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Background: Tenecteplase is a genetically-modified variant of the tissue plasminogen activator alteplase, with increased fibrin-specificity, administered as a more convenient intravenous bolus. Recent data, from the AcT trial, have shown tenecteplase to be non-inferior to alteplase in patients with acute ischemic stroke (AIS) treated within 4.5 hours from symptom onset, the direction of effect favoring tenecteplase. As a result, the Heart and Stroke Foundation of Canada has added tenecteplase to the Stroke Best Practice Recommendations. However, its cost-effectiveness in the Canadian setting remains unknown. Methods: An analysis was performed to estimate the cost-effectiveness of tenecteplase compared to alteplase in the AIS population. The model structure combines a decision tree for the first 90 days post index stroke, where the 7 modified Rankin Scale (mRS) states are informed by the AcT trial, and a Markov model for the remainder of the lifetime horizon. Cost and utility values were derived from the literature and public sources. Canadian health care system and hospital perspectives were used. Results: This economic analysis demonstrates that tenecteplase is dominant compared to alteplase, providing more quality-adjusted life years at lower costs. Conclusions: Adding tenecteplase to hospital formularies for AIS would generate savings for the health care system while providing more benefits.
This article examines the agency of women in a state programme which, although its original aim was not focused on improving the situation of women, has had the effect of helping women from poor sectors along a gender path. The analysis uses the concept of agency to explore contradictions between gender roles, the sexual division of labour, and women’s emancipation. While the programme reinforced some traditional gender roles, it also enabled women to develop a certain level of autonomy through emancipatory strategies, such as creating new spaces where they can discuss gender issues and share their experiences. Key findings relate to the role of community activities in building alternatives to current living conditions. The programme helped women save time and money and provided opportunities to step out of their private spaces. In its final year, the programme came to incorporate a feminist perspective, thanks to the efforts of both the feminist movement and the women beneficiaries of the programme. Analysis of the text of interviews and a final focus group provides an assessment of the programme’s outcomes and allows an evaluation of the level of agency achieved.
Background: Adverse effects and risks associated with glucocorticoid (GC) treatment are frequently encountered in immune-mediated neuromuscular disorders. However, significant variability exists in the management of these complications. Our aim was to establish international consensus guidance on the management of GC-related complications in neuromuscular disorders. Methods: An international task force of 15 experts was assembled to develop clinical recommendations for managing GC-related complications in neuromuscular patients. The RAND/UCLA Appropriateness Method (RAM) was employed to formulate consensus guidance statements. Initial statements were drafted following a comprehensive literature review and were refined based on anonymous expert feedback, with up to three rounds of email voting to achieve consensus. Results: Consensus was reached on statements addressing general patient care, monitoring during GC therapy, osteoporosis prevention, vaccinations, infection screening, and prophylaxis for Pneumocystis jiroveci pneumonia. A multidisciplinary approach to managing GC-related complications was highlighted as a key recommendation. Conclusions: This represents the first consensus guidance in the neurological literature on GC complications, and offer clinicians structured guidance on mitigating and managing common adverse effects associated with both short- and long-term GC use. They also provide a foundation for future debate, quality improvement, research work in this area.
Background: Epilepsia partialis continua (EPC) is a form of focal status epilepticus, often requiring multiple anti-seizure medications (ASM). There are no established guidelines for pharmacological management. Perampanel (PER), an AMPA receptor antagonist, has gained attention in treating status epilepticus based on limited case reports. This study evaluates the efficacy of PER in treating EPC. Methods: We retrospectively analyzed the treatment response and adverse effects of PER in patients with EPC at our local hospital from January 2024 to January 2025. Seven patients with EPC were included. The loading dose of PER ranged from 6 mg to 20 mg. The etiology of EPC was intracranial hemorrhage (70%) and glioblastoma (30%). A clinical response was defined as seizure freedom within 72 hours of initiating PER, with PER being the last ASM added. Results: PER resulted in seizure termination in 6 of 7 patients. Time to response ranged from 24 to 72 hours. Oral PER, up to a dose of 16 mg, was well-tolerated in conscious patients. Common side effects included sedation, delirium, agitation, and nausea. Conclusions: Our real-world data suggest that PER can be an effective and well-tolerated early adjunct therapy in EPC, particularly at higher oral loading doses in conscious patients.
Background: Balamuthia mandrillaris is a rare protozoan pathogen that causes severe central nervous system (CNS) infections in humans. Given the complexity and rarity of these infections, understanding the radiological features is key for early diagnosis and management. This case series aims to elucidate the spectrum of imaging findings in microbiologically confirmed Balamuthia CNS infection cases. Methods: A retrospective study analyzing imaging findings of 20 patients with confirmed Balamuthia CNS infections collected from the hospital’s archives, all of whom had positive CSF cultures and underwent gadolinium-enhanced MRI scans. Results: Patients presented with non-specific symptoms including headaches and seizures. Imaging revealed multiple intra-axial enhancing lesions with surrounding vasogenic edema, some demonstrating ring enhancement and typical imaging features of intracranial abscesses. Cerebritis, hemorrhagic infarcts and necrosis were also noted. Conclusions: CNS infections have a diverse group of causative organisms, including amoebic ones like Balamuthia, and often present with overlapping symptoms, complicating diagnosis. Accurate and timely imaging recognition, combined with CSF analysis, is essential for diagnosing and managing patients promptly, improving overall patients outcome in Balamuthia mandrillaris CNS infections.
Background: In the Phase 3 MycarinG study (MG0003/NCT03971422), one 6-week cycle of rozanolixizumab significantly improved myasthenia gravis (MG)-specific outcomes versus placebo. After MycarinG, patients could enrol in open-label extension studies (MG0004 then MG0007, or MG0007 directly). Methods: In MG0004 (NCT04124965), patients received once-weekly rozanolixizumab 7mg/kg or 10mg/kg for ≤52 weeks. In MG0007 (NCT04650854), after a cycle of rozanolixizumab 7mg/kg or 10mg/kg, subsequent cycles were based on symptom worsening at the investigator’s discretion. Pooled data are reported across MycarinG, MG0004 (first 6 weeks) and MG0007 (final data) for patients receiving ≥2 symptom-driven cycles (efficacy; ≤13 cycles) or ≥1 cycle (safety). Results: 196 patients received ≥1 rozanolixizumab dose of whom 129 received ≥2 symptom-driven cycles (7mg/kg: n=70; 10mg/kg: n=59). Treatment response was maintained from Cycles 1–13: mean change from baseline to Day 43 in MG-Activities of Daily Living score ranged from -3.2 to -4.9 (7mg/kg) and -3.2 to -6.7 (10mg/kg). Quantitative MG and MG Composite scores also improved. Treatment-emergent adverse events (TEAEs) did not increase with repeated cyclic treatment, and most were mild/moderate; the most common event was headache. Conclusions: Rozanolixizumab showed consistent improvements across MG-specific outcomes up to 13 cycles and repeated cyclic treatment was generally well tolerated. Funding: UCB.
Background: Treatment for sagittal craniosynostosis often involves endoscopic suturectomy (ES) followed by helmet therapy, with cranial shape improvement assessed via cephalic index (CI). The effect of adding barrel-stave osteotomy (BSO) to ES on CI outcomes remains controversial. This study evaluated the impact of BSO on operative burden and postoperative cranial deformity in patients undergoing surgical correction of sagittal craniosynostosis. Methods: A retrospective review of 85 patients treated for sagittal craniosynostosis at BC Children’s Hospital (2010–2021) compared patients undergoing ES alone (n=18) and ES+BSO (n=67). Demographics, operative burden (anesthesia and surgical time, blood loss, hospital stay), and longitudinal CI measurements were analyzed. Mixed effects modeling controlled for age, preoperative CI, and helmet duration. Results: Operative burden did not differ significantly between treatment groups (p > 0.05). The median follow-up duration for CI measurements was 56.0 months. While preoperative CI was similar (67.4 vs. 66.8, p=0.61), CI was significantly improved in the ES+BSO group at all postoperative intervals (p ≤ 0.02). Mixed effects modeling confirmed that BSO independently improved CI (effect size 2.21, p=0.001). Conclusions: In our series, the addition of BSO to ES significantly improved immediate and long-term cranial deformity without increasing operative burden, supporting its use in sagittal craniosynostosis correction.
How should epistemologists respond to skepticism about knowledge of the external world? Michael Bergmann advocates noninferential antiskepticism. The thought is that, to reply to a skeptical argument, we should start with premises that do not require inference. I argue that Bergmann’s reasoning runs into the problem of easy knowledge and propose an alternative inferential antiskepticism. This view faces the problem of vicious circularity. I agree that, if we go down the inferential path, a certain type of circularity is unavoidable. I deny, however, that this type of circularity is vicious.
Background: Large language models (LLMs) have gained popularity in medicine, however, their roles in neuroradiology remain underexplored. This study aimed to evaluate the current landscape, identify evidence gaps, and propose future directions for LLMs in neuroradiology. Methods: A systematic literature search of PubMed, Embase, Web of Science, and Scopus was conducted to identify relevant studies published between January 1, 2010, and October 1, 2024. Two reviewers screened eligible studies and selected original research applying LLMs in neuroradiology for inclusion. Included studies were evaluated using thematic and geographical analyses to identify trends. Results: Of 287 identified studies, 57 met the inclusion criteria. Findings revealed a significant upward trend in publications since 2018, with an annual growth rate of 78.2%. Three main themes emerged: Operational Workflow Optimization (n=26, 45.6%), Diagnostic Decision Support (n=20, 35.1%), and Education and Training (n=11, 19.3%). Geographically, most studies originated from North America (n=23, 40.4%), Europe (n=19, 33.3%), and Asia (n=12, 21.1%), with limited contribution from other regions (n=3, 5.3%). Key knowledge gaps included strategies to mitigate hallucinations, enhance transparency, and safeguard patient privacy. Conclusions: LLMs are being applied in neuroradiology to support diagnostics, streamline workflows, and enhance education. Future research should prioritize clinical validation, promote ethical practices, and expand global involvement.
Background: Electroencephalography (EEG) has emerged as a minimally invasive technique to quantify functional changes in neural activity associated with neurodegenerative disorders such as Alzheimer’s Disease (AD). Given its non-invasive approach, EEG has the potential to fill the pressing gap forearly, accurate, and accessible methods to detect and characterize disease progression in AD. Methods: To address these challenges, we conducted a pilot analysis of a custom machine learning-based automated preprocessing and feature extraction pipeline to identify indicators of AD and correlates of disease progression. Results: Our pipeline successfully detected several new and previously established EEG-based measures indicative of AD status and progression. Key findings included alterations in delta and theta band power, network connectivity disruptions, and increased slowing of brain rhythms. Additionally, we observed strong correlations between EEG-derived metrics and clinical measures such as Mini-Mental State Examination (MMSE) scores, supporting the external validity of our approach. These findings highlight the sensitivity of EEG biomarkers in differentiating between early and late stages of AD. Conclusions: Our findings suggest that this automated approach provides a promising initial framework for implementing EEG biomarkers in the AD patient population, paving the way for improved diagnostic and monitoring strategies.
The question of whether PCR is reliable sounds strange at first. However, looking at the scientific literature from the 1950s and 60s, one will find many publications on the physicochemistry of DNA that have been forgotten meanwhile. Quite a few of these studies have shown that DNA is thermolabile, which consequently raises the question of whether this thermolability is relevant in the context of PCR, namely in the denaturation phase. However, it can be shown that this is not the case: losses due to thermal hydrolysis are irrelevant for the performance of contemporary PCR protocols and their specificity as well as for the significance of their results. There is now a huge amount of scientifically verified and published data on technical and molecular aspects of PCR, a small selection of which we quote here. In addition, we present some primary data that also clearly demonstrate the reliability of PCR.
Background: Duchenne muscular dystrophy (DMD) typically presents with painless weakness which may contribute to its delayed recognition. Methods: Retrospective chart review was performed for patients with DMD at CHEO over 15 years (2009-2023). Our data will later be combined with that from two other centers. Inclusion criteria: 1) confirmed DMD; 2) symptom onset <6 yo. Exclusion criteria: incomplete records or family history of DMD. Results: We identified 72 DMD patients. Total of N=49 were analyzed. Subjects were excluded for: incomplete data N=10 (e.g. diagnosis at another centre); symptom onset ≥6 yo (N=4); family history (N=9). First symptoms were reported at a mean age of 2.7 yo (range: 0-5.9 yo) with diagnosis at mean age of 5.2 yo (range: 0.5 to 9.6 yo), representing a mean delay of 2.5 years (range: 0-6.8 yrs). Initial symptoms included: weakness (61.2%), sports difficulty (61.2%), calf pseudohypertrophy (10.2%), language difficulties (8.2%) or muscle pain (2.0%). Learning disability was reported in 36 (73.5%) subjects with 7 (14.3%) having autistic spectrum disorder. Conclusions: The mean delay to diagnosis of patients followed at our centre was similar to the United Kingdom (MDSTARnet). We advocate for increased education to identify DMD earlier, particularly given emerging therapies for this disorder.
Background: Middle meningeal artery embolization (MMAE) is increasingly used to treat chronic subdural hematomas, arteriovenous fistulas and meningiomas. Less commonly, MMAE is performed for pseudoaneurysms and aneurysms. While procedural safety and efficacy in the context of the former diseases is well-documented, data for MMA aneurysm/pseudoaneurysm treatment are scarce. Methods: We conducted a systematic review using PubMed/Medline and GoogleScholar, targeting studies published in English since 1994. Original research studies and case reports involving adult patients (≥18 years) with aneurysms or pseudo-aneurysms treated with MMAE were included. Data on complications, outcomes, procedural techniques, and embolization materials were analyzed using descriptive statistics. Results: Of 1,690 identified studies, 600 underwent full-text review, and 27 studies/case reports focusing on MMAE for pseudoaneurysms and aneurysms were included in the final analysis. In most cases, the treatment was successful, with complete (pseudo-)aneurysm occlusion in all patients and symptom improvement in 24 of 28 patients (85.7%). Complications were rare, occurring in <5%, and mild, such as transient headaches (n=1) which resolved spontaneously. Conclusions: MMAE appears to be a safe and effective treatment for pseudoaneurysms and aneurysms, with minimal complications and high success rates. However, available data are scarce and from case reports only, limiting generalizability. Confirmation in larger, multi-center studies is needed.
Background: Recent research highlights the glymphatic system’s role in clearing waste from the central nervous system. Its dysfunction is linked to neurodegenerative diseases like Alzheimer’s and Parkinson’s, but its impact on multiple sclerosis (MS) remains unclear. This retrospective study examines glymphatic function in MS and its link to clinical disability using MRI. Methods: The study included 18 patients diagnosed with MS, comprising 3 with primary progressive MS and 15 with secondary progressive MS, along with 7 healthy control participants. All subjects underwent neurological evaluations and MRI assessments, which included high-resolution T1, T2, and diffusion-weighted imaging. Statistical comparisons between the groups were conducted using a two-sample t-test. Results: MS patients exhibited a reduced diffusion along the perivascular space index (DTI-ALPS) compared to healthy controls. Patients with primary progressive MS demonstrated lower DTI-ALPS values than those with secondary progressive MS. Lower DTI-ALPS was associated with a higher Expanded Disability Status Scale (EDSS) score, indicating a correlation between glymphatic system dysfunction and greater clinical disability in MS. Conclusions: The study suggests that glymphatic system dysfunction is present in MS and is inversely associated with the severity of disability. This impairment may contribute to the disease’s pathological mechanisms.
Background: Stroke survivors have a higher risk of depression and suicide, but how hospitalization for major depression modifies the risk of suicide after stroke is not well-known. Methods: We conducted a population-based matched cohort study of adults hospitalized with first-ever stroke between 2008 to 2017 matched 1:1 to the general Ontario population on age, sex, neighbourhood-level income, rurality, and comorbidities. Patients with major depression or deliberate self-harm prior to index event were excluded from both groups. We used cause-specific proportional hazards models to evaluate the association between stroke and suicide (defined as self-harm or death by suicide) and used an interaction term to assess effect modification of depression on stroke-suicide association. Results: We included 64,719 matched pairs of patients with stroke and without (45.5% female, mean age 71.4 years). Compared to matched controls, stroke survivors had a higher rate of suicide (11.1 vs. 3.2, HR 2.87 [2.35-3.51]). Depression was associated with a higher rate of suicide in both groups (HR 13.8 [8.82-21.61]). The interaction between stroke and depression was not significant (Pstroke*depression = 0.51). Conclusions: Hospitalization for depression does not modify the rate of suicide after stroke, suggesting the need to better understand the pathways leading to suicide after stroke.
From December 2023 to November 2024, regular surveys were conducted to document finfish bycatch in the trawl fishery landing at Veraval Fishing Harbour, northeastern coast of the Arabian Sea. As an outcome of this exploration, three male specimens of Callionymus gardineri and five (four males and one female) specimens of C. omanensis were collected. Both species were recorded for the first time from the north-western Arabian Sea, coastal waters of India, accompanied by a new maximum length record for C. omanensis (Lmax = 122.1 mm standard length). Callionymus omanensis was originally described based on a single male specimen, whereas the description of female C. omanensis was interpreted. While the exact justification for their distribution in this new locality remains unknown, both dragonet species likely moved eastwards from their native habitats along the western Arabian Sea coast. This strongly suggests a significant research gap in our understanding of low-value deep-sea trawl bycatch, necessitating further exploration to improve biodiversity assessments. Herein, the detailed meristic counts and morphometric measurements are compared, and updated distributional information is collated.