To investigate the effect of age at growth hormone (GH) treatment start on near adult height (NAH) in children with isolated GH deficiency (GHD).
NordiNet® International Outcome Study (IOS) ...(Nbib960128), a non-interventional, multicentre study, evaluates the long-term effectiveness and safety of Norditropin® (somatropin) (Novo Nordisk A/S) in the real-life clinical setting.
Patients (
= 172) treated to NAH (height at ≥18 years, or height velocity <2 cm/year at ≥16 (boys) or ≥15 (girls) years) were grouped by age (years) at treatment start (early (girls, <8; boys, <9), intermediate (girls, 8-10; boys, 9-11) or late (girls, >10; boys, >11)) and GHD severity (<3 ng/mL or 3 to ≤10 ng/mL). Multiple regression analysis was used to evaluate the effect of age at treatment start (as a categorical and continuous variable) on NAH standard deviation score (SDS).
Age at treatment start had a marked effect on NAH SDS; NAH SDS achieved by patients starting treatment early (
= 40 (boys, 70.0%); least squares mean (standard error) -0.76 (0.14)) exceeded that achieved by those starting later (intermediate,
= 42 (boys, 57.1%); -1.14 (0.15); late,
= 90 (boys, 68.9%); -1.21 (0.10)). Multiple regression analysis showed a significant association between NAH SDS and age at treatment start (
< 0.0242), baseline height SDS (HSDS) (
< 0.0001), target HSDS (
< 0.0001), and GHD severity (
= 0.0012). Most (78.5%) patients achieved a normal NAH irrespective of age at treatment start.
Early initiation of GH treatment in children with isolated GHD improves their chance of achieving their genetic height potential.
Against the background of increasing incidence, pediatric differentiated thyroid carcinoma (DTC) frequently presents with advanced disease and high recurrence rates while prognosis remains excellent.
...We investigated the use of a pediatric classification and an adult response to therapy risk stratification for pediatric DTC patients and their implications for adaptation of treatment and follow-up.
Data from patients aged <18 years with a diagnosis of primary DTC, registered with the German Pediatric Oncology Hematology-Malignant Endocrine Tumor registry since 1995, were analyzed. For risk prediction, patients were retrospectively assigned to the American Thyroid Association (ATA) risk groups and evaluated for response to therapy.
By October 2019, 354 patients with DTC had been reported (median age at diagnosis 13.7 years, range 3.6-17.9) with lymph node and distant metastases in 74.3% and 24.5%. Mean follow-up was 4.1 years (range 0-20.6). Ten-year overall and event-free survival (EFS) rates were 98.9% and 78.1%. EFS was impaired for patients with lymph node and distant metastases (P < .001), positive postoperative thyroglobulin (P = .006), incomplete resection (P = .002), sequential surgeries to achieve total thyroidectomy (P = .042), invasion of capsule (P < .001) and lymph vessels (P = .005), infiltration of surrounding soft tissues (P < .001), tumor multifocality (P < .001), ATA intermediate- and high-risk group (P < .001), and age <10 years (P < .001). Multivariate analysis revealed age <10 years at diagnosis, ATA high-risk level, and poor response to therapy as significant negative prognostic factors for EFS.
Age, ATA risk group, and response to therapy emerged as significant prognostic factors for EFS in pediatric patients with DTC, requiring risk-adapted individualized therapy and follow-up.
The life expectancy of individuals with trisomy 21 (Down syndrome, DS) has risen to more than 60 years over the past few decades. As a result, diseases arising in mid and later life have become an ...issue of major concern in the care of individuals with DS. This article discusses and summarizes, from a multidisciplinary perspective, the diseases commonly affecting this population.
This narrative review is based on publications identified by a selective literature search, extrapolation of the available evidence, and the authors' personal experience.
Robust epidemiological evidence indicates that many different diseases, which are dealt with by many different medical specialties, are more common in individuals with DS. The genetic background of some of these diseases is now understood down to the molecular level, e.g., primary hypothyroidism or Alzheimer's disease in DS. Recent gains in epidemiological and pathophysiological understanding contrast with a dearth of evidence on treatment for most of these disorders.
In view of the complexity of DS-associated morbidity, it would be desirable for DS-specific multidisciplinary care to be made available to patients with DS.
Abstract
Context
Growth hormone (GH) treatment has a generally good safety profile; however, concerns about increased mortality risk in adulthood have been raised.
Objective
This work aims to assess ...the long-term safety of GH treatment in clinical practice.
Methods
Data were collected from 676 clinics participating in 2 multicenter longitudinal observational studies: the NordiNet International Outcome Study (2006-2016, Europe) and ANSWER Program (2002-2016, USA). Pediatric patients treated with GH were classified into 3 risk groups based on diagnosis. Intervention consisted of daily GH treatment, and main outcome measures included incidence rates (events/1000 patient-years) of adverse drug reactions (ADRs), serious adverse events (SAEs), and serious ADRs, and their relationship to GH dose.
Results
The combined studies comprised 37 702 patients (68.4% in low-risk, 27.5% in intermediate-risk, and 4.1% in high-risk groups) and 130 476 patient-years of exposure. The low-risk group included children born small for gestational age (SGA; 20.7%) and non-SGA children (eg, with GH deficiency; 79.3%). Average GH dose up to the first adverse event (AE) decreased with increasing risk category. Patients without AEs received higher average GH doses than patients with more than one AE across all groups. A significant inverse relationship with GH dose was shown for ADR and SAE incidence rates in the low-risk group (P = .003 and P = .001, respectively) and the non-SGA subgroup (both P = .002), and for SAEs in the intermediate- and high-risk groups (P = .002 and P = .05, respectively).
Conclusions
We observed no indication of increased mortality risk nor AE incidence related to GH dose in any risk group. A short visual summary of our work is available (1).
Abstract
Context
Understanding real-world prescribing of GH may help improve treatment of eligible patients.
Objective
Overall: to assess real-world effectiveness and safety of GH (Norditropin). This ...analysis: to compare clinical characteristics of GH-treated children in the United States and Europe.
Design
The American Norditropin Studies: Web-Enabled Research Program (ANSWER; 2002 to 2016, United States) and the NordiNet International Outcome Study (NordiNet IOS; 2006 to 2016, Europe) were multicenter longitudinal observational cohort studies.
Setting
Data were recorded in 207 (United States) and 469 (Europe) clinics.
Participants
Patients with GH deficiency, Turner syndrome, Noonan syndrome, idiopathic short stature, Prader–Willi syndrome, or born small for gestational age, who commenced GH treatment aged <1 year.
Intervention
GH was prescribed by treating physicians according to local practice.
Main Outcomes Measures
Baseline data and drug doses were recorded. Data on effectiveness and safety were collected.
Results
ANSWER had 19,847 patients in the full analysis set (FAS; patients with birthdate information and one or more GH prescription) and 12,660 in the effectiveness analysis set (EAS; GH-naive patients with valid baseline information). NordiNet IOS had 17,711 (FAS) and 11,967 (EAS). Boys accounted for 69% (ANSWER) and 57% (NordiNet IOS). Treatment start occurred later than optimal to improve growth. The proportion of boys treated was generally larger, children were older at treatment start, and GH doses were higher in the United States vs Europe. No new safety signals of concern were noted.
Conclusions
In most indications, more boys than girls were treated, and treatment started late. Earlier diagnosis of GH-related disorders is needed. The data support a favorable benefit–risk profile of GH therapy in children.
Two large noninterventional studies (ANSWER and NordiNet IOS) examined real-world use of GH across six indications in children. Prescribing differences were found between the United States and Europe.
Adherence to daily growth hormone (GH) injections optimizes treatment benefit; however, adherence rates are sometimes poor. Reasons for poor adherence and persistence are multifaceted. GH injection ...devices are undergoing continual improvement to enhance adherence. Areas covered: This review evaluates published data on the evolution of GH injection devices to meet patients' needs and preferences, patients' perception of new devices and the projected impact of device developments on adherence. Published studies were identified through literature database searches including EMBASE and PubMed (January 1985-November 2015). Expert opinion: Patient needs and preferences trend towards convenient, easy-to-use devices that enable self-injection, minimize injection preparation steps by reducing the medication reconstitution and storage requirements, and reduce injection pain. In comparative studies, devices that patients considered easier to use than comparator devices were associated with reduced handling errors, fear of injection (needle anxiety/needle phobia) and pain upon needle insertion, and were thus preferred. A combination of the following items are expected to increase patient motivation to better adhere to therapy and improve treatment outcomes: advances in GH injection devices, educating patients regarding injection device and injection technique, and ongoing support from healthcare professionals, including comprehensive education about their condition, medication and expected outcomes.
Background. Infections and autoimmune disorders are more frequent in Down syndrome, suggesting abnormality of adaptive immunity. Although the role of B cells and antibodies is well characterized, ...knowledge regarding T cells is limited. Methods. Lymphocyte subpopulations of 40 children and adolescents with Down syndrome and 51 controls were quantified, and phenotype and functionality of antigen-specific effector T cells were analyzed with flow cytometry after polyclonal and pathogen-specific stimulation (with varicella-zoster virus VZV and cytomegalovirus CMV). Results were correlated with immunoglobulin (Ig) G responses. Results. Apart from general alterations in the percentage of lymphocytes, regulatory T cells, and T-helper 1 and 17 cells, all major T-cell subpopulations showed higher expression of the inhibitory receptor PD-1. Polyclonally stimulated effector CD4⁺ T-cell frequencies were significantly higher in subjects with Down syndrome, whereas their inhibitory receptor expression (programmed cell death 1 PD-1 and cytotoxic T-lymphocyte antigen 4 CTLA-4) was similar to that of controls and cytokine expression profiles were only marginally altered. Pathogen-specific immunity showed age-appropriate levels of endemic infection, with correlation of CMV-specific cellular and humoral immunity in all subjects. Among VZV IgG–positive individuals, a higher percentage of VZV-specific T-cell-positive subjects was seen in those with Down syndrome. Conclusions. Despite alterations in lymphocyte subpopulations, individuals with Down syndrome can mount effector T-cell responses with similar phenotype and functionality as controls but may require higher effector T-cell frequencies to ensure pathogen control.
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