Neurology and Therapy最新文献

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Factors and Reasons Associated with Hesitating to Seek Care for Migraine: Results of the OVERCOME (US) Study. 与偏头痛患者不愿就医有关的因素和原因:OVERCOME(美国)研究结果。
IF 3.9 3区 医学
Neurology and Therapy Pub Date : 2024-11-02 DOI: 10.1007/s40120-024-00668-9
Robert E Shapiro, Eva Jolanda Muenzel, Robert A Nicholson, Anthony J Zagar, Michael L Reed, Dawn C Buse, Susan Hutchinson, Sait Ashina, Eric M Pearlman, Richard B Lipton
{"title":"Factors and Reasons Associated with Hesitating to Seek Care for Migraine: Results of the OVERCOME (US) Study.","authors":"Robert E Shapiro, Eva Jolanda Muenzel, Robert A Nicholson, Anthony J Zagar, Michael L Reed, Dawn C Buse, Susan Hutchinson, Sait Ashina, Eric M Pearlman, Richard B Lipton","doi":"10.1007/s40120-024-00668-9","DOIUrl":"https://doi.org/10.1007/s40120-024-00668-9","url":null,"abstract":"<p><strong>Introduction: </strong>Despite a variety of available treatment options for migraine, many people with migraine do not seek medical care, thereby reducing opportunities for diagnosis and effective treatment and potentially leading to missed opportunities to reduce the burden of disease. Understanding why people hesitate to seek care for migraine may help healthcare professionals and advocates address barriers and improve outcomes. The aim of this study, in a large adult population sample in the United States (US), was to identify factors associated with and reasons for hesitating to seek healthcare for migraine.</p><p><strong>Methods: </strong>The web-based OVERCOME (US) survey study identified adults with active migraine in a demographically representative US sample who answered questions about hesitating to seek care from a healthcare provider for migraine and reasons for hesitating. Supervised machine learning (random forest, least absolute shrinkage and selection operator) identified factors associated with hesitation; logistic regression models assessed association of factors on hesitation.</p><p><strong>Results: </strong>The study results show that of the 58,403 participants with active migraine who completed the OVERCOME (US) baseline survey and provided responses to the question on hesitating to seek care for migraine, 45.1% (n = 26,330/58,403) with migraine indicated that they had ever hesitated to seek care for migraine. Factors most associated with hesitating to seek care were hiding migraine (odds ratio [OR] = 2.69; 95% confidence interval [CI]: 2.50, 2.89), experiencing migraine-related stigma (OR = 2.13; 95% CI 1.95, 2.33), higher migraine-related disability (OR = 1.30; 95% CI 1.23, 1.38), and higher ictal cutaneous allodynia (OR = 1.26; 95% CI 1.19, 1.35). The most common reasons participants stated for hesitating included (1) 44.2% wanting to try and take care of migraine on their own, (2) 33.8% feeling that their migraine or headache would not be taken seriously, (3) 29.2% thinking that their migraine was not serious/painful enough, and (4) 27.4% not being able to afford it or not wanting to spend the money. The main limitation of the study includes the requirement for respondents to have internet, access which may have reflected cohort bias, and the quota sampling rather than random sampling to create a demographically representative sample.</p><p><strong>Conclusions: </strong>Hesitating to seek migraine care is common and is most strongly associated with hiding the disease and migraine-related stigma. Those experiencing higher migraine-related burden are more hesitant to seek the care that might alleviate the burden. These findings suggest that migraine's social context (e.g., stigma) is a major determinant of hesitance to seek migraine care.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Clinical Characteristics and Outcomes in Patients with Ruptured Middle Cerebral Artery Aneurysms: A Multicenter Study in Northern China. 大脑中动脉瘤破裂患者的临床特征和预后:中国北方多中心研究
IF 3.9 3区 医学
Neurology and Therapy Pub Date : 2024-11-01 DOI: 10.1007/s40120-024-00673-y
Xiuhu An, Jingliang Su, Bingxin Duan, Long Zhao, Bangyue Wang, Yan Zhao, Tianxing Li, Shuai Zhou, Xinyu Yang, Zhenbo Liu
{"title":"Clinical Characteristics and Outcomes in Patients with Ruptured Middle Cerebral Artery Aneurysms: A Multicenter Study in Northern China.","authors":"Xiuhu An, Jingliang Su, Bingxin Duan, Long Zhao, Bangyue Wang, Yan Zhao, Tianxing Li, Shuai Zhou, Xinyu Yang, Zhenbo Liu","doi":"10.1007/s40120-024-00673-y","DOIUrl":"https://doi.org/10.1007/s40120-024-00673-y","url":null,"abstract":"<p><strong>Introduction: </strong>The long-term prognosis of ruptured middle cerebral artery aneurysms (MCAAs) in northern China remains unclear. The aim of this study is to analyze the epidemiological characteristics and long-term outcomes of ruptured MCAAs in northern China.</p><p><strong>Methods: </strong>We included patients who were consecutively admitted for ruptured MCAAs to 12 tertiary care centers in northern China from January 2017 to December 2020. Kaplan‒Meier curves were used to compare survival in hazard strata. The Cox proportional hazards model was used to analyze risk factors and mortality risk, whereas logistic regression was used to identify factors influencing 2-year survival. Subgroup analyses were performed to verify the robustness of the results.</p><p><strong>Results: </strong>Data on 959 patients with ruptured MCAAs were analyzed; 16.4% of these patients had ruptured intracranial aneurysms (RIAs) and were registered in the Chinese cerebral aneurysm database. The mean follow-up duration was 3.0 years (range 0-6.2 years). The 3-month and 2-year mortality rates were 15.5% and 18.2%, respectively. The risk factors for mortality were identified via Cox regression and were as follows: age > 70 years, previous stroke, combined intracerebral hemorrhage (ICH)/intraventricular hemorrhage (IVH), poor Hunt and Hess grade, multiple aneurysms, and conservative treatment (CT). The positive association between the risk of death and CT was consistent across subgroups. According to logistic regression, hypertension, previous stroke, combined ICH/IVH, Hunt and Hess grade, and WFNS (World Federation of Neurological Surgeons) score were identified as factors negatively influencing 2-year survival.</p><p><strong>Conclusion: </strong>We detail the epidemiologic characteristics and long-term outcomes of MCAAs. The risk factors for mortality included age > 70 years, previous stroke, combined ICH/IVH, poor Hunt and Hess grade, and multiple aneurysms. Compared with microsurgical treatment (MST), CT is associated with an increased risk of mortality, while the risk of mortality associated with endovascular treatment (EVT) is not significantly different. Two-year survival was associated with hypertension, previous stroke, ICH/IVH, and poor grades at admission.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142562484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Huntington Disease Health Related Quality of Life, Function and Well Being: The Patient's Perspective. 亨廷顿病与健康相关的生活质量、功能和福祉:患者的视角。
IF 3.9 3区 医学
Neurology and Therapy Pub Date : 2024-10-07 DOI: 10.1007/s40120-024-00655-0
Jesús Pérez-Pérez, Sofía García-López, Tamara Fernández Valle, Cèlia Painous, Maria Rosa Querol-Pascual, Pedro J García Ruiz, Elena Bellosta Diago, Esther Cubo Delgado, Barbara Vives Pastor, María Carmen Peiró Villaplana, Idaira Martín Santana, María Blázquez Estrada, Matilde Calopa Garride, Pablo Mir Ribera, Carmen Álvarez, Jorge Maurino, Anna de Prado, José Luis López-Sendón
{"title":"Huntington Disease Health Related Quality of Life, Function and Well Being: The Patient's Perspective.","authors":"Jesús Pérez-Pérez, Sofía García-López, Tamara Fernández Valle, Cèlia Painous, Maria Rosa Querol-Pascual, Pedro J García Ruiz, Elena Bellosta Diago, Esther Cubo Delgado, Barbara Vives Pastor, María Carmen Peiró Villaplana, Idaira Martín Santana, María Blázquez Estrada, Matilde Calopa Garride, Pablo Mir Ribera, Carmen Álvarez, Jorge Maurino, Anna de Prado, José Luis López-Sendón","doi":"10.1007/s40120-024-00655-0","DOIUrl":"https://doi.org/10.1007/s40120-024-00655-0","url":null,"abstract":"<p><strong>Background: </strong>Limited information is available on patients' experience living with Huntington's disease (HD). The primary objective of this study was to assess the health-related quality of life and well being of patients with HD.</p><p><strong>Methods: </strong>A non-interventional, cross-sectional study was conducted in 17 hospitals-based movement disorders units in Spain. Patients aged ≥ 18 years, genetically HD diagnosed [with a diagnostic confidence level score of 4, and an Independence Scale (IS) score ≥ 70] were included. The primary variables were the Huntington's Disease Health-related Quality of Life (HDQLIFE) scores and results of the Satisfaction with Life Scale (SWLS). Secondary outcomes include the Unified HD Rating Scale (UHDRS), Beck Hopelessness Scale (BHS), Stigma Scale for Chronic Illness (SSCI-8), Beck Depression Inventory-Fast Screen (BDI-FS) and Problem Behaviours Assessment for HD short Version (PBA-S).</p><p><strong>Results: </strong>A total of 102 patients were included. The mean age (SD) was 53.1 (12.1) years and 56% were male. Most of the patients (99.0%) showed motor symptoms (87.3%), behavioural and psychiatric disturbances (59.8%), or cognitive impairment (20.6%). HDQLIFE domain score means (SD) includes concern with death and dying 45.97 (9.60) end-of-life planning 37.91 (8.84), and meaning and purpose 44.74 (9.05). SWLS score mean was 24.25 (7.33). Depressive symptoms were found in 37.4% of patients and moderate-to-severe feelings of hopelessness in 32.9%. The prevalence of stigma was 55.9% (n = 57).</p><p><strong>Conclusion: </strong>HD impacted quality of life, with prevalent motor, psychiatric symptoms and cognitive impairment. Patient perspectives may provide complementary information to implement specific interventions.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Safety and Effectiveness of Satralizumab in Japanese Patients with Neuromyelitis Optica Spectrum Disorder: A 6-month Interim Analysis of Post-marketing Surveillance. 日本神经脊髓炎谱系障碍患者使用萨曲珠单抗的安全性和有效性:上市后监测的 6 个月中期分析》。
IF 3.9 3区 医学
Neurology and Therapy Pub Date : 2024-10-01 Epub Date: 2024-07-16 DOI: 10.1007/s40120-024-00640-7
Takashi Yamamura, Noriko Isobe, Izumi Kawachi, Chiyoko Nohara, Yusei Miyazaki, Minami Tomita, Takahiko Tsumuraya, Katsuhisa Yamashita, Jin Nakahara, Ichiro Nakashima, Kazuo Fujihara
{"title":"Safety and Effectiveness of Satralizumab in Japanese Patients with Neuromyelitis Optica Spectrum Disorder: A 6-month Interim Analysis of Post-marketing Surveillance.","authors":"Takashi Yamamura, Noriko Isobe, Izumi Kawachi, Chiyoko Nohara, Yusei Miyazaki, Minami Tomita, Takahiko Tsumuraya, Katsuhisa Yamashita, Jin Nakahara, Ichiro Nakashima, Kazuo Fujihara","doi":"10.1007/s40120-024-00640-7","DOIUrl":"10.1007/s40120-024-00640-7","url":null,"abstract":"<p><strong>Introduction: </strong>Satralizumab, an anti-interleukin-6 receptor antibody, is approved in Japan for relapse prevention in neuromyelitis optica spectrum disorder (NMOSD) and is undergoing post-marketing surveillance (PMS) of clinical use. We aimed to describe the real-world safety and effectiveness of satralizumab in Japanese patients with NMOSD.</p><p><strong>Methods: </strong>This is an ongoing PMS (planned completion: February 2027). This 6-month interim analysis assessed the safety and effectiveness of satralizumab in Japanese patients with NMOSD using data collected from August 2020 to July 2021.</p><p><strong>Results: </strong>Among 570 patients who participated, 523 (91.75%) were female and the mean ± standard deviation (SD) age was 52.4 ± 14.1 years. At baseline, NMOSD expanded disability status scale mean ± SD was 4.19 ± 2.19; 490 (85.96%) patients used glucocorticoids and 277 (48.59%) patients used immunosuppressants concomitantly. Of 570 satralizumab-treated patients, 85 (14.91%) had discontinued satralizumab treatment at 6 months. For the overall adverse drug reactions (ADRs), 76.22 (66.07-87.48) events/100 person-years occurred in 118 (20.70%) patients, and infections occurred in 28 (4.91%) patients. Serious infections occurred in 18 (3.15%) patients, with an event rate of 9.05 (5.80-13.47) events/100 person-years. Of the 24 events of serious infections, respiratory tract infections (29.17%; 7) and urinary tract infections (25.00%; 6) were the most common serious infection events. One fatal ADR (septic shock) suspected to be related to satralizumab was reported. The mean ± SD glucocorticoid dose reduced from 12.28 ± 10.17 mg/day at the index date to 8.11 ± 7.30 mg/day at 6 months. The Kaplan-Meier cumulative relapse-free rate (95% confidence interval) was 94.59% (92.25-96.23) at 6 months.</p><p><strong>Conclusion: </strong>In this study, satralizumab was found to be safe, well tolerated, and effective in patients with NMOSD in routine clinical practice. The results are consistent with those of previous clinical trials. The safety and effectiveness of satralizumab in Japanese patients with NMOSD will be analyzed over the 6-year surveillance period.</p><p><strong>Trial registration: </strong>UMIN Clinical Trials Registry, UMIN000041047.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11393251/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141620513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Quantitative Analysis of White Matter Hyperintensities as a Predictor of 1-Year Risk for Ischemic Stroke Recurrence. 白质过度密集的定量分析可预测缺血性中风 1 年后的复发风险。
IF 3.9 3区 医学
Neurology and Therapy Pub Date : 2024-10-01 Epub Date: 2024-08-13 DOI: 10.1007/s40120-024-00652-3
Yi Sun, Wenping Xia, Ran Wei, Zedong Dai, Xilin Sun, Jie Zhu, Bin Song, Hao Wang
{"title":"Quantitative Analysis of White Matter Hyperintensities as a Predictor of 1-Year Risk for Ischemic Stroke Recurrence.","authors":"Yi Sun, Wenping Xia, Ran Wei, Zedong Dai, Xilin Sun, Jie Zhu, Bin Song, Hao Wang","doi":"10.1007/s40120-024-00652-3","DOIUrl":"10.1007/s40120-024-00652-3","url":null,"abstract":"<p><strong>Introduction: </strong>This study evaluates the role of quantitative characteristics of white matter hyperintensities (WMHs) in predicting the 1-year recurrence risk of ischemic stroke.</p><p><strong>Methods: </strong>We conducted a retrospective analysis of 1061 patients with ischemic stroke from January 2018 to April 2021. WMHs were automatically segmented using a cluster-based method to quantify their volume and number of clusters (NoC). Additionally, two radiologists independently rated periventricular and deep WMHs using the Fazekas scale. The cohort was divided into a training set (70%) and a testing set (30%). We employed Cox proportional hazards models to develop predictors based on quantitative WMH characteristics, Fazekas scores, and clinical factors, and compared their performance using the concordance index (C-index).</p><p><strong>Results: </strong>A total of 180 quantitative variables related to WMHs were extracted. A higher NoC in deep white matter and brainstem, advanced age (> 90 years old), specific stroke subtypes, and absence of discharge antiplatelets showed stronger associations with the risk of ischemic stroke recurrence within 1 year. The nomogram incorporating quantitative WMHs data showed superior discrimination compared to those based on the Fazekas scale or clinical factors alone, with C-index values of 0.709 versus 0.647 and 0.648, respectively, in the testing set. Notably, a combined model including both WMHs and clinical factors achieved the highest predictive accuracy, with a C-index of 0.735 in the testing set.</p><p><strong>Conclusion: </strong>Quantitative assessment of WMHs provides a valuable neuro-imaging tool for enhancing the prediction of ischemic stroke recurrence risk.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11393268/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Effectiveness of Nusinersen in Adolescents and Adults with Spinal Muscular Atrophy: Systematic Review and Meta-analysis. Nusinersen 对青少年和成人脊髓性肌肉萎缩症患者的疗效:系统回顾与元分析》。
IF 3.9 3区 医学
Neurology and Therapy Pub Date : 2024-10-01 Epub Date: 2024-09-02 DOI: 10.1007/s40120-024-00653-2
Tim Hagenacker, Lorenzo Maggi, Giorgia Coratti, Bora Youn, Stephanie Raynaud, Angela D Paradis, Eugenio Mercuri
{"title":"Effectiveness of Nusinersen in Adolescents and Adults with Spinal Muscular Atrophy: Systematic Review and Meta-analysis.","authors":"Tim Hagenacker, Lorenzo Maggi, Giorgia Coratti, Bora Youn, Stephanie Raynaud, Angela D Paradis, Eugenio Mercuri","doi":"10.1007/s40120-024-00653-2","DOIUrl":"10.1007/s40120-024-00653-2","url":null,"abstract":"<p><strong>Introduction: </strong>Nusinersen clinical trials have limited data on adolescents and adults with 5q-associated spinal muscular atrophy (SMA). We conducted a systematic literature review (SLR) and meta-analysis to assess effectiveness of nusinersen in adolescents and adults with SMA in clinical practice.</p><p><strong>Methods: </strong>Our search included papers published 12/23/2016 through 07/01/2022 with ≥ 5 individuals ≥ 13 years of age and with ≥ 6 months' data on ≥ 1 selected motor function outcomes [Hammersmith Functional Motor Scale-Expanded (HFMSE), Revised Upper Limb Module (RULM), and Six-Minute Walk Test (6MWT)]. For meta-analysis, effect sizes were pooled using random-effects models. To understand treatment effects by disease severity, subgroup meta-analysis by SMA type and ambulatory status was conducted.</p><p><strong>Results: </strong>Fourteen publications including 539 patients followed up to 24 months met inclusion criteria for the SLR. Patients were age 13-72 years and most (99%) had SMA Type II or III. Modest improvement or stability in motor function was consistently observed at the group level. Significant mean increases from baseline were observed in HFMSE [2.3 points (95% CI 1.3-3.3)] with 32.1% (21.7-44.6) of patients demonstrating a clinically meaningful increase (≥ 3 points) at 18 months. Significant increases in RULM were consistently found, with a mean increase of 1.1 points (0.7-1.4) and 38.3% (30.3-47.1) showing a clinically meaningful improvement (≥ 2 points) at 14 months. Among ambulatory patients, there was a significant increase in mean 6MWT distance of 25.0 m (8.9-41.2) with 50.9% (33.4-68.2) demonstrating a clinically meaningful improvement (≥ 30 m) at 14 months. The increases in HFMSE were greater for less severely affected patients, whereas more severely affected patients showed greater improvement in RULM.</p><p><strong>Conclusions: </strong>Findings provide consolidated evidence that nusinersen is effective in improving or stabilizing motor function in many adolescents and adults with a broad spectrum of SMA.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11393259/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142109932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Population Pharmacokinetic Modeling and Simulation for Dose Optimization of GB-5001, a Long-Acting Intramuscular Injection of Donepezil, in Healthy Participants. 为优化多奈哌齐长效肌内注射剂 GB-5001 在健康参试者中的剂量而进行的群体药代动力学建模和模拟。
IF 3.9 3区 医学
Neurology and Therapy Pub Date : 2024-10-01 Epub Date: 2024-08-10 DOI: 10.1007/s40120-024-00643-4
Juyoung Khwarg, Heeyong Lee, Kyung-Sang Yu, Eunyoung Seol, Jae-Yong Chung
{"title":"Population Pharmacokinetic Modeling and Simulation for Dose Optimization of GB-5001, a Long-Acting Intramuscular Injection of Donepezil, in Healthy Participants.","authors":"Juyoung Khwarg, Heeyong Lee, Kyung-Sang Yu, Eunyoung Seol, Jae-Yong Chung","doi":"10.1007/s40120-024-00643-4","DOIUrl":"10.1007/s40120-024-00643-4","url":null,"abstract":"<p><strong>Introduction: </strong>GB-5001 is an intramuscular (IM) formulation of donepezil under development for the treatment of Alzheimer's disease. The objective of this study was to develop a population pharmacokinetic (PK) model for donepezil in both IM and oral formulations, and to optimize the IM dosage of GB-5001 using bioequivalence (BE) simulation.</p><p><strong>Methods: </strong>A population PK model of donepezil was developed using NONMEM. It was based on plasma concentration data from a Phase 1 dose escalation study, which involved a single administration of donepezil IM formulation at doses of 70, 140, and 280 mg, and the oral formulation at 10 mg. The model was evaluated based on goodness-of-fit plots, conditional weighted residuals, visual predictive checks, and bootstrapping. BE simulations were conducted using a parallel design between various doses of the IM formulation and the 10-mg dose of oral formulation.</p><p><strong>Results: </strong>The PKs of donepezil were best described by a two-compartment model, which incorporated distinct absorption compartments for the IM (dual first-order absorption and simultaneous zero-order absorption with lag time) and oral (first-order absorption with lag time) formulations. Based on the simulation results, an IM dosage range of 210-215 mg in a sample size of over 92 was estimated to achieve a success rate of approximately 80% for BE.</p><p><strong>Conclusion: </strong>The population PK model well explained the PKs of donepezil following administration of both the IM and oral formulations. This model could be applied for the design and dose selection of future BE trials.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier, NCT05525780.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11393366/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141913410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Presurgical Use of Cenobamate for Adult and Pediatric Patients Referred for Epilepsy Surgery: Expert Panel Recommendations. 对转诊接受癫痫手术的成人和儿童患者在术前使用塞诺巴马酯:专家组建议。
IF 3.9 3区 医学
Neurology and Therapy Pub Date : 2024-10-01 Epub Date: 2024-08-18 DOI: 10.1007/s40120-024-00651-4
Kenneth D Laxer, Christopher J Elder, Giancarlo Di Gennaro, Louis Ferrari, Gregory L Krauss, Jacob Pellinen, William E Rosenfeld, Vicente Villanueva
{"title":"Presurgical Use of Cenobamate for Adult and Pediatric Patients Referred for Epilepsy Surgery: Expert Panel Recommendations.","authors":"Kenneth D Laxer, Christopher J Elder, Giancarlo Di Gennaro, Louis Ferrari, Gregory L Krauss, Jacob Pellinen, William E Rosenfeld, Vicente Villanueva","doi":"10.1007/s40120-024-00651-4","DOIUrl":"10.1007/s40120-024-00651-4","url":null,"abstract":"<p><p>Cenobamate has demonstrated efficacy in patients with treatment-resistant epilepsy, including patients who continued to have seizures after epilepsy surgery. This article provides recommendations for cenobamate use in patients referred for epilepsy surgery evaluation. A panel of six senior epileptologists from the United States and Europe with experience in presurgical evaluation of patients with epilepsy and in the use of antiseizure medications (ASMs) was convened to provide consensus recommendations for the use of cenobamate in patients referred for epilepsy surgery evaluation. Many patients referred for surgical evaluation may benefit from ASM optimization; both ASM and surgical treatment should be individualized. Based on previous clinical studies and the authors' clinical experience with cenobamate, a substantial proportion of patients with treatment-resistant epilepsy can become seizure-free with cenobamate. We recommend a cenobamate trial and ASM optimization in parallel with presurgical evaluations. Cenobamate can be started before phase two monitoring, especially in patients who are found to be suboptimal surgery candidates. As neurostimulation therapies are generally palliative, we recommend trying cenobamate before vagus nerve stimulation (VNS), deep brain stimulation, or responsive neurostimulation (RNS). In surgically remediable cases (mesial temporal sclerosis, benign discrete lesion in non-eloquent cortex, cavernous angioma, etc.), cenobamate use should not delay imminent surgery; however, a patient may decide to defer or even cancel surgery should they achieve sustained seizure freedom with cenobamate. This decision should be made on an individual, case-by-case basis based on seizure etiology, patient preferences, potential surgical risks (mortality and morbidity), and likely surgical outcome. The addition of cenobamate after unsuccessful surgery or palliative neuromodulation may also be associated with better outcomes.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11393364/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Population-Based Analysis of 6534 Seizure Emergency Cases from Emergency Medical Services Data. 对来自紧急医疗服务数据的 6534 例癫痫发作急诊病例进行基于人群的分析。
IF 3.9 3区 医学
Neurology and Therapy Pub Date : 2024-10-01 Epub Date: 2024-07-02 DOI: 10.1007/s40120-024-00641-6
Angela Gerhard, Felix Rosenow, Luis Möckel, Lars Jöres, Yuanjun Ma, Heidi Shiow Chyong Liou, Adam Strzelczyk
{"title":"Population-Based Analysis of 6534 Seizure Emergency Cases from Emergency Medical Services Data.","authors":"Angela Gerhard, Felix Rosenow, Luis Möckel, Lars Jöres, Yuanjun Ma, Heidi Shiow Chyong Liou, Adam Strzelczyk","doi":"10.1007/s40120-024-00641-6","DOIUrl":"10.1007/s40120-024-00641-6","url":null,"abstract":"<p><strong>Introduction: </strong>Seizures are common reasons to call an ambulance, and this study aims to analyze the burden of seizures in the prehospital setting based on incidence, hospital admission rate, and costs.</p><p><strong>Methods: </strong>This was a population-based, cross-sectional analysis of prehospital emergency medical services (EMS) data on suspected seizure cases from the federal state of Hesse, Germany, in 2019.</p><p><strong>Results: </strong>A total of 6534 suspected seizure cases were identified, of which most were those with a known seizure disorder. Incidence rate for epilepsy-related seizures (ES; pediatric epilepsy, first seizure [1stS], seizure with known seizure disorder [SEPI]) was 205.7 per 100,000 inhabitants and incidence rate for pediatric febrile seizures (PFS) was 36.7 per 100,000 inhabitants, corresponding to 171,275 ES and 28,500 PFS (99.3% < 18 years) cases in Germany. A prehospital EMS physician was involved in 40.0% (SEPI) to 54.4% (PFS) of suspected seizure cases. Depending on the type of seizure, 70.7% (SEPI) to 80.9% (1stS) were admitted to hospital for inpatient stay of ≥ 24 h. An additional 4% (PFS) to 16% (1stS) of cases needed immediate intervention at hospital. Prehospital EMS staff needed 8:24 min:s (SD 7:24; n = 5004) after the emergency call to arrive at the scene of the ES and 10:58 min:s (SD 27:39; n = 321) for PFS. ES and PFS cases caused estimated costs of 48.5 and 8.1 million euros for Germany in 2019, respectively, not including hospital treatment-related costs.</p><p><strong>Conclusion: </strong>This study identified a high number of suspected seizure-related emergency cases and proportion of patients admitted to hospitals, as well as high associated costs in Germany.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11393217/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141492819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Patient Preference for Subcutaneous Versus Intravenous Administration with Every-6-Week Natalizumab (Tysabri®) Dosing: NOVA Phase IIIb Extension Study (Part 2). 患者对每 6 周一次纳他珠单抗 (Tysabri®) 皮下给药与静脉给药的偏好:NOVA IIIb 期扩展研究(第二部分)。
IF 3.9 3区 医学
Neurology and Therapy Pub Date : 2024-10-01 Epub Date: 2024-07-24 DOI: 10.1007/s40120-024-00647-0
Heinz Wiendl, John Foley, Gilles Defer, Lana Zhovtis Ryerson, Jeffrey A Cohen, Douglas L Arnold, Helmut Butzkueven, Gary R Cutter, Gavin Giovannoni, Joep Killestein, Rose Domingo-Horne, Marie Toukam, Aimie Nunn, Amir-Hadi Maghzi, Robert Kuhelj, Tyler Lasky
{"title":"Patient Preference for Subcutaneous Versus Intravenous Administration with Every-6-Week Natalizumab (Tysabri<sup>®</sup>) Dosing: NOVA Phase IIIb Extension Study (Part 2).","authors":"Heinz Wiendl, John Foley, Gilles Defer, Lana Zhovtis Ryerson, Jeffrey A Cohen, Douglas L Arnold, Helmut Butzkueven, Gary R Cutter, Gavin Giovannoni, Joep Killestein, Rose Domingo-Horne, Marie Toukam, Aimie Nunn, Amir-Hadi Maghzi, Robert Kuhelj, Tyler Lasky","doi":"10.1007/s40120-024-00647-0","DOIUrl":"10.1007/s40120-024-00647-0","url":null,"abstract":"<p><strong>Introduction: </strong>Following NOVA (part 1) and the approval of the subcutaneous (SC) route of administration of natalizumab by the European Medicines Agency, an extension phase of the NOVA phase IIIb study (part 2) was initiated to collect patient preference data for SC versus intravenous (IV) dosing in patients receiving every-6-week (Q6W) dosing of natalizumab. This study was performed to evaluate patient preference for SC versus IV natalizumab administration and explore the efficacy, safety, and pharmacology characteristics of both routes of administration.</p><p><strong>Methods: </strong>In part 2, participants received natalizumab (Tysabri<sup>®</sup>) 300 mg via IV infusion Q6W for 36 weeks and then were randomized to 48 weeks of crossover treatment (24 weeks SC Q6W and 24 weeks IV Q6W, or vice versa). The primary endpoint was the proportion of participants who indicated a preference for natalizumab SC administration on the Patient Preference Questionnaire.</p><p><strong>Results: </strong>A total of 153 participants were randomized in NOVA part 2. Of 123 with patient preference data, 108 (87.8%) preferred the SC route of administration for natalizumab over the IV route; 102 (82.9%) specified \"requires less time in the clinic\" as the reason for the SC preference.</p><p><strong>Conclusion: </strong>In NOVA (part 2), most participants on Q6W dosing of natalizumab preferred SC administration versus IV administration.</p><p><strong>Clinicaltrials: </strong>GOV: NCT03689972. INFOGRAPHIC.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11393236/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141752247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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