PDF(Pubmed)
Abstract：
UNASSIGNED: The objective of this study was to describe predictors of loss of ambulation in Duchenne muscular dystrophy (DMD).
UNASSIGNED: This systematic review and meta-analysis included searches of MEDLINE ALL, Embase, and the Cochrane Database of Systematic Reviews from January 1, 2000, to December 31, 2022, for predictors of loss of ambulation in DMD. Search terms included \"Duchenne muscular dystrophy\" as a Medical Subject Heading or free text term, in combination with variations of the term \"predictor\". Risk of bias was assessed using the Newcastle-Ottawa Scale. We performed meta-analysis pooling of hazard ratios of the effects of glucocorticoids (vs. no glucocorticoid therapy) by fitting a common-effect inverse-variance model.
UNASSIGNED: The bibliographic searches resulted in the inclusion of 45 studies of children and adults with DMD from 17 countries across Europe, Asia, and North America. Glucocorticoid therapy was associated with delayed loss of ambulation (overall meta-analysis HR deflazacort/prednisone/prednisolone: 0.44 [95% CI: 0.40-0.48]) (n = 25 studies). Earlier onset of first signs or symptoms, earlier loss of developmental milestones, lower baseline 6MWT (i.e.,<350 vs. ≥350 metres and <330 vs. ≥330 metres), and lower baseline NSAA were associated with earlier loss of ambulation (n = 5 studies). Deletion of exons 3-7, proximal mutations (upstream intron 44), single exon 45 deletions, and mutations amenable of skipping exon 8, exon 44, and exon 53, were associated with prolonged ambulation; distal mutations (intron 44 and downstream), deletion of exons 49-50, and mutations amenable of skipping exon 45, and exon 51 were associated with earlier loss of ambulation (n = 13 studies). Specific single-nucleotide polymorphisms in CD40 gene rs1883832, LTBP4 gene rs10880, SPP1 gene rs2835709 and rs11730582, and TCTEX1D1 gene rs1060575 (n = 7 studies), as well as race/ethnicity and level of family/patient deprivation (n = 3 studies), were associated with loss of ambulation. Treatment with ataluren (n = 2 studies) and eteplirsen (n = 3 studies) were associated with prolonged ambulation. Magnetic resonance biomarkers (MRI and MRS) were identified as significant predictors of loss of ambulation (n = 6 studies). In total, 33% of studies exhibited some risk of bias.
UNASSIGNED: Our synthesis of predictors of loss of ambulation in DMD contributes to the understanding the natural history of disease and informs the design of new trials of novel therapies targeting this heavily burdened patient population.
UNASSIGNED: This systematic review and meta-analysis included searches of MEDLINE ALL, Embase, and the Cochrane Database of Systematic Reviews from January 1, 2000, to December 31, 2022, for predictors of loss of ambulation in DMD. Search terms included \"Duchenne muscular dystrophy\" as a Medical Subject Heading or free text term, in combination with variations of the term \"predictor\". Risk of bias was assessed using the Newcastle-Ottawa Scale. We performed meta-analysis pooling of hazard ratios of the effects of glucocorticoids (vs. no glucocorticoid therapy) by fitting a common-effect inverse-variance model.
UNASSIGNED: The bibliographic searches resulted in the inclusion of 45 studies of children and adults with DMD from 17 countries across Europe, Asia, and North America. Glucocorticoid therapy was associated with delayed loss of ambulation (overall meta-analysis HR deflazacort/prednisone/prednisolone: 0.44 [95% CI: 0.40-0.48]) (n = 25 studies). Earlier onset of first signs or symptoms, earlier loss of developmental milestones, lower baseline 6MWT (i.e.,<350 vs. ≥350 metres and <330 vs. ≥330 metres), and lower baseline NSAA were associated with earlier loss of ambulation (n = 5 studies). Deletion of exons 3-7, proximal mutations (upstream intron 44), single exon 45 deletions, and mutations amenable of skipping exon 8, exon 44, and exon 53, were associated with prolonged ambulation; distal mutations (intron 44 and downstream), deletion of exons 49-50, and mutations amenable of skipping exon 45, and exon 51 were associated with earlier loss of ambulation (n = 13 studies). Specific single-nucleotide polymorphisms in CD40 gene rs1883832, LTBP4 gene rs10880, SPP1 gene rs2835709 and rs11730582, and TCTEX1D1 gene rs1060575 (n = 7 studies), as well as race/ethnicity and level of family/patient deprivation (n = 3 studies), were associated with loss of ambulation. Treatment with ataluren (n = 2 studies) and eteplirsen (n = 3 studies) were associated with prolonged ambulation. Magnetic resonance biomarkers (MRI and MRS) were identified as significant predictors of loss of ambulation (n = 6 studies). In total, 33% of studies exhibited some risk of bias.
UNASSIGNED: Our synthesis of predictors of loss of ambulation in DMD contributes to the understanding the natural history of disease and informs the design of new trials of novel therapies targeting this heavily burdened patient population.
摘要：
■这项研究的目的是描述杜氏肌营养不良症（DMD）中步行丧失的预测因素。
■本系统综述和荟萃分析包括搜索MEDLINEALL，Embase,以及2000年1月1日至2022年12月31日的Cochrane系统评价数据库，用于预测DMD中步行损失的预测因素。搜索词包括“Duchenne肌营养不良症”作为医学主题标题或自由文本术语，结合术语“预测因子”的变体。使用纽卡斯尔-渥太华量表评估偏倚风险。我们对糖皮质激素影响的风险比进行了荟萃分析（与无糖皮质激素治疗）通过拟合共同效应逆方差模型。
■书目搜索结果纳入了来自欧洲17个国家的45项儿童和成人患有DMD的研究，亚洲,和北美。糖皮质激素治疗与下床延迟丢失相关（总体荟萃分析HRdeflazacort/泼尼松/泼尼松龙：0.44[95％CI：0.40-0.48]）（n=25项研究）。早期出现的体征或症状，早期发展里程碑的丧失，较低基线6MWT(即，<350vs.≥350米和<330米vs.≥330米),较低的基线NSAA与较早的步行丧失相关(n=5项研究)。外显子3-7的缺失，近端突变（上游内含子44），单个外显子45缺失，和跳跃外显子8，外显子44和外显子53的突变，与长时间的行走有关;远端突变（内含子44和下游），外显子49-50的缺失，以及跳越外显子45和外显子51的突变与较早的行走丧失有关（n=13项研究）。CD40基因rs1883832，LTBP4基因rs10880，SPP1基因rs2835709和rs11730582以及TCTEX1D1基因rs1060575中的特定单核苷酸多态性（n=7项研究），以及种族/民族和家庭/患者剥夺水平(n=3项研究)，与步行障碍有关。用ataluren（n=2项研究）和eteplirsen（n=3项研究）治疗与延长下床活动有关。磁共振生物标志物（MRI和MRS）被确定为步行丧失的重要预测因子（n=6项研究）。总的来说,33%的研究表现出一定的偏倚风险。
■我们对DMD中步行丧失的预测因子的合成有助于了解疾病的自然史，并为针对这一负担沉重的患者群体的新疗法的新试验设计提供信息。
■本系统综述和荟萃分析包括搜索MEDLINEALL，Embase,以及2000年1月1日至2022年12月31日的Cochrane系统评价数据库，用于预测DMD中步行损失的预测因素。搜索词包括“Duchenne肌营养不良症”作为医学主题标题或自由文本术语，结合术语“预测因子”的变体。使用纽卡斯尔-渥太华量表评估偏倚风险。我们对糖皮质激素影响的风险比进行了荟萃分析（与无糖皮质激素治疗）通过拟合共同效应逆方差模型。
■书目搜索结果纳入了来自欧洲17个国家的45项儿童和成人患有DMD的研究，亚洲,和北美。糖皮质激素治疗与下床延迟丢失相关（总体荟萃分析HRdeflazacort/泼尼松/泼尼松龙：0.44[95％CI：0.40-0.48]）（n=25项研究）。早期出现的体征或症状，早期发展里程碑的丧失，较低基线6MWT(即，<350vs.≥350米和<330米vs.≥330米),较低的基线NSAA与较早的步行丧失相关(n=5项研究)。外显子3-7的缺失，近端突变（上游内含子44），单个外显子45缺失，和跳跃外显子8，外显子44和外显子53的突变，与长时间的行走有关;远端突变（内含子44和下游），外显子49-50的缺失，以及跳越外显子45和外显子51的突变与较早的行走丧失有关（n=13项研究）。CD40基因rs1883832，LTBP4基因rs10880，SPP1基因rs2835709和rs11730582以及TCTEX1D1基因rs1060575中的特定单核苷酸多态性（n=7项研究），以及种族/民族和家庭/患者剥夺水平(n=3项研究)，与步行障碍有关。用ataluren（n=2项研究）和eteplirsen（n=3项研究）治疗与延长下床活动有关。磁共振生物标志物（MRI和MRS）被确定为步行丧失的重要预测因子（n=6项研究）。总的来说,33%的研究表现出一定的偏倚风险。
■我们对DMD中步行丧失的预测因子的合成有助于了解疾病的自然史，并为针对这一负担沉重的患者群体的新疗法的新试验设计提供信息。
