Factors Associated With Adherence to First-line Antiviral Therapy Among Commercially Insured Patients With Chronic Hepatitis B.

Background: Nonadherence to antiviral therapy can lead to poor clinical outcomes among patients with chronic hepatitis B (CHB). We used a claims database to evaluate risk factors for nonadherence to antiviral therapy among commercially insured patients with CHB in the United States. Methods: We obtained data for commercially insured adult patients with CHB prescribed entecavir or tenofovir disoproxil fumarate (TDF) in 2019. Primary outcomes were adherence to entecavir and adherence to TDF. Enrollees with a proportion of days covered (PDC) ≥80% were considered adherent. We presented adjusted odds ratios (AORs) from multivariate logistic regressions. Results: Eighty-three percent (n = 640) of entecavir patients were adherent, and 81% (n = 687) of TDF patients were adherent. Ninety-day supply (vs 30-day supply; AOR, 2.21; P < .01), mixed supply (vs 30-day supply; AOR, 2.19; P = .04), and ever using a mail order pharmacy (AOR, 1.92, P = .03) were associated with adherence to entecavir. Ninety-day supply (vs 30-day supply; AOR, 2.51; P < .01), mixed supply (vs 30-day supply; AOR, 1.82; P = .04), and use of a high-deductible health plan (vs no high-deductible health plan; AOR, 2.29; P = .01) were associated with adherence to TDF. Out-of-pocket spending of >$25 per 30-day supply of TDF was associated with reduced odds of adherence to TDF (vs <$5 per 30-day supply of TDF; AOR, 0.34; P < .01). Conclusions: Ninety-day and mixed-duration supplies of entecavir and TDF were associated with higher fill rates as compared with 30-day supplies among commercially insured patients with CHB.

Outcome of COVID-19 in allogeneic stem cell transplant recipients: Results from the EPICOVIDEHA registry

Background The outcome of COVID-19 in allogeneic hematopoietic stem cell transplantation (HSCT) recipients is almost uniformely considered poor. The aim of present study was to retrospectively analyse the outcome and risk factors for mortality in a large series of patients who developed COVID-19 infection after an allogeneic HSCT. Methods This multicenter retrospective study promoted by the European Hematology Association – Infections in Hematology Study Working Group, included 326 adult HSCT patients who had COVID-19 between January 2020 and March 2022. Results The median time from HSCT to the diagnosis of COVID-19 was 268 days (IQR 86-713;range 0-185 days). COVID-19 severity was mild in 21% of the patients, severe in 39% and critical in 16% of the patients. In multivariable analysis factors associated with a higher risk of mortality were, age above 50 years, presence of 3 or more comorbidities, active hematologic disease at time of COVID-19 infection, development of COVID-19 within 12 months of HSCT, and severe/critical infections. Overall mortality rate was 21% (n=68): COVID-19 was the main or secondary cause of death in 16% of the patients (n=53). Conclusions Mortality in HSCT recipients who develop COVID-19 is high and largely dependent on age, comorbidities, active hematologic disease, timing from transplant and severity of the infection.

Outcome of COVID-19 in allogeneic stem cell transplant recipients: Results from the EPICOVIDEHA registry.

Background: The outcome of COVID-19 in allogeneic hematopoietic stem cell transplantation (HSCT) recipients is almost uniformely considered poor. The aim of present study was to retrospectively analyse the outcome and risk factors for mortality in a large series of patients who developed COVID-19 infection after an allogeneic HSCT. Methods: This multicenter retrospective study promoted by the European Hematology Association - Infections in Hematology Study Working Group, included 326 adult HSCT patients who had COVID-19 between January 2020 and March 2022. Results: The median time from HSCT to the diagnosis of COVID-19 was 268 days (IQR 86-713; range 0-185 days). COVID-19 severity was mild in 21% of the patients, severe in 39% and critical in 16% of the patients. In multivariable analysis factors associated with a higher risk of mortality were, age above 50 years, presence of 3 or more comorbidities, active hematologic disease at time of COVID-19 infection, development of COVID-19 within 12 months of HSCT, and severe/critical infections. Overall mortality rate was 21% (n=68): COVID-19 was the main or secondary cause of death in 16% of the patients (n=53). Conclusions: Mortality in HSCT recipients who develop COVID-19 is high and largely dependent on age, comorbidities, active hematologic disease, timing from transplant and severity of the infection.

Pneumocystis jirovecii Infections Among COVID-19 Patients: A Case Series and Literature Review.

Background: Pneumocystis jirovecii pneumonia (PCP) is a serious, emerging complication of coronavirus disease 2019 (COVID-19). Methods: We performed a systematic review of published cases. We describe 6 new cases of PCP/COVID-19 coinfection. Among our cases (n = 6) and those in the literature (n = 69) with available data, the median age (interquartile range [IQR]) was 59 (44-77) years (n = 38), 72% (47/65) were male, and the mortality rate was 30.9% (21/68). Results: Long-term corticosteroid use was noted in 45.1% (23/51), advanced HIV infection (defined as a CD4 count <200 cells/µL) in 17.6% (9/51), and antineoplastic chemotherapy in 13.7% (7/51), consistent with known PCP risk factors. Notably, 56.7% (38/47) had verifiable risk factors for PCP (high-dose corticosteroids, immunosuppressive therapy, and HIV infection) before COVID-19 infection. A median absolute lymphocyte count (IQR) of 0.61 (0.28-0.92) ×103 cells/mm3 (n = 23) and CD4 count (IQR) of 66 (33-291.5) cells/mm3 (n = 20) were also discovered among the study population. Conclusions: These findings suggest a need for greater attention to PCP risk factors among COVID-19 patients and consideration of PCP prophylaxis in these high-risk populations.

Disseminated Histoplasmosis with Underlying Sarcoidosis-Rheumatoid Arthritis Overlap Syndrome: An Example of Diagnostic Test Threshold of Detection Affecting Test Results and Patient Care.

Histoplasmosis is common in many parts of the world but with areas of hyperendemicity. Disseminated histoplasmosis is the deadliest form of histoplasmosis and is most common among immunocompromised patients. Timely diagnosis is crucial to improve outcomes. We describe a patient on azathioprine and rituximab with disseminated histoplasmosis in which diagnosis was delayed in part because of negative early Histoplasma antigen testing, which was positive later in the course. This case serves as an example of the concept of "threshold of detection" in which a certain concentration of a microbe must be present for it to be detected by a diagnostic test that focuses on detection of a microbe or its components. This concept applies to many tests used to diagnose infectious diseases.

Assessing Provider Utilization of COVID-19 Inflammatory Marker Trends in Hospitalized Patients and Implications in Optimizing Value-Based Care During a Pandemic.

Introduction: Numerous inflammatory markers may serve a role in prognostication of patients hospitalized with COVID-19 infection. Early in the pandemic, our health system created an admission order set which included daily d-dimer, c-reactive protein (CRP), lactate dehydrogenase (LDH), and ferritin. Given more available outcomes data, limiting standing order of labs that do not affect daily management could result in significant cost savings to the health system without adverse patient outcomes. The purpose of this study was to determine ordering and utilization patterns of inflammatory markers by physicians caring for patients hospitalized with COVID-19 infection. Methods: An anonymous 10-question survey was distributed to 125 physicians (Infectious Disease, Hospitalist, Pulmonary and Critical Care faculty). Responses were tallied and values greater than 50% were identified as the majority of the surveyed group. Results: Of the 125 physicians surveyed, 77 (62%) responded. A total of 57.1% (44/77) of physicians reported ordering daily inflammatory markers for 3 - 10 days from admission. Another 31.2% (24/77) ordered markers until clinical improvement or hospital discharge. D-dimer was used for care decisions by 83.1% (64/77) of respondents; 93.8% (60/64) of those reported utilizing it in determining anticoagulation dose. CRP was used by 61% (47/77) of physicians to help identify a secondary infection or determine steroid dose or duration. LDH and ferritin were not used for management decisions by the majority of physicians. Inflammatory markers were not used routinely after isolation precautions had been discontinued, even when ongoing care required mechanical ventilation. Conclusions: Of the markers studied, both d-dimer and CRP were considered useful by most respondents. LDH and ferritin were used less frequently and were not considered as useful in guiding medical decision making. Discontinuation of standing daily LDH and ferritin orders is believed to have potential to result in cost savings to the health care system with no adverse patient outcomes.

An Open Label Trial to Assess Safety of Losartan for Treating Worsening Respiratory Illness in COVID-19.

Rationale: Coronavirus disease 2019 (COVID-19) can cause disruption of the renin-angiotensin system in the lungs, possibly contributing to pulmonary capillary leakage. Thus, angiotensin receptor blockers (ARBs) may improve respiratory failure. Objective: Assess safety of losartan for use in respiratory failure related to COVID-19 (NCT04335123). Methods: Single arm, open label trial of losartan in those hospitalized with respiratory failure related to COVID-19. Oral losartan (25 mg daily for 3 days, then 50 mg) was administered from enrollment until day 14 or hospital discharge. A post-hoc external control group with patients who met all inclusion criteria was matched 1:1 to the treatment group using propensity scores for comparison. Measures: Primary outcome was cumulative incidence of any adverse events. Secondary, explorative endpoints included measures of respiratory failure, length of stay and vital status. Results: Of the 34 participants enrolled in the trial, 30 completed the study with a mean age SD of 53.8 ± 17.7 years and 17 males (57%). On losartan, 24/30 (80%) experienced an adverse event as opposed to 29/30 (97%) of controls, with a lower average number of adverse events on losartan relative to control (2.2 vs. 3.3). Using Poisson regression and controlling for age, sex, race, date of enrollment, disease severity at enrollment, and history of high-risk comorbidities, the incidence rate ratio of adverse events on losartan relative to control was 0.69 (95% CI: 0.49-0.97) Conclusions: Losartan appeared safe for COVID-19-related acute respiratory compromise. To assess true efficacy, randomized trials are needed.

Clinical characteristics, laboratory findings, radiographic signs and outcomes of 61,742 patients with confirmed COVID-19 infection: A systematic review and meta-analysis.

INTRODUCTION: In the current time where we face a COVID-19 pandemic, there is no vaccine or effective treatment at this time. Therefore, the prevention of COVID-19 and the rapid diagnosis of infected patients is crucial. METHOD: We searched all relevant literature published up to February 28, 2020. We used Random-effect models to analyze the appropriateness of the pooled results. RESULT: Eighty studies were included in the meta-analysis, including 61,742 patients with confirmed COVID-19 infection. 62.5% (95% CI 54.5-79, p < 0.001) of patients had a history of recent travel endemic area or contact with them. The most common symptoms among COVID-19 infected patients were fever 87% (95% CI 73-93, p < 0.001), and cough 68% (95% CI 55.5-74, p < 0.001)), respectively. The laboratory analysis showed that thrombocytosis was present in 61% (95% CI 41-78, p < 0.001) CRP was elevated in 79% (95% CI 65-91, p < 0.001), and lymphopenia in 57.5% (95% CI 42-79, p < 0.001). The most common radiographic signs were bilateral involvement in 81% (95% CI 62.5-87, p < 0.001), consolidation in 73.5% (95% CI 50.5-91, p < 0.001), and ground-glass opacity 73.5% (95% CI 40-90, p < 0.001) of patients. Case fatality rate (CFR) in <15 years old was 0.6%, in >50 years old was 39.5%, and in all range group was 6%. CONCLUSIONS: Fever and cough are the most common symptoms of COVID-19 infection in the literature published to date. Thombocytosis, lymphopenia, and increased CRP were common lab findings although most patients included in the overall analysis did not have laboratory values reported. Among Chinese patients with COVID-19, rates of hospitalization, critical condition, and hospitalization were high in this study, but these findings may be biased by reporting only confirmed cases.

Comparison of confirmed COVID-19 with SARS and MERS cases - Clinical characteristics, laboratory findings, radiographic signs and outcomes: A systematic review and meta-analysis.

INTRODUCTION: Within this large-scale study, we compared clinical symptoms, laboratory findings, radiographic signs, and outcomes of COVID-19, SARS, and MERS to find unique features. METHOD: We searched all relevant literature published up to February 28, 2020. Depending on the heterogeneity test, we used either random or fixed-effect models to analyze the appropriateness of the pooled results. Study has been registered in the PROSPERO database (ID 176106). RESULT: Overall 114 articles included in this study; 52 251 COVID-19 confirmed patients (20 studies), 10 037 SARS (51 studies), and 8139 MERS patients (43 studies) were included. The most common symptom was fever; COVID-19 (85.6%, P < .001), SARS (96%, P < .001), and MERS (74%, P < .001), respectively. Analysis showed that 84% of Covid-19 patients, 86% of SARS patients, and 74.7% of MERS patients had an abnormal chest X-ray. The mortality rate in COVID-19 (5.6%, P < .001) was lower than SARS (13%, P < .001) and MERS (35%, P < .001) between all confirmed patients. CONCLUSIONS: At the time of submission, the mortality rate in COVID-19 confirmed cases is lower than in SARS- and MERS-infected patients. Clinical outcomes and findings would be biased by reporting only confirmed cases, and this should be considered when interpreting the data.