report the operating characteristics of all ICU-related revenue center codes for intensive and coronary care, excluding nursery, intermediate, and incremental care, to identify ICU stays. We use a classification and regression tree model to further refine identification of ICU stays using administrative data. The gold standard for classifying ICU admission was an electronic patient location tracking system. SETTING: The University of Pennsylvania Health System in Philadelphia, PA, United States. PATIENTS: All adult inpatient hospital admissions between July 1, 2013, and June 30, 2015. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 127,680 hospital admissions, the proposed combination of revenue center codes had 94.6% sensitivity (95% CI, 94.3-94.9%) and 96.1% specificity (95% CI, 96.0-96.3%) for correctly identifying hospital admissions with an ICU stay. The classification and regression tree algorithm had 92.3% sensitivity (95% CI, 91.6-93.1%) and 97.4% specificity (95% CI, 97.2-97.6%), with an overall improved accuracy (χ = 398; p < 0.001). CONCLUSIONS: Use of the proposed combination of revenue center codes has excellent sensitivity and specificity for identifying true ICU admission. A classification and regression tree algorithm with additional administrative variables offers further improvements to accuracy.

Successful long-term management of invasive cerebral fungal infection following liver transplantation.

Central nervous system (CNS) infections after liver transplantation may be fungal in aetiology, with involvement from either common organisms such as Cryptococcus neoformans and Aspergillus spp. as well as less common organisms, such as the Mucorales and Scedosporium spp. Although the mortality of CNS fungal infections was nearly 100% in early series, more recent data has suggested that good outcomes can be achieved. This may be due to both improved diagnostic capabilities, such as the ability to obtain fungal susceptibilities and therapeutic drug levels, and improved therapeutic options, such as the newer triazoles- voriconazole and posaconazole. Due to improved outcomes, issues have now arisen around the long-term tolerability of these agents. The following two cases of invasive cerebral fungal infections following liver transplantation, one with Aspergillus flavus, and the other with Scedosporium boydii/apiospermum highlight the success that can be seen with the modern management of a previously fatal diagnosis. In particular, we highlight the issues around therapeutic monitoring and discontinuation of therapy.

The Association of Pregnancy With Outcomes Among Critically Ill Reproductive-Aged Women: A Propensity Score-Matched Retrospective Cohort Analysis.

BACKGROUND: The maternal mortality rate in the United States is unacceptably high. However, the relative contribution of pregnancy to these outcomes is unknown. Studies comparing outcomes among pregnant vs nonpregnant critically ill patients show mixed results and are limited by small sample sizes. RESEARCH QUESTION: What is the association of pregnancy with critical illness outcomes? STUDY DESIGN AND METHODS: We performed a retrospective cohort study of women 18 to 55 years of age who received invasive mechanical ventilation (MV) on hospital day 0 or 1 or who demonstrated sepsis on admission (infection with organ failure) discharged from Premier Healthcare Database hospitals from 2008 through 2021. The exposure was pregnancy. The primary outcome was in-hospital mortality. We created propensity scores for pregnancy (using patient and hospital characteristics) and performed 1:1 propensity score matching without replacement within age strata (to ensure exact age matching). We performed multilevel multivariable mixed-effects logistic regression for propensity-matched pairs with pair as a random effect. RESULTS: Three thousand ninety-three pairs were included in the matched MV cohort, and 13,002 pairs were included in the sepsis cohort. The characteristics of both cohorts were well balanced (all standard mean differences, < 0.1). Among matched pairs, unadjusted mortality was 8.0% vs 13.8% for MV and 1.4% vs 2.3% for sepsis among pregnant and nonpregnant patients, respectively. In adjusted regression, pregnancy was associated with lower odds of in-hospital mortality (MV: OR, 0.50; 95% CI, 0.41-0.60; P < .001; sepsis: OR, 0.52; 95% CI, 0.40-0.67; P < .001). INTERPRETATION: In this large US cohort, critically ill pregnant women receiving MV or with sepsis showed better survival than propensity score-matched nonpregnant women. These findings must be interpreted in the context of likely residual confounding.

Defining the Time-limited Trial for Patients with Critical Illness: An Official American Thoracic Society Workshop Report.

In critical care, the specific, structured approach to patient care known as a "time-limited trial" has been promoted in the literature to help patients, surrogate decision makers, and clinicians navigate consequential decisions about life-sustaining therapy in the face of uncertainty. Despite promotion of the time-limited trial approach, a lack of consensus about its definition and essential elements prevents optimal clinical use and rigorous evaluation of its impact. The objectives of this American Thoracic Society Workshop Committee were to establish a consensus definition of a time-limited trial in critical care, identify the essential elements for conducting a time-limited trial, and prioritize directions for future work. We achieved these objectives through a structured search of the literature, a modified Delphi process with 100 interdisciplinary and interprofessional stakeholders, and iterative committee discussions. We conclude that a time-limited trial for patients with critical illness is a collaborative plan among clinicians and a patient and/or their surrogate decision makers to use life-sustaining therapy for a defined duration, after which the patient's response to therapy informs the decision to continue care directed toward recovery, transition to care focused exclusively on comfort, or extend the trial's duration. The plan's 16 essential elements follow four sequential phases: consider, plan, support, and reassess. We acknowledge considerable gaps in evidence about the impact of time-limited trials and highlight a concern that if inadequately implemented, time-limited trials may perpetuate unintended harm. Future work is needed to better implement this defined, specific approach to care in practice through a person-centered equity lens and to evaluate its impact on patients, surrogates, and clinicians.

Do windows or natural views affect outcomes or costs among patients in ICUs?

OBJECTIVE: To determine whether potential exposure to natural light via windows or to more pleasing views through windows affects outcomes or costs among critically ill patients. DESIGN: Retrospective cohort study. SETTING: An academic hospital in Philadelphia, PA. PATIENTS: Six thousand one hundred thirty-eight patients admitted to a 24-bed medical ICU and 6,631 patients admitted to a 24-bed surgical ICU from July 1, 2006, to June 30, 2010. INTERVENTIONS: Assignment to medical ICU rooms with vs. without windows and to surgical ICU rooms with natural vs. industrial views based on bed availability. MEASUREMENTS AND MAIN RESULTS: In primary analyses adjusting for patient characteristics, medical ICU patients admitted to rooms with (n = 4,093) versus without (n = 2,243) windows did not differ in rates of ICU (p = 0.25) or in-hospital (p = 0.94) mortality, ICU readmissions (p = 0.37), or delirium (p = 0.56). Surgical ICU patients admitted to rooms with natural (n = 3,072) versus industrial (n = 3,588) views experienced slightly shorter ICU lengths of stay and slightly lower variable costs. Instrumental variable analyses based on initial bed assignment and exposure time did not show any differences in any outcomes in either the medical ICU or surgical ICU cohorts, and none of the differences noted in primary analyses remained statistically significant when adjusting for multiple comparisons. In a prespecified subgroup analysis among patients with ICU length of stay greater than 72 hours, MICU windows were associated with reduced ICU (p = 0.02) and hospital mortality (p = 0.04); these results did not meet criteria for significance after adjustment for multiple comparisons. CONCLUSIONS: ICU rooms with windows or natural views do not improve outcomes or reduce costs of in-hospital care for general populations of medical and surgical ICU patients. Future work is needed to determine whether targeting light from windows directly toward patients influences outcomes and to explore these effects in patients at high risk for adverse outcomes.

Geographic cohorting by clinical care team: a narrative review.

BACKGROUND AND OBJECTIVE: Geographic cohorting refers to localization of inpatients to designated hospital areas (typically a unit or a set of beds) based on specified criteria. One such criterion that has been commonly discussed and studied since the early days of the hospitalist movement in the US is a patient's assigned clinical care team. Because implementing cohorting of this type requires substantial operational investment, it is important to understand the benefits and the tradeoffs associated with bringing patients into closer spatial proximity with their full team of providers and allowing clinicians to work within a defined clinical space. METHODS: We conducted a narrative review of the evidence around geographic cohorting of patients by clinical care team. We performed a comprehensive search of the PubMed, Embase, Cinahl and Scopus databases, identifying relevant English language articles. We used an inductive approach to developing thematic domains for categorization of article content. KEY CONTENT AND FINDINGS: We reviewed eighteen articles published between 2008 and 2022, and identified four thematic outcomes domains: patient-centered outcomes, communication, efficiency, and satisfaction. The existing literature demonstrates associations with improved communication and staff satisfaction. The data regarding patient outcomes and overall work efficiency, on the other hand, are equivocal and, in general, limited by study methodology. CONCLUSIONS: Geographic cohorting of inpatients according to clinical care team offers some promise for improved workplace culture. More rigorously designed studies are needed, however, to understand its impact on patient outcomes, and there should be added attention paid to throughput metrics and tradeoffs that often limit its implementation.

Associations of Race With Sedation Depth Among Mechanically Ventilated Adults: A Retrospective Cohort Study.

OBJECTIVES: To evaluate the association of race with proportion of time in deep sedation among mechanically ventilated adults. DESIGN: Retrospective cohort study from October 2017 to December 2019. SETTING: Five hospitals within a single health system. PATIENTS: Adult patients who identified race as Black or White who were mechanically ventilated for greater than or equal to 24 hours in one of 12 medical, surgical, cardiovascular, cardiothoracic, or mixed ICUs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The exposure was White compared with Black race. The primary outcome was the proportion of time in deep sedation during the first 48 hours of mechanical ventilation, defined as Richmond Agitation-Sedation Scale values of -3 to -5. For the primary analysis, we performed mixed-effects linear regression models including ICU as a random effect, and adjusting for age, sex, English as preferred language, body mass index, Elixhauser comorbidity index, Laboratory-based Acute Physiology Score, Version 2, ICU admission source, admission for a major surgical procedure, and the presence of septic shock. Of the 3337 included patients, 1242 (37%) identified as Black, 1367 (41%) were female, and 1002 (30%) were admitted to a medical ICU. Black patients spent 48% of the first 48 hours of mechanical ventilation in deep sedation, compared with 43% among White patients in unadjusted analysis. After risk adjustment, Black race was significantly associated with more time in early deep sedation (mean difference, 5%; 95% CI, 2-7%; p < 0.01). CONCLUSIONS: There are disparities in sedation during the first 48 hours of mechanical ventilation between Black and White patients across a diverse set of ICUs. Future work is needed to determine the clinical significance of these findings, given the known poorer outcomes for patients who experience early deep sedation.

Association of Time of Day with Delays in Antimicrobial Initiation among Ward Patients with Hospital-Onset Sepsis.

Rationale: Although the mainstay of sepsis treatment is timely initiation of broad-spectrum antimicrobials, treatment delays are common, especially among patients who develop hospital-onset sepsis. The time of day has been associated with suboptimal clinical care in several contexts, but its association with treatment initiation among patients with hospital-onset sepsis is unknown. Objectives: Assess the association of time of day with antimicrobial initiation among ward patients with hospital-onset sepsis. Methods: This retrospective cohort study included ward patients who developed hospital-onset sepsis while admitted to five acute care hospitals in a single health system from July 2017 through December 2019. Hospital-onset sepsis was defined by the Centers for Disease Control and Prevention Adult Sepsis Event criteria. We estimated the association between the hour of day and antimicrobial initiation among patients with hospital-onset sepsis using a discrete-time time-to-event model, accounting for time elapsed from sepsis onset. In a secondary analysis, we fit a quantile regression model to estimate the association between the hour of day of sepsis onset and time to antimicrobial initiation. Results: Among 1,672 patients with hospital-onset sepsis, the probability of antimicrobial initiation at any given hour varied nearly fivefold throughout the day, ranging from 3.0% (95% confidence interval [CI], 1.8-4.1%) at 7 a.m. to 13.9% (95% CI, 11.3-16.5%) at 6 p.m., with nadirs at 7 a.m. and 7 p.m. and progressive decline throughout the night shift (13.4% [95% CI, 10.7-16.0%] at 9 p.m. to 3.2% [95% CI, 2.0-4.0] at 6 a.m.). The standardized predicted median time to antimicrobial initiation was 3.2 hours (interquartile range [IQR], 2.5-3.8 h) for sepsis onset during the day shift (7 a.m.-7 p.m.) and 12.9 hours (IQR, 10.9-14.9 h) during the night shift (7 p.m.-7 a.m.). Conclusions: The probability of antimicrobial initiation among patients with new hospital-onset sepsis declined at shift changes and overnight. Time to antimicrobial initiation for patients with sepsis onset overnight was four times longer than for patients with onset during the day. These findings indicate that time of day is associated with important care processes for ward patients with hospital-onset sepsis. Future work should validate these findings in other settings and elucidate underlying mechanisms to inform quality-enhancing interventions.