Real-world effectiveness of sotrovimab in preventing hospitalization and mortality in high-risk patients with COVID-19 in the United States: A cohort study from the Mayo Clinic electronic health records.

BACKGROUND: To describe outcomes of high-risk patients with coronavirus disease 2019 (COVID-19) treated with sotrovimab, other monoclonal antibodies (mAbs), or antivirals, and patients who did not receive early COVID-19 treatment. We also evaluate the comparative effectiveness of sotrovimab versus no treatment in preventing severe clinical outcomes. METHODS: This observational retrospective cohort study analyzed Mayo Clinic electronic health records. Non-hospitalized adult patients diagnosed with COVID-19 from May 26, 2021 and April 23, 2022 and at high risk of COVID-19 progression were eligible. The primary outcome was 29-day all-cause hospitalization and/or death. Outcomes were described for patients treated with sotrovimab, other mAbs, or antivirals, and eligible but untreated patients, and compared between sotrovimab-treated and propensity score (PS)-matched untreated cohorts. RESULTS: We included 35,485 patients (sotrovimab, 1369; other mAbs, 6488; antivirals, 133; high-risk untreated, 27,495). A low proportion of patients treated with sotrovimab (n = 33/1369, 2.4%), other mAbs (n = 147/6488, 2.3%), or antivirals (n = 2/133, 1.5%) experienced all-cause hospitalization or death. Among high-risk untreated patients, the percentage of all-cause hospitalization or death was 3.3% (n = 910/27,495). In the PS-matched analysis, 2.5% (n = 21/854) of sotrovimab-treated patients experienced all-cause hospitalization and/or death versus 2.8% (n = 48/1708) of untreated patients (difference, -0.4%; p = 0.66). Significantly fewer sotrovimab-treated patients required intensive care unit admission (0.5% vs 1.8%; difference, -1.3%; p = 0.002) or respiratory support (3.5% vs 8.7%; difference, -5.2%; p < 0.001). CONCLUSIONS: There was no significant difference in the proportion of sotrovimab-treated and PS-matched untreated patients experiencing 29-day all-cause hospitalization or mortality, although significantly fewer sotrovimab-treated patients required intensive care unit admission or respiratory support.

Development and validation of a preliminary multivariable diagnostic model for identifying unusual infections in hospitalized patients.

Diagnostic delay leads to poor outcomes in infections, and it occurs more often when the causative agent is unusual. Delays are attributable to failing to consider such diagnoses in a timely fashion. Using routinely collected electronic health record (EHR) data, we built a preliminary multivariable diagnostic model for early identification of unusual fungal infections and tuberculosis in hospitalized patients. We conducted a two-gate case-control study. Cases encompassed adult patients admitted to 19 Mayo Clinic enterprise hospitals between January 2010 and March 2023 diagnosed with blastomycosis, cryptococcosis, histoplasmosis, mucormycosis, pneumocystosis, or tuberculosis. Control groups were drawn from all admitted patients (random controls) and those with community-acquired infections (ID-controls). Development and validation datasets were created using randomization for dividing cases and controls (7:3), with a secondary validation using ID-controls. A logistic regression model was constructed using baseline and laboratory variables, with the unusual infections of interest outcome. The derivation dataset comprised 1043 cases and 7000 random controls, while the 451 cases were compared to 3000 random controls and 1990 ID-controls for validation. Within the derivation dataset, the model achieved an area under the curve (AUC) of 0.88 (95% confidence interval [CI]: 0.87-0.89) with a good calibration accuracy (Hosmer-Lemeshow P = 0.623). Comparable performance was observed in the primary (AUC = 0.88; 95% CI: 0.86-0.9) and secondary validation datasets (AUC = 0.84; 95% CI: 0.82-0.86). In this multicenter study, an EHR-based preliminary diagnostic model accurately identified five unusual fungal infections and tuberculosis in hospitalized patients. With further validation, this model could help decrease time to diagnosis.

Sequential Time to Positivity as a Prognostic Indicator in Staphylococcus aureus Bacteremia.

Background: We aimed to determine the factors associated with sequential blood culture time to positivity (STTP) and validate the previously defined time to positivity (TTP) ratio threshold of 1.5 in predicting adverse disease outcomes and mortality of Staphylococcus aureus bacteremia (SAB). Methods: We conducted an observational study of adult patients with SAB. The TTP ratio was calculated by dividing the TTP of the second blood culture by that of the first. Results: Of 186 patients, 69 (37%) were female, with a mean age of 63.6 years. Median TTP was 12 hours (interquartile range [IQR], 10-15 hours) from the initial and 21 hours (17-29) from sequential blood cultures. Methicillin-resistant S aureus (MRSA)-infected patients had significantly shorter STTPs (P < .001) and lower TTP ratios (P < .001) compared to patients with methicillin-susceptible S aureus (MSSA). A significant correlation between initial and STTP was observed in patients with MRSA (r = 0.42, P = .002) but not in those with MSSA. A higher rate of native valve endocarditis (NVE) significantly correlated with a TTP ratio of ≤1.5 (odds ratio, 2.65 [95% confidence interval, 1.3-5.6]; P = .01). The subgroup having an initial TTP <12 hours combined with a TTP ratio ≤1.5 showed the highest prevalence of NVE. Conclusions: The STTP varies based on methicillin susceptibility of S aureus isolate. This study suggests a potential clinical utility of the STTP to identify patients at a higher risk of NVE. However, prospective studies are required to validate these findings.

A Pragmatic Study of Cardiovascular Disease During Long-Term COVID-19.

BACKGROUND: Many patients diagnosed with COVID-19 have persistent cardiovascular symptoms, but whether this represents a true cardiac process is unclear. This study assessed whether symptoms associated with long COVID among patients referred for cardiovascular evaluation are associated with objective abnormalities on cardiac testing to explain their clinical presentation. METHODS: A retrospective cohort study of 40,462 unique patients diagnosed with COVID-19 at our tertiary referral was conducted and identified 363 patients with persistent cardiovascular symptoms a minimum of 4 weeks after polymerase chain reaction confirmed COVID-19 infection. Patients had no cardiovascular symptoms prior to COVID-19 infection. Each patient was referred for cardiovascular evaluation at a tertiary referral center. The incidence and etiology of abnormalities on cardiovascular testing among patients with long COVID symptoms are reported here. The cohort was subsequently divided into 3 categories based on the dominant circulating severe acute respiratory syndrome coronavirus 2 variant at the time of initial infection for further analysis. RESULTS: Among 40,462 unique patients diagnosed with COVID-19 at our tertiary referral center from April 2020 to March 2022, 363 (0.9%) patients with long COVID were evaluated by Cardiology for possible cardiac sequelae from COVID and formed the main study cohort. Of these, 229 (63%) were vaccinated and 47 (12.9%) had severe initial infection, receiving inpatient treatment for COVID prior to developing long COVID symptoms. Symptoms were associated with a cardiac cause in 85 (23.4%), of which 52 (14.3%) were attributed to COVID; 39 (10.7%) with new cardiac disease from COVID, and 13 (3.6%) to worsening of pre-existing cardiac disease after COVID infection. The median troponin change in 45 patients with troponin measurements within 4 weeks of acute infection was +4 ng/dL (9 to 13 ng/dL). Among the total cohort with long COVID, 83.7% were diagnosed during the pre-Delta phase, 13.2% during the Delta phase, and 3.1% during the Omicron phase of the pandemic. There were 6 cases of myocarditis, 11 rhythm disorders, 8 cases of pericarditis, 5 suspected cases of endothelial dysfunction, and 33 cases of autonomic dysfunction. CONCLUSION: This pragmatic retrospective cohort study suggests that patients with long COVID referred for cardiovascular evaluation infrequently have new, objective cardiovascular disease to explain their clinical presentation. A multidisciplinary, patient-centered approach is warranted for symptom management along with conservative use of diagnostic testing.

Understanding clinical implementation coordinators' experiences in deploying evidence-based interventions.

PURPOSE: The fluoroquinolone restriction for the prevention of Clostridioides difficile infection (FIRST) trial is a multisite clinical study in which sites carry out a preauthorization process via electronic health record-based best-practice alert (BPA) to optimize the use of fluoroquinolone antibiotics in acute care settings. Our research team worked closely with clinical implementation coordinators to facilitate the dissemination and implementation of this evidence-based intervention. Clinical implementation coordinators within the antibiotic stewardship team (AST) played a pivotal role in the implementation process; however, considerable research is needed to further understand their role. In this study, we aimed to (1) describe the roles and responsibilities of clinical implementation coordinators within ASTs and (2) identify facilitators and barriers coordinators experienced within the implementation process. METHODS: We conducted a directed content analysis of semistructured interviews, implementation diaries, and check-in meetings utilizing the conceptual framework of middle managers' roles in innovation implementation in healthcare from Urquhart et al. RESULTS: Clinical implementation coordinators performed a variety of roles vital to the implementation's success, including gathering and compiling information for BPA design, preparing staff, organizing meetings, connecting relevant stakeholders, evaluating clinical efficacy, and participating in the innovation as clinicians. Coordinators identified organizational staffing models and COVID-19 interruptions as the main barriers. Facilitators included AST empowerment, positive relationships with staff and oversight/governance committees, and using diverse implementation strategies. CONCLUSION: When implementing healthcare innovations, clinical implementation coordinators facilitated the implementation process through their roles and responsibilities and acted as strategic partners in improving the adoption and sustainability of a fluoroquinolone preauthorization protocol.

COVID-19 outcome is not affected by anti-CD20 or high-titer convalescent plasma in immunosuppressed patients.

The role of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) convalescent plasma in the treatment of Coronavirus Disease 2019 (COVID-19) in immunosuppressed individuals remains controversial. We describe the course of COVID-19 in patients who had received anti-CD20 therapy within the 3 years prior to infection. We compared outcomes between those treated with and those not treated with high titer SARS-CoV2 convalescent plasma. We identified 144 adults treated at Mayo clinic sites who had received anti-CD20 therapies within a median of 5.9 months prior to the COVID-19 index date. About one-third (34.7%) were hospitalized within 14 days and nearly half (47.9%) within 90 days. COVID-19 directed therapy included anti-spike monoclonal antibodies (n = 30, 20.8%), and, among those hospitalized within 14 days (n = 50), remdesivir (n = 45, 90.0%), glucocorticoids (n = 36, 72.0%) and convalescent plasma (n = 24, 48.0%). The duration from receipt of last dose of anti-CD20 therapy did not correlate with outcomes. The overall 90-day mortality rate was 14.7%. Administration of convalescent plasma within 14 days of the COVID-19 diagnosis was not significantly associated with any study outcome. Further study of COVID-19 in CD20-depleted individuals is needed focusing on the early administration of new and potentially combination antiviral agents, associated or not with vaccine-boosted convalescent plasma.

Genomic epidemiology reveals the dominance of Hennepin County in the transmission of SARS-CoV-2 in Minnesota from 2020 to 2022.

IMPORTANCE: We analyzed over 22,000 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes of patient samples tested at Mayo Clinic Laboratories during a 2-year period in the COVID-19 pandemic, which included Alpha, Delta, and Omicron variants of concern to examine the roles and relationships of Minnesota virus transmission. We found that Hennepin County, the most populous county, drove the transmission of SARS-CoV-2 viruses in the state after including the formation of earlier clades including 20A, 20C, and 20G, as well as variants of concern Alpha and Delta. We also found that Hennepin County was the source for most of the county-to-county introductions after an initial predicted introduction with the virus in early 2020 from an international source, while other counties acted as transmission "sinks." In addition, major policies, such as the end of the lockdown period in 2020 or the end of all restrictions in 2021, did not appear to have an impact on virus diversity across individual counties.

The Diagnostic Accuracy of Metagenomic Next-Generation Sequencing in Diagnosing Pneumocystis Pneumonia: A Systemic Review and Meta-analysis.

Background: Pneumocystis pneumonia (PCP) is a growing concern as the immunocompromised population expands. Current laboratory approaches are limited. This systematic review aimed to evaluate metagenomic next-generation sequencing (MNGS) tests' performance in detecting PCP. Methods: Five databases were searched through December 19, 2022, to identify original studies comparing MNGS with clinically diagnosed PCP. To assess the accuracy, symmetric hierarchical summary receiver operating characteristic models were used. Results: Eleven observational studies reporting 1442 patients (424 with PCP) were included. Six studies focused exclusively on recipients of biologic immunosuppression (none with HIV-associated immunosuppression). Six were exclusively on bronchoalveolar lavage, while 1 was on blood samples. The sensitivity of MGNS was 0.96 (95% CI, 0.90-0.99), and specificity was 0.96 (95% CI, 0.92-0.98), with negative and positive likelihood ratios of 0.02 (95% CI, 0.01-0.05) and 19.31 (95% CI, 10.26-36.36), respectively. A subgroup analysis of studies exclusively including bronchoalveolar lavage (BAL) and blood samples demonstrated a sensitivity of 0.94 (95% CI, 0.78-0.99) and 0.93 (95% CI, 0.80-0.98) and a specificity of 0.96 (95% CI, 0.88-0.99) and 0.98 (95% CI, 0.76-1.00), respectively. The sensitivity analysis on recipients of biologic immunosuppression showed a sensitivity and specificity of 0.96 (95% CI, 0.90-0.98) and 0.94 (95% CI, 0.84-0.98), respectively. The overall confidence in the estimates was low. Conclusions: Despite the low certainty of evidence, MNGS detects PCP with high sensitivity and specificity. This also applies to recipients of biologic immunosuppression and tests performed exclusively on blood samples without the need for BAL. Further studies are required in individuals with HIV-associated immunosuppression.

The Influence of Social Determinants on Receiving Outpatient Treatment with Monoclonal Antibodies, Disease Risk, and Effectiveness for COVID-19.

BACKGROUND: Limited research has studied the influence of social determinants of health (SDoH) on the receipt, disease risk, and subsequent effectiveness of neutralizing monoclonal antibodies (nMAbs) for outpatient treatment of COVID-19. OBJECTIVE: To examine the influence of SDoH variables on receiving nMAb treatments and the risk of a poor COVID-19 outcome, as well as nMAb treatment effectiveness across SDoH subgroups. DESIGN: Retrospective observational study utilizing electronic health record data from four health systems. SDoH variables analyzed included race, ethnicity, insurance, marital status, Area Deprivation Index, and population density. PARTICIPANTS: COVID-19 patients who met at least one emergency use authorization criterion for nMAb treatment. MAIN MEASURE: We used binary logistic regression to examine the influence of SDoH variables on receiving nMAb treatments and risk of a poor outcome from COVID-19 and marginal structural models to study treatment effectiveness. RESULTS: The study population included 25,241 (15.1%) nMAb-treated and 141,942 (84.9%) non-treated patients. Black or African American patients were less likely to receive treatment than white non-Hispanic patients (adjusted odds ratio (OR) = 0.86; 95% CI = 0.82-0.91). Patients who were on Medicaid, divorced or widowed, living in rural areas, or living in areas with the highest Area Deprivation Index (most vulnerable) had lower odds of receiving nMAb treatment, but a higher risk of a poor outcome. For example, compared to patients on private insurance, Medicaid patients had 0.89 (95% CI = 0.84-0.93) times the odds of receiving nMAb treatment, but 1.18 (95% CI = 1.13-1.24) times the odds of a poor COVID-19 outcome. Age, comorbidities, and COVID-19 vaccination status had a stronger influence on risk of a poor outcome than SDoH variables. nMAb treatment benefited all SDoH subgroups with lower rates of 14-day hospitalization and 30-day mortality. CONCLUSION: Disparities existed in receiving nMAbs within SDoH subgroups despite the benefit of treatment across subgroups.

Left Ventricular Assist Device: Review of Antimicrobial Prophylaxis Strategies and Incidence of Infections at a Tertiary Care Center 12-Year Experience.

Background: Left ventricular assist devices (LVAD) have an associated infection rate of 13%-80% postimplant. An optimal strategy for surgical infection prophylaxis (SIP) at the time of implantation has not been well defined. We aimed to evaluate the different LVAD implantation antibiotic prophylaxis regimens as well as the incidence of LVAD infection at our institution. Methods: We performed a single-center, retrospective study of patients who underwent LVAD implantation between February 2007 and June 2019. The primary outcome was the incidence of LVAD infection (LVADI), within 3 months and 1 year of placement, between patients who received expanded or narrow-spectrum regimens for SIP. We assessed outcomes using Kaplan-Meier, time-to-first event. We used a noninferiority analysis, which was established if the narrow-spectrum event rate was no more than 5% greater than the expanded-spectrum event rate. Results: We included 399 patients, 305 (76.4%) patients received narrow-spectrum SIP, whereas the remaining 94 (23.6%) patients received the expanded-spectrum regimen. Statistical noninferiority of the narrow spectrum to the multiple drug regimen was demonstrated at both time points, and statistical superiority of the narrow-spectrum group across 12-month follow up was further evident (P = .037). Conclusions: We report evidence supporting noninferiority, or even superiority, of the narrow-spectrum over expanded-spectrum antimicrobial prophylaxis strategy with respect to LVADI. These findings support data-driven antimicrobial prophylaxis strategies.

Bloodstream Infection Due to Coagulase-Negative Staphylococci: Impact of Species on Prevalence of Infective Endocarditis.

(1) Background: Coagulase-negative staphylococci (CoNS) are an important group of organisms that can cause bloodstream infection (BSI) and infective endocarditis (IE). The prevalence of IE in patients with BSI due to different CoNS species, however, has received limited attention; (2) Methods: A retrospective study of adults with monomicrobial CoNS BSI who had undergone echocardiography and a risk factor analysis was done to determine the most common CoNS species that cause definite IE; (3) Results: 247 patients with CoNS BSI were included in the investigation; 49 (19.8%) had definite IE, 124 (50.2%) possible IE, and 74 (30.0%) BSI only. The latter two entities were grouped in one category for further analysis. The most common species in CoNS BSI was Staphylococcus epidermidis (79.4%) and most patients (83.2%) had possible IE/BSI only. 59.1% of patients with BSI due to S. lugdunensis had definite IE. The majority of CoNS were healthcare-associated/nosocomial bacteremia. Multivariable analysis demonstrated that valve disease (p = 0.002) and a foreign cardiovascular material (p < 0.001) were risk factors associated with definite IE. Patients with S. lugdunensis BSI had an 8-fold higher risk of definite IE than did those with S. epidermidis BSI and nearly a 13-fold higher risk than did patients with BSI due to other species of CoNS (p = 0.002); (4) Conclusions: The prevalence of definite IE in patients with BSI due to different CoNS species was significant. CoNS bacteremia, particularly with S. lugdunensis, confers a significant risk of IE, particularly in patients with a valve disease or intravascular foreign body material and should not be immediately dismissed as a contaminant.

Infectious disease physician characteristics and prescription of meropenem in the hospital.

Objective: Physician characteristics may be correlated with medical treatment decisions and patient outcomes. This study examined the correlations between characteristics of infectious disease (ID) physicians and the use of the restricted antimicrobial meropenem. Design: This was a retrospective cohort study following 27 attending ID physicians for 5 years at a large academic medical center. Methods: All inpatient ID clinical encounters between 2013 and 2018 were assessed for physician and patient characteristics, including patient Charlson Comorbidity Index, patient sex, ID service seeing the patient, physician career stage, physician training location, and physician sex. Adjusted and unadjusted odds ratios were calculated for the receipt of meropenem on the same day as an ID clinical note. Results: Between 2013 and 2018, meropenem was administered on the same day as 9046 (11.1%) of 81,787 inpatient ID encounters. After adjustment for patient and practice-specific factors, physician career stage was associated with administration of meropenem. Patients seen by mid-career and late-career ID physicians were more likely to receive meropenem than those seen by early-career physicians (aOR 1.22 95% confidence interval [CI 1.13-1.31 and aOR 1.17 95% CI 1.10-1.25, respectively). Conclusions: ID provider characteristics may help target future antimicrobial stewardship program interventions.

Body temperature and infection in critically ill patients on continuous kidney replacement therapy.

PURPOSE: Continuous kidney replacement therapy (CKRT) is an increasingly common intervention for critically ill patients with kidney failure. Because CKRT affects body temperature, detecting infections in patients on CKRT is challenging. Understanding the relation between CKRT and body temperature may facilitate earlier detection of infection. METHODS: We retrospectively reviewed adult patients (≥ 18 years) admitted to the intensive care unit at Mayo Clinic in Rochester, Minnesota, from December 1, 2006, through November 31, 2015, who required CKRT. We summarized central body temperatures for these patients according to the presence or absence of infection. RESULTS: We identified 587 patients who underwent CKRT during the study period, of whom 365 had infections, and 222 did not have infections. We observed no statistically significant differences in minimum (P = .70), maximum (P = .22), or mean (P = .55) central body temperature for patients on CKRT with infection vs. those without infection. While not on CKRT (before CKRT initiation and after cessation), all three body temperature measurements were significantly higher in patients with infection than in those without infection (all P < .02). CONCLUSION: Body temperature is insufficient to indicate an infection in critically ill patients on CKRT. Clinicians should remain watchful for other signs, symptoms, and indications of infection in patients on CKRT because of expected high infection rates.

Septic shock definitions and associated outcomes in blood culture positive critically ill patients.

Background: The proposed definition of septic shock in the Sepsis-3 consensus statement has been previously validated in critically ill patients. However, the subset of critically ill patients with sepsis and positive blood cultures needs further evaluation. To compare the combined (old and new septic shock) versus old definition of septic shock in sepsis patients that have positive blood cultures and are critically ill. Methods: A retrospective cohort study of adult patients (age ≥18 years), who had evidence of positive blood cultures, requiring intensive care unit (ICU) admission at a large tertiary care academic center from January 2009 through October 2015. Eligible subjects who opted out of research participation, those requiring intensive care admission after elective surgery, and those who were deemed to have a low probability of infection were excluded. Basic demographics data, clinical and laboratory parameters, and outcomes of interest were pulled from the validated institutional database/repository and contrasted between the patients who qualified the new and old definitions criteria (combined) of septic shock versus the group meeting the old septic shock criteria only. Results: We included a total of 477 patients in the final analysis who qualified for old and new septic shock definitions. For the entire cohort, median age was 65.6 (IQR, 55-75) years, with male predominance (N=258, 54%). When compared to patients in the group who only met the old definition (N=206), the patients who met the combined (new or both new and old, N=271) definition had a higher APACHE III scores, 92 (IQR, 76-112) vs. 76 (IQR, 61-95), P<0.001; a higher SOFA day-1 score of 10 (IQR, 8-13) vs. 7 (IQR, 4-10), P<0.001, but did not differ significantly in age 65.5 years (IQR, 55-74) vs. 66 years (IQR, 55-76) years, P=0.47. The patients who met the combined (new or both new and old) definition had higher chances of having conservative resuscitation preferences (DNI/DNR); 77 (28.4) vs. 22 (10.7), P<0.001. The same group also had worse outcomes in terms of hospital mortality (34.3% vs. 18%, P<0.001) and standardized mortality ratio (0.76 vs. 0.52, P<0.04). Conclusions: In patients with sepsis with positive blood cultures, the group of patients meeting the combined definition (new or both new and old) have higher severity of illness, higher mortality, and a worse standardized mortality ratio as compared to patients meeting the old definition of septic shock.

Neutralizing Monoclonal Antibody Use and COVID-19 Infection Outcomes.

Importance: Evidence on the effectiveness and safety of COVID-19 therapies across a diverse population with varied risk factors is needed to inform clinical practice. Objective: To assess the safety of neutralizing monoclonal antibodies (nMAbs) for the treatment of COVID-19 and their association with adverse outcomes. Design, Setting, and Participants: This retrospective cohort study included 167 183 patients from a consortium of 4 health care systems based in California, Minnesota, Texas, and Utah. The study included nonhospitalized patients 12 years and older with a positive COVID-19 laboratory test collected between November 9, 2020, and January 31, 2022, who met at least 1 emergency use authorization criterion for risk of a poor outcome. Exposure: Four nMAb products (bamlanivimab, bamlanivimab-etesevimab, casirivimab-imdevimab, and sotrovimab) administered in the outpatient setting. Main Outcomes and Measures: Clinical and SARS-CoV-2 genomic sequence data and propensity-adjusted marginal structural models were used to assess the association between treatment with nMAbs and 4 outcomes: all-cause emergency department (ED) visits, hospitalization, death, and a composite of hospitalization or death within 14 days and 30 days of the index date (defined as the date of the first positive COVID-19 test or the date of referral). Patient index dates were categorized into 4 variant epochs: pre-Delta (November 9, 2020, to June 30, 2021), Delta (July 1 to November 30, 2021), Delta and Omicron BA.1 (December 1 to 31, 2021), and Omicron BA.1 (January 1 to 31, 2022). Results: Among 167 183 patients, the mean (SD) age was 47.0 (18.5) years; 95 669 patients (57.2%) were female at birth, 139 379 (83.4%) were White, and 138 900 (83.1%) were non-Hispanic. A total of 25 241 patients received treatment with nMAbs. Treatment with nMAbs was associated with lower odds of ED visits within 14 days (odds ratio [OR], 0.76; 95% CI, 0.68-0.85), hospitalization within 14 days (OR, 0.52; 95% CI, 0.45-0.59), and death within 30 days (OR, 0.14; 95% CI, 0.10-0.20). The association between nMAbs and reduced risk of hospitalization was stronger in unvaccinated patients (14-day hospitalization: OR, 0.51; 95% CI, 0.44-0.59), and the associations with hospitalization and death were stronger in immunocompromised patients (hospitalization within 14 days: OR, 0.31 [95% CI, 0.24-0.41]; death within 30 days: OR, 0.13 [95% CI, 0.06-0.27]). The strength of associations of nMAbs increased incrementally among patients with a greater probability of poor outcomes; for example, the ORs for hospitalization within 14 days were 0.58 (95% CI, 0.48-0.72) among those in the third (moderate) risk stratum and 0.41 (95% CI, 0.32-0.53) among those in the fifth (highest) risk stratum. The association of nMAb treatment with reduced risk of hospitalizations within 14 days was strongest during the Delta variant epoch (OR, 0.37; 95% CI, 0.31-0.43) but not during the Omicron BA.1 epoch (OR, 1.29; 95% CI, 0.68-2.47). These findings were corroborated in the subset of patients with viral genomic data. Treatment with nMAbs was associated with a significant mortality benefit in all variant epochs (pre-Delta: OR, 0.16 [95% CI, 0.08-0.33]; Delta: OR, 0.14 [95% CI, 0.09-0.22]; Delta and Omicron BA.1: OR, 0.10 [95% CI, 0.03-0.35]; and Omicron BA.1: OR, 0.13 [95% CI, 0.02-0.93]). Potential adverse drug events were identified in 38 treated patients (0.2%). Conclusions and Relevance: In this study, nMAb treatment for COVID-19 was safe and associated with reductions in ED visits, hospitalization, and death, although it was not associated with reduced risk of hospitalization during the Omicron BA.1 epoch. These findings suggest that targeted risk stratification strategies may help optimize future nMAb treatment decisions.

Relationships Between EHR-Based Audit Log Data and Physician Burnout and Clinical Practice Process Measures.

OBJECTIVE: To explore the relationship of electronic health record (EHR)-based audit log data with physician burnout and clinical practice process measures. METHODS: From September 4 to October 7, 2019, we surveyed physicians in a larger academic medical department and matched responses to August 1 through October 31, 2019, EHR-based audit log data. Multivariable regression analysis evaluated the relationship between log data and burnout and the interrelationship between log data and turnaround time for In Basket messages and percentage of encounters closed within 24 hours. RESULTS: Of the 537 physicians surveyed, 413 (77%) responded. On multivariable analysis, number of In Basket messages received per day (each additional message: odds ratio, 1.04 [95% CI, 1.02 to 1.07]; P<.001) and time spent in the EHR outside scheduled patient care (each additional hour: odds ratio, 1.01 [95% CI, 1.00 to 1.02]; P=.04) were associated with burnout. Time spent doing In Basket work (each additional minute: parameter estimate, -0.11 [95% CI, -0.19 to -0.03]; P=.01) and in the EHR outside scheduled patient care (each additional hour: parameter estimate, 0.04 [95% CI, 0.01 to 0.06]; P=.002) were associated with turnaround time (days per message) for In Basket messages. None of the variables explored were independently associated with percentage of encounters closed within 24 hours. CONCLUSION: Electronic health record-based audit log data of workload relate to odds of burnout and responsiveness to patient-related inquiries and results. Further study is needed to determine whether interventions that reduce the number of and time spent doing In Basket messages or time spent in the EHR outside scheduled patient care reduce physician burnout and improve clinical practice process measures.

Paediatric safety assessment of BNT162b2 vaccination in a multistate hospital-based electronic health record system in the USA: a retrospective analysis.

BACKGROUND: The emergency use authorisation of BNT162b2 (tozinameran; Comirnaty, Pfizer-BioNTech) for children aged 5-17 years has resulted in rapid vaccination in the paediatric population. However, there are few studies of adverse events associated with vaccination in children. The aim of this study was to systematically assess the adverse events of two-dose BNT162b2 vaccination in the paediatric population. METHODS: We conducted a retrospective analysis of patient electronic health records (EHRs) of children aged 5-17 years who received the primary two-dose series of the BNT162b2 vaccine between Jan 5, 2021, and Aug 5, 2022, at the Mayo Clinic Health System (MN, FL, AZ, IA, and WI), USA. Using natural language processing, we automatically curated adverse events reported by physicians in EHR clinical notes before and after vaccination. To determine significant adverse events after BNT162b2 vaccination, we calculated risk differences, which was defined as the percentage difference between the rate of children with an adverse event after a vaccine dose and the baseline rate of children with an adverse event before vaccination. 95% CIs and p values were calculated using the Miettinen and Nurminen score method. FINDINGS: 56 436 individuals aged 5-17 years (20 227 aged 5-11 years and 36 209 aged 12-17 years) with EHRs in the Mayo Clinic Health Systems were included in the study. Overall, the reporting of adverse events remained low in passive surveillance. Serious adverse events were rare after the first and second doses of BNT162b2, with rates of anaphylaxis (six [0·01%] of 56 436), myocarditis (five [0·01%]), and pericarditis (three [0·01%]) consistent with previous studies. Among the 20 227 5-11-year-olds, there were increased risks of fatigue (58 after second dose vs 41 before first dose; risk difference [RD]dose2 0·08% [95% CI -0·01 to 0·18], p=0·044) and fever (104 after second dose vs 77 before first dose; RDdose2 0·13% [0·00 to 0·27], p=0·022) after the second dose. Among the 36 209 12-17-year-olds, there were increased risks of arthralgia (69 after second dose vs 48 before first dose; RDdose2 0·06% [-0·00 to 0·12], p=0·026), chills (58 after second dose vs 40 before first dose; RDdose2 0·05% [-0·00 to 0·11], p=0·034), and myalgia (96 after second dose vs 73 before first dose; RDdose2 0·06% [-0·01 to 0·14], p=0·038) after the second dose. Although the overall incidence was low, there was an increased risk of myocarditis in males aged 12-17 years after the second dose (five after second dose vs zero before first dose; RDdose2 0·03% [0·01 to 0·07], p=0·013), with median age being 15 years (IQR 14 to 16). INTERPRETATION: Overall, this data suggests that vaccination with BNT162b2 in the paediatric population is generally safe and well-tolerated. Further research is warranted to investigate the basis for the increased risk of myocarditis in adolescent males. Additionally, further studies are needed to confirm whether the findings in our study population apply to the whole vaccinated paediatric population. FUNDING: nference.

Comparing Complication Rates of Midline Catheter vs Peripherally Inserted Central Catheter. A Systematic Review and Meta-analysis.

Background: Peripherally inserted central catheters (PICCs) and midlines are commonly used devices for reliable vascular access. Infection and thrombosis are the main adverse effects of these catheters. We aimed to evaluate the relative risk of complications from midlines and PICCs. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies. The primary outcomes were catheter-related bloodstream infection (CRBSI) and thrombosis. Secondary outcomes evaluated included mortality, failure to complete therapy, catheter occlusion, phlebitis, and catheter fracture. The certainty of evidence was assessed using the GRADE approach. Results: Of 8368 citations identified, 20 studies met the eligibility criteria, including 1 RCT and 19 observational studies. Midline use was associated with fewer patients with CRBSI compared with PICCs (odds ratio [OR], 0.24; 95% CI, 0.15-0.38). This association was not observed when we evaluated risk per catheter. No significant association was found between catheters when evaluating risk of localized thrombosis and pulmonary embolism. A subgroup analysis based on location of thrombosis showed higher rates of superficial venous thrombosis in patients using midlines (OR, 2.30; 95% CI, 1.48-3.57). We did not identify any significant difference between midlines and PICCs for the secondary outcomes. Conclusions: Our findings suggest that patients who use midlines might experience fewer CRBSIs than those who use PICCs. However, the use of midline catheters was associated with greater risk of superficial vein thrombosis. These findings can help guide future cost-benefit analyses and direct comparative RCTs to further characterize the efficacy and risks of PICCs vs midline catheters.