scholarly journals A Data-Driven Intervention Framework for Improving Adherence to Growth Hormone Therapy Based on Clustering Analysis and Traffic Light Alerting Systems

2021 ◽  
Author(s):  
Matheus Araújo ◽  
Paula van Dommelen ◽  
Jaideep Srivastava ◽  
Ekaterina Koledova
Keyword(s):  
Growth Hormone ◽  
Clustering Algorithm ◽  
Characteristic Curve ◽  
Recombinant Human Growth Hormone ◽  
Gaussian Mixture ◽  
Data Driven ◽  
Hormone Deficiency ◽  
Traffic Light ◽  
Traffic Lights ◽  
The Hours

Recombinant human growth hormone (r-hGH) is an established therapy for growth hormone deficiency (GHD); yet, some patients fail to achieve their full height potential, with poor adherence and persistence with the prescribed regimen often a contributing factor. A data-driven clinical decision support system based on “traffic light” visualizations for adherence risk management of patients receiving r-hGH treatment was developed. This research was feasible thanks to data-sharing agreements that allowed the creation of these models using real-world data of r-hGH adherence from easypod™ connect; data was retrieved for 11,015 children receiving r-hGH therapy for ≥180 days. Patients’ adherence to therapy was represented using four values (mean and standard deviation [SD] of daily adherence and hours to next injection). Cluster analysis was used to categorize adherence patterns using a Gaussian mixture model. Following a traffic lights-inspired visualization approach, the algorithm was set to generate three clusters: green, yellow, or red status, corresponding to high, medium, and low adherence, respectively. The area under the receiver operating characteristic curve (AUC-ROC) was used to find optimum thresholds for independent traffic lights according to each metric. The most appropriate traffic light used the SD of the hours to the next injection, with an AUC-ROC value of 0.85 when compared to the complex clustering algorithm. For the daily adherence-based traffic lights, optimum thresholds were >0.82 (SD, <0.37), 0.53–0.82 (SD, 0.37–0.61), and <0.53 (SD, >0.61) for high, medium, and low adherence, respectively. For hours to next injection, the corresponding optimum thresholds were <27.18 (SD, <10.06), 27.18–34.01 (SD, 10.06–29.63), and >34.01 (SD, >29.63). Our research indicates that implementation of a practical data-driven alert system based on recognised traffic-light coding would enable healthcare practitioners to monitor sub-optimally-adherent patients to r-hGH treatment for early intervention to improve treatment outcomes.

scholarly journals Insulin-like growth factor-1 level is a poor diagnostic indicator of growth hormone deficiency

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hideyuki Iwayama ◽  
Sachiko Kitagawa ◽  
Jyun Sada ◽  
Ryosuke Miyamoto ◽  
Tomohito Hayakawa ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Diagnostic Accuracy ◽  
Growth Hormone Deficiency ◽  
Screening Test ◽  
Characteristic Curve ◽  
Hormone Deficiency ◽  
Height Velocity ◽  
Insulin Like Growth Factor ◽  
Predictive Values

AbstractWe evaluated the diagnostic accuracy of insulin-like growth factor-1 (IGF-1) for screening growth hormone deficiency (GHD) to determine the usefulness of IGF-1 as a screening test. Among 298 consecutive children who had short stature or decreased height velocity, we measured IGF-1 levels and performed growth hormone (GH) secretion test using clonidine, arginine, and, in cases with different results of the two tests, L-dopa. Patients with congenital abnormalities were excluded. GHD was defined as peak GH ≤ 6.0 ng/mL in the two tests. We identified 60 and 238 patients with and without GHD, respectively. The mean IGF-1 standard deviation (SD) was not significantly different between the GHD and non-GHD groups (p = 0.23). Receiver operating characteristic curve analysis demonstrated the best diagnostic accuracy at an IGF-1 cutoff of − 1.493 SD, with 0.685 sensitivity, 0.417 specificity, 0.25 positive and 0.823 negative predictive values, and 0.517 area under the curve. Correlation analysis revealed that none of the items of patients’ characteristics increased the diagnostic power of IGF-1. IGF-1 level had poor diagnostic accuracy as a screening test for GHD. Therefore, IGF-1 should not be used alone for GHD screening. A predictive biomarker for GHD should be developed in the future.

scholarly journals 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)

2021 ◽  
Vol 12 ◽  
Author(s):  
Regis Coutant ◽  
Jordi Bosch Muñoz ◽  
Cristina Patricia Dumitrescu ◽  
Dirk Schnabel ◽  
Caroline Sert ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Deficiency ◽  
Adult Height ◽  
Recombinant Human Growth Hormone ◽  
Standard Deviation Score ◽  
Hormone Deficiency ◽  
Growth Disorders ◽  
Growth Study ◽  
Post Marketing Surveillance ◽  
European Registry

ObjectiveThe 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.MethodsOpen-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).Results2792 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).ConclusionsThere was an improvement in mean height SDS in all aetiology subgroups after rhGH treatment. No new safety concerns were identified.

scholarly journals Low FT4 Concentrations around the Start of Recombinant Human Growth Hormone Treatment: Predictor of Congenital Structural Hypothalamic-Pituitary Abnormalities?

2018 ◽  
Vol 89 (2) ◽  
pp. 98-107 ◽  
Author(s):  
Laura van Iersel ◽  
Hanneke M. van Santen ◽  
Gladys R.J. Zandwijken ◽  
Nitash Zwaveling-Soonawala ◽  
Anita C.S. Hokken-Koelega ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Treatment ◽  
Recombinant Human Growth Hormone ◽  
Human Growth ◽  
Hormone Treatment ◽  
Hormone Deficiency ◽  
Pituitary Hormone ◽  
Gh Treatment ◽  
Central Hypothyroidism ◽  
Pituitary Disease

Background: Growth hormone (GH) treatment may unmask central hypothyroidism (CeH). This was first observed in children with GH deficiency (GHD), later also in adults with GHD due to acquired “organic” pituitary disease. We hypothesized that newly diagnosed CeH in children after starting GH treatment for nonacquired, apparent isolated GHD points to congenital “organic” pituitary disease. Methods: Nationwide, retrospective cohort study including all children with nonacquired GHD between 2001 and 2011 in The Netherlands. The prevalence of CeH, hypothalamic-pituitary (HP) abnormalities, and neonatal congenital hypothyroidism screening results were evaluated. Results: Twenty-three (6.3%) of 367 children with apparent isolated GHD were prescribed LT4 for presumed CeH within 2 years after starting GH treatment. Similarly to children already diagnosed with multiple pituitary hormone deficiency, 75% of these 23 had structural HP abnormalities. In children not prescribed LT4, low pre- or post-GH treatment FT4 concentrations were also associated with structural HP abnormalities. Neonatal screening results of only 4 of the 23 children could be retrieved. Conclusion: In children with nonacquired, apparent isolated GHD, a diagnosis of CeH after, or a low FT4 concentration around the start of GH treatment, is associated with congenital structural HP abnormalities, i.e., “organic” pituitary disease. Neonatal values could not be judged reliably.

Diagnostic accuracy of IGF-1 for screening growth hormone deficiency: a prospective, single-center, diagnostic accuracy study

2021 ◽  
Author(s):  
Hideyuki Iwayama ◽  
Sachiko Kitagawa ◽  
Jyun Sada ◽  
Ryosuke Miyamoto ◽  
Tomohito Hayakawa ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Diagnostic Accuracy ◽  
Growth Hormone Deficiency ◽  
Predictive Value ◽  
Screening Test ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
Rank Correlation ◽  
Hormone Deficiency ◽  
Height Velocity

Abstract Purpose We evaluated the diagnostic accuracy of insulin-like growth factor-1 (IGF-1) for screening growth hormone deficiency (GHD) to determine the usefulness of IGF-1 as a screening test. Methods On 298 consecutive children who had short stature or decreased height velocity, we measured IGF-1 levels and performed growth hormone (GH) secretion test using clonidine, arginine, and, in cases with different results of the two tests, L-dopa. Patients with congenital abnormalities were excluded. GHD was defined as peak GH ≤ 6.0 ng/mL in the two tests. Results We identified 60 and 238 patients with and without GHD, respectively. The mean IGF-1 (SD) was not significantly different between the GHD and non-GHD groups (p = 0.23). Receiver operating characteristic curve analysis demonstrated the best diagnostic accuracy at an IGF-1 cutoff of −1.493 SD, with sensitivity of 0.685, specificity of 0.417, positive predictive value of 0.25, negative predictive value of 0.823, and area under the curve of 0.517. Spearman’s rank correlation coefficient showed that IGF-1 (SD) was weakly correlated with age, bone age, height velocity before examination, weight (SD), and BMI (SD) and very weakly correlated with height (SD), target height (SD), and maximum GH peak. Conclusion IGF-1 level had poor diagnostic accuracy as a screening test for GHD. Correlation analysis revealed that none of the items increased the diagnostic power of IGF-1. Therefore, IGF-1 should not be used alone in the screening of GHD. A predictive biomarker for GHD should be developed in the future.

The Angle of Trunk Rotation in Children With Growth Hormone Deficiency

2020 ◽  
Author(s):  
Magdalena Kobylińska ◽  
Roksana Ewa Malak ◽  
Katarzyna Majewska ◽  
Włodzimierz Samborski ◽  
Andrzej Kędzia
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Deficiency ◽  
Human Growth Hormone ◽  
Bone Structure ◽  
Recombinant Human Growth Hormone ◽  
Human Growth ◽  
Hormone Deficiency ◽  
Trunk Rotation ◽  
Sport Activities ◽  
Rhgh Treatment

Abstract Background. Growth hormone plays a vital role in the human body. Its deficiency can lead to numerous disorders, including musculoskeletal system defects. Treatment with recombinant human growth hormone (rhGH) in children suffering from growth hormone deficiency (GHD) increases muscle mass and improves bone structure.Aim. The purpose of this study was to evaluate the angle of trunk rotation (ATR) in patients diagnosed with GHD treated with rhGH and to observe the incidence of scoliosis.Material and Methods. The study was conducted among 50 children diagnosed with GHD. The group consisted of 11 girls and 39 boys aged 6-16. The study group included 50 children: 10 children just qualified for rhGH treatment and 40 patients undergoing this treatment, with different therapy duration. ATR was measured using a Bunnell scoliometer on five levels of the spine: cervical 7 / thoracic 1, thoracic 6, thoracic 12 / lumbar 1, lumbar 3, lumbar 5 / sacral 1.Results. The most numerous asymmetries among the examined group were in the thoracolumbar segment and at the thoracic 6 level. Girls had greater asymmetries compared to boys especially at thoraco – lumbar and lumbar 3 level. There were no statistically significant differences in ATR at any level comparing patients before hormonal treatment and patients undergoing rhGH treatment. The age of the beginning of the therapy, the duration of rhGH therapy, and body mass index (BMI) also had no effect on ATR. Sport activities had a positive impact on the results obtained by scoliometer assessment.Conclusions. The angle of trunk rotation is higher in growth hormone-deficient females than in males. Weight, height, BMI, the time of growth hormone therapy beginning and the duration of this therapy do not influence ATR. The more sport activities, the lower value of the angle of trunk rotation, especially in male patients. Obtained results support the thesis, that treatment with recombinant human growth hormone does not increase the incidence of scoliosis.

Adult growth hormone deficiency

2011 ◽  
pp. 152-165
Author(s):  
Aurora Aragon-Alonso ◽  
Mark Sherlock ◽  
Andrew A. Toogood
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Deficiency ◽  
Replacement Therapy ◽  
Recombinant Human Growth Hormone ◽  
Hormone Replacement ◽  
Adult Life ◽  
Growth Failure ◽  
Clinical Syndrome ◽  
Hormone Deficiency ◽  
Recombinant Dna Technology

It has been known for many years that growth hormone is essential for normal linear growth, but over the past few years, with the advent of recombinant human growth hormone therapy, the importance of growth hormone during adult life has been described in detail. The growth hormone peptide was first isolated from bovine pituitaries in the 1940s (1), but was found to be species specific and inactive in humans. In 1956, growth hormone was extracted from human cadaveric pituitary tissue (2) and a year later was administered to a 13-year-old boy with hypopituitarism, resulting in an increased growth velocity (3). The first report suggesting growth hormone could have beneficial actions in adulthood was published in 1962 in which a 35-year-old woman with hypopituitarism reported increased vigour, ambition, and wellbeing after 2 months treatment with cadaveric growth hormone (4). However, the limited supply of pituitary-derived growth hormone confined its use to the treatment of children with severe growth failure caused by proven growth hormone deficiency (GHD). In 1985, the association of cadaveric growth hormone treatment with Creutzfeldt–Jakob disease led to its withdrawal from use worldwide (5). Since then, all growth hormone in clinical use has been produced using recombinant DNA technology. The first placebo-controlled trials of growth hormone replacement therapy in adults with GHD were published in 1989 (6, 7). These and subsequent studies have led to the recognition of adult GHD as a specific clinical syndrome and the impact of GHD and replacement therapy in adults with GHD has been studied in detail.

scholarly journals Validating genetic markers of response to recombinant human growth hormone in children with growth hormone deficiency and Turner syndrome: the PREDICT validation study

2016 ◽  
Vol 175 (6) ◽  
pp. 633-643 ◽  
Author(s):  
Adam Stevens ◽  
Philip Murray ◽  
Jerome Wojcik ◽  
John Raelson ◽  
Ekaterina Koledova ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Random Forest ◽  
Growth Hormone Deficiency ◽  
Genetic Markers ◽  
Validation Study ◽  
Growth Response ◽  
Recombinant Human Growth Hormone ◽  
Human Growth ◽  
Hormone Deficiency ◽  
First Year

Objective Single-nucleotide polymorphisms (SNPs) associated with the response to recombinant human growth hormone (r-hGH) have previously been identified in growth hormone deficiency (GHD) and Turner syndrome (TS) children in the PREDICT long-term follow-up (LTFU) study (Nbib699855). Here, we describe the PREDICT validation (VAL) study (Nbib1419249), which aimed to confirm these genetic associations. Design and methods Children with GHD (n = 293) or TS (n = 132) were recruited retrospectively from 29 sites in nine countries. All children had completed 1 year of r-hGH therapy. 48 SNPs previously identified as associated with first year growth response to r-hGH were genotyped. Regression analysis was used to assess the association between genotype and growth response using clinical/auxological variables as covariates. Further analysis was undertaken using random forest classification. Results The children were younger, and the growth response was higher in VAL study. Direct genotype analysis did not replicate what was found in the LTFU study. However, using exploratory regression models with covariates, a consistent relationship with growth response in both VAL and LTFU was shown for four genes – SOS1 and INPPL1 in GHD and ESR1 and PTPN1 in TS. The random forest analysis demonstrated that only clinical covariates were important in the prediction of growth response in mild GHD (>4 to <10 μg/L on GH stimulation test), however, in severe GHD (≤4 μg/L) several SNPs contributed (in IGF2, GRB10, FOS, IGFBP3 and GHRHR). Conclusions The PREDICT validation study supports, in an independent cohort, the association of four of 48 genetic markers with growth response to r-hGH treatment in both pre-pubertal GHD and TS children after controlling for clinical/auxological covariates. However, the contribution of these SNPs in a prediction model of first-year response is not sufficient for routine clinical use.

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