Quality of Life After Intravenous Thrombolysis for Acute Ischemic Stroke: Results From the AcT Randomized Controlled Trial.

BACKGROUND: Recent evidence from thrombolysis trials indicates the noninferiority of intravenous tenecteplase to intravenous alteplase with respect to good functional outcomes in patients with acute stroke. We examined whether the health-related quality of life (HRQOL) of patients with acute stroke differs by the type of thrombolysis treatment received. In addition, we examined the association between the modified Rankin Scale score 0 to 1 and HRQOL and patient-reported return to prebaseline stroke functioning at 90 days. METHODS: Data were from all patients included in the AcT trial (Alteplase Compared to Tenecteplase), a pragmatic, registry-linked randomized trial comparing tenecteplase with alteplase. HRQOL at 90-day post-randomization was assessed using the 5-item EuroQOL questionnaire (EQ5D), which consists of 5 items and a visual analog scale (VAS). EQ5D index values were estimated from the EQ5D items using the time tradeoff approach based on Canadian norms. Tobit regression and quantile regression models were used to evaluate the adjusted effect of tenecteplase versus alteplase treatment on the EQ5D index values and VAS score, respectively. The association between return to prebaseline stroke functioning and the modified Rankin Scale score 0 to 1 and HRQOL was quantified using correlation coefficient (r) with 95% CI. RESULTS: Of 1577 included in the intention-to-treat analysis patients, 1503 (95.3%) had complete data on the EQ5D. Of this, 769 (51.2%) were administered tenecteplase and 717 (47.7%) were female. The mean EQ5D VAS score and EQ5D index values were not significantly higher for those who received intravenous tenecteplase compared with those who received intravenous alteplase (P=0.10). Older age (P<0.01), more severe stroke assessed using the National Institutes of Health Stroke Scale (P<0.01), and longer stroke onset-to-needle time (P=0.004) were associated with lower EQ5D index and VAS scores. There was a strong association (r, 0.85 [95% CI, 0.81-0.89]) between patient-reported return to prebaseline functioning and modified Rankin Scale score 0 to 1 Similarly, there was a moderate association between return to prebaseline functioning and EQ5D index (r, 0.45 [95% CI, 0.40-0.49]) and EQ5D VAS scores (r, 0.42 [95% CI, 0.37-0.46]). CONCLUSIONS: Although there is no differential effect of thrombolysis type on patient-reported global HRQOL and EQ 5D-5L index values in patients with acute stroke, sex- and age-related differences in HRQOL were noted in this study. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03889249.

Effect of Time to Thrombolysis on Clinical Outcomes in Patients With Acute Ischemic Stroke Treated With Tenecteplase Compared to Alteplase: Analysis From the AcT Randomized Controlled Trial.

BACKGROUND: The AcT (Alteplase Compared to Tenecteplase) randomized controlled trial showed that tenecteplase is noninferior to alteplase in treating patients with acute ischemic stroke within 4.5 hours of symptom onset. The effect of time to treatment on clinical outcomes with alteplase is well known; however, the nature of this relationship is yet to be described with tenecteplase. We assessed whether the association of time to thrombolysis treatment with clinical outcomes in patients with acute ischemic stroke differs by whether they receive intravenous tenecteplase versus alteplase. METHODS: Patients included were from AcT, a pragmatic, registry-linked, phase 3 randomized controlled trial comparing intravenous tenecteplase to alteplase in patients with acute ischemic stroke. Eligible patients were >18 years old, with disabling neurological deficits, presenting within 4.5 hours of symptom onset, and eligible for thrombolysis. Primary outcome was modified Rankin Scale score 0 to 1 at 90 days. Safety outcomes included 24-hour symptomatic intracerebral hemorrhage and 90-day mortality rates. Mixed-effects logistic regression was used to assess the following: (a) the association of stroke symptom onset to needle time; (b) door (hospital arrival) to needle time with outcomes; and (c) if these associations were modified by type of thrombolytic administered (tenecteplase versus alteplase), after adjusting for age, sex, baseline stroke severity, and site of intracranial occlusion. RESULTS: Of the 1538 patients included in this analysis, 1146 (74.5%; 591 tenecteplase and 555 alteplase) presented within 3 hours versus 392 (25.5%; 196: TNK and 196 alteplase) who presented within 3 to 4.5 hours of symptom onset. Baseline patient characteristics in the 0 to 3 hours versus 3- to 4.5-hour time window were similar, except patients in the 3- to 4.5-hour window had lower median baseline National Institutes of Health Stroke Severity Scale (10 versus 7, respectively) and lower proportion of patients with large vessel occlusion on baseline CT angiography (26.9% versus 18.7%, respectively). Type of thrombolytic agent (tenecteplase versus alteplase) did not modify the association between continuous onset to needle time (Pinteraction=0.161) or door-to-needle time (Pinteraction=0.972) and primary clinical outcome. Irrespective of the thrombolytic agent used, each 30-minute reduction in onset to needle time was associated with a 1.8% increase while every 10 minutes reduction in door-to-needle time was associated with a 0.2% increase in the probability of achieving 90-day modified Rankin Scale score 0 to 1, respectively. CONCLUSIONS: The effect of time to tenecteplase administration on clinical outcomes is like that of alteplase, with faster administration resulting in better clinical outcomes. REGISTRATION: URL: https://classic. CLINICALTRIALS: gov; Unique identifier: NCT03889249.

Ethnic differences in the consistency and accuracy of perceived exertion.

OBJECTIVES: This study investigated the effect of weight loss and weight regain on accuracy of perceived exertion (APE) in previously overweight African American (AA) and European American (EA) women. METHODS: Formerly overweight women (n = 102, age 20-44 years) completed a weight loss program to achieve BMI < 25 kg/m(2) . Physiological variable of exertion and rating of perceived exertion (RPE, Borg's 6-20 Scale) were recorded during submaximal aerobic exercise prior to, immediately following, and approximately 1 year after weight loss. APE was defined as the composite score of physiological variables (heart rate, ventilation rate, and respiratory exchange ratio) minus RPE. RESULTS: APE was significantly different from the composite score of physiological variables at baseline and at 1-year follow-up for EA women (0.347 ± 0.88 P < 0.05 and 0.53 ± 0.92, P < 0.01, respectively) and at 1-year follow-up for AA (-0.37 ± 1.1, P < 0.01). EA women had lower physiological effort at baseline and 1-year follow-up states (-0.24 ± 0.66 P < 0.05; and, -0.27 ± 0.84 P < 0.05, respectively). AA women had higher physiological effort, at 1-year follow-up state (0.21 ± 0.61, P < 0.01). CONCLUSIONS: Physiologic effort and perceived exertion contributed independently to the racial differences in APE, and APE may be an important trait to evaluate before planning an exercise intervention. Am. J. Hum. Biol. 28:398-404, 2016. © 2015 Wiley Periodicals, Inc.

Safety and efficacy of tenecteplase versus alteplase in stroke patients with carotid tandem lesions: Results from the AcT trial.

BACKGROUND: Carotid tandem lesions ((TL) ⩾70% stenosis or occlusion) account for 15-20% of acute stroke with large vessel occlusion. AIMS: We investigated the safety and efficacy of intravenous tenecteplase (0.25 mg/kg) versus intravenous alteplase (0.9 mg/kg) in patients with carotid TL. METHODS: This is a substudy of the alteplase compared with the tenecteplase trial. Patients with ⩾70% stenosis of the extracranial internal carotid artery (ICA) and concomitant occlusion of the intracranial ICA, M1 or M2 segments of the middle cerebral artery on baseline computed tomography angiography (CTA) were included. Primary outcome was 90-day-modified Rankin Scale (mRS) 0-1. Secondary outcomes were mRS 0-2, mortality, and symptomatic ICH (sICH). Angiographic outcomes were successful recanalization (revised Arterial Occlusive Lesion (rAOL) 2b-3) on first and successful reperfusion (eTICI 2b-3) on final angiographic acquisitions. Multivariable mixed-effects logistic regression was performed. RESULTS: Among 1577 alteplase versus tenecteplase randomized controlled trial (AcT) patients, 128 (18.8%) had carotid TL. Of these, 93 (72.7%) underwent intravenous thrombolysis plus endovascular thrombectomy (IVT + EVT), while 35 (27.3%) were treated with IVT alone. In the IVT + EVT group, tenecteplase was associated with higher odds of 90-day-mRS 0-1 (46.0% vs. 32.6%, adjusted OR (aOR) 3.21; 95% CI = 1.06-9.71) compared with alteplase. No statistically significant differences in rates of mRS 0-2 (aOR 1.53; 95% CI = 0.51-4.55), initial rAOL 2b-3 (16.3% vs. 28.6%), final eTICI 2b-3 (83.7% vs. 85.7%), and mortality (18.0% vs. 16.3%) were found. SICH only occurred in one patient. There were no differences in outcomes between thrombolytic agents in the IVT-only group. CONCLUSION: In patients with carotid TL treated with EVT, intravenous tenecteplase may be associated with similar or better clinical outcomes, similar angiographic reperfusion rates, and safety outcomes as compared with alteplase.

Safety and Efficacy of Tenecteplase Compared With Alteplase in Patients With Large Vessel Occlusion Stroke: A Prespecified Secondary Analysis of the ACT Randomized Clinical Trial.

Importance: It is unknown whether intravenous thrombolysis using tenecteplase is noninferior or preferable compared with alteplase for patients with acute ischemic stroke. Objective: To examine the safety and efficacy of tenecteplase compared to alteplase among patients with large vessel occlusion (LVO) stroke. Design, Setting, and Participants: This was a prespecified analysis of the Intravenous Tenecteplase Compared With Alteplase for Acute Ischaemic Stroke in Canada (ACT) randomized clinical trial that enrolled patients from 22 primary and comprehensive stroke centers across Canada between December 10, 2019, and January 25, 2022. Patients 18 years and older with a disabling ischemic stroke within 4.5 hours of symptom onset were randomly assigned (1:1) to either intravenous tenecteplase or alteplase and were monitored for up to 120 days. Patients with baseline intracranial internal carotid artery (ICA), M1-middle cerebral artery (MCA), M2-MCA, and basilar occlusions were included in this analysis. A total of 1600 patients were enrolled, and 23 withdrew consent. Exposures: Intravenous tenecteplase (0.25 mg/kg) vs intravenous alteplase (0.9 mg/kg). Main Outcomes and Measures: The primary outcome was the proportion of modified Rankin scale (mRS) score 0-1 at 90 days. Secondary outcomes were an mRS score from 0 to 2, mortality, and symptomatic intracerebral hemorrhage. Angiographic outcomes were successful reperfusion (extended Thrombolysis in Cerebral Infarction scale score 2b-3) on first and final angiographic acquisitions. Multivariable analyses (adjusting for age, sex, National Institute of Health Stroke Scale score, onset-to-needle time, and occlusion location) were carried out. Results: Among 1577 patients, 520 (33.0%) had LVO (median [IQR] age, 74 [64-83] years; 283 [54.4%] women): 135 (26.0%) with ICA occlusion, 237 (45.6%) with M1-MCA, 117 (22.5%) with M2-MCA, and 31 (6.0%) with basilar occlusions. The primary outcome (mRS score 0-1) was achieved in 86 participants (32.7%) in the tenecteplase group vs 76 (29.6%) in the alteplase group. Rates of mRS 0-2 (129 [49.0%] vs 131 [51.0%]), symptomatic intracerebral hemorrhage (16 [6.1%] vs 11 [4.3%]), and mortality (19.9% vs 18.1%) were similar in the tenecteplase and alteplase groups, respectively. No difference was noted in successful reperfusion rates in the first (19 [9.2%] vs 21 [10.5%]) and final angiogram (174 [84.5%] vs 177 [88.9%]) among 405 patients who underwent thrombectomy. Conclusions and Relevance: The findings in this study indicate that intravenous tenecteplase conferred similar reperfusion, safety, and functional outcomes compared to alteplase among patients with LVO.

Association between ketosis and metabolic adaptation at the level of resting metabolic rate.

BACKGROUND: The ketone body ß-hydroxybutyrate (ßHB) has been shown to act as a signaling molecule that regulates metabolism and energy homeostasis during starvation in animal models. A potential association between ßHB and metabolic adaptation (a reduction in energy expenditure below predicted levels) in humans has never been explored. OBJECTIVE: To determine if metabolic adaptation at the level of resting metabolic rate (RMR) was associated with the magnitude of ketosis induced by a very-low energy diet (VLED). A secondary aim was to investigate if the association was modulated by sex. METHODS: Sixty-four individuals with obesity (BMI: 34.5 ± 3.4 kg/m2; age: 45.7 ± 8.0 years; 31 males) enrolled in a 1000 kcal/day diet for 8 weeks. Body weight/composition, RMR and ßHB (as a measure of ketosis) were determined at baseline and week 9 (W9). Metabolic adaptation was defined as a significantly lower measured versus predicted RMR (from own regression model). RESULTS: Participants lost on average 14.0 ± 3.9 kg and were ketotic (ßHB: 0.76 ± 0.51 mM) at W9. A significant metabolic adaptation was seen (-84 ± 106 kcal/day, P < 0.001), with no significant differences between sexes. [ßHB] was positively correlated with the magnitude of metabolic adaptation in females (r = 0.432, P = 0.012, n = 33), but not in males (r = 0.089, P = 0.634, n = 31). CONCLUSION: In females with obesity, but not males, the larger the [ßHB] under VLED, the greater the metabolic adaptation at the level of RMR. More studies are needed to confirm these findings and to explore the mechanisms behind the sex difference in the association between ketosis and metabolic adaptation. TRIAL REGISTRATION NAME: Clinicaltrials.gov. STUDY REGISTRATION ID: NCT02944253. URL: https://clinicaltrials.gov/ct2/show/NCT02944253.

Why intensity is not a bad word: Optimizing health status at any age.

Age-related declines in health and function make locomotion increasingly difficult leading to reductions in non-exercise activity thermogenesis (NEAT), skeletal muscle size and strength, and increased adiposity. Exercise is an important strategy to attenuate loss of function through the life cycle. Despite claims to the contrary, high-intensity exercise is important for the prevention of obesity and sarcopenia with advancing age. Therefore, the purpose of this mini-review is to present literature supporting the contention that low volume, high-intensity aerobic and/or resistance training can slow sarcopenia, sustain ease of movement, stimulate NEAT, and attenuate the accretion of fat mass.

Exercise following Mental Work Prevented Overeating.

UNLABELLED: Mental work may promote caloric intake, whereas exercise may offset positive energy balance by decreasing energy intake and increasing energy expenditure. PURPOSE: This study aimed to replicate previous findings that mental work increases caloric intake compared with a rest condition and assess whether exercise after mental work can offset this effect. METHODS: Thirty-eight male and female university students were randomly assigned to mental work + rest (MW + R) or mental work + exercise (MW + E). Participants also completed a baseline rest (BR) visit consisting of no mental work or exercise. Visit order was counterbalanced. During the MW + R or MW + E visit, participants completed a 20-min mental task and either a 15-min rest (MW + R) or a 15-min interval exercise (MW + E). Each visit ended with an ad libitum pizza lunch. A two-way repeated-measures ANOVA was used to compare eating behavior between groups. RESULTS: Participants in the MW + R condition consumed an average of 100 more kilocalories compared with BR (633.3 ± 72.9 and 533.9 ± 67.7, respectively, P = 0.02), and participants in MW + E consumed an average of 25 kcal less compared with BR (432.3 ± 69.2 and 456.5 ± 64.2, respectively, P > 0.05). When including the estimated energy expenditure of exercise in the MW + E conditions, participants were in negative energy balance by an average of 98.5 ± 41.5 kcal, resulting in a significant difference in energy balance between the two groups (P = 0.001). CONCLUSION: An acute bout of interval exercise after mental work resulted in significantly decreased food consumption compared with a nonexercise condition. These results suggest that an acute bout of exercise may be used to offset positive energy balance induced by mental tasks.

Changes in vascular hemodynamics in older women following 16 weeks of combined aerobic and resistance training.

The purpose of this study was to determine whether combined (aerobic and anaerobic) training decreases blood pressure (BP) and improves vascular properties. Seventy-nine postmenopausal women were randomly assigned to 3 groups that trained at different frequencies. Maximum oxygen uptake, body composition, BP, and arterial elasticity were evaluated prior to training and after 16 weeks of training. There was a significant time effect (decrease) for resting systolic BP (SBP) and rate pressure product. Exercise SBP, diastolic BP (DBP), heart rate, and RPP also decreased. Changes in total vascular impedance were related to SBP and changes in systemic vascular resistance were related to changes in DBP independent of body composition changes. Our findings suggest that combined training reduces SBP and improves vascular properties and that combined training 1 d/wk decreases BP similar to more frequent combined training. Training-induced changes in arterial resistance and impedance may be involved in inducing changes in BP.

Vitamin D intake is associated with insulin sensitivity in African American, but not European American, women.

BACKGROUND: The prevalence of type 2 diabetes is higher among African Americans (AA) vs European Americans (EA), independent of obesity and other known confounders. Although the reason for this disparity is not known, it is possible that relatively low levels of vitamin D among AA may contribute, as vitamin D has been positively associated with insulin sensitivity in some studies. The objective of this study was to test the hypothesis that dietary vitamin D would be associated with a robust measure of insulin sensitivity in AA and EA women. METHODS: Subjects were 115 African American (AA) and 137 European American (EA) healthy, premenopausal women. Dietary intake was determined with 4-day food records; the insulin sensitivity index (SI) with a frequently-sampled intravenous glucose tolerance test and minimal modeling; the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) with fasting insulin and glucose; and body composition with dual-energy X-ray absorptiometry. RESULTS: Vitamin D intake was positively associated with SI (standardized beta = 0.18, P = 0.05) and inversely associated with HOMA-IR (standardized beta = -0.26, P = 0.007) in AA, and the relationships were independent of age, total body fat, energy intake, and % kcal from fat. Vitamin D intake was not significantly associated with indices of insulin sensitivity/resistance in EA (standardized beta = 0.03, P = 0.74 and standardized beta = 0.02, P = 0.85 for SI and HOMA-IR, respectively). Similar to vitamin D, dietary calcium was associated with SI and HOMA-IR among AA but not EA. CONCLUSIONS: This study provides novel findings that dietary vitamin D and calcium were independently associated with insulin sensitivity in AA, but not EA. Promotion of these nutrients in the diet may reduce health disparities in type 2 diabetes risk among AA, although longitudinal and intervention studies are required.