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Background: Cerebral venous thrombosis (CVT) is a rare cause of stroke, with 10–15% of patients experiencing dependence or death. The role of endovascular therapy (EVT) in the management of CVT remains controversial and practice patterns are not well-known. Methods: We distributed a comprehensive 53-question survey to neurologists, neuro-interventionalists, neurosurgeons and other relevant clinicians globally from May 2023 to October 2023. The survey asked about practice patterns and perspectives on EVT for CVT and assessed opinions regarding future clinical trials. Results: The overall response rate was 31% (863 respondents from 2744 invited participants) across 61 countries. A majority (74%) supported use of EVT for certain CVT cases. Key considerations for EVT included worsening level of consciousness (86%) and other clinical deficits (76%). Mechanical thrombectomy with aspiration (22%) and stent retriever (19%) were the most utilized techniques, with regional variations. Post-procedurally, low molecular weight heparin was the predominant anticoagulant administered (40%), although North American respondents favored unfractionated heparin. Most respondents supported future trials of EVT (90%). Conclusions: Our survey reveals significant heterogeneity in approaches to EVT for CVT, highlighting the necessity for adequately powered clinical trials to guide standard-of-care practices.
Medical aid in dying (MAiD), despite being legal in many jurisdictions, remains controversial ethically. Existing surveys of physicians’ perceptions of MAiD tend to focus on the legal or moral permissibility of MAiD in general. Using a novel sampling strategy, we surveyed physicians likely to have engaged in MAiD-related activities in Colorado to assess their attitudes toward contemporary ethical issues in MAiD.
Background: The presence of intraluminal thrombi (ILT) in acutely symptomatic carotid stenosis (“hot carotid”) represents a therapeutic dilemma for physicians. With little evidence to guide treatment, current ILT management approaches rely on individual or institutional preferences. Methods: This mixed methods study analyzed themes from semi-structured interviews with 22 stroke physicians from 16 centers, paired with a worldwide case-based survey of 628 stroke physicians conducted through the “Practice Current” section of Neurology: Clinical Practice. Results: In the thematic analysis of the interviews and quantitative analysis of the survey, participants favoured using anticoagulation with or without antiplatelet agents in patients with ILT (463/628, 74%). Despite a preference for anticoagulation, uncertainty regarding optimal antithrombotic management was noted in the thematic analysis. Additional themes identified included a preference for re-imaging patients in 3-5 days after initiating treatment to look for complete or partial clot resolution, at which point most experts would then be comfortable proceeding with revascularization if indicated, though uncertainty regarding the optimal timing of revascularization was noted. Conclusions: In cases of ILT in the “hot carotid” practice patterns of global experts show a preference for using anticoagulation and reimaging patients in 3-5 days, though there is considerable equipoise regarding the most appropriate management of these patients.
Background: Patient registries are an effective tool in tracking the natural history of rare diseases as well as post-marketing surveillance of novel therapies. The Canadian Neuromuscular Disease Registry (CNDR) is a pan-neuromuscular disease registry that prospectively collects Spinal Muscular Atrophy (SMA)-specific data in 28 clinics across Canada. The objective of this study is to describe real-world data from the CNDR-SMA patient population. Methods: We report cross-sectional data from Canadian SMA patients. Patients were included in analysis if they were active (alive and with follow-up within 24 months). Results: Of 171 SMA patients included in analyses, 37% currently use non-invasive ventilation, 2% invasive ventilation, and 61% no ventilation support. Feeding tubes are used by 27% of patients. and 28% of patients have a history of scoliosis surgery. Of the 171 patients, 137 have had disease-modifying therapy: 96 on nusinersen, 22 on risdiplam, and 19 on onasemnogene abeparvovec (OA). Median (min,max) years of age at therapy initiation was 7 (0,54), 20.5 (5,53), and 1 (0,6), respectively. At therapy initiation, functional status was 32% non-sitters, 38% sitters, and 30% walkers. Conclusions: The CNDR captures a comprehensive SMA dataset that prospectively evaluates real-world data, supporting post-marketing surveillance of novel therapies in Canada.
Background: Little evidence exists to guide the management of symptomatic non-stenotic carotid disease (SyNC). SyNC, which refers to carotid lesions with less than 50% artery stenosis, has been increasingly implicated as a cause of stroke and TIA. Methods: Semi-structured interviews with 22 stroke physicians from 16 centers were conducted as part of the Hot Carotid Qualitative Study. This study explored decision-making approaches, opinions and attitudes regarding the management of symptomatic carotid disease. Presented here are a subset of results related to the decision to revascularize patients with SyNC. Results: Thematic analysis revealed equipoise in the decision to revascularize patients with SyNC. Participants discussed a desire to use imaging features (e.g plaque rupture and plaque morphology) to inform the decision to revascularize, though significant uncertainty remains in appraising the risk conferred by certain features. Experts support further study to better understand the use of these features in risk appraisal for patients with SyNC. Conclusions: The decision to revascularize patients with SyNC is an area with significant equipoise. Experts identify the use of imaging features as an important tool in informing the decision to pursue revascularization in patients with SyNC though more study is required in this area to better inform practice.
OBJECTIVES/GOALS: Patients who have experienced conjunctive mild traumatic brain injuries (mTBIs) suffer from a number of comorbidities, including chronic pain. Despite extensive studies investigating the underlying mechanisms of mTBI-associated chronic pain, the role of inflammation after mTBI and its contribution to long-term pain are still poorly understood. METHODS/STUDY POPULATION: Given the shifting dynamics of inflammation, it is important to understand the spatial-longitudinal changes and their effects on TBI-related pain. Utilizing a recently developed transgenic caspase-1 luciferase reporter mouse, we characterized the bioluminescence signal evident in both in vivo and ex vivo tissues following repetitive closed head mTBIs. This allowed us to reveal the spatiotemporal dynamics of caspase-1 activation in individual animals over time. Furthermore, we utilize various proteomic and behavioral assays to evaluate the role of caspase-1 mediated inflammation in the development and progression of injury-associated chronic pain. Lastly, by blocking inflammasome caspase-1 activation with a specific inhibitor, we assess its clinical potential as the next therapeutic approach to pain. RESULTS/ANTICIPATED RESULTS: We established that there were significant increases in bioluminescent signals upon protease cleavage in the brain, thorax, abdomen, and paws in vivo, which lasted for at least one week after each injury. Enhanced inflammation was also observed in ex vivo brain slice preparations following injury events that lasted for at least 3 days. Concurrent with the in vivo detection of the bioluminescent signal were persistent decreases in mouse hind paw withdrawal thresholds that lasted for more than two months postinjury. Using MCC950, a potent small molecule inhibitor of NLRP3 inflammasome-caspase 1 activity, we observed reductions in both caspase-1 bioluminescent signals in vivo and caspase-1 p45 expression by immunoblotting and an increase in hind paw withdrawal thresholds. DISCUSSION/SIGNIFICANCE: Overall, these findings suggest that neuroinflammation in the brain following repeated mTBIs is coincidental with a chronic nociplastic pain state, and repeated mTBI-associated events can be ameliorated by a highly specific small molecule inhibitor of NLRP3 inflammasome activation.
The provisioning of foraging opportunities to primates has been shown to be an effective means of enriching the laboratory environment. In this study artificial turf was used as the substrate for a particulate food given to the subjects as an environmental enrichment technique. Eight rhesus monkeys exhibited a significant reduction in behavioural pathology when allowed to extend the amount of time they spent in consummatory activities. An increasing trend in time spent foraging with a concomitant decline in aberrant behaviour over a period of six months was particularly noteworthy. No significant difference in preference for particulate monkey chow or more flavourful particulate food treats was expressed by the primates.
The global trend of urbanization coupled with an increasing awareness of the importance of food systems resilience, has led to an increasing interest in urban agriculture to sustainably feed the rapidly growing urban population and mitigate against food supply chain disruptions. While home and community gardens have been long studied, there has been relatively little empirical research focused specifically on commercial urban agriculture (CUA) operations. The purpose of this study was to characterize commercial urban farms, and to identify their primary barriers to business development and expansion, their perceptions of future opportunities, and their specific informational needs. Because CUA has received relatively less attention in previous empirical research, a qualitative approach was used for this needs assessment to collect rich, contextualized information to help differentiate the specific barriers, opportunities and needs of CUA operations as opposed to their rural counterparts. We conducted semi-structured interviews (n = 29) of CUA producers in Florida. These interviews revealed that CUA operations face many of the same barriers that are common to establishing and growing small farms, with additional barriers due to local government regulations and tensions associated with farming on land that is not traditionally used for agriculture. Despite these difficulties, CUA operators believe their urban location is a key benefit to their operation and they see a variety of opportunities for future business and market expansion.
The phenomenon of peasant revolt in the Andean area of South America has been both sustained and violent from Spanish colonial times to the present. The revolt of Túpac Amaru II, who led a rebellion against Spanish colonialism near Cuzco in 1780, has been the best-known incidence of this phenomenon, although the southern highlands region, sometimes known as the mancha india (“Indian stain”), was the center of numerous local revolts during the period 1860–1920, and the focus of several peasant land invasions during the two decades 1950–70.
Peru has a durable tradition of peasant rebellion, most recently described by José Matos Mar (1967) and Oscar Cornblit (1970), which dates far back to the eighteenth century movements led by Juan Santos Atahuallpa and José Gabriel Túpac Amaru. Twentieth century guerrilla leaders have tried to identify with this tradition by echoing their predecessors' concern for the Indians' right to work their own land and to be free from exploitation. They have named their fronts for Túpac Amaru, Pumacahua, Pachacutec, and other native revolutionaries of an earlier era, and they have proposed fundamental changes in Peruvian society, notably agrarian reform, in a conscious effort to complete a struggle that has gone on for more than two centuries to secure land and dignity for campesinos.
Background: There are uncertainties regarding the optimal management of acutely symptomatic carotid stenosis (“hot carotids”). We sought to explore the approaches of stroke physicians to anti-thrombotic management, imaging, and revascularization in patients with “hot carotids”. Methods: We used a qualitative descriptive methodology to examine decision-making approaches of physicians regarding the management of hot carotids. We conducted semi-structured interviews with 22 stroke physicians from various specialties in 16 centers across 4 continents. Results: Important themes regarding anti-thrombotic included limitations of existing clinical trial evidence, competing physician preferences, antiplatelet therapy while awaiting revascularization and various regional differences. Timely imaging availability, breadth of information gained, and surgeon/interventionalist preferences were important themes influencing the choice of imaging modality. The choice of revascularization intervention was influenced by healthcare system factors such as use of multidisciplinary review and operating room/angiography suite availability, and patient factors like age and infarct size. Many themes related to uncertainties in the management of hot carotids were also discussed. Conclusions: Our study revealed themes that are important to international stroke experts. We highlight common and divergent practices while underscoring important areas of clinical equipoise and uncertainty. Teams designing international carotid trials may wish to accommodate identified variations in practice patterns and areas of uncertainty.
Post study questionnaires are used in design studies to uncover data about design reasoning and intent. A study was conducted where activities the study participants performed were compared to the participants’ statements about those activities, collected immediately after the study via a questionnaire. The goal was to explore the reliability of post study evaluations. Disagreements between performed and reported activities were identified, and recommendations made to, where possible, include more objective measures of design activity.
Ecotoxicology offers a comprehensive overview of the science underpinning the recognition and management of environmental contamination. It describes the toxicology of environmental contaminants, the methods used for assessing their toxicity and ecological impacts, and approaches employed to mitigate pollution and ecological health risks globally. Chapters cover the latest advances in research, including genomics, natural toxins, endocrine disruption and the toxicology of radioactive substances. The second half of the book focuses on applications, such as cradle-to-grave effects of selected industries, legal and economic approaches to environmental regulation, ecological risk assessment, and contaminated site remediation. With short capsules written by invited experts, numerous case studies from around the world and further reading lists, this textbook is designed for advanced undergraduate and graduate one-semester courses. It is also a valuable reference for graduate students and professionals. Online resources for instructors and students are also available.