In the US, states enacted nonpharmaceutical interventions, including school closure, to reduce the spread of coronavirus disease 2019 (COVID-19). All 50 states closed schools in March 2020 despite uncertainty if school closure would be effective. OBJECTIVE To determine if school closure and its timing were associated with decreased COVID-19 incidence and mortality. DESIGN, SETTING, AND PARTICIPANTS US population-based observational study conducted between March 9, 2020, and May 7, 2020, using interrupted time series analyses incorporating a lag period to allow for potential policy-associated changes to occur. To isolate the association of school closure with outcomes, state-level nonpharmaceutical interventions and attributes were included in negative binomial regression models. States were examined in quartiles based on state-level COVID-19 cumulative incidence per 100 000 residents at the time of school closure. Models were used to derive the estimated absolute differences between schools that closed and schools that remained open as well as the number of cases and deaths if states had closed schools when the cumulative incidence of COVID-19 was in the lowest quartile compared with the highest quartile. EXPOSURES Closure of primary and secondary schools. MAIN OUTCOMES AND MEASURES COVID-19 daily incidence and mortality per 100 000 residents. RESULTS COVID-19 cumulative incidence in states at the time of school closure ranged from 0 to 14.75 cases per 100 000 population. School closure was associated with a significant decline in the incidence of COVID-19 (adjusted relative change per week, −62% [95% CI, −71% to −49%]) and mortality (adjusted relative change per week, −58% [95% CI, −68% to −46%]). Both of these associations were largest in states with low cumulative incidence of COVID-19 at the time of school closure. For example, states with the lowest incidence of COVID-19 had a −72% (95% CI, −79% to −62%) relative change in incidence compared with −49% (95% CI, −62% to −33%) for those states with the highest cumulative incidence. In a model derived from this analysis, it was estimated that closing schools when the cumulative incidence of COVID-19 was in the lowest quartile compared with the highest quartile was associated with 128.7 fewer cases per 100 000 population over 26 days and with 1.5 fewer deaths per 100 000 population over 16 days. CONCLUSIONS AND RELEVANCE Between March 9, 2020, and May 7, 2020, school closure in the US was temporally associated with decreased COVID-19 incidence and mortality; states that closed schools earlier, when cumulative incidence of COVID-19 was low, had the largest relative reduction in incidence and mortality. However, it remains possible that some of the reduction may have been related to other concurrent nonpharmaceutical interventions.

Muscle contractions evoke an immediate rise in blood flow. Distribution of this hyperemia within the capillary bed may be deterministic for muscle O(2) diffusing capacity and remains unresolved. We developed the exteriorized rat (n = 4) spinotrapezius muscle for evaluation of capillary hemodynamics before (rest), during, and immediately after (post) a bout of twitch contractions to resolve (second-by-second) alterations in red blood cell velocity (V(RBC)) and flux (f(RBC)). Contractions increased (all P < 0.05) capillary V(RBC) (rest: 270 +/- 62 microm/s; post: 428 +/- 47 microm/s), f(RBC) (rest: 22.4 +/- 5.5 cells/s; post: 44.3 +/- 5.5 cells/s), and hematocrit but not the percentage of capillaries supporting continuous RBC flow (rest: 84.0 +/- 0.7%; post: 89.5+/-1.4%; P > 0.05). V(RBC) peaked within the first one or two contractions, whereas f(RBC) increased to an initial short plateau (first 12-20 s) followed by a secondary rise to steady state. Hemodynamic temporal profiles were such that capillary hematocrit tended to decrease rather than increase over the first approximately 15 s of contractions. We conclude that contraction-induced alterations in capillary RBC flux and distribution augment both convective and diffusive mechanisms for blood-myocyte O(2) transfer. However, across the first 10-15 s of contractions, the immediate and precipitous rise in V(RBC) compared with the biphasic and prolonged increase of f(RBC) may act to lower O(2) diffusing capacity by not only reducing capillary transit time but by delaying the increase in the instantaneous RBC-to-capillary surface contact thought crucial for blood-myocyte O(2) flux.

Chronic heart failure (CHF) reduces muscle blood flow at rest and during exercise and impairs muscle function. Using intravital microscopy techniques, we tested the hypothesis that the speed and amplitude of the capillary red blood cell (RBC) velocity (VRBC) and flux (FRBC) response to contractions would be reduced in CHF compared with control (C) spinotrapezius muscle. The proportion of capillaries supporting continuous RBC flow was less (P < 0.05) in CHF (0.66 +/- 0.04) compared with C (0.84 +/- 0.01) muscle at rest and was not significantly altered with contractions. At rest, VRBC (C, 270 +/- 62; CHF, 179 +/- 14 microm/s) and FRBC (C, 22.4 +/- 5.5 vs. CHF, 15.2 +/- 1.2 RBCs/s) were reduced (both P < 0.05) in CHF vs. C muscle. Contractions significantly (both P < 0.05) elevated VRBC (C, 428 +/- 47 vs. CHF, 222 +/- 15 microm/s) and FRBC (C, 44.3 +/- 5.5 vs. CHF, 24.0 +/- 1.2 RBCs/s) in C and CHF muscle; however, both remained significantly lower in CHF than C. The time to 50% of the final response was slowed (both P < 0.05) in CHF compared with C for both VRBC (C, 8 +/- 4; CHF, 56 +/- 11 s) and FRBC (C, 11 +/- 3; CHF, 65 +/- 11 s). Capillary hematocrit increased with contractions in C and CHF muscle but was not different (P > 0.05) between CHF and C. Thus CHF impairs diffusive and conductive O2 delivery across the rest-to-contractions transition in rat skeletal muscle, which may help explain the slowed O2 uptake on-kinetics manifested in CHF patients at exercise onset.

Children with medical complexity disproportionately use the majority of ICU resources in children's hospitals. Efforts to improve quality and provide cost-effective care should focus on this population.

This is a prepublication version of an article that has undergone peer review and been accepted for publication but is not the final version of record. This paper may be cited using the DOI and date of access. This paper may contain information that has errors in facts, figures, and statements, and will be corrected in the final published version. The journal is providing an early version of this article to expedite access to this information. The American Academy of Pediatrics, the editors, and authors are not responsible for inaccurate information and data described in this version.

Key Points• Rates of pediatric PE in hospitalized patients increased 184% from 2001 to 2014.• Mortality as a result of PE in children has decreased over time and is now comparable to that from VTE.Although rare in children, pulmonary embolism (PE) can cause significant morbidity and mortality. Overall rates of venous thromboembolism (VTE) are increasing in hospitalized children. By using the Pediatric Health Information System database, we evaluated incidence, treatment, and outcome of PE in children younger than age 18 years from 2001 to 2014.Demographic characteristics for those admitted with VTE alone and those admitted with PE were compared. Rates of PE by year were compared with the number of hospital and VTE admissions. Trends in medication use were analyzed. Over the period of the study, patients with PE made up 15.8% of VTE discharges. The overall rate of PE increased 200%(P , .001). Compared with all other age groups, adolescents (age 13-18 years) had the highest prevalence (55%; P , .001), the rate of which increased from 9.8 to 24.7 per 10 000 hospital discharges (152%; P , .001), and from 17.5 to 34.1 per 100 VTE discharges (95%; P , .001). Individuals with PE had a higher mortality (8.3% vs 6%; P , .001) and were less likely to have a complex chronic condition (58% vs 65%; P , .001) than those with VTE alone. However, PE mortality rates decreased over the time period studied. AfricanAmerican and Hispanic patients were more likely to experience recurrent PE than white patients (12% and 10.7% vs 8%; P 5 .002). During the study period, the use of unfractionated heparin decreased (P , .001), and the use of low molecular weight heparin increased (P , .001). Further research is required to determine what factors contribute to the higher rate of PE in adolescents and influence recurrence in African American and Hispanic patients.

BACKGROUND: Recent publications should have resulted in increased hydroxyurea usage in children with sickle cell disease (SCD). We hypothesized that hydroxyurea use in children with SCD increased over time and was associated with decreased acute care visits. METHODS: This was a secondary analysis of the Truven Health Analytics–IBM Watson Health MarketScan Medicaid database from 2009 to 2015. The multistate, population-based cohort included children 1 to 19 years old with an International Classification of Diseases, Ninth or 10th Revision diagnosis of SCD between 2009 and 2015. Changes in hydroxyurea were measured across study years. The primary outcome was the receipt of hydroxyurea, identified through filled prescription claims. Acute care visits (emergency department visits and hospitalizations) were extracted from billing data. RESULTS: A mean of 5138 children each year were included. Hydroxyurea use increased from 14.3% in 2009 to 28.2% in 2015 (P &lt; .001). During the study period, the acute-care-visit rate decreased from 1.20 acute care visits per person-year in 2009 to 1.04 acute care visits per person-year in 2015 (P &lt; .001); however, the drop in acute care visits was exclusively in the youngest and oldest age groups and was not seen when only children enrolled continuously from 2009 to 2015 were analyzed. CONCLUSIONS: There was a significant increase in hydroxyurea use in children with SCD between 2009 and 2015. However, in 2015, only ∼1 in 4 children with SCD received hydroxyurea at least once. Increases in hydroxyurea were not associated with consistently decreased acute care visits in this population-based study of children insured by Medicaid.

Initiating a guideline for HFNC use on the general pediatric wards was associated with an increase in the use of the intervention with no significant change in total hospital length of stay, PICU length of stay and transfer rate, intubation rate, or 30-day readmission for patients with bronchiolitis.