Pharmacological treatment for pubertal progression in boys with delayed or slow progression of puberty: A small-scale randomized study with testosterone enanthate and testosterone undecanoate treatment.

Context: The use of testosterone enanthate (TE), 50-75 mg intramuscularly (i.m.)/month, for the treatment of boys with delayed puberty or slow progression to induce puberty is the standard of care (SoC) in Sweden.

Efficacy and safety of dapagliflozin in children and young adults with type 2 diabetes: a prospective, multicentre, randomised, parallel group, phase 3 study.

Background: Since there are few treatment options for young people with type 2 diabetes, we aimed to assess the efficacy and safety of dapagliflozin as add-on therapy in children, adolescents, and young adults with type 2 diabetes receiving metformin, insulin, or both.

Methods: This multicentre, placebo-controlled, double-blind, randomised phase 3 study was undertaken at 30 centres in five countries (Hungary, Israel, Mexico, Russia, and the USA). Participants aged 10-24 years with type 2 diabetes and HbA1c concentration of 6·5-11% (48-97 mmol/mol) were randomly assigned 1:1 to oral dapagliflozin 10 mg or placebo during a 24 week double-blind period, which was then followed by a 28 week open-label safety extension in which all participants received dapagliflozin.

Correction to: How is the Pharmaceutical Industry Structured to Optimize Pediatric Drug Development? Existing Pediatric Structure Models and Proposed Recommendations for Structural Enhancement.

The article How is the Pharmaceutical Industry Structured to Optimize Pediatric Drug Development? Existing Pediatric Structure Models and Proposed Recommendations for Structural Enhancement, written by Thomas Severin et al. was originally published electronically on the publisher's internet portal on February 6, 2020 without open access. With the author(s)' decision to opt for Open Choice the copyright of the article changed on April 22, 2020 to © The Author(s) 2020 and the article is forthwith distributed under a Creative Commons Attribution 4.

How is the Pharmaceutical Industry Structured to Optimize Pediatric Drug Development? Existing Pediatric Structure Models and Proposed Recommendations for Structural Enhancement.

Background: Pediatric regulations enacted in both Europe and the USA have disrupted the pharmaceutical industry, challenging business and drug development processes, and organizational structures. Over the last decade, with science and innovation evolving, industry has moved from a reactive to a proactive mode, investing in building appropriate structures and capabilities as part of their business strategy to better tackle the challenges and opportunities of pediatric drug development.

Methods: The EFGCP Children's Medicines Working Party and the IQ Pediatric working group have joined their efforts to survey their member company representatives to understand how pharmaceutical companies are organized to fulfill their regulatory obligations and optimize their pediatric drug development programs.

Prevalence of Premature Thelarche at 18 Months of Age: A Population- and Hospital-Based Study of Prevalence and Incidence in Girls Born at Northern Älvsborg County Hospital in Sweden.

Objective: The aim of this work was to investigate the prevalence of premature thelarche (PT) in 18-month-old girls, and the incidence of clinically evaluated PT for girls aged 18-36 months.

Methods: In the prevalence substudy, a prospective population-based cohort of 3,140 girls born at Northern Älvsborg county hospital (NÄL) in Trollhättan, Sweden, was followed for 2 years. Girls with breast development at the 18-month health check were referred to one pediatric center in NÄL for evaluation.

17β-Estradiol and Gonadotropin Levels for the Diagnosis of the Benign Form of Breast Development in Girls Aged up to 4 Years in Real-Life Clinical Practice.

Background: Early onset of breast development in a young girl is usually a benign and isolated prepubertal condition, i.e., premature thelarche (PT), but can sometimes be progressive and the first sign of pubertal precocity (PP).

First Morning Voided Urinary Gonadotropin Measurements as an Alternative to the GnRH Test.

Aims: We studied whether first morning voided (FMV) urinary gonadotropin measurements could be used as a noninvasive alternative to the GnRH test in the assessment of the hypothalamic-pituitary-gonadal function in children.

Methods: In a single-center study, we compared FMV urinary gonadotropin concentrations with basal and GnRH-stimulated serum gonadotropin levels in 274 children and adolescents (78 girls, 196 boys) aged 5-17 years referred for growth and pubertal disorders. The concordance between FMV urinary gonadotropin concentrations and GnRH test results was assessed.

Sex Steroid Replacement Therapy in Female Hypogonadism from Childhood to Young Adulthood.

The overall goal of pubertal sex hormone replacement therapy (HRT) in girls is not only about development of secondary sexual characteristics, but also to establish an adult endocrine and metabolic milieu, as well as adult cognitive function. Estradiol (E2) is the first choice for HRT compared to ethinyl estradiol (EE2). E2 is the most potent endogenous estrogen in the circulation, with established levels during spontaneous puberty.

Sensitive RIA measures testosterone concentrations in prepubertal and pubertal children comparable to tandem mass spectrometry.

Background: Immunoassays have been criticized for poor accuracy at low testosterone concentrations. Mass spectrometry (MS) has been proposed as the only reliable method for testosterone determination. The aim of this study was to compare a sensitive testosterone radioimmunoassay (RIA) with results from different MS.

Physiological estrogen replacement therapy for puberty induction in girls: a clinical observational study.

Background/aim: The goal of estrogen replacement therapy (ERT) in girls with hypogonadism is to achieve the endocrine milieu similar to natural puberty, where transdermal administration is the most physiological route. The aim of the study was to evaluate guidelines for the induction of puberty with transdermal estradiol (E2) patches in a large outpatient setting.

Methods: In a retrospective study, serum E2 levels from 18 clinics were analyzed at the Göteborg Pediatric Growth Research Center laboratory, as part of the initiation of ERT in girls with hypogonadism.

Comparison of methods for evaluation of the suppressive effects of prednisolone on the HPA axis and bone turnover: changes in s-DHEAS are as sensitive as the ACTH test.

Objective: Different hypothalamic-pituitary-adrenal (HPA) axis function tests are used for diagnosing disease and evaluating suppressive effects of corticosteroid treatment. Our objectives were to evaluate sensitivity and precision of different HPA axis tests to be able to select one that combines good performance with good practicability, suitable for investigation of new corticosteroids in clinical trials.

Methods: In this descriptive, double-blind, parallel-group study, 60 healthy male volunteers were treated with once-daily morning doses of prednisolone for 2 weeks.

Pubertal growth and serum testosterone and estradiol levels in boys.

Background/aims: To study serum testosterone and estradiol in healthy boys in relation to growth during puberty up to peak height velocity (PHV).

Methods: Growth velocity was analyzed through testosterone (n = 41) and 17β-estradiol (n = 37) 24-hour profiles in a dose-response model. Participants were 26 healthy boys admitted for short or tall stature or participating as healthy volunteers at the Queen Silvia Children's Hospital.

Age at adiposity rebound is associated with fat mass in young adult males-the GOOD study.

Objective: Age at adiposity rebound (AR) is associated with obesity and Type 2 Diabetes in adults. The aim of the present study was to investigate the role of age at AR in adult fat mass, fat distribution and pubertal timing for a Swedish cohort.

Patients And Methods: This is a retrospective cohort study.

Estradiol and pubertal growth in girls.

Aim: The objective of this study was to determine estradiol levels and assess their relationship to pubertal growth in girls.

Methods: Thirty-seven 24-hour profiles of serum 17β-estradiol were retrospectively analyzed in relation to growth in 27 healthy girls admitted for short/tall stature (n = 20) or recruited as healthy volunteers at Göteborg Pediatric Growth Research Center (GP-GRC).

Inclusion Criteria: Birth weight and length above -2 SDS, gestational age 37-42 weeks, prepubertal height and weight within ± SDS and normal growth hormone secretion.

The glucokinase activator AZD6370 decreases fasting and postprandial glucose in type 2 diabetes mellitus patients with effects influenced by dosing regimen and food.

Aims: To investigate the pharmacodynamics, pharmacokinetics and safety of the glucokinase activator AZD6370 after 1 day of administration under fed and fasted conditions in patients with type 2 diabetes mellitus (T2DM).

Methods: This was a two-part study. In Part A, patients received a single oral dose of AZD6370 (20, 60 or 180 mg) or placebo in the fasted or fed states (both n=8).

Tolerability, pharmacokinetics, and pharmacodynamics of the glucokinase activator AZD1656, after single ascending doses in healthy subjects during euglycemic clamp.

Objectives: AZD1656 is a novel glucokinase activator with a postulated dual mechanism of action by activating glucokinase in both the pancreas and the liver, and with the potential to deliver effective glucose-lowering in Type 2 diabetes mellitus. Here, we present the tolerability, pharmacokinetics and pharmacodynamics of AZD1656 in two single-blind, randomized, placebo-controlled studies, one with Western and the other with Japanese healthy adult male subjects.

Methods: Both studies evaluated oral single ascending doses of AZD1656 of up to 180 mg, administered during euglycemic clamp conditions to explore a wide dose range without risking hypoglycemia.

Glucokinase activators AZD6370 and AZD1656 do not affect the central counterregulatory response to hypoglycemia in healthy males.

Context: Glucokinase is expressed in the hypothalamus, but effects of glucokinase activators (GKAs) on counterregulatory responses to hypoglycemia are unknown.

Objective: Two separate studies assessed the counterregulatory hormone responses to hypoglycemia induced by the GKAs, AZD6370 and AZD1656, compared with insulin infusion.

Design And Setting: Both studies were randomized, open, two-way crossover studies, conducted in separate clinical research centers.

Longitudinal assessment of bone mineral density in children and adolescents with inflammatory bowel disease.

Objectives: Low bone mineral density (BMD) is recognized as a potential problem in children with inflammatory bowel disease (IBD). We aimed to describe the longitudinal development of BMD in a population of Swedish pediatric patients with IBD.

Methods: A total of 144 patients with IBD (93 males; 83 with ulcerative colitis [UC], 45 with Crohn disease [CD]) were examined with dual-energy x-ray absorptiometry at baseline.

Pubertal timing predicts leg length and childhood body mass index predicts sitting height in young adult men.

Objective: To investigate the impact of pubertal timing and childhood body mass index (BMI), both within normal range, on adult anthropometrics.

Study Design: Detailed growth charts were retrieved for the men participating in the population-based Gothenburg Osteoporosis and Obesity Determinants study. Age at peak height velocity and childhood BMI were calculated (n = 527), and anthropometric measurements were performed.

Familial resemblance of bone mineral density in children with inflammatory bowel disease.

Background And Aim: Low bone mineral density (BMD) has recently been recognized as a potential health problem in children with inflammatory bowel disease (IBD). Our aim was to investigate the familial resemblance of BMD in pediatric patients with IBD.

Patients And Methods: In this population-based study from western Sweden, we assessed 144 children with IBD, 83 with ulcerative colitis, 45 with Crohn disease, 16 with indeterminate colitis, and their parents (136 mothers and 130 fathers) with dual-energy X-ray absorptiometry (DEXA).

Low bone mineral density in children and adolescents with inflammatory bowel disease: a population-based study from Western Sweden.

Background: Low bone mineral density (BMD) has been recognized as a potential problem in children with inflammatory bowel disease (IBD). The aim of the study was to investigate BMD in Swedish children and adolescents with IBD and to evaluate possible factors affecting BMD.

Methods: To evaluate BMD, all patients (n = 144) underwent a dual-energy X-ray absorptiometry (DXA) of the whole body and the spine.

BMI changes during childhood and adolescence as predictors of amount of adult subcutaneous and visceral adipose tissue in men: the GOOD Study.

Objective: The amount of visceral adipose tissue is a risk factor for the metabolic syndrome. It is unclear how BMI changes during childhood and adolescence predict adult fat distribution. We hypothesized that there are critical periods during development for the prediction of adult subcutaneous and visceral fat mass by BMI changes during childhood and adolescence.