Publications by authors named "Zhiji Zhang"

5 Publications

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Clinical and Economic Burden of Multiple Double-Stranded DNA Viral Infections after Allogeneic Hematopoietic Cell Transplantation.

Transplant Cell Ther 2022 Jun 25. Epub 2022 Jun 25.

Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon.

Conditioning regimens for allogeneic hematopoietic cell transplantation (allo-HCT) are immunosuppressive and increase the risk for reactivation of and infection with double-stranded DNA (dsDNA) viruses, which contribute to morbidity and mortality after allo-HCT. This retrospective observational study evaluated the association of dsDNA viral infections with clinical outcomes, health resource utilization (HRU), and health care reimbursement after allo-HCT. Patients who underwent allo-HCT between 2012 and 2017 were identified from a US open-source claims database (Decision Resource Group Real-World Evidence Data Repository; n = 13,363) and categorized according to the presence or absence of dsDNA viral infection, defined as having ≥1 diagnosis code for cytomegalovirus (CMV), adenovirus (AdV), human herpesvirus 6 (HHV-6), or BK virus (BKV)/Epstein-Barr virus (EBV)/John Cunningham virus (JCV) (grouped together given a lack of specific diagnoses codes) within 1 year after allo-HCT. Only first allo-HCT data were used in patients who underwent multiple procedures. Study outcomes included clinical outcomes (eg, time to all-cause mortality, new diagnosis of renal impairment), HRU (hospital and intensive care unit length of stay [LOS], readmission rates), and health care reimbursement (total, inpatient, and outpatient costs as reported reimbursements from insurance claims). For all outcomes, patients were stratified by the presence/absence of any dsDNA viral infection and number (none, 1, 2, or ≥3) and type(s) of infection. The effect of graft-versus-host disease (GVHD) was assessed as well. Twenty-nine percent of patients were diagnosed with CMV, 13% with BKV/EBV/JCV, 5% with AdV, and 4% with HHV-6 in the year following their first allo-HCT. A single dsDNA viral infection was documented in 30% of individuals, 2 in 8%, and ≥3 in 2%. Patients with no viral infections had an overall hospital LOS (index hospitalization plus readmissions) of 41.3 days and a total health care reimbursement of $266,345. These numbers increased for every additional viral infection, regardless of the presence or absence of GVHD; the overall hospital LOS was 61.4 days and total healthcare reimbursement was $431,614 in patients with 1 viral infection, 77.0 days and $639,097 in patients with 2 viral infections, and 103.3 days and $964,378 in patients with ≥3 viral infections. An increase in the number of dsDNA viral infections was associated with a significantly higher adjusted hazard of all-cause mortality (1 versus 0 dsDNA viral infections: hazard ratio [HR], 1.5; [95% confidence interval (CI), 1.3 to 1.6]; 2 versus 0: HR, 2.0 [95% CI, 1.7 to 2.3]; ≥3 versus 0: HR, 2.4 [95% CI, 1.8 to 3.3]) and a significantly higher incidence of new diagnosis of renal impairment, regardless of the presence of GVHD (35% of patients with ≥3 infections, 31% of patients with 2 infections, 26% of patients with 1 infection, and 19% of patients with no infection). These results indicate that more directed prevention and treatment strategies for dsDNA viral infections could substantially improve clinical outcomes and reduce HRU.
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June 2022

Economic and clinical burden associated with respiratory viral infections after allogeneic hematopoietic cell transplant in the United States.

Transpl Infect Dis 2022 Aug 1;24(4):e13866. Epub 2022 Jun 1.

Certara, New York, New York, USA.

Background: Allogeneic hematopoietic cell transplant (allo-HCT) recipients are at increased risk for respiratory viral infections (RVIs), which invoke substantial morbidity and mortality. Limited effective antiviral options and drug resistance often hamper successful RVI treatment, creating additional burden for patients and the health care system.

Methods: Using an open-source health care claims database, we examined differences in clinical outcomes, health resource utilization, and total reimbursements during the 1-year period following allo-HCT in patients with and without any RVI infection (respiratory syncytial virus, influenza, parainfluenza virus, and human metapneumovirus). RVIs were diagnosed at any time ≤1 year after allo-HCT and identified by International Classification of Disease codes. Analyses were stratified by the presence or absence of acute or chronic graft-versus-host disease (GVHD).

Results: The study included 13 363 allo-HCT patients, 1368 (10.2%) of whom had a diagnostic code for any RVI. A higher proportion of patients with any RVI had pneumonia ≤1 year after allo-HCT compared to patients without any RVI, with or without GVHD. Patients with any RVI had higher all-cause mortality risk, longer length of post-allo-HCT hospital stay, higher readmission rate, and higher number of hospital days after allo-HCT compared to patients without the infection (all p < .05). Total unadjusted median reimbursements were higher for those with any RVI and each specific RVI assessed than those without the specific infection, with or without GVHD.

Conclusion: Allo-HCT patients with RVIs had significantly worse clinical outcomes and increased health resource utilization and reimbursements during the year following allo-HCT, with or without GVHD.
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August 2022

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

Open Forum Infect Dis 2022 Jan 28;9(1):ofab498. Epub 2021 Sep 28.

Gilead Sciences, Foster City, California, USA.

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.
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January 2022

Remdesivir treatment in hospitalized patients with COVID-19: a comparative analysis of in-hospital all-cause mortality in a large multi-center observational cohort.

Clin Infect Dis 2021 Oct 1. Epub 2021 Oct 1.

Gilead Sciences, 333 Lakeside Drive, Foster City, CA, USA.

Background: Remdesivir (RDV) improved clinical outcomes among hospitalized COVID-19 patients in randomized trials, but data from clinical practice are limited.

Methods: We examined survival outcomes for US patients hospitalized with COVID-19 between Aug-Nov 2020 and treated with RDV within two-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/non-invasive ventilation (HFO/NIV) and invasive mechanical ventilation/ECMO (IMV/ECMO) and two-month admission window and excluded if discharged within 3-days of admission (to exclude anticipated discharges/transfers within 72-hrs consistent with 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: 28,855 RDV patients were matched to 16,687 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 (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 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 COVID-19 patients. Our findings complement ACTT-1 and support RDV as a foundational treatment for hospitalized COVID-19 patients.
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October 2021

Economic and Clinical Burden of Virus-Associated Hemorrhagic Cystitis in Patients Following Allogeneic Hematopoietic Stem Cell Transplantation in the United States.

Transplant Cell Ther 2021 06 26;27(6):505.e1-505.e9. Epub 2021 Feb 26.

Memorial Sloan Kettering Cancer Center, New York, New York.

Hemorrhagic cystitis (HC) caused by viral infections such as BK virus, cytomegalovirus, and/or adenovirus after allogeneic hematopoietic stem cell transplantation (allo-HCT) causes morbidity and mortality, affects quality of life, and poses a substantial burden to the health care system. At present, HC management is purely supportive, as there are no approved or recommended antivirals for virus-associated HC. The objective of this retrospective observational study was to compare the economic burden, health resource utilization (HRU), and clinical outcomes among allo-HCT recipients with virus-associated HC to those without virus-associated HC using a large US claims database. Claims data obtained from the Decision Resources Group Real-World Evidence Data Repository were used to identify patients with first (index) allo-HCT procedure from January 1, 2012, through December 31, 2017. Outcomes were examined 1 year after allo-HCT and included total health care reimbursements, HRU, and clinical outcomes for allo-HCT patients with virus-associated HC versus those without. Further, a generalized linear model was used to determine adjusted reimbursements stratified by the presence or absence of any acute or chronic graft-versus-host disease (GVHD) after adjusting for age, health plan, underlying disease, stem cell source, number of comorbidities, baseline reimbursements, and follow-up time. Of 13,363 allo-HCT recipients, 759 (5.7%) patients met the prespecified criteria for virus-associated HC. Total unadjusted mean reimbursement was $632,870 for patients with virus-associated HC and $340,469 for patients without virus-associated HC. In a multivariable model, after adjusting for confounders, the adjusted reimbursements were significantly higher for virus-associated HC patients with and without GVHD compared to patients without virus-associated HC (P < .0001). Patients with virus-associated HC stayed 7.9 additional days in the hospital (P < .0001) and 6.1 additional days (P = .0009) in the intensive care unit (ICU) for the index hospitalization, as compared to patients without virus-associated HC. The hospital readmission rate was higher for allo-HCT patients with versus without virus-associated HC (P < .0001), resulting in 12.9 more days in the hospital (P < .0001) and 7.3 more days in the ICU (P < .0001) after the index hospitalization. Among patients with GVHD, those with virus-associated HC had significantly higher all-cause mortality as compared to those without virus-associated HC (23.2% versus 18.4%; P = .0035). In an adjusted analysis, patients with virus-associated HC had a significantly higher risk of mortality, regardless of the presence of GVHD. When stratified by GVHD, there were no significant differences in the baseline risk for renal impairment; virus-associated HC was associated with increased risk for renal impairment in the follow-up period in patients with or without GVHD (P < .0001 for both). After allo-HCT, patients with virus-associated HC have significantly higher health care reimbursements and HRU, with worse clinical outcomes, including renal impairment, irrespective of the presence of GVHD and significantly higher all-cause mortality in the presence of GVHD. Our results highlight the unmet clinical need for effective strategies to prevent and treat virus-associated HC in HCT recipients that may also reduce costs among these patients.
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June 2021