Publications by authors named "Vithal Madhira"

6 Publications

  • Page 1 of 1

COVID-19 in Solid Organ Transplantation: Results of the National COVID Cohort Collaborative.

Transplant Direct 2021 Nov 6;7(11):e775. Epub 2021 Oct 6.

Division of Nephology, Department of Medicine, University of Nebraska Medical Center, Omaha, NE.

Coronavirus disease 2019 (COVID-19) has resulted in significant morbidity and mortality in solid organ transplant (SOT) recipients. The National COVID Cohort Collaborative was developed to facilitate analysis of patient-level data for those tested for COVID-19 across the United States.

Methods: In this study, we identified a cohort of SOT recipients testing positive or negative for COVID-19 (COVID+ and COVID-, respectively) between January 1, 2020, and November 20, 2020. Univariable and multivariable logistic regression were used to determine predictors of a positive result among those tested. Outcomes following COVID-19 diagnosis were also explored.

Results: Of 18 121 SOT patients tested, 1925 were positive (10.6%). COVID+ SOT patients were more likely to have a kidney transplant and be non-White race. Comorbidities were common in all SOT patients but significantly more common in those who were COVID+. Of COVID+ SOT, 42.9% required hospital admission. COVID+ status was the strongest predictor of acute kidney injury (AKI), rejection, and graft failure in the 90 d after testing. A total of 40.9% of COVID+ SOT experienced a major adverse renal or cardiac event, 16.3% experienced a major adverse cardiac event, 35.3% experienced AKI, and 1.5% experienced graft loss.

Conclusions: In the largest US cohort of COVID+ SOT recipients to date, we identified patient factors associated with the diagnosis of COVID-19 and outcomes following infection, including a high incidence of major adverse renal or cardiac event and AKI.
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http://dx.doi.org/10.1097/TXD.0000000000001234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8500600PMC
November 2021

Sex and Organ-Specific Risk of Major Adverse Renal or Cardiac Events in Solid Organ Transplant Recipients with COVID-19.

Am J Transplant 2021 Oct 12. Epub 2021 Oct 12.

Division of Nephology, Department of Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA.

While older males are at highest risk for poor COVID-19 outcomes, it is not known if this applies to the immunosuppressed recipient of a solid organ transplant (SOT), nor how the type of allograft transplanted may impact outcomes. In a cohort study of adult (>18 years) patients testing positive for COVID-19 (Jan 01, 2020-June 21, 2021) from 56 sites across the United States identified using the National COVID Cohort Collaborative (N3C) Enclave, we used multivariable Cox proportional hazards models to assess time to MARCE after COVID-19 diagnosis in those with and without SOT. We examined the exposure of age-stratified recipient sex overall and separately in kidney, liver, lung, and heart transplant recipients. 3,996 (36.4%) SOT and 91,646 (4.8%) non-SOT patients developed MARCE. Risk of post-COVID outcomes differed by transplant allograft type with heart and kidney recipients at highest risk. Males with SOT were at increased risk of MARCE, but to a lesser degree than the non-SOT cohort (HR 0.89, 95% CI 0.81-0.98 for SOT and HR 0.61, 95% CI 0.60-0.62 for non-SOT (females versus males)). This represents the largest COVID-19 SOT cohort to date and the first-time sex-age stratified and allograft-specific COVID-19 outcomes have been explored in those with SOT.
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http://dx.doi.org/10.1111/ajt.16865DOI Listing
October 2021

Reply to K. Takada et al.

J Clin Oncol 2021 Oct 8:JCO2102150. Epub 2021 Oct 8.

Noha Sharafeldin, MD, MSc, PhD, University of Alabama at Birmingham, School of Medicine, Birmingham, AL; Benjamin Bates, MD, Rutgers University, New Brunswick, NJ; Qianqian Song, PhD, Wake Forest School of Medicine, Winston-Salem, NC; Vithal Madhira, MS, Palila Software LLC, Reno, NV; Yu Raymond Shao, MD, PhD, Duke University Medical Center, Durham, NC; Feifan Liu, PhD, University of Massachusetts Medical School, Boston, MA; Timothy Bergquist, PhD, Sage Bionetworks, Seattle, WA; Jing Su, PhD, Department of Biostatistics, Indiana University School of Medicine, Indianapolis, IN; and Umit Topaloglu, PhD, Wake Forest School of Medicine, Winston-Salem, NC.

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http://dx.doi.org/10.1200/JCO.21.02150DOI Listing
October 2021

Use of Hydroxychloroquine, Remdesivir, and Dexamethasone Among Adults Hospitalized With COVID-19 in the United States : A Retrospective Cohort Study.

Ann Intern Med 2021 Aug 17. Epub 2021 Aug 17.

Johns Hopkins Bloomberg School of Public Health and Johns Hopkins School of Medicine, Baltimore, Maryland (G.C.A.).

Background: Relatively little is known about the use patterns of potential pharmacologic treatments of COVID-19 in the United States.

Objective: To use the National COVID Cohort Collaborative (N3C), a large, multicenter, longitudinal cohort, to characterize the use of hydroxychloroquine, remdesivir, and dexamethasone, overall as well as across individuals, health systems, and time.

Design: Retrospective cohort study.

Setting: 43 health systems in the United States.

Participants: 137 870 adults hospitalized with COVID-19 between 1 February 2020 and 28 February 2021.

Measurements: Inpatient use of hydroxychloroquine, remdesivir, or dexamethasone.

Results: Among 137 870 persons hospitalized with confirmed or suspected COVID-19, 8754 (6.3%) received hydroxychloroquine, 29 272 (21.2%) remdesivir, and 53 909 (39.1%) dexamethasone during the study period. Since the release of results from the RECOVERY (Randomised Evaluation of COVID-19 Therapy) trial in mid-June, approximately 78% to 84% of people who have had invasive mechanical ventilation have received dexamethasone or other glucocorticoids. The use of hydroxychloroquine increased during March 2020, peaking at 42%, and started declining by April 2020. By contrast, remdesivir and dexamethasone use gradually increased over the study period. Dexamethasone and remdesivir use varied substantially across health centers (intraclass correlation coefficient, 14.2% for dexamethasone and 84.6% for remdesivir).

Limitation: Because most N3C data contributors are academic medical centers, findings may not reflect the experience of community hospitals.

Conclusion: Dexamethasone, an evidence-based treatment of COVID-19, may be underused among persons who are mechanically ventilated. The use of remdesivir and dexamethasone varied across health systems, suggesting variation in patient case mix, drug access, treatment protocols, and quality of care.

Primary Funding Source: National Center for Advancing Translational Sciences; National Heart, Lung, and Blood Institute; and National Institute on Aging.
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http://dx.doi.org/10.7326/M21-0857DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8372837PMC
August 2021

COVID-19 Disease Severity among People with HIV Infection or Solid Organ Transplant in the United States: A Nationally-representative, Multicenter, Observational Cohort Study.

medRxiv 2021 Jul 28. Epub 2021 Jul 28.

Background: Individuals with immune dysfunction, including people with HIV (PWH) or solid organ transplant recipients (SOT), might have worse outcomes from COVID-19. We compared odds of COVID-19 outcomes between patients with and without immune dysfunction.

Methods: We evaluated data from the National COVID-19 Cohort Collaborative (N3C), a multicenter retrospective cohort of electronic medical record (EMR) data from across the United States, on. 1,446,913 adult patients with laboratory-confirmed SARS-CoV-2 infection. HIV, SOT, comorbidity, and HIV markers were identified from EMR data prior to SARS-CoV-2 infection. COVID-19 disease severity within 45 days of SARS-CoV-2 infection was classified into 5 categories: asymptomatic/mild disease with outpatient care; mild disease with emergency department (ED) visit; moderate disease requiring hospitalization; severe disease requiring ventilation or extracorporeal membrane oxygenation (ECMO); and death. We used multivariable, multinomial logistic regression models to compare odds of COVID-19 outcomes between patients with and without immune dysfunction.

Findings: Compared to patients without immune dysfunction, PWH and SOT had a greater likelihood of having ED visits (adjusted odds ratio [aOR]: 1.28, 95% confidence interval [CI] 1.27-1.29; aOR: 2.61, CI: 2.58-2.65, respectively), requiring ventilation or ECMO (aOR: 1.43, CI: 1.43-1.43; aOR: 4.82, CI: 4.78-4.86, respectively), and death (aOR: 1.20, CI: 1.19-1.20; aOR: 3.38, CI: 3.35-3.41, respectively). Associations were independent of sociodemographic and comorbidity burden. Compared to PWH with CD4>500 cells/mm , PWH with CD4<350 cells/mm were independently at 4.4-, 5.4-, and 7.6-times higher odds for hospitalization, requiring ventilation, and death, respectively. Increased COVID-19 severity was associated with higher levels of HIV viremia.

Interpretation: Individuals with immune dysfunction have greater risk for severe COVID-19 outcomes. More advanced HIV disease (greater immunosuppression and HIV viremia) was associated with higher odds of severe COVID-19 outcomes. Appropriate prevention and treatment strategies should be investigated to reduce the higher morbidity and mortality associated with COVID-19 among PWH and SOT.
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http://dx.doi.org/10.1101/2021.07.26.21261028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8328066PMC
July 2021

Outcomes of COVID-19 in Patients With Cancer: Report From the National COVID Cohort Collaborative (N3C).

J Clin Oncol 2021 07 4;39(20):2232-2246. Epub 2021 Jun 4.

Wake Forest School of Medicine, Winston-Salem, NC.

Purpose: Variation in risk of adverse clinical outcomes in patients with cancer and COVID-19 has been reported from relatively small cohorts. The NCATS' National COVID Cohort Collaborative (N3C) is a centralized data resource representing the largest multicenter cohort of COVID-19 cases and controls nationwide. We aimed to construct and characterize the cancer cohort within N3C and identify risk factors for all-cause mortality from COVID-19.

Methods: We used 4,382,085 patients from 50 US medical centers to construct a cohort of patients with cancer. We restricted analyses to adults ≥ 18 years old with a COVID-19-positive or COVID-19-negative diagnosis between January 1, 2020, and March 25, 2021. We followed N3C selection of an index encounter per patient for analyses. All analyses were performed in the N3C Data Enclave Palantir platform.

Results: A total of 398,579 adult patients with cancer were identified from the N3C cohort; 63,413 (15.9%) were COVID-19-positive. Most common represented cancers were skin (13.8%), breast (13.7%), prostate (10.6%), hematologic (10.5%), and GI cancers (10%). COVID-19 positivity was significantly associated with increased risk of all-cause mortality (hazard ratio, 1.20; 95% CI, 1.15 to 1.24). Among COVID-19-positive patients, age ≥ 65 years, male gender, Southern or Western US residence, an adjusted Charlson Comorbidity Index score ≥ 4, hematologic malignancy, multitumor sites, and recent cytotoxic therapy were associated with increased risk of all-cause mortality. Patients who received recent immunotherapies or targeted therapies did not have higher risk of overall mortality.

Conclusion: Using N3C, we assembled the largest nationally representative cohort of patients with cancer and COVID-19 to date. We identified demographic and clinical factors associated with increased all-cause mortality in patients with cancer. Full characterization of the cohort will provide further insights into the effects of COVID-19 on cancer outcomes and the ability to continue specific cancer treatments.
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http://dx.doi.org/10.1200/JCO.21.01074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260918PMC
July 2021
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