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The New England Journal of Medicine Jun 2023The effect of early as compared with later initiation of direct oral anticoagulants (DOACs) in persons with atrial fibrillation who have had an acute ischemic stroke is... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
The effect of early as compared with later initiation of direct oral anticoagulants (DOACs) in persons with atrial fibrillation who have had an acute ischemic stroke is unclear.
METHODS
We performed an investigator-initiated, open-label trial at 103 sites in 15 countries. Participants were randomly assigned in a 1:1 ratio to early anticoagulation (within 48 hours after a minor or moderate stroke or on day 6 or 7 after a major stroke) or later anticoagulation (day 3 or 4 after a minor stroke, day 6 or 7 after a moderate stroke, or day 12, 13, or 14 after a major stroke). Assessors were unaware of the trial-group assignments. The primary outcome was a composite of recurrent ischemic stroke, systemic embolism, major extracranial bleeding, symptomatic intracranial hemorrhage, or vascular death within 30 days after randomization. Secondary outcomes included the components of the composite primary outcome at 30 and 90 days.
RESULTS
Of 2013 participants (37% with minor stroke, 40% with moderate stroke, and 23% with major stroke), 1006 were assigned to early anticoagulation and 1007 to later anticoagulation. A primary-outcome event occurred in 29 participants (2.9%) in the early-treatment group and 41 participants (4.1%) in the later-treatment group (risk difference, -1.18 percentage points; 95% confidence interval [CI], -2.84 to 0.47) by 30 days. Recurrent ischemic stroke occurred in 14 participants (1.4%) in the early-treatment group and 25 participants (2.5%) in the later-treatment group (odds ratio, 0.57; 95% CI, 0.29 to 1.07) by 30 days and in 18 participants (1.9%) and 30 participants (3.1%), respectively, by 90 days (odds ratio, 0.60; 95% CI, 0.33 to 1.06). Symptomatic intracranial hemorrhage occurred in 2 participants (0.2%) in both groups by 30 days.
CONCLUSIONS
In this trial, the incidence of recurrent ischemic stroke, systemic embolism, major extracranial bleeding, symptomatic intracranial hemorrhage, or vascular death at 30 days was estimated to range from 2.8 percentage points lower to 0.5 percentage points higher (based on the 95% confidence interval) with early than with later use of DOACs. (Funded by the Swiss National Science Foundation and others; ELAN ClinicalTrials.gov number, NCT03148457.).
Topics: Humans; Anticoagulants; Atrial Fibrillation; Embolism; Hemorrhage; Intracranial Hemorrhages; Ischemic Stroke; Stroke; Treatment Outcome; Time Factors; Factor Xa Inhibitors; Recurrence
PubMed: 37222476
DOI: 10.1056/NEJMoa2303048 -
Journal of Alternative and... Oct 2020The aim of this systematic review with meta-analysis was to describe the status on the effects of physical scar treatments on pain, pigmentation, pliability, pruritus,... (Meta-Analysis)
Meta-Analysis
The aim of this systematic review with meta-analysis was to describe the status on the effects of physical scar treatments on pain, pigmentation, pliability, pruritus, scar thickening, and surface area. Systematic review and meta-analysis. Adults with any kind of scar tissue. Physical scar management versus control or no scar management. Pain, pigmentation, pliability, pruritus, surface area, scar thickness. The overall results revealed that physical scar management is beneficial compared with the control treatment regarding the management of pain ( = 0.012), pruritus ( < 0.001), pigmentation ( = 0.010), pliability ( < 0.001), surface area ( < 0.001), and thickness ( = 0.022) of scar tissue in adults. The observed risk of bias was high for blinding of participants and personnel (47%) and low for other bias (100%). Physical scar management demonstrates moderate-to-strong effects on improvement of scar issues as related to signs and symptoms. These results show the importance of specific physical management of scar tissue.
Topics: Cicatrix; Female; Humans; Male; Pigmentation Disorders; Postoperative Complications; Pruritus; Wound Healing
PubMed: 32589450
DOI: 10.1089/acm.2020.0109 -
Journal of Neurochemistry Sep 2019Parkinson's disease is the second most common neurodegenerative disorder after Alzheimer's disease and is estimated to affect approximately 1-4% of individuals aged over... (Review)
Review
Parkinson's disease is the second most common neurodegenerative disorder after Alzheimer's disease and is estimated to affect approximately 1-4% of individuals aged over 60 years old. Although considerable efforts have been invested into developing disease-modifying therapies for Parkinson's disease, such efforts have been confounded by the difficulty in accurately diagnosing Parkinson's disease during life to enable accurate patient stratification for clinical trialling of candidate therapeutics. Therefore, the search for effective biomarkers that can be accurately evaluated during life with non-invasive means is a pressing issue in the field. Since the discovery of α-synuclein (α-syn) as a protein linked to a familial form of Parkinson's disease, later identified as the major protein component of the neuropathological hallmark of idiopathic Parkinson's disease, considerable interest has focused on this protein and its distinct conformers. We describe here the progress that has been made in the area of Parkinson's disease biomarker discovery with a focus on α-synuclein. In particular, we highlight the novel assays that have been employed and the increasing complexity in evaluating α-synuclein with regard to the considerable diversity of conformers that exist in the biofluids and peripheral tissues under disease conditions. "This article is part of the Special Issue Synuclein."
Topics: Biomarkers; Blotting, Western; Body Fluids; Brain; Cross-Sectional Studies; Disease Progression; Early Diagnosis; Enzyme-Linked Immunosorbent Assay; Gonads; Humans; Longitudinal Studies; Mass Spectrometry; Mucous Membrane; Organ Specificity; Parkinson Disease; Phosphorylation; Positron-Emission Tomography; Protein Aggregates; Protein Processing, Post-Translational; Salivary Glands; Skin; alpha-Synuclein
PubMed: 31265130
DOI: 10.1111/jnc.14809 -
Brain : a Journal of Neurology Apr 2023Plasma phospho-tau (p-tau) species have emerged as the most promising blood-based biomarkers of Alzheimer's disease. Here, we performed a head-to-head comparison of...
Plasma phospho-tau (p-tau) species have emerged as the most promising blood-based biomarkers of Alzheimer's disease. Here, we performed a head-to-head comparison of p-tau181, p-tau217 and p-tau231 measured using 10 assays to detect abnormal brain amyloid-β (Aβ) status and predict future progression to Alzheimer's dementia. The study included 135 patients with baseline diagnosis of mild cognitive impairment (mean age 72.4 years; 60.7% women) who were followed for an average of 4.9 years. Seventy-one participants had abnormal Aβ-status (i.e. abnormal CSF Aβ42/40) at baseline; and 45 of these Aβ-positive participants progressed to Alzheimer's dementia during follow-up. P-tau concentrations were determined in baseline plasma and CSF. P-tau217 and p-tau181 were both measured using immunoassays developed by Lilly Research Laboratories (Lilly) and mass spectrometry assays developed at Washington University (WashU). P-tau217 was also analysed using Simoa immunoassay developed by Janssen Research and Development (Janss). P-tau181 was measured using Simoa immunoassay from ADxNeurosciences (ADx), Lumipulse immunoassay from Fujirebio (Fuji) and Splex immunoassay from Mesoscale Discovery (Splex). Both p-tau181 and p-tau231 were quantified using Simoa immunoassay developed at the University of Gothenburg (UGOT). We found that the mass spectrometry-based p-tau217 (p-tau217WashU) exhibited significantly better performance than all other plasma p-tau biomarkers when detecting abnormal Aβ status [area under curve (AUC) = 0.947; Pdiff < 0.015] or progression to Alzheimer's dementia (AUC = 0.932; Pdiff < 0.027). Among immunoassays, p-tau217Lilly had the highest AUCs (0.886-0.889), which was not significantly different from the AUCs of p-tau217Janss, p-tau181ADx and p-tau181WashU (AUCrange 0.835-0.872; Pdiff > 0.09), but higher compared with AUC of p-tau231UGOT, p-tau181Lilly, p-tau181UGOT, p-tau181Fuji and p-tau181Splex (AUCrange 0.642-0.813; Pdiff ≤ 0.029). Correlations between plasma and CSF values were strongest for p-tau217WashU (R = 0.891) followed by p-tau217Lilly (R = 0.755; Pdiff = 0.003 versus p-tau217WashU) and weak to moderate for the rest of the p-tau biomarkers (Rrange 0.320-0.669). In conclusion, our findings suggest that among all tested plasma p-tau assays, mass spectrometry-based measures of p-tau217 perform best when identifying mild cognitive impairment patients with abnormal brain Aβ or those who will subsequently progress to Alzheimer's dementia. Several other assays (p-tau217Lilly, p-tau217Janss, p-tau181ADx and p-tau181WashU) showed relatively high and consistent accuracy across both outcomes. The results further indicate that the highest performing assays have performance metrics that rival the gold standards of Aβ-PET and CSF. If further validated, our findings will have significant impacts in diagnosis, screening and treatment for Alzheimer's dementia in the future.
Topics: Humans; Female; Aged; Male; Alzheimer Disease; tau Proteins; Amyloid beta-Peptides; Cognitive Dysfunction; Brain; Biomarkers
PubMed: 36087307
DOI: 10.1093/brain/awac333 -
International Journal of Sports... 2022Lifting something off the ground is an essential task and lifting is a documented risk factor for low back pain (LBP). The standard lifting techniques are stoop (lifting...
UNLABELLED
Lifting something off the ground is an essential task and lifting is a documented risk factor for low back pain (LBP). The standard lifting techniques are stoop (lifting with your back), squat (lifting with your legs), and semi-squat (midway between stoop and squat). Most clinicians believe the squat technique is optimal; however, training on squat lifting does not prevent LBP and utilizing greater lumbar flexion (i.e. stoop) when lifting is not a risk factor for LBP. The disconnect between what occurs in clinical practice and what the evidence suggests has resulted in ongoing debate. Clinicians must ask the right questions in order to apply the evidence appropriately. A proposed clinical framework of calm tissue down, build tissue up, improve work capacity can be used to determine which lifting technique is optimal for a patient at any given time. When applying this clinical framework, clinicians should consider metabolic, biomechanical, physical stress tolerance, and pain factors in order to address the movement system. For example, stoop lifting is more metabolically efficient and less challenging to the cardiopulmonary system. There may be few biomechanical differences in spinal postures and gross loads on the lumbar spine between stoop, squat, and semi-squat lifting; however, each lift has distinct kinematic patterns that affects muscle activation patterns, and ultimately the movement system. Clinicians must find the optimal dosage of physical stress to address all aspects of the movement system to minimize the risk of injury. There is no universal consensus on the optimal lifting technique which will satisfy every situation; however, there may be a lifting technique that optimizes movement to achieve a specific outcome. The calm tissue down, build tissue up, improve work capacity framework offers an approach to determine the best lifting technique for an individual patient at any give time.
LEVEL OF EVIDENCE
5.
PubMed: 35024210
DOI: 10.26603/001c.30023 -
Scandinavian Journal of Medicine &... Mar 2020This randomized controlled trial examined the effects of cold-water immersion (CWI), partial-body cryotherapy (PBC), or a passive control (CON) on physiological and... (Randomized Controlled Trial)
Randomized Controlled Trial
This randomized controlled trial examined the effects of cold-water immersion (CWI), partial-body cryotherapy (PBC), or a passive control (CON) on physiological and recovery variables following exercise-induced muscle damage (EIMD, 5 × 20 drop jumps) in females. Twenty-eight females were allocated to PBC (30 seconds at -60°C, 2 minutes at -135°C), CWI (10 minutes at 10°C), or CON (10 minutes resting). Muscle oxygen saturation (SmO ), cutaneous vascular conductance (CVC), mean arterial pressure (MAP), and local skin temperature were assessed at baseline and through 60 minutes (10-minute intervals), while delayed onset of muscle soreness (DOMS), muscle swelling, maximum voluntary isometric contraction (MVIC), and vertical jump performance (VJP) were assessed up to 72 hours (24-hour intervals) following treatments. SmO was lower in PBC (Δ-2.77 ± 13.08%) and CWI (Δ-5.91 ± 11.80%) compared with CON (Δ18.96 ± 1.46%) throughout the 60-minute follow-up period (P < .001). CVC was lower from PBC (92.7 ± 25.0%, 90.5 ± 23.4%) and CWI (90.3 ± 23.5%, 88.1 ± 22.9%) compared with CON (119.0 ± 5.1 and 116.1 ± 6.6%, respectively) between 20 and 30 minutes (P < .05). Mean skin temperature was lower from CWI vs PBC (between 10 and 40 minutes, P < .05). Mean skin temperature was higher in CON compared with CWI up to 60 minutes and compared with PBC up to 30 minutes (P < .05). DOMS was lower following both PBC and CWI compared with CON through 72-hour (P < .05), with no difference between groups. No main group differences for swelling, MVIC, and VJP were observed. In conclusion, CWI elicited generally greater physiological effects compared with PBC while both interventions were more effective than CON in reducing DOMS in females, but had no effect on functional measures or swelling.
Topics: Adult; Cold Temperature; Cryotherapy; Female; Humans; Immersion; Isometric Contraction; Muscle, Skeletal; Myalgia; Skin Temperature; Water; Young Adult
PubMed: 31677292
DOI: 10.1111/sms.13593 -
Frontiers in Bioengineering and... 2021Lifting up objects from the floor has been identified as a risk factor for low back pain, whereby a flexed spine during lifting is often associated with producing higher...
Lifting up objects from the floor has been identified as a risk factor for low back pain, whereby a flexed spine during lifting is often associated with producing higher loads in the lumbar spine. Even though recent biomechanical studies challenge these assumptions, conclusive evidence is still lacking. This study therefore aimed at comparing lumbar loads among different lifting styles using a comprehensive state-of-the-art motion capture-driven musculoskeletal modeling approach. Thirty healthy pain-free individuals were enrolled in this study and asked to repetitively lift a 15 kg-box by applying 1) a freestyle, 2) a squat and 3) a stoop lifting technique. Whole-body kinematics were recorded using a 16-camera optical motion capture system and used to drive a full-body musculoskeletal model including a detailed thoracolumbar spine. Continuous as well as peak compressive, anterior-posterior shear and total loads (resultant load vector of the compressive and shear load vectors) were calculated based on a static optimization approach and expressed as factor body weight (BW). In addition, lumbar lordosis angles and total lifting time were calculated. All parameters were compared among the lifting styles using a repeated measures design. For each lifting style, loads increased towards the caudal end of the lumbar spine. For all lumbar segments, stoop lifting showed significantly lower compressive and total loads (-0.3 to -1.0BW) when compared to freestyle and squat lifting. Stoop lifting produced higher shear loads (+0.1 to +0.8BW) in the segments T12/L1 to L4/L5, but lower loads in L5/S1 (-0.2 to -0.4BW). Peak compressive and total loads during squat lifting occurred approximately 30% earlier in the lifting cycle compared to stoop lifting. Stoop lifting showed larger lumbar lordosis range of motion (35.9 ± 10.1°) than freestyle (24.2 ± 7.3°) and squat (25.1 ± 8.2°) lifting. Lifting time differed significantly with freestyle being executed the fastest (4.6 ± 0.7 s), followed by squat (4.9 ± 0.7 s) and stoop (5.9 ± 1.1 s). Stoop lifting produced lower total and compressive lumbar loads than squat lifting. Shear loads were generally higher during stoop lifting, except for the L5/S1 segment, where anterior shear loads were higher during squat lifting. Lifting time was identified as another important factor, considering that slower speeds seem to result in lower loads.
PubMed: 34805121
DOI: 10.3389/fbioe.2021.769117 -
Nature Neuroscience Apr 2023Task-free functional connectivity in animal models provides an experimental framework to examine connectivity phenomena under controlled conditions and allows for...
Task-free functional connectivity in animal models provides an experimental framework to examine connectivity phenomena under controlled conditions and allows for comparisons with data modalities collected under invasive or terminal procedures. Currently, animal acquisitions are performed with varying protocols and analyses that hamper result comparison and integration. Here we introduce StandardRat, a consensus rat functional magnetic resonance imaging acquisition protocol tested across 20 centers. To develop this protocol with optimized acquisition and processing parameters, we initially aggregated 65 functional imaging datasets acquired from rats across 46 centers. We developed a reproducible pipeline for analyzing rat data acquired with diverse protocols and determined experimental and processing parameters associated with the robust detection of functional connectivity across centers. We show that the standardized protocol enhances biologically plausible functional connectivity patterns relative to previous acquisitions. The protocol and processing pipeline described here is openly shared with the neuroimaging community to promote interoperability and cooperation toward tackling the most important challenges in neuroscience.
Topics: Rats; Animals; Brain; Brain Mapping; Consensus; Neuroimaging; Magnetic Resonance Imaging
PubMed: 36973511
DOI: 10.1038/s41593-023-01286-8 -
Alzheimer's & Dementia : the Journal of... May 2023Direct comparisons of the main blood phosphorylated tau immunoassays in memory clinic populations are needed to understand possible differences.
INTRODUCTION
Direct comparisons of the main blood phosphorylated tau immunoassays in memory clinic populations are needed to understand possible differences.
METHODS
In the BIODEGMAR study, 197 participants presenting with cognitive complaints were classified into an Alzheimer's disease (AD) or a non-AD cerebrospinal fluid (CSF) profile group, according to their amyloid beta 42/ phosphorylated tau (Aβ42/p-tau) ratio. We performed a head-to-head comparison of nine plasma and nine CSF tau immunoassays and determined their accuracy to discriminate abnormal CSF Aβ42/p-tau ratio.
RESULTS
All studied plasma tau biomarkers were significantly higher in the AD CSF profile group compared to the non-AD CSF profile group and significantly discriminated abnormal CSF Aβ42/p-tau ratio. For plasma p-tau biomarkers, the higher discrimination accuracy was shown by Janssen p-tau217 (r = 0.76; area under the curve [AUC] = 0.96), ADx p-tau181 (r = 0.73; AUC = 0.94), and Lilly p-tau217 (r = 0.73; AUC = 0.94).
DISCUSSION
Several plasma p-tau biomarkers can be used in a specialized memory clinic as a stand-alone biomarker to detect biologically-defined AD.
HIGHLIGHTS
Patients with an Alzheimer's disease cerebrospinal fluid (AD CSF) profile have higher plasma phosphorylated tau (p-tau) levels than the non-AD CSF profile group. All plasma p-tau biomarkers significantly discriminate patients with an AD CSF profile from the non-AD CSF profile group. Janssen p-tau217, ADx p-tau181, and Lilly p-tau217 in plasma show the highest accuracy to detect biologically defined AD. Janssen p-tau217, ADx p-tau181, Lilly p-tau217, Lilly p-tau181, and UGot p-tau231 in plasma show performances that are comparable to their CSF counterparts.
Topics: Humans; Alzheimer Disease; Amyloid beta-Peptides; Biomarkers; Cognitive Dysfunction; Enzyme-Linked Immunosorbent Assay; Immunoassay; tau Proteins
PubMed: 36370462
DOI: 10.1002/alz.12841