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Harmonizing multisite data with the ComBat method for enhanced Parkinson’s disease diagnosis via DAT-SPECT 利用 ComBat 方法协调多站点数据,通过 DAT-SPECT 提高帕金森病诊断水平
Pub Date : 2024-02-19 DOI: 10.3389/fneur.2024.1306546
Noritaka Wakasugi, Harumasa Takano, Mitsunari Abe, N. Sawamoto, Toshiya Murai, Toshiki Mizuno, Teruyuki Matsuoka, Ryo Yamakuni, Hirooki Yabe, Hiroshi Matsuda, Takashi Hanakawa
Dopamine transporter single-photon emission computed tomography (DAT-SPECT) is a crucial tool for evaluating patients with Parkinson’s disease (PD). However, its implication is limited by inter-site variability in large multisite clinical trials. To overcome the limitation, a conventional prospective correction method employs linear regression with phantom scanning, which is effective yet available only in a prospective manner. An alternative, although relatively underexplored, involves retrospective modeling using a statistical method known as “combatting batch effects when combining batches of gene expression microarray data” (ComBat).We analyzed DAT-SPECT-specific binding ratios (SBRs) derived from 72 healthy older adults and 81 patients with PD registered in four clinical sites. We applied both the prospective correction and the retrospective ComBat correction to the original SBRs. Next, we compared the performance of the original and two corrected SBRs to differentiate the PD patients from the healthy controls. Diagnostic accuracy was assessed using the area under the receiver operating characteristic curve (AUC-ROC).The original SBRs were 6.13 ± 1.54 (mean ± standard deviation) and 2.03 ± 1.41 in the control and PD groups, respectively. After the prospective correction, the mean SBRs were 6.52 ± 1.06 and 2.40 ± 0.99 in the control and PD groups, respectively. After the retrospective ComBat correction, the SBRs were 5.25 ± 0.89 and 2.01 ± 0.73 in the control and PD groups, respectively, resulting in substantial changes in mean values with fewer variances. The original SBRs demonstrated fair performance in differentiating PD from controls (Hedges’s g = 2.76; AUC-ROC = 0.936). Both correction methods improved discrimination performance. The ComBat-corrected SBR demonstrated comparable performance (g = 3.99 and AUC-ROC = 0.987) to the prospectively corrected SBR (g = 4.32 and AUC-ROC = 0.992) for discrimination.Although we confirmed that SBRs fairly discriminated PD from healthy older adults without any correction, the correction methods improved their discrimination performance in a multisite setting. Our results support the utility of harmonization methods with ComBat for consolidating SBR-based diagnosis or stratification of PD in multisite studies. Nonetheless, given the substantial changes in the mean values of ComBat-corrected SBRs, caution is advised when interpreting them.
多巴胺转运体单光子发射计算机断层扫描(DAT-SPECT)是评估帕金森病(PD)患者的重要工具。然而,在大型多点临床试验中,它的作用受到了试验点间变异性的限制。为了克服这一局限性,传统的前瞻性校正方法采用了线性回归和模型扫描,这种方法虽然有效,但只能以前瞻性的方式使用。我们分析了在四个临床试验机构登记的 72 名健康老年人和 81 名帕金森病患者的 DAT-SPECT 特异性结合率(SBR)。我们对原始 SBR 进行了前瞻性校正和回顾性 ComBat 校正。接下来,我们比较了原始 SBR 和两种校正 SBR 在区分帕金森病患者和健康对照组方面的性能。对照组和帕金森病组的原始 SBR 分别为 6.13 ± 1.54(平均值 ± 标准差)和 2.03 ± 1.41。经过前瞻性校正后,对照组和腹膜透析组的平均 SBR 分别为 6.52 ± 1.06 和 2.40 ± 0.99。经过 ComBat 追溯校正后,对照组和帕金森病组的 SBR 分别为 5.25 ± 0.89 和 2.01 ± 0.73,平均值发生了很大变化,但方差较小。原始 SBR 在区分帕金森病和对照组方面表现尚可(Hedges's g = 2.76;AUC-ROC = 0.936)。两种校正方法都提高了区分性能。ComBat校正后的SBR与前瞻性校正后的SBR(g = 4.32,AUC-ROC = 0.992)具有相当的区分性能(g = 3.99,AUC-ROC = 0.987)。我们的研究结果支持在多地点研究中采用与ComBat统一的方法来巩固基于SBR的PD诊断或分层。尽管如此,鉴于ComBat校正后的SBR平均值变化很大,在对其进行解释时仍需谨慎。
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引用次数: 0
Long-term safety, tolerability, and efficacy of efgartigimod (ADAPT+): interim results from a phase 3 open-label extension study in participants with generalized myasthenia gravis 依加替莫德(ADAPT+)的长期安全性、耐受性和疗效:针对全身性肌无力患者的第3期开放标签扩展研究的中期结果
Pub Date : 2024-01-17 DOI: 10.3389/fneur.2023.1284444
James F. Howard, V. Bril, Tuan Vu, C. Karam, S. Peric, J. L. De Bleecker, H. Murai, A. Meisel, S. Beydoun, M. Pasnoor, Antonio Guglietta, B. van Hoorick, S. Steeland, C. T’joen, K. Utsugisawa, J. Verschuuren, Renato Mantegazza
ADAPT+ assessed the long-term safety, tolerability, and efficacy of efgartigimod in adult participants with generalized myasthenia gravis (gMG).ADAPT+ was an open-label, single-arm, multicenter, up to 3-year extension of the pivotal phase 3 ADAPT study. Efgartigimod was administered in treatment cycles of 4 intravenous infusions (one 10 mg/kg infusion per week). Initiation of subsequent treatment cycles was individualized based on clinical evaluation. Safety endpoints included incidence and severity of adverse events. Efficacy endpoints assessed disease severity using Myasthenia Gravis-Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) scores.As of January 2022, 151 participants had rolled over to ADAPT+ and 145 had received ≥1 dose of efgartigimod, of whom, 111 (76.6%) were AChR-Ab+ and 34 (23.4%) were AChR-Ab−. Mean study duration (treatment plus follow-up) was 548 days, and participants received up to 17 treatment cycles, corresponding to 217.6 participant-years of exposure. In the overall population, 123 (84.8%) participants reported ≥1 treatment-emergent adverse event; most frequent were headache (36 [24.8%]), COVID-19 (22 [15.2%]), and nasopharyngitis (20 [13.8%]). Clinically meaningful improvement (CMI) in mean MG-ADL and QMG scores was seen as early as 1 week following the first infusion across multiple cycles in AChR-Ab+ and AChR-Ab− participants. Maximal MG-ADL and QMG improvements aligned with onset and magnitude of total IgG and AChR-Ab reductions. For AChR-Ab+ participants at any time point in each of the first 10 treatment cycles, more than 90% had a maximum reduction of ≥2 points (CMI) in MG-ADL total score; across the 7 cycles in which QMG was measured, 69.4% to 91.3% of participants demonstrated a maximum reduction of ≥3 points (CMI) in QMG total score. Many participants demonstrated improvements well beyond CMI thresholds. In AChR-Ab+ participants with ≥1 year of combined follow-up between ADAPT and ADAPT+, mean number of annualized cycles was 4.7 per year (median [range] 5.0 [0.5–7.6]).Results of ADAPT+ corroborate the substantial clinical improvements seen with efgartigimod in ADAPT and support its long-term safety, tolerability, and efficacy, as well as an individualized dosing regimen for treatment of gMG.https://classic.clinicaltrials.gov/ct2/show/NCT03770403, NCT03770403.
ADAPT+评估了依加替莫德对全身性肌无力(gMG)成年患者的长期安全性、耐受性和疗效。ADAPT+是关键性的ADAPT 3期研究的一项开放标签、单臂、多中心、长达3年的扩展研究。依加替莫德以4次静脉输注为一个治疗周期(每周一次,每次10毫克/千克)。后续治疗周期的启动根据临床评估进行个体化。安全性终点包括不良事件的发生率和严重程度。截至2022年1月,151名参与者转入ADAPT+,145名参与者接受了≥1个剂量的依加替莫德治疗,其中111人(76.6%)为AChR-Ab+患者,34人(23.4%)为AChR-Ab-患者。平均研究持续时间(治疗加随访)为 548 天,参与者最多接受了 17 个治疗周期,相当于 217.6 个参与者年。在所有参与者中,123 人(84.8%)报告了≥1 次治疗引起的不良反应;最常见的不良反应是头痛(36 [24.8%])、COVID-19(22 [15.2%])和鼻咽炎(20 [13.8%])。AChR-Ab+ 和 AChR-Ab- 参与者的 MG-ADL 和 QMG 平均得分最早在首次输注后 1 周就出现了有临床意义的改善(CMI)。MG-ADL 和 QMG 的最大改善与总 IgG 和 AChR-Ab 降低的开始时间和幅度一致。对于 AChR-Ab+ 参与者,在前 10 个治疗周期的每个周期的任何时间点,90% 以上的参与者 MG-ADL 总分最大降幅≥2 分(CMI);在测量 QMG 的 7 个周期中,69.4% 到 91.3% 的参与者 QMG 总分最大降幅≥3 分(CMI)。许多参与者的改善远远超过了 CMI 临界值。在ADAPT和ADAPT+联合随访≥1年的AChR-Ab+参与者中,平均年化周期数为每年4.7个(中位数[范围]为5.0[0.5-7.6])。ADAPT+的结果证实了依加替莫德在ADAPT中的显著临床改善,并支持其长期安全性、耐受性和疗效,以及治疗gMG的个体化给药方案。https://classic.clinicaltrials.gov/ct2/show/NCT03770403,NCT03770403。
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引用次数: 0
Editorial: Clinical experience of open cerebral revascularization (bypass surgery) for the management of ischemic or hemorrhagic stroke 社论:治疗缺血性或出血性脑卒中的开放性脑血管再通(搭桥手术)临床经验
Pub Date : 2024-01-04 DOI: 10.3389/fneur.2023.1354100
Alexander F. Kuffer, Danielle Golub, Amir R. Dehdashti
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引用次数: 0
Editorial: Neurological dysfunction and diseases in high altitude 社论:高海拔地区的神经功能障碍和疾病
Pub Date : 2024-01-04 DOI: 10.3389/fneur.2023.1343786
Xudong Wen, Pan Long
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引用次数: 0
Editorial: Advances in hearing loss, tinnitus, and vertigo: mechanisms and treatment 社论:听力损失、耳鸣和眩晕的研究进展:机制与治疗
Pub Date : 2024-01-03 DOI: 10.3389/fneur.2023.1344956
Lidong Zhao, Wei Sun, Heng-Wai Yuen, Michael C. F. Tong
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引用次数: 0
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