Joan Bel

Variability in adherence to rhGH treatment: Socioeconomic causes and effect on children's growth

BACKGROUND In children with growth disorders, mean final height is associated to poor adherence to Growth Hormone therapy. The primary goal of this study is to identify patients who do not adhere to GH therapy and determine the influence of adherence in response to the treatment. The role of serum IGF-I and influence of socio-economic factors on the therapeutic adherence will also be evaluated. METHODS 158 children under treatment with rhGH were included in the study. Age, gender, etiology, Tanner stage, duration of treatment, growth rate, IGF-I serum values, daily dose, and annual rhGH dose data were collected. Adherence to therapy was defined as moderate-to-poor when the patient had taken less than 92% of the prescribed medication. A subgroup of 106 patients completed a questionnaire to assess social and environmental effects. RESULTS Moderate-to-poor adherence to rhGH treatment was determined in 33.5% of study patients. A decrease in adherence was associated to treatment duration (p=0.001). A significant correlation was determined between adherence and height velocity (p=0.002) and IGF-I (p<0.0001) levels. Adherence rates were associated to the mothers educational level (p=0.007). CONCLUSION Poor adherence to GH therapy was observed in one-third of study patients, resulting in suboptimal growth. IGF-I levels can be helpful to identify patients with poor adherence to GH medication. Physicians should pay special attention to certain characteristics of the patient and their environment, and encourage desirable therapeutic compliance.

Analytical performance and clinical usefulness of two binding assays for growth hormone binding protein (GHBP) measurement: high performance liquid chromatography (HPLC)-gel filtration and dextran-coated charcoal adsorption

We compared two binding assays for growth hormone binding protein (GHBP) measurements, which differ in the method of bound and free GH separation: HPLC-gel filtration or dextran coated-charcoal adsorption (DCC). Two pools of sera (high and medium GHBP activity) were used for quality-control assessment. Moreover, 62 samples from 34 children and 28 adults with different nutritional status were studied. Total, between- and intra-iodination coefficients of variation (CVs) from the two methods were not different. Although percentage binding measured in the pool sera significantly differed, the concentrations assessed by Scatchard plot were comparable. Results obtained by the two methods in the 62 sera were significantly correlated (r = 0.77, P < 0.001). With both methods GHBP activity correlated with chronological age and body mass index (BMI) and differed among groups with different nutritional status. Although HPLC and DCC separation methods for GHBP measurement differ in their practicability, our study demonstrates that performance and the clinical usefulness of the two methods are comparable.

Retraso de crecimiento y estado nutricional en niños ingresados en una institución de acogida

Fundamento Se determino la incidencia de retraso de crecimiento en ninos con problemas socialesque ingresaban en una institucion de acogida y valoramos la recuperacion de dicho retrasotras su paso por el centro. En una segunda fase se analizo el estado nutriticional como posiblecausa del retraso de crecimiento en ninos con problemas sociales. Sujetos y metodo Se estudiaron dos cohortes de ninos ingresados en el centro de acogida Estels.Se procedio al analisis retrospectivo del peso y la talla en el momento del ingreso y delalta en el centro de la cohorte A, formada por 118 ninos (47 varones y 71 ninas) de edadescomprendidas entre un mes y los 15 anos. Se determinaron los parametros nutricionales albumina,prealbumina, proteina transportadora de retinol, y los parametros hormonales IGF-I,IGFBP-3, GHBP y leptina en la cohorte B, compuesta por 31 ninos (16 varones y 15 ninas) de1 a 11 anos de edad, a su ingreso en el centro de acogida. Resultados Grupo A. El 26,2% (31 sujetos) de los ninos que ingresaron en el centro de acogidapresento una talla inferior a –2 desviaciones estandar (DE), 32 (27,1%) presentaron crecimientorecuperador tras su paso por el mismo, y 15 (46,8%) de ellos presentaron una recuperacionde talla superior a 0,5 DE. Los menores de 2 anos de edad fueron los mas afectados; el45% de ellos presento talla inferior a –2 DE al ingreso.Grupo B. El estudio nutricional objetivo unos resultados hormonales (IGF-I, IGFBP-3, GHBP yleptina) dentro de la normalidad. Se observaron las siguientes correlaciones significativas entreparametros hormonales y auxologicos: IGF-I con peso y talla IGFBP-3 con peso y talla, GHBPcon IMC y leptina con IMC. Conclusiones Una proporcion significativa de los ninos que ingresan en una institucion de acogidapresenta retraso de crecimiento. En nuestro estudio se detecto crecimiento recuperador enun grupo importante de todos ellos tras su paso por el centro. La malnutricion no es una causaprincipal del retraso de crecimiento presentado por estos ninos.

Baja sensibilidad del IGF-I, la IGFBP-3 y la GH urinaria en el diagnóstico de la insuficiencia de la hormona del crecimiento en niños y adolescentes varones con talla baja y velocidad de crecimiento disminuida

The usefulness of IGF-I, IGFBP-3, and the urinary GH excretion in the diagnostic evaluation of growth retardation in boys with short stature was studied.

Intervenciones clínicas en sobrepeso y obesidad: revisión sistemática de la literatura 2009-2014

OBJECTIVE To update the literature review on the effectiveness of clinical interventions on childhood obesity, proposed in Clinical Practice Guidelines, excluding prevention and pharmacological and surgical treatments. METHOD A systematic review was carried out in electronic databases of the Cochrane Database of Systematic Reviews (The Cochrane Library), MEDLINE, and SCOPUS, replicating the search for the Clinical Practice Guidelines, from 2009 to 2014. The Clinical Practice Guidelines of National Institute for Health and Care Excellence were taken as a reference. Systematic reviews were given priority, and the quality of the studies was assessed. RESULTS Out of a total of 3,703 documents initially identified, 48 were finally included. Studies showed great heterogeneity in the type and duration of interventions, and in outcome measures. Adherence to treatment was, in general, low. Multi-component interventions including diet, physical activity, sedentary lifestyle, and behaviour changes, involving the family, and starting at early ages, were the most effective for reducing body mass index. There is no consensus on criteria for referral to specialised care. CONCLUSIONS It is recommended to implement multi-component programs conducted by professionals with previous training, involving the family, and addressing behavioural, individual and socio-demographic aspects. Lack of adherence is one of the reasons for failure of interventions. Diagnostic and referral criteria, the outcome measures, and the type and duration of interventions need to be improved and standardised.

Remission Phase in Paediatric Type 1 Diabetes: New Understanding and Emerging Biomarkers

Type 1 diabetes (T1D) is a metabolic disease of unknown aetiology that results from the autoimmune destruction of the β-cells. Clinical onset with classic hyperglycaemic symptoms occurs much more frequently in children and young adults, when less than 30% of β-cells remain. Exogenous insulin administration is the only treatment for patients. However, due to glucose dysregulation, severe complications develop gradually. Recently, an increase in T1D incidence has been reported worldwide, especially in children. Shortly after diagnosis, T1D patients often experience partial remission called “honeymoon phase,” which lasts a few months, with minor requirements of exogenous insulin. In this stage, the remaining β-cells are still able to produce enough insulin to reduce the administration of exogenous insulin. A recovery of immunological tolerance to β-cell autoantigens could explain the regeneration attempt in this remission phase. This mini-review focuses on the remission phase in childhood T1D. Understanding this period and finding those peripheral biomarkers that are signs of immunoregulation or islet regeneration could contribute to the identification of patients with a better glycaemic prognosis and a lower risk of secondary complications. This remission phase could be a good checkpoint for the administration of future immunotherapies.

Measured free 25-hydroxyvitamin D in healthy children and relationship to total 25-hydroxyvitamin D, calculated free 25-hydroxyvitamin D and vitamin D binding protein

BACKGROUND vitamin D deficiency in children is still a global health problem. Measuring free 25-hydroxyvitamin D concentrations could provide a better estimate of the vitamin D status than total 25-hydroxyvitamin D (25(OH)D) levels. OBJECTIVE To assess the relationship between measured free vitamin D (m-f25(OH)D) and calculated free 25(OH)D (c-f25(OH)D), total 25(OH)D, intact parathyroid hormone (iPTH) and other markers of phosphocalcic metabolism. To establish serum m-f25(OH)D concentrations corresponding to a total 25(OH)D > 50 nmol/L which is accepted as vitamin D-sufficiency status in children. DESIGN Prospective cohort study. SETTING January and February 2017 in a Mediterranean population. PATIENTS healthy children. MEASUREMENTS m-f25(OH)D and vitamin D binding protein (VDBP) by ELISA. Free 25(OH)D was calculated using the formula described by Bikle. RESULTS m-f25(OH)D directly correlated with total 25(OH)D (r:0.804,p < .001), serum calcium (r:0.26,p:0.035), and c-f25(OH)D (r:0.553,p:0.016); and inversely with iPTH (r:-0.374, p:0.002), alkaline phosphatase (r:-0.28, p:0.026), and age (r:-0.289, p:0.018). Total 25(OH)D correlated with the same parameters as m-f25(OH)D except for serum calcium. However, c-f25(OH)D correlated only with total 25(OH)D and VDBP, both included in the calculation formula. Multiple regression analysis showed that m-f25(OH)D variations were independently explained by calcium (β:0.156, p:0.026) and total 25(OH)D (β:0.043, p < .001). The optimal m-f25(OH)D cut-off for discriminating between insufficient and sufficient total 25(OH)D was >9.8 pmol/L (Area Under Curve (AUC): 0.897 (95% confidence interval (CI): (0.798-0.958); p < .001; sensitivity:72.7% (95%CI: 49.8-89.3); specificity: 95.5% (95%CI: 84.5-99.4)). CONCLUSIONS Directly measured free vitamin D correlated better with markers of phosphocalcic metabolism than total 25(OH)D and c-f25(OH)D in a population of healthy children.