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      Effectiveness and Overall Safety of NutropinAq ® for Growth Hormone Deficiency and Other Paediatric Growth Hormone Disorders: Completion of the International Cooperative Growth Study, NutropinAq ® European Registry (iNCGS)

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          Abstract

          Objective

          The International Cooperative Growth Study, NutropinAq ® European Registry (iNCGS) (NCT00455728) monitored long-term safety and effectiveness of recombinant human growth hormone (rhGH; NutropinAq ® [somatropin]) in paediatric growth disorders.

          Methods

          Open-label, non-interventional, post-marketing surveillance study recruiting children with growth disorders. Endpoints included gain in height standard deviation score (SDS), adult height, and occurrence of adverse events (AEs).

          Results

          2792 patients were enrolled. 2082 patients (74.6%) had growth hormone deficiency (GHD), which was isolated idiopathic in 1825 patients (87.7%). Non-GHD diagnoses included Turner syndrome (TS) (n=199), chronic renal insufficiency (CRI) (n=10), other non-GHD (n=498), and missing data for three participants. Improvements from baseline height SDS occurred at all time points to Month 132, and in all subgroups by disease aetiology. At Month 12, mean (95% CI) change in height SDS by aetiology was: idiopathic GHD 0.63 (0.61;0.66), organic GHD 0.71 (0.62;0.80), TS 0.59 (0.53; 0.65), CRI 0.54 (-0.49;1.56), and other non-GHD 0.64 (0.59;0.69). Mean height ( ± SD) at the last visit among the 235 patients with adult or near-adult height recorded was 154.0 cm ( ± 8.0) for girls and 166.7 cm ( ± 8.0) for boys. The most frequent biological and clinical non-serious drug-related AEs were increased insulin-like growth factor concentrations (314 events) and injection site haematoma (99 events). Serious AEs related to rhGH according to investigators were reported (n=30); the most frequent were scoliosis (4 events), epiphysiolysis (3 events), and strabismus (2 events).

          Conclusions

          There was an improvement in mean height SDS in all aetiology subgroups after rhGH treatment. No new safety concerns were identified.

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          The LMS method for constructing normalized growth standards.

          T. J. Cole (1990)
          It is now common practice to express child growth status in the form of SD scores. The LMS method provides a way of obtaining normalized growth centile standards which simplifies this assessment, and which deals quite generally with skewness which may be present in the distribution of the measurement (eg height, weight, circumferences or skinfolds). It assumes that the data can be normalized by using a power transformation, which stretches one tail of the distribution and shrinks the other, removing the skewness. The optimal power to obtain normality is calculated for each of a series of age groups and the trend summarized by a smooth (L) curve. Trends in the mean (M) and coefficient of variation (S) are similarly smoothed. The resulting L, M and S curves contain the information to draw any centile curve, and to convert measurements (even extreme values) into exact SD scores. A table giving approximate standard errors for the smoothed centiles is provided. The method, which is illustrated with US girls' weight data, should prove useful both for the construction and application of growth standards.
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            Guidelines for Growth Hormone and Insulin-Like Growth Factor-I Treatment in Children and Adolescents: Growth Hormone Deficiency, Idiopathic Short Stature, and Primary Insulin-Like Growth Factor-I Deficiency

            Background/Aims: On behalf of the Drug and Therapeutics, and Ethics Committees of the Pediatric Endocrine Society, we sought to update the guidelines published in 2003 on the use of growth hormone (GH). Because idiopathic short stature (ISS) remains a controversial indication, and diagnostic challenges often blur the distinction between ISS, GH deficiency (GHD), and primary IGF-I deficiency (PIGFD), we focused on these three diagnoses, thereby adding recombinant IGF-I therapy to the GH guidelines for the first time. Methods: This guideline was developed following the GRADE approach (Grading of Recommendations, Assessment, Development, and Evaluation). Results: This guideline provides recommendations for the clinical management of children and adolescents with growth failure from GHD, ISS, or PIGFD using the best available evidence. Conclusion: The taskforce suggests that the recommendations be applied in clinical practice with consideration of the evolving literature and the risks and benefits to each individual patient. In many instances, careful review highlights areas that need further research.
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              Perzentile für den Body-mass-Index für das Kindes- und Jugendalter unter Heranziehung verschiedener deutscher Stichproben

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                Author and article information

                Contributors
                Journal
                Front Endocrinol (Lausanne)
                Front Endocrinol (Lausanne)
                Front. Endocrinol.
                Frontiers in Endocrinology
                Frontiers Media S.A.
                1664-2392
                25 May 2021
                2021
                : 12
                : 676083
                Affiliations
                [1] 1 Pediatric Endocrinology, Centre Hospitalier Universitaire d’Angers , Angers, France
                [2] 2 Pediatric Endocrinology, Hospital Arnau de Vilanova , Lleida, Spain
                [3] 3 Pediatric Endocrinology, Constantin Ion Parhon (C.I.) Parhon National Institute of Endocrinology , Bucharest, Romania
                [4] 4 Center for Chronic Sick Children, Pediatric Endocrinology, Charitè, University Medicine , Berlin, Germany
                [5] 5 Ipsen , Boulogne-Billancourt, France
                [6] 6 University College London (UCL) Great Ormond Street (GOS) Institute of Child Health and Great Ormond Street Hospital for Children , London, United Kingdom
                Author notes

                Edited by: Mohamad Maghnie, University of Genoa, Italy

                Reviewed by: Stefano Zucchini, Sant’Orsola-Malpighi Polyclinic, Italy; Bradley Scott Miller, University of Minnesota Children’s Hospital, United States; Paul Saenger, New York University Winthrop Hospital, United States

                This article was submitted to Pediatric Endocrinology, a section of the journal Frontiers in Endocrinology

                Article
                10.3389/fendo.2021.676083
                8185283
                34113318
                daecf0b2-733a-4b8c-b596-8003f9ffad7c
                Copyright © 2021 Coutant, Bosch Muñoz, Dumitrescu, Schnabel, Sert, Perrot and Dattani

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 04 March 2021
                : 05 May 2021
                Page count
                Figures: 3, Tables: 3, Equations: 0, References: 32, Pages: 10, Words: 5552
                Funding
                Funded by: Ipsen 10.13039/501100014382
                Categories
                Endocrinology
                Original Research

                Endocrinology & Diabetes
                nutropinaq® (somatropin),rhgh, recombinant human gh,growth hormone deficiency,paediatric gh disorders,safety

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