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 Treatment in Hospitalized Patients With Coronavirus Disease 2019 (COVID-19): A Comparative Analysis of In-hospital All-cause Mortality in a Large Multicenter Observational Cohort.

BACKGROUND: Remdesivir (RDV) improved clinical outcomes among hospitalized patients with coronavirus disease 2019 (COVID-19) in randomized trials, but data from clinical practice are limited. METHODS: We examined survival outcomes for US patients hospitalized with COVID-19 between August and November 2020 and treated with RDV within 2 days of hospitalization vs those not receiving RDV during their hospitalization using the Premier Healthcare Database. Preferential within-hospital propensity score matching with replacement was used. Additionally, patients were also matched on baseline oxygenation level (no supplemental oxygen charges [NSO], low-flow oxygen [LFO], high-flow oxygen/noninvasive ventilation [HFO/NIV], and invasive mechanical ventilation/extracorporeal membrane oxygenation [IMV/ECMO]) and 2-month admission window and excluded if discharged within 3 days of admission (to exclude anticipated discharges/transfers within 72 hours, consistent with the Adaptive COVID-19 Treatment Trial [ACTT-1] study). Cox proportional hazards models were used to assess time to 14-/28-day mortality overall and for patients on NSO, LFO, HFO/NIV, and IMV/ECMO. RESULTS: A total of 28855 RDV patients were matched to 16687 unique non-RDV patients. Overall, 10.6% and 15.4% RDV patients died within 14 and 28 days, respectively, compared with 15.4% and 19.1% non-RDV patients. Overall, RDV was associated with a reduction in mortality at 14 days (hazard ratio [95% confidence interval]: 0.76 [0.70-0.83]) and 28 days (0.89 [0.82-0.96]). This mortality benefit was also seen for NSO, LFO, and IMV/ECMO at 14 days (NSO: 0.69 [0.57-0.83], LFO: 0.68 [0.80-0.77], IMV/ECMO: 0.70 [0.58-0.84]) and 28 days (NSO: 0.80 [0.68-0.94], LFO: 0.77 [0.68-0.86], IMV/ECMO: 0.81 [0.69-0.94]). Additionally, HFO/NIV RDV group had a lower risk of mortality at 14 days (0.81 [0.70-0.93]) but no statistical significance at 28 days. CONCLUSIONS: RDV initiated upon hospital admission was associated with improved survival among patients with COVID-19. Our findings complement ACTT-1 and support RDV as a foundational treatment for hospitalized COVID-19 patients.

Practice patterns and incidence of adenovirus infection in allogeneic hematopoietic cell transplant recipients: Multicenter survey of transplant centers in the United States.

BACKGROUND: Adenovirus (AdV) is increasingly recognized as a threat to successful outcomes after allogeneic hematopoietic cell transplantation (allo-HCT). Guidelines have been developed to inform AdV screening and treatment practices, but the extent to which they are followed in clinical practice in the United States is still unknown. The incidence of AdV in the United States is also not well documented. The main objectives of the AdVance US study were thus to characterize current AdV screening and treatment practices in the United States and to estimate the incidence of AdV infection in allo-HCT recipients across multiple pediatric and adult transplant centers. METHODS: Fifteen pediatric centers and 6 adult centers completed a practice patterns survey, and 15 pediatric centers and four adult centers completed an incidence survey. RESULTS: The practice patterns survey results confirm that pediatric transplant centers are more likely than adult centers to routinely screen for AdV, and are also more likely to have a preemptive AdV treatment approach compared to adult centers. Perceived risk of AdV infection is a determining factor for whether routine screening and preemptive treatment are implemented. Most pediatric centers screen higher-risk patients for AdV weekly, in blood, and have a preemptive AdV treatment approach. The incidence survey results show that from 2015 to 2017, a total of 1230 patients underwent an allo-HCT at the 15 pediatric transplant centers, and 1815 patients underwent an allo-HCT at the 4 adult transplant centers. The incidences of AdV infection, AdV viremia, and AdV viremia ≥ 1000 copies/mL within 6 months after the first allo-HCT were 23%, 16%, and 9%, respectively, for patients at pediatric centers, and 5%, 3%, and 2%, respectively, for patients at adult centers. CONCLUSIONS: These findings provide a more recent estimate of the incidence of AdV infection in the United States, as well as a multicenter view of practice patterns around AdV infection screening and intervention criteria, in pediatric and adult allo-HCT recipients.

Incidence of Adenovirus Infection in Hematopoietic Stem Cell Transplantation Recipients: Findings from the AdVance Study.

Adenovirus (AdV) is an increasingly recognized threat to recipients of allogeneic hematopoietic stem cell transplantation (allo-HCT), particularly when infection is prolonged and unresolved. AdVance is the first multinational, multicenter study to evaluate the incidence of AdV infection in both pediatric and adult allo-HCT recipients across European transplantation centers. Medical records for patients undergoing first allo-HCT between January 2013 and September 2015 at 50 participating centers were reviewed. The cumulative incidence of AdV infection (in any sample using any assay) during the 6 months after allo-HCT was 32% (95% confidence interval [CI], 30.9% to 33.4%) among pediatric allo-HCT recipients (n = 1736) and 6% (95% CI, 4.7% to 6.4%) among adult allo-HCT recipients (n = 2540). The incidence of AdV viremia ≥1000copies/mL (a common threshold for initiation of preemptive treatment) was 14% (95% CI, 13.0% to 14.8%) in pediatric recipients and 1.5% (95% CI, 1.1% to 2.0%) in adult recipients. Baseline risk factors for developing AdV viremia ≥1000copies/mL included younger age, use of T cell depletion, and donor type other than matched related. Baseline demographic factors were broadly comparable across patients of all ages and identified by multivariate analyses. Notably, the incidence of AdV infection decreased stepwise with increasing age; younger adults (age 18 to 34 years) had a similar incidence as older pediatric patients (<18 years). This study provides a contemporary multicenter understanding of the incidence and risk factors for AdV infection following allo-HCT. Our findings may help optimize infection screening and intervention criteria, particularly for younger at-risk adults.

Current practices in the management of adenovirus infection in allogeneic hematopoietic stem cell transplant recipients in Europe: The AdVance study.

OBJECTIVE: Adenovirus (AdV) infections are potentially life-threatening for allogeneic hematopoietic stem cell transplant (allo-HCT) recipients. The AdVance study aimed to evaluate the incidence, management, and outcomes of AdV infections in European allo-HCT recipients. METHODS: As part of the study, physician surveys were conducted to determine current AdV screening and treatment practices at their center. RESULTS: All of the 28 respondents who treat pediatric patients reported routine AdV screening practices, with 93% screening all allo-HCT recipients and others screening those with transplant-related risk factors. Nearly all centers take a pre-emptive approach to AdV treatment in both high- (89%) and low-risk patients (75%). Among the 14 respondents who treat adult patients, 5 (36%) reported routine screening practices and few (21%) screen all allo-HCT recipients unless risk factors are present. In adults, pre-emptive AdV treatment is uncommon and quantitative AdV thresholds are rare. Typical treatment for all patients with symptomatic AdV infection is off-label intravenous cidofovir. CONCLUSIONS: Our findings confirm that screening for AdV is more common in pediatric patients. Antiviral treatment is employed in both pediatric and adult patients, although adults are generally treated when AdV disease is diagnosed. The approach to AdV screening and treatment is risk-based and consistent with clinical guidelines.

Estimation of potential cost savings associated with reduced rates of cardiovascular hospitalization among atrial fibrillation/flutter patients treated with dronedarone in the ATHENA trial.

The aim of this study was to estimate, from a US payer perspective, potential cost savings resulting from the reduction in cardiovascular (CV) hospitalizations obtained with dronedarone in the ATHENA (A Placebo-Controlled, Double-Blind, Parallel Arm Trial to Assess the Efficacy of Dronedarone 400 mg bid for the Prevention of Cardiovascular Hospitalization or Death from any Cause in PatiENts with Atrial Fibrillation/Atrial Flutter) trial. ATHENA randomized atrial fibrillation/flutter patients to dronedarone (n=2301) or placebo (n=2327) plus standard care. Dronedarone significantly reduced first CV hospitalization/all-cause mortality over 12-30 months of follow-up. CV hospitalization costs (2008 values) from a US cohort of ATHENA-like atrial fibrillation/flutter patients with Medicare supplemental insurance (n=10,200) and diagnosis-related group costs of adverse event-related hospitalizations were applied to hospitalizations occurring in ATHENA. The impact of cost variation was assessed using Monte Carlo simulation. In ATHENA, dronedarone reduced the overall CV hospitalization rate (vs. placebo) by 29% over the first 12 months (33.36 vs. 47.19 events per 100 patients) and by 25% over the full study (51.15 vs. 68.55 events per 100 patients). Adverse event-related hospitalization rates (dronedarone vs. placebo) were low (0.48 vs. 0.21 and 0.56 vs. 0.26 events per 100 patients over 12 months and the full study, respectively). Overall hospitalization cost savings were estimated at $1329 and $1763 per patient over 12 months and the full study, respectively. Cost savings were relatively stable [mean (95% confidence interval): $1330 ($994-$1676) for the first 12 months and $1763 ($1369-$2184) for the full study] over 10,000 cycles of random variation.

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.

Remdesivir is Associated with Reduced Mortality in Patients Hospitalized for COVID-19 Not Requiring Supplemental Oxygen.

Background: Remdesivir has demonstrated benefit in some hospitalized patients with coronavirus disease 2019 (COVID-19) on supplemental oxygen and in nonhospitalized patients breathing room air. The durability of this benefit across time periods with different circulating severe acute respiratory syndrome coronavirus 2 variants of concern (VOC) is unknown. This comparative effectiveness study in patients hospitalized for COVID-19 and not receiving supplemental oxygen at admission compared those starting remdesivir treatment in the first 2 days of admission with those receiving no remdesivir during their hospitalization across different VOC periods. Method: Using a large, multicenter US hospital database, in-hospital mortality rates were compared among patients hospitalized for COVID-19 but not requiring supplemental oxygen at admission between December 2020 and April 2022. Patients receiving remdesivir at hospital admission were matched 1:1 to those not receiving remdesivir during hospitalization, using propensity score matching. Cox proportional hazards models were used to assess 14- and 28-day in-hospital mortality rates or discharge to hospice. Results: Among the 121 336 eligible patients, 58 188 remdesivir-treated patients were matched to 17 574 unique patients not receiving remdesivir. Overall, 5.4% of remdesivir-treated and 7.3% in the non-remdesivir group died within 14 days, and 8.0% and 9.8%, respectively, died within 28 days. Remdesivir treatment was associated with a statistically significant reduction in the in-hospital mortality rate compared with non-remdesivir treatment (14-day and 28-day adjusted hazard ratios [95% confidence interval], 0.75 [0.68-0.83] and 0.83 [0.76-0.90], respectively). This significant mortality benefit endured across the different VOC periods. Conclusions: Remdesivir initiation in patients hospitalized for COVID-19 and not requiring supplemental oxygen at admission was associated with a significantly reduced in-hospital mortality rate. These findings highlight a potential survival benefit when clinicians initiated remdesivir on admission across the dominant variant eras of the evolving pandemic.

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.

Clinical outcomes by supplemental oxygen use in remdesivir-treated, hospitalised adults with COVID-19.

BACKGROUND: Clinical trials show different effects of remdesivir on clinical outcomes relative to COVID-19 severity at hospital admission; in Europe, there are few real-world data. METHODS: A multicentre, multinational retrospective cohort study in adult patients hospitalised with PCR-confirmed COVID-19 was conducted to understand remdesivir clinical use in different countries and to describe outcomes for patients receiving remdesivir stratified by oxygen use. Primary endpoints were all-cause mortality at day 28 and hospitalisation duration. Patients were categorised by baseline disease severity: no supplemental oxygen (NSO); low flow oxygen ≤ 6 litres (l)/minute (LFO); high flow oxygen > 6 l/minute (HFO). RESULTS: Four hundred and forty-eight (448) patients (72 [16.1%] HFO; 295 [65.8%] LFO; 81 (18.1%] NSO) were included; median age was 65 years and 64% were male. Mortality was higher in patients on HFO (rate 23.6%) compared to LFO (10.2%; p = 0.001) or NSO (6.2%; p = 0.002). Duration of hospitalisation was longer in patients on HFO (13 days) compared to LFO (9 days; p = 0.003) and NSO (9 days; p = 0.021). Patients who initiated remdesivir ≥ 2 days compared to within a day of hospitalisation had a 4.2 times higher risk of death, irrespective of age, sex, comorbidities, and oxygen support at baseline. Requirement for mechanical ventilation/ECMO and readmission within 28 days of discharge was similar across groups. Remdesivir use and outcomes differed by country. CONCLUSIONS: A higher mortality rate and duration of hospitalisation was seen in remdesivir-treated COVID-19 patients on HFO compared to LFO and NSO. Initiation of remdesivir upon admission as opposed to delayed initiation has a mortality benefit. CLINICAL TRIALS REGISTRATION: NCT04847622.

Economic impact of applying the AASLD-IDSA simplified treatment algorithm on the real-world management of hepatitis C.

BACKGROUND: The American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) recommended in May 2019 that patients with hepatitis C virus (HCV) could be assessed for treatment initiation with a simplified treatment algorithm. This approach uses standard blood and fibrosis tests, rather than genotype testing, to guide the initiation of pan-genotypic direct-acting antiviral agents (DAAs) sofosbuvir/velpatasvir (SOF/VEL) or glecaprevir/pibrentasvir (GLE/PIB) treatment. OBJECTIVE: To compare health care resource utilization (HCRU) and costs for patients who initiated treatment via the simplified vs nonsimplified algorithm (genotype testing). METHODS: We identified adults with commercial and Medicare Advantage coverage who were diagnosed with HCV who initiated SOF/VEL or GLE/PIB from July 1, 2016, through August 31, 2019, in a nationally representative US administrative claims database. The index date was defined as the first pharmacy SOF/VEL or GLE/PIB fill date. Continuous enrollment 12 months before and ≥6 months after index date was required. Patients with claims for hepatitis B, HIV, decompensated liver, or prior DAAs were excluded. Patients were propensity score-matched (1:1) and grouped as "simplified" or "nonsimplified." HCV-related HCRU and costs were compared for the post-matched groups. RESULTS: 3,539 HCV patients were included, and 16.6% initiated SOF/VEL or GLE/PIB via the simplified algorithm. Pre-matched treatments were SOF/VEL (52.8%) and GLE/PIB (47.2%). More than half (55.7%) of SOF/VEL and 44.3% of GLE/PIB patients started treatment via the simplified algorithm. HCV patients initiating via the simplified algorithm were more likely to be male (65.1% vs 60.6%; P = 0.041), commercially insured (53.3% vs 46.5%; P = 0.003), and in the Midwest (25.7% vs 19.3%; P < 0.001) vs nonsimplified patients. The nonsimplified group had more liver disease (52.1% vs 46.9%; P = 0.019), metabolic disorders (45.8% vs 39.2%; P = 0.003), and dyslipidemia (39.9% vs 35.4%; P = 0.041) vs the simplified group. Of the index prescriptions, 58.9% were written by gastroenterology or infectious disease specialists, and 68.1% (simplified) vs 75.4% (nonsimplified) had a specialist visit within 90 days prior to index DAA fill (P < 0.001). Matching resulted in 584 well-matched patients in each group. At post-match baseline, the simplified treatment group had significantly lower median (interquartile range [IQR]) HCV-related medical health care costs vs the matched nonsimplified group: $373 ($201-$684) vs $727 ($456-$1,185; P < 0.001). Median noninpatient/emergency department health plan-paid costs were also significantly lower in the simplified cohort ($257 vs $504; P < 0.001). During follow-up, medical HCV-related health care costs were similar across the groups. CONCLUSIONS: This study compared economic outcomes of HCV treatment initiation via the simplified and nonsimplified algorithms. The simplified approach resulted in lower use of health care resources, greater cost savings, and greater ability of patients to access care from both specialist and nonspecialist providers. While additional studies are needed, these early findings suggest a feasible path for simplified HCV treatment in real-world managed care settings. DISCLOSURES: Funding support for this study was provided by Gilead Sciences, Inc. Majethia, Lee, Mozaffari, Wolf, and Hsiao are employees of Gilead Sciences, Inc. Bunner and Chastek are employees of Optum Life Sciences, which received funding from Gilead Sciences, Inc. to conduct this study. Bunner owns stock in UnitedHealth group, parent company of Optum. A poster based on selected data from this study was presented at the AMCP 2021 Virtual Meeting, April 12-16, 2021.

Clinical Management of Hospitalized Coronavirus Disease 2019 Patients in the United States.

BACKGROUND: The objective of this study was to characterize hospitalized coronavirus disease 2019 (COVID-19) patients and describe their real-world treatment patterns and outcomes over time. METHODS: Adult patients hospitalized on May 1, 2020-December 31, 2020 with a discharge diagnosis of COVID-19 were identified from the Premier Healthcare Database. Patient and hospital characteristics, treatments, baseline severity based on oxygen support, length of stay (LOS), intensive care unit (ICU) utilization, and mortality were examined. RESULTS: The study included 295657 patients (847 hospitals), with median age of 66 (interquartile range, 54-77) years. Among each set of demographic comparators, the majority were male, white, and over 65. Approximately 85% had no supplemental oxygen charges (NSOc) or low-flow oxygen (LFO) at baseline, whereas 75% received no more than NSOc or LFO as maximal oxygen support at any time during hospitalization. Remdesivir (RDV) and corticosteroid treatment utilization increased over time. By December, 50% were receiving RDV and 80% were receiving corticosteroids. A higher proportion initiated COVID-19 treatments within 2 days of hospitalization in December versus May (RDV, 87% vs 40%; corticosteroids, 93% vs 62%; convalescent plasma, 68% vs 26%). There was a shift toward initiating RDV in patients on NSOc or LFO (68.0% [May] vs 83.1% [December]). Median LOS decreased over time. Overall mortality was 13.5% and it was highest for severe patients (invasive mechanical ventilation/extracorporeal membrane oxygenation [IMV/ECMO], 53.7%; high-flow oxygen/noninvasive ventilation [HFO/NIV], 32.2%; LFO, 11.7%; NSOc, 7.3%). The ICU use decreased, whereas mortality decreased for NSOc and LFO. CONCLUSIONS: Clinical management of COVID-19 is rapidly evolving. This large observational study found that use of evidence-based treatments increased from May to December 2020, whereas improvement in outcomes occurred over this time-period.

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.

Association between adenovirus viral load and mortality in pediatric allo-HCT recipients: the multinational AdVance study.

This multivariable analysis from the AdVance multicenter observational study assessed adenovirus (AdV) viremia peak, duration, and overall AdV viral burden-measured as time-averaged area under the viremia curve over 16 weeks (AAUC0-16)-as predictors of all-cause mortality in pediatric allo-HCT recipients with AdV viremia. In the 6 months following allo-HCT, 241 patients had AdV viremia ≥ 1000 copies/ml. Among these, 18% (43/241) died within 6 months of first AdV ≥ 1000 copies/ml. Measures of AdV viral peak, duration, and overall burden of infection consistently correlate with all-cause mortality. In multivariable analyses, controlling for lymphocyte recovery, patients with AdV AAUC0-16 in the highest quartile had a hazard ratio of 11.1 versus the lowest quartile (confidence interval 5.3-23.6); for peak AdV viremia, the hazard ratio was 2.2 for the highest versus lowest quartile. Both the peak level and duration of AdV viremia were correlated with short-term mortality, independent of other known risk factors for AdV-related mortality, such as lymphocyte recovery. AdV AAUC0-16, which assesses both peak and duration of AdV viremia, is highly correlated with mortality under the current standard of care. New therapeutic agents that decrease AdV AAUC0-16 have the potential of reducing mortality in this at-risk patient population.

Glaucoma management among individuals enrolled in a single comprehensive insurance plan.

OBJECTIVE: To determine the management patterns for glaucoma and suspect glaucoma in a nationally representative sample of newly treated persons. DESIGN: Retrospective cohort study of persons enrolled in a large managed care organization. PARTICIPANTS: One thousand seven hundred twelve diagnosed suspects and 3623 diagnosed glaucoma patients. METHODS: Linked pharmacy and patient care data were used to examine the glaucoma management and treatment patterns in this cohort of persons insured by a single managed care organization. Rates of monitoring and treatment were calculated for the 3 study groups. MAIN OUTCOME MEASURES: Probability of monitoring (return visits, visual fields [VFs], and optic nerve head imaging or photography) and treatment (argon laser trabeculoplasty [ALT] and surgery) for newly treated persons with suspect and glaucoma diagnoses. RESULTS: After a median follow-up of 440 days, 83% of treated diagnosed suspects had had a billed follow-up office visit to either an optometrist or an ophthalmologist at any time during follow-up, 46% had had at least one billed VF, and 13% had had some form of optic nerve head imaging. Rates were slightly higher for those with diagnosed glaucoma (P>0.05). Surgery and ALT were performed rarely in this treated population (1%-6% at 2 years). CONCLUSIONS: This study suggests that a large proportion of individuals felt to require treatment for glaucoma or suspect glaucoma are falling out of care and are being monitored at rates lower than expected from recommendations of published guidelines. More research is needed to confirm these findings and to determine the reasons for loss to follow-up and low monitoring rates.

Variations in treatment among adult-onset open-angle glaucoma patients.

OBJECTIVE: To determine the predictors of treatment for glaucoma and suspect glaucoma in a nationally representative sample of diagnosed persons. DESIGN: Retrospective cohort study of persons enrolled in a large managed care organization. PARTICIPANTS: Thirty-five thousand seven hundred fifty-four diagnosed suspects, 5265 diagnosed glaucoma persons, and 2633 individuals coded as having cupping of the optic disc. METHODS: Linked pharmacy and patient care information were used to examine the predictors of initiating glaucoma treatment in this cohort of persons insured by a single managed care organization. Predictors entered into logistic regression models included diagnostic group (suspect vs. diagnosed), age group, gender, region of the country, provider type at the initial visit (optometrist or ophthalmologist), diagnosis index date divided into 2 periods (1995-1998 and 1999-2001), and health plan enrollment duration after the initial diagnosis. MAIN OUTCOME MEASURES: Occurrence of and factors associated with treatment for glaucoma (argon laser trabeculoplasty [ALT], surgery, or topical ocular hypotensives). RESULTS: A logistic regression model adjusting for glaucoma status, age, region, clinician seen at initial visit, and index date found that women were less likely to undergo treatment (topical ocular hypotensives, ALT, or surgery) than men (odds ratio, 0.76; 95% confidence interval, 0.71-0.80). Factors other than gender that were associated with greater likelihood of treatment were glaucoma diagnosis, older age, region, and longer follow-up. CONCLUSIONS: We have documented wide variation in treatment among individuals diagnosed as having glaucoma or as glaucoma suspects. Women were 24% less likely to be treated than men, and younger individuals were far less likely to be treated than older ones. Furthermore, treatment varied by region of the country. Understanding the sources of these variations will help in determining how to arrive at better management strategies for individuals with glaucoma and suspect glaucoma.

Persistence and adherence with topical glaucoma therapy.

PURPOSE: The present study describes the patterns and predictors of treatment persistence and adherence among patients who are diagnosed with glaucoma or as glaucoma suspects (based on claims codes). DESIGN: A retrospective cohort study using health insurance claims data. METHODS: Newly treated individuals with diagnosed glaucoma (n = 3623) and suspect glaucoma (n = 1677) were obtained from healthcare claims data in the Ingenix Research Database. For each of these two diagnostic groups, we calculated the duration of continuous treatment with the initially prescribed medication (persistence) and the prevalence of use of the initial medication at various time points (adherence). Four drug classes were included: beta-blockers, alpha-agonists, carbonic anhydrase inhibitors, and prostaglandin analogs. RESULTS: Nearly one half of the individuals who had filled a glaucoma prescription discontinued all topical ocular hypotensive therapy within six months, and just 37% of these individuals recently had refilled their initial medication at three years after the first dispensing. Prostaglandins were associated with better persistence than any other drug class, which was indicated by hazard ratios for discontinuation of prostaglandins compared with beta-blockers of 0.40 (95% confidence interval, 0.35-0.44) for diagnosed patients and 0.44 (95% confidence interval, 0.37-0.52) for patients with suspect glaucoma. Prostaglandins showed a similar advantage in adherence. Furthermore, patients with diagnosed glaucoma were more likely to adhere to therapy than patients with suspect glaucoma (relative risk = 1.11; 95% confidence interval, 1.05-1.18). CONCLUSION: Persistence and adherence were substantially better with prostaglandins than with other drug classes, and patients with diagnosed open-angle glaucoma were more likely to adhere to treatment than suspected glaucoma.

Management of hypertension and hypercholesterolaemia in primary care in The Netherlands.

OBJECTIVE: Screening, treatment and monitoring guidelines for hypertension and hypercholesterolaemia have been developed to assist physicians in providing evidence-based health care. We conducted a retrospective study to assess the management of patients with these single or combined conditions. RESEARCH DESIGN AND METHODS: This was a retrospective cohort study conducted using data from the Integrated Primary Care Information (IPCI) project based in The Netherlands. Management of hypertension and hypercholesterolaemia was assessed from 2000-2003 by measuring the numbers of patients screened for these conditions, treated pharmacologically and monitored for treatment success. RESULTS: Approximately 11%, 3% and 10% of participants were eligible for screening for hypertension alone, hypercholesterolaemia alone and both conditions, respectively. Blood pressure screening was high in patients eligible for both blood pressure and cholesterol screening (> 86%), whereas cholesterol screening was low (< 56%). Among patients newly identified with hypertension or hypercholesterolaemia who were eligible for pharmacotherapy, 29% and 43% respectively were not treated within one year of diagnosis. Undertreatment was significantly lower in patients with both conditions (24% and 37% for antihypertensive and lipid-lowering treatment, respectively and 28% were not treated for both). Among newly treated patients, in the first year of treatment there was no record of a blood pressure or cholesterol assessment, for 35% and 72%, respectively. CONCLUSION: Management was sub-optimal in patients with hypertension or hypercholesterolaemia as well as in those with both of these conditions. The results of this study are likely to be widely applicable, particularly to other European and industrialised countries that have similar free-access health care systems to The Netherlands.