Neurology and Therapy最新文献

Introduction: The availability of anti-amyloid therapy for mild cognitive impairment (MCI) due to Alzheimer's disease and mild Alzheimer's dementia (AD) has underscored the need for realistic estimates of the population with AD/MCI within the healthcare system to assure adequate preparedness. We hypothesize that administrative databases can provide real-world epidemiologic estimates reflecting the population with diagnosed (known) MCI and AD. This study was conducted to estimate diagnostic incidence and prevalence of AD and all-cause MCI among the Medicare fee-for-service (FFS) and Medicare Advantage (MA) beneficiaries in the United States.

Methods: This was a retrospective analysis of Medicare beneficiaries (aged 65 and older) with identified diagnoses of AD/MCI based on ≥ 2 diagnostic codes ≥ 30 days apart. Incidence/prevalence estimates were reported per 10,000 person-years.

Results: In FFS, AD incidence (2008-2018) decreased (138 to 104); MCI incidence increased (8 to 47), but the sum (MCI + AD) was relatively stable (146 to 151). Prevalence (2008-2017) increased for AD (318 to 354), and MCI (13 to 99). In MA (2016) epidemiological estimates were consistent with FFS. In 2017, older age, female sex and the Northeastern region were consistently associated with higher AD/MCI prevalence among FFS beneficiaries.

Conclusion: In FFS, AD/MCI diagnostic prevalence increased over 10 years, especially for MCI; prevalence estimates in MA (2016) were comparable. Diagnostic prevalence in 2016 (FFS + MA) was 3.4% for AD and 0.85% for MCI. Our findings address the reality of Alzheimer's disease in clinical practice in the United States that is confronted by healthcare professionals, payors, healthcare decision-makers, patients, and caregivers, and may offer a realistic gauge for patient triage for treatment, healthcare resource allocation, and health-systems' operational prioritization. With the availability of anti-amyloid treatments, we anticipate that the population with diagnosed MCI/AD within the Medicare database may rise over time; therefore, periodic updates of incidence/prevalence estimates may provide support for timely healthcare decision-making.

Introduction: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Introduction: Post-stroke spasticity (PSS) occurs in ~25-43% of patients between 2 weeks and 3 months following a stroke. This retrospective claims study examined the occurrence of spasticity, treatment patterns, healthcare resource utilization, and healthcare costs among patients who experienced a stroke over a 2-year period.

Methods: Analyses were conducted using healthcare claims from the IQVIA PharMetrics Plus database of commercially/self-insured members from 2015 to 2021. Patients were selected based on two International Classification of Diseases, 10th revision diagnosis codes for stroke requiring an inpatient stay (index date) with continuous enrollment with medical/pharmacy benefits 12 months before (pre-index) and 24 months starting on the index date (post-index). PSS was defined by a diagnosis code for spastic hemiplegia or muscle contracture starting ≥ 7 days post-index, or claims indicating PSS treatment [botulinum toxin A (BoNT-A) or muscle relaxants] any time in the post-index period. A generalized linear model was developed to estimate cost ratios between patients with and without PSS.

Results: Overall, 7851 patients fulfilled study criteria; 47.7% were treated with physical or occupational therapy, 11.3% with muscle relaxants, and 0.8% with BoNT-A; 12.4% met the post-index definition of PSS; 84.2% were identified using muscle relaxant or BoNT-A codes, 6.6% using diagnosis codes, and 9.2% using both. Median time to codes identifying PSS was 213 days. Patients treated with BoNT-A received an average of three treatments, starting 253 days (median) post-stroke. Mean all-cause healthcare costs were US$62,875 among patients with PSS versus $44,472 among patients without (P < 0.001), representing 39.6% higher adjusted all-cause healthcare costs among patients with PSS versus patients without PSS.

Conclusion: Patients with PSS utilized numerous treatment modalities and experienced higher mean all-cause healthcare costs than did those without PSS. Earlier identification to optimize treatment of PSS may represent an opportunity for cost savings within managed healthcare systems.

Background: Despite considerable evidence for the efficacy and safety of stiripentol in Dravet syndrome (DS), some aspects of stiripentol use remain challenging in clinical practice, such as dose titration and the adjustment of concomitant antiseizure medications (ASMs) to prevent potential adverse effects.

Aim: To (1) provide practical recommendations on the initiation of stiripentol treatment in patients with DS, (2) evaluate its effectiveness in the patient, and (3) guide the management of drug interactions and other aspects of treatment monitoring.

Methods: Six Spanish neurologists (the authors) with expertise in the management of pediatric and adult patients with DS held a meeting in early 2024 to develop expert recommendations regarding the use of stiripentol in DS, based on a review of the literature and their common clinical experience.

Results: According to these recommendations, stiripentol can be administered to patients with DS of any age, although its initiation and titration vary according to age group. Individualized adjustment of concomitant ASMs, such as valproic acid and clobazam or drugs specifically for DS (i.e., fenfluramine), at initiation and during stiripentol treatment, can mitigate drug interactions, thereby increasing the long-term tolerability of stiripentol treatment. In specific cases, stiripentol doses of > 50 mg/kg/day may be contemplated, and acute stiripentol administration may be considered to control refractory status epilepticus. Blood tests should be performed before starting stiripentol, at 3, 6, and 12 months after starting treatment, and then annually, except in the event of adverse effects, when additional testing may be necessary. Most adverse effects can be adequately managed by adjusting concomitant medications.

Conclusion: These practical recommendations may be easily adapted for use in different countries, and should increase physicians' confidence in the initiation and monitoring of stiripentol treatment, thus facilitating effective management of patients with DS and improving clinical outcomes.

Optical coherence tomography angiography (OCT-A) is a state-of-the-art imaging technique for the retinal vasculature to accurately segment the capillary network and assign it to retinal layers. OCT-A is a promising technique to better understand neurological diseases with visual system manifestations, such as multiple sclerosis (MS), and to identify and characterize vascular biomarkers. Initial studies suggested vascular changes in MS and its differential diagnoses such as myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and neuromyelitis optica spectrum disorder (NMOSD). Here we review clinical and technical aspects of OCT-A imaging and discuss the potential for the MS field as well as barriers that need to be overcome before OCT-A can be established in clinical application.

Introduction: Friedreich Ataxia (FA) is a multisystem neurodegenerative disease. Affected individuals rely on mobility assistive technologies (MAT) (e.g. wheelchairs) and require long-term treatments and care. To analyse the patients' health-related quality of life (HRQoL), the EuroQol 5 Dimension 3 Level survey (EQ-5D-3L)-a widely used and recommended generic measure-is used in clinical and in health economic studies. Concerns about using the instrument in mobility-impaired individuals who might have difficulties finding appropriate response options for mobility-related items led us to investigate how the 3L dimensions perform in patients with FA using or not using MAT.

Methods: Using longitudinal data from 607 patients with FA of the EFACTS study (from baseline to the 3-year follow-up), we analysed the acceptability, distribution properties, validity, and responsiveness of the EQ-5D-3L, focusing on the mobility item. Analyses were stratified for patients without and with different MAT-usage.

Results: We identified that n = 177 patients used no MAT, n = 299 a wheelchair and n = 131 walking aids. The mobility item non-response was highest in wheelchair users (6.8%) and lowest in patients without MAT. Walking aid users showed the least variability, all selecting the mid-response option "some problems" for mobility. The mobility item correlated moderately with disease severity (r_sp = 0.35) and the activities of daily living scale (r_sp = 0.36) in wheelchair users. No correlation exists for walking aid users. The strongest health changes occurred for wheelchair users, the weakest for walking aid users. The mobility dimensions showed the highest amount of no changes.

Conclusion: The EQ-5D-3L's mobility item has limitations in MAT users, particularly in walking aid users, due to a tendency towards mid-responses. These limitations may affect the efficacy and (cost)effectiveness conclusions drawn from interventions and clinical trials with mobility-impaired individuals. Further research is needed to explore the understanding and interpretation of responses of the EQ-5D in patients with FA with mobility support.

Trial registration: ClinicalTrials.gov identifier NCT02069509.

Introduction: Dimethyl fumarate (DMF) has demonstrated a favorable benefit-risk profile in patients with relapsing-remitting multiple sclerosis (RRMS) in clinical and real-world studies. The ESTEEM study (NCT02047097) was conducted to assess the long-term safety and effectiveness of delayed-release DMF in patients with relapsing forms of MS in routine clinical practice. We report final outcomes from ESTEEM with up to 6.5 years of follow-up.

Methods: Patients newly prescribed DMF were recruited from 393 sites globally. The primary objective was to assess the incidence and type of serious adverse events (SAEs) and adverse events (AEs) leading to discontinuation of DMF. Secondary objectives included assessment of DMF effectiveness on annualized relapse rate (ARR) and patient-reported outcomes (PROs).

Results: Overall, 5124 patients received ≥ 1 dose of DMF. The mean (standard deviation [SD]) age at enrollment was 40.0 (11.2) years; 74% of patients were female. Patients received DMF for a mean (SD) duration of 31.0 (22.7) months. Primary reasons for discontinuation were AEs (n = 1237; 24%); the most common were gastrointestinal AEs (n = 469; 9%), blood and lymphatic disorders (n = 218; 4%), and vascular disorders (n = 200; 4%). SAEs occurred in 391 (8%) patients, most commonly infections and infestations (n = 102; 2%). Adjusted ARR declined by 90% (95% confidence interval [CI]: 90-91%; p < 0.0001), from 0.81 (95% CI 0.79-0.84) 12 months before enrollment to 0.08 (95% CI 0.08-0.09) 6 years after enrollment. The estimated proportion of patients free from confirmed disability progression sustained over 48 weeks was 87.0% at month 60. Mean scores for physical and psychological impact, fatigue, health, and productivity remained stable over 5 years.

Conclusion: DMF demonstrated a safety profile in real-world clinical practice consistent with the known profile of DMF. Relapse rates were low and both ARR and PROs remained stable over time.

Trial registration: ClinicalTrials.gov Identifier NCT02047097.

Introduction: The emergence of high-efficacy disease-modifying therapies (HE DMT) for multiple sclerosis (MS) may pose challenges to the administration and monitoring burden of the therapies. This article presents the results of the Delphi consensus method to generate insights from experts on the administration and monitoring burden of HE DMT in Saudi Arabia with a special focus on cladribine.

Methods: Between January and March 2023, a two-round modified Delphi method was used to establish consensus regarding the administration and monitoring burden of HE DMTs used for MS. Through a questionnaire, the advisors evaluated 17 properties of six individual HE DMTs on the basis of their clinical experience. Advisors were required to rank each property on a scale of 1-5, with 1 being the lowest burden and 5 being the highest burden.

Results: Experts ranked cladribine as having the lowest monitoring burden, followed by ofatumumab and ocrelizumab. Natalizumab and fingolimod were ranked fourth, and alemtuzumab had the highest burden. During the first round, experts agreed on the scores of the administration burden properties, except for hospital visit time and facility use during administration for ofatumumab, route of administration for fingolimod, monitoring of specific side effects and frequency of lab tests at follow-up, and the washout period for natalizumab. During the second round, there was agreement on all properties.

Conclusion: In the absence of alternative scientific data, recommendations from experts and their consensus provide useful insights into the administration and monitoring burden of HE DMTs used for MS in Saudi Arabia.

Introduction: For patients with psychosis, early, intensive therapeutic intervention is thought to improve long-term outcomes. Furthermore, patients with a first-episode psychosis (FEP) who experience a good early response to antipsychotic medication show a clinical and functional benefit over the longer term if they continue low-dose antipsychotic treatment. Lurasidone is an atypical antipsychotic agent which is approved in Europe for the treatment of schizophrenia in adults and adolescents (13-17 years). The efficacy and tolerability of lurasidone have been demonstrated in both antipsychotic-naïve and previously treated patients.

Areas covered: This paper provides a review and commentary regarding the use of lurasidone in patients with FEP. Case studies based on the authors' clinical experiences with lurasidone in real-world practice are provided.

Expert opinion: In our experience, lurasidone has shown efficacy in FEP in different patient profiles, including those with psychoses associated with substance use disorders. Lurasidone provides clinically relevant benefits, especially in patients with affective symptomatology, and has a good tolerability profile.

Introduction: 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.

Methods: 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.

Results: 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.

Conclusions: 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.