Race, Ethnicity, and Ancestry in Clinical Pathways: A Framework for Evaluation.

Clinical algorithms, or "pathways," promote the delivery of medical care that is consistent and equitable. Race, ethnicity, and/or ancestry terms are sometimes included in these types of guidelines, but it is unclear if this is appropriate for clinical decision-making. At our institution, we developed and applied a structured framework to determine whether race, ethnicity, or ancestry terms identified in our clinical pathways library should be retained, modified, or removed. First, we reviewed all text and associated reference documents for 132 institutionally-developed clinical pathways and identified 8 pathways that included race, ethnicity, or ancestry terms. Five pathways had clear evidence or a change in institutional policy that supported removal of the term. Multispecialty teams conducted additional in-depth evaluation of the 3 remaining pathways (Acute Viral Illness, Hyperbilirubinemia, and Weight Management) by applying the framework. In total, based on these reviews, race, ethnicity, or ancestry terms were removed (n = 6) or modified (n = 2) in all 8 pathways. Application of the framework established several recommended practices, including: (1) define race, ethnicity, and ancestry rigorously; (2) assess the most likely mechanisms underlying epidemiologic associations; (3) consider whether inclusion of the term is likely to mitigate or exacerbate existing inequities; and (4) exercise caution when applying population-level data to individual patient encounters. This process and framework may be useful to other institutional programs and national organizations in evaluating the inclusion of race, ethnicity, and ancestry in clinical guidelines.

Accuracy of identifying pediatric acute bacterial sinusitis diagnoses in outpatient claims data.

PURPOSE: Acute bacterial sinusitis is among the most frequent outpatient infections in children and adolescents and is well suited to study in large healthcare utilization databases, but the validity of International Classification of Diseases, 10th Revision (ICD-10) codes together with antibiotic prescriptions to identify cases of acute bacterial sinusitis has not been established. We aimed to evaluate the validity of ICD-10 codes combined with antibiotic prescriptions to identify new diagnoses of acute bacterial sinusitis among pediatric patients evaluated in the outpatient setting. METHODS: Children and adolescents aged 17 years and younger with an outpatient diagnosis of acute sinusitis along with an antibiotic prescription from an ambulatory facility affiliated with the Mass General Brigham health system were identified via a clinical data warehouse. Patients were stratified by age (0-5 years, 6-11 years, and 12-17 years), and 50 cases per age group were randomly sampled. Medical records were independently reviewed by two pediatric infectious diseases physicians to assess for the documentation of a clinician-defined diagnosis of acute bacterial sinusitis. Positive predictive values (PPVs) and 95% confidence intervals (CIs) were calculated. RESULTS: A total of 150 patients were included in the final cohort. Frontal, maxillary, and "unspecified" sinuses accounted for 88% of the diagnoses. The positive predictive value of the algorithm to identify clinician-defined diagnoses of acute bacterial sinusitis was 92% (95% CI 87%, 95%). The PPVs were consistent across age strata. CONCLUSIONS: ICD-10 codes for acute sinusitis, when paired with a same-day antibiotic prescription, have a high positive predictive value among a cohort of pediatric patients, suggesting that they can be used to study new acute bacterial sinusitis diagnoses with claims.

Correlation of SARS-CoV-2 Nucleocapsid Antigen and RNA Concentrations in Nasopharyngeal Samples from Children and Adults Using an Ultrasensitive and Quantitative Antigen Assay.

Diagnosis of COVID-19 by PCR offers high sensitivity, but the utility of detecting samples with high cycle threshold (CT ) values remains controversial. Currently available rapid diagnostic tests (RDTs) for SARS-CoV-2 nucleocapsid antigens (Ag) have sensitivity well below PCR. The correlation of Ag and RNA quantities in clinical nasopharyngeal (NP) samples is unknown. An ultrasensitive, quantitative electrochemiluminescence immunoassay for SARS-CoV-2 nucleocapsid (the MSD S-PLEX SARS-CoV-2 N assay) was used to measure Ag in clinical NP samples from adults and children previously tested by PCR. The S-PLEX Ag assay had a limit of detection (LOD) of 0.16 pg/ml and a cutoff of 0.32 pg/ml. Ag concentrations measured in clinical NP samples (collected in 3.0 ml of media) ranged from less than 160 fg/ml to 2.7 µg/ml. Log-transformed Ag concentrations correlated tightly with CT values. In 35 adult and 101 pediatric PCR-positive samples, the sensitivities were 91% (95% confidence interval, 77 to 98%) and 79% (70 to 87%), respectively. In samples with a CT of ≤35, the sensitivities were 100% (88 to 100%) and 96% (88 to 99%), respectively. In 50 adult and 40 pediatric PCR-negative specimens, the specificities were 100% (93 to 100%) and 98% (87 to 100%), respectively. Nucleocapsid concentrations in clinical NP samples span 8 orders of magnitude and correlate closely with RNA concentrations (CT values). The S-PLEX Ag assay showed 96 to 100% sensitivity in samples from children and adults with CT values of ≤35, and a specificity of 98 to 100%. These results clarify Ag concentration distributions in clinical samples, providing insight into the performance of Ag RDTs and offering a new approach to diagnosis of COVID-19.

Comparison of Upper Respiratory Viral Load Distributions in Asymptomatic and Symptomatic Children Diagnosed with SARS-CoV-2 Infection in Pediatric Hospital Testing Programs.

The distribution of upper respiratory viral loads (VL) in asymptomatic children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unknown. We assessed PCR cycle threshold (Ct) values and estimated VL in infected asymptomatic children diagnosed in nine pediatric hospital testing programs. Records for asymptomatic and symptomatic patients with positive clinical SARS-CoV-2 tests were reviewed. Ct values were (i) adjusted by centering each value around the institutional median Ct value from symptomatic children tested with that assay and (ii) converted to estimated VL (numbers of copies per milliliter) using internal or manufacturer data. Adjusted Ct values and estimated VL for asymptomatic versus symptomatic children (118 asymptomatic versus 197 symptomatic children aged 0 to 4 years, 79 asymptomatic versus 97 symptomatic children aged 5 to 9 years, 69 asymptomatic versus 75 symptomatic children aged 10 to 13 years, 73 asymptomatic versus 109 symptomatic children aged 14 to 17 years) were compared. The median adjusted Ct value for asymptomatic children was 10.3 cycles higher than for symptomatic children (P < 0.0001), and VL were 3 to 4 logs lower than for symptomatic children (P < 0.0001); differences were consistent (P < 0.0001) across all four age brackets. These differences were consistent across all institutions and by sex, ethnicity, and race. Asymptomatic children with diabetes (odds ratio [OR], 6.5; P = 0.01), a recent contact (OR, 2.3; P = 0.02), and testing for surveillance (OR, 2.7; P = 0.005) had higher estimated risks of having a Ct value in the lowest quartile than children without, while an immunocompromised status had no effect. Children with asymptomatic SARS-CoV-2 infection had lower levels of virus in their nasopharynx/oropharynx than symptomatic children, but the timing of infection relative to diagnosis likely impacted levels in asymptomatic children. Caution is recommended when choosing diagnostic tests for screening of asymptomatic children.

Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Febrile Neonates.

Most severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in pediatric patients are mild or asymptomatic. However, infants have emerged at higher risk of hospitalization and severe outcomes in pediatric coronavirus disease 2019 (COVID-19). We report a case series of 4 full-term neonates hospitalized with fever and found to have SARS-CoV-2 infection with a spectrum of illness severities. Two neonates required admission to the intensive care unit for respiratory insufficiency and end organ involvement. Half of the patients were found to have a coinfection. One neonate received antiviral therapy with remdesivir and is, to our knowledge, the youngest patient to receive this drug for COVID-19. All neonates had favorable outcomes.