Oxygen-Saturation Targets and Cognitive and Functional Outcomes in Mechanically Ventilated Adults.

Rationale: Among mechanically ventilated critically ill adults, the PILOT (Pragmatic Investigation of Optimal Oxygen Targets) trial demonstrated no difference in ventilator-free days among lower, intermediate, and higher oxygen-saturation targets. The effects on long-term cognition and related outcomes are unknown.Objectives: To compare the effects of lower (90% [range, 88-92%]), intermediate (94% [range, 92-96%]), and higher (98% [range, 96-100%]) oxygen-saturation targets on long-term outcomes.Methods: Twelve months after enrollment in the PILOT trial, blinded neuropsychological raters conducted assessments of cognition, disability, employment status, and quality of life. The primary outcome was global cognition as measured using the Telephone Montreal Cognitive Assessment. In a subset of patients, an expanded neuropsychological battery measured executive function, attention, immediate and delayed memory, verbal fluency, and abstraction.Measurements and Main Results: A total of 501 patients completed follow-up, including 142 in the lower, 186 in the intermediate, and 173 in the higher oxygen target groups. Median (interquartile range) peripheral oxygen saturation values in the lower, intermediate, and higher target groups were 94% (91-96%), 95% (93-97%), and 97% (95-99%), respectively. Telephone Montreal Cognitive Assessment score did not differ between lower and intermediate (adjusted odds ratio [OR], 1.36 [95% confidence interval (CI), 0.92-2.00]), intermediate and higher (adjusted OR, 0.90 [95% CI, 0.62-1.29]), or higher and lower (adjusted OR, 1.22 [95% CI, 0.83-1.79]) target groups. There was also no difference in individual cognitive domains, disability, employment, or quality of life.Conclusions: Among mechanically ventilated critically ill adults who completed follow-up at 12 months, oxygen-saturation targets were not associated with cognition or related outcomes.

Frequency of cardiotoxicity following intramuscular administration of epinephrine in emergency department patients with anaphylaxis.

Objectives: Epinephrine can be a life-saving treatment for patients with anaphylaxis. Potential cardiovascular side effects of epinephrine may contribute to clinician hesitancy to use it. However, the frequency of cardiotoxicity resulting from epinephrine treatment for anaphylaxis is not well described. We sought to describe the frequency of cardiotoxicity following intramuscular (IM) administration of epinephrine in adult emergency department (ED) patients with anaphylaxis. Methods: We conducted a retrospective observational study at a single, quaternary care academic ED in Tennessee. We identified consecutive ED visits with the diagnosis of anaphylaxis from 2017 to 2021 who received at least one intramuscular (IM) dose of epinephrine in the ED. Analysis was primarily descriptive. The primary outcome was cardiotoxicity, the occurrence of any of the following after epinephrine administration: ischemic electrocardiogram changes, systolic blood pressure >200 mmHg, or cardiac arrest ≤4 h; elevated troponin ≤12 h; or percutaneous coronary intervention or depressed ejection fraction ≤72 h. Results: Among 338 included patients, 16 (4.7%; 95%CI: 2.8-7.6%) experienced cardiotoxicity. Cardiotoxic events included eight (2.4%) ischemic electrocardiogram changes, six (1.8%) episodes of elevated troponin, five (1.5%) atrial arrhythmias, one (0.3%) ventricular arrythmia, and one (0.3%) depressed ejection fraction. Patients with cardiotoxicity were significantly older, had more comorbidities, and were more likely to have received multiple doses of epinephrine or an epinephrine infusion compared with a single IM dose of epinephrine. Conclusions: Among 338 consecutive adult ED patients who received IM epinephrine for anaphylaxis during a recent 4-year period, cardiotoxic side effects were observed in approximately 5% of patients.

Cefepime vs Piperacillin-Tazobactam in Adults Hospitalized With Acute Infection: The ACORN Randomized Clinical Trial.

Importance: Cefepime and piperacillin-tazobactam are commonly administered to hospitalized adults for empirical treatment of infection. Although piperacillin-tazobactam has been hypothesized to cause acute kidney injury and cefepime has been hypothesized to cause neurological dysfunction, their comparative safety has not been evaluated in a randomized clinical trial. Objective: To determine whether the choice between cefepime and piperacillin-tazobactam affects the risks of acute kidney injury or neurological dysfunction. Design, Setting, and Participants: The Antibiotic Choice on Renal Outcomes (ACORN) randomized clinical trial compared cefepime vs piperacillin-tazobactam in adults for whom a clinician initiated an order for antipseudomonal antibiotics within 12 hours of presentation to the hospital in the emergency department or medical intensive care unit at an academic medical center in the US between November 10, 2021, and October 7, 2022. The final date of follow-up was November 4, 2022. Interventions: Patients were randomized in a 1:1 ratio to cefepime or piperacillin-tazobactam. Main Outcomes and Measures: The primary outcome was the highest stage of acute kidney injury or death by day 14, measured on a 5-level ordinal scale ranging from no acute kidney injury to death. The 2 secondary outcomes were the incidence of major adverse kidney events at day 14 and the number of days alive and free of delirium and coma within 14 days. Results: There were 2511 patients included in the primary analysis (median age, 58 years [IQR, 43-69 years]; 42.7% were female; 16.3% were Non-Hispanic Black; 5.4% were Hispanic; 94.7% were enrolled in the emergency department; and 77.2% were receiving vancomycin at enrollment). The highest stage of acute kidney injury or death was not significantly different between the cefepime group and the piperacillin-tazobactam group; there were 85 patients (n = 1214; 7.0%) in the cefepime group with stage 3 acute kidney injury and 92 (7.6%) who died vs 97 patients (n = 1297; 7.5%) in the piperacillin-tazobactam group with stage 3 acute kidney injury and 78 (6.0%) who died (odds ratio, 0.95 [95% CI, 0.80 to 1.13], P = .56). The incidence of major adverse kidney events at day 14 did not differ between groups (124 patients [10.2%] in the cefepime group vs 114 patients [8.8%] in the piperacillin-tazobactam group; absolute difference, 1.4% [95% CI, -1.0% to 3.8%]). Patients in the cefepime group experienced fewer days alive and free of delirium and coma within 14 days (mean [SD], 11.9 [4.6] days vs 12.2 [4.3] days in the piperacillin-tazobactam group; odds ratio, 0.79 [95% CI, 0.65 to 0.95]). Conclusions and Relevance: Among hospitalized adults in this randomized clinical trial, treatment with piperacillin-tazobactam did not increase the incidence of acute kidney injury or death. Treatment with cefepime resulted in more neurological dysfunction. Trial Registration: ClinicalTrials.gov Identifier: NCT05094154.

Using intervention mapping to design and implement a multicomponent intervention to improve antibiotic and NSAID prescribing.

Successfully changing prescribing behavior to reduce inappropriate antibiotic and nonsteroidal anti-inflammatory drug (NSAID) prescriptions often requires combining components into a multicomponent intervention. However, multicomponent interventions often fail because of development and implementation complexity. To increase the likelihood of successfully changing prescribing behavior, we applied a systematic process to design and implement a multicomponent intervention. We used Intervention Mapping to create a roadmap for a multicomponent intervention in unscheduled outpatient care settings in the Veterans Health Administration. Intervention Mapping is a systematic process consisting of six steps that we grouped into three phases: (i) understand behavioral determinants and barriers to implementation, (ii) develop the intervention, and (iii) define evaluation plan and implementation strategies. A targeted literature review, combined with 25 prescriber and 25 stakeholder interviews, helped identify key behavioral determinants to inappropriate prescribing (e.g. perceived social pressure from patients to prescribe). We targeted three desired prescriber behaviors: (i) review guideline-concordant prescribing and patient outcomes, (ii) manage diagnostic and treatment uncertainty, and (iii) educate patients and caregivers. The intervention consisted of components for academic detailing, prescribing feedback, and alternative prescription order sets. Implementation strategies consisted of preparing clinical champions, conducting readiness assessments, and incentivizing use of the intervention. We chose a mixed-method study design with a commonly used evaluation framework to assess effectiveness and implementation outcomes in a subsequent trial. This study furthers knowledge about causes of inappropriate antibiotic and NSAID prescribing and demonstrates how theoretical, empirical, and practical information can be systematically applied to develop a multicomponent intervention to help address these causes.

Reducing adverse drug events from antibiotics and nonsteroidal anti-inflammatory drugs (NSAIDs) is a patient safety priority. Successfully changing prescribing behavior to reduce inappropriate prescriptions can require combining intervention components, each with different mechanisms for behavior change, into a multicomponent intervention. However, multicomponent interventions often fail because of development and implementation complexity. To increase the chance of successfully changing antibiotic and NSAID prescribing, the objective this study was to apply a systematic process to design and implement a multicomponent intervention. Three desired prescriber behaviors were targeted: (i) review guideline-concordant prescribing and patient outcomes, (ii) manage diagnostic and treatment uncertainty, and (iii) educate patients and caregivers. The designed intervention consisted of components for prescribing feedback, academic detailing, and alternative prescription order sets. Strategies to improve use of the intervention consisted of preparing clinical champions, conducting readiness assessments prior to study onset, and incentivizing use of the intervention. We chose a mixed-method study design with a commonly used evaluation framework to assess effectiveness and implementation outcomes of the multicomponent intervention in a subsequent trial.

Delirium and Delirium Prevention in the Emergency Department.

This article covers the epidemiology of delirium and the overlapping condition of altered mental status and encephalopathy that is relevant to those who practice in the emergency department.

Disease Severity of Respiratory Syncytial Virus Compared with COVID-19 and Influenza Among Hospitalized Adults Aged ≥60 Years - IVY Network, 20 U.S. States, February 2022-May 2023.

On June 21, 2023, CDC's Advisory Committee on Immunization Practices recommended respiratory syncytial virus (RSV) vaccination for adults aged ≥60 years, offered to individual adults using shared clinical decision-making. Informed use of these vaccines requires an understanding of RSV disease severity. To characterize RSV-associated severity, 5,784 adults aged ≥60 years hospitalized with acute respiratory illness and laboratory-confirmed RSV, SARS-CoV-2, or influenza infection were prospectively enrolled from 25 hospitals in 20 U.S. states during February 1, 2022-May 31, 2023. Multivariable logistic regression was used to compare RSV disease severity with COVID-19 and influenza severity on the basis of the following outcomes: 1) standard flow (<30 L/minute) oxygen therapy, 2) high-flow nasal cannula (HFNC) or noninvasive ventilation (NIV), 3) intensive care unit (ICU) admission, and 4) invasive mechanical ventilation (IMV) or death. Overall, 304 (5.3%) enrolled adults were hospitalized with RSV, 4,734 (81.8%) with COVID-19 and 746 (12.9%) with influenza. Patients hospitalized with RSV were more likely to receive standard flow oxygen, HFNC or NIV, and ICU admission than were those hospitalized with COVID-19 or influenza. Patients hospitalized with RSV were more likely to receive IMV or die compared with patients hospitalized with influenza (adjusted odds ratio = 2.08; 95% CI = 1.33-3.26). Among hospitalized older adults, RSV was less common, but was associated with more severe disease than COVID-19 or influenza. High disease severity in older adults hospitalized with RSV is important to consider in shared clinical decision-making regarding RSV vaccination.

Modifiable in-hospital factors for 12-month global cognition, post-traumatic stress disorder symptoms, and depression symptoms in adults hospitalized with COVID-19.

BACKGROUND: We sought to identify potentially modifiable in-hospital factors associated with global cognition, post-traumatic stress disorder (PTSD) symptoms, and depression symptoms at 12 months. METHODS: This was a multi-center prospective cohort study in adult hospitalized patients with acute COVID-19. The following in-hospital factors were assessed: delirium; frequency of in-person and virtual visits by friends and family; and hydroxychloroquine, corticosteroid, and remdesivir administration. Twelve-month global cognition was characterized by the MOCA-Blind. Twelve-month PTSD and depression were characterized using the PTSD Checklist for the DSM-V and Hospital Anxiety Depression Scale, respectively. FINDINGS: Two hundred three patients completed the 12-month follow-up assessments. Remdesivir use was associated with significantly higher cognition at 12 months based on the MOCA-Blind (adjusted odds ratio [aOR] = 1.98, 95% CI: 1.06, 3.70). Delirium was associated with worsening 12-month PTSD (aOR = 3.44, 95% CI: 1.89, 6.28) and depression (aOR = 2.18, 95% CI: 1.23, 3.84) symptoms. Multiple virtual visits per day during hospitalization was associated with lower 12-month depression symptoms compared to those with less than daily virtual visits (aOR = 0.40, 95% CI: 0.19, 0.85). CONCLUSION: Potentially modifiable factors associated with better long-term outcomes included remdesivir use (associated with better cognitive function), avoidance of delirium (associated with less PTSD and depression symptoms), and increased virtual interactions with friends and family (associated with less depression symptoms).

Randomized controlled trial of urinE chemiStry guided aCute heArt faiLure treATmEnt (ESCALATE): Rationale and design.

Diuresis to achieve decongestion is a central aim of therapy in patients hospitalized for acute decompensated heart failure (ADHF). While multiple clinical trials have investigated initial diuretic strategies for a designated period of time, there is a paucity of evidence to guide diuretic titration strategies continued until decongestion is achieved. The use of urine chemistries (urine sodium and creatinine) in a natriuretic response prediction equation accurately estimates natriuresis in response to diuretic dosing, but a randomized clinical trial is needed to compare a urine chemistry-guided diuresis strategy with a strategy of usual care. The urinE chemiStry guided aCute heArt faiLure treATmEnt (ESCALATE) trial is designed to test the hypothesis that protocolized diuretic therapy guided by spot urine chemistry through completion of intravenous diuresis will be superior to usual care and improve outcomes over the 14 days following randomization. ESCALATE will randomize and obtain complete data on 450 patients with acute heart failure to a diuretic strategy guided by urine chemistry or a usual care strategy. Key inclusion criteria include an objective measure of hypervolemia with at least 10 pounds of estimated excess volume, and key exclusion criteria include significant valvular stenosis, hypotension, and a chronic need for dialysis. Our primary outcome is days of benefit over the 14 days after randomization. Days of benefit combines patient symptoms captured by global clinical status with clinical state quantifying the need for hospitalization and intravenous diuresis. CLINICAL TRIAL REGISTRATION: NCT04481919.

Trends in paediatric firearm-related encounters during the COVID-19 pandemic by age group, race/ethnicity and schooling mode in Tennessee.

BACKGROUND: Increases in paediatric firearm-related injuries during the COVID-19 pandemic may be due to changes in where children and adolescents spent their time. This study examines changes in the frequency of paediatric firearm-related encounters as a function of schooling mode overall and by race/ethnicity and age group at a large trauma centre through 2021. METHODS: We use data from a large paediatric and adult trauma centre in Tennessee from January 2018 to December 2021 (N=211 encounters) and geographically linked schooling mode data. We use Poisson regressions to estimate smoothed monthly paediatric firearm-related encounters as a function of schooling mode overall and stratified by race and age. RESULTS: Compared with pre pandemic, we find a 42% increase in paediatric encounters per month during March 2020 to August 2020, when schools were closed, no significant increase during virtual/hybrid instruction, and a 23% increase in encounters after schools returned to in-person instruction. The effects of schooling mode are heterogeneous by patient race/ethnicity and age. Encounters increased among non-Hispanic black children across all periods relative to pre pandemic. Among non-Hispanic white children, encounters increased during the closure period and decreased on return to in-person instruction. Compared with pre pandemic, paediatric firearm-related encounters increased 205% for children aged 5-11 and 69% for adolescents aged 12-15 during the school closure period. CONCLUSION: COVID-19-related changes to school instruction mode in 2020 and 2021 are associated with changes in the frequency and composition of paediatric firearm-related encounters at a major trauma centre in Tennessee.

Assessment of Symptom, Disability, and Financial Trajectories in Patients Hospitalized for COVID-19 at 6 Months.

Importance: Individuals who survived COVID-19 often report persistent symptoms, disabilities, and financial consequences. However, national longitudinal estimates of symptom burden remain limited. Objective: To measure the incidence and changes over time in symptoms, disability, and financial status after COVID-19-related hospitalization. Design, Setting, and Participants: A national US multicenter prospective cohort study with 1-, 3-, and 6-month postdischarge visits was conducted at 44 sites participating in the National Heart, Lung, and Blood Institute Prevention and Early Treatment of Acute Lung Injury Network's Biology and Longitudinal Epidemiology: COVID-19 Observational (BLUE CORAL) study. Participants included hospitalized English- or Spanish-speaking adults without severe prehospitalization disabilities or cognitive impairment. Participants were enrolled between August 24, 2020, and July 20, 2021, with follow-up occurring through March 30, 2022. Exposure: Hospitalization for COVID-19 as identified with a positive SARS-CoV-2 molecular test. Main Outcomes and Measures: New or worsened cardiopulmonary symptoms, financial problems, functional impairments, perceived return to baseline health, and quality of life. Logistic regression was used to identify factors associated with new cardiopulmonary symptoms or financial problems at 6 months. Results: A total of 825 adults (444 [54.0%] were male, and 379 [46.0%] were female) met eligibility criteria and completed at least 1 follow-up survey. Median age was 56 (IQR, 43-66) years; 253 (30.7%) participants were Hispanic, 145 (17.6%) were non-Hispanic Black, and 360 (43.6%) were non-Hispanic White. Symptoms, disabilities, and financial problems remained highly prevalent among hospitalization survivors at month 6. Rates increased between months 1 and 6 for cardiopulmonary symptoms (from 67.3% to 75.4%; P = .001) and fatigue (from 40.7% to 50.8%; P < .001). Decreases were noted over the same interval for prevalent financial problems (from 66.1% to 56.4%; P < .001) and functional limitations (from 55.3% to 47.3%; P = .004). Participants not reporting problems at month 1 often reported new symptoms (60.0%), financial problems (23.7%), disabilities (23.8%), or fatigue (41.4%) at month 6. Conclusions and Relevance: The findings of this cohort study of people discharged after COVID-19 hospitalization suggest that recovery in symptoms, functional status, and fatigue was limited at 6 months, and some participants reported new problems 6 months after hospital discharge.

Effect of physical and occupational therapy on delirium duration in older emergency department patients who are hospitalized.

Objective: Delirium in older emergency department (ED) adults is associated with poorer long-term physical function and cognition. We sought to evaluate if the time to and intensity of physical and/or occupational therapy (PT/OT) are associated with the duration of ED delirium into hospitalization (ED delirium duration). Methods: This is a secondary analysis of a prospective cohort study conducted from March 2012 to November 2014 at an urban, academic, tertiary care hospital. Patients aged ≥65 years presenting to the ED and who received PT/OT during their hospitalization were included. Days from enrollment to the first PT/OT session and PT/OT duration relative to hospital length of stay (PT/OT intensity) were abstracted from the medical record. ED delirium duration was defined as the duration of delirium detected in the ED using the Brief Confusion Assessment Method. Data were analyzed using a proportional odds logistic regression adjusted for multiple variables. Adjusted odds ratios (ORs) were calculated with 95% confidence intervals (95%CI). Results: The median log PT/OT intensity was 0.5% (interquartile range [IQR]: 0.3%, 0.9%) and was associated with shorter delirium duration (adjusted OR, 0.39; 95% CI, 0.21-0.73). The median time to the first PT/OT session was 2 days (IQR: 1, 3 days) and was not associated with delirium duration (adjusted OR, 1.02; 95% CI, 0.82-1.27). Conclusion: In older hospitalized adults, higher PT/OT intensity may be a useful intervention to shorten delirium duration. Time to first PT/OT session was not associated with delirium duration but was initiated a full 2 days after the ED presentation.

The effect of telemental versus in-person mental health consults in the emergency department on 30-day utilization and processes of care.

OBJECTIVES: We sought to characterize how telemental health (TMH) versus in-person mental health consults affected 30-day postevaluation utilization outcomes and processes of care in Veterans presenting to the emergency department (ED) and urgent care clinic (UCC) with acute psychiatric complaints. METHODS: This exploratory retrospective cohort study was conducted in an ED and UCC located in a single Veterans Affairs system. A mental health provider administered TMH via iPad. The primary outcome was a composite of return ED/UCC visits, rehospitalizations, or death within 30 days. The following processes of care were collected during the index visit: changes to home psychiatric medications, admission, involuntary psychiatric hold placement, parenteral benzodiazepine or antipsychotic medication use, and physical restraints or seclusion. Data were abstracted from the Veterans Affairs electronic health record and the Clinical Data Warehouse. Multivariable logistic regression was performed. Adjusted odds ratios (aORs) with their 95% confidence intervals (95% CIs) were reported. RESULTS: Of the 496 Veterans in this analysis, 346 (69.8%) received TMH, and 150 (30.2%) received an in-person mental health evaluation. There was no significant difference in the primary outcome of 30-day return ED/UCC, rehospitalization, or death (aOR 1.47, 95% CI 0.87-2.49) between the TMH and in-person groups. TMH was significantly associated with increased ED/UCC length of stay (aOR 1.46, 95% CI 1.03-2.06) and decreased use of involuntary psychiatric holds (aOR 0.42, 95% CI 0.23-0.75). There were no associations between TMH and the other processes-of-care outcomes. CONCLUSIONS: TMH was not significantly associated with the 30-day composite outcome of return ED/UCC visits, rehospitalizations, and death compared with traditional in-person mental health evaluations. TMH was significantly associated with increased ED/UCC length of stay and decreased odds of placing an involuntary psychiatric hold. Future studies are required to confirm these findings and, if confirmed, explore the potential mechanisms for these associations.

Diagnostic Accuracy of a Bacterial and Viral Biomarker Point-of-Care Test in the Outpatient Setting.

Importance: Acute respiratory infections (ARIs) account for most outpatient visits. Discriminating bacterial vs viral etiology is a diagnostic challenge with therapeutic implications. Objective: To investigate whether FebriDx, a rapid, point-of-care immunoassay, can differentiate bacterial- from viral-associated host immune response in ARI through measurement of myxovirus resistance protein A (MxA) and C-reactive protein (CRP) from finger-stick blood. Design, Setting, and Participants: This diagnostic study enrolled adults and children who were symptomatic for ARI and individuals in a control group who were asymptomatic between October 2019 and April 2021. Included participants were a convenience sample of patients in outpatient settings (ie, emergency department, urgent care, and primary care) who were symptomatic, aged 1 year or older, and had suspected ARI and fever within 72 hours. Individuals with immunocompromised state and recent vaccine, antibiotics, stroke, surgery, major burn, or myocardial infarction were excluded. Of 1685 individuals assessed for eligibility, 259 individuals declined participation, 718 individuals were excluded, and 708 individuals were enrolled (520 patients with ARI, 170 patients without ARI, and 18 individuals who dropped out). Exposures: Bacterial and viral immunoassay testing was performed using finger-stick blood. Results were read at 10 minutes, and treating clinicians and adjudicators were blinded to results. Main Outcomes and Measures: Bacterial- or viral-associated systemic host response to an ARI as determined by a predefined comparator algorithm with adjudication classified infection etiology. Results: Among 520 participants with ARI (230 male patients [44.2%] and 290 female patients [55.8%]; mean [SD] age, 35.3 [17.7] years), 24 participants with missing laboratory information were classified as unknown (4.6%). Among 496 participants with a final diagnosis, 73 individuals (14.7%) were classified as having a bacterial-associated response, 296 individuals (59.7%) as having a viral-associated response, and 127 individuals (25.6%) as negative by the reference standard. The bacterial and viral test correctly classified 68 of 73 bacterial infections, demonstrating a sensitivity of 93.2% (95% CI, 84.9%-97.0%), specificity of 374 of 423 participants (88.4% [95% CI, 85.0%-91.1%]), positive predictive value (PPV) of 68 of 117 participants (58.1% [95% CI, 49.1%-66.7%), and negative predictive value (NPV) of 374 of 379 participants (98.7% [95% CI, 96.9%-99.4%]).The test correctly classified 208 of 296 viral infections, for a sensitivity of 70.3% (95% CI, 64.8%-75.2%), a specificity of 176 of 200 participants (88.0% [95% CI, 82.8%-91.8%]), a PPV of 208 of 232 participants (89.7% [95% CI, 85.1%-92.9%]), and an NPV of 176 of 264 participants (66.7% [95% CI, 60.8%-72.1%]). Conclusions and Relevance: In this study, a rapid diagnostic test demonstrated diagnostic performance that may inform clinicians when assessing for bacterial or viral etiology of ARI symptoms.

Oxygen-Saturation Targets for Critically Ill Adults Receiving Mechanical Ventilation.

BACKGROUND: Invasive mechanical ventilation in critically ill adults involves adjusting the fraction of inspired oxygen to maintain arterial oxygen saturation. The oxygen-saturation target that will optimize clinical outcomes in this patient population remains unknown. METHODS: In a pragmatic, cluster-randomized, cluster-crossover trial conducted in the emergency department and medical intensive care unit at an academic center, we assigned adults who were receiving mechanical ventilation to a lower target for oxygen saturation as measured by pulse oximetry (Spo2) (90%; goal range, 88 to 92%), an intermediate target (94%; goal range, 92 to 96%), or a higher target (98%; goal range, 96 to 100%). The primary outcome was the number of days alive and free of mechanical ventilation (ventilator-free days) through day 28. The secondary outcome was death by day 28, with data censored at hospital discharge. RESULTS: A total of 2541 patients were included in the primary analysis. The median number of ventilator-free days was 20 (interquartile range, 0 to 25) in the lower-target group, 21 (interquartile range, 0 to 25) in the intermediate-target group, and 21 (interquartile range, 0 to 26) in the higher-target group (P = 0.81). In-hospital death by day 28 occurred in 281 of the 808 patients (34.8%) in the lower-target group, 292 of the 859 patients (34.0%) in the intermediate-target group, and 290 of the 874 patients (33.2%) in the higher-target group. The incidences of cardiac arrest, arrhythmia, myocardial infarction, stroke, and pneumothorax were similar in the three groups. CONCLUSIONS: Among critically ill adults receiving invasive mechanical ventilation, the number of ventilator-free days did not differ among groups in which a lower, intermediate, or higher Spo2 target was used. (Supported by the National Heart, Lung, and Blood Institute and others; PILOT ClinicalTrials.gov number, NCT03537937.).

Non-targeted hepatitis C virus screening in acute care healthcare settings in the Southern Appalachian region.

Objectives: The objective of this study was to evaluate the performance of non-targeted hepatitis C virus (HCV) screening in emergency departments (EDs) and other healthcare settings in terms of patients identified with HCV infection and linked to HCV care. Methods: In the Southern Appalachian region of the United States, we developed non-targeted HCV screening and linkage-to-care programs in 10 institutions at different healthcare settings, including EDs, outpatient clinics, and inpatient units. Serum samples were tested for HCV antibodies, and if positive, reflexed to HCV ribonucleic acid (RNA) testing as a confirmatory test for active infection. Patients with positive RNA tests were contacted to link them to HCV care. Results: Between 2017 and 2019, among 195,152 patients screened for HCV infection, 16,529 (8.5%) were positive by antibody testing, 10,139 (5.2% of screened patients and 61.3% of patients positive by antibody test) were positive by RNA testing, and 5778 (3.0% of screened patients and 57.0% of patients positive by RNA test) were successfully linked to HCV care. Among 83,645 patients screened in EDs, 9060 (10.8%) were positive by HCV antibody, and 5243 (6.3%) were positive by RNA test. Among patients positive by RNA testing, linkage to care was lower for patients screened in the ED (44.1%) compared with outpatient clinics (67.6%) (P < 0.01) and inpatient units (50.9%) (P < 0.01). Conclusions: Non-targeted HCV screening in acute care settings can identify large numbers of people with HCV infection. To optimize the utility of these screening programs, future work is needed to develop best practices that consistently link these patients to HCV care.

Delirium and its association with short-term outcomes in younger and older patients with acute heart failure.

Younger patients (18 to 65 years old) are often excluded from delirium outcome studies. We sought to determine if delirium was associated with short-term adverse outcomes in a diverse cohort of younger and older patients with acute heart failure (AHF). We conducted a multi-center prospective cohort study that included adult emergency department patients with confirmed AHF. Delirium was ascertained using the Brief Confusion Assessment Method (bCAM). The primary outcome was a composite outcome of 30-day all-cause death, 30-day all-cause rehospitalization, and prolonged index hospital length of stay. Multivariable logistic regression was performed, adjusting for demographics, cognitive impairment without delirium, and HF risk factors. Older age (≥ 65 years old)*delirium interaction was also incorporated into the model. Odds ratios (OR) with their 95% confidence intervals (95%CI) were reported. A total of 1044 patients with AHF were enrolled; 617 AHF patients were < 65 years old and 427 AHF patients were ≥ 65 years old, and 47 (7.6%) and 40 (9.4%) patients were delirious at enrollment, respectively. Delirium was significantly associated with the composite outcome (adjusted OR = 1.64, 95%CI: 1.02 to 2.64). The older age*delirium interaction p-value was 0.47. In conclusion, delirium was common in both younger and older patients with AHF and was associated with poorer short-term outcomes in both cohorts. Younger patients with acute heart failure should be included in future delirium outcome studies.

Troponin is unrelated to outcomes in heart failure patients discharged from the emergency department.

Background: Prior data has demonstrated increased mortality in hospitalized patients with acute heart failure (AHF) and troponin elevation. No data has specifically examined the prognostic significance of troponin elevation in patients with AHF discharged after emergency department (ED) management. Objective: Evaluate the relationship between troponin elevation and outcomes in patients with AHF who are treated and released from the ED. Methods: This was a secondary analysis of the Get with the Guidelines to Reduce Disparities in AHF Patients Discharged from the ED (GUIDED-HF) trial, a randomized, controlled trial of ED patients with AHF who were discharged. Patients with elevated conventional troponin not due to acute coronary syndrome (ACS) were included. Our primary outcome was a composite endpoint: time to 30-day cardiovascular death and/or heart failure-related events. Results: Of the 491 subjects included in the GUIDED-HF trial, 418 had troponin measured during the ED evaluation and 66 (16%) had troponin values above the 99th percentile. Median age was 63 years (interquartile range, 54-70), 62% (n = 261) were male, 63% (n = 265) were Black, and 16% (n = 67) experienced our primary outcome. There were no differences in our primary outcome between those with and without troponin elevation (12/66, 18.1% vs 55/352, 15.6%; P = 0.60). This effect was maintained regardless of assignment to usual care or the intervention arm. In multivariable regression analysis, there was no association between our primary outcome and elevated troponin (hazard ratio, 1.00; 95% confidence interval,  0.49-2.01, P = 0.994). Conclusion: If confirmed in a larger cohort, these findings may facilitate safe ED discharge for a group of patients with AHF without ACS when an elevated troponin is the primary reason for admission.

Associations between persistent symptoms after mild COVID-19 and long-term health status, quality of life, and psychological distress.

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

Improvement in Kansas City Cardiomyopathy Questionnaire Scores After a Self-Care Intervention in Patients With Acute Heart Failure Discharged From the Emergency Department.

BACKGROUND: We conducted a secondary analysis of changes in the Kansas City Cardiomyopathy Questionnaire (KCCQ)-12 over 30 days in a randomized trial of self-care coaching versus structured usual care in patients with acute heart failure who were discharged from the emergency department. METHODS: Patients in 15 emergency departments completed the KCCQ-12 at emergency department discharge and at 30 days. We compared change in KCCQ-12 scores between the intervention and usual care arms, adjusted for enrollment KCCQ-12 and demographic characteristics. We used linear regression to describe changes in KCCQ-12 summary scores and logistic regression to characterize clinically meaningful KCCQ-12 subdomain changes at 30 days. RESULTS: There were 350 patients with both enrollment and 30-day KCCQ summary scores available; 166 allocated to usual care and 184 to the intervention arm. Median age was 64 years (interquartile range, 55-70), 37% were female participants, 63% were Black, median KCCQ-12 summary score at enrollment was 47 (interquartile range, 33-64). Self-care coaching resulted in significantly greater improvement in health status compared with structured usual care (5.4-point greater improvement, 95% CI, 1.12-9.68; P=0.01). Improvements in health status in the intervention arm were driven by improvements within the symptom frequency (adjusted odds ratio, 1.62 [95% CI, 1.01-2.59]) and quality of life (adjusted odds ratio, 2.39 [95% CI, 1.46-3.90]) subdomains. CONCLUSIONS: In this secondary analysis, patients with acute heart failure who received a tailored, self-care intervention after emergency department discharge had clinically significant improvements in health status at 30 days compared with structured usual care largely due to improvements within the symptom frequency and quality of life subdomains of the KCCQ-12. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02519283.

Risk Factors for Delirium in Older Adults in the Emergency Department: A Systematic Review and Meta-Analysis.

We conducted a systematic review and meta-analysis to identify risk factors for delirium in geriatric patients in the emergency department and to identify emergency department (ED)-based modifiable risk factors for developing delirium during hospitalization. We searched evidence based medicine reviews, EMBASE, MEDLINE, Scopus, and Web of Science for observational studies from the time of their inception to July 2020. We included studies that evaluated potential risk factors for either prevalent or incident delirium among older adults (age ≥ 60 years) presenting to the ED. When appropriate, we meta-analyzed estimates for risk factors using a random-effects model. The certainty of evidence was evaluated using the grading of recommendations assessment, development and evaluation approach. The study's protocol was registered in PROSPERO (CDR42020175261). A total of 4,513 citations were reviewed, and 34 studies met the criteria for inclusion: 27 evaluating risk factors for ED delirium (13,412 patients) and 7 evaluating ED-based risk factors for developing delirium during hospitalization (2,238 patients). The prevalence of ED delirium ranged from 7% to 35%. Four factors had strong associations with ED delirium and were graded as high-certainty evidence, including nursing home residence (4 studies; odds ratio [OR], 3.45; 95% confidence interval [CI], 2.17 to 5.48), cognitive impairment (7 studies; OR, 4.46; 95% CI, 3.38 to 5.89), hearing impairment (3 studies, OR, 2.57; 95% CI, 1.03 to 6.41), and a history of stroke (3 studies; OR, 3.20; 95% CI, 1.17 to 8.75). The rate of developing delirium during hospitalization ranged from 11% to 27%. A length of stay of more than 10 hours in ED was associated with a higher risk of delirium (1 study; OR, 2.23; 95% CI, 1.13 to 4.41). One study reported that severe pain, rather than the use of opioids, was associated with the development of delirium. These findings can be used to prioritize delirium screening in the ED and develop novel ED delirium risk scores or prevention interventions.