Quality of antibiotic prescribing to children through the coronavirus disease 2019 (COVID-19) pandemic

Objective: To describe pediatric outpatient visits and antibiotic prescribing during the coronavirus disease 2019 (COVID-19) pandemic. Design: An observational, retrospective control study from January 2019 to October 2021. Setting: Outpatient clinics, including 27 family medicine clinics, 27 pediatric clinics, and 26 urgent or prompt care clinics. Patients: Children aged 0–19 years receiving care in an outpatient setting. Methods: Data were extracted from the electronic health record. The COVID-19 era was defined as April 1, 2020, to October 31, 2021. Virtual visits were identified by coded encounter or visit type variables. Visit diagnoses were assigned using a 3-tier classification system based on appropriateness of antibiotic prescribing and a subanalysis of respiratory visits was performed to compare changes in the COVID-19 era compared to baseline. Results: Through October 2021, we detected an overall sustained reduction of 18.2% in antibiotic prescribing to children. Disproportionate changes occurred in the percentages of antibiotic visits in respiratory visits for children by age, race or ethnicity, practice setting, and prescriber type. Virtual visits were minimal during the study period but did not result in higher rates of antibiotic visits or in-person follow-up visits. Conclusions: These findings suggest that reductions in antibiotic prescribing have been sustained despite increases in outpatient visits. However, additional studies are warranted to better understand disproportionate rates of antibiotic visits.

Statistical methods for assessing drug interactions using observational data

With advances in medicine, many drugs and treatments become available. On the one hand, polydrug use (i.e. using more than one drug at a time) has been used to treat patients with multiple morbid conditions, and polydrug use may cause severe side effects. On the other hand, combination treatments have been successfully developed to treat severe diseases such as cancer and chronic diseases. Observational data, such as electronic health record data, may provide useful information for assessing drug interactions. In this article, we propose using marginal structural models to assess the average treatment effect and causal interaction of two drugs by controlling confounding variables. The causal effect and the interaction of two drugs are assessed using the weighted likelihood approach, with weights being the inverse probability of the treatment assigned. Simulation studies were conducted to examine the performance of the proposed method, which showed that the proposed method was able to estimate the causal parameters consistently. Case studies were conducted to examine the joint effect of metformin and glyburide use on reducing the hospital readmission for type 2 diabetic patients, and to examine the joint effect of antecedent statins and opioids use on the immune and inflammatory biomarkers for COVID-19 hospitalized patients. [ FROM AUTHOR] Copyright of Journal of Applied Statistics is the property of Routledge and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

P014. Risk Factors for Cardiovascular Events In Hospitalized Patients with COVID-19

Background Between 25%-50% of patients hospitalized with (COVID-19) suffer cardiovascular events. Limited information is available to identify those at greatest risk for cardiac complications. Objectives Objectives were to analyze risk factors associated with cardiovascular events (CE);analyze whether risk factors and outcomes were influenced by race;and analyze survival differences among various groups. Methods This retrospective cohort study of 700 inpatients with COVID-19 was conducted at nine hospitals within a large urban midwestern city. Data was collected from March 9, 2020, to June 20, 2020. Inclusion criteria included all COVID-19 inpatients and excluded non-inpatients. Predictor variables included demographics, comorbidities, and current clinical data. The outcomes were heart failure (HF), deep-vein thrombosis, myocardial infarction, pulmonary edema, stroke, cardiomyopathy, myocarditis, reduced ejection fraction, cardiac arrhythmias, cardiogenic shock, and cardiac arrest. Pearson's correlation coefficients were used to evaluate the correlation between different variables. Multiple logistics regression analyses were conducted to examine which variables predict cardiovascular events for the entire cohort, African American patients, and white patients, respectively. Mann-Whitney U, Chi-square, or Fisher's exact tests were used to examine differences in groups with and without CE and Kaplan-Meier was conducted for survival comparisons between groups. Results Of 700 COVID-19 positive inpatients, 126 experienced cardiovascular events and 574 did not. The incidence of cardiovascular events in our sample population was 18%. As shown in Table 1, we found the following factors were highly associated with the odds of new-onset of CEs: advanced age in years, males, non-Hispanic African American, presence of comorbidities, and decreased saturation levels. Numerous laboratory values were significantly associated with the risk of CEs (Table 1). African Americans had greater odds of CEs in the presence of diabetes and cardiovascular comorbidities (p=0.008, p=0.014, respectively). However, multiple logistics analysis was used to examine the joint effect of the risk factors which suggested that lower serum albumin and neoplastic/immune compromised diseases count were highly associated with CEs for African American COVID-19 inpatients (p=0.001, p=0.044, respectively). SaO2/FiO2 ratio and cardiovascular comorbidities were significantly associated with CEs for white inpatients (p=<0.001, p=0.007, respectively). As shown in Figure 1, Kaplan-Meier survival analysis revealed inpatients with CEs had a much higher mortality rate than those without CEs (45.2% vs. 8.7%). Median survival for patients with CEs was 18 days as opposed to 100 days for those that did not experience CEs. African Americans with CEs experienced higher mortality than those without CEs (43.9% vs. 7.8%). White COVID-19 inpatients' mortality rates were 46.3% and 9.0% for those with and without CEs, respectively. Of the 126 COVID-19 inpatients who had a CE, 14.3% had cardiac arrhythmias and 8.7% had new onset of HF diagnoses, and 4.8% had acute myocardial infarctions. Conclusion Multiple risk factors for CEs and death were identified in this sample of hospitalized patients with COVID-19, and mortality was increased significantly in those inpatients who had CEs. HF, cardiac arrhythmia, and acute myocardial infarction were the most frequently cited CEs implicating the need for long-term follow-up.

A specific low-density neutrophil population correlates with hypercoagulation and disease severity in hospitalized COVID-19 patients.

SARS coronavirus 2 (SARS-CoV-2) is a novel viral pathogen that causes a clinical disease called coronavirus disease 2019 (COVID-19). Although most COVID-19 cases are asymptomatic or involve mild upper respiratory tract symptoms, a significant number of patients develop severe or critical disease. Patients with severe COVID-19 commonly present with viral pneumonia that may progress to life-threatening acute respiratory distress syndrome (ARDS). Patients with COVID-19 are also predisposed to venous and arterial thromboses that are associated with a poorer prognosis. The present study identified the emergence of a low-density inflammatory neutrophil (LDN) population expressing intermediate levels of CD16 (CD16Int) in patients with COVID-19. These cells demonstrated proinflammatory gene signatures, activated platelets, spontaneously formed neutrophil extracellular traps, and enhanced phagocytic capacity and cytokine production. Strikingly, CD16Int neutrophils were also the major immune cells within the bronchoalveolar lavage fluid, exhibiting increased CXCR3 but loss of CD44 and CD38 expression. The percentage of circulating CD16Int LDNs was associated with D-dimer, ferritin, and systemic IL-6 and TNF-α levels and changed over time with altered disease status. Our data suggest that the CD16Int LDN subset contributes to COVID-19-associated coagulopathy, systemic inflammation, and ARDS. The frequency of that LDN subset in the circulation could serve as an adjunct clinical marker to monitor disease status and progression.

Outcomes and Risk Factors for Cardiovascular Events in Hospitalized COVID-19 Patients.

OBJECTIVE: To analyze outcomes and risk factors of cardiovascular events in a metropolitan coronavirus disease 2019 (COVID-19) database, and to perform a subgroup analysis in African American populations to determine whether outcomes and risk factors are influenced by race. DESIGN: Retrospective cohort analysis from March 9, 2020 to June 20, 2020. SETTING: Population-based study in Louisville, KY, USA. PARTICIPANTS: Seven hundred adult inpatients hospitalized with COVID-19. INTERVENTIONS: N/A. MEASUREMENTS AND MAIN RESULTS: This cohort consisted of 126 patients (18%) with cardiovascular events and 574 patients without cardiovascular events. Patients with cardiovascular events had a much higher mortality rate than those without cardiovascular events (45.2% v 8.7%, p < 0.001). There was no difference between African American and white patients regarding mortality (43.9% v 46.3%, p = 1) and length of stay for survivors (11 days v 9.5 days, p = 0.301). Multiple logistics regression analysis suggested that male, race, lower SaO2/FIO2, higher serum potassium, lower serum albumin, and number of cardiovascular comorbidities were highly associated with the occurrence of cardiovascular events in COVID-19 patients. Lower serum albumin and neoplastic and/or immune-compromised diseases were highly associated with cardiovascular events for African American COVID-19 patients. SaO2/FIO2 ratio and cardiovascular comorbidity count were significantly associated with cardiovascular events in white patients. CONCLUSIONS: Cardiovascular events were prevalent and associated with worse outcomes in hospitalized patients with COVID-19. Outcomes of cardiovascular events in African American and white COVID-19 patients were similar after propensity score matching analysis. There were common and unique risk factors for cardiovascular events in African American COVID-19 patients when compared with white patients.

Repurposing Treatment of Wernicke-Korsakoff Syndrome for Th-17 Cell Immune Storm Syndrome and Neurological Symptoms in COVID-19: Thiamine Efficacy and Safety, In-Vitro Evidence and Pharmacokinetic Profile.

Coronavirus disease identified in 2019 (COVID-19) can be complicated by the Th17 cell-mediated IL-17 proinflammatory response. We tested if thiamine can effectively lower the Th17 response in a clinical study [Proinflammatory state in alcohol use disorder patients termed as disease controls (DC)] and corroborated the results using an in vitro study. We developed an effective dose range and model for key pharmacokinetic measures with the potential of targeting the cytokine storm and neurological symptoms of COVID-19. Three-week 200 mg dose of thiamine was administered to sixteen DC patients. Eight healthy volunteers (HV) were also included in this investigation. A subsequent in vitro study was performed to validate the effectiveness of thiamine [100 mg/day equivalent (0.01 µg/ml)] treatment in lowering the Th17 proinflammatory response in a mouse macrophage cell line (RAW264.7) treated with ethanol. Based on recent publications, we compared the results of the IL-17 response from our clinical and in vitro study to those found in other proinflammatory disease conditions (metabolic conditions, septic shock, viral infections and COVID-19) and effective and safe dose ranges of thiamine. We developed a pharmacokinetic profile for thiamine dose range as a novel intervention strategy in COVID-19. DC group showed significantly elevated proinflammatory cytokines compared to HV. Thiamine-treated DC patients showed significant lowering in IL-17 and increase in the IL-22 levels. In humans, a range of 79-474 mg daily of thiamine was estimated to be effective and safe as an intervention for the COVID-19 cytokine storm. A literature review showed that several neurological symptoms of COVID-19 (∼45.5% of the severe cases) occur in other viral infections and neuroinflammatory states that may also respond to thiamine treatment. Thiamine, a very safe drug even at very high doses, could be repurposed for treating the Th17 mediated IL-17 immune storm, and the subsequent neurological symptoms observed in COVID-19. Further studies using thiamine as an intervention/prevention strategy in COVID-19 patients could identify its precise anti-inflammatory role.