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Baricitinib is approved for the treatment of rheumatoid arthritis (RA) in more than 70 countries, and juvenile idiopathic arthritis (JIA) in the European Union. Population pharmacokinetic (PK) models were developed in a phase 3 trial to characterize PK in pediatric patients with JIA and identify weight‐based dosing regimens. The phase 3, randomized, double‐blind, placebo‐controlled withdrawal, efficacy and safety trial, JUVE‐BASIS, enrolled patients (aged 2 to <18 years) with polyarticular course JIA. During a safety/PK period, baricitinib concentration data from age‐based dose cohorts were compared to concentrations from adult patients receiving 4‐mg QD. PK data were used to develop a population PK model with allometric scaling to determine a weight‐based posology in pediatric patients with JIA that matched the adult 4‐mg exposure. Baricitinib plasma concentrations from 217 pediatric patients were used to characterize PK. Based on the adult model, pediatric PK was best described using a 2‐compartment model with allometric scaling on clearance and volume of distribution and renal function (estimated with glomerular filtration rate [GFR], a known covariate affecting PK of baricitinib) on clearance. The PK modeling suggested the optimal dosing regimen based on weight for pediatric patients as: 2‐mg QD for patients 10 to <30 kg and 4‐mg QD for patients ≥30 kg. The use of a population PK model of baricitinib treatment in adult patients with RA, with the addition of allometric scaling for weight on clearance and volume terms, was useful to predict exposures and identify weight‐based dosing in pediatric patients with JIA. [ABSTRACT FROM AUTHOR]

Objectives: To develop a new Body Mass Index (BMI) reference (MULT) based on longitudinal data of multi‐ethnic populations and to compare it to international BMI references. Methods: The MULT BMI reference was constructed through the LMS method and the Generalized Additive Models for Location Scale and Shape (GAMLSS), with 81 310 observations of 17 505 subjects aged 0–22 years old, from the United Kingdom, Ethiopia, Peru, India, Vietnam, Brazil, and Portugal. Outlier values were removed based on weight z‐scores (population level) and based on BMI z‐scores using the linear mixed effects model (individual level). The MULT M, S and L curves were compared to the ones of the World Health Organization (WHO), Centers for Disease Control and Prevention (CDC), International Obesity Task Force (IOTF), and Dutch Growth Study (DUTCH). The MULT BMI percentile cutoffs for overweight and obesity were calculated using the adult BMI values of 25 and 30 kg/m2 at 17, 18, 19, and 20 years old. Results: MULT presented the lowest mean BMI values for the ages 102–240 months for boys and 114–220 months for girls. MULT S values were similar to the WHO and IOTF for children under 60 months of age and the highest during puberty, while the L curve showed to be more symmetric than the other BMI references. Conclusion: The MULT BMI reference was constructed based on recent data of populations from 10 countries, being a good option to assess the nutritional status of multi‐ethnic populations. [ABSTRACT FROM AUTHOR]

Objectives: To develop new height references (MULT) based on longitudinal data of multi‐ethnic populations and to compare them to the height references from the Dutch Growth Study, from the Centers for Disease Control and Prevention (CDC) and from the World Health Organization (WHO). Methods: The MUL height references were developed through the LMS method and the Generalized Additive Models for Location Scale and Shape. They were constructed based on 2611 subjects (15 292 measurements) from the advantaged quintile of the Young Lives (Younger Cohort), Millennium Cohort Study, Adolescent Nutritional Assessment Longitudinal Study, and Epidemiological Health Investigation of Teenagers in Porto studies. The M, S curves were described to compare the growth trajectory of the MULT, DUTCH, CDC and WHO height references. For the population comparative analysis, we used the total sample of the studies (91 063 observations, 17 641 subjects). The Lin's concordance correlation coefficient (CCC) and Cohen's kappa coefficient (K) were used to verify the agreement between MULT, WHO and CDC height references. Results: The MULT height references showed taller boys for the periods of 61–174 months and 196–240 months and taller girls for 61–147 and 181–240 months, when compared to CDC and WHO height references. There was an almost perfect agreement between WHO and MULT height references (CCC >0.99) for the subjects aged 2 to 5 years. Conclusions: MULT height references presented a taller population and a high agreement with WHO growth charts, especially for children under 5 years, indicating that it could be useful to assess nutritional status of multi‐ethnic populations. [ABSTRACT FROM AUTHOR]

We compared different growth models parameterizations regarding (i) adjustment of weight-for-height, as denoted by body mass index (BMI); (ii) adjustment for different covariates, ie, age or height; and (iii) the use of different smoothing methods, ie, polynomial, fractional polynomial, or linear splines. A total of 11 459 measurements of weight and height from 719 participants were used, obtained from the EPITeen cohort at 13, 17, and 21 years, and extracted from child health books. The individual growth curves were modeled using mixed-effects polynomial, fractional polynomial, and linear splines, and each model parameterization included as covariate age or height. The goodness-of-fit of the model parametrizations was compared using the relative squared error (RSE) and the relative absolute error (RAE). The adjustment of weight-for-height as denoted by BMI was found to be biased, especially for extreme values of height and presented the worst fit indexes from all model parameterizations tested (RSE = 12.46%; RAE = 22.63%). Regardless of the smoothing method, the weight-for-height retrieved the best fit indexes in comparison to the adjustment for age. With regard to the smoothing methods and comparing weight-for-height model parameterizations, the fractional polynomial model performed better (RSE = 0.75%; RAE = 5.70%), followed by linear splines (RSE = 0.77%; RAE = 5.82%), and conventional polynomial (RSE = 0.91%; RAE = 6.82%). Therefore, growth modeling in pediatric age should be based on the modeling of weight-for-height because the use of BMI leaves residual confounding for height. Regarding the smoothing methods, although differences were relatively small, the fractional polynomials performed better in comparison to conventional polynomials and linear splines. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the association between sleep duration and blood pressure using a cross-sectional and longitudinal approach. As part of a population-based cohort, 1403 adolescents were evaluated at 13 and 17 years old. Sleep duration was estimated by the difference between self-reported usual bedtime and wake-up time. Blood pressure was measured using the auscultatory method. Regression coefficients ( β) and respective 95% confidence intervals were computed to evaluate the association between sleep duration and blood pressure, using linear regression models adjusted for practice of sports and body mass index at 17 years old. The mean (standard deviation) sleep duration at 13 years old was 9.0 (0.76) h per day, and on average it decreased by 46 min up to 17 years old. The median (25th-75th) systolic blood pressure at 17 years old was 110.0 (103.5-119.0) mmHg in females and 114.0 (106.0-122.0)mmHg in males ( P < 0.001); for diastolic blood pressure the values were 66.0 (60.0-71.0) and 69.0 (62.0-75.0) mmHg, respectively ( P < 0.001). In cross-sectional analysis, at 17 years old, after adjustment, a positive association was found between sleep duration and blood pressure, significant only for systolic blood pressure among females [ β = 0.730 (0.005; 1.455)]. In girls, no significant association was found between sleep duration at 13 years old and blood pressure at 17 years old, but in males an inverse association was found between sleep duration at 13 years old and blood pressure at 17 years old significant only for systolic blood pressure [ β = −1.938 (−3.229; −0.647)]. This study found no association between sleep duration at 13 years old and blood pressure at 17 years old in girls, but among males an inverse association was found. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the prevalence of body dissatisfaction and the association with depressive symptoms in 13-year-old adolescents, according to gender, and also to analyse the possible modifying effect of body mass index on this association. Methods: We evaluated 1868 adolescents as part of a population-based study in an urban community in Porto, Portugal. Using the Figure Rating Scale, participants choose their perceived and their desired figures; body dissatisfaction was measured by the difference between these values. The Beck Disorder Inventory II was used to measure depressive symptoms. Weight and height were measured by trained interviewers. To quantify the association between depressive symptoms and body dissatisfaction, regression parameters and 95% confidence intervals (CIs) were obtained by linear regression and bootstrapping. Results: Among females, 15.8% desired a bigger figure and 41.4% desired a thinner figure. Among males, this occurred for 34.1% and 33.5%, respectively. After adjustment, we found that body dissatisfaction was associated with increased depressive symptoms, in both genders, especially in those participants who wish to be thinner and in those presenting higher discrepancy between figures ( B = 6.5, 95% CI 4.1;9.3 for females, B = 3.3, 95% CI 1.3;6.8 for males). The association between body dissatisfaction and depressive symptoms was stronger among non-overweight (for participants who wish to be thinner: B = 5.18 95% CI 3.56; 6.95 vs. B = 3.49, 95% CI 1.70; 5.29 among females and B = 2.47, 95% CI 0.73; 4.76 vs. B = 1.60, 95% CI 0.34; 2.88 among males). Conclusions: The direct association between the wish to be thinner and depressive symptoms was stronger among the non-overweight youth. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to quantify the relationship between insulin resistance and haematological parameters from adolescence to adulthood.Methods: Participants from the EPITeen cohort were evaluated at 13, 17, and 21 years, through standardized procedures. A fasting blood sample was obtained, and insulin resistance was evaluated by the homeostatic model assessment (HOMA-IR). The cross-sectional association between HOMA-IR and haematological parameters at 21 years was quantified in 1671 participants by multivariate linear regression coefficients (β) and 95% confidence intervals (95%CI). For the longitudinal analysis (n = 496), trajectories of insulin and glucose were estimated using model-based clustering, and haematological parameters were compared according to trajectories using ANOVA.Results: At 21 years, after adjustment for BMI, positive associations (β [95%CI]) were found between HOMA-IR and red blood count (0.05 [0.03;0.07] in females; 0.02 [0.00;0.04] in males); and haematocrit (0.29 [0.12;0.46] in females; 0.21 [0.04,0.38] in males). In females, HOMA-IR was inversely associated with packed cell volume (PCV) (-0.35 [-0.66;-0.05]) and iron levels (-3.98 [-6.94,-1.03]) but positively associated with white blood cells (0.31 [0.19;0.43]) and platelets (7.66 [3.93;11.39]). In males, a higher HOMA-IR was significantly associated with higher haemoglobin (0.09 [0.03;0.16]). Regarding the longitudinal analysis, similar trends were found, but statistical significance was not reached.Conclusions: Both longitudinal and cross-sectional analyses support the hypothesis that insulin resistance is associated with increased red blood cells count and haematocrit in young adults, even within normal ranges of insulin and glucose. [ABSTRACT FROM AUTHOR]