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Growth Hormone Treatment for Adults With Prader-Willi Syndrome: A Meta-Analysis.
Rosenberg, AGW, Passone, CGB, Pellikaan, K, Damiani, D, van der Lely, AJ, Polak, M, Bernardo, WM, de Graaff, LCG
The Journal of clinical endocrinology and metabolism. 2021;(10):3068-3091
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Abstract
CONTEXT Features of Prader-Willi syndrome (PWS) overlap with features of growth hormone (GH) deficiency, like small hands and feet, short stature, increased body fat, and low muscle mass and strength. In children with PWS, GH treatment (GHt) improves physical health and cognition. GHt has become the standard of care in PWS children, but in adults this is not yet the case. OBJECTIVE This work aims to provide an overview of the current knowledge on GHt in PWS adults. METHODS Medline, Embase, and the Cochrane Central Register of Controlled Trials databases were searched. Study selection included randomized clinical trials (RCTs) and nonrandomized (un)controlled trials (NRCTs) that reported data for adults with PWS, who received GHt for at least 6 months. Data on body composition, body mass index (BMI), cardiovascular end points, bone, cognitive function, quality of life, and safety were extracted. RESULTS Nine RCTs and 20 NRCTs were included. Body composition improved during 12 months of GHt with an increase in mean (95% CI) lean body mass of 1.95 kg (0.04 to 3.87 kg) and a reduction of mean (95% CI) fat mass of -2.23% (-4.10% to -0.36%). BMI, low-density lipoprotein cholesterol levels, fasting glucose levels, and bone mineral density did not change during GHt. There were no major safety issues. CONCLUSION GHt appears to be safe and improves body composition in adults with PWS. Because poor body composition is closely linked to the observed high incidence of cardiovascular morbidity in adults with PWS, improving body composition might reduce cardiovascular complications in this vulnerable patient group.
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Recombinant growth hormone therapy for cystic fibrosis in children and young adults.
Thaker, V, Carter, B, Putman, M
The Cochrane database of systematic reviews. 2018;(12):CD008901
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Abstract
BACKGROUND Cystic fibrosis (CF) is an inherited condition causing disease most noticeably in the lungs, digestive tract and pancreas. People with CF often have malnutrition and growth delay. Adequate nutritional supplementation does not improve growth optimally and hence an anabolic agent, recombinant human growth hormone (rhGH), has been proposed as a potential intervention. This is an update of a previously published review. OBJECTIVES To evaluate the effectiveness and safety of rhGH therapy in improving lung function, quality of life and clinical status of children and young adults with CF. SEARCH METHODS We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Date of latest search: 22 October 2018.We also searched ongoing trials registers in clinicaltrials.gov from the United States and WHO International Clinical Trials Registry Platform (ICTRP). Date of latest search: 05 March 2018.We conducted a search of relevant endocrine journals and proceedings of the Endocrinology Society meetings using Web of Science, Scopus and Proceedings First. Date of latest search: 04 March 2018. SELECTION CRITERIA Randomised and quasi-randomised controlled trials of all preparations of rhGH compared to either no treatment, or placebo, or each other at any dose (high-dose and low-dose) or route and for any duration, in children or young adults (aged up to 25 years) diagnosed with CF (by sweat test or genetic testing). DATA COLLECTION AND ANALYSIS Two authors independently screened papers, extracted trial details and assessed their risk of bias. We assessed the quality of the evidence using the GRADE system. MAIN RESULTS We included eight trials (291 participants, aged between five and 23 years) in this revision of the review. Seven trials compared standard-dose rhGH (approximately 0.3 mg/kg/week) to no treatment and one three-arm trial (63 participants) compared placebo, standard-dose rhGH (0.3 mg/kg/week) and high-dose rhGH (0.5 mg/kg/week). Six trials lasted for one year and two trials for six months. We found that rhGH treatment may improve some of the pulmonary function outcomes but there was no difference between standard and high-dose levels (low-quality evidence, limited by inconsistency across the trials, small number of participants and short duration of therapy). The trials show evidence of improvement in the anthropometric parameters (height, weight and lean body mass) with rhGH therapy, again no differences between dose levels. We found improvement in height for all comparisons (very low- to low quality evidence), but improvements in weight and lean body mass were only reported for standard-dose rhGH versus no treatment (very low-quality evidence). There is some evidence indicating a change in the level of fasting blood glucose with rhGH therapy, however, it did not cross the clinical threshold for diagnosis of diabetes in the trials of short duration (low-quality evidence). There is low- to very low-quality evidence for improvement of pulmonary exacerbations with no further significant adverse effects, but this is limited by the short duration of trials and the small number of participants. One small trial provided inconsistent evidence on improvement in quality of life (very low-quality evidence). There is limited evidence from three trials in improvements in exercise capacity (low-quality evidence). None of the trials have systematically compared the expense of therapy on overall healthcare costs. AUTHORS' CONCLUSIONS When compared with no treatment, rhGH therapy is effective in improving the intermediate outcomes in height, weight and lean body mass. Some measures of pulmonary function showed moderate improvement, but no consistent benefit was seen across all trials. The significant change in blood glucose levels, although not causing diabetes, emphasizes the need for careful monitoring of this adverse effect with therapy in a population predisposed to CF-related diabetes. No significant changes in quality of life, clinical status or side-effects were observed in this review due to the small number of participants. Long-term, well-designed randomised controlled trials of rhGH in individuals with CF are required prior to routine clinical use of rhGH in CF.
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GH Supplementation Effects on Cardiovascular Risk in GH Deficient Adult Patients: A Systematic Review and Meta-analysis.
Giagulli, VA, Castellana, M, Perrone, R, Guastamacchia, E, Iacoviello, M, Triggiani, V
Endocrine, metabolic & immune disorders drug targets. 2017;(4):285-296
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Abstract
BACKGROUND AND OBJECTIVE The current meta-analysis aims at evaluating whether the existing clinical evidence may ascertain the effects of growth hormone (GH) replacement therapy on cardiovascular risk, both in isolated GH deficiency (GHD) and in compensated panhypopituitarism including GH deficit. METHODS Original articles published from 1991 to 2015 were searched on Medline (Pubmed). Among an overall number of 181 potentially suitable studies, 24 fulfilled the selection criteria and were included in the analysis. Data aggregation was carried out through the calculation of the absolute risk reduction. The meta-analysis was then conducted by means of a fixed-effects model, according to the heterogeneity test (Chi-square statistic). RESULTS Fat-free mass (FFM) increase and fat mass (FM) reduction were found, together with a C-LDL reduction, a wide variation in glycaemia and a neutral effect on glycated haemoglobin (HbA1c) and blood pressure. These effects were valid both for isolated GHD patients and for those with compensated panhypopituitarism. The global outcome D showed a nonsignificant reduction of the overall cardiovascular risk (0.53; 95% C.I. -1.23, 2.85). CONCLUSION Our meta-analysis shows no signnificatly positive trend in cardiovascular risk after both short and long-term GH supplementation therapy in adult GHD patients. However, a reduction of LDL cholesterol levels has been found. No differences were found between isolated GHD participants and those affected by panhypopituitarism well compensated since at least 3 months.
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Recombinant growth hormone therapy for cystic fibrosis in children and young adults.
Thaker, V, Haagensen, AL, Carter, B, Fedorowicz, Z, Houston, BW
The Cochrane database of systematic reviews. 2015;(5):CD008901
Abstract
BACKGROUND Cystic fibrosis is an inherited condition causing disease most noticeably in the lungs, digestive tract and pancreas. People with cystic fibrosis often have malnutrition and growth delay. Adequate nutritional supplementation does not improve growth optimally and hence an anabolic agent, recombinant growth hormone, has been proposed as a potential intervention. OBJECTIVES To evaluate the effectiveness and safety of recombinant human growth hormone therapy in improving lung function, quality of life and clinical status of children and young adults with cystic fibrosis. SEARCH METHODS We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Date of latest search: 11 February 2015.We conducted a search of relevant endocrine journals and proceedings of the Endocrinology Society meetings using Scopus and Proceedings First. Date of latest search: 04 March 2015. SELECTION CRITERIA Randomised and quasi-randomised controlled trials of all preparations of recombinant growth hormone compared to either no treatment, or placebo, or each other at any dose (high-dose and low-dose) or route and for any duration, in children or young adults aged up to 25 years diagnosed with cystic fibrosis (by sweat test or genetic testing). DATA COLLECTION AND ANALYSIS Two authors independently screened papers, extracted trial details and assessed their risk of bias. MAIN RESULTS Four controlled trials were included in this review (with 161 participants in total), each with an unclear risk of bias. Analysis of data obtained from these trials shows improvement in height for all comparisons, but improvements in weight and lean tissue mass were only reported in the comparison of standard dose recombinant growth hormone versus no treatment. One study showed moderate improvement at one time point in one parameter of pulmonary function tests, forced vital capacity (per cent predicted) when comparing standard dose recombinant growth hormone and no treatment, but there was no consistent benefit in lung function across all studies. Little evidence was found for improvement in quality of life. An improvement in fasting blood glucose levels was reported when comparing rhGH to placebo only. Exercise capacity improved in participants receiving standard dose recombinant growth hormone versus no treatment, but not for any other comparison. There is insufficient evidence to conclude any changes in hospitalisations, antibiotic use or significant adverse effects. AUTHORS' CONCLUSIONS Recombinant growth hormone therapy is effective in improving the intermediate outcomes in height, weight and lean tissue mass when compared with no treatment. One measure of pulmonary function test showed moderate improvement at a single time point, but no consistent benefit was seen across all studies. No significant changes in quality of life, clinical status or side-effects were observed in this review. Long-term, well-designed randomised controlled trials of recombinant growth hormone therapy in people with cystic fibrosis are required prior to evaluation of human growth hormone treatment for routine use.
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Recombinant growth hormone therapy for cystic fibrosis in children and young adults.
Thaker, V, Haagensen, AL, Carter, B, Fedorowicz, Z, Houston, BW
The Cochrane database of systematic reviews. 2013;(6):CD008901
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Abstract
BACKGROUND Cystic fibrosis is an inherited condition causing disease most noticeably in the lungs, digestive tract and pancreas. People with cystic fibrosis often have malnutrition and growth delay. Adequate nutritional supplementation does not improve growth optimally and hence an anabolic agent, recombinant growth hormone, has been proposed as a potential intervention. OBJECTIVES To evaluate the effectiveness and safety of recombinant human growth hormone therapy in improving lung function, quality of life and clinical status of children and young adults with cystic fibrosis. SEARCH METHODS We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Date of latest search: 15 May 2013.We conducted a search of relevant endocrine journals and proceedings of the Endocrinology Society meetings using Scopus and Proceedings First. Date of latest search: 15 March 2012. SELECTION CRITERIA Randomised and quasi-randomised controlled trials of all preparations of recombinant growth hormone compared to either no treatment, or placebo, or each other at any dose (high-dose and low-dose) or route and for any duration, in children or young adults aged up to 25 years diagnosed with cystic fibrosis (by sweat test or genetic testing). DATA COLLECTION AND ANALYSIS Two authors independently screened papers, extracted trial details and assessed their risk of bias. MAIN RESULTS Four controlled trials were included in this review (with 161 participants in total), each with an unclear risk of bias. Analysis of data obtained from these trials shows improvement in height for all comparisons, but improvements in weight and lean tissue mass were only reported in the comparison of standard dose recombinant growth hormone versus no treatment. There is moderate improvement in one parameter of pulmonary function tests, functional vital capacity (per cent predicted) when comparing standard dose recombinant growth hormone and no treatment. Little evidence was found for improvement in quality of life. An improvement in fasting blood glucose levels was reported when comparing rhGH to placebo only. Exercise capacity improved in participants receiving standard dose recombinant growth hormone versus no treatment, but not for any other comparison. There is insufficient evidence to conclude any changes in hospitalisations, antibiotic use or significant adverse effects. AUTHORS' CONCLUSIONS Recombinant growth hormone therapy is effective in improving the intermediate outcomes in height, weight and lean tissue mass when compared with no treatment. One measure of pulmonary function test showed moderate improvement. No significant changes in quality of life, clinical status or side-effects were observed in this review. Long-term, well-designed randomised controlled trials of recombinant growth hormone therapy in patients with cystic fibrosis are required prior to evaluation of human growth hormone treatment for routine use in patients.
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Clinical evidence of growth hormone, glutamine and a modified diet for short bowel syndrome: meta-analysis of clinical trials.
Zhou, Y, Wu, XT, Yang, G, Zhuang, W, Wei, ML
Asia Pacific journal of clinical nutrition. 2005;(1):98-102
Abstract
This study assessed the safety and efficacy of growth hormone (GH) and glutamine (GLN) combined with a modified (high-carbohydrate-low-fat, HCLF) diet in patients with short bowel syndrome. A meta-analysis of all the relevant clinical trials was performed. Clinical trials were identified from the following electronic databases: MEDLINE, EMBASE, the Cochrane Controlled Trials Register, Chinese Bio-medicine Database. The search was undertaken in May 2004. Language was restricted to Chinese and English. Literature references were checked at the same time. Clinical trials were extracted and evaluated by two reviewers independently of each other. The statistical analysis was performed by RevMan4.2 software which was provided by the Cochrane Collaboration. A P value of < 0.05 was considered statistically significant. Thirteen trials involving 258 patients were included. The combined results showed that GH, GLN and HCLF diet had positive treatment effect on body weight (weighted mean difference [WMD] = 2.44, 95%CI [1.62, 3.27], P<0.00001), stool output (WMD = -376.49, 95%CI [-600.35, -152.63], P=0.001), lean body mass (WMD = 2.16, 95%CI [0.91, 3.41], P=0.0007), absorption of carbohydrates (WMD = 6.21, 95%CI [5.27, 7.15], P< 0.00001), absorption of nitrogen (WMD = 10.83, 95%CI [5.22, 16.44], P=0.0002), absorption of D-xylose (WMD = 0.37, 95%CI [0.29, 0.44], P<0.00001), and off TPN (total parenteral nutrition) (odds ratios [OR] = 64.63, 95%CI [15.51, 269.22], P<0.00001). But there were no improvements in fat mass (WMD = -1.50, 95%CI [-3.48, 0.48], P=0.14), absorption of energy (WMD = 7.48, 95%CI [-7.22, 22.17], P=0.32), and absorption of fat (WMD = 7.16, 95%CI [-2.95, 17.28], P=0.17). Most patients had side effects that are known to occur during treatment with high doses (0.14 mg/kg/day) of GH. No serious adverse effects occurred during active treatment with low doses (< or =0.1 mg/kg/day) of GH. Treatment with a combination of low-dose GH, GLN and HCLF diet is effective without any major adverse effects in patients with short bowel syndrome. Further trials are required, especially in children, with sufficient size and rigorous design.
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Impact of growth hormone (GH) treatment on cardiovascular risk factors in GH-deficient adults: a Metaanalysis of Blinded, Randomized, Placebo-Controlled Trials.
Maison, P, Griffin, S, Nicoue-Beglah, M, Haddad, N, Balkau, B, Chanson, P, ,
The Journal of clinical endocrinology and metabolism. 2004;(5):2192-9
Abstract
Patients with hypopituitarism have an increased risk of cardiovascular mortality. GH treatment could modify the cardiovascular risk in adults with GH deficiency, but most published clinical trials involved few patients and the results are variable. We conducted a systematic review of blinded, randomized, placebo-controlled trials of GH treatment in adult patients with GH deficiency published up to August 2003. Thirty-seven trials were identified. We combined the results for effects on lean and fat body mass; body mass index; triglyceride and cholesterol [high-density lipoprotein, low-density lipoprotein (LDL), and total] levels; blood pressure; glycemia; and insulinemia. Overall effect size was used to evaluate significance, and weighted differences between GH and placebo were used to appreciate the size of the effect. GH treatment significantly reduced LDL cholesterol [-0.5 (SD 0.3) mmol/liter], total cholesterol [-0.3 (0.3) mmol/liter], fat mass [-3.1 (3.3) kg], and diastolic blood pressure [-1.8 (3.8) mm Hg] and significantly increased lean body mass [+2.7 (2.6) kg], fasting plasma glucose [+0.2 (0.1) mmol/liter], and insulin [+8.7 (7.0) pmol/liter]. All effect sizes remained significant in trials with low doses and long-duration GH treatment. Thus, GH treatment has beneficial effects on lean and fat body mass, total and LDL cholesterol levels, and diastolic blood pressure but reduces insulin sensitivity. The global cardiovascular benefit remains to be determined in large trials with appropriate clinical endpoints.
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Systematic review and meta-analysis of interventions for postoperative fatigue.
Rubin, GJ, Hotopf, M
The British journal of surgery. 2002;(8):971-84
Abstract
BACKGROUND Postoperative fatigue is common, even after uncomplicated operations. Various theories have been presented regarding its aetiology, each suggesting different possible interventions. The purpose of this review was to identify all studies that have assessed interventions for postoperative fatigue and to evaluate these interventions using meta-analytical techniques. METHODS Randomized controlled trials of interventions, identified from a systematic search of relevant databases, were evaluated according to standardized criteria and categorized according to intervention modality. Data relating to the efficacy of each intervention at four different postoperative time-points were collated and data synthesis by meta-analysis was performed. RESULTS Analgesia is effective in reducing fatigue immediately after operation. Perioperative administration of human growth hormone reduces fatigue between 8 and 30 days after abdominal surgery. Weaker evidence was found to suggest an influence of glucocorticoid administration and of surgical technique on fatigue in the first week after operation. No evidence was found to support the theory that psychosocial or nutritional interventions affect the symptom. CONCLUSION While the results demonstrate that improved analgesia can attenuate immediate postoperative fatigue in most patient groups, further research is needed to determine whether the efficacy of human growth hormone and glucocorticoids extends beyond abdominal surgery. The paucity of research into cognitive-behavioural, sleep and activity-based interventions also needs to be addressed.