ABSTRACT
Background. Tocilizumab (TCZ) was approved by the Food and Drug Administration under emergency use authorization for treatment of COVID-19 in patients requiring supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation. Despite multiple clinical trials, there remain unanswered questions surrounding TCZ use. Methods. This multi-hospital retrospective cohort study included patients who received TCZ for COVID-19 between January 29th, 2021 and June 30th, 2021 at five University of Pennsylvania Health System (UPHS) hospitals. Patients were eligible for TCZ per UPHS criteria if they scored >= 5 on the World Health Organization (WHO) ordinal scale for <= 24 hours and experienced < 14 days of acute COVID-19 symptoms. Descriptive statistics were performed to characterize usage within the health system. Results. This study evaluated 134 patients who received TCZ for the treatment of COVID-19. TCZ was ordered a median of 22 hours (interquartile range [IQR], 13.2 - 41.5) after hospital admission. A majority of patients (76.1%) were admitted to the intensive care unit and a small portion (12.7%) had a WHO ordinal scale that was >5 at time of TCZ order entry. All patients received concomitant dexamethasone therapy at a total prednisone equivalent of 400 mg (IQR, 335.6 - 480). Overall 33.6% of patients experienced an adverse event (ADE) within 30 days of TCZ administration (Table 1). Most common ADEs included bacterial infection (29.9%), hepatitis (6.7%), and fungal infection (3%);other etiologies of ADEs were not accounted for. All-cause mortality (Table 2) at day 30 occurred in 20.9% of patients and median time from TCZ administration to mortality was 12.5 days (IQR 5 - 18.3). Ninety-six patients in the cohort (71.6%) were discharged by day 30. Of the subgroup discharged by day 30, the majority (70.8%) were discharged to home. Conclusion. Patients who received TCZ for severe COVID-19 experienced 20.9% mortality;mortality was higher among those with higher ordinal scale at the time of TCZ dosing. A large portion of patients (70.8%) were discharged to home within 30 days. One third of patients experienced an adverse event, primarily bacterial or fungal infection. Our experience may be useful in counseling patients about anticipated effects of TCZ.
ABSTRACT
Background. Limiting antibiotic prescribing to the shortest effective duration reduces antibiotic-associated adverse events and resistance. Up to two-thirds of patients receive excessive durations of therapy for pneumonia. This study evaluated the effect of a stewardship intervention to reduce excess antibiotic duration for inpatients with pneumonia. Methods. A dashboard was developed to generate real-time alerts when inpatients at an academic medical center received antibiotics with an indication of community- or hospital-acquired pneumonia for more than 5 or 7 days, respectively. From November 2019 through April 2021, alerts were regularly reviewed by the antibiotic stewardship (AS) team and intervened upon when patients exceeded the guideline recommended duration of therapy for pneumonia without additional indications for continuing antibiotics. We compared inappropriate duration of therapy pre- and post-implementation of the dashboard by calculating the mean number of excess days of antibiotics beyond the recommended duration. Patients with SARS-CoV-2 infection and patients on hospital services that care for patients with cysticfibrosis, bronchiectasis, or immunocompromising conditions were excluded. Four other hospitals within the same health system that did not utilize the dashboard generated alerts served as a comparison group. Results. During the intervention period, the AS team reviewed 834 patients with dashboard alerts and documented 115 interventions. For alerts reviewed without intervention, reasons for lack of intervention included active Infectious Diseases consult, additional infection diagnosis requiring a longer duration, and delayed clinical improvement. In the post-implementation period there was a mean of 1.28 excess days of antibiotics for pneumonia compared to the pre-implementation mean of 1.36 excess days. In comparison, aggregating data from the hospitals not utilizing the dashboard, there was a mean of 0.67 excess days post-intervention, compared to a mean 0.62 days pre-intervention. Conclusion. The pneumonia dashboard is a potentially valuable stewardship tool which may reduce excess days of antibiotics for pneumonia. The dashboard's impact may be improved by daily review and excluding patients with additional infection diagnoses.
ABSTRACT
Background. With the onset of the coronavirus disease 2019 (COVID-19) pandemic, pediatric primary care delivery changed rapidly. Prior studies have demonstrated a reduction in ambulatory encounters and antibiotic prescriptions with the pandemic onset;however, the durability of these reductions in pediatric primary care in the United States has not been assessed. Methods. We conducted a retrospective cohort study to assess the impact of the COVID-19 pandemic and associated public health measures (e.g. social distancing, masking, school closures, and increased availability of telemedicine) on antibiotic prescribing and encounter volume in 27 pediatric primary care practices, and the duration of these changes. Patients under age 19 with an encounter from January 1, 2018 through December 31, 2020 were included. The primary outcome was monthly antibiotic prescriptions per 1000 patients, in the overall population and a subset of encounters with infectious diagnoses, including respiratory tract infections (RTIs). Interrupted time series (ITS) analysis was performed. Results. There were 60,562 total antibiotic prescriptions from April to December in 2019 and 14,605 antibiotic prescriptions during the same months in 2020, a 76% reduction. The reduction in RTI encounter prescriptions accounted for 91.5% of the overall reduction in prescriptions from 2019 to 2020. Using ITS analysis, there was an immediate decrease from 31.6 to 7.4 prescriptions/1000 patients (predicted means) in April 2020 (-24.2 prescriptions/1000 patients;95% CI: -31.9, -16.4) (Figures 1 and 2). This was followed by a stable rate of antibiotic prescriptions that remained flat through December 2020. For RTI encounters, a similar pattern was seen, with a decrease by 21.8 prescriptions/1000 patients;95% CI: -29.5, -14.2) (Figures 1 and 2). Encounter volume also decreased immediately, and while overall encounter volume began returning to a pre-pandemic baseline volume toward the end of the study period, RTI encounter volume remained persistently lower through December 2020 (Figure 3). RTI = respiratory tract infection;UTI = urinary tract infection;SSTI = skin and soft tissue infection. Months are numbered sequentially, starting with January (number 1). Dashed line indicates first full month of the pandemic, April 2020. Interrupted time series analysis for antibiotic prescriptions per 1000 patients by month from January 2018 to December 2020 for (A) all antibiotics as well as antibiotics prescribed at encounters with (B) respiratory tract infections (RTIs), (C) urinary tract infections (UTIs), and (D) skin and soft tissue infections (SSTIs) Intervention starts in April 2020 (dashed line). Months are numbered sequentially, starting with January (number 1). Dashed line indicates first full month of the pandemic, April 2020. Antibiotic prescriptions per 1000 billed encounters by month from January 2018 to December 2020 for (A) all encounters, as well as antibiotics prescribed at encounters with (B) respiratory tract infections (RTIs), (C) urinary tract infections (UTIs), and (D) skin and soft tissue infections (SSTIs) Months are numbered sequentially, starting with January (number 1). Conclusion. Dramatic reductions in antibiotic prescribing in pediatric primary care during the COVID-19 pandemic were sustained through 2020, primarily driven by reductions in RTI encounters.
ABSTRACT
Background. Although SARS-CoV-2 predominantly targets the respiratory system, it has also been associated with vascular complications including stroke. Identifying COVID-19 patients at elevated risk for stroke can help inform target anticoagulation strategies. We sought to understand how symptoms and laboratory markers at presentation with COVID-19 relate to stroke risk. Methods. We enrolled a cohort of 1324 subjects who were hospitalized with COVID-19 across six PennMedicine hospitals between April and August 2020 and performed retrospective, manual chart review to measure exposures including presenting symptoms and admission inflammatory markers. Data were organized with a REDCap database, and analyses were performed using R statistical software, with Bayesian binomial regression models fit using Stan Hamiltonian Monte Carlo via the "brms" package. Results. Among 1324 subjects, 19 stroke events were observed within 30 days of COVID-19 diagnosis. Admission inflammatory markers, including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), ferritin, and D-dimer, were poor predictors of stroke risk. Among presenting symptoms, including respiratory, gastrointestinal, dermatologic, and neurologic features of COVID-19 disease, only altered mental status documented on presentation (in 529 subjects) was significantly associated with stroke risk (odds ratio 6.06, 95% credible interval 2.16 - 18.7). Conclusion. Inflammatory markers associated with COVID-19 disease severity did not discriminate patients at high versus low risk of stroke in this cohort. Altered mental status documented on presentation was significantly associated with incident stroke during COVID-19 disease.
ABSTRACT
Background. SARS-CoV-2 monoclonal antibodies (SMA) have demonstrated efficacy in treatment of early, mild to moderate COVID-19 in patients at high risk for progression to severe COVID-19. We created an SMA infusion clinic at a large, urban academic medical center using both internal and community-based referral mechanisms to promote the equitable distribution of treatment. Methods. Data were analyzed from clinic referrals from December 13, 2020 through April 20, 2021. Patient demographics, census-based area deprivation index (ADI) scores (scale of 1-10, with 1 representing least socioeconomic deprivation and 10 representing most), and relevant comorbidities were collected. Outcomes included days of symptoms until referral, patient receipt of SMA therapy after referral, adverse events, and ER visits and hospitalizations within 14 days of SMA administration. Association between demographic factors and relevant outcomes were determined using chi-square or Wilcoxon rank-sum tests as appropriate. Results. 47/433 (11%) referred patients were ineligible based on inclusion and exclusion criteria. Of eligible patients, 310/386 (80%) received treatment;patients who did not receive treatment either declined (93%), could not be contacted (5%), no-showed (1%), or were admitted for hypoxia (1%). Of treated patients, only 3 (1%) had adverse reactions. Within 14 days of SMA administration, 28 (9%) patients visited the ER or were admitted for COVID-19. Black patients had a longer median duration of symptoms prior to referral compared to White patients (5 vs. 3 days, p < 0.01) (Figure 1). White patients were more likely to receive SMA after referral compared to Black patients (88% vs. 64%, p < 0.01), as were patients with ADI score 1-5 compared to those with ADI score 6-10 (88% vs. 70%, p < 0.01) (Figures 2 and 3). Black patients who received SMA had a higher rate of ER visits or admissions than White patients, although the difference was not statistically significant (14% vs. 7%, p = 0.10). Conclusion. Rate of adverse reactions and COVID-related ER visits or admissions were low in patients who received SMA. Despite efforts to promote the equitable distribution of treatment through multiple referral mechanisms, racial and socioeconomic disparities still exist.