- 作者列表："Ngim CF","Lai NM","Hong JY","Tan SL","Ramadas A","Muthukumarasamy P","Thong MK
BACKGROUND:Thalassaemia is a recessively-inherited blood disorder that leads to anaemia of varying severity. In those affected by the more severe forms, regular blood transfusions are required which may lead to iron overload. Accumulated iron from blood transfusions may be deposited in vital organs including the heart, liver and endocrine organs such as the pituitary glands which can affect growth hormone production. Growth hormone deficiency is one of the factors that can lead to short stature, a common complication in people with thalassaemia. Growth hormone replacement therapy has been used in children with thalassaemia who have short stature and growth hormone deficiency. This review on the role of growth hormone was originally published in September 2017 and updated in April 2020. OBJECTIVES:To assess the benefits and safety of growth hormone therapy in people with thalassaemia. SEARCH METHODS:We searched the Cochrane Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. Date of latest search: 14 November 2019. We also searched the reference lists of relevant articles, reviews and clinical trial registries. Date of latest search: 06 January 2020. SELECTION CRITERIA:Randomised and quasi-randomised controlled trials comparing the use of growth hormone therapy to placebo or standard care in people with thalassaemia of any type or severity. DATA COLLECTION AND ANALYSIS:Two authors independently selected trials for inclusion. Data extraction and assessment of risk of bias were also conducted independently by two authors. The certainty of the evidence was assessed using GRADE criteria. MAIN RESULTS:We included one parallel trial conducted in Turkey. The trial recruited 20 children with homozygous beta thalassaemia who had short stature; 10 children received growth hormone therapy administered subcutaneously on a daily basis at a dose of 0.7 IU/kg per week and 10 children received standard care. The overall risk of bias in this trial was low except for the selection criteria and attrition bias which were unclear. The certainty of the evidence for all major outcomes was moderate, the main concern was imprecision of the estimates due to the small sample size leading to wide confidence intervals. Final height (cm) (the review's pre-specified primary outcome) and change in height were not assessed in the included trial. The trial reported no clear difference between groups in height standard deviation (SD) score after one year, mean difference (MD) -0.09 (95% confidence interval (CI) -0.33 to 0.15 (moderate-certainty evidence). However, modest improvements appeared to be observed in the following key outcomes in children receiving growth hormone therapy compared to control (moderate-certainty evidence): change between baseline and final visit in height SD score, MD 0.26 (95% CI 0.13 to 0.39); height velocity, MD 2.28 cm/year (95% CI 1.76 to 2.80); height velocity SD score, MD 3.31 (95% CI 2.43 to 4.19); and change in height velocity SD score between baseline and final visit, MD 3.41 (95% CI 2.45 to 4.37). No adverse effects of treatment were reported in either group; however, while there was no clear difference between groups in the oral glucose tolerance test at one year, fasting blood glucose was significantly higher in the growth hormone therapy group compared to control, although both results were still within the normal range, MD 6.67 mg/dL (95% CI 2.66 to 10.68). There were no data beyond the one-year trial period. AUTHORS' CONCLUSIONS:A small single trial contributed evidence of moderate certainty that the use of growth hormone for a year may improve height velocity of children with thalassaemia although height SD score in the treatment group was similar to the control group. There are no randomised controlled trials in adults or trials that address the use of growth hormone therapy over a longer period and assess its effect on final height and quality of life. The optimal dosage of growth hormone and the ideal time to start this therapy remain uncertain. Large well-designed randomised controlled trials over a longer period with sufficient duration of follow up are needed.
背景: 地中海贫血是一种隐性遗传性血液病，可导致不同程度的贫血。在受更严重形式影响的患者中，需要定期输血，这可能导致铁过载。从输血中积累的铁可以沉积在重要器官中，包括心脏、肝脏和内分泌器官，例如垂体，其可以影响生长激素的产生。生长激素缺乏症是可导致身材矮小的因素之一，这是地贫患者常见的并发症。生长激素替代疗法已用于身材矮小和生长激素缺乏症的地贫儿童。这篇关于生长激素作用的综述最初发表于2017年9月，并于2020年4月更新。 目的: 评估生长激素治疗地中海贫血患者的益处和安全性。 检索方法: 我们检索了Cochrane血红蛋白病试验登记簿，该登记簿由电子数据库检索和手工检索期刊和会议摘要书籍汇编而成。最新搜索日期: 2019年11月14日。我们还检索了相关文章、综述和临床试验注册的参考文献列表。最新搜索日期: 2020年1月6日。 选择标准: 在任何类型或严重程度的地中海贫血患者中比较使用生长激素疗法与安慰剂或标准护理的随机和半随机对照试验。 数据收集和分析: 两名作者独立选择试验纳入。数据提取和偏倚风险评估也由两位作者独立进行。使用GRADE标准评估证据的确定性。 主要结果: 我们纳入了在土耳其进行的一项平行试验。该试验招募了20名身材矮小的纯合 β 地中海贫血患儿; 10名患儿接受生长激素治疗，每日皮下注射，剂量为每周0.7 IU/kg，10名患儿接受标准治疗.本试验中偏倚的总体风险较低，但选择标准和磨耗偏倚不明确。所有主要结局的证据的确定性都是中等的，主要担心的是由于样本量小导致置信区间宽而导致的估计不精确.最终身高 (cm) (审查预先指定的主要结局) 和身高变化未在纳入的试验中进行评估.试验报告1年后两组间身高标准差 (SD) 评分无明显差异，平均差 (MD) -0.09 (95% 置信区间 (CI) -0.33至0.15 (中等确定性证据)。然而，与对照组相比，接受生长激素治疗的儿童的以下关键结局似乎有适度改善 (中等确定性证据): 基线和最终访视之间身高SD评分的变化，MD 0.26 (95% CI 0.13至0.39); 身高速度，MD 2.28厘米/年 (95% CI 1.76 to 2.80);身高速度SD评分，MD 3.31 (95% CI 2.43至4.19); 基线和最终访视之间的身高速度SD评分变化，MD 3.41 (95% CI 2.45至4.37)。两组均未报告治疗的不良反应; 然而，虽然在1年的口服葡萄糖耐量试验中，组间无明显差异，但与对照组相比，生长激素治疗组的空腹血糖显著升高，尽管两项结果仍在正常范围内，MD 6.67 mg/dL (95% CI 2.66至10.68)。没有超过一年试验期的数据. 作者的结论: 一项小型的单一试验提供了中度确定性的证据，即使用生长激素一年可以改善地中海贫血患儿的身高速度，尽管治疗组的身高SD评分与对照组相似。没有在成人中进行随机对照试验，也没有在更长时间内使用生长激素治疗并评估其对最终身高和生活质量的影响的试验。生长激素的最佳剂量和开始这种治疗的理想时间仍不确定。需要在更长的时间内进行大型设计良好的随机对照试验，并有足够的随访时间。
METHODS:BACKGROUND:Thalassemia is one of the most common monogenetic diseases in the south of China and Southeast Asia. Hemoglobin Bart's hydrops fetalis syndrome was caused by a homozygous Southeast Asian deletion (-/-) in the HBA gene. Few studies have proved the potential of screen for Bart's hydrops fetalis using fetal cell-free DNA. However, the number of cases is still relatively small. Clinical trials of large samples would be needed. OBJECTIVE:In this study, we aimed to develop a noninvasive method of target-captured sequencing and genotyping by the Bayesian method using cell-free fetal DNA to identify the fetal genotype in pregnant women who are at risk of having hemoglobin Bart hydrops fetalis in a large-scale study. STUDY DESIGN:In total, 192,173 couples from 30 hospitals were enrolled in our study and 878 couples were recruited, among whom both the pregnant women and their husbands were detected to be carriers of Southeast Asian type (-/αα) of α-thalassemia. Prenatal diagnosis was performed by chorionic villus sampling, amniocentesis, or cordocentesis using gap-polymerase chain reaction considered as the golden standard. RESULTS:As a result, we found that the sensitivity and specificity of our noninvasive method were 98.81% and 94.72%, respectively, in the training set as well as 100% and 99.31%, respectively, in the testing set. Moreover, our method could identify all of 885 maternal samples with the Southeast Asian carrier and 36 trisomy samples with 100% of sensitivity in T13, T18, and T21 and 99.89% (1 of 917) and 99.88% (1 of 888) of specificity in T18 and T21, respectively. CONCLUSION:Our method opens the possibility of early screening for maternal genotyping of α-thalassemia, fetal aneuploidies in chromosomes 13/18/21, and hemoglobin Bart hydrops fetalis detection in 1 tube of maternal plasma.
METHODS:OBJECTIVES:Sickle cell disease (SCD) is a serious illness with disabling acute and chronic pain that needs better therapies, but insufficient patient participation in research is a major impediment to advancing SCD pain management. The purpose of this article is to discuss the challenges of conducting an SCD study and approaches to successfully overcoming those challenges. DESIGN:In a repeated-measures, longitudinal study designed to characterize SCD pain phenotypes, we recruited 311 adults of African ancestry. Adults with SCD completed 4 study visits 6 months apart, and age- and gender-matched healthy controls completed 1 visit. RESULTS:We recruited and completed measures on 186 patients with SCD and 125 healthy controls. We retained 151 patients with SCD with data at 4 time points over 18 months and 125 healthy controls (1 time point) but encountered many challenges in recruitment and study visit completion. Enrollment delays often arose from patients' difficulty in taking time from their complicated lives and frequent pain episodes. Once scheduled, participants with SCD cancelled 49% of visits often because of pain; controls canceled 30% of their scheduled visits. To facilitate recruitment and retention, we implemented a number of strategies that were invaluable in our success. CONCLUSION:Patients' struggles with illness, chronic pain, and their life situations resulted in many challenges to recruitment and completion of study visits. Important to overcoming challenges was gaining the trust of patients with SCD and a participant-centered approach. Early identification of potential problems allowed strategies to be instituted proactively, leading to success.
METHODS:OBJECTIVES:Sickle cell anemia is the commonest genetic disorder in India, and the frequency of the sickle cell gene is very high in the remote tribal areas where facilities are generally limited. Therefore, a rapid and affordable point-of-care test for sickle cell disease is needed. METHODS:The diagnostic accuracy of HemoTypeSC was evaluated against automated high-performance liquid chromatography (HPLC) as the gold standard for its efficacy in a newborn screening program. RESULTS:A total of 1,559 individuals (980 newborns and 579 adults) from four participating centers were analyzed by both methods. HemoTypeSC correctly identified 209 of 211 total hemoglobin (Hb) SS cases, for a 99.1%/99.9% total HbSS sensitivity/specificity. Overall, HemoTypeSC exhibited sensitivity and specificity of 98.1% and 99.1% for all possible phenotypes (HbAA, HbAS, and HbSS) detected. HPLC is relatively expensive and not available in most laboratories in remote tribal areas. CONCLUSIONS:We conclude that the rapid, point-of-care testing device HemoTypeSC test is suitable for population and newborn screening for the HbS phenotype.