Yang Chen

• Livingston, M. H.; Mahant, S.; Connolly, B.; MacLusky, I.; Laberge, S.; Giglia, L.; Yang, C.; Roberts, A.; Shawyer, A.; Brindle, M., et al., 2020, "Effectiveness of Intrapleural Tissue Plasminogen Activator and Dornase Alfa vs Tissue Plasminogen Activator Alone in Children with Pleural Empyema A Randomized Clinical Trial", JAMA pediatrics, February 174(4): 332 - 340.
  Abstract: Importance Clinical guidelines recommend that children with pleural empyema be treated with chest tube insertion and intrapleural fibrinolytics. The addition of dornase alfa (DNase) has been reported to improve outcomes in adults but remains unproven in children. Objective To determine if intrapleural tissue plasminogen activator (tPA) and DNase is more effective than tPA and placebo at reducing hospital length of stay in children with pleural empyema. Design, Setting, and Participants This multicenter, parallel-group, placebo-controlled, superiority randomized clinical trial included children diagnosed as having pleural empyema requiring drainage aged 6 months to 18 years treated at 6 tertiary Canadian children’s hospitals. A total of 379 children were assessed for eligibility; 281 were excluded and 98 were randomized. One child was excluded after randomization for not meeting the inclusion criteria. Data were collected from March 4, 2013, to December 13, 2017. Interventions Participants underwent chest tube insertion and 3 daily administrations of intrapleural tPA, 4 mg, followed by DNase, 5 mg (intervention group), or 5 mL of normal saline (placebo; control group). Participants, families, clinical staff, and members of the study team were blinded to allocation. Main Outcomes and Measures The primary outcome was hospital length of stay from chest tube insertion to discharge. Secondary outcomes included time to meeting discharge criteria, time to chest tube removal, mean fever duration, additional pleural drainage procedures, hospital readmissions, and total health care cost. Results Of the 97 analyzed children with pleural empyema, 52 (54%) were male, and the mean (SD) age was 5.1 (3.6) years. A total of 49 children were randomized to tPA and DNase and 48 were randomized to tPA and placebo. Treatment with tPA and DNase was not associated with decreased hospital length of stay compared with tPA and placebo (mean [SD] length of stay, 9.0 [4.9] vs 9.1 [5.3] days; mean difference, −0.1 days; 95% CI, −2.0 to 2.1; P = .96). Similarly, no significant differences were observed for any of the secondary outcomes. Of the 14 adverse events in the tPA and DNase group, 6 (43%) were serious; of the 21 adverse events in the tPA and placebo group, 8 (38%) were serious. There were no deaths. Conclusions and Relevance The addition of DNase to intrapleural tPA for children with pleural empyema had no effect on hospital length of stay or other outcomes compared with tPA with placebo. Clinical practice guidelines should continue to support the use of chest tube insertion and intrapleural fibrinolytics alone as first-line treatment for pediatric empyema.

  Link(s) to publication:

  http://dx.doi.org/10.1001/jamapediatrics.2019.5863

• Eny, K.; Chen, S.; Anderson, L. N.; Chen, Y.; Lebovic, G.; Pullenayegum, E.; Parkin, P. C.; Maguire, J. L.; Birken, C. S.; TARGet Kids! Collaboration, ., et al., 2018, "Breastfeeding duration, maternal body mass index, and birth weight are associated with differences in body mass index growth trajectories in early childhood", The American Journal of Clinical Nutrition, April 107(4): 584 - 592.
  Abstract: Background Accelerated postnatal growth is an important predictor for obesity risk. It is unknown whether early-life obesity-related risk factors affect body mass index (BMI) growth rates during distinct growth periods from early infancy through preschool years. Objective We examined whether breastfeeding duration, maternal BMI, and birth weight are associated with growth trajectories of age- and sex-standardized WHO BMI z scores (zBMIs) in young children. Design Children (n = 5905) in The Applied Research Group for Kids (TARGet Kids!) prospective cohort study underwent repeated measures of weight and length or height from birth to 10 y of age. Piecewise linear mixed models were used to determine whether zBMI growth rates differ for each risk factor during periods of growth between birth and 1, 3, 18, 36, and 72 mo of age. Results Children who were breastfed <6 mo compared with ≥6 mo showed a higher growth rate between 1–3 and 3–18 mo, resulting in higher standardized BMIs (zBMIs) of +0.24, +0.12, and +0.19 at 18, 36, and 72 mo, respectively. Maternal BMI (in kg/m2) ≥30 compared with <30 resulted in higher growth rates between 1–3 and 36–72 mo and higher zBMIs of +0.22, +0.14, +0.18, and +0.41 at 3, 18, 36, and 72 mo, respectively. Infants weighing <2.5 kg at birth (compared with 2.5–4 kg) experienced higher growth rates between 1–3 and 3–18 mo but had lower zBMIs at all time points (zBMI: −1.45 to −0.21). Infants weighing ≥4 kg at birth (compared with 2.5–4 kg) had significantly lower growth rates in the first 3 mo but higher zBMIs at all time points (zBMI: +1.16 to +0.27). Conclusions Differences in zBMI growth rates by breastfeeding duration, maternal BMI, and birth weight are seen in early infancy and contribute to differences in zBMI, which persist into midchildhood.

  Link(s) to publication:

  http://dx.doi.org/10.1093/ajcn/nqx081

• Plumptre, L.; Anderson, L. N.; Chen, Y.; Carsley, S.; Narang, I.; Hamilton, J.; McCrindle, B.; Parkin, P. C.; Maguire, J.; Birken, C. S., et al., 2017, "Longitudinal Analysis of Sleep Duration and Cardiometabolic Risk in Young Children", Childhood Obesity, August 13(4): 291 - 299.
  Abstract: Background: The aim of this study is to determine if sleep duration in early childhood is associated with cardiometabolic risk (CMR) in later childhood as assessed by a CMR cluster score [sum of age- and sex-standardized z-scores of waist circumference (WC), systolic blood pressure, triglycerides, glucose, and (inverse) high-density lipoprotein (HDL)]. Secondary objectives included examining sleep duration and the individual CMR factors and BMI z-score. Patients and Methods: A prospective cohort study was conducted using data from the TARGet Kids! practice-based research network in Toronto, Canada. Children (n = 597) with parent-reported 24-hour sleep duration in early childhood (12–36 months) and a follow-up visit (36–96 months) with all five CMR factors were included in the analysis. Multivariable linear regression was used to assess the relationship between early childhood sleep duration and later childhood CMR, adjusting for relevant covariates. Results: Average 24-hour sleep duration in early childhood [mean age: 28.1 (6.6) months] was 11.8 (1.4) hours, with 87% meeting or exceeding total sleep recommendations for their age. Sleep duration in early childhood was not associated with the CMR cluster score in later childhood. Shorter sleep duration was associated with higher HDL concentrations [adjusted β = −0.028 (95% confidence interval: −0.049 to −0.007), p = 0.009]. Conclusions: Further research is needed to determine if early childhood sleep duration is associated with HDL in later childhood. Future studies, which investigate sleep quality in addition to sleep duration, may be helpful.

  Link(s) to publication:

  http://dx.doi.org/10.1089/chi.2016.0279

• Aglipay, M.; Birken, C. S.; Parkin, P. C.; Loeb, M. B.; Thorpe, K.; Chen, Y.; Laupacis, A.; Mamdani, M.; Macarthur, C.; Hoch, J. S., et al., 2017, "Effect of High-Dose vs Standard-Dose Wintertime Vitamin D Supplementation on Viral Upper Respiratory Tract Infections in Young Healthy Children", Journal of the American Medical Association (JAMA), July 318(3): 245 - 254.
  Abstract: Importance Epidemiological studies support a link between low 25-hydroxyvitamin D levels and a higher risk of viral upper respiratory tract infections. However, whether winter supplementation of vitamin D reduces the risk among children is unknown. Objective To determine whether high-dose vs standard-dose vitamin D supplementation reduces the incidence of wintertime upper respiratory tract infections in young children. Design, Setting, and Participants A randomized clinical trial was conducted during the winter months between September 13, 2011, and June 30, 2015, among children aged 1 through 5 years enrolled in TARGet Kids!, a multisite primary care practice–based research network in Toronto, Ontario, Canada. Interventions Three hundred forty-nine participants were randomized to receive 2000 IU/d of vitamin D oral supplementation (high-dose group) vs 354 participants who were randomized to receive 400 IU/d (standard-dose group) for a minimum of 4 months between September and May. Main Outcome Measures The primary outcome was the number of laboratory-confirmed viral upper respiratory tract infections based on parent-collected nasal swabs over the winter months. Secondary outcomes included the number of influenza infections, noninfluenza infections, parent-reported upper respiratory tract illnesses, time to first upper respiratory tract infection, and serum 25-hydroxyvitamin D levels at study termination. Results Among 703 participants who were randomized (mean age, 2.7 years, 57.7% boys), 699 (99.4%) completed the trial. The mean number of laboratory-confirmed upper respiratory tract infections per child was 1.05 (95% CI, 0.91-1.19) for the high-dose group and 1.03 (95% CI, 0.90-1.16) for the standard-dose group, for a between-group difference of 0.02 (95% CI, −0.17 to 0.21) per child. There was no statistically significant difference in number of laboratory-confirmed infections between groups (incidence rate ratio [RR], 0.97; 95% CI, 0.80-1.16). There was also no significant difference in the median time to the first laboratory-confirmed infection: 3.95 months (95% CI, 3.02-5.95 months) for the high-dose group vs 3.29 months (95% CI, 2.66-4.14 months) for the standard-dose group, or number of parent-reported upper respiratory tract illnesses between groups (625 for high-dose vs 600 for standard-dose groups, incidence RR, 1.01; 95% CI, 0.88-1.16). At study termination, serum 25-hydroxyvitamin D levels were 48.7 ng/mL (95% CI, 46.9-50.5 ng/mL) in the high-dose group and 36.8 ng/mL (95% CI, 35.4-38.2 ng/mL) in the standard-dose group. Conclusions and Relevance Among healthy children aged 1 to 5 years, daily administration of 2000 IU compared with 400 IU of vitamin D supplementation did not reduce overall wintertime upper respiratory tract infections. These findings do not support the routine use of high-dose vitamin D supplementation in children for the prevention of viral upper respiratory tract infections.

  Link(s) to publication:

  http://dx.doi.org/10.1001/jama.2017.8708

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