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Can the early use of botulinum toxin in post stroke spasticity reduce contracture development? A randomised controlled trial.
Lindsay, C, Ispoglou, S, Helliwell, B, Hicklin, D, Sturman, S, Pandyan, A
Clinical rehabilitation. 2021;(3):399-409
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Abstract
OBJECTIVE Does early treatment of spasticity with botulinum-toxin (BoNTA), in (hyper)acute stroke patients without arm-function, reduce contractures and improve function. DESIGN Randomised placebo-controlled-trial. SETTING Specialised stroke-unit. PARTICIPANTS & INTERVENTION Patients with an Action Research Arm Test (ARAT) grasp-score⩽2 who developed spasticity within six-weeks of a first stroke were randomised to receive injections of: 0.9%sodium-chloride solution (placebo) or onabotulinumtoxin-A (treatment). OUTCOME-MEASURES Spasticity, contractures, splint use and arm function (ARAT) were taken at baseline, 12-weeks post-injection and six-months after stroke. Additionally, spasticity and contractures were measured at weeks-two, four and six post-injection. RESULTS Ninety three patients were randomised. Mean time to intervention was 18-days (standard deviation = 9.3). Spasticity was lower in the treatment group with difference being significant between week-2 to 12 (elbow) and week-2 to 6 (wrist). Mean-difference (MD) varied between -8.5(95% CI -17 to 0) to -9.4(95% CI -14 to -5) µV.Contracture formation was slower in the treatment group. Passive range of motion was higher in the treatment group and was significant at week-12 (elbow MD6.6 (95% CI -0.7 to -12.6)) and week-6 (wrist MD11.8 (95% CI 3.8 to 19.8)). The use of splints was lower in the treatment group odds ratio was 7.2 (95% CI 1.5 to 34.1) and 4.2 (95% CI 1.3 to 14.0) at week-12 and month-6 respectively.Arm-function was not significantly different between the groups MD2.4 (95% CI -5.3 to 10.1) and 2.9 (95% CI -5.8 to 11.6) at week-12 and month-6 respectively. CONCLUSION BoNTA reduced spasticity and contractures after stroke and effects lasted for approximately 12-weeks. BoNTA reduced the need for concomitant contracture treatment and did not interfere with recovery of arm function. TRIAL REGISTRATION EudraCT (2010-021257-39) and ClinicalTrials.gov-Identifier: NCT01882556.
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Platelet function in stroke/transient ischemic attack patients treated with tocotrienol.
Slivka, A, Rink, C, Paoletto, D, Sen, CK
FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2020;(9):11838-11843
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The purpose of this study was to characterize the effects of tocotrienol form of vitamin E (TCT) on platelet function in patients with stroke or transient ischemic attack (TIA). A double blind, randomized, single center phase II clinical trial was conducted comparing placebo (PBO) and 400 and 800 mg TCT daily for a year in 150 patients with a sentinel ischemic stroke or TIA event in the prior 6 months. Platelet function was measured at baseline and then, at 3 month intervals for a year, using light transmission aggregometry. The incidence of aspirin resistance in aspirin-treated patients or platelet inhibition in patients on clopidogrel alone was compared between the three treatment groups. Results showed that in patients taking aspirin and clopidogrel, the incidence of aspirin resistance was significantly decreased from 40% in PBO-treated patients to 9% in the 400 mg TCT group and 25% in the TCT 800 mg group (P = .03). In conclusion, patients on aspirin and clopidogrel had a higher incidence of aspirin resistance than all patients treated with aspirin alone and TCT decreased the frequency of aspirin resistance in this group.
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Matrix Gla protein polymorphism rs1800801 associates with recurrence of ischemic stroke.
Hendrix, P, Sofoluke, N, Adams, M, Kunaprayoon, S, Zand, R, Kolinovsky, AN, Person, TN, Gupta, M, Goren, O, Kirchner, HL, et al
PloS one. 2020;(6):e0235122
Abstract
The MGP single nucleotide polymorphism (SNP) rs1800801 has previously been associated with recurrent ischemic stroke in a Spanish cohort. Here, we tested for association of this SNP with ischemic stroke recurrence in a North American Caucasian cohort. Acute ischemic stroke patients admitted between 10/2009 and 12/2016 at three hospitals within a large healthcare system in the northeastern United States that were enrolled in a healthcare system-wide exome sequencing program were retrospectively reviewed. Patients with recurrent stroke within 1 year after index event were compared to those without recurrence. Of 9,348 suspected acute ischemic strokes admitted between 10/2009 and 12/2016, 1,727 (18.5%) enrolled in the exome-sequencing program. Among those, 1,068 patients had exome sequencing completed and were eligible for inclusion. Recurrent stroke within the first year of stroke was observed in 79 patients (7.4%). In multivariable analysis, stroke prior to the index stroke (OR 9.694, 95% CI 5.793-16.224, p ≤ 0.001), pro-coagulant status (OR = 3.563, 95% CI 1.504-8.443, p = 0.004) and the AA genotype of SNP rs1800801 (OR = 2.408, 95% CI 1.079-4.389, p = 0.004) were independently associated with recurrent stroke within the first year. The AA genotype of the MGP SNP rs1800801 is associated with recurrence within the first year after ischemic stroke in North American Caucasians. Study of stroke subtypes and additional populations will be required to determine if incorporation of allelic status at this SNP into current risk scores improves prediction of recurrent ischemic stroke.
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Effect of a gum-based thickener on the safety of swallowing in patients with poststroke oropharyngeal dysphagia.
Bolivar-Prados, M, Rofes, L, Arreola, V, Guida, S, Nascimento, WV, Martin, A, Vilardell, N, Ortega Fernández, O, Ripken, D, Lansink, M, et al
Neurogastroenterology and motility. 2019;(11):e13695
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BACKGROUND Increasing viscosity with thickening agents is a valid therapeutic strategy for oropharyngeal dysphagia (OD). To assess the therapeutic effect of a xanthan gum-based thickener (Nutilis Clear® ) at six viscosities compared with thin liquid in poststroke OD (PSOD) patients. METHODS A total of 120 patients with PSOD were studied in this controlled, multiple-dose, fixed-order, and single-blind study using videofluoroscopy (VFSS). A series of boluses of 10 mL thin liquid and 2000, 1400, 800, 450, 250, and 150 mPa s viscosities were given in duplicate, interrupted in case of aspiration. We assessed the safety and efficacy of swallow and the kinematics of the swallow response. KEY RESULTS A total of 41.2% patients had safe swallow at thin liquid which significantly increased for all viscosities from 71.9% at 150 mPa s to 95.6% at 1400 mPa s (P < .001). PAS score (3.7 ± 2.3) at thin liquid was also reduced by increasing bolus viscosity (P < .001). The prevalence of patients with aspiration at thin liquid was 17.5% and decreased at all viscosities (P < .01), except at 150 mPa s. Increasing viscosity shortened time to laryngeal vestibule closure (LVC) at all viscosities (P < .01) and reduced bolus velocity at ≥450 mPa s (P < .05). The prevalence of patients with pharyngeal residue at each viscosity 37.7%-44.7% was similar to that at thin liquid (41.2%). CONCLUSIONS AND INFERENCES The prevalence of unsafe swallow with thin liquids is very high in PSOD. Increasing shear bolus viscosity with this xanthan gum-based thickener significantly increased the safety of swallow in patients with PSOD in a viscosity-dependent manner without increasing the prevalence of pharyngeal residue.
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PCSK9 inhibition in patients with and without prior myocardial infarction or ischemic stroke: A pooled analysis of nine randomized-controlled studies of alirocumab.
Bruckert, E, Kereiakes, DJ, Koren, MJ, Louie, MJ, Letierce, A, Miller, K, Cannon, CP
Journal of clinical lipidology. 2019;(3):443-454
Abstract
BACKGROUND Patients with prior cardiovascular events are at very high risk of recurrent events and may benefit from low-density lipoprotein cholesterol (LDL-C) lowering beyond that achieved with maximally tolerated statins. OBJECTIVE To assess potential differences between the efficacy and safety of the proprotein convertase subtilisin/kexin type 9 inhibitor, alirocumab, in patients with vs without prior myocardial infarction (MI)/ischemic stroke. METHODS Data (n = 4880) were pooled from nine ODYSSEY phase 3 trials of alirocumab 75/150 mg or 150 mg every 2 weeks, mostly on background statins ± other lipid-lowering therapies. Analyses were performed according to statin status, alirocumab dose, and control (placebo or ezetimibe). RESULTS Baseline LDL-C, non-high-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and apolipoprotein B levels were lower and lipoprotein(a) higher in patients with than without prior MI/ischemic stroke. LDL-C levels were reduced from baseline to week 24 in patients with (51.1%-62.9%) and without (43.6%-58.3%) prior MI/ischemic stroke, with no significant interaction between prior MI/ischemic stroke status and LDL-C-lowering efficacy of alirocumab vs controls. Alirocumab significantly reduced other lipid/lipoproteins (including lipoprotein[a]) similarly in patients with/without MI/ischemic stroke. Week 24 LDL-C goal attainment rates for subgroups with/without prior MI/ischemic stroke on background statins were 74.1%-84.8% and 63.7%-74.7%, respectively. The safety profile of alirocumab was generally similar regardless of prior MI/ischemic stroke status. CONCLUSIONS Alirocumab significantly reduced LDL-C and other atherogenic lipids/lipoproteins in patients with prior MI/ischemic stroke, and the majority of this very high cardiovascular risk population achieved LDL-C goals; efficacy and safety results were similar in patients without prior MI/ischemic stroke.
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Health literacy and knowledge of chronic transfusion therapy in adolescents with sickle cell disease and caregivers.
Yee, MEM, Meyer, EK, Fasano, RM, Lane, PA, Josephson, CD, Brega, AG
Pediatric blood & cancer. 2019;(7):e27733
Abstract
BACKGROUND Patients with sickle cell disease (SCD) may require chronic transfusion therapy (CTT) for prevention of stroke or other complications. Limited health literacy (HL) is common and is associated with poor health-related knowledge and outcomes in chronic disease. We sought to assess HL and transfusion knowledge in patients with SCD on CTT and their caregivers. METHODS A cross-sectional study of patients was conducted in outpatient hematology clinics. Forty-five pairs of adolescent patients and caregivers and 20 caregivers of pre-adolescent patients completed the Newest Vital Sign HL assessment and answered questions assessing SCD and transfusion knowledge. Community-level median income and unemployment rates were estimated from Census data. We computed the correlation of HL with knowledge and compared each to Census variables, payor status, educational attainment, and stroke. RESULTS HL was inadequate in 22 (34%) caregivers and 31 (69%) adolescents. Adequate caregiver HL was associated with higher educational attainment but not community-level socioeconomics or payor status. Mean knowledge score was lower in adolescents than in caregivers and correlated with age in adolescents (r = 0.42, P = .004). HL correlated with knowledge (r = 0.46, P < .0001). There were no significant correlations of HL or knowledge between adolescents and their caregivers. Neither HL nor knowledge was associated with prior stroke. The greatest knowledge was demonstrated for iron overload and SCD genotype, whereas knowledge gaps existed in alloimmunization, indication for CTT, and SCD curative therapy. CONCLUSIONS Enhanced educational resources in transfusion therapy, alloimmunization, and curative therapy are needed for patients with SCD and caregivers of all HL levels.
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Rationale and design to assess the efficacy and safety of HT047 in patients with acute ischemic stroke: A multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase II trial.
Heo, SH, Song, J, Kim, BJ, Kim, H, Chang, DI, ,
Medicine. 2019;(43):e17655
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BACKGROUND Though several neuroprotective agents have been evaluated as potential treatments for acute ischemic stroke, none have demonstrated a definitive treatment efficacy, which remains elusive. HT047 is an herbal extract of Scutellaria baicalensis and Pueraria lobata, both of which have been widely used to treat ischemic stroke in traditional Korean medicine. The aims of this trial are to investigate whether HT047 can improve neurologic status, particularly motor function, in acute ischemic stroke patients, and to determine the safety of HT047. METHODS A multicenter, double-blind, randomized, placebo-controlled, 3-arm parallel group, phase II trial will be conducted in patients who have had an acute ischemic stroke within the past 14 days. The participating patients must have a Fugl-Meyer assessment (FMA) motor score ≤55, with arm or leg weakness, and Korean version of the National Institutes of Health Stroke scale (K-NIHSS) score of ≥4 and ≤15. Seventy-eight participants will be randomized in a 1:1:1 ratio and given high-dose HT047 (750 mg 3 times a day), low-dose HT047 (500 mg 3 times a day), or a placebo for 12 weeks. The primary endpoint is the change in FMA motor score between baseline and week 12. Secondary endpoints are as follows: the change in FMA motor score at weeks 4 and 8 from baseline; the change in FMA motor score at weeks 4, 8, and 12 from baseline according to the timing of treatment initiation (either within 1 week, or 1-2 weeks), or according to the presence of prognostic risk factors (hypertension, diabetes, dyslipidemia, etc); the change in K-NIHSS and Korean versions of the modified Rankin scale (K-mRS) and the modified Barthel index at weeks 4 and 12 from baseline; and the proportion of subjects at week 12 with a K-NIHSS score of 0 to 2, or with K-mRS scores of 0, ≤1, and ≤2. DISCUSSION This study is a 1st-in-human trial of HT047 to explore the efficacy and safety in acute ischemic stroke patients. The results will provide the appropriate dosage and evidence of therapeutic benefit of HT047 for stroke recovery. TRIAL REGISTRATION ClinicalTrials.gov (NCT02828540) Registered July 11, 2016.
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Epidemiology of coronary artery disease and stroke and associated risk factors in Gaza community -Palestine.
Jamee Shahwan, A, Abed, Y, Desormais, I, Magne, J, Preux, PM, Aboyans, V, Lacroix, P
PloS one. 2019;(1):e0211131
Abstract
AIM OF STUDY To determine the prevalence of cardiovascular disease and associated risk factors in the population of Gaza strip in Palestine. METHODS A cross-sectional stratified cluster sample design was applied in this study. A sample of 2240 participant (1121 males and 1119 females) aged ≥25 years participated in the study. For each individual, trained staff administered a questionnaire, where all variables of interest followed WHO's STEP wise approach to surveillance chronic disease risk factors (STEPS) (WHO, 2001). Sociodemographic data, anthropometric measure (body mass index, blood pressure), and biochemical test (blood sugar and lipids profiles) were measured. Short International Physical Activity (IPAQ) questionnaire form was used. Bivariate analysis and logistic regression were used with SPSS (version 22.0) to analyze the data. RESULTS The most common condition was coronary artery disease (8.3%), followed by stroke events (3%). The associated risk factors were obesity (47.8%), hypertension (28.4%), current smoking account for (23.2%), diabetes mellitus (19.1%), high cholesterol level (8.8%), and high triglycerides level (40.2%). Additionally, the proportion of being physical active was found to be low (48.3%); particularly with increasing age. More than 30% of the population has less than 4 days of consumption of fruit and vegetables per week and 65.9% has less than 2 servings per day. CONCLUSION The burden of CVDs and their associated risk factors is considerable in Gaza and represents a major public health concern. Effective strategies in management, education and healthcare centers are required for an accurate management and implementation of preventive measure in this area.
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A single session of trip-specific training modifies trunk control following treadmill induced balance perturbations in stroke survivors.
Nevisipour, M, Grabiner, MD, Honeycutt, CF
Gait & posture. 2019;:222-228
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BACKGROUND Individuals with stroke are at significant risk of falling. Trip-specific training is a targeted training approach that has been shown to reduce falls in older adults and amputees by enhancing the compensatory stepping response required to prevent a fall. Still, individuals with stroke have unique deficits (e.g. spasticity) which draws into question if this type of training will be effective for this population. OBJECTIVE Evaluate if a single session of trip-specific training can modify the compensatory stepping response (trunk movement, step length/duration, reaction time) of individuals with chronic stroke. METHODS Sixteen individuals with unilateral chronic stroke participated in a single session of trip-specific training consisting of 15 treadmill perturbations. A falls assessment consisting of 3 perturbations was completed before and after training. Recovery step kinematics measured during the pre- and post-test were compared using a repeated measures design. Furthermore, Fallers (those who experienced at least one fall during the pre- or post-test) were compared to Non-fallers. RESULTS Trip-specific training decreased trunk movement post perturbation. Specifically following training, Trunk flexion was 48 and 19 percent smaller on the small and medium perturbations at the end of the first compensatory step. Fallers (9 out of 16 subjects) post-training resembled Non-Fallers pre-training. Specifically, Trunk flexion at the completion of the first step during small and medium perturbations was not different between Fallers post-training and Non-Fallers pre-training. Still enthusiasm was tempered because Trunk flexion at the largest perturbation (where most falls occurred) was not changed and therefore total falls were not reduced as a result of this training. SIGNIFICANCE Our results indicate that trip-specific training modifies the dynamic falls response immediately following trip-like treadmill perturbations. However, the incidence of falls was not reduced with a single training session. Further study of the implications and length of the observed intervention effect are warranted.
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Rivaroxaban or aspirin for patent foramen ovale and embolic stroke of undetermined source: a prespecified subgroup analysis from the NAVIGATE ESUS trial.
Kasner, SE, Swaminathan, B, Lavados, P, Sharma, M, Muir, K, Veltkamp, R, Ameriso, SF, Endres, M, Lutsep, H, Messé, SR, et al
The Lancet. Neurology. 2018;(12):1053-1060
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BACKGROUND Patent foramen ovale (PFO) is a contributor to embolic stroke of undetermined source (ESUS). Subgroup analyses from previous studies suggest that anticoagulation could reduce recurrent stroke compared with antiplatelet therapy. We hypothesised that anticoagulant treatment with rivaroxaban, an oral factor Xa inhibitor, would reduce the risk of recurrent ischaemic stroke compared with aspirin among patients with PFO enrolled in the NAVIGATE ESUS trial. METHODS NAVIGATE ESUS was a double-blinded, randomised, phase 3 trial done at 459 centres in 31 countries that assessed the efficacy and safety of rivaroxaban versus aspirin for secondary stroke prevention in patients with ESUS. For this prespecified subgroup analysis, cohorts with and without PFO were defined on the basis of transthoracic echocardiography (TTE) and transoesophageal echocardiography (TOE). The primary efficacy outcome was time to recurrent ischaemic stroke between treatment groups. The primary safety outcome was major bleeding, according to the criteria of the International Society of Thrombosis and Haemostasis. The primary analyses were based on the intention-to-treat population. Additionally, we did a systematic review and random-effects meta-analysis of studies in which patients with cryptogenic stroke and PFO were randomly assigned to receive anticoagulant or antiplatelet therapy. FINDINGS Between Dec 23, 2014, and Sept 20, 2017, 7213 participants were enrolled and assigned to receive rivaroxaban (n=3609) or aspirin (n=3604). Patients were followed up for a mean of 11 months because of early trial termination. PFO was reported as present in 534 (7·4%) patients on the basis of either TTE or TOE. Patients with PFO assigned to receive aspirin had a recurrent ischaemic stroke rate of 4·8 events per 100 person-years compared with 2·6 events per 100 person-years in those treated with rivaroxaban. Among patients with known PFO, there was insufficient evidence to support a difference in risk of recurrent ischaemic stroke between rivaroxaban and aspirin (hazard ratio [HR] 0·54; 95% CI 0·22-1·36), and the risk was similar for those without known PFO (1·06; 0·84-1·33; pinteraction=0·18). The risks of major bleeding with rivaroxaban versus aspirin were similar in patients with PFO detected (HR 2·05; 95% CI 0·51-8·18) and in those without PFO detected (HR 2·82; 95% CI 1·69-4·70; pinteraction=0·68). The random-effects meta-analysis combined data from NAVIGATE ESUS with data from two previous trials (PICSS and CLOSE) and yielded a summary odds ratio of 0·48 (95% CI 0·24-0·96; p=0·04) for ischaemic stroke in favour of anticoagulation, without evidence of heterogeneity. INTERPRETATION Among patients with ESUS who have PFO, anticoagulation might reduce the risk of recurrent stroke by about half, although substantial imprecision remains. Dedicated trials of anticoagulation versus antiplatelet therapy or PFO closure, or both, are warranted. FUNDING Bayer and Janssen.