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MW01‐6‐189WH (MW189) is a novel central nervous system–penetrant small‐molecule drug candidate that selectively attenuates stressor‐induced proinflammatory cytokine overproduction and is efficacious in intracerebral hemorrhage and traumatic brain injury animal models. We report first‐in‐human, randomized, double‐blind, placebo‐controlled phase 1 studies to evaluate the safety, tolerability, and pharmacokinetics (PK) of single and multiple ascending intravenous doses of MW189 in healthy adult volunteers. MW189 was safe and well tolerated in single and multiple doses up to 0.25 mg/kg, with no clinically significant concerns. The most common drug‐related treatment‐emergent adverse event was infusion‐site reactions, likely related to drug solution acidity. No clinically concerning changes were seen in vital signs, electrocardiograms, physical or neurological examinations, or safety laboratory results. PK analysis showed dose‐proportional increases in plasma concentrations of MW189 after single or multiple doses, with approximately linear kinetics and no significant drug accumulation. Steady state was achieved by dose 3 for all dosing cohorts. A pilot pharmacodynamic study administering low‐dose endotoxin to induce a systemic inflammatory response was done to evaluate the effects of a single intravenous dose of MW189 on plasma cytokine levels. MW189 treatment resulted in lower levels of the proinflammatory cytokine TNF‐α and higher levels of the anti‐inflammatory cytokine IL‐10 compared with placebo treatment. The outcomes are consistent with the pharmacological mechanism of MW189. Overall, the safety profile, PK properties, and pharmacodynamic effect support further development of MW189 for patients with acute brain injury. [ABSTRACT FROM AUTHOR]

Many cities have implemented programs to improve the recreational built environment. We evaluated whether neighborhood recreational built environmental changes are associated with change in body mass index (BMI). We performed a longitudinal assessment of association between the recreational built environment and BMI percent of 95th percentile (BMIp95). Patient data from 2012 to 2017 were collected from electronic medical records including height, weight, sex, race/ethnicity, insurance type, and address. BMIp95 was calculated. Environmental data including sidewalks, trails, Healthy Mile Trails, and parks were collected. Patients' neighborhood environments were characterized using proximity of features from home address. Multilevel linear regressions with multiple encounters per patient estimated effects of recreational features on BMIp95 and stratified models estimated effect differences. Of 8282 total patients, 27.7% were non-Hispanic White, half were insured by Medicaid, and 29.5% changed residence. Median BMIp95 was 86.3%. A decrease in BMIp95 was associated with park proximity in the full cohort (−2.85; 95% CI [confidence interval]: −5.47, −0.24; P =.032), children with obesity at baseline (−6.50; 95% CI: −12.36, −0.64; P =.030) and privately insured children (−4.77; 95% CI: −9.14, −0.40; P =.032). Healthy Mile Trails were associated with an increase in BMIp95 among children without obesity (1.00; 95% CI 0.11, 1.89; P =.027) and children living in higher income areas (6.43; 95% CI: 0.23, 12.64; P =.042). Differences in effect indicate that built environment changes may improve or exacerbate disparities. Improving obesity disparities may require addressing family-level barriers to the use of recreational features in addition to proximity. [ABSTRACT FROM AUTHOR]

Care plans can reduce care fragmentation for children with medical complexity (CMC); however, implementation is challenging. Mobile health innovations could improve implementation. This mixed methods study's objectives were to (1) evaluate feasibility of mobile complex care plans (MCCPs) for CMC enrolled in a complex care program and (2) study MCCPs' impact on parent engagement, parent experience, and care coordination. MCCPs were individualized, updated quarterly, integrated within the electronic health record, and visible on parents' mobile devices via an online portal. In 1 year (September 1, 2016, to August 31, 2017), 94% of eligible patients (n = 47) received 162 MCCPs. Seventy-four percent of parents (n = 35) reviewed MCCPs online. Forty-six percent of these parents (n = 16) sent a follow-up message, and the care team responded within 8 hours (median time = 7.2 hours). In interviews, parents identified MCCPs as an important reference and communication tool. MCCPs for CMC in a complex care program were feasible, facilitated parental engagement, and delivered timely communication. [ABSTRACT FROM AUTHOR]

The article reports on a study that examines the link between mortality and maximum oxygenation index (OI) during mechanical ventilation among subjects who were mechanically ventilated for less than a day. Highlights include reasons for the poor predictive ability of OI for mortality among children with pediatric acute respiratory distress syndrome (ARDS), a patient's trajectory early in the course of illness, confounders of the relationship between OI and mortality among children with ARDS.