Neurology and Therapy最新文献

{"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":" ","pages":"1349-1360"},"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}

{"title":"Predicted Expenditure for Prescription Drugs for Multiple Sclerosis in the Italian Market Between 2023 and 2028: Results of the Oracle Project.","authors":"Damiano Paolicelli, Giovanna Borriello, Raffaella Clerici, Elena Colombo, Davide Croce, Emanuele D'Amico, Nicola De Rossi, Alessia Di Sapio, Giuseppe Fenu, Davide Maimone, Girolama A Marfia, Marcello Moccia, Paola Perini, Maria G Piscaglia, Lorenzo Razzolini, Massimo Riccaboni, Elisabetta Signoriello, Gianluca Agostoni, Alberto Farina, Margaret Mondino, Francesco Berruto, Alessia Tettamanti, Francesca Donnaloja, Carla Tortorella","doi":"10.1007/s40120-024-00644-3","DOIUrl":"10.1007/s40120-024-00644-3","url":null,"abstract":"<p><strong>Introduction: </strong>Multiple sclerosis (MS) is a chronic neurodegenerative disease that leads to impaired cognitive function and accumulation of disability, with significant socioeconomic burden. Serious unmet need in the context of managing MS has given rise to ongoing research efforts, leading to the launch of new drugs planned for the near future, and subsequent concerns about the sustainability of healthcare systems. This study assessed the changes in the Italian MS market and their impact on the expenditures of the Italian National Healthcare Service between 2023 and 2028.</p><p><strong>Methods: </strong>A horizon-scanning model was developed to estimate annual expenditure from 2023 to 2028. Annual expenditure for MS was calculated by combining the number of patients treated with each product (clinical inputs) and the yearly costs of therapy (economic inputs). Baseline inputs (2020-2022) were collected from IQVIA^® real-world data, while input estimation for the 5-year forecast was integrated with analog analyses and the insights of clinicians and former payers.</p><p><strong>Results: </strong>The number of equivalent patients treated in 2028 in Italy was estimated at around 67,000, with an increase of 10% versus 2022. In terms of treatment pattern evolution, first-line treatments are expected to reduce their shares from 47% in 2022 to 27% in 2028, and Bruton tyrosine kinase inhibitors are expected to reach 23% of patient shares. Overall, expenditure for MS is estimated to decrease from €721 million in 2022 to €551 million in 2028, mainly due to losses of exclusivity and renegotiation of drug prices.</p><p><strong>Conclusion: </strong>Despite the increase in the number of patients treated for MS and the launch of new molecules that will reach high market penetration, the model confirmed sustainability for the Italian National Healthcare Service.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"1415-1430"},"PeriodicalIF":3.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11393242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141875501","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":"Systemic Inflammatory Response Index and the Short-Term Functional Outcome of Patients with Acute Ischemic Stroke: A Meta-analysis.","authors":"Ying Han, Nan Lin","doi":"10.1007/s40120-024-00645-2","DOIUrl":"10.1007/s40120-024-00645-2","url":null,"abstract":"<p><strong>Introduction: </strong>The systemic inflammatory response index (SIRI) is a novel indicator of systemic inflammation derived from the absolute counts of neutrophils, monocytes, and lymphocytes. The aim of this meta-analysis was to evaluate the association between SIRI and functional outcome in patients with acute ischemic stroke (AIS).</p><p><strong>Methods: </strong>The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed in this meta-analysis. Relevant cohort studies were retrieved by a search of electronic databases including PubMed, Web of Science, Embase, Wanfang, and China National Knowledge Infrastructure from database inception to February 9, 2024. A poor functional outcome was defined as a modified Rankin Scale ≥ 3 within 3 months after disease onset. A random-effects model was used to combine the data by incorporating the influence of between-study heterogeneity. The protocol of the meta-analysis was not prospectively registered in PROSPERO.</p><p><strong>Results: </strong>Fourteen cohort studies were included. Pooled results showed that a high SIRI at admission was associated with increased risk of poor functional outcome within 3 months (odds ratio [OR]: 1.57, 95% confidence interval: 1.39 to 1.78, p < 0.001; I² = 0%). Results of the meta-regression analysis suggested that the cutoff for defining a high SIRI was positively related to the OR for the association between SIRI and the risk of poor functional outcome (coefficient = 0.13, p = 0.03), while other variables including sample size, mean age, severity of stroke at admission, percentage of men, current smokers, or patients with diabetes did not significantly modify the results. Subgroup analyses according to study design, main treatments, and study quality scores showed similar results.</p><p><strong>Conclusion: </strong>A high SIRI may be associated with a poor functional outcome in patients after AIS.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"1431-1451"},"PeriodicalIF":3.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11393365/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141907273","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":"Correction to: Assessing the Long-Term (48-Week) Effectiveness, Safety, and Tolerability of Fremanezumab in Migraine in Real Life: Insights from the Multicenter, Prospective, FRIEND3 Study.","authors":"Piero Barbanti, Gabriella Egeo, Stefania Proietti, Florindo d'Onofrio, Cinzia Aurilia, Cinzia Finocchi, Laura Di Clemente, Maurizio Zucco, Alberto Doretti, Stefano Messina, Massimo Autunno, Angelo Ranieri, Antonio Carnevale, Bruno Colombo, Massimo Filippi, Miriam Tasillo, Steno Rinalduzzi, Pietro Querzani, Giuliano Sette, Lorenzo Forino, Francesco Zoroddu, Micaela Robotti, Alessandro Valenza, Cecilia Camarda, Laura Borrello, Marco Aguggia, Giovanna Viticchi, Carlo Tomino, Giulia Fiorentini, Bianca Orlando, Stefano Bonassi, Paola Torelli","doi":"10.1007/s40120-024-00648-z","DOIUrl":"10.1007/s40120-024-00648-z","url":null,"abstract":"","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"1505-1506"},"PeriodicalIF":3.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11393228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893923","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":"Practical Recommendations from the Gulf Region on the Therapeutic Use of Cladribine Tablets for the Management of Relapsing Multiple Sclerosis: Impact of the Latest Real-World Evidence on Clinical Practice.","authors":"Bassem Yamout, Raed Alroughani, Jihad Inshasi, Samar Farouk, Fatema Abdulla, Namareq Y Al-Jarki, Abdulla Alasmi, Sarmad Al Fahad, Jaber Alkhabouri, Khalid Al-Saffar, Beatrice Benedetti, Beatriz Canibano, Dirk Deleu, Ali Hassan, Pournamy Sarathchandran, Ahmed Shatila, Mohammad Abouelnaga, Mona Thakre, Miklos Szolics, Amir Boshra","doi":"10.1007/s40120-024-00650-5","DOIUrl":"10.1007/s40120-024-00650-5","url":null,"abstract":"<p><p>Cladribine tablets (CladT), like alemtuzumab, acts as an immune reconstitution therapy. However, CladT is administered orally (alemtuzumab is given by infusion) and without the potential for serious side effects that limit the therapeutic use of alemtuzumab in multiple sclerosis (MS). Treatment with CladT, given initially as short courses of treatment 1 year apart, provides years of freedom from MS disease activity in responders to treatment. The appearance of mild or moderate MS disease activity after the initial 2 years of treatment may prompt careful follow-up or a further course of CladT, depending on the nature of the activity and individual circumstances. The appearance of severe MS disease activity requires a switch to an alternative high-efficacy disease-modifying treatment (DMT). The accumulating data from CladT-treated people with MS in real-world studies, including those with follow-up durations extending for years beyond the initial treatment, have demonstrated long-term freedom from MS disease activity in a good proportion of patients. This clinical experience has also confirmed that treatment with CladT is generally safe and well tolerated. The best time to prescribe a high-efficacy DMT is the subject of debate, with evidence that earlier versus later use of such agents may provide more effective long-term protection from disability progression. High-efficacy DMTs have traditionally been reserved for use in people with MS and high disease activity on presentation or breakthrough disease on one or more DMTs, as per the current product labels. The latest evidence from real-world studies suggests that CladT is effective and safe in DMT-naïve patients, including those with shorter disease duration.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"1321-1335"},"PeriodicalIF":3.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11393234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889843","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":"Evaluating the Efficacy of CortexID Quantitative Analysis in Localization of the Epileptogenic Zone in Patients with Temporal Lobe Epilepsy.","authors":"Shuangshuang Li, Kun Guo, Yuanyuan Wang, Dianwei Wu, Yang Wang, Lanlan Feng, Junling Wang, Xiaoli Meng, Lei Ma, Hua He, Fei Kang","doi":"10.1007/s40120-024-00646-1","DOIUrl":"10.1007/s40120-024-00646-1","url":null,"abstract":"<p><strong>Introduction: </strong>There remains a critical need for precise localization of the epileptogenic foci in individuals with drug-resistant epilepsy (DRE). ¹⁸F-Fluorodeoxyglucose positron emission tomography (FDG-PET) imaging can reveal hypometabolic regions during the interval between seizures in patients with epilepsy. However, visual-based qualitative analysis is time-consuming and strongly influenced by physician experience. CortexID Suite is a quantitative analysis software that helps to evaluate PET imaging of the human brain. Therefore, we aimed to evaluate the efficacy of CortexID quantitative analysis in the localization of the epileptogenic zone in patients with temporal lobe epilepsy (TLE).</p><p><strong>Methods: </strong>A total of 102 patients with epilepsy who underwent ¹⁸F-FDG-PET examinations were included in this retrospective study. The PET visual analysis was interpreted by two nuclear medicine physicians, and the quantitative analysis was performed automatically using CortexID analysis software. The assumed epileptogenic zone was evaluated comprehensively by two skilled neurologists in the preoperative assessment of epilepsy. The accuracy of epileptogenic zone localization in PET visual analysis was compared with that in CortexID quantitative analysis.</p><p><strong>Results: </strong>The diagnostic threshold for the difference in the metabolic Z-score between the right and left sides of medial temporal lobe epilepsy (MTLE) was calculated as 0.87, and that for lateral temporal lobe epilepsy (LTLE) was 2.175. In patients with MTLE, the area under the curve (AUC) was 0.922 for PET visual analysis, 0.853 for CortexID quantitative analysis, and 0.971 for the combined diagnosis. In patients with LTLE, the AUC was 0.842 for PET visual analysis, 0.831 for CortexID quantitative analysis, and 0.897 for the combined diagnosis. These results indicate that the diagnostic efficacy of CortexID quantitative analysis is not inferior to PET visual analysis (p > 0.05), while combined analysis significantly increases diagnostic efficacy (p < 0.05). Among the 23 patients who underwent surgery, the sensitivity and specificity of PET visual analysis for localization were 95.4% and 66.7%, and the sensitivity and specificity of CortexID quantitative analysis were 100% and 50%.</p><p><strong>Conclusion: </strong>The diagnostic efficacy of CortexID quantitative analysis is comparable to PET visual analysis in the localization of the epileptogenic zone in patients with TLE. CortexID quantitative analysis combined with visual analysis can further improve the accuracy of epileptogenic zone localization.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"1403-1414"},"PeriodicalIF":3.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11393372/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141875500","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":"Pharmacotherapies for the Treatment of Progressive Supranuclear Palsy: A Narrative Review.","authors":"Elise E Dunning, Boris Decourt, Nasser H Zawia, Holly A Shill, Marwan N Sabbagh","doi":"10.1007/s40120-024-00614-9","DOIUrl":"10.1007/s40120-024-00614-9","url":null,"abstract":"<p><p>Progressive supranuclear palsy (PSP) is a neurodegenerative disorder resulting from the deposition of misfolded and neurotoxic forms of tau protein in specific areas of the midbrain, basal ganglia, and cortex. It is one of the most representative forms of tauopathy. PSP presents in several different phenotypic variations and is often accompanied by the development of concurrent neurodegenerative disorders. PSP is universally fatal, and effective disease-modifying therapies for PSP have not yet been identified. Several tau-targeting treatment modalities, including vaccines, monoclonal antibodies, and microtubule-stabilizing agents, have been investigated and have had no efficacy. The need to treat PSP and other tauopathies is critical, and many clinical trials investigating tau-targeted treatments are underway. In this review, the PubMed database was queried to collect information about preclinical and clinical research on PSP treatment. Additionally, the US National Library of Medicine's ClinicalTrials.gov website was queried to identify past and ongoing clinical trials relevant to PSP treatment. This narrative review summarizes our findings regarding these reports, which include potential disease-modifying drug trials, modifiable risk factor management, and symptom treatments.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"975-1013"},"PeriodicalIF":3.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11263316/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140922214","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":"Lymphopenia is Not the Primary Therapeutic Mechanism of Diroximel Fumarate in Relapsing-Remitting Multiple Sclerosis: Subgroup Analyses of the EVOLVE-MS-1 Study.","authors":"Barry A Singer, Sibyl Wray, Mark Gudesblatt, Barbara Bumstead, Tjalf Ziemssen, Ashley Bonnell, Matthew Scaramozza, Seth Levin, Mathura Shanmugasundaram, Hailu Chen, Jason P Mendoza, James B Lewin, Sai L Shankar","doi":"10.1007/s40120-024-00637-2","DOIUrl":"10.1007/s40120-024-00637-2","url":null,"abstract":"<p><strong>Introduction: </strong>In EVOLVE-MS-1 (NCT02634307), mean absolute lymphocyte count (ALC) on diroximel fumarate (DRF) declined from baseline by approximately 28% in year 1, then stabilized, similar to ALC decline observed with dimethyl fumarate (DMF). Prior studies reported that clinical efficacy of DMF was not substantially different in patients with and without lymphopenia.</p><p><strong>Methods: </strong>EVOLVE-MS-1-an open-label, 96-week, phase 3 study-assessed DRF safety and exploratory efficacy in patients with relapsing-remitting multiple sclerosis. This study analyzes efficacy-related outcomes comparing (1) patients with lymphopenia (≥ 1 ALC below lower limit of normal [LLN]) and without (all ALCs ≥ LLN); (2) across quartiles stratified by week 96 ALC decline from baseline: Q1 (≥ 47% decline); Q2 (30% to < 47% decline); Q3 (12% to < 30% decline); Q4 (< 12% decline).</p><p><strong>Results: </strong>Baseline characteristics were similar between patients without (n = 593) and with lymphopenia (n = 452). At week 96, adjusted annualized relapse rate (ARR; 95% confidence interval) was 0.14 (0.11-0.17) without lymphopenia and 0.12 (0.09-0.15) with lymphopenia. Estimated proportions with 12-week confirmed disability progression (CDP12) at week 96 were 10.2% without and 9.3% with lymphopenia. When stratified by quartiles (Q1-Q4), ARR at week 96 was 0.11 (Q1), 0.09 (Q2), 0.13 (Q3), and 0.17 (Q4). Estimated proportions with CDP12 at week 96 were 9.6% (Q1), 10.2% (Q2), 5.7% (Q3), and 10.9% (Q4). At week 96, no evidence of disease activity was achieved by 47.2% (Q1), 47.8% (Q2), 45.4% (Q3), and 37.3% (Q4) of patients.</p><p><strong>Conclusion: </strong>In DRF-treated patients in EVOLVE-MS-1, clinical and radiological measurements indicated reduced disease activity regardless of lymphopenia or magnitude of ALC decline from baseline; however, patients who had greater ALC declines appeared to have numerically lower ARR and higher proportions free from relapses and gadolinium-enhancing lesions compared with those with smallest decline. This supports prior evidence that, while lymphopenia may contribute to fumarate efficacy outcomes, it is not the primary mechanism of action.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier NCT02634307.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"1273-1285"},"PeriodicalIF":3.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11263526/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141458307","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":"An Ethnographic Study of Patient Life Experience in Early-Stage Parkinson's Disease in the United States and Germany.","authors":"Todd Carmody, Rebekah Park, Elisabeth Bennett, Emily Kuret, Beyza Klein, Àngels Costa, Simon Messner, Amelia Hursey","doi":"10.1007/s40120-024-00632-7","DOIUrl":"10.1007/s40120-024-00632-7","url":null,"abstract":"<p><strong>Introduction: </strong>Existing qualitative research on early-stage Parkinson's disease draws on patients' reported disease experience, aiming to capture the symptoms and impacts most relevant to patients living with the disease. As a complement to this research, the present study investigated the patient experience of early-stage Parkinson's disease from a holistic, ethnographic perspective. We explored the attitudes, beliefs, and social structures that shape how people understand and adapt to life with early-stage Parkinson's disease.</p><p><strong>Methods: </strong>Researchers interviewed 30 people with early-stage Parkinson's disease, 10 relatives, and 10 neurologists and movement disorder specialists in the USA and Germany. Many of these interviews took place in-person, allowing researchers to spend time in participants' homes and witness their daily lives. A multidisciplinary team of social scientists, clinical researchers, and patient organization representatives led the mixed-methods study design and analysis. In-depth ethnographic interviews yielded qualitative insights, with a quantitative survey following to assess their prevalence in a larger sample of 150 patients.</p><p><strong>Results: </strong>In addition to developing a patient life experience pathway of early-stage Parkinson's disease, we identified five key thematic findings that provide insight into how the clinical features of the disease become meaningful to patients on the context of their daily lives, family relations, and subjective well-being: (1) People with early-stage Parkinson's disease start coming to terms with their disease before receiving a medical diagnosis; (2) Acceptance is not a finalized achievement, but a cyclical process; (3) People with early-stage Parkinson's disease \"live in the moment\" to make the future more manageable; (4) Slowing disease progression is an important goal driving the actions of people with early-stage Parkinson's; and (5) People with early-stage Parkinson's disease value information that is grounded in lived experience and relevant to their stage of disease progression.</p><p><strong>Conclusion: </strong>This holistic, ethnographic approach to patient life experience provided five key thematic findings that complement insights from qualitative and quantitative datasets on early-stage Parkinson's disease. An enhanced understanding of how early-stage Parkinson's symptoms impact patients' health-related quality of life and their broader social lives can help us better understand how patients make decisions about their usage of healthcare services and therapies.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"1219-1235"},"PeriodicalIF":3.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11263318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141306364","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":"Relative Bioavailability Study of Midazolam Intramuscularly Administered with the Needle-Free Auto-Injector ZENEO^® in Healthy Adults.","authors":"Olivier Lacombe, Yannick Pletan, Jean-Marie Grouin, Aislinn Brennan, Olivier Giré","doi":"10.1007/s40120-024-00627-4","DOIUrl":"10.1007/s40120-024-00627-4","url":null,"abstract":"<p><strong>Introduction: </strong>Intramuscular (IM) midazolam is indicated for the treatment of status epilepticus. Administration must be efficient to rapidly terminate prolonged seizures and prevent complications. The objective of this study was to compare, in terms of relative bioavailability and bioequivalence, IM midazolam injection by needle-free auto-injector, in different settings, to IM midazolam injection by a conventional syringe and needle.</p><p><strong>Methods: </strong>In this open-label, randomized, four-period crossover study, healthy adults received single doses of midazolam (10 mg) under fasting conditions. The reference treatment (conventional syringe) was administered once, on bare skin in the thigh. The tested treatment (the needle-free auto-injector ZENEO^®) was administered three times: on bare skin in the thigh, on bare skin in the ventrogluteal area, and through clothing in the thigh. Repeated plasma samples were collected to obtain 36-h pharmacokinetic (PK) profiles. Primary PK parameters were area under the plasma concentration-time curve, from time zero to the last measurable time point (AUC_0-t) and from time zero to infinity (AUC_0-∞), and the maximum observed plasma concentration (C_max).</p><p><strong>Results: </strong>Forty adults were enrolled and included in the PK analysis set. In all comparisons, the 90% confidence interval (CI) of the least-squares geometric mean ratios for AUC_0-t and AUC_0-∞ were within the bioequivalence range of 80-125%, with low intra-individual coefficients of variation (< 20.5% for all parameters in all comparisons). Bioequivalence was also met for C_max in all comparisons except when comparing the tested treatment through clothing versus the reference treatment, where the 90% CI lower limit was slightly outside the bioequivalence range (78.8%). With all tested treatments C_max was slightly lower, but early mean plasma concentrations (first 10 min post-dosing) were higher when compared to the reference treatment. In general, all treatments were well tolerated, with maximum sedation 0.5-1 h post-injection.</p><p><strong>Discussion/conclusion: </strong>This study establishes that IM midazolam injection on bare skin in the thigh with the ZENEO^® is bioequivalent to IM midazolam injection with a syringe and needle. An acceptable relative bioavailability, compatible with emergency practice, was also shown in multiple settings. Higher mean concentrations within the first 10 min with the ZENEO^® device, and quicker two-step injection suggest a faster onset of action, and thereby an earlier seizure termination, thus preventing the occurrence of prolonged seizure and neurological complications.</p><p><strong>Trial registration information: </strong>ClinicalTrials.gov identifier: NCT05026567. Registration first posted August 30, 2021, first patient enrolled May 9, 2022.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"1155-1172"},"PeriodicalIF":3.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11263531/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141161781","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}