Three-year outcomes of de novo tacrolimus extended-release tablets (LCPT) compared to twice-daily tacrolimus in adult heart transplantation.

BACKGROUND: Extended-release tacrolimus for prophylaxis of allograft rejection in heart transplant (HT) recipients is currently not FDA-approved. One such extended-release formulation of tacrolimus known as LCPT allows once-daily dosing and improves bioavailability compared to immediate-release (IR-) tacrolimus. We compared long-term efficacy and safety of LCPT to IR-tacrolimus applied de novo in adult OHT recipients. METHODS: 25 prospective recipients on LCPT at our center from 2017 to 2019 were matched 1:2 with historical control recipients treated with IR-tacrolimus based on age, gender, and baseline creatinine. The primary composite outcome of death, acute cellular rejection, and/or new graft dysfunction within 3 years following transplant was compared between groups using non-inferiority analysis. RESULTS: LCPT demonstrated non-inferiority to IR-tacrolimus, with a primary outcome risk reduction of 16% (90%CI, -37%, -1%, non-inferiority p = 0.002) up to 3 years following heart transplant. Up to 3-years post-transplant, 14 patients remained on once-daily LCPT and 10 patients were switched to IR-tacrolimus due to lack of insurance coverage. There were no significant differences in the rate of chronic kidney disease requiring dialysis, cytomegalovirus requiring treatment, cardiac allograft vasculopathy, and malignancy within 3 years following transplant. CONCLUSION: LCPT is non-inferior in efficacy to IR-tacrolimus in heart transplantation with a similar safety profile. Narrowly-constrained FDA labels specific to kidney transplant remain a barrier to consistent access to many immunosuppressant medications for recipients of non-kidney solid organs. We recommend the FDA consider developing facile pathways for expanding the approved label of extended-release tacrolimus formulations to heart transplant recipients.

Treatment of patients hospitalized for COVID-19 with remdesivir is associated with lower likelihood of 30-day readmission: a retrospective observational study.

Aim: This observational study investigated the association between remdesivir treatment during hospitalization for COVID-19 and 30-day COVID-19-related and all-cause readmission across different variants time periods. Patients & methods: Hospitalization records for adult patients discharged from a COVID-19 hospitalization between 1 May 2020 to 30 April 2022 were extracted from the US PINC AI Healthcare Database. Likelihood of 30-day readmission was compared among remdesivir-treated and nonremdesivir-treated patients using multivariable logistic regression models adjusted for age, corticosteroid treatment, Charlson comorbidity index and intensive care unit stay during the COVID-19 hospitalization. Analyses were stratified by maximum supplemental oxygen requirement and variant time period (pre-Delta, Delta and Omicron). Results: Of the 440,601 patients discharged alive after a COVID-19 hospitalization, 248,785 (56.5%) patients received remdesivir. Overall, remdesivir patients had a 30-day COVID-19-related readmission rate of 3.0% and all-cause readmission rate of 6.3% compared with 5.4% and 9.1%, respectively, for patients who did not receive remdesivir during their COVID-19 hospitalization. After adjusting for demographics and clinical characteristics, remdesivir treatment was associated with significantly lower odds of 30-day COVID-19-related readmission (odds ratio 0.60 [95% confidence interval: 0.58-0.62]), and all-cause readmission (0.73 [0.72-0.75]). Significantly lower odds of 30-day readmission in remdesivir-treated patients was observed across all variant time periods. Conclusion: Treating patients hospitalized for COVID-19 with remdesivir is associated with a statistically significant reduction in 30-day COVID-19-related and all-cause readmission across variant time periods. These findings indicate that the clinical benefit of remdesivir may extend beyond the COVID-19 hospitalization.

Racial and Ethnic Disparities in COVID-19 Treatments in the United States.

INTRODUCTION: Racial and ethnic disparities in patient outcomes following COVID-19 exist, in part, due to factors involving healthcare delivery. The aim of the study was to characterize disparities in the administration of evidence-based COVID-19 treatments among patients hospitalized for COVID-19. METHODS: Using a large, US hospital database, initiation of COVID-19 treatments was compared among patients hospitalized for COVID-19 between May 2020 and April 2022 according to patient race and ethnicity. Multivariate logistic regression models were used to examine the effect of race and ethnicity on the likelihood of receiving COVID-19 treatments, stratified by baseline supplemental oxygen requirement. RESULTS: The identified population comprised 317,918 White, 76,715 Black, 9297 Asian, and 50,821 patients of other or unknown race. There were 329,940 non-Hispanic, 74,199 Hispanic, and 50,622 patients of unknown ethnicity. White patients were more likely to receive COVID-19 treatments, and specifically corticosteroids, compared to Black, Asian, and other patients (COVID-19 treatment: 87% vs. 81% vs. 85% vs. 84%, corticosteroids: 85% vs. 79% vs. 82% vs. 82%). After covariate adjustment, White patients were significantly more likely to receive COVID-19 treatments than Black patients across all levels of supplemental oxygen requirement. No clear trend in COVID-19 treatments according to ethnicity (Hispanic vs. non-Hispanic) was observed. CONCLUSION: There were important racial disparities in inpatient COVID-19 treatment initiation, including the undertreatment of Black patients and overtreatment of White patients. Our new findings reveal the actual magnitude of this issue in routine clinical practice to clinicians, policymakers, and guideline developers. This is crucial to ensuring equitable and appropriate access to evidence-based therapies.

Vaccine Effectiveness Against Influenza A-Associated Hospitalization, Organ Failure, and Death: United States, 2022-2023.

BACKGROUND: Influenza circulation during the 2022-2023 season in the United States largely returned to pre-coronavirus disease 2019 (COVID-19)-pandemic patterns and levels. Influenza A(H3N2) viruses were detected most frequently this season, predominately clade 3C.2a1b.2a, a close antigenic match to the vaccine strain. METHODS: To understand effectiveness of the 2022-2023 influenza vaccine against influenza-associated hospitalization, organ failure, and death, a multicenter sentinel surveillance network in the United States prospectively enrolled adults hospitalized with acute respiratory illness between 1 October 2022, and 28 February 2023. Using the test-negative design, vaccine effectiveness (VE) estimates against influenza-associated hospitalization, organ failures, and death were measured by comparing the odds of current-season influenza vaccination in influenza-positive case-patients and influenza-negative, SARS-CoV-2-negative control-patients. RESULTS: A total of 3707 patients, including 714 influenza cases (33% vaccinated) and 2993 influenza- and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-negative controls (49% vaccinated) were analyzed. VE against influenza-associated hospitalization was 37% (95% confidence interval [CI]: 27%-46%) and varied by age (18-64 years: 47% [30%-60%]; ≥65 years: 28% [10%-43%]), and virus (A[H3N2]: 29% [6%-46%], A[H1N1]: 47% [23%-64%]). VE against more severe influenza-associated outcomes included: 41% (29%-50%) against influenza with hypoxemia treated with supplemental oxygen; 65% (56%-72%) against influenza with respiratory, cardiovascular, or renal failure treated with organ support; and 66% (40%-81%) against influenza with respiratory failure treated with invasive mechanical ventilation. CONCLUSIONS: During an early 2022-2023 influenza season with a well-matched influenza vaccine, vaccination was associated with reduced risk of influenza-associated hospitalization and organ failure.

Patisiran Treatment in Patients with Transthyretin Cardiac Amyloidosis.

BACKGROUND: Transthyretin amyloidosis, also called ATTR amyloidosis, is associated with accumulation of ATTR amyloid deposits in the heart and commonly manifests as progressive cardiomyopathy. Patisiran, an RNA interference therapeutic agent, inhibits the production of hepatic transthyretin. METHODS: In this phase 3, double-blind, randomized trial, we assigned patients with hereditary, also known as variant, or wild-type ATTR cardiac amyloidosis, in a 1:1 ratio, to receive patisiran (0.3 mg per kilogram of body weight) or placebo once every 3 weeks for 12 months. A hierarchical procedure was used to test the primary and three secondary end points. The primary end point was the change from baseline in the distance covered on the 6-minute walk test at 12 months. The first secondary end point was the change from baseline to month 12 in the Kansas City Cardiomyopathy Questionnaire-Overall Summary (KCCQ-OS) score (with higher scores indicating better health status). The second secondary end point was a composite of death from any cause, cardiovascular events, and change from baseline in the 6-minute walk test distance over 12 months. The third secondary end point was a composite of death from any cause, hospitalizations for any cause, and urgent heart failure visits over 12 months. RESULTS: A total of 360 patients were randomly assigned to receive patisiran (181 patients) or placebo (179 patients). At month 12, the decline in the 6-minute walk distance was lower in the patisiran group than in the placebo group (Hodges-Lehmann estimate of median difference, 14.69 m; 95% confidence interval [CI], 0.69 to 28.69; P = 0.02); the KCCQ-OS score increased in the patisiran group and declined in the placebo group (least-squares mean difference, 3.7 points; 95% CI, 0.2 to 7.2; P = 0.04). Significant benefits were not observed for the second secondary end point. Infusion-related reactions, arthralgia, and muscle spasms occurred more often among patients in the patisiran group than among those in the placebo group. CONCLUSIONS: In this trial, administration of patisiran over a period of 12 months resulted in preserved functional capacity in patients with ATTR cardiac amyloidosis. (Funded by Alnylam Pharmaceuticals; APOLLO-B ClinicalTrials.gov number, NCT03997383.).

Remdesivir Is Associated With Reduced Mortality in COVID-19 Patients Requiring Supplemental Oxygen Including Invasive Mechanical Ventilation Across SARS-CoV-2 Variants.

Background: This comparative effectiveness study investigated the effect of remdesivir on in-hospital mortality among patients hospitalized for coronavirus disease 2019 (COVID-19) requiring supplemental oxygen including low-flow oxygen (LFO), high-flow oxygen/noninvasive ventilation (HFO/NIV), or invasive mechanical ventilation/extracorporeal membrane oxygenation (IMV/ECMO) across variant of concern (VOC) periods. Methods: Patients hospitalized for COVID-19 between December 2020 and April 2022 and administered remdesivir upon admission were 1:1 propensity score matched to patients not administered remdesivir during their COVID-19 hospitalization. Analyses were stratified by supplemental oxygen requirement upon admission and VOC period. Cox proportional hazards models were used to derive adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for 14- and 28-day mortality. Results: Patients treated with remdesivir (67 582 LFO, 34 857 HFO/NIV, and 4164 IMV/ECMO) were matched to non-remdesivir patients. Unadjusted mortality rates were significantly lower for remdesivir-treated patients at 14 days (LFO: 6.4% vs. 8.8%; HFO/NIV: 16.8% vs. 19.4%; IMV/ECMO: 27.8% vs. 35.3%) and 28 days (LFO: 9.8% vs. 12.3%; HFO/NIV: 25.8% vs. 28.3%; IMV/ECMO: 41.4% vs. 50.6%). After adjustment, remdesivir treatment was associated with a statistically significant reduction in in-hospital mortality at 14 days (LFO: aHR, 0.72; 95% CI, 0.66-0.79; HFO/NIV: aHR, 0.83; 95% CI, 0.77-0.89; IMV/ECMO: aHR, 0.73; 95% CI, 0.65-0.82) and 28 days (LFO: aHR, 0.79; 95% CI, 0.73-0.85; HFO/NIV: aHR, 0.88; 95% CI, 0.82-0.93; IMV/ECMO: aHR, 0.74; 95% CI, 0.67-0.82) compared with non-remdesivir treatment. Lower risk of mortality among remdesivir-treated patients was observed across VOC periods. Conclusions: Remdesivir treatment is associated with significantly reduced mortality among patients hospitalized for COVID-19 requiring supplemental oxygen upon admission, including those requiring HFO/NIV or IMV/ECMO with severe or critical disease, across VOC periods.

Associations of Mental Health and Experience of the COVID-19 Pandemic with United States Adults' Intentions to Be Vaccinated.

COVID-19 vaccine uptake in the United States has proved challenging. A deeper characterization extending beyond demographics and political ideologies of those hesitating or resisting is needed to guide ongoing conversations. This study examined associations between US adults' vaccination intentions and mental health history, experience of the COVID-19 pandemic, and mental health outcomes. An online population-based cross-sectional survey was administered nationwide during January 4-7, 2021. Participants were questioned about past and current mental health, and completed the Patient Health Questionnaire 8 (PHQ-8), Generalized Anxiety Disorder 7-item (GAD-7), and Posttraumatic Diagnostic Scale (PDS)-5 (to capture symptoms of depression, anxiety, and traumatic stress, respectively). Experience of the pandemic included cumulative county-level COVID case and death rates, self-reported COVID-19 testing/exposure/diagnosis, and self-reported impact on routines, resources, and relationships. Of 936 respondents, 66% intended to be vaccinated, 14.7% responded "maybe," and 19.6% "no." Past diagnosis of obsessive compulsive disorder, less impact on routines or social supports, not having been screened or tested for COVID-19, not knowing someone who tested positive, and not self-isolating were associated with less intention to vaccinate. After controlling for demographic and pandemic experience factors, symptoms of traumatic stress, but not other mental health outcomes, were associated with less intention to vaccinate. The apparent contradiction between less negative impact of the pandemic and symptoms of traumatic stress being associated with less intention to be vaccinated indicates the complex nature of barriers to vaccine uptake. Results from this study contribute to the evidence base needed to improve ongoing and future communications about, and strategies to increase uptake of, vaccination.

Remdesivir Reduced Mortality in Immunocompromised Patients Hospitalized for COVID-19 Across Variant Waves: Findings From Routine Clinical Practice.

BACKGROUND: Immunocompromised patients are at high risk of severe coronavirus disease 2019 (COVID-19) and death, yet treatment strategies for immunocompromised patients hospitalized for COVID-19 reflect variations in clinical practice. In this comparative effectiveness study, we investigated the effect of remdesivir treatment on inpatient mortality among immunocompromised patients hospitalized for COVID-19 across all variants of concern (VOC) periods. METHODS: Data for immunocompromised patients hospitalized for COVID-19 between December 2020 and April 2022 were extracted from the US PINC AITM Healthcare Database. Patients who received remdesivir within 2 days of hospitalization were matched 1:1 using propensity score matching to patients who did not receive remdesivir. Additional matching criteria included admission month, age group, and hospital. Cox proportional hazards models were used to examine the effect of remdesivir on risk of 14- and 28-day mortality during VOC periods. RESULTS: A total of 19 184 remdesivir patients were matched to 11 213 non-remdesivir patients. Overall, 11.1% and 17.7% of remdesivir patients died within 14 and 28 days, respectively, compared with 15.4% and 22.4% of non-remdesivir patients. Remdesivir was associated with a reduction in mortality at 14 (hazard ratio [HR], 0.70; 95% confidence interval, .62-.78) and 28 days (HR, 0.75; 95% CI, .68-.83). The survival benefit remained significant during the pre-Delta, Delta, and Omicron periods. CONCLUSIONS: Prompt initiation of remdesivir in immunocompromised patients hospitalized for COVID-19 is associated with significant survival benefit across all variant waves. These findings provide much-needed evidence relating to the effectiveness of a foundational treatment for hospitalized COVID-19 patients among a high-risk population.

Remdesivir for Hospitalized COVID-19 Patients in the United States: Optimization of Health Care Resources.

INTRODUCTION: In addition to significant morbidity and mortality, the coronavirus disease (COVID-19) has strained health care systems globally. This study investigated the cost-effectiveness of remdesivir + standard of care (SOC) for hospitalized COVID-19 patients in the USA. METHODS: This cost-effectiveness analysis considered direct and indirect costs of remdesivir + SOC versus SOC alone among hospitalized COVID-19 patients in the US. Patients entered the model stratified according to their baseline ordinal score. At day 15, patients could transition to another health state, and on day 29, they were assumed to have either died or been discharged. Patients were then followed over a 1-year time horizon, where they could transition to death or be rehospitalized. RESULTS: Treatment with remdesivir + SOC avoided, per patient, a total of 4 hospitalization days: two general ward days and a day for both the intensive care unit and the intensive care unit plus invasive mechanical ventilation compared to SOC alone. Treatment with remdesivir + SOC presented net cost savings due to lower hospitalization and lost productivity costs compared to SOC alone. In increased and decreased hospital capacity scenarios, remdesivir + SOC resulted in more beds and ventilators being available versus SOC alone. CONCLUSIONS: Remdesivir + SOC alone represents a cost-effective treatment for hospitalized patients with COVID-19. This analysis can aid in future decisions on the allocation of healthcare resources.

Consistent Effects of Early Remdesivir on Symptoms and Disease Progression Across At-Risk Outpatient Subgroups: Treatment Effect Heterogeneity in PINETREE Study.

INTRODUCTION: In the PINETREE study, early remdesivir treatment reduced risk of coronavirus disease 2019 (COVID-19)-related hospitalizations or all-cause death versus placebo by 87% by day 28 in high-risk, non-hospitalized patients. Here we report results of assessment of heterogeneity of treatment effect (HTE) of early outpatient remdesivir, focusing on time from symptom onset and number of baseline risk factors (RFs). METHODS: PINETREE was a double-blind, placebo-controlled trial of non-hospitalized patients with COVID-19 who were randomized within 7 days of symptom onset and had ≥ 1 RF for disease progression (age ≥ 60 years, obesity [body mass index ≥ 30], or certain coexisting medical conditions). Patients received remdesivir intravenously (200 mg on day 1 and 100 mg on days 2 and 3) or placebo. RESULTS: In this subgroup analysis, HTE of remdesivir by time from symptom onset at treatment initiation and number of baseline RFs was not detected. Treatment with remdesivir reduced COVID-19-related hospitalizations independent of stratification by time from symptom onset to randomization. Of patients enrolled ≤ 5 days from symptom onset, 1/201 (0.5%) receiving remdesivir and 9/194 (4.6%) receiving placebo were hospitalized (hazard ratio [HR] 0.10; 95% confidence interval [CI] 0.01-0.82). Of those enrolled at > 5 days from symptom onset, 1/78 (1.3%) receiving remdesivir and 6/89 (6.7%) receiving placebo were hospitalized (HR 0.19; 95% CI 0.02-1.61). Remdesivir was also effective in reducing COVID-19-related hospitalizations when stratified by number of baseline RFs for severe disease. Of patients with ≤ 2 RFs, 0/159 (0.0%) receiving remdesivir and 4/164 (2.4%) receiving placebo were hospitalized; of those with ≥ 3 RFs, 2/120 (1.7%) receiving remdesivir and 11/119 (9.2%) receiving placebo were hospitalized (HR 0.16; 95% CI 0.04-0.73). CONCLUSIONS: In the outpatient setting, benefit of remdesivir initiated within 7 days of symptoms appeared to be consistent across patients with RFs. Therefore, it may be reasonable to broadly treat patients with remdesivir regardless of comorbidities. TRIAL REGISTRATION: ClinicalTrials.gov number NCT04501952.

Effects of cloth face masks on physical and cognitive performance during maximal exercise testing.

Wearing a cloth face mask has been shown to impair exercise performance; it is essential to understand the impact wearing a cloth face mask may have on cognitive performance. Participants completed two maximal cardiopulmonary exercise tests on a cycle ergometer (with and without a cloth face mask) with a concurrent cognitive task. Blood pressure, heart rate, oxygen saturation, perceived exertion, shortness of breath, accuracy, and reaction time were measured at rest, during each exercise stage, and following a 4-minute recovery period. The final sample included 35 adults (age = 26.1 ± 5.8 years; 12 female/23 male). Wearing a cloth face mask was associated with significant decreases in exercise duration (-2:00 ± 3:40 min, P = 0.003), peak measures of maximal oxygen uptake (-818.9 ± 473.3 mL/min, -19.0 ± 48 mL·min-1·kg-1, P < 0.001), respiratory exchange ratio (-0.04 ± 0.08, P = 0.005), minute ventilation (-36.9 ± 18 L/min), oxygen pulse (-3.9 ± 2.3, P < 0.001), heart rate (-7.9 ± 12.6 bpm, P < 0.001), oxygen saturation (-1.5 ± 2.8%, P = 0.004), and blood lactate (-1.7 ± 2.5 mmol/L, P < 0.001). While wearing a cloth face mask significantly impaired exercise performance during maximal exercise testing, cognitive performance was unaffected in this selected group of young, active adults.

Monoclonal Antibodies in Hospitalised Patients with COVID-19: The Role of SARS-COV-2 Serostatus in an Evolving Pandemic.

Appropriately selected neutralising monoclonal antibodies (nmAbs) are an effective treatment for patients with mild or moderate coronavirus disease 2019 (COVID-19) who are at high risk of progression to severe disease. In contrast, the efficacy of nmAbs in patients hospitalised with COVID-19 has been mixed, and clinical benefit has largely been restricted to seronegative patients [i.e. those lacking endogenous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies] in the trials with positive outcomes. This review summarises the major clinical trial data investigating nmAb treatment for hospitalised patients with COVID-19, and explores current definitions of seropositivity, what they mean in a late-pandemic context and discusses the current late-pandemic challenges associated with defining 'seroprotection' in a clinically meaningful way. We conclude that following widespread vaccination, increasing numbers of prior infections and emerging viral variants, seropositivity now reflects a range of immune coverage rather than a binary tool with which to aid decision-making on a clinically actionable timescale. Treatment decisions with nmAbs in a late-pandemic context would therefore likely best rely on information regarding clinical status, time since symptom onset, underlying patient condition(s) and the dominant circulating variant, should they be approved for future use in hospitalised patients with COVID-19.

A Randomized Trial of Mesenchymal Stromal Cells for Moderate to Severe Acute Respiratory Distress Syndrome from COVID-19.

Rationale: There are limited therapeutic options for patients with coronavirus disease (COVID-19)-related acute respiratory distress syndrome with inflammation-mediated lung injury. Mesenchymal stromal cells offer promise as immunomodulatory agents. Objectives: Evaluation of efficacy and safety of allogeneic mesenchymal cells in mechanically-ventilated patients with moderate or severe COVID-19-induced respiratory failure. Methods: Patients were randomized to two infusions of 2 million cells/kg or sham infusions, in addition to the standard of care. We hypothesized that cell therapy would be superior to sham control for the primary endpoint of 30-day mortality. The key secondary endpoint was ventilator-free survival within 60 days, accounting for deaths and withdrawals in a ranked analysis. Measurements and Main Results: At the third interim analysis, the data and safety monitoring board recommended that the trial halt enrollment as the prespecified mortality reduction from 40% to 23% was unlikely to be achieved (n = 222 out of planned 300). Thirty-day mortality was 37.5% (42/112) in cell recipients versus 42.7% (47/110) in control patients (relative risk [RR], 0.88; 95% confidence interval, 0.64-1.21; P = 0.43). There were no significant differences in days alive off ventilation within 60 days (median rank, 117.3 [interquartile range, 60.0-169.5] in cell patients and 102.0 [interquartile range, 54.0-162.5] in control subjects; higher is better). Resolution or improvement of acute respiratory distress syndrome at 30 days was observed in 51/104 (49.0%) cell recipients and 46/106 (43.4%) control patients (odds ratio, 1.36; 95% confidence interval, 0.57-3.21). There were no infusion-related toxicities and overall serious adverse events over 30 days were similar. Conclusions: Mesenchymal cells, while safe, did not improve 30-day survival or 60-day ventilator-free days in patients with moderate and/or severe COVID-19-related acute respiratory distress syndrome.

Intentions to receive COVID-19 vaccines in the united states: Sociodemographic factors and personal experiences with COVID-19.

OBJECTIVES: Information regarding vaccination and the association with individuals' characteristics, experiences, and information sources is important for crafting public health campaigns to maximize uptake. Our objective was to investigate factors associated with intentions for COVID-19 vaccination among a sample of U.S. adults using a population-based cross-sectional survey. METHOD: Data were collected via an online questionnaire administered nationwide from January 4, to January 7, 2021 following the emergency use authorization for two SARS-CoV-2 mRNA-based vaccines. RESULTS: Of 936 U.S. adult respondents, 66% stated an intention to be vaccinated once a COVID-19 vaccine was available to them; 14.7% responded "maybe" and 19.6% "no." Unadjusted and multivariate associations revealed "no/maybe" vaccination intentions were associated with younger age, female, Black race, lower income, history of not receiving the influenza vaccine, lower fear of COVID-19, suffering moderate to severe reduction in access to food/nutrition, and lower trust in health care authorities, personal health care providers, and/or traditional news media as sources of COVID-19 information. Of respondents "maybe" intending to be vaccinated, 65% reported "a lot" of trust in personal health care providers as sources of COVID-19 information. Respondents stating "no" intention to be vaccinated were skeptical of all COVID-19 information sources considered. CONCLUSIONS: Our findings confirm observations predating COVID-19 vaccine availability regarding sociodemographic characteristics associated with vaccine hesitancy in the United States. We further identify personal health care providers as the most trusted information source among people who "maybe" intend to get vaccinated and demonstrate the challenge in reaching people not intending to be vaccinated. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Association of Remdesivir Treatment With Mortality Among Hospitalized Adults With COVID-19 in the United States.

Importance: SARS-CoV-2, which causes COVID-19, poses considerable morbidity and mortality risks. Studies using data collected during routine clinical practice can supplement randomized clinical trials to provide needed evidence, especially during a global pandemic, and can yield markedly larger sample sizes to assess outcomes for important patient subgroups. Objective: To evaluate the association of remdesivir treatment with inpatient mortality among patients with COVID-19 outside of the clinical trial setting. Design, Setting, and Participants: A retrospective cohort study in US hospitals using health insurance claims data linked to hospital chargemaster data from December 1, 2018, to May 3, 2021, was conducted among 24 856 adults hospitalized between May 1, 2020, and May 3, 2021, with newly diagnosed COVID-19 who received remdesivir and 24 856 propensity score-matched control patients. Exposure: Remdesivir treatment. Main Outcomes and Measures: All-cause inpatient mortality within 28 days of the start of remdesivir treatment for the remdesivir-exposed group or the matched index date for the control group. Results: A total of 24 856 remdesivir-exposed patients (12 596 men [50.7%]; mean [SD] age, 66.8 [15.4] years) and 24 856 propensity score-matched control patients (12 621 men [50.8%]; mean [SD] age, 66.8 [15.4] years) were included in the study. Median follow-up was 6 days (IQR, 4-11 days) in the remdesivir group and 5 days (IQR, 2-10 days) in the control group. There were 3557 mortality events (14.3%) in the remdesivir group and 3775 mortality events (15.2%) in the control group. The 28-day mortality rate was 0.5 per person-month in the remdesivir group and 0.6 per person-month in the control group. Remdesivir treatment was associated with a statistically significant 17% reduction in inpatient mortality among patients hospitalized with COVID-19 compared with propensity score-matched control patients (hazard ratio, 0.83 [95% CI, 0.79-0.87]). Conclusions and Relevance: In this retrospective cohort study using health insurance claims and hospital chargemaster data, remdesivir treatment was associated with a significantly reduced inpatient mortality overall among patients hospitalized with COVID-19. Results of this analysis using data collected during routine clinical practice and state-of-the-art methods complement results from randomized clinical trials. Future areas of research include assessing the association of remdesivir treatment with inpatient mortality during the circulation of different variants and relative to time from symptom onset.

Multi-center matched cohort study of convalescent plasma for hospitalized patients with COVID-19.

BACKGROUND: Although frequently used in the early pandemic, data on the effectiveness of COVID-19 convalescent plasma (CCP) remain mixed. We investigated the effectiveness and safety of CCP in hospitalized COVID-19 patients in real-world practices during the first two waves of the pandemic in a multi-hospital healthcare system in Texas. METHODS AND FINDINGS: Among 11,322 hospitalized patients with confirmed COVID-19 infection from July 1, 2020 to April 15, 2021, we included patients who received CCP and matched them with those who did not receive CCP within ±2 days of the transfusion date across sites within strata of sex, age groups, days and use of dexamethasone from hospital admission to the match date, and oxygen requirements 4-12 hours prior to the match date. Cox proportional hazards model estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for effectiveness outcomes in a propensity score 1:1 matched cohort. Pre-defined safety outcomes were described. We included 1,245 patients each in the CCP treated and untreated groups. Oxygen support was required by 93% of patients at the baseline. The pre-defined primary effectiveness outcome of 28-day in-hospital all-cause mortality (HR = 0.85; 95%CI: 0.66,1.10) were similar between treatment groups. Sensitivity and stratified analyses found similar null results. CCP-treated patients were less likely to be discharged alive (HR = 0.82; 95%CI: 0.74, 0.91), and more likely to receive mechanical ventilation (HR = 1.48; 95%CI: 1.12, 1.96). Safety outcomes were rare and similar between treatment groups. CONCLUSION: The findings in this large, matched cohort of patients hospitalized with COVID-19 and mostly requiring oxygen support at the time of treatment, do not support a clinical benefit in 28-day in-hospital all-cause mortality for CCP. Future studies should assess the potential benefits with specifically high-titer units in perhaps certain subgroups of patients (e.g. those with early disease or immunocompromised).

Efficacy and Safety of Ensovibep for Adults Hospitalized With COVID-19 : A Randomized Controlled Trial.

BACKGROUND: Ensovibep (MP0420) is a designed ankyrin repeat protein, a novel class of engineered proteins, under investigation as a treatment of SARS-CoV-2 infection. OBJECTIVE: To investigate if ensovibep, in addition to remdesivir and other standard care, improves clinical outcomes among patients hospitalized with COVID-19 compared with standard care alone. DESIGN: Double-blind, randomized, placebo-controlled, clinical trial. (ClinicalTrials.gov: NCT04501978). SETTING: Multinational, multicenter trial. PARTICIPANTS: Adults hospitalized with COVID-19. INTERVENTION: Intravenous ensovibep, 600 mg, or placebo. MEASUREMENTS: Ensovibep was assessed for early futility on the basis of pulmonary ordinal scores at day 5. The primary outcome was time to sustained recovery through day 90, defined as 14 consecutive days at home or place of usual residence after hospital discharge. A composite safety outcome that included death, serious adverse events, end-organ disease, and serious infections was assessed through day 90. RESULTS: An independent data and safety monitoring board recommended that enrollment be halted for early futility after 485 patients were randomly assigned and received an infusion of ensovibep (n = 247) or placebo (n = 238). The odds ratio (OR) for a more favorable pulmonary outcome in the ensovibep (vs. placebo) group at day 5 was 0.93 (95% CI, 0.67 to 1.30; P = 0.68; OR > 1 would favor ensovibep). The 90-day cumulative incidence of sustained recovery was 82% for ensovibep and 80% for placebo (subhazard ratio [sHR], 1.06 [CI, 0.88 to 1.28]; sHR > 1 would favor ensovibep). The primary composite safety outcome at day 90 occurred in 78 ensovibep participants (32%) and 70 placebo participants (29%) (HR, 1.07 [CI, 0.77 to 1.47]; HR < 1 would favor ensovibep). LIMITATION: The trial was prematurely stopped because of futility, limiting power for the primary outcome. CONCLUSION: Compared with placebo, ensovibep did not improve clinical outcomes for hospitalized participants with COVID-19 receiving standard care, including remdesivir; no safety concerns were identified. PRIMARY FUNDING SOURCE: National Institutes of Health.