| 1. |
- Dilliott, Allison A., et al.
(författare)
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Clinical testing panels for ALS : global distribution, consistency, and challenges
- 2023
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Ingår i: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. - : Taylor & Francis. - 2167-8421 .- 2167-9223. ; 24:5-6, s. 420-435
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Tidskriftsartikel (refereegranskat)abstract
- Objective: In 2021, the Clinical Genome Resource (ClinGen) amyotrophic lateral sclerosis (ALS) spectrum disorders Gene Curation Expert Panel (GCEP) was established to evaluate the strength of evidence for genes previously reported to be associated with ALS. Through this endeavor, we will provide standardized guidance to laboratories on which genes should be included in clinical genetic testing panels for ALS. In this manuscript, we aimed to assess the heterogeneity in the current global landscape of clinical genetic testing for ALS.Methods: We reviewed the National Institutes of Health (NIH) Genetic Testing Registry (GTR) and members of the ALS GCEP to source frequently used testing panels and compare the genes included on the tests.Results: 14 clinical panels specific to ALS from 14 laboratories covered 4 to 54 genes. All panels report on ANG, SOD1, TARDBP, and VAPB; 50% included or offered the option of including C9orf72 hexanucleotide repeat expansion (HRE) analysis. Of the 91 genes included in at least one of the panels, 40 (44.0%) were included on only a single panel. We could not find a direct link to ALS in the literature for 14 (15.4%) included genes.Conclusions: The variability across the surveyed clinical genetic panels is concerning due to the possibility of reduced diagnostic yields in clinical practice and risk of a missed diagnoses for patients. Our results highlight the necessity for consensus regarding the appropriateness of gene inclusions in clinical genetic ALS tests to improve its application for patients living with ALS and their families.
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| 2. |
- Rasmussen, Mads, et al.
(författare)
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Blood Pressure Thresholds and Neurologic Outcomes After Endovascular Therapy for Acute Ischemic Stroke: An Analysis of Individual Patient Data From 3 Randomized Clinical Trials.
- 2020
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Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 77:5, s. 622-31
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Tidskriftsartikel (refereegranskat)abstract
- The optimal blood pressure targets during endovascular therapy (EVT) for acute ischemic stroke (AIS) are unknown.To study whether procedural blood pressure parameters, including specific blood pressure thresholds, are associated with neurologic outcomes after EVT.This retrospective cohort study included adults with anterior-circulation AIS who were enrolled in randomized clinical trials assessing anesthetic strategy for EVT between February 2014 and February 2017. The trials had comparable blood pressure protocols, and patients were followed up for 90 days. A total of 3630 patients were initially approached, and 3265 patients were excluded.Endovascular therapy.The primary efficacy variable was functional outcome as defined by the modified Rankin Scale (mRS) score at 90 days. Associations of blood pressure parameters and time less than and greater than mean arterial blood pressure (MABP) thresholds with outcome were analyzed.Of the 365 patients included in the analysis, the mean (SD) age was 71.4 (13.0) years, 163 were women (44.6%), and the median National Institutes of Health Stroke Scale score was 17 (interquartile range [IQR], 14-21). For the entire cohort, 182 (49.9%) received general anesthesia and 183 (50.1%) received procedural sedation. A cumulated period of minimum 10 minutes with less than 70 mm Hg MABP (adjusted OR, 1.51; 95% CI, 1.02-2.22) and a continuous episode of minimum 20 minutes with less than 70 mm Hg MABP (adjusted OR, 2.30; 95% CI, 1.11-4.75) were associated with a shift toward higher 90-day mRS scores, corresponding to a number needed to harm of 10 and 4, respectively. A cumulated period of minimum 45 minutes with greater than 90 mm Hg MABP (adjusted OR, 1.49; 95% CI, 1.11-2.02) and a continuous episode of minimum 115 minutes with greater than 90 mm Hg MABP (adjusted OR, 1.89; 95% CI, 1.01-3.54) were associated with a shift toward higher 90-day mRS scores, corresponding to a number needed to harm of 10 and 6, respectively.Critical MABP thresholds and durations for poor outcome were found to be MABP less than 70 mm Hg for more than 10 minutes and MABP greater than 90 mm Hg for more than 45 minutes, both durations with a number needed to harm of 10 patients. Mean arterial blood pressure may be a modifiable therapeutic target to prevent or reduce poor functional outcome after EVT.
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| 3. |
- Simonsen, C. Z., et al.
(författare)
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General anesthesia during endovascular therapy for acute ischemic stroke: benefits beyond better reperfusion?
- 2022
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Ingår i: Journal of Neurointerventional Surgery. - : BMJ. - 1759-8478 .- 1759-8486. ; 14:8, s. 767-771
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Tidskriftsartikel (refereegranskat)abstract
- Background Endovascular therapy (EVT) is standard of care for stroke caused by large vessel occlusion. Whether EVT should be performed under general anesthesia (GA) or conscious sedation (CS) is controversial. While a meta-analysis of randomized trials showed better outcome for EVT under GA, observational studies suggested the opposite. A proposed advantage of GA is better reperfusion achieved via more successful handling of the immobile patient. The aim of this study was to investigate if the good outcome seen in patients treated under GA was mediated by better reperfusion. Methods The meta-analysis included 368 individual patients from three randomized controlled trials, of whom 185 patients were randomized to CS. A mediator analysis was performed to examine if the better outcome in the GA arm was driven by higher reperfusion rate. Results The total effect showed a risk difference (RD) of 0.15 (95% CI 0.04 to 0.25), associating GA with a beneficial outcome. The direct effect of GA constituted a large portion, with an RD of 0.12 (95% CI 0.01 to 0.22), while only a small portion was mediated through the degree of reperfusion, with an RD of 0.03 (95% CI 0.02 to 0.04). Conclusion The better outcome after EVT in the GA arm was mainly a direct effect-that is, an effect that was not explained by better reperfusion. We also found a better outcome in the GA arm when reperfusion was not achieved. Whether this is an effect of the stable condition and blood pressure under GA or a neuroprotective effect will need to be investigated in future research.
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