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Pharmacological Research Jul 2023We evaluated the efficacy, safety, adherence, quality of life (QoL) and cost-effectiveness of long-acting growth hormone (LAGH) vs daily growth hormone (GH) preparations... (Meta-Analysis)
Meta-Analysis Review
Efficacy, safety, quality of life, adherence and cost-effectiveness of long-acting growth hormone replacement therapy compared to daily growth hormone in children with growth hormone deficiency: A systematic review and meta-analysis.
We evaluated the efficacy, safety, adherence, quality of life (QoL) and cost-effectiveness of long-acting growth hormone (LAGH) vs daily growth hormone (GH) preparations in the treatment of growth hormone deficiency (GHD) in children. Systematic searches were performed in PubMed, Embase and Web of Science up to July 2022 on randomized and non-randomized studies involving children with GHD receiving LAGH as compared to daily GH. Meta-analyses for efficacy and safety were performed comparing different LAGH/daily GH formulations. From the initial 1393 records, we included 16 studies for efficacy and safety, 8 studies for adherence and 2 studies for QoL. No studies reporting cost-effectiveness were found. Pooled mean differences of mean annualized height velocity (cm/year) showed no difference between LAGH and daily GH: Eutropin Plus® vs Eutropin® [- 0.14 (-0.43, 0.15)], Eutropin Plus® vs Genotropin® [- 0.74 (-1.83, 0.34)], Jintrolong® vs Jintropin AQ® [0.05 (-0.54, 0.65)], Somatrogon vs Genotropin® [- 1.40 (-2.91, 0.10)], TransCon vs Genotropin® [0.93 (0.26, 1.61)]. Also, other efficacy and safety outcomes, QoL and adherence were comparable for LAGH and daily GH. Our results showed that, although most of the included studies had some concerns for risk of bias, regarding efficacy and safety all the LAGH formulations were similar to daily GH. Future high quality studies are needed to confirm these data. Adherence and QoL should be addressed from real-world data studies for both the mid and long term and in a larger population. Cost-effectiveness studies are needed to measure the economic impact of LAGH from the healthcare payer's perspective.
Topics: Humans; Child; Human Growth Hormone; Growth Hormone; Quality of Life; Cost-Benefit Analysis; Dwarfism, Pituitary; Hormone Replacement Therapy
PubMed: 37236413
DOI: 10.1016/j.phrs.2023.106805 -
Advances in Therapy Sep 2023Achondroplasia is the most common form of skeletal dysplasia. Recent advances in therapeutic options have highlighted the need for understanding the burden and treatment... (Review)
Review
BACKGROUND
Achondroplasia is the most common form of skeletal dysplasia. Recent advances in therapeutic options have highlighted the need for understanding the burden and treatment landscape of the condition. This systematic literature review (SLR) aimed to identify health-related quality of life (HRQoL)/utilities, healthcare resource use (HCRU), costs, efficacy, safety and economic evaluation data in achondroplasia and to identify gaps in the research.
METHODS
Searches of MEDLINE, Embase, the University of York Centre for Reviews and Dissemination (CRD), the Cochrane Library and grey literature were performed. Articles were screened against pre-specified eligibility criteria by two individuals and study quality was assessed using published checklists. Additional targeted searches were conducted to identify management guidelines.
RESULTS
Fifty-nine unique studies were included. Results demonstrated a substantial HRQoL and HCRU/cost-related burden of achondroplasia on affected individuals and their families throughout their lifetimes, particularly in emotional wellbeing and hospitalisation costs and resource use. Vosoritide, growth hormone (GH) and limb lengthening all conferred benefits for height or growth velocity; however, the long-term effects of GH therapy were unclear, data for vosoritide were from a limited number of studies, and limb lengthening was associated with complications. Included management guidelines varied widely in their scope, with the first global effort to standardise achondroplasia management represented by the International Achondroplasia Consensus Statement published at the end of 2021. Current evidence gaps include a lack of utility and cost-effectiveness data for achondroplasia and its treatments.
CONCLUSIONS
This SLR provides a comprehensive overview of the current burden and treatment landscape for achondroplasia, along with areas where evidence is lacking. This review should be updated as new evidence becomes available on emerging therapies.
Topics: Humans; Quality of Life; Achondroplasia; Human Growth Hormone; Cost-Benefit Analysis
PubMed: 37382866
DOI: 10.1007/s12325-023-02549-3 -
International Journal of Molecular... Nov 2022Spinal stenosis (SS) is a multifactorial polyetiological condition characterized by the narrowing of the spinal canal. This condition is a common source of pain among... (Review)
Review
Spinal stenosis (SS) is a multifactorial polyetiological condition characterized by the narrowing of the spinal canal. This condition is a common source of pain among people over 50 years old. We perform a systematic review of molecular and genetic mechanisms that cause SS. The five main mechanisms of SS were found to be ossification of the posterior longitudinal ligament (OPLL), hypertrophy and ossification of the ligamentum flavum (HLF/OLF), facet joint (FJ) osteoarthritis, herniation of the intervertebral disc (IVD), and achondroplasia. FJ osteoarthritis, OPLL, and HLF/OLFLF/OLF have all been associated with an over-abundance of transforming growth factor beta and genes related to this phenomenon. OPLL has also been associated with increased bone morphogenetic protein 2. FJ osteoarthritis is additionally associated with Wnt/β-catenin signaling and genes. IVD herniation is associated with collagen type I alpha 1 and 2 gene mutations and subsequent protein dysregulation. Finally, achondroplasia is associated with fibroblast growth factor receptor 3 gene mutations and fibroblast growth factor signaling. Although most publications lack data on a direct relationship between the mutation and SS formation, it is clear that genetics has a direct impact on the formation of any pathology, including SS. Further studies are necessary to understand the genetic and molecular changes associated with SS.
Topics: Humans; Middle Aged; Spinal Stenosis; Ossification of Posterior Longitudinal Ligament; Ligamentum Flavum; Achondroplasia; Osteoarthritis
PubMed: 36362274
DOI: 10.3390/ijms232113479 -
Clinical Genetics Jan 2020This article provides an overview of the current knowledge on medical complications, health characteristics, and psychosocial issues in adults with achondroplasia. We... (Review)
Review
This article provides an overview of the current knowledge on medical complications, health characteristics, and psychosocial issues in adults with achondroplasia. We have used a scoping review methodology particularly recommended for mapping and summarizing existing research evidence, and to identify knowledge gaps. The review process was conducted in accordance with the PRISMA-ScR guidelines (Preferred Reporting Items for Systematic reviews and Meta-Analyses Extension for Scoping Reviews). The selection of studies was based on criteria predefined in a review protocol. Twenty-nine publications were included; 2 reviews, and 27 primary studies. Key information such as reference details, study characteristics, topics of interest, main findings and the study author's conclusion are presented in text and tables. Over the past decades, there has only been a slight increase in publications on adults with achondroplasia. The reported morbidity rates and prevalence of medical complications are often based on a few studies where the methodology and representativeness can be questioned. Studies on sleep-related disorders and pregnancy-related complications were lacking. Multicenter natural history studies have recently been initiated. Future studies should report in accordance to methodological reference standards, to strengthen the reliability and generalizability of the findings, and to increase the relevance for implementing in clinical practice.
Topics: Achondroplasia; Adult; Bone Diseases; Female; Female Urogenital Diseases; Humans; Obesity; Otorhinolaryngologic Diseases; Pain; Pregnancy; Quality of Life; Reproducibility of Results; Respiration Disorders; Sleep Wake Disorders; Spinal Stenosis
PubMed: 30916780
DOI: 10.1111/cge.13542 -
European Journal of Medical Genetics Nov 2023The clinical features of achondroplasia can cause acute self-limited pain that can evolve into chronic pain. Pain causes a low quality of life, in terms of physical,...
The clinical features of achondroplasia can cause acute self-limited pain that can evolve into chronic pain. Pain causes a low quality of life, in terms of physical, emotional, social, and school functioning in both adult and children with achondroplasia. We conducted a systematic review according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement to describe prevalence, assessment tools, causes and management strategies of pain in this rare disease. We found that shoulder and knee pain is typically referred during infancy, while knee pain is generally referred around 5-6 years of age. The prevalence of general pain in adolescence can be as high as 90%. Chronic pain in the achondroplasia population increases with age, with up to 70% of adults reporting general pain and back pain. Recognizing the multiple determinants of acute and chronic pain in patients with achondroplasia may enable physicians to better understand and manage this burden, particularly with the advent of new drugs that may modify some of the striking features of achondroplasia.
Topics: Adolescent; Humans; Child; Adult; Quality of Life; Chronic Pain; Achondroplasia
PubMed: 37758167
DOI: 10.1016/j.ejmg.2023.104850 -
Journal of Thoracic Disease Mar 2020Patients with achondroplasia and other causes of dwarfism suffer from increased rates of cardiovascular disease relative to the remainder of the population. Few studies... (Review)
Review
Patients with achondroplasia and other causes of dwarfism suffer from increased rates of cardiovascular disease relative to the remainder of the population. Few studies have examined these patients when undergoing cardiac surgery or percutaneous intervention. This systematic review examines the literature to determine outcomes following cardiac intervention in this unique population. An electronic search was performed in the English literature to identify all reports of achondroplasia, dwarfism, and cardiac intervention. Of the 5,274 articles identified, 14 articles with 14 cases met inclusion criteria. Patient-level data was extracted and analyzed. Median patient age was 55.5 [interquartile ranges (IQR), 43.8, 59.8] years, median height 102.0 [98.8, 112.5] cm, median BMI 32.1 [27.0, 45.9], and 57.1% (8/14) were male. Of these 14 patients, nine had the following documented skeletal abnormalities: 66.7% (6/9) had scoliosis, 66.7% (6/9) had kyphosis, 11.1% (1/9) had lordosis, 11.1% (1/9) pectus carinatum and 11.1% (1/9) spinal stenosis. Coronary artery disease was present in 53.8% (7/13), and 30.8% (4/13) patients previously suffered a myocardial infarction. Of the eight patients who underwent cardiac surgery, 37.5% (3/8) underwent multivessel coronary artery bypass grafting, 37.5% (3/8) underwent aortic valve replacement, 25.0% (2/8) underwent type A aortic dissection repair, and the remaining 12.5% (1/8) underwent pulmonary thromboendarterectomy. Six patients underwent percutaneous intervention. Median cardiopulmonary bypass time was 136.5 [110.0, 178.8] minutes. Median arterial cannula size was 20.0 [20.0, 24.0] Fr. Bicaval cannulation was performed in all cases describing cannulation strategy (5/5). Median superior vena cava cannula size was 28.0 [28.0, 28.0] Fr, and inferior vena cava cannula size was 28.0 [28.0, 28.0] Fr. No mortality was reported with a median follow up time of 6.0 [6.0, 10.5] months. In conclusion, Common cardiac procedures can be performed with reasonable safety in this patient population. Operative adjustments may need to be made with respect to equipment to accommodate patient-specific needs.
PubMed: 32274169
DOI: 10.21037/jtd.2020.02.05 -
The Plant Journal : For Cell and... Mar 2023High yield and stress resistance are the major prerequisites for successful crop cultivation, and can be achieved by modifying plant architecture. Evolutionarily... (Review)
Review
High yield and stress resistance are the major prerequisites for successful crop cultivation, and can be achieved by modifying plant architecture. Evolutionarily conserved growth-regulating factors (GRFs) control the growth of different tissues and organs of plants. Here, we provide a systematic overview of the expression patterns of GRF genes and the structural features of GRF proteins in different plant species. Moreover, we illustrate the conserved and divergent roles of GRFs, microRNA396 (miR396), and GRF-interacting factors (GIFs) in leaf, root, and flower development. We also describe the molecular networks involving the miR396-GRF-GIF module, and illustrate how this module coordinates with different signaling molecules and transcriptional regulators to control development of different plant species. GRFs promote leaf growth, accelerate grain filling, and increase grain size and weight. We also provide some molecular insight into how coordination between GRFs and other signaling modules enhances crop productivity; for instance, how the GRF-DELLA interaction confers yield-enhancing dwarfism while increasing grain yield. Finally, we discuss how the GRF-GIF chimera substantially improves plant transformation efficiency by accelerating shoot formation. Overall, we systematically review the conserved and divergent roles of GRFs and the miR396-GRF-GIF module in growth regulation, and also provide insights into how GRFs can be utilized to improve the productivity and nutrient content of crop plants.
Topics: Plants, Genetically Modified; Gene Expression Regulation, Plant; MicroRNAs; Plant Development; Plant Leaves; Intercellular Signaling Peptides and Proteins
PubMed: 36582168
DOI: 10.1111/tpj.16090 -
Frontiers in Endocrinology 2023Growth hormone (GH) affects metabolism and regulates growth in childhood. The most prominent feature of GH deficiency (GHD) in children is diminished height velocity...
BACKGROUND
Growth hormone (GH) affects metabolism and regulates growth in childhood. The most prominent feature of GH deficiency (GHD) in children is diminished height velocity that eventually leads to short stature. In adult-onset GHD, lean body mass (LBM) is reduced, and visceral fat mass (FM) increased. Beneficial effects of GH treatment on body composition in adults with GHD, including an increase in muscle mass and a decrease in FM, are well established. Relatively few studies have investigated the effects of GH treatment on the body composition of pediatric patients with idiopathic or hypothalamic-pituitary disease-associated GH deficiency. This systematic review aimed to summarize available evidence relating to the effects of GH treatment on body composition in children with GHD.
METHODS
The PubMed, Science Direct, Cochrane Trials, and Embase databases, were searched with keywords including "GH", "body composition", "children", and "growth hormone" for English-language articles, published between January 1999 and March 2021. Two reviewers independently evaluated the search results and identified studies for inclusion based on the following criteria: participants had a confirmed diagnosis of GHD (as defined in each study); participants were pediatric patients who were receiving GH or had stopped GH treatment, regardless of whether they were pre- or post-pubertal; the intervention was recombinant human GH (rhGH; somatropin); and outcomes included changes in body composition during or after stopping GH therapy. Data extracted from each study included study quality, study sample characteristics, study interventions, and body composition. Data on fat-free mass and LBM were combined into a single category of LBM.
RESULTS
Sixteen studies reporting changes in body composition (i.e., FM and LBM) associated with GH treatment in children with GHD were identified and included in the review. Collectively, these studies demonstrated that FM decreased, and LBM increased in response to GH replacement therapy.
CONCLUSION
Despite study limitations (i.e., potential effects of diet and physical activity were not considered), we concluded that a periodic body composition assessment is required to ensure that a satisfactory body composition is achieved during GH replacement therapy in children with GHD.
Topics: Child; Humans; Body Composition; Dwarfism, Pituitary; Growth Hormone; Human Growth Hormone; Hypopituitarism
PubMed: 36843617
DOI: 10.3389/fendo.2023.1093691 -
Annals of Global Health Jun 2021Blood transfusion is a traditional treatment for β-thalassemia (β-thal) that improves the patients' anemia and lifespan, but it may lead to iron overload in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Blood transfusion is a traditional treatment for β-thalassemia (β-thal) that improves the patients' anemia and lifespan, but it may lead to iron overload in parenchymal tissue organs and endocrine glands that cause their dysfunctions as the iron regulatory system can't excrete excess iron from the bloodstream.
OBJECTIVE
To evaluate the prevalence of iron-related complications (short stature, growth retardation, and growth hormone deficiency) in β-thalassemia major (TM) patients.
METHODS
We performed an electronic search in PubMed, Scopus, and Web of Sciences to evaluate the prevalence of growth hormone impairment in β-thalassemia major (TM) patients worldwide. Qualities of eligible studies were assessed by the Joanna Briggs Institute checklist for the prevalence study. We used Comprehensive Meta-Analysis (Version 2) to calculate the event rate with 95% CIs, using a random-effects model for all analyses.
FINDINGS
Seventy-four studies were included from five continents between 1978 and 2019; 70.27% (Asia), 16.21% (Europe), 6.75% (Africa), 2.70% (America), 1.35% (Oceania), and 2.70% (Multicenter). The overall mean age of the participants was about 14 years. The pooled prevalence of short stature (ST) was 48.9% (95% CI 35.3-62.6) and in male was higher than female (61.9%, 95% CI 53.4-69.7 vs. 50.9%, CI 41.8-59.9). The pooled prevalence of growth retardation (GR) was 41.1% and in male was higher than in female (51.6%, 95% CI 17.8-84 vs. 33.1%, CI 9.4-70.2). The pooled prevalence of growth hormone deficiency (GHD) was 26.6% (95% CI 16-40.8).
CONCLUSION
Our study revealed that near half of thalassemia patients suffer from growth impairments. However, regular evaluation of serum ferritin levels, close monitoring in a proper institute, suitable and acceptable treatment methods besides regular chelation therapy could significantly reduce the patients' complications.
Topics: Adolescent; Blood Transfusion; Body Height; Dwarfism; Endocrine System Diseases; Female; Humans; Iron Overload; Male; beta-Thalassemia
PubMed: 34164261
DOI: 10.5334/aogh.3184 -
The Cochrane Database of Systematic... Jan 2009Congenital hypothyroidism (CHT) affects approximately one in 3000 to 4000 infants. CHT is one of the most common preventable causes of learning difficulties. Optimal... (Review)
Review
BACKGROUND
Congenital hypothyroidism (CHT) affects approximately one in 3000 to 4000 infants. CHT is one of the most common preventable causes of learning difficulties. Optimal management of CHT requires early diagnosis and prompt treatment to avoid abnormal neurodevelopmental outcome. One of the main issues in the management of CHT relates to the initial dose of levothyroxine to be used in order to achieve optimal results in terms of intellectual development. Currently, it remains unclear whether high dose thyroid hormone replacement is more effective than low dose in the treatment of CHT. Further research is required to determine an appropriate dose that improves mental and psychomotor developmental outcomes.
OBJECTIVES
To determine the effects of high versus low dose of initial thyroid hormone replacement for congenital hypothyroidism.
SEARCH STRATEGY
Randomised controlled trials were identified by searching The Cochrane Library, MEDLINE and EMBASE and reference lists of published papers.
SELECTION CRITERIA
Randomised controlled clinical trials investigating the effects of high versus low dose of initial thyroid hormone replacement for congenital hypothyroidism were included.
DATA COLLECTION AND ANALYSIS
Both authors independently selected trials, assessed risk of bias and extracted data.
MAIN RESULTS
The initial search identified 1014 records which identified 13 publications for further examination. After screening the full text of the 13 selected papers, only one study evaluating 47 babies finally met the inclusion criteria. Using the same cohort at two different time periods, the study investigated the effects of high versus low dose thyroid hormone replacement in relation to (1) time taken to achieve euthyroid status and (2) neurodevelopmental outcome. The study reported that a high dose is more effective in rising serum thyroxine and free thyroxine concentrations to the target range and earlier normalisation of thyroid stimulating hormone compared to a lower dose. Similarly, full scale intelligence quotient was noted to be significantly higher in children who received the high dose compared to the lower dose. However, the verbal intelligence quotient and performance intelligence quotient were similar in both groups. Growth and adverse effects were not reported in the included trial.
AUTHORS' CONCLUSIONS
There is currently only one randomised controlled trial evaluating the effects of high versus low dose of initial thyroid hormone replacement for CHT. There is inadequate evidence to suggest that a high dose is more beneficial compared to a low dose initial thyroid hormone replacement in the treatment of CHT.
Topics: Congenital Hypothyroidism; Hormone Replacement Therapy; Humans; Infant; Infant, Newborn; Thyroxine
PubMed: 19160309
DOI: 10.1002/14651858.CD006972.pub2