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Background: There is limited information on effectiveness of COVID-19 therapies in immunocompromised patients, who are at higher risk of hospitalizations, complications, and mortality due to COVID-19. We examined hospital all-cause mortality for early RDV use vs. no RDV use among immunocompromised COVID-19 patients across several distinct dominant variants of concern (VOC) periods: pre-Delta (Dec'20-Apr'21), Delta (May-Nov'21) and Omicron (Dec'21-Apr'22). Method(s): Using the Premier Healthcare Database, we identified adults with an immunocompromised condition (cancer, solid organ and hematopoietic stem cell transplant, hematologic malignancies, primary immunodeficiencies, asplenia, bone marrow failure/aplastic anemia, severe combined immunodeficiencies or HIV), hospitalized with a primary diagnosis of COVID-19. Patients treated with RDV in first 2 days of admission vs. those not treated with RDV during the hospitalization were matched using 1:1 preferential withinhospital propensity matching with replacement. Patients were excluded if discharged within 3 days of RDV initiation. Cox Proportional Hazards Model was used to examine time to 14-and 28-day mortality. Result(s): Overall (Dec'20-Apr'22), 14,169 RDV-treated patients were matched to 5,341 unique non-RDV patients. Post-matching balance was achieved with 59% being 65+ years, 40.5% with no supplementary oxygen charges, 39% received low-flow oxygen, 19% on high-flow oxygen/non-invasive ventilation and 1.5% on invasive mechanical ventilation/ECMO at baseline. During the study period, unadjusted mortality rate was significantly lower for RDV patients at 14 days (11% [95% CI: 11%-12%] vs 15% [15%-16%];p< .0001) and 28 days (18% [17%-18%];p< .0001 vs 22% [22%-23%];p< .0001) as compared to patients that did not receive RDV. After adjusting for baseline and clinical covariates, 14-day results showed that RDV had significantly lower mortality risk compared to non-RDV across all VOC periods [overall (30% lower risk), pre-delta (41%), Delta (23%), Omicron (25%)]. Similarly, 28-day results showed that RDV had significantly lower mortality risk compared to non-RDV across all VOC periods [overall (25%), pre-delta (35%), Delta (21%), Omicron (16%)] (Fig). Conclusion(s): Timely initiation of RDV in first two days of hospital admission demonstrated significant mortality reduction in immunocompromised patients hospitalized with primary diagnosis of COVID-19. RDV demonstrated consistent benefit in an immunocompromised cohort across all variant periods of the pandemic.
ABSTRACT
Background: Clinical management of COVID-19 based on oxygenation requirements continues to change over time as variants of concern (VOC) evolve. We examine hospital all-cause mortality for early hospital RDV use vs. no RDV use across dominant VOC periods: pre-Delta (Dec'20-Apr'21), Delta (May-Nov'21) and Omicron (Dec'21-Apr'22). Method(s): We examined adults with a primary discharge diagnosis of COVID-19 (ICD-10: U07.1) using the Premier Healthcare Database. Patients treated with RDV in the first 2 days of admission vs. those not treated with RDV during the hospitalization were matched using a 1:1 preferential within-hospital propensity matching with replacement. Patients were excluded if discharged within 3 days of RDV initiation. Time to mortality at 14-and 28-days was examined for patients with no supplemental oxygen charges (NSOc), low-flow oxygen (LFO), high-flow oxygen/non-invasive ventilation (HFO/NIV) and invasive mechanical ventilation/ECMO (IMV/ECMO) at baseline. Baseline was defined as first 2 days of hospitalization. Result(s): 164,791 RDV-treated patients were matched to 48,473 unique non-RDV patients. Post-matching balance was achieved across groups with different baseline oxygenation levels and VOC periods. In the matched weighted cohort, 35% required NSOc, 41% LFO, 21% HFO/NIV and 3% IMV/ECMO. During the overall study period (Dec'20-Apr'22), unadjusted mortality rate was significantly lower for RDV patients across all oxygenation levels at 14 days (NSOc: 5.4% vs. 7.3%, LFO: 6.4% vs. 8.8%, HFO/NIV: 16.8% vs. 19.4%, IMV/ECMO: 27.8% vs. 35.3%) and 28 days (NSOc: 8.0% vs. 9.8%, LFO: 9.8% vs. 12.3%, HFO/ NIV: 25.8% vs. 28.3%, IMV/ECMO: 41.4% vs. 50.6%). After adjusting for baseline and clinical covariates, 14-day mortality results showed that RDV significantly lower risk compared to non-RDV across all oxygenation levels at baseline [NSO (26%), LFO (28%), HFO/NIV (17%), IMV/ ECMO (27%)]. Similarly, 28-day mortality results showed that RDV significantly lower risk compared to non-RDV across all oxygenation levels at baseline [NSO (19%), LFO (21%), HFO/NIV (12%), IMV/ECMO (26%)]. This lower mortality risk associated with RDV was consistently observed across all variant periods (Figure). Conclusion(s): Timely initiation of RDV within first two days of hospital admission demonstrated significant mortality reduction in patients hospitalized for a primary diagnosis of COVID-19 across all oxygenation levels. Remdesivir demonstrated consistent benefit across all variant periods of the pandemic to-date.
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Methods: This retrospective study included adults with COVID-19 (ICD-10: U07.1) and pneumonia (ICD-10 subcodes within J11.x - J16.x, J18.x) May 2020-December 2021 in the Premier Healthcare Database, analyzing severity, treatment patterns and clinical outcomes. Result(s): Between May 2020 and December 2021: N=338,930 patients in 856 hospitals 79% of patients received any dexamethasone(DEX);>50% received any remdesivir(RDV) Combination therapy use increased: DEX+RDV only from <1% of patients to 29%;DEX+RDV with baricitinib or tocilizumab from <1% to 19% RDV initiation in the first 2 days of hospitalization increased 41% to 88% Overall all-cause mortality increased 19% to 24% with large differences between severity subgroups: in December 2021, 20%, 32%, 46% and 60%, respectively, in no supplementary oxygen(NSOc), low-flow(LFO), highflow/non-invasive(HFO/NIV) and invasive mechanical ventilation/ECMO(IMV/ECMO) Overall median hospital LOS and ICU LOS remained between 6-10 days, with notable variation by severity subgroup and over time Overall ICU use was 35%-38%, with large differences by severity subgroups: in December 2021, 28%, 47%, 67% and 94%, respectively, in NSOc, LFO, HFO/NIV and IMV/EC Conclusion(s): COVID-19 can result in severe outcomes;understanding treatment and severity trends can improve prognosis.
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Purpose: To characterize demographics, treatment patterns, and outcomes among 3,998 transplant patients hospitalized for COVID-19 over 16 months of the pandemic (May '20-Aug '21). Method(s): Adult patients in a transplant cohort (TC) and non-transplant cohort (NTC) hospitalized with COVID-19 (ICD-10: U07.1) were compared in the Premier Healthcare Database from May '20-Aug '21. Baseline measures in first two days, demographics, comorbidity, COVID-19 treatments and immunosuppressants were analyzed. Outcomes included mortality (discharge status expired or hospice) and hospital and ICU LOS. Result(s): 3,998 TC patients were hospitalized for COVID-19 in 587 US hospitals. Compared to NTC, TC were younger (61 vs 64 yrs;p<.0001), less likely to be white (59% vs 67%;p<.0001), obese (24% vs 33%;p<.0001) or have COPD (17% vs 24%;p<.0001). TC had higher rates hypertension (84% vs 69%;p<.0001), renal disease (80% vs 22%, p<.0001), diabetes (48% vs 29%;p<.0001) and chronic heart failure (23% vs 18%;p<.0001). During hospitalization, a lower proportion of TC needed any oxygen therapy compared to NTC (p<.05). Compared to NTC, fewer TC received remdesivir (RDV) (44% vs 48%;p<.0001), but more received corticosteroids (87% vs 78%;p<.0001), anticoagulants (44% vs 29%;p<.0001) and convalescent plasma (18% vs 16%;p=0.007). In TC, 44% received MMF, 73% calcineurin inhibitors and 5% mTOR. Use of MMF did not change over time (43% May-Jul 2020;43% Aug- Dec 2020;45% 2021). TC had higher ICU admission rates (31% vs 28%;p.001), but similar hospital LOS and ICU LOS compared to NTC. All-cause mortality in NTC (15% overall;16% May-Jul 2020;16% Aug-Dec 2020;14% 2021) was not significantly different than TC over time (16% overall;13% May-Jul 2020;16% Aug-Dec 2020;16% 2021). Conclusion(s): Very few large studies have assessed COVID-19 management in transplant patients over time. All-cause mortality was comparable in both cohorts despite TC immunosuppression. RDV use was lower in TC. Uncertainty around MMF use in COVID-19 patients did not impact reported use of MMF. Further analyses are needed to evaluate confounding factors (medication sequence, time since transplant, disease severity) and impact of external factors such as earlier testing and treatment for COVID-19, vaccination, and new variants. (Table Presented).
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Background. Remdesivir (RDV) reduced time to recovery and mortality in some subgroups of hospitalized patients in the NIAID ACTT-1 RCT compared to placebo. Comparative effectiveness data in clinical practice are limited. Methods. Using the Premier Healthcare Database, we compared survival for adult non-mechanically ventilated hospitalized COVID-19 patients between Aug-Nov 2020 and treated with RDV within 2 days of hospitalization vs. those who did not receive RDV. Preferential within-hospital propensity score matching with replacement was used. Patients were matched on baseline O2 and 2-month admission period and were excluded if discharged within 3 days of RDV initiation (to exclude anticipated discharges/transfers within 72 hrs consistent with ACTT-1 study). Time to 14- and 28-day mortality was examined separately for patients on high-flow/non-invasive ventilation (NIV), low-flow, and no supplemental O2 using Cox Proportional Hazards models. Results. RDV patients (n=27,559) were matched to unique non-RDV patients (n=15,617) (Fig 1). The two groups were balanced;median age 66 yrs and 73% white (RDV);68 yrs and 74% white (non-RDV), and 55% male. At baseline, 21% required high-flow O2, 50% low-flow O2, and 29% no O2, overall. Mortality in RDV patients was 9.6% and 13.8% on days 14 and 28, respectively. For non-RDV patients, mortality was 14.0% and 17.3% on days 14 and 28, respectively. Kaplan-Meier curves for time to mortality are shown in Fig 2. After adjusting for baseline and clinical covariates, RDV patients on no O2 and low-flow O2 had a significantly lower risk of death within 14 days (no O2, HR: 0.69, 95% CI: 0.57-0.83;low-flow, HR: 0.67, 95% CI: 0.59-0.77) and 28 days (no O2, HR: 0.80, 95% CI: 0.68-0.94;low-flow, HR: 0.76, 95% CI: 0.68-0.86). Additionally, RDV patients on high-flow O2/NIV had a significantly lower risk of death within 14 days (HR: 0.81, 95% CI: 0.70-0.93);but not at 28 days (Fig 3). Conclusion. In this large study of patients in clinical care hospitalized with COVID-19, we observed a significant reduction of mortality in RDV vs. non-RDV treated patients in those on no O2 or low-flow O2. Mortality reduction was also seen in patients on high-flow O2 at day 14, but not day 28. These data support the use of RDV early in the course of COVID-19 in hospitalized patients.
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Background. Evidence on outcomes after COVID-19 hospitalization is limited. This study aimed to characterize 30-day readmission beyond the initial COVID-19 hospitalization. Methods. This descriptive retrospective cohort study included adult patients admitted between 07/01/2020 and 01/31/2021 with a discharge diagnosis of COVID-19 (ICD-10-CM: U07.1), using a large hospital inpatient chargemaster with a linked open claims dataset. The first COVID-19 hospitalization was considered index hospitalization;baseline was defined as first 2 days of index hospitalization;readmission was assessed within 30 days of discharge from index hospitalization. We describe the demographics, treatments and outcomes of the index hospitalization and readmission. Results. For index hospitalization, we identified 111,624 COVID-19 patients from 327 hospitals across US. Mean age was 63 and 54% were male. Over the study period, use of remdesivir (RDV) increased from 11% to 50% while use of steroids (66% -73%) and anticoagulants (32% - 35%) remained relatively stable (Figure 1). Overall, 21% required ICU or CCU admission, 13% died, and median length of stay (LOS) was 7 days (range 4 -11 days). Among 61,182 (55%) with ≥ 30-day follow-up post discharge, all-cause 30-day readmission was 16% and remained stable (15% - 17%) over the study period;median days to readmission was 6 days (range 1-30). All-cause readmission (13 % vs 17%) was lower in patients treated with RDV during index hospitalization over time (Figure 2), particularly in those requiring high flow oxygen (17% vs 18%), low flow oxygen (13% vs 16%) or no oxygen (12% vs 17%), but not in ECMO or invasive ventilation (33% vs 29%). Compared to non-readmitted, readmitted patients were older (60 vs 65), had more comorbidities such as COPD (24% vs 37%) (see Table 1) and LOS (6 vs 7 days) in index hospitalization. Overall, the most frequent diagnoses of readmission were COVID-19 (63%), other viral pneumonia (36%), and acute respiratory failure with hypoxia (34%). Conclusion. In a large, geographically diverse cohort of hospitalized COVID-19 patients, 16% required readmission, especially in those with greater age and comorbidities. Over the study period, all-cause readmission remained stable and was lower in RDV treated patients.
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Objectives: This study aimed to characterize the 30-day readmission in hospitalized COVID-19 patients. Methods: We conducted an observational cohort study including adult hospitalized COVID-19 patients admitted between 07/01/2020 and 01/31/2021 using a large inpatient chargemaster (billing) linked with open administrative healthcare claims database. The first COVID-19 hospitalization in the study period was considered as the index hospitalization. Readmission was assessed within 30 days of discharge. Results: We identified 111,624 COVID-19 patients admitted to 327 hospitals with 13% (N=14,763) mortality rate during index hospitalization. Among 61,182 patients discharged alive with ≥30-day follow-up, the overall all-cause readmission rate was 16% (N=9,748) and remained stable between 15% and 17% over the study period. 32% (N=19,770) of the discharged patients were treated with remdesivir (RDV) during their index hospitalization, and readmission was lower in RDV-treated patients (13%, N=2,627) compared to those not treated with RDV during their index hospitalization (17%, N=7,121). Among patients who received RDV in their initial hospitalization, those who started therapy upon admission (Day 1 or 2) had lower readmission rates (12%), compared to those who received RDV later in the hospitalization course, 15% (Day 3-5) and 27% (Day >5). The most frequent diagnoses upon readmission were COVID-19 (63%), other viral pneumonia (36%), and acute respiratory failure with hypoxia (34%). Compared to non-readmitted, readmitted patients were older (60 vs 65), had more comorbidities such as COPD (24% vs 37%) and congestive heart failure (28% vs 44%), and longer median LOS (6 vs 7 days) during index hospitalization. Conclusions: This study of a large and geographically diverse population revealed substantial burden on patients beyond the initial COVID-19 hospitalization, as 16% of the patients were re-admitted within 30-days. Over the study period, lower readmission was observed in patients who were treated with RDV during their index hospitalization.
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Objectives: In this comparative effectiveness study, we compare the survival outcomes for hospitalized COVID-19 patients treated with remdesivir (RDV) upon admission vs. those not treated with RDV. Methods: We used the Premier Healthcare Database to examine patients hospitalized between Aug-Nov 2020 and treated with RDV within 2 days of hospitalization vs. those who did not receive RDV during their hospitalization. Preferential within-hospital propensity score matching with replacement was used. Patients were matched on baseline oxygen requirement and 2-month admission period and were excluded if discharged within 3 days of RDV initiation (to exclude anticipated discharges/transfers within 72 hrs consistent with ACTT-1 study). Cox Proportional Hazards models were used to examine 14- and 28-day mortality overall and for patients on no supplemental oxygen (NSO), low-flow oxygen (LFO), high-flow oxygen/non-invasive ventilation (HFO/NIV) and invasive mechanical ventilation/ECMO (IMV/ECMO) separately. Results: RDV patients (n=28,855) were matched to unique non-RDV patients (n=16,687). The two groups were balanced. At baseline, 28% required NSO, 48% LFO, 20% HFO/NIV and 4% IMV/ECMO. Mortality in RDV patients was 10.6% and 15.4% on days 14 and 28, respectively. For non-RDV patients, mortality was 15.4% and 19.1% on days 14 and 28, respectively. After adjusting for baseline and clinical covariates, RDV patients had significantly lower risk of mortality at 14-days (HR[95% CI]: 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 patients 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 patients had a significantly lower risk of mortality at 14-days (0.81[0.70−0.93]);but not at 28-days. Conclusions: In this observational study, treatment with RDV was associated with statistically significant reduction in mortality among hospitalized COVID-19 patients. These results complement the findings from the ACTT-1 and contribute to the growing body of evidence on the survival benefits of RDV.
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Objectives: Remdesivir is an FDA approved treatment for hospitalized patients with COVID-19 infection and, in randomized controlled trials, RDV shortened time to recovery and improved clinical outcomes. Data are scarce on RDV utilization in real-world settings or how use has changed over the course of the pandemic. Using chargemaster inpatient data from the Premier Healthcare Database, we describe the patient population and use of RDV following Emergency Use Authorization. Methods: In this retrospective cohort study, adult patients admitted May 1st - Nov 30th 2020 with a primary or secondary discharge diagnosis of COVID-19 (ICD-10-CM: U07.1) were identified and their first COVID-related hospital admission was considered. Descriptive statistics were reported for demographic characteristics of RDV and non-RDV treated patients. RDV utilization over time and by region was examined. Results: Of the 190,529 patients hospitalized for COVID-19 in 823 hospitals, 55,030 (29%) were treated with RDV in 589 hospitals. RDV utilization over time increased from 5% of patients in May to 47% in Nov 2020. In Nov, RDV utilization was 57% in the West, followed by 49% in the South, 48% in the Midwest and 27% in the Northeast. Over time, RDV was initiated earlier in the course of hospitalization. Initiation within the first 2 days of hospitalization increased from 40% to 85% from May to Nov 2020. The average age was 63.6 years (SD=15.3) and 63.5 years (SD=17.3) for RDV-treated and non-RDV treated patients, respectively. More than half of the patients were male (RDV: 56%;Non-RDV: 52%) and about a quarter had commercial insurance (RDV: 28%;Non-RDV: 22%). Racial distribution (white, black, and other) was similar between RDV and non-RDV patients. Conclusions: Overall use of RDV and initiation within the first two days of hospitalization have substantially increased over the course of the pandemic in the United States.
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Background: Clinical practice patterns for hospitalized COVID-19 patients have rapidly evolved, including specific treatment utilization. In turn, outcomes including time to improvement and mortality have also changed, but some reports have shown disproportionate mortality in Blacks. Data on the use of COVID-19 treatments over time and temporal association with hospital mortality and length of stay (LOS), along with assessments by race, are lacking. Methods: This was a retrospective cohort study of adult patients with a discharge diagnosis of COVID-19 (ICD-10-CM: U07.1) admitted between May-Nov 2020 using the chargemaster inpatient data from the Premier Healthcare Database. Demographic characteristics of the cohort were summarized. Utilization of remdesivir (RDV), dexamethasone, anticoagulants, tocilizumab, sarilumab and baricitinib were examined. Median hospital and intensive care unit (ICU) LOS were assessed over time. In-hospital mortality was identified through discharge status. Unadjusted mortality rates over time are reported. Results: Between May-Nov 2020, 190,529 patients were hospitalized for COVID-19 in 823 US hospitals. Patients had a mean age of 64 years, 64% were White, 19% Black, 53% male and 65% had Medicare/ Medicaid as primary payor. Black patients were younger than White (mean 60 vs. 66 years). Significant comorbidities (>20%) were similar between overall cohort and Black patients and included chronic pulmonary disease, hypertension and obesity. From May to Nov, overall RDV utilization increased from 5% to 47%, dexamethasone utilization increased from 7% to 77% and anticoagulant treatment utilization decreased from 32% to 24% (Figure). Few patients received tocilizumab (5%), sarilumab (0.02%) and baricitinib (0.003%). Among Black patients, RDV use increased from 5% to 39% and dexamethasone use increased from 6% to 74%. The median LOS of the overall cohort and Black cohort decreased from 6 days in May to 5 days in Nov, and overall ICU LOS for patients decreased from 5 to 4 days during this time;5 to 3 in Black patients. Overall in-hospital mortality rate decreased by 35%, and by 38% in Black patients. Conclusion:In US hospitalized patients, use of both dexamethasone and RDV has increased approximately 10-fold from May to Nov. Over this same time, a 35% reduction in mortality, a 17% reduction in LOS and 20% reduction in ICU stay were observed. Besides age, no notable differences were apparent by race. Understanding the drivers of improvement in outcomes requires further analyses.
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The Databionic swarm (DBS) is a flexible and robust clustering framework that consists of three independent modules: swarm based projection, high-dimensional data visualization and representation guided clustering. The first module is the parameter-free projection method Pswarm, which exploits concepts of self-organization and emergence, game theory, and swarm intelligence. The second module is a parameter-free high-dimensional data visualization technique called topographic map. It uses the generalized U-matrix, which enables to estimate first, if any cluster tendency exists and second, the estimation of the number of clusters. The third module offers a clustering method which can be verified by the visualization and vice versa. Benchmarking w.r.t. conventional algorithms demonstrated that DBS can outperform them. Several applications showed that cluster structures provided by DBS are meaningful. Exemplary, a clustering of worldwide country-related data w.r.t. the COVID-19 pandemic is presented here. Code and data is made available via open source. © 2020 Inst. Sci. inf., Univ. Defence in Belgrade. All rights reserved.