Intraoperative Oxygen Treatment, Oxidative Stress, and Organ Injury Following Cardiac Surgery: A Randomized Clinical Trial.

Importance: Liberal oxygen (hyperoxia) is commonly administered to patients during surgery, and oxygenation is known to impact mechanisms of perioperative organ injury. Objective: To evaluate the effect of intraoperative hyperoxia compared to maintaining normoxia on oxidative stress, kidney injury, and other organ dysfunctions after cardiac surgery. Design, Setting, and Participants: This was a participant- and assessor-blinded, randomized clinical trial conducted from April 2016 to October 2020 with 1 year of follow-up at a single tertiary care medical center. Adult patients (>18 years) presenting for elective open cardiac surgery without preoperative oxygen requirement, acute coronary syndrome, carotid stenosis, or dialysis were included. Of 3919 patients assessed, 2501 were considered eligible and 213 provided consent. Of these, 12 were excluded prior to randomization and 1 following randomization whose surgery was cancelled, leaving 100 participants in each group. Interventions: Participants were randomly assigned to hyperoxia (1.00 fraction of inspired oxygen [FiO2]) or normoxia (minimum FiO2 to maintain oxygen saturation 95%-97%) throughout surgery. Main Outcomes and Measures: Participants were assessed for oxidative stress by measuring F2-isoprostanes and isofurans, for acute kidney injury (AKI), and for delirium, myocardial injury, atrial fibrillation, and additional secondary outcomes. Participants were monitored for 1 year following surgery. Results: Two hundred participants were studied (median [IQR] age, 66 [59-72] years; 140 male and 60 female; 82 [41.0%] with diabetes). F2-isoprostanes and isofurans (primary mechanistic end point) increased on average throughout surgery, from a median (IQR) of 73.3 (53.1-101.1) pg/mL at baseline to a peak of 85.5 (64.0-109.8) pg/mL at admission to the intensive care unit and were 9.2 pg/mL (95% CI, 1.0-17.4; P = .03) higher during surgery in patients assigned to hyperoxia. Median (IQR) change in serum creatinine (primary clinical end point) from baseline to postoperative day 2 was 0.01 mg/dL (-0.12 to 0.19) in participants assigned hyperoxia and -0.01 mg/dL (-0.16 to 0.19) in those assigned normoxia (median difference, 0.03; 95% CI, -0.04 to 0.10; P = .45). AKI occurred in 21 participants (21%) in each group. Intraoperative oxygen treatment did not affect additional acute organ injuries, safety events, or kidney, neuropsychological, and functional outcomes at 1 year. Conclusions: Among adults receiving cardiac surgery, intraoperative hyperoxia increased intraoperative oxidative stress compared to normoxia but did not affect kidney injury or additional measurements of organ injury including delirium, myocardial injury, and atrial fibrillation. Trial Registration: ClinicalTrials.gov Identifier: NCT02361944.

A Randomized Controlled Comparison of Guardian-Perceived Cosmetic Outcome of Simple Lacerations Repaired With Either Dermabond, Steri-Strips, or Absorbable Sutures.

OBJECTIVES: The aim of this study was to compare the guardian-perceived 3-month cosmetic outcome for pediatric lacerations repaired with absorbable sutures, Dermabond, or Steri-Strips. Secondarily, pain and satisfaction with the procedure from both guardian and provider perspectives were compared. METHODS: In this randomized controlled trial, we enrolled a convenience sample of children aged 0 to <18 years who presented with simple linear lacerations (≤5 cm in length, ≤0.5 cm in width, and <12 hours old) to a pediatric emergency department. Children were randomized to receive laceration repair with absorbable sutures, Dermabond, or Steri-Strips. Topical L.E.T. solution (lidocaine, epinephrine, tetracaine) was applied to wounds which were then closed by the primary team. Guardians and providers completed questionnaires regarding perceived pain and satisfaction with the procedure. Guardians were contacted 3 months after the repair and asked to email a picture of the scar with their perception of cosmesis rated on a visual analog scale from 0 to 100. RESULTS: Fifty-five patients were enrolled, of whom 30 completed 3-month follow-up (12 suture, 7 Dermabond, 11 Steri-strips). There was no statistical evidence of an association between scar appearance and closure method based on medians and interquartile ranges for cosmetic ratings of scar: suture median 70.5 (IQR 59.8-76.8), Dermabond median 85 (IQR 73-90), Steri-strips median 67 (IQR 55-78) (P = 0.254). Guardian satisfaction with length of stay, guardian and physician satisfaction with the procedure, and guardian and physician-perceived pain also showed no differences. CONCLUSIONS: No differences were observed in guardian-perceived cosmesis of simple lacerations repaired with sutures, Dermabond, or Steri-Strips when evaluated 3 months after intervention. In addition, there were no differences in guardian or physician-perceived pain or satisfaction with the closure methods. The results of this study suggest that all 3 closure methods appear to be clinically equivalent, which is largely consistent with other evidence. Further study should be expanded to a larger demographic.

Swab Testing to Optimize Pneumonia treatment with empiric Vancomycin (STOP-Vanc): study protocol for a randomized controlled trial.

Background: Vancomycin, an antibiotic with activity against Methicillin-resistant Staphylococcus aureus (MRSA), is frequently included in empiric treatment for community-acquired pneumonia (CAP) despite the fact that MRSA is rarely implicated in CAP. Conducting polymerase chain reaction (PCR) testing on nasal swabs to identify the presence of MRSA colonization has been proposed as an antimicrobial stewardship intervention to reduce the use of vancomycin. Observational studies have shown reductions in vancomycin use after implementation of MRSA colonization testing, and this approach has been adopted by CAP guidelines. However, the ability of this intervention to safely reduce vancomycin use has yet to be tested in a randomized controlled trial. Methods: STOP-Vanc is a pragmatic, prospective, single center, non-blinded randomized trial. Adult patients with suspicion for CAP who are receiving vancomycin and admitted to the Medical Intensive Care Unit at Vanderbilt University Medical Center will be screened for eligibility. Eligible patients will be enrolled and randomized in a 1:1 ratio to either receive MRSA nasal swab PCR testing in addition to usual care (intervention group), or usual care alone (control group). PCR testing results will be transmitted through the electronic health record to the treating clinicians. Primary providers of intervention group patients with negative swab results will also receive a page providing clinical guidance recommending discontinuation of vancomycin. The primary outcome will be vancomycin-free hours alive, defined as the number of hours alive and free of the use of vancomycin within the first seven days following trial enrollment estimated using a proportional odds ratio model. Secondary outcomes include 30-day all-cause mortality and time alive off vancomycin. Discussion: STOP-Vanc will provide the first randomized controlled trial data regarding the use of MRSA nasal swab PCR testing to guide antibiotic de-escalation. This study will provide important information regarding the effect of MRSA PCR testing and antimicrobial stewardship guidance on clinical outcomes in an intensive care unit setting. Trial registration: This trial was registered on ClinicalTrials.gov on February 22, 2024. (ClinicalTrials.gov identifier: NCT06272994).

Effect of a Co-Located Bridging Recovery Initiative on Hospital Length of Stay Among Patients With Opioid Use Disorder: The BRIDGE Randomized Clinical Trial.

Importance: Co-located bridge clinics aim to facilitate a timely transition to outpatient care for inpatients with opioid use disorder (OUD); however, their effect on hospital length of stay (LOS) and postdischarge outcomes remains unclear. Objective: To evaluate the effect of a co-located bridge clinic on hospital LOS among inpatients with OUD. Design, Setting, and Participants: This parallel-group randomized clinical trial recruited 335 adult inpatients with OUD seen by an addiction consultation service and without an existing outpatient clinician to provide medication for OUD (MOUD) between November 25, 2019, and September 28, 2021, at a tertiary care hospital affiliated with a large academic medical center and its bridge clinic. Intervention: The bridge clinic included enhanced case management before and after hospital discharge, MOUD prescription, and referral to a co-located bridge clinic. Usual care included MOUD prescription and referrals to community health care professionals who provided MOUD. Main Outcomes and Measures: The primary outcome was the index admission LOS. Secondary outcomes, assessed at 16 weeks, were linkage to health care professionals who provided MOUD, MOUD refills, same-center emergency department (ED) and hospital use, recurrent opioid use, quality of life (measured by the Schwartz Outcome Scale-10), overdose, mortality, and cost. Analysis was performed on an intent-to-treat basis. Results: Of 335 participants recruited (167 randomized to the bridge clinic and 168 to usual care), the median age was 38.0 years (IQR, 31.9-45.7 years), and 194 (57.9%) were male. The median LOS did not differ between arms (adjusted odds ratio [AOR], 0.94 [95% CI, 0.65-1.37]; P = .74). At the 16-week follow-up, participants referred to the bridge clinic had fewer hospital-free days (AOR, 0.54 [95% CI, 0.32-0.92]), more readmissions (AOR, 2.17 [95% CI, 1.25-3.76]), and higher care costs (AOR, 2.25 [95% CI, 1.51-3.35]), with no differences in ED visits (AOR, 1.15 [95% CI, 0.68-1.94]) or deaths (AOR, 0.48 [95% CI, 0.08-2.72]) compared with those receiving usual care. Follow-up calls were completed for 88 participants (26.3%). Participants referred to the bridge clinic were more likely to receive linkage to health care professionals who provided MOUD (AOR, 2.37 [95% CI, 1.32-4.26]) and have more MOUD refills (AOR, 6.17 [95% CI, 3.69-10.30]) and less likely to experience an overdose (AOR, 0.11 [95% CI, 0.03-0.41]). Conclusions and Relevance: This randomized clinical trial found that among inpatients with OUD, bridge clinic referrals did not improve hospital LOS. Referrals may improve outpatient metrics but with higher resource use and expenditure. Bending the cost curve may require broader community and regional partnerships. Trial Registration: ClinicalTrials.gov Identifier: NCT04084392.

Public Perceptions and Informational Needs Regarding Surgical Residents.

OBJECTIVE: Identify what topics are of most interest to patients regarding surgical residents. DESIGN: Survey of general public describing a hypothetical surgery and then assessing comfort level with resident involvement in surgery, reactions to disclosure statements regarding resident involvement, and desires for additional information. This data was used to produce an amended statement about surgical residents and their involvement in a hypothetical surgery to determine the impact of increased information on participant comfort. SETTING: Online survey via Mechanical Turk. PARTICIPANTS: Our sample was broadly representative of the United States based on race and age, but with higher education level than United States census data. RESULTS: Using a combination of hierarchical clustering, weighted averages, and VAS scoring, questions that were most highly valued by participants were related to what the resident will be doing in the operation and the impact of resident involvement. Participants who had a past negative experience with residents assigned higher importance to all questions, even those that may be seen as not clinically relevant. Increasing the amount of proactively provided information did not have a significant effect on comfort (p = 0.219) when compared to our baseline statement, except with those who reported past negative experience with residents (p = 0.039). CONCLUSIONS: These results demonstrate that the majority of potential patients want to know specific details about the residents' skills, what they will be doing in their surgery, and the impact of their participation. Surgeons should be attuned to patients with past negative experiences, who may desire more information. Additional information alone may not be sufficient to comfort some patients, and future research should consider information delivery styles and interpersonal effects on patient comfort level.

COVID-19 severity and cardiovascular outcomes in SARS-CoV-2-infected patients with cancer and cardiovascular disease.

Background: Data regarding outcomes among patients with cancer and co-morbid cardiovascular disease (CVD)/cardiovascular risk factors (CVRF) after SARS-CoV-2 infection are limited. Objectives: To compare Coronavirus disease 2019 (COVID-19) related complications among cancer patients with and without co-morbid CVD/CVRF. Methods: Retrospective cohort study of patients with cancer and laboratory-confirmed SARS-CoV-2, reported to the COVID-19 and Cancer Consortium (CCC19) registry from 03/17/2020 to 12/31/2021. CVD/CVRF was defined as established CVD or no established CVD, male ≥ 55 or female ≥ 60 years, and one additional CVRF. The primary endpoint was an ordinal COVID-19 severity outcome including need for hospitalization, supplemental oxygen, intensive care unit (ICU), mechanical ventilation, ICU or mechanical ventilation plus vasopressors, and death. Secondary endpoints included incident adverse CV events. Ordinal logistic regression models estimated associations of CVD/CVRF with COVID-19 severity. Effect modification by recent cancer therapy was evaluated. Results: Among 10,876 SARS-CoV-2 infected patients with cancer (median age 65 [IQR 54-74] years, 53% female, 52% White), 6253 patients (57%) had co-morbid CVD/CVRF. Co-morbid CVD/CVRF was associated with higher COVID-19 severity (adjusted OR: 1.25 [95% CI 1.11-1.40]). Adverse CV events were significantly higher in patients with CVD/CVRF (all p<0.001). CVD/CVRF was associated with worse COVID-19 severity in patients who had not received recent cancer therapy, but not in those undergoing active cancer therapy (OR 1.51 [95% CI 1.31-1.74] vs. OR 1.04 [95% CI 0.90-1.20], pinteraction <0.001). Conclusions: Co-morbid CVD/CVRF is associated with higher COVID-19 severity among patients with cancer, particularly those not receiving active cancer therapy. While infrequent, COVID-19 related CV complications were higher in patients with comorbid CVD/CVRF. (COVID-19 and Cancer Consortium Registry [CCC19]; NCT04354701).

Impact of COVID-19 in patients on active melanoma therapy and with history of melanoma.

INTRODUCTION: COVID-19 particularly impacted patients with co-morbid conditions, including cancer. Patients with melanoma have not been specifically studied in large numbers. Here, we sought to identify factors that associated with COVID-19 severity among patients with melanoma, particularly assessing outcomes of patients on active targeted or immune therapy. METHODS: Using the COVID-19 and Cancer Consortium (CCC19) registry, we identified 307 patients with melanoma diagnosed with COVID-19. We used multivariable models to assess demographic, cancer-related, and treatment-related factors associated with COVID-19 severity on a 6-level ordinal severity scale. We assessed whether treatment was associated with increased cardiac or pulmonary dysfunction among hospitalized patients and assessed mortality among patients with a history of melanoma compared with other cancer survivors. RESULTS: Of 307 patients, 52 received immunotherapy (17%), and 32 targeted therapy (10%) in the previous 3 months. Using multivariable analyses, these treatments were not associated with COVID-19 severity (immunotherapy OR 0.51, 95% CI 0.19 - 1.39; targeted therapy OR 1.89, 95% CI 0.64 - 5.55). Among hospitalized patients, no signals of increased cardiac or pulmonary organ dysfunction, as measured by troponin, brain natriuretic peptide, and oxygenation were noted. Patients with a history of melanoma had similar 90-day mortality compared with other cancer survivors (OR 1.21, 95% CI 0.62 - 2.35). CONCLUSIONS: Melanoma therapies did not appear to be associated with increased severity of COVID-19 or worsening organ dysfunction. Patients with history of melanoma had similar 90-day survival following COVID-19 compared with other cancer survivors.

Oxygen administration during surgery and postoperative organ injury: observational cohort study.

OBJECTIVE: To examine whether supraphysiological oxygen administration during surgery is associated with lower or higher postoperative kidney, heart, and lung injury. DESIGN: Observational cohort study. SETTING: 42 medical centers across the United States participating in the Multicenter Perioperative Outcomes Group data registry. PARTICIPANTS: Adult patients undergoing surgical procedures ≥120 minutes' duration with general anesthesia and endotracheal intubation who were admitted to hospital after surgery between January 2016 and November 2018. INTERVENTION: Supraphysiological oxygen administration, defined as the area under the curve of the fraction of inspired oxygen above air (21%) during minutes when the hemoglobin oxygen saturation was greater than 92%. MAIN OUTCOMES: Primary endpoints were acute kidney injury defined using Kidney Disease Improving Global Outcomes criteria, myocardial injury defined as serum troponin >0.04 ng/mL within 72 hours of surgery, and lung injury defined using international classification of diseases hospital discharge diagnosis codes. RESULTS: The cohort comprised 350 647 patients with median age 59 years (interquartile range 46-69 years), 180 546 women (51.5%), and median duration of surgery 205 minutes (interquartile range 158-279 minutes). Acute kidney injury was diagnosed in 19 207 of 297 554 patients (6.5%), myocardial injury in 8972 of 320 527 (2.8%), and lung injury in 13 789 of 312 161 (4.4%). The median fraction of inspired oxygen was 54.0% (interquartile range 47.5%-60.0%), and the area under the curve of supraphysiological inspired oxygen was 7951% min (5870-11 107% min), equivalent to an 80% fraction of inspired oxygen throughout a 135 minute procedure, for example. After accounting for baseline covariates and other potential confounding variables, increased oxygen exposure was associated with a higher risk of acute kidney injury, myocardial injury, and lung injury. Patients at the 75th centile for the area under the curve of the fraction of inspired oxygen had 26% greater odds of acute kidney injury (95% confidence interval 22% to 30%), 12% greater odds of myocardial injury (7% to 17%), and 14% greater odds of lung injury (12% to 16%) compared with patients at the 25th centile. Sensitivity analyses evaluating alternative definitions of the exposure, restricting the cohort, and conducting an instrumental variable analysis confirmed these observations. CONCLUSIONS: Increased supraphysiological oxygen administration during surgery was associated with a higher incidence of kidney, myocardial, and lung injury. Residual confounding of these associations cannot be excluded. TRIAL REGISTRATION: Open Science Framework osf.io/cfd2m.

Demographics, Outcomes, and Risk Factors for Patients with Sarcoma and COVID-19: A CCC19-Registry Based Retrospective Cohort Study.

BACKGROUND: Patients with sarcoma often require individualized treatment strategies and are likely to receive aggressive immunosuppressive therapies, which may place them at higher risk for severe COVID-19. We aimed to describe demographics, risk factors, and outcomes for patients with sarcoma and COVID-19. METHODS: We performed a retrospective cohort study of patients with sarcoma and COVID-19 reported to the COVID-19 and Cancer Consortium (CCC19) registry (NCT04354701) from 17 March 2020 to 30 September 2021. Demographics, sarcoma histologic type, treatments, and COVID-19 outcomes were analyzed. RESULTS: of 281 patients, 49% (n = 139) were hospitalized, 33% (n = 93) received supplemental oxygen, 11% (n = 31) were admitted to the ICU, and 6% (n = 16) received mechanical ventilation. A total of 23 (8%) died within 30 days of COVID-19 diagnosis and 44 (16%) died overall at the time of analysis. When evaluated by sarcoma subtype, patients with bone sarcoma and COVID-19 had a higher mortality rate than patients from a matched SEER cohort (13.5% vs 4.4%). Older age, poor performance status, recent systemic anti-cancer therapy, and lung metastases all contributed to higher COVID-19 severity. CONCLUSIONS: Patients with sarcoma have high rates of severe COVID-19 and those with bone sarcoma may have the greatest risk of death.

Potentially avoidable interfacility transfers following reduced emergency department volumes due to COVID-19 "Safer-at-Home" orders.

OBJECTIVES: We sought to assess if a state-wide lockdown implemented due to COVID-19 was associated with increased odds of being a potentially avoidable transfer (PAT). METHODS: We conducted a retrospective observational analysis using hospital administrative data of interfacility ED-to-ED transfers to a single, quaternary care adult ED after "Safer at Home" orders were issued March 23rd, 2020 in [Blinded for submission]. Using the PAT classification to identify transfers rapidly discharged from the ED or hospital and may not require in-person care, we used a multivariable logistic regression model to examine the association of the lockdown order with odds of a transfer being a PAT. We compared the period January 1, 2018 to March 23, 2020 with March 24, 2020 to September 30, 2020, adjusting for seasonality, patient, and situational factors. RESULTS: There were 20,978 ED-to-ED transfers from during this period that were eligible and 4806 (23%) that met PAT criteria. While the first month post-lockdown saw a decrease in PATs (28%), this was not sustained. In the multivariable model there was a significant seasonal effect; May through September had the highest number of transfers as well as PATs. After adjusting for seasonality, the lockdown was not associated with PATs (adjusted odds ratio [aOR] 0.99, 95% CI 0.2, 5.2) and PATs decreased over time. CONCLUSIONS: We did not find an effect of the COVID-19 lockdown on PATs though there was a considerable seasonal effect and an overall downward trend in PATs over time.

SOLUBLE GUANYLYL CYCLASE ACTIVATION RESCUES HYPEROXIA-INDUCED DYSFUNCTION OF VASCULAR RELAXATION.

ABSTRACT: Introduction: Perioperative alterations in perfusion lead to ischemia and reperfusion injury, and supplemental oxygen is administered during surgery to limit hypoxic injury but can lead to hyperoxia. We hypothesized that hyperoxia impairs endothelium-dependent and endothelium-independent vasodilation but not the vasodilatory response to heme-independent soluble guanylyl cyclase activation. Methods: We measured the effect of oxygen on vascular reactivity in mouse aortas. Mice were ventilated with 21% (normoxia), 60% (moderate hyperoxia), or 100% (severe hyperoxia) oxygen during 30 minutes of renal ischemia and 30 minutes of reperfusion. After sacrifice, the thoracic aorta was isolated, and segments mounted on a wire myograph. We measured endothelium-dependent and endothelium-independent vasodilation with escalating concentrations of acetylcholine (ACh) and sodium nitroprusside (SNP), respectively, and we measured the response to heme-independent soluble guanylyl cyclase activation with cinaciguat. Vasodilator responses to each agonist were quantified as the maximal theoretical response ( Emax ) and the effective concentration to elicit 50% relaxation (EC 50 ) using a sigmoid model and nonlinear mixed-effects regression. Aortic superoxide was measured with dihydroethidium probe and high-performance liquid chromatography quantification of the specific superoxide product 2-hydroxyethidium. Results: Hyperoxia impaired endothelium-dependent (ACh) and endothelium-independent (SNP) vasodilation compared with normoxia and had no effect on cinaciguat-induced vasodilation. The median ACh Emax was 76.4% (95% confidence interval = 69.6 to 83.3) in the normoxia group, 53.5% (46.7 to 60.3) in the moderate hyperoxia group, and 53.1% (46.3 to 60.0) in the severe hyperoxia group ( P < 0.001, effect across groups), while the ACh EC 50 was not different among groups. The SNP Emax was 133.1% (122.9 to 143.3) in normoxia, 128.3% (118.1 to 138.6) in moderate hyperoxia, and 114.8% (104.6 to 125.0) in severe hyperoxia ( P < 0.001, effect across groups), and the SNP EC 50 was 0.38 log M greater in moderate hyperoxia than in normoxia (95% confidence interval = 0.18 to 0.58, P < 0.001). Cinaciguat Emax and EC 50 were not different among oxygen treatment groups (median range Emax = 78.0% to 79.4% and EC 50 = -18.0 to -18.2 log M across oxygen groups). Aorta 2-hydroxyethidium was 1419 pmol/mg of protein (25th-75th percentile = 1178-1513) in normoxia, 1993 (1831-2473) in moderate hyperoxia, and 2078 (1936-2922) in severe hyperoxia ( P = 0.008, effect across groups). Conclusions: Hyperoxia, compared with normoxia, impaired endothelium-dependent and endothelium-independent vasodilation but not the response to heme-independent soluble guanylyl cyclase activation, and hyperoxia increased vascular superoxide production. Results from this study could have important implications for patients receiving high concentrations of oxygen and at risk for ischemia reperfusion-mediated organ injury.

Effect of Smartphone App-Based Education on Clinician Prescribing Habits in a Learning Health Care System: A Randomized Cluster Crossover Trial.

Importance: Effective methods for engaging clinicians in continuing education for learning-based practice improvement remain unknown. Objective: To determine whether a smartphone-based app using spaced education with retrieval practice is an effective method to increase evidence-based practice. Design, Setting, and Participants: A prospective, unblinded, single-center, crossover randomized clinical trial was conducted at a single academic medical center from January 6 to April 24, 2020. Vanderbilt University Medical Center clinicians prescribing intravenous fluids were invited to participate in this study. Interventions: All clinicians received two 4-week education modules: 1 on prescribing intravenous fluids and 1 on prescribing opioid and nonopioid medications (counterbalancing measure), over a 12-week period. The order of delivery was randomized 1:1 such that 1 group received the fluid management module first, followed by the pain management module after a 4-week break, and the other group received the pain management module first, followed by the fluid management module after a 4-week break. Main Outcomes and Measures: The primary outcome was evidence-based clinician prescribing behavior concerning intravenous fluids in the inpatient setting and pain medication prescribing on discharge from the hospital. Results: A total of 354 participants were enrolled and randomized, with 177 in group 1 (fluid then pain management education) and 177 in group 2 (pain management then fluid education). During the overall study period, 16 868 questions were sent to 349 learners, with 11 783 (70.0%) being opened: 10 885 (92.4%) of those opened were answered and 7175 (65.9%) of those answered were answered correctly. The differences between groups changed significantly over time, indicated by the significant interaction between educational intervention and time (P = .002). Briefly, at baseline evidence-concordant IV fluid ordered 7.2% less frequently in group 1 than group 2 (95% CI, -19.2% to 4.9%). This was reversed after training at 4% higher (95% CI, -8.2% to 16.0%) in group 1 than group 2, a more than doubling in the odds of evidence-concordant ordering (OR, 2.56, 95% CI, 0.80-8.21). Postintervention, all gains had been reversed with less frequent ordering in group 1 than group 2 (-9.5%, 95% CI, -21.6% to 2.7%). There was no measurable change in opioid prescribing behaviors at any time point. Conclusions and Relevance: In this randomized clinical trial, use of smartphone app learning modules resulted in statistically significant short-term improvement in some prescribing behaviors. However, this effect was not sustained over the long-term. Additional research is needed to understand how to sustain improvements in care delivery as a result of continuous professional development at the institutional level. Trial Registration: ClinicalTrials.gov Identifier: NCT03771482.

Assessment of Awake Prone Positioning in Hospitalized Adults With COVID-19: A Nonrandomized Controlled Trial.

Importance: Awake prone positioning may improve hypoxemia among patients with COVID-19, but whether it is associated with improved clinical outcomes remains unknown. Objective: To determine whether the recommendation of awake prone positioning is associated with improved outcomes among patients with COVID-19-related hypoxemia who have not received mechanical ventilation. Design, Setting, and Participants: This pragmatic nonrandomized controlled trial was conducted at 2 academic medical centers (Vanderbilt University Medical Center and NorthShore University HealthSystem) during the COVID-19 pandemic. A total of 501 adult patients with COVID-19-associated hypoxemia who had not received mechanical ventilation were enrolled from May 13 to December 11, 2020. Interventions: Patients were assigned 1:1 to receive either the practitioner-recommended awake prone positioning intervention (intervention group) or usual care (usual care group). Main Outcomes and Measures: Primary outcome analyses were performed using a bayesian proportional odds model with covariate adjustment for clinical severity ranking based on the World Health Organization ordinal outcome scale, which was modified to highlight the worst level of hypoxemia on study day 5. Results: A total of 501 patients (mean [SD] age, 61.0 [15.3] years; 284 [56.7%] were male; and most [417 (83.2%)] were self-reported non-Hispanic or non-Latinx) were included. Baseline severity was comparable between the intervention vs usual care groups, with 170 patients (65.9%) vs 162 patients (66.7%) receiving oxygen via standard low-flow nasal cannula, 71 patients (27.5%) vs 62 patients (25.5%) receiving oxygen via high-flow nasal cannula, and 16 patients (6.2%) vs 19 patients (7.8%) receiving noninvasive positive-pressure ventilation. Nursing observations estimated that patients in the intervention group spent a median of 4.2 hours (IQR, 1.8-6.7 hours) in the prone position per day compared with 0 hours (IQR, 0-0.7 hours) per day in the usual care group. On study day 5, the bayesian posterior probability of the intervention group having worse outcomes than the usual care group on the modified World Health Organization ordinal outcome scale was 0.998 (posterior median adjusted odds ratio [aOR], 1.63; 95% credibility interval [CrI], 1.16-2.31). However, on study days 14 and 28, the posterior probabilities of harm were 0.874 (aOR, 1.29; 95% CrI, 0.84-1.99) and 0.673 (aOR, 1.12; 95% CrI, 0.67-1.86), respectively. Exploratory outcomes (progression to mechanical ventilation, length of stay, and 28-day mortality) did not differ between groups. Conclusions and Relevance: In this nonrandomized controlled trial, prone positioning offered no observed clinical benefit among patients with COVID-19-associated hypoxemia who had not received mechanical ventilation. Moreover, there was substantial evidence of worsened clinical outcomes at study day 5 among patients recommended to receive the awake prone positioning intervention, suggesting potential harm. Trial Registration: ClinicalTrials.gov Identifier: NCT04359797.

Racial Disparities in COVID-19 Outcomes Among Black and White Patients With Cancer.

Importance: Non-Hispanic Black individuals experience a higher burden of COVID-19 than the general population; hence, there is an urgent need to characterize the unique clinical course and outcomes of COVID-19 in Black patients with cancer. Objective: To investigate racial disparities in severity of COVID-19 presentation, clinical complications, and outcomes between Black patients and non-Hispanic White patients with cancer and COVID-19. Design, Setting, and Participants: This retrospective cohort study used data from the COVID-19 and Cancer Consortium registry from March 17, 2020, to November 18, 2020, to examine the clinical characteristics and outcomes of COVID-19 in Black patients with cancer. Data analysis was performed from December 2020 to February 2021. Exposures: Black and White race recorded in patient's electronic health record. Main Outcomes and Measures: An a priori 5-level ordinal scale including hospitalization intensive care unit admission, mechanical ventilation, and all-cause death. Results: Among 3506 included patients (1768 women [50%]; median [IQR] age, 67 [58-77] years), 1068 (30%) were Black and 2438 (70%) were White. Black patients had higher rates of preexisting comorbidities compared with White patients, including obesity (480 Black patients [45%] vs 925 White patients [38%]), diabetes (411 Black patients [38%] vs 574 White patients [24%]), and kidney disease (248 Black patients [23%] vs 392 White patients [16%]). Despite the similar distribution of cancer type, cancer status, and anticancer therapy at the time of COVID-19 diagnosis, Black patients presented with worse illness and had significantly worse COVID-19 severity (unweighted odds ratio, 1.34 [95% CI, 1.15-1.58]; weighted odds ratio, 1.21 [95% CI, 1.11-1.33]). Conclusions and Relevance: These findings suggest that Black patients with cancer experience worse COVID-19 outcomes compared with White patients. Understanding and addressing racial inequities within the causal framework of structural racism is essential to reduce the disproportionate burden of diseases, such as COVID-19 and cancer, in Black patients.

Geriatric risk factors for serious COVID-19 outcomes among older adults with cancer: a cohort study from the COVID-19 and Cancer Consortium.

BACKGROUND: Older age is associated with poorer outcomes of SARS-CoV-2 infection, although the heterogeneity of ageing results in some older adults being at greater risk than others. The objective of this study was to quantify the association of a novel geriatric risk index, comprising age, modified Charlson comorbidity index, and Eastern Cooperative Oncology Group performance status, with COVID-19 severity and 30-day mortality among older adults with cancer. METHODS: In this cohort study, we enrolled patients aged 60 years and older with a current or previous cancer diagnosis (excluding those with non-invasive cancers and premalignant or non-malignant conditions) and a current or previous laboratory-confirmed COVID-19 diagnosis who reported to the COVID-19 and Cancer Consortium (CCC19) multinational, multicentre, registry between March 17, 2020, and June 6, 2021. Patients were also excluded for unknown age, missing data resulting in unknown geriatric risk measure, inadequate data quality, or incomplete follow-up resulting in unknown COVID-19 severity. The exposure of interest was the CCC19 geriatric risk index. The primary outcome was COVID-19 severity and the secondary outcome was 30-day all-cause mortality; both were assessed in the full dataset. Adjusted odds ratios (ORs) and 95% CIs were estimated from ordinal and binary logistic regression models. FINDINGS: 5671 patients with cancer and COVID-19 were included in the analysis. Median follow-up time was 56 days (IQR 22-120), and median age was 72 years (IQR 66-79). The CCC19 geriatric risk index identified 2365 (41·7%) patients as standard risk, 2217 (39·1%) patients as intermediate risk, and 1089 (19·2%) as high risk. 36 (0·6%) patients were excluded due to non-calculable geriatric risk index. Compared with standard-risk patients, high-risk patients had significantly higher COVID-19 severity (adjusted OR 7·24; 95% CI 6·20-8·45). 920 (16·2%) of 5671 patients died within 30 days of a COVID-19 diagnosis, including 161 (6·8%) of 2365 standard-risk patients, 409 (18·5%) of 2217 intermediate-risk patients, and 350 (32·1%) of 1089 high-risk patients. High-risk patients had higher adjusted odds of 30-day mortality (adjusted OR 10·7; 95% CI 8·54-13·5) than standard-risk patients. INTERPRETATION: The CCC19 geriatric risk index was strongly associated with COVID-19 severity and 30-day mortality. Our CCC19 geriatric risk index, based on readily available clinical factors, might provide clinicians with an easy-to-use risk stratification method to identify older adults most at risk for severe COVID-19 as well as mortality. FUNDING: US National Institutes of Health National Cancer Institute Cancer Center.