"Like One Long Battle:" Employee Perspectives of the Simultaneous Impact of COVID-19 and an Electronic Health Record Transition.

BACKGROUND: Healthcare organizations regularly manage external stressors that threaten patient care, but experiences handling concurrent stressors are not well characterized. OBJECTIVE: To evaluate the experience of Veterans Affairs (VA) clinicians and staff navigating simultaneous organizational stressors-an electronic health record (EHR) transition and the COVID-19 pandemic-and identify potential strategies to optimize management of co-occurring stressors. DESIGN: Qualitative case study describing employee experiences at VA's initial EHR transition site. PARTICIPANTS: Clinicians, nurses, allied health professionals, and local leaders at VA's initial EHR transition site. APPROACH: We collected longitudinal qualitative interview data between July 2020 and November 2021 once before and 2-4 times after the date on which the health system transitioned; this timing corresponded with local surges of COVID-19 cases. Interviewers conducted coding and analysis of interview transcripts. For this study, we focused on quotes related to COVID-19 and performed content analysis to describe recurring themes describing the simultaneous impact of COVID-19 and an EHR transition. KEY RESULTS: We identified five themes related to participants' experiences: (1) efforts to mitigate COVID-19 transmission led to insufficient access to EHR training and support, (2) clinical practice changes in response to the pandemic impacted EHR workflows in unexpected ways, (3) lack of clear communication and inconsistent enforcement of COVID-19 policies intensified pre-existing frustrations with the EHR, (4) managing concurrent organizational stressors increased work dissatisfaction and feelings of burnout, and (5) participants had limited bandwidth to manage competing demands that arose from concurrent organizational stressors. CONCLUSION: The expected challenges of an EHR transition were compounded by co-occurrence of the COVID-19 pandemic, which had negative impacts on clinician experience and patient care. During simultaneous organizational stressors, health care facilities should be prepared to address the complex interplay of two stressors on employee experience.

Assessing Electronic Health Record (EHR) Use during a Major EHR Transition: An Innovative Mixed Methods Approach.

BACKGROUND: Electronic health record (EHR) transitions are inherently disruptive to healthcare workers who must rapidly learn a new EHR and adapt to altered clinical workflows. Healthcare workers' perceptions of EHR usability and their EHR use patterns following transitions are poorly understood. The Department of Veterans Affairs (VA) is currently replacing its homegrown EHR with a commercial Cerner EHR, presenting a unique opportunity to examine EHR use trends and usability perceptions. OBJECTIVE: To assess EHR usability and uptake up to 1-year post-transition at the first VA EHR transition site using a novel longitudinal, mixed methods approach. DESIGN: A concurrent mixed methods strategy using EHR use metrics and qualitative interview data. PARTICIPANTS: 141 clinicians with data from select EHR use metrics in Cerner Lights On Network®. Interviews with 25 healthcare workers in various clinical and administrative roles. APPROACH: We assessed changes in total EHR time, documentation time, and order time per patient post-transition. Interview transcripts (n = 90) were coded and analyzed for content specific to EHR usability. KEY RESULTS: Total EHR time, documentation time, and order time all decreased precipitously within the first four months after go-live and demonstrated gradual improvements over 12 months. Interview participants expressed ongoing concerns with the EHR's usability and functionality up to a year after go-live such as tasks taking longer than the old system and inefficiencies related to inadequate training and inherent features of the new system. These sentiments did not seem to reflect the observed improvements in EHR use metrics. CONCLUSIONS: The integration of quantitative and qualitative data yielded a complex picture of EHR usability. Participants described persistent challenges with EHR usability 1 year after go-live contrasting with observed improvements in EHR use metrics. Combining findings across methods can provide a clearer, contextualized understanding of EHR adoption and use patterns during EHR transitions.

"Everything's so Role-Specific": VA Employee Perspectives' on Electronic Health Record (EHR) Transition Implications for Roles and Responsibilities.

BACKGROUND: Electronic health record (EHR) transitions are increasingly widespread and often highly disruptive. It is imperative we learn from past experiences to anticipate and mitigate such disruptions. Veterans Affairs (VA) is undergoing a large-scale transition from its homegrown EHR (CPRS/Vista) to a commercial EHR (Cerner), creating a unique opportunity of shedding light on large-scale EHR-to-EHR transition challenges. OBJECTIVE: To explore one facet of the organizational impact of VA's EHR transition: its implications for employees' roles and responsibilities at the first VA site to implement Cerner Millennium EHR. DESIGN: As part of a formative evaluation of frontline staff experiences with VA's EHR transition, we conducted brief (~ 15 min) and full-length interviews (~ 60 min) with clinicians and staff at Mann-Grandstaff VA Medical Center in Spokane, WA, before, during, and after transition (July 2020-November 2021). PARTICIPANTS: We conducted 111 interviews with 26 Spokane clinicians and staff, recruited via snowball sampling. APPROACH: We conducted audio interviews using a semi-structured guide with grounded prompts. We coded interview transcripts using a priori and emergent codes, followed by qualitative content analysis. KEY RESULTS: Unlike VA's previous EHR, Cerner imposes additional restrictions on access to its EHR functionality based upon "roles" assigned to users. Participants described a mismatch between established institutional duties and their EHR permissions, unanticipated changes in scope of duties brought upon by the transition, as well as impediments to communication and collaboration due to different role-based views. CONCLUSIONS: Health systems should anticipate substantive impacts on professional workflows when EHR role settings do not reflect prior workflows. Such changes may increase user error, dissatisfaction, and patient care disruptions. To mitigate employee dissatisfaction and safety risks, health systems should proactively plan for and communicate about expected modifications and monitor for unintended role-related consequences of EHR transitions, while vendors should ensure accurate role configuration and assignment.

Association between Troponin I Levels during Sepsis and Postsepsis Cardiovascular Complications.

Rationale: Sepsis commonly results in elevated serum troponin levels and increased risk for postsepsis cardiovascular complications; however, the association between troponin levels during sepsis and cardiovascular complications after sepsis is unclear.Objectives: To evaluate the association between serum troponin levels during sepsis and 1 year after sepsis cardiovascular events.Methods: We analyzed adults aged ⩾40 years without preexisting cardiovascular disease within 5 years, admitted with sepsis across 21 hospitals from 2011 to 2017. Peak serum troponin I levels during sepsis were grouped as normal (⩽0.04 ng/ml) or tertiles of abnormal (>0.04 to ⩽0.09 ng/ml, >0.09 to ⩽0.42 ng/ml, or >0.42 ng/ml). Multivariable adjusted cause-specific Cox proportional hazards models with death as a competing risk were used to assess associations between peak troponin I levels and a composite cardiovascular outcome (atherosclerotic cardiovascular disease, atrial fibrillation, and heart failure) in the year following sepsis. Models were adjusted for presepsis and intrasepsis factors considered potential confounders.Measurements and Main Results: Among 14,046 eligible adults with troponin I measured, 2,012 (14.3%) experienced the composite cardiovascular outcome, including 832 (10.9%) patients with normal troponin levels, as compared with 370 (17.3%), 376 (17.6%), and 434 (20.3%) patients within each sequential abnormal troponin tertile, respectively (P < 0.001). Patients within the elevated troponin tertiles had increased risks of adverse cardiovascular events (adjusted hazard ratio [aHR]troponin0.04-0.09 = 1.37; 95% confidence interval [CI], 1.20-1.55; aHRtroponin0.09-0.42 = 1.44; 95% CI, 1.27-1.63; and aHRtroponin>0.42 = 1.77; 95% CI, 1.56-2.00).Conclusions: Among patients without preexisting cardiovascular disease, troponin elevation during sepsis identified patients at increased risk for postsepsis cardiovascular complications. Strategies to mitigate cardiovascular complications among this high-risk subset of patients are warranted.

Variation in Sedative and Analgesic Use During the COVID-19 Pandemic and Associated Outcomes.

BACKGROUND: Providing analgesia and sedation is an essential component of caring for many mechanically ventilated patients. The selection of analgesic and sedative medications during the COVID-19 pandemic, and the impact of these sedation practices on patient outcomes, remain incompletely characterized. RESEARCH QUESTION: What were the hospital patterns of analgesic and sedative use for patients with COVID-19 who received mechanical ventilation (MV), and what differences in clinical patient outcomes were observed across prevailing sedation practices? STUDY DESIGN AND METHODS: We conducted an observational cohort study of hospitalized adults who received MV for COVID-19 from February 2020 through April 2021 within the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS) COVID-19 Registry. To describe common sedation practices, we used hierarchical clustering to group hospitals based on the percentage of patients who received various analgesic and sedative medications. We then used multivariable regression models to evaluate the association between hospital analgesia and sedation cluster and duration of MV (with a placement of death [POD] approach to account for competing risks). RESULTS: We identified 1,313 adults across 35 hospitals admitted with COVID-19 who received MV. Two clusters of analgesia and sedation practices were identified. Cluster 1 hospitals generally administered opioids and propofol with occasional use of additional sedatives (eg, benzodiazepines, alpha-agonists, and ketamine); cluster 2 hospitals predominantly used opioids and benzodiazepines without other sedatives. As compared with patients in cluster 2, patients admitted to cluster 1 hospitals underwent a shorter adjusted median duration of MV with POD (ß-estimate, -5.9; 95% CI, -11.2 to -0.6; P = .03). INTERPRETATION: Patients who received MV for COVID-19 in hospitals that prioritized opioids and propofol for analgesia and sedation experienced shorter adjusted median duration of MV with POD as compared with patients who received MV in hospitals that primarily used opioids and benzodiazepines.

Intravenous Opioid Administration During Mechanical Ventilation and Use After Hospital Discharge.

Importance: Guidelines recommend an analgesia-first strategy for sedation during mechanical ventilation, but associations between opioids provided during mechanical ventilation and posthospitalization opioid-related outcomes are unclear. Objective: To evaluate associations between an intravenous opioid dose received during mechanical ventilation and postdischarge opioid-related outcomes in medical (nonsurgical) patients. Design, Setting, and Participants: This retrospective cohort study evaluated adults receiving mechanical ventilation lasting 24 hours or more for acute respiratory failure and surviving hospitalization. Participants from 21 Kaiser Permanente Northern California hospitals from January 1, 2012, to December 31, 2019, were included. Data were analyzed from October 1, 2020, to October 31, 2023. Exposures: Terciles of median daily intravenous fentanyl equivalents during mechanical ventilation. Main Outcomes and Measures: The primary outcome was the first filled opioid prescription in 1 year after discharge. Secondary outcomes included persistent opioid use and opioid-associated complications. Secondary analyses tested for interaction between opioid doses during mechanical ventilation, prior opioid use, and posthospitalization opioid use. Estimates were based on multivariable-adjusted time-to-event analyses, with death as a competing risk, and censored for hospice or palliative care referral, rehospitalization with receipt of opioid, or loss of Kaiser Permanente plan membership. Results: The study included 6746 patients across 21 hospitals (median age, 67 years [IQR, 57-76 years]; 53.0% male). Of the participants, 3114 (46.2%) filled an opioid prescription in the year prior to admission. The median daily fentanyl equivalent during mechanical ventilation was 200 µg (IQR, 40-1000 µg), with terciles of 0 to 67 µg, more than 67 to 700 µg, and more than 700 µg. Compared with patients who did not receive opioids during mechanical ventilation (n = 1013), a higher daily opioid dose was associated with opioid prescriptions in the year after discharge (n = 2942 outcomes; tercile 1: adjusted hazard ratio [AHR], 1.00 [95% CI, 0.85-1.17], tercile 2: AHR, 1.20 [95% CI, 1.03-1.40], and tercile 3: AHR, 1.25 [95% CI, 1.07-1.47]). Higher doses of opioids during mechanical ventilation were also associated with persistent opioid use after hospitalization (n = 1410 outcomes; tercile 3 vs no opioids: odds ratio, 1.44 [95% CI, 1.14-1.83]). No interaction was observed between opioid dose during mechanical ventilation, prior opioid use, and posthospitalization opioid use. Conclusions and Relevance: In this retrospective cohort study of patients receiving mechanical ventilation, opioids administered during mechanical ventilation were associated with opioid prescriptions following hospital discharge. Additional studies to evaluate risks and benefits of strategies using lower opioid doses are warranted.

Smartphone-Guided Self-prone Positioning vs Usual Care in Nonintubated Hospital Ward Patients With COVID-19: A Pragmatic Randomized Clinical Trial.

BACKGROUND: Safe, effective, and easily implementable treatments that reduce the progression of respiratory failure in COVID-19 are urgently needed. Despite the increased adoption of prone positioning during the pandemic, the effectiveness of this technique on progression of respiratory failure among nonintubated patients is unclear. RESEARCH QUESTION: What is the effectiveness of smartphone-guided self-prone positioning recommendations and instructions compared with usual care in reducing progression of respiratory failure among nonintubated patients with COVID-19? STUDY DESIGN AND METHODS: Awake Prone Position for Early Hypoxemia in COVID-19 (APPEX-19) is a multicenter randomized clinical trial that randomized nonintubated adults with COVID-19 on < 6 L/min of supplemental oxygen to receive a smartphone-guided self-prone positioning intervention or usual care. The primary outcome was the composite of respiratory deterioration (an increase in supplemental oxygen requirement) or ICU transfer. Using a Bayesian statistical approach, the posterior probability of superiority within each treatment arm (superiority threshold 95%) was calculated. RESULTS: The trial was stopped early for slow enrollment. A total of 293 participants were included in the modified intention-to-treat analysis (159 self-prone positioning intervention and 134 usual care). Among participants who self-reported body positioning (n = 139 [70 intervention, 69 usual care]), 71.4% in the intervention arm and 59.4% in the usual care arm attempted prone positioning. Thirty-one participants (posterior mean, 24.7%; 95% credible interval, 18.6-31.4) receiving usual care and 32 participants (posterior mean, 22.1%; 95% credible interval, 16.6-28.1) receiving the self-prone positioning intervention experienced the primary outcome; the posterior probability of superiority for the self-prone positioning intervention was 72.1%, less than the 95% threshold for superiority. Adverse events occurred in 26.9% of participants in the usual care arm and in 11.9% of participants in the intervention arm. INTERPRETATION: Among nonintubated patients with COVID-19, smartphone-guided self-prone positioning recommendations and instructions did not promote strong adherence to prone positioning. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT04344587; URL: www. CLINICALTRIALS: gov.

TRIM5α associates with proteasomal subunits in cells while in complex with HIV-1 virions.

BACKGROUND: The TRIM5 proteins are cellular restriction factors that prevent retroviral infection in a species-specific manner. Multiple experiments indicate that restriction activity requires accessory host factors, including E2-enzymes. To better understand the mechanism of restriction, we conducted yeast-two hybrid screens to identify proteins that bind to two TRIM5 orthologues. RESULTS: The only cDNAs that scored on repeat testing with both TRIM5 orthologues were the proteasome subunit PSMC2 and ubiquitin. Using co-immunoprecipitation assays, we demonstrated an interaction between TRIM5α and PSMC2, as well as numerous other proteasome subunits. Fluorescence microscopy revealed co-localization of proteasomes and TRIM5α cytoplasmic bodies. Forster resonance energy transfer (FRET) analysis indicated that the interaction between TRIM5 and PSMC2 was direct. Previous imaging experiments demonstrated that, when cells are challenged with fluorescently-labeled HIV-1 virions, restrictive TRIM5α orthologues assemble cytoplasmic bodies around incoming virion particles. Following virus challenge, we observed localization of proteasome subunits to rhTRIM5α cytoplasmic bodies that contained fluorescently labeled HIV-1 virions. CONCLUSIONS: Taken together, the results presented here suggest that localization of the proteasome to TRIM5α cytoplasmic bodies makes an important contribution to TRIM5α-mediated restriction.

Comparative Effectiveness of Heart Rate Control Medications for the Treatment of Sepsis-Associated Atrial Fibrillation.

BACKGROUND: Atrial fibrillation (AF) with rapid ventricular response frequently complicates the management of critically ill patients with sepsis and may necessitate the initiation of medication to avoid hemodynamic compromise. However, the optimal medication to achieve rate control for AF with rapid ventricular response in sepsis is unclear. RESEARCH QUESTION: What is the comparative effectiveness of frequently used AF medications (ß-blockers, calcium channel blockers, amiodarone, and digoxin) on heart rate (HR) reduction among critically ill patients with sepsis and AF with rapid ventricular response? STUDY DESIGN AND METHODS: We conducted a multicenter retrospective cohort study among patients with sepsis and AF with rapid ventricular response (HR > 110 beats/min). We compared the rate control effectiveness of ß-blockers to calcium channel blockers, amiodarone, and digoxin using multivariate-adjusted, time-varying exposures in competing risk models (for death and addition of another AF medication), adjusting for fixed and time-varying confounders. RESULTS: Among 666 included patients, 50.6% initially received amiodarone, 10.1% received a ß-blocker, 33.8% received a calcium channel blocker, and 5.6% received digoxin. The adjusted hazard ratio for HR of < 110 beats/min by 1 h was 0.50 (95% CI, 0.34-0.74) for amiodarone vs ß-blocker, 0.37 (95% CI, 0.18-0.77) for digoxin vs ß-blocker, and 0.75 (95% CI, 0.51-1.11) for calcium channel blocker vs ß-blocker. By 6 h, the adjusted hazard ratio for HR < 110 beats/min was 0.67 (95% CI, 0.47-0.97) for amiodarone vs ß-blocker, 0.60 (95% CI, 0.36-1.004) for digoxin vs ß-blocker, and 1.03 (95% CI, 0.71-1.49) for calcium channel blocker vs ß-blocker. INTERPRETATION: In a large cohort of patients with sepsis and AF with rapid ventricular response, a ß-blocker treatment strategy was associated with improved HR control at 1 h, but generally similar HR control at 6 h compared with amiodarone, calcium channel blocker, or digoxin.

Rationale and Design of the Awake Prone Position for Early Hypoxemia in COVID-19 Study Protocol: A Clinical Trial.

The unprecedented public health burdens of coronavirus disease (COVID-19) have intensified the urgency of identifying effective, low-cost treatments that limit the need for advanced life support measures and improve clinical outcomes. However, personal protective equipment and staffing shortages, disease virulence, and infectivity have created significant barriers to traditional clinical trial practices. We present the novel design of a pragmatic, adaptive, multicenter, international, prospective randomized controlled clinical trial evaluating the safety and effectiveness of awake prone positioning in spontaneously breathing patients with COVID-19 (APPEX-19 [Awake Prone Position for Early Hypoxemia in COVID-19]). Key innovations of this trial include 1) a novel smartphone-based communication process that facilitates rapid enrollment and intervention delivery while allowing social distancing and conservation of personal protective equipment, 2) Bayesian response-adaptive randomization to allow preferential assignment to the most effective intervention and expedite trial completion compared with frequentist designs, 3) remote electronic collection of patient-reported outcomes and electronic medical record data, and 4) pragmatic prospective use of patient-reported data and data collected as part of routine clinical care. Clinical trial registered with www.clinicaltrials.gov (NCT04344587).