Effectiveness of Structured Care Coordination for Children With Medical Complexity: The Complex Care for Kids Ontario (CCKO) Randomized Clinical Trial.

Importance: Children with medical complexity (CMC) have chronic conditions and high health needs and may experience fragmented care. Objective: To compare the effectiveness of a structured complex care program, Complex Care for Kids Ontario (CCKO), with usual care. Design, Setting, and Participants: This randomized clinical trial used a waitlist variation for randomizing patients from 12 complex care clinics in Ontario, Canada, over 2 years. The study was conducted from December 2016 to June 2021. Participants were identified based on complex care clinic referral and randomly allocated into an intervention group, seen at the next available clinic appointment, or a control group that was placed on a waitlist to receive the intervention after 12 months. Intervention: Assignment of a nurse practitioner-pediatrician dyad partnering with families in a structured complex care clinic to provide intensive care coordination and comprehensive plans of care. Main Outcomes and Measures: Co-primary outcomes, assessed at baseline and at 6, 12, and 24 months postrandomization, were service delivery indicators from the Family Experiences With Coordination of Care that scored (1) coordination of care among health care professionals, (2) coordination of care between health care professionals and families, and (3) utility of care planning tools. Secondary outcomes included child and parent health outcomes and child health care system utilization and cost. Results: Of 144 participants randomized, 141 had complete health administrative data, and 139 had complete baseline surveys. The median (IQR) age of the participants was 29 months (9-102); 83 (60%) were male. At 12 months, scores for utility of care planning tools improved in the intervention group compared with the waitlist group (adjusted odds ratio, 9.3; 95% CI, 3.9-21.9; P < .001), with no difference between groups for the other 2 co-primary outcomes. There were no group differences for secondary outcomes of child outcomes, parent outcomes, and health care system utilization and cost. At 24 months, when both groups were receiving the intervention, no primary outcome differences were observed. Total health care costs in the second year were lower for the intervention group (median, CAD$17 891; IQR, 6098-61 346; vs CAD$37 524; IQR, 9338-119 547 [US $13 415; IQR, 4572-45 998; vs US $28 136; IQR, 7002-89 637]; P = .01). Conclusions and Relevance: The CCKO program improved the perceived utility of care planning tools but not other outcomes at 1 year. Extended evaluation periods may be helpful in assessing pediatric complex care interventions. Trial Registration: ClinicalTrials.gov Identifier: NCT02928757.

Trends in Health Service Use for Canadian Adults With Dementia and Parkinson Disease During the First Wave of the COVID-19 Pandemic.

Importance: Persons with dementia and Parkinson disease (PD) are vulnerable to disruptions in health care and services. Objective: To examine changes in health service use among community-dwelling persons with dementia, persons with PD, and older adults without neurodegenerative disease during the first wave of the COVID-19 pandemic. Design Setting and Participants: Repeated cross-sectional analysis using population-based administrative data among community-dwelling persons with dementia, persons with PD, and adults 65 years and older at the start of each week from March 1 through the week of September 20, 2020 (pandemic period), and March 3 through the week of September 22, 2019 (historical period), in Ontario, Canada. Exposures: COVID-19 pandemic as of March 1, 2020. Main Outcomes and Measures: Main outcomes were weekly rates of emergency department visits, hospitalizations, nursing home admissions, home care, virtual and in-person physician visits, and all-cause mortality. Poisson regression models were used to calculate weekly rate ratios (RRs) with 95% CIs comparing pandemic weeks with historical levels. Results: Among those living in the community as of March 1, 2020, persons with dementia (n = 131 466; mean [SD] age, 80.1 [10.1] years) were older than persons with PD (n = 30 606; 73.7 [10.2] years) and older adults (n = 2 363 742; 74.0 [7.1] years). While all services experienced declines, the largest drops occurred in nursing home admissions (RR for dementia: 0.10; 95% CI, 0.07-0.15; RR for PD: 0.03; 95% CI, 0.00-0.21; RR for older adults: 0.11; 95% CI, 0.06-0.18) and emergency department visits (RR for dementia: 0.45; 95% CI, 0.41-0.48; RR for PD: 0.40; 95% CI, 0.34-0.48; RR for older adults: 0.45; 95% CI, 0.44-0.47). After the first wave, most services returned to historical levels except physician visits, which remained elevated (RR for dementia: 1.07; 95% CI, 1.05-1.09; RR for PD: 1.10, 95% CI, 1.06-1.13) and shifted toward virtual visits. Older adults continued to experience lower hospitalizations. All-cause mortality was elevated across cohorts. Conclusions and Relevance: In this population-based repeated cross-sectional study in Ontario, Canada, those with dementia, those with PD, and older adults sought hospital care far less than usual, were not admitted to nursing homes, and experienced excess mortality during the first wave of the pandemic. Most services returned to historical levels, but virtual physician visits remained a feature of care. While issues of equity and quality of care are still emerging among persons with neurodegenerative diseases, policies to support virtual care are necessary.

Visits to the emergency department by community-dwelling people with dementia during the first 2 waves of the COVID-19 pandemic in Ontario: a repeated cross-sectional analysis.

BACKGROUND: Community-dwelling people with dementia have been affected by COVID-19 pandemic health risks and control measures that resulted in worsened access to health care and service cancellation. One critical access point in health systems is the emergency department. We aimed to determine the change in weekly rates of visits to the emergency department of community-dwelling people with dementia in Ontario during the first 2 waves of the COVID-19 pandemic compared with historical patterns. METHODS: We conducted a population-based repeated cross-sectional study and used health administrative databases to compare rates of visits to the emergency department among community-dwelling people with dementia who were aged 40 years and older in Ontario during the first 2 waves of the COVID-19 pandemic (March 2020-February 2021) with the rates of a historical period (March 2019-February 2020). Weekly rates of visits to the emergency department were evaluated overall, by urgency and by chapter from the International Statistical Classification of Diseases and Related Health Problems, 10th Revision. We used Poisson models to compare pandemic and historical rates at the week of the lowest rate during the pandemic period and the latest week. RESULTS: We observed large immediate declines in rates of visits to the emergency department during the COVID-19 pandemic (rate ratio [RR] 0.50, 95% confidence interval [CI] 0.47-0.53), which remained below historical levels by the end of the second wave (RR 0.88, 95% CI 0.83-0.92). Rates of both nonurgent (RR 0.33, 95% CI 0.28-0.39) and urgent (RR 0.51, 95% CI 0.48-0.55) visits to the emergency department also declined and remained low (RR 0.68, 95% CI 0.59-0.79, RR 0.91, 95% CI 0.86-0.96), respectively. Visits for injuries, and circulatory, respiratory and musculoskeletal diseases declined and remained below historical levels. INTERPRETATION: Prolonged reductions in visits to the emergency department among people with dementia during the first 2 pandemic waves raise concerns about patients who delay seeking acute care services. Understanding the long-term effects of these reductions requires further research.

Effect of maternal prenatal and postpartum vitamin D supplementation on offspring bone mass and muscle strength in early childhood: follow-up of a randomized controlled trial.

BACKGROUND: Maternal vitamin D status during pregnancy and lactation is a modifiable factor that may influence offspring musculoskeletal outcomes. However, few randomized trials have tested the effects of prenatal or postpartum vitamin D supplementation on offspring bone and muscle development. OBJECTIVES: The aim was to examine hypothesized effects of improvements in early-life vitamin D status on childhood musculoskeletal health in Dhaka, Bangladesh. METHODS: In a previously completed, double-blind, dose-ranging trial, healthy pregnant women (n = 1300) were recruited at 17-24 weeks' gestation and randomly assigned to a prenatal/postpartum regimen of 0/0, 4200/0, 16,800/0, 28,000/0, or 28,000/28,000 IU cholecalciferol (vitamin D3)/wk until 26 wk postpartum. In this new report, we describe additional follow-up at 4 y of age (n = 642) for longer-term outcomes. Bone mineral content (BMC) and areal bone mineral density (aBMD) were measured by DXA. Grip strength was tested using a hand-held dynamometer. The primary comparison was children of women assigned to 28,000 IU/wk prenatally compared with placebo. Differences are expressed as means and 95% CIs. RESULTS: Total-body-less-head (TBLH) BMC, TBLH aBMD, and grip strength were similar in the combined high-dose prenatal (28,000/0 and 28,000/28,000 IU/wk) compared with placebo groups (mean difference [95% CI] = 0.61 g [-10.90, 12.13], 0.0004 g/cm2 [-0.0089, 0.0097], and 0.02 kg [-0.26, 0.31], respectively). In dose-ranging analyses, TBLH BMC and aBMD, whole-body BMC and aBMD, and grip strength in each of the prenatal vitamin D groups were not significantly different from placebo (P > 0.05 for all comparisons). Only head aBMD was greater in children of women assigned to the 28,000/28,000-IU regimen compared with placebo (mean difference [95% CI] = 0.024 g/cm2 [0.0009, 0.047], P = 0.042); the effect was attenuated upon adjustment for child height, weight, and sex (P = 0.11). CONCLUSIONS: Maternal prenatal, with or without postpartum, vitamin D supplementation does not improve child BMC, aBMD, or grip strength at 4 y of age. The MDIG trial and present follow-up study were registered prospectively at www.clinicaltrials.gov as NCT01924013 and NCT03537443, respectively.

Medications Reconciled at Discharge Versus Admission Among Inpatients at a Children's Hospital.

BACKGROUND AND OBJECTIVES: Discharge prescription practices may contribute to medication overuse and polypharmacy. We aimed to estimate changes in the number and types of medications reported at inpatient discharge (versus admission) at a tertiary care pediatric hospital. METHODS: Electronic medication reconciliation data were extracted for inpatient admissions at The Hospital for Sick Children from January 1, 2016, to December 31, 2017 (n = 22 058). Relative changes in the number of medications and relative risks (RRs) of specific types and subclasses of medications at discharge (versus admission) were estimated overall and stratified by the following: sex, age group, diagnosis of a complex chronic condition, surgery, or ICU (PICU) admission. Micronutrient supplements, nonopioid analgesics, cathartics, laxatives, and antibiotics were excluded in primary analyses. RESULTS: Medication counts at discharge were 1.27-fold (95% confidence interval [CI]: 1.25-1.29) greater than admission. The change in medications at discharge (versus admission) was increased by younger age, absence of a complex chronic condition, surgery, PICU admission, and discharge from a surgical service. The most common drug subclasses at discharge were opioids (22% of discharges), proton pump inhibitors (18%), bronchodilators (10%), antiemetics (9%), and corticosteroids (9%). Postsurgical patients had higher RRs of opioid prescriptions at discharge (versus admission; RR: 13.3 [95% CI: 11.5-15.3]) compared with nonsurgical patients (RR: 2.38 [95% CI: 2.22-2.56]). CONCLUSIONS: Pediatric inpatients were discharged from the hospital with more medications than admission, frequently with drugs that may be discretionary rather than essential. The high frequency of opioid prescriptions in postsurgical patients is a priority target for educational and clinical decision support interventions.

Publication Trends of Pediatric and Adult Randomized Controlled Trials in General Medical Journals, 2005-2018: A Citation Analysis.

Policy has been developed to promote the conduct of high-quality pediatric randomized controlled trials (RCTs). Whether these strategies have influenced publication trends in high-impact journals is unknown. We aim to evaluate characteristics, citation patterns, and publication trends of pediatric RCTs published in general medical journals (GMJs) compared with adult RCTs over a 13-year period. Studies were identified using Medline, and impact metrics were collected from Web of Science and Scopus. All RCTs published from 2005-2018 in 7 GMJs with the highest impact factors were identified for analysis. A random sample of matched pediatric and adult RCTs were assessed for publication characteristics, academic and non-academic citation. Citations were counted from publication until June 2019. Among 4146 RCTs, 2794 (67.3%) enrolled adults, 591 (14.2%) enrolled children, and 761 RCTs (18.3%) enrolled adult and pediatric patients. Adult RCTs published in GMJs grew by 5.1 publications per year (95% CI: 3.3-6.9), while the number of pediatric RCTs did not show significant change (-0.4 RCTs/year, 95% CI: -1.4-0.6). Adult RCTs were cited more than pediatric RCTs (median(IQR): 29.9 (68.5-462.8) citations/year vs. 13.2 (6.8-24.9) citations/year; p < 0.001); however, social media attention was similar (median(IQR) Altmetric Attention Score: 37 (13.75-133.8) vs. 26 (6.2-107.5); p = 0.25). Despite policies which may facilitate conduct of pediatric RCTs, the publishing gap in high-impact GMJs is widening.

Deletion of Myeloid GSK3α Attenuates Atherosclerosis and Promotes an M2 Macrophage Phenotype.

OBJECTIVE: Glycogen synthase kinase (GSK)-3α/ß has been implicated in the pathogenesis of diabetes mellitus, cancer, Alzheimer, and atherosclerosis. The tissue- and homolog-specific functions of GSK3α and ß in atherosclerosis are unknown. This study examines the effect of hepatocyte or myeloid cell deletion of GSK3α or GSK3ß on atherosclerosis in low-density lipoprotein receptor (LDLR)(-/-) mice. APPROACH AND RESULTS: We ablated GSK3α or GSK3ß expression in hepatic or myeloid cells of LDLR(-/-) mice, and mice were fed a high-fat diet for 10 weeks. GSK3α or GSK3ß deficiency in hepatic or myeloid cells did not affect metabolic parameters, including plasma lipid levels. Hepatic deletion of GSK3α or GSK3ß did not affect the development of atherosclerosis or hepatic lipid content. Myeloid deletion of GSK3α, but not of GSK3ß, reduced atherosclerotic lesion volume and lesion complexity. Mice lacking GSK3α in myeloid cells had a less inflammatory and more anti-inflammatory plasma cytokine profile. Macrophages within atherosclerotic lesions of myeloid GSK3α-deficient mice, but not of GSK3ß-deficient mice, displayed reduced expression of markers associated with M1 macrophage polarization and enhanced expression of the M2 markers. Finally, bone marrow-derived macrophages were isolated and differentiated into classical M1 macrophages or alternative M2 macrophages in vitro. GSK3α deletion, but not GSK3ß deletion, attenuated the expression of genes associated with M1 polarization while promoting the expression of genes associated with M2 polarization by modulating STAT3 and STAT6 activation. CONCLUSIONS: Our findings suggest that deletion of myeloid GSK3α attenuates the progression of atherosclerosis by promoting an M2 macrophage phenotype.