Neurology and Therapy最新文献

{"title":"Clinical and Polysomnographic Characteristics of Adult Patients with Suspected Obstructive Sleep Apnea from Different Sleep Clinics at a Single Tertiary Center.","authors":"Eunmi Lee, Hyunjo Lee","doi":"10.1007/s40120-024-00581-1","DOIUrl":"10.1007/s40120-024-00581-1","url":null,"abstract":"<p><strong>Introduction: </strong>The characteristics of patients across different sleep clinics may vary because they selectively visit specific specialists on the basis of their primary symptoms. This study aimed to compare the clinical and polysomnography (PSG) features of patients with suspected obstructive sleep apnea (OSA) at three sleep specialty clinics (otolaryngology [ENT], neurology [NR], and psychiatry [PSY]).</p><p><strong>Methods: </strong>We retrospectively analyzed the medical records and PSG reports of adult patients who underwent full-night PSG between January 2022 and June 2023 at a tertiary medical center. The demographic, questionnaire, and PSG variables were compared.</p><p><strong>Results: </strong>Of the 407 patients, 83.0% exhibited sleep-disordered breathing (apnea-hypopnea index ≥ 5) with varying severity among the specialty pathways. Patients in the ENT group (n = 231) were the youngest and had the shortest sleep latency and most severe OSA markers with the highest positive airway pressure (PAP) acceptance, while those in the NR group (n = 79) had similar OSA-related PSG parameters to those in the ENT group but were older and had more OSA-related comorbidities, although their PAP acceptance was relatively low. The PSY group (n = 97) included a significant proportion of patients with normal or mild OSA, a female majority, high levels of depression, and subjective sleep distress.</p><p><strong>Conclusion: </strong>Our results highlight the multidisciplinary aspects of sleep medicine and diverse patients, and specialist needs for diagnosing sleep disorders and PAP acceptance. Exploring the potential differences in prognosis and treatment responses across various sleep specialty clinics would facilitate the development of personalized strategies.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"399-414"},"PeriodicalIF":3.7,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10951132/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139681247","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}

{"title":"Twenty Years of Subcutaneous Interferon-Beta-1a for Multiple Sclerosis: Contemporary Perspectives.","authors":"Mark S Freedman, Patricia K Coyle, Kerstin Hellwig, Barry Singer, Daniel Wynn, Bianca Weinstock-Guttman, Silva Markovic-Plese, Andrew Galazka, Fernando Dangond, Julie Korich, Anthony T Reder","doi":"10.1007/s40120-023-00565-7","DOIUrl":"10.1007/s40120-023-00565-7","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is a chronic, progressive, inflammatory disorder of the central nervous system. Relapsing-remitting MS (RRMS), the most common form of the disease, is characterized by transient neurological dysfunction with concurrent accumulation of disability. Over the past three decades, disease-modifying therapies (DMTs) capable of reducing the frequency of relapses and slowing disability worsening have been studied and approved for use in patients with RRMS. The first DMTs were interferon-betas (IFN-βs), which were approved in the 1990s. Among them was IFN-β-1a for subcutaneous (sc) injection (Rebif^®), which was approved for the treatment of MS in Europe and Canada in 1998 and in the USA in 2002. Twenty years of clinical data and experience have supported the efficacy and safety of IFN-β-1a sc in the treatment of RRMS, including pivotal trials, real-world data, and extension studies lasting up to 15 years past initial treatment. Today, IFN-β-1a sc remains an important therapeutic option in clinical use, especially around pregnancy planning and lactation, and may also be considered for aging patients, in which MS activity declines and long-term immunosuppression associated with some alternative therapies is a concern. In addition, IFN-β-1a sc is used as a comparator in many clinical studies and provides a framework for research into the mechanisms by which MS begins and progresses.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"283-322"},"PeriodicalIF":3.7,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10951191/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139417588","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}

{"title":"Dyskinesia and Pain in Advanced Parkinson's Disease: Post Hoc Analysis from the Phase 3b, Open-Label, Randomized DYSCOVER Study.","authors":"Eric Freire-Alvarez, Paola Vanni, Egon Kurča, Lydia Lopez-Manzanares, Norbert Kovács, Cleanthe Spanaki, Tianming Gao, Lars Bergmann, Olga Sánchez-Soliño","doi":"10.1007/s40120-024-00583-z","DOIUrl":"10.1007/s40120-024-00583-z","url":null,"abstract":"<p><strong>Introduction: </strong>The DYSCOVER study was a phase 3b, open-label, randomized trial (NCT02799381) that evaluated levodopa-carbidopa intestinal gel (LCIG) versus optimized medical treatment (OMT) in patients with Parkinson's disease (PD) and a high burden of dyskinesia at baseline (defined as Unified Dyskinesia Rating Scale [UDysRS] total score ≥ 30). At week 12, patients receiving LCIG versus OMT experienced significant improvements in dyskinesia, pain, and health-related outcomes. The objective of this analysis was to examine correlations between dyskinesia, pain, and health-related outcomes in PD.</p><p><strong>Methods: </strong>This post hoc analysis assessed correlations between UDysRS, King's Parkinson's Disease Pain Scale (KPPS), 8-item Parkinson's Disease Questionnaire (PDQ-8), Unified Parkinson's Disease Rating Scale part II, Clinical Global Impression of Severity (CGI-S) or Change (CGI-C), and \"On\" time without troublesome dyskinesia at baseline and after 12 weeks of LCIG or OMT. Correlations were assessed by Pearson correlation coefficients (categorization: weak, r = 0.20-0.39; moderate, r = 0.40-0.59; strong, r ≥ 0.60).</p><p><strong>Results: </strong>Among 61 patients, moderate-to-strong positive and significant correlations were observed between UDysRS and KPPS scores (baseline, r = 0.47; week 12 change from baseline [CFB], r = 0.63; all p < 0.001). UDysRS and KPPS scores had moderate-to-strong positive and highly significant correlations with PDQ-8 scores (baseline, r = 0.45 and 0.46, respectively; CFB, r = 0.54 and 0.64, respectively; all p < 0.001). Moderate positive and significant correlations were observed between UDysRS and CGI-S/CGI-C scores (baseline, r = 0.41; CFB, r = 0.47; all p < 0.001).</p><p><strong>Conclusions: </strong>In patients with high dyskinesia burden, positive correlations were observed between dyskinesia, pain, and health-related quality of life (HRQoL) at baseline. Improvements in dyskinesia and pain were associated with improvements in HRQoL, demonstrating the clinical burden of troublesome dyskinesia.</p><p><strong>Trial registration number: </strong>Clinicaltrials.gov identifier NCT02799381.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"437-447"},"PeriodicalIF":3.7,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10951158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139723484","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}

{"title":"Long-Term Effectiveness of Galcanezumab in the Prevention of Migraine: An Italian Retrospective Analysis (REALITY).","authors":"Fabrizio Vernieri, Luigi Francesco Iannone, Simona Guerzoni, Antonio Russo, Piero Barbanti, Grazia Sances, Sabina Cevoli, Renata Rao, Carlo Lovati, Anna Ambrosini, Carlotta Buzzoni, Federico Battisti, Laura Vatteone, Steffy Martin Luther King, Federico Torelli","doi":"10.1007/s40120-024-00582-0","DOIUrl":"10.1007/s40120-024-00582-0","url":null,"abstract":"<p><strong>Background: </strong>Galcanezumab is approved in the European Union (EU) as migraine prophylaxis in adults with at least four migraine days per month. The aim of this retrospective observational study was to evaluate the long-term effectiveness of galcanezumab on migraine-related burdens and its impact on the use of healthcare resources for migraine prophylaxis in an Italian setting.</p><p><strong>Methods: </strong>This retrospective study was conducted in patients with migraine who initiated treatment with galcanezumab for migraine prevention between September 2019 and December 2020. Patient data for monthly migraine days (MMDs) and MMDs with acute medication intake were obtained by medical chart reviews. Information on patient-reported outcomes (using the Migraine Disability Assessment [MIDAS] questionnaire and Headache Impact Test 6 [HIT-6] questionnaire) and on the use of healthcare resources were also collected. The time points of interest were 1, 3, 6, 9, 12 months after the initiation of galcanezumab, and the most recent time point available during follow-up.</p><p><strong>Results: </strong>A total of 207 patients were enrolled in the study. Starting from month 3 after treatment initiation, more than half of the patients presented at least a 50% reduction in MMDs, and approximately one-third of non-responders at month 3 became responders at month 6. From month 3 to month 12, MMDs decreased on average by 10 days. Headache impact and disability, as well as migraine-associated health resource utilization decreased significantly during the treatment period. A positive significant association among the three dimensions of clinical burden (MMDs, MIDAS and days of acute medication intake) was also observed.</p><p><strong>Conclusion: </strong>The results of this Italian real-world study confirmed that galcanezumab has a rapid onset of effect and provides a long-term response among patients over different migraine-related burdens. The use of healthcare resources was also remarkably reduced.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"415-435"},"PeriodicalIF":3.7,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10951161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139703047","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}

{"title":"Safety and Tolerability of Combining CGRP Monoclonal Antibodies with Gepants in Patients with Migraine: A Retrospective Study.","authors":"Taoufik Alsaadi, Reem Suliman, Vanessa Santos, Ibrahim Al Qaisi, Princess Carmina, Batool Aldaher, Shadi Haddad, Yazan Bader","doi":"10.1007/s40120-024-00586-w","DOIUrl":"10.1007/s40120-024-00586-w","url":null,"abstract":"<p><strong>Introduction: </strong>The introduction of clacitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) has revolutionized the treatment of migraines. In clinical practice gepants might be considered as a valid option to treat acute attacks in patients with migraine who are treated with mAbs. However, the safety and tolerability of such a combination is not well addressed in the real-world setting. We designed this study to evaluate the safety and tolerability of combining CGRP mAbs with gepants in the management of migraines.</p><p><strong>Methods: </strong>This was a retrospective, real-world, exploratory study. The participants included within the study were adult (≥ 18 years) patients diagnosed with migraine. Screening for patients who were treated with at least one GCRP mAbs was done. Data was collected from one site, the American Center for Psychiatry and Neurology, Abu Dhabi UAE. A total of 516 patients taking CGRP mAbs were identified. Extracted data from patients' electronic medical records included patient demographics, migraine characteristics, prescribed treatments, and adverse events (AEs). The tolerability and safety of the combination therapy was evaluated on the basis of documented AEs.</p><p><strong>Results: </strong>Among the identified 516 patients, 234 were administered gepants in addition to the CRGP mAb (215, rimegepant; 19, ubrogepant). Eleven of the 234 patients switched from rimegepant to urogepant as a result of lack of efficacy; one patient switched from urogepant to zolmitriptan because of the lack of insurance coverage of the former medication. Among all the patients included in this study, three AEs were documented. These AEs were generally mild and transient and hence did not lead to discontinuation of treatment. Moreover, 42 of the 234 (17.9%) patients were switched from one class of CGRP mAbs to another at least once while continuing treatment with the assigned gepants.</p><p><strong>Conclusion: </strong>The findings of this study demonstrate that combining CGRP mAbs with gepants is a safe and well-tolerated treatment approach for migraine. Future studies are warranted to further validate these findings and explore long-term outcomes.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"465-473"},"PeriodicalIF":3.7,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10951184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139741530","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}

{"title":"Understanding the Symptoms and Impacts Experienced by People with Relapsing-Remitting MS: A Qualitative Investigation Using Semi-Structured Interviews.","authors":"Amy Barrett, Oyebimpe Olayinka-Amao, Tjalf Ziemssen, Trishna Bharadia, Christian Henke, Paul Kamudoni","doi":"10.1007/s40120-024-00584-y","DOIUrl":"10.1007/s40120-024-00584-y","url":null,"abstract":"<p><strong>Introduction: </strong>Multiple sclerosis (MS) is a disabling disease with unpredictable clinical manifestations. As clinical assessments may not fully capture the impact of MS on quality of life, they can be complemented by patient-reported outcome (PRO) measures to provide a more comprehensive picture of MS disease state and impact. The objectives of this study were to explore the experiences of people with relapsing-remitting MS, including symptoms and impacts on daily life, and to provide a conceptual model of MS outcomes.</p><p><strong>Methods: </strong>A literature review of studies that evaluated the experiences of people with MS was completed and combined with semi-structured concept elicitation interviews conducted with 14 people with relapsing-remitting MS in the USA.</p><p><strong>Results: </strong>The average age of the 14 participants was 43.9 (range 25-64) years, most were White (78.6%) and female (78.6%), and the mean duration since diagnosis was 6.6 (2-10) years. The most bothersome symptoms identified included fatigue (n = 9), cognitive dysfunction (n = 5), mobility/difficulty with walking (n = 3), and vision problems (n = 3). The most commonly reported impacts on daily life were balance problems/instability (n = 13), work life/productivity (n = 12), difficulty walking (n = 11), daily activities/household chores (n = 11), and leisure activities (n = 10).</p><p><strong>Conclusion: </strong>There was a high frequency of concepts associated with physical function, fatigue, and sensory-motor actions. A conceptual model was developed that captures the disease symptoms, impairments, and impacts identified in the interviews as well as known processes and symptoms identified in the literature search. This model underpins the appropriateness of PRO instruments, such as the PROMIS Fatigue (MS) 8a and PROMIS Physical Function (MS) 15a, which evaluate symptoms and impacts that matter most to people with MS.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"449-464"},"PeriodicalIF":3.7,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10951163/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139723485","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}

{"title":"Acute Treatment of Migraine: Expert Consensus Statements from the United Arab Emirates (UAE).","authors":"Taoufik Alsaadi, Deeb M Kayed, Abubaker Al-Madani, Ali Mohamed Hassan, Derk Krieger, Naji Riachi, Pournamy Sarathchandran, Suhail Al-Rukn","doi":"10.1007/s40120-023-00576-4","DOIUrl":"10.1007/s40120-023-00576-4","url":null,"abstract":"<p><strong>Introduction: </strong>Migraine, characterized by recurrent headaches and often accompanied by other symptoms like nausea, vomiting, and sensitivity to light and sound, significantly impacts patients' quality of life (QoL) and daily functioning. The global burden of migraines is reflected not only in terms of reduced QoL but also in the form of increased healthcare costs and missed work or school days. While UAE (United Arab Emirates)-specific consensus-based recommendations for the effective use of preventive calcitonin gene-related peptide (CGRP)-based migraine therapies have been published previously, an absence of such regional guidance on the management of acute migraine represents a gap that needs to be urgently addressed.</p><p><strong>Methods: </strong>A task force of eight neurologists from the UAE with expertise in migraine management conducted a comprehensive literature search and developed a set of expert statements on the management of acute migraine that were specific to the UAE context. To ensure diverse perspectives are considered, a Delphi panel comprising 16 neurologists plus the task force members was set up. Consensus was achieved using a modified Delphi survey method. Consensus was predefined as a median rating of 7 or higher without discordance (if > 25% of the Delphi panelists rate an expert statement as 3 or lower on the Likert scale). Expert statements achieving consensus were adopted.</p><p><strong>Results: </strong>The Modified Delphi method was used successfully to achieve consensus on all nine expert statements drafted by the task force. These consensus statements aim to provide a comprehensive guide for UAE healthcare professionals in treating acute migraine. The statements cover all aspects of acute migraine treatment, including what goals to set, the timing of treatment, treatment strategy to use in case of inadequate response to triptans, safety aspects of combining gepants for acute attacks with preventive CGRP-based therapies, special population (pregnant and pediatric patients) considerations, and the management of the most bothersome symptoms (MBS).</p><p><strong>Conclusions: </strong>Adopting these consensus statements on the treatment of acute migraine can help enhance patient care, improve outcomes, and standardize treatment practices in the UAE. The collaborative effort of experts with diverse experiences in developing these consensus statements will strengthen the credibility and applicability of these statements to various healthcare settings in the country.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"257-281"},"PeriodicalIF":3.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10951165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139491442","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}

{"title":"Impact of Istradefylline on Levodopa Dose Escalation in Parkinson's Disease: ISTRA ADJUST PD Study, a Multicenter, Open-Label, Randomized, Parallel-Group Controlled Study.","authors":"Taku Hatano, Renpei Sengoku, Hiroshi Nagayama, Naotake Yanagisawa, Asako Yoritaka, Keisuke Suzuki, Noriko Nishikawa, Yohei Mukai, Kyoichi Nomura, Norihito Yoshida, Morinobu Seki, Miho Kawabe Matsukawa, Hiroo Terashi, Katsuo Kimura, Jun Tashiro, Shigeki Hirano, Hidetomo Murakami, Hideto Joki, Tsuyoshi Uchiyama, Hideki Shimura, Kotaro Ogaki, Jiro Fukae, Yoshio Tsuboi, Kazushi Takahashi, Toshimasa Yamamoto, Kenichi Kaida, Ryoko Ihara, Kazutomi Kanemaru, Osamu Kano","doi":"10.1007/s40120-023-00574-6","DOIUrl":"10.1007/s40120-023-00574-6","url":null,"abstract":"<p><strong>Introduction: </strong>A higher levodopa dose is a risk factor for motor complications in Parkinson's disease (PD). Istradefylline (IST) is used as adjunctive treatment to levodopa in PD patients with off episodes, but its impact on levodopa dose titration remains unclear. The objective of this study was to investigate the effect of IST on levodopa dose escalation in PD patients with wearing-off.</p><p><strong>Methods: </strong>This was a multicenter, open-label, randomized, parallel-group controlled study (ISTRA ADJUST PD) in which PD patients experiencing wearing-off (n = 114) who were receiving levodopa 300-400 mg/day were randomized to receive IST or no IST (control). Levodopa dose was escalated according to clinical severity. The primary endpoint was cumulative additional levodopa dose, and secondary endpoints were changes in symptom rating scales, motor activity determined by a wearable device, and safety outcomes.</p><p><strong>Results: </strong>The cumulative additional levodopa dose throughout 37 weeks and dose increase over 36 weeks were significantly lower in the IST group than in the control group (both p < 0.0001). The Movement Disorder Society Unified Parkinson's Disease Rating Scale Part I and device-evaluated motor activities improved significantly from baseline to 36 weeks in the IST group only (all p < 0.05). Other secondary endpoints were comparable between the groups. Adverse drug reactions (ADRs) occurred in 28.8% and 13.2% of patients in the IST and control groups, respectively, with no serious ADRs in either group.</p><p><strong>Conclusion: </strong>IST treatment reduced levodopa dose escalation in PD patients, resulting in less cumulative levodopa use. Adjunctive IST may improve motor function more objectively than increased levodopa dose in patients with PD.</p><p><strong>Trial registration: </strong>Japan Registry of Clinical Trials: jRCTs031180248.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"323-338"},"PeriodicalIF":3.7,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10951171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139472789","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}

{"title":"Population Pharmacokinetic Analysis to Support and Facilitate Switching from Risperidone Formulations to Rykindo in Patients with Schizophrenia.","authors":"Wenyan Wang, Xiaofeng Wang, Ying Dong, David P Walling, Pinglan Liu, Wanhui Liu, Yanan Shi, Kaoxiang Sun","doi":"10.1007/s40120-024-00578-w","DOIUrl":"10.1007/s40120-024-00578-w","url":null,"abstract":"<p><strong>Introduction: </strong>RYKINDO® (Rykindo) is a novel, long-acting injectable risperidone formulation administered biweekly (Q2W) through intramuscular gluteal injection for the treatment of schizophrenia in adult patients. This analysis was conducted to demonstrate that the clinical outcomes of Rykindo are equivalent to those of RISPERDAL CONSTA® (Consta; Q2W), and to establish a dosing methodology to switch from Consta to Rykindo, as well as to introduce Rykindo to patients who are currently on oral RISPERDAL® (Risperdal).</p><p><strong>Methods: </strong>Population pharmacokinetic (PK) models for Rykindo and Consta were developed using a nonlinear mixed-effects model with the data from phase 1 studies. A model-based simulation was also conducted using NONMEM.</p><p><strong>Results: </strong>The PK profiles of Rykindo and Consta were adequately represented by a one-compartment model with an immediate release followed by an intermediate and third main release. Drug release of Rykindo was faster than for Consta, reaching steady state approximately 2-3 weeks earlier. The exposures of the active moiety of Rykindo and Consta were comparable at steady state. Model-based simulation indicated that switching from Consta to Rykindo requires administration of the first Rykindo injection within 4-5 weeks following the last Consta injection. For patients taking Risperdal, introducing Rykindo with 1 week of Risperdal supplemental for once-daily dosing (QD) can achieve comparable or superior exposure to that of Consta with 3 weeks of oral QD supplements. A dosing window of ± 3 days for Rykindo was recommended.</p><p><strong>Conclusions: </strong>This established approach provides guidance to physicians to initiate Rykindo therapy in adult patients with schizophrenia.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier, NCT02055287, NCT02186769 and NCT02091388.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"355-372"},"PeriodicalIF":3.7,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10951188/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139513438","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}

{"title":"Monitoring of Perioperative Microcirculation Dysfunction by Near-Infrared Spectroscopy for Neurological Deterioration and Prognosis of Aneurysmal Subarachnoid Hemorrhage: An Observational, Longitudinal Cohort Study.","authors":"Shunyan Yang, Binbin Tan, Jie Lin, Xia Wang, Congying Fu, Kaishan Wang, Jinyu Qian, Jin Liu, Jishu Xian, Liang Tan, Hua Feng, Yujie Chen, Lihua Wang","doi":"10.1007/s40120-024-00585-x","DOIUrl":"10.1007/s40120-024-00585-x","url":null,"abstract":"<p><strong>Introduction: </strong>No evidence has established a direct causal relationship between early microcirculation disturbance after aneurysmal subarachnoid hemorrhage (aSAH) and neurological function prognosis, which is the key pathophysiological mechanism of early brain injury (EBI) in patients with aSAH.</p><p><strong>Methods: </strong>A total of 252 patients with aSAH were enrolled in the Neurosurgical Intensive Care Unit of Southwest Hospital between January 2020 and December 2022 and divided into the no neurological deterioration, early neurological deterioration, and delayed neurological deterioration groups. Indicators of microcirculation disorders in EBI included regional cerebral oxygen saturation (rSO₂) measured by near-infrared spectroscopy (NIRS), brain oxygen monitoring, and other clinical parameters for evaluating neurological function and determining the prognosis of patients with aSAH.</p><p><strong>Results: </strong>Our data suggest that the rSO₂ is generally lower in patients who develop neurological deterioration than in those who do not and that there is at least one time point in the population of patients who develop neurological deterioration where left and right cerebral hemisphere differences can be significantly monitored by NIRS. An unordered multiple-classification logistic regression model was constructed, and the results revealed that multiple factors were effective predictors of early neurological deterioration: reoperation, history of brain surgery, World Federation of Neurosurgical Societies (WFNS) grade 4-5, Fisher grade 3-4, SAFIRE grade 3-5, abnormal serum sodium and potassium levels, and reduced rSO₂ during the perioperative period. However, for delayed neurological deterioration in patients with aSAH, only a history of brain surgery and perioperative RBC count were predictive indicators.</p><p><strong>Conclusions: </strong>The rSO₂ concentration in patients with neurological deterioration is generally lower than that in patients without neurological deterioration, and at least one time point in the population with neurological deterioration can be significantly monitored via NIRS. However, further studies are needed to determine the role of microcirculation and other predictive factors in the neurocritical management of EBI after aSAH, as these factors can reduce the incidence of adverse outcomes and mortality during hospitalization.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"475-495"},"PeriodicalIF":3.7,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10951157/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139898162","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}