Combined growth hormone and insulin-like growth factor-1 rescues growth retardation in glucocorticoid-treated mdxmice but does not prevent osteopenia.

Short stature and osteoporosis are common in Duchenne muscular dystrophy (DMD) and its pathophysiology may include an abnormality of the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis, which is further exacerbated by long-term glucocorticoid (GC) treatment. Hence, an agent that has anabolic properties and may improve linear growth would be beneficial in this setting and therefore requires further exploration. A 5-week-old x-linked muscular dystrophy (mdx) mice were used as a model of DMD. They were treated with prednisolone ± GH + IGF-1 for 4 weeks and then compared to control mdx mice to allow the study of both growth and skeletal structure. GC reduced cortical bone area, bone fraction, tissue area and volume and cortical bone volume, as assessed by micro computed tomography (CT) In addition, GC caused somatic and skeletal growth retardation but improved grip strength. The addition of GH + IGF-1 therapy rescued the somatic growth retardation and induced additional improvements in grip strength (16.9% increase, P < 0.05 compared to control). There was no improvement in bone microarchitecture (assessed by micro-CT and static histomorphometry) or biomechanical properties (assessed by three-point bending). Serum bone turnover markers (Serum procollagen 1 intact N-terminal propeptide (P1NP), alpha C-terminal telopeptide (αCTX)) also remained unaffected. Further work is needed to maximise these gains before proceeding to clinical trials in boys with DMD.

Parent-reported outcomes in young children with disorders/differences of sex development.

BACKGROUND: There is a paucity of tools that can be used in routine clinical practice to assess the psychosocial impact of Disorders/Differences of Sex Development (DSD) on parents and children. OBJECTIVE: To evaluate the use of short Parent Self-Report and Parent Proxy-Report questionnaires that can be used in the outpatient setting. METHODS: Previously validated DSD-specific and generic items were combined to develop a Parent Self-Report questionnaire and a Parent Proxy-Report questionnaire for children under 7 years. Of 111 children approached at one tertiary paediatric hospital, the parents of 95 children (86%) with DSD or other Endocrine conditions completed these questionnaires. RESULTS: Questionnaires took under 10 min to complete and were found to be easy to understand. Compared to reference, fathers of children with DSD reported less stress associated with Clinic Visits (p = 0.02) and managing their child's Medication (p = 0.04). However, parents of children with either DSD or other Endocrine conditions reported more symptoms of Depression (p = 0.03). Mothers of children with DSD reported greater Future Concerns in relation to their child's condition (median SDS - 0.28; range - 2.14, 1.73) than mothers of children with other Endocrine conditions (SDS 1.17; - 2.00, 1.73) (p = 0.02). Similarly, fathers of children with DSD expressed greater Future Concerns (median SDS -1.60; - 4.21, 1.00) than fathers of children with other Endocrine conditions (SDS 0.48; - 2.13, 1.52) (p = 0.04). CONCLUSION: DSD was associated with greater parental concerns over the child's future than other Endocrine conditions. Brief parent-report tools in DSD can be routinely used in the outpatient setting to assess and monitor parent and patient needs.

Single-Centre Experience of Testosterone Therapy for Boys with Hypogonadism.

BACKGROUND: Hypogonadism in boys is one of the commonest conditions encountered in paediatric endocrinology. AIMS: To study variations in management in a contemporary group of boys at a single specialist centre. METHODS: Retrospective review of case records of all boys treated with testosterone at a tertiary endocrine service from 2012 to 2017. RESULTS: Of the 358 boys reviewed for hypogonadism, 46 (13%) were initiated on testosterone therapy at a median age (range) of 14.2 years (12.1, 17.7). Indications for therapy included a functional delay of puberty that was constitutional in 17 (37%) or related to chronic disease in 10 (22%) or organic hypogonadism due to primary gonadal failure in 7 (15%), multiple pituitary hormone deficiency in 6 (13%), and isolated hypogonadotropic hypogonadism in 6 (13%). Of the 46 boys, 40 (89%) were started on intramuscular testosterone, 4 (9%) on oral testosterone, and 1 (2%) on transdermal gel. Of the 19 boys (40%) with organic hypogonadism re-quiring long-term therapy, 12 (63%) had assessment of liver function, 6 (32%) had a haematocrit, and 2 (11%) had a DXA scan in the year of commencing treatment. CONCLUSIONS: Testosterone therapy is administered in about 13% of boys reviewed for hypogonadism and its monitoring requires standardisation.

Animal models to explore the effects of glucocorticoids on skeletal growth and structure.

Glucocorticoids (GCs) are effective for the treatment of many chronic conditions, but their use is associated with frequent and wide-ranging adverse effects including osteoporosis and growth retardation. The mechanisms that underlie the undesirable effects of GCs on skeletal development are unclear, and there is no proven effective treatment to combat them. An in vivo model that investigates the development and progression of GC-induced changes in bone is, therefore, important and a well-characterized pre-clinical model is vital for the evaluation of new interventions. Currently, there is no established animal model to investigate GC effects on skeletal development and there are pros and cons to consider with the different protocols used to induce osteoporosis and growth retardation. This review will summarize the literature and highlight the models and techniques employed in experimental studies to date.

Diminishing Effect Sizes with Repeated Exposure to Evidence-Based Practice Training in Entry-Level Health Professional Students: A Longitudinal Study.

PURPOSE: To investigate the magnitude of change in outcomes after repeated exposure to evidence-based practice (EBP) training in entry-level health professional students. METHOD: Using an observational cross-sectional analytic design, the study tracked 78 students in physiotherapy, podiatry, health science, medical radiations, and human movement before and after two sequential EBP courses. The first EBP course was aimed at developing foundational knowledge of and skills in the five steps of EBP; the second was designed to teach students to apply these steps. Two EBP instruments were used to collect objective (actual knowledge) and self-reported (terminology, confidence, practice, relevance, sympathy) data. Participants completed both instruments before and after each course. RESULTS: Effect sizes were larger after the first course than after the second for relevance (0.72 and 0.26, respectively), practice (1.23 and 0.43), terminology (2.73 and 0.84), and actual knowledge (1.92 and 1.45); effect sizes were larger after the second course for sympathy (0.03 and 0.14) and confidence (0.81 and 1.12). CONCLUSIONS: Knowledge and relevance changed most meaningfully (i.e., showed the largest effect size) for participants with minimal prior exposure to training. Changes in participants' confidence and attitudes may require a longer time frame and repeated training exposure.

Objet : Étudier l'ordre de grandeur du changement au niveau des résultats suivant une exposition répétée à la pratique factuelle au cours de la formation des futurs professionnels de la santé au niveau débutant. Méthode : Basée sur un concept d'analyse transversale par observation, l'étude a suivi 78 étudiants en physiothérapie, podiatrie, sciences de la santé, rayonnements médicaux et mouvement humain avant et après deux cours consécutifs sur la pratique factuelle. Le premier visait à produire des connaissances générales et techniques fondamentales sur les cinq étapes de la pratique factuelle. Le deuxième visait à apprendre aux étudiants à appliquer ces étapes. On a utilisé deux instruments relatifs à la pratique factuelle pour réunir des données objectives (connaissances réelles) et autodéclarées (terminologie, confiance, pratique, pertinence, sympathie). Les participants ont rempli les deux questionnaires avant et après chaque cours. Résultats : L'ordre de grandeur de l'effet était plus important après le premier cours qu'après le deuxième pour ce qui est de la pertinence (0,72, 0,26), de la pratique (1,23, 0,43), de la terminologie (2,73, 0,84) et des connaissances réelles (1,92, 1,45). Le changement était plus important après le deuxième cours dans le cas de la sympathie (0,03, 0,14) et dans celui de la confiance (0,81, 1,12). Conclusions : Les connaissances et la pertinence ont changé le plus (c.-à-d., ont montré l'effet le plus important) chez les participants qui avaient une exposition antérieure minime à la formation. Les changements aux niveaux de la confiance et des attitudes des participants peuvent prendre plus de temps et nécessiter une exposition répétée à la formation.

Cyclooxygenase-2 expression in advanced nasopharyngeal carcinoma--a prognostic evaluation and correlation with hypoxia inducible factor 1alpha and vascular endothelial growth factor.

Cycloxygenase-2 (COX-2), hypoxia inducible factor 1-alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) can be induced by the Epstein-Barr virus oncoprotein latent membrane protein-1 (LMP-1) in nasopharyngeal cancer (NPC) cell lines. This study examined the prognostic relevance of COX-2 and its relationship with HIF-1alpha and VEGF expression in NPC biopsies. Primary tumor biopsies were obtained from 78 participants of a randomized trial who received radiotherapy (RT) with or without concurrent chemotherapy for locoregionally advanced NPC. These were analyzed for COX-2 expression and then correlated with age, sex, disease stage, treatment arm, survival and disease recurrence, VEGF and HIF-1alpha expression in a regression model. 83% of tumors expressed COX-2, 47% co-expressed COX-2 and VEGF, 38% co-expressed COX-2 and HIF-1alpha. On univariate analysis, COX-2 expression did not correlate with survival and recurrence, but moderate to high COX-2 expression was associated with advanced nodal stage (p=0.03). Although univariate analysis showed that COX-2-HIF-1alpha co-expression was associated with worse progression-free survival (p=0.046), time to local (p=0.004) and regional recurrence (p=0.007), multivariate analysis failed to confirm any correlation between COX-2-HIF-1alpha or COX-2-VEGF co-expression and survival or disease recurrence. Contrary to previous report, this study failed to demonstrate any prognostic significance of COX-2 expression alone or co-expression with HIF-1alpha or VEGF in advanced NPC.