Background Early National Institutes of Health Stroke Scale (NIHSS) assessment may provide practical benefits over 90‐day modified Rankin Scale (mRS), but it is unclear how it compares in adjudicating randomized clinical trial (RCT) results in acute ischemic stroke. Methods and Results We searched Ovid Medline (inception to April 1, 2023) and included RCTs of acute therapies for acute ischemic stroke with data for both 90‐day mRS and NIHSS within 7 days. Primary outcome was agreement between trial results (classified as positive, negative, or neutral) based on 24‐hour NIHSS and 90‐day mRS scores. We additionally assessed agreement for 2‐hour, 48‐hour, 72‐ to 96‐hour, and 5‐ to 7‐day NIHSS scores. We aimed to validate our findings using individual patient data from the ESCAPE (Randomized Assessment of Rapid Endovascular Treatment of Ischemic Stroke) and ESCAPE‐NA1 (Safety and Efficacy of Nerinetide [NA‐1] in Subjects Undergoing Endovascular Thrombectomy for Stroke) RCTs. We included 116 trials (44 387 patients), contributing 165 NIHSS assessments. The 24‐hour NIHSS scores resulted in the same classification as 90‐day mRS scores in 61/73 (83.6%) trials (Cohen's kappa, 0.64 [95% CI: 0.45–0.83] and Gwet's agreement coefficient 1, 0.79 [95% CI: 0.67–0.90]). Agreement was not statistically different by timing of NIHSS assessments (range 75%–100%, P=0.33). Individual patient data showed higher agreement for assessments between 48 hours and 7 days, varying by NIHSS dichotomization cutoffs (NIHSS score, 0–2; 2 hours, 56.6%; 24 hours, 66.6%; 48 hours, 71.8%; 5–7 days: 76.5%, P<0.01; NIHSS score, 0–7; 2 hours, 72.8%; 24 hours, 80.5%; 48 hours, 83.1%; 5–7 days: 84.7%, P<0.01). Conclusions The 24‐hour NIHSS scores aligned with 90‐day mRS scores in 84% of RCT results, indicating intermediate‐to‐good agreement. However, individual patient data showed that early NIHSS risks misclassifying around 1/4 patients. These data contribute to a better understanding of the nuances of early NIHSS score as an outcome in acute ischemic stroke RCTs.

INTRODUCTION:Endovascular thrombectomy has shown significant benefits for patients with large-vessel ischaemic stroke. However, many countries face challenges establishing effective thrombectomy delivery systems, even when thrombolysis services are already in place. Moreover, there is limited research on implementing thrombectomy care delivery, particularly for scale-ups in low- and middle-income countries. This study identifies the key drivers of enhancing thrombectomy delivery systems in three Canadian regions and provides lessons for health systems in transition. METHODS:A qualitative research design with a phenomenological approach was employed. From January to December 2022, at three comprehensive ischaemic stroke centres in Canada, we involved non-participant observation and in-depth interviews with 91 key informants, including care providers and administrators engaged in large-vessel stroke care. Guided by the Behaviour Change Wheel and Theoretical Domains Framework, the data were transcribed and analysed using thematic content analysis. RESULTS:Three critical themes emerged. First, establishing a cohesive, goal-oriented, multidisciplinary patient care team with an egalitarian culture is vital. Second, integrating specific feedback data is essential for continuous quality improvement and for optimising workflow through collective leadership. Lastly, even with existing thrombolytic services, centralised regional planning and outreach to local thrombectomy implementers is necessary. Development must occur at stroke centres and their associated peripheral hospitals to build effective thrombectomy care delivery systems. CONCLUSIONS:Enhancing thrombectomy care delivery systems requires a stepwise approach: first, establishing multidisciplinary teams at the micro-level; next, fostering collective leadership for continuous quality improvement at the meso-level and finally, coordinating regional outreach and centralised planning at the macro-level. The Canadian experience highlights the importance of addressing these interconnected levels and underscores the critical role of central planning and collaboration between policymakers and care providers. These strategies offer a structured pathway for improving stroke care globally, particularly in transitioning health systems.

The medical research community widely endorses the importance of ensuring that research outputs are relevant and accessible to knowledge users, as well as the value of engaging the latter in the conduct of research to achieve these goals. However, it appears these principles are reflected in actual medical research practices to a limited extent. To better understand this dissonance, we conducted a qualitative investigation into the perspectives of key stakeholders on bridging the knowledge-to-action gap and patient and public engagement. The Priorities and Expectations of Researchers, Donors, Patients and the Public Regarding the Funding and Conduct of Medical Research (PERSPECT) qualitative study involved in-depth, semi-structured interviews with representatives of four stakeholder groups. Among other topics, participants were asked to discuss issues related to moving medical research knowledge into action (knowledge translation), including patient and public engagement during the research journey as a prerequisite to the success of this process. We analysed collected data employing an interpretative grounded theory approach. Data collection was ended once thematic saturation had been attained. A total of 41 interviews were completed and analysed (with 10 patients, 10 members of the general public, 11 researchers and 10 funders). Many participants expressed a belief in the importance of engaging patients in the research process, as well as ensuring that study findings reach beyond academic communities. However, multiple challenges and barriers were identified to implementing these values in practice, including: researchers having limited knowledge and tools to foster partnerships with community members; research outputs being inaccessible to the wider public; and the public having insufficient capacity – in view of the required time, effort and knowledge – to assimilate findings and contribute to ongoing research. Cumulatively, interviews indicated a continuing disconnect between research and lay communities, where each stakeholder group holds some responsibility for improving the current paradigm. Existing gaps in communication, knowledge and relevant competencies are fuelling a disconnect between research and lay communities. Successfully moving research knowledge into action requires joint efforts of multiple stakeholder groups with support from external resources to ensure necessary training, expertise and credible dissemination platforms.

Background: Stroke research is underfunded, but there is a paucity of data on the perspectives of researchers, funders, patients and the public about current funding paradigms. Understanding their priorities and opinions is important to guide meaningful innovation. Methods: The PERSPECT (Priorities & Expectations of Researchers, Donors, Patients and the Public Regarding the Funding & Conduct of Stroke Research) study involved in-depth, semi-structured one-on-one interviews with stroke researchers, funding organization representatives/philanthropists, patients, and members of the public. Participants were sampled using three axes (age, sex, ethnicity) to ensure diversity. They were asked to discuss thoughts about the state of stroke research funding and any potential or desired alternatives to current funding models. Qualitative analyses of transcripts included constant comparison and grounded theory content analysis. The study ended when the standard of thematic saturation was attained. Results: Forty-one interviews were completed (11 researchers, 10 research funders/philanthropists, 10 patients, 10 lay citizens). Researchers, philanthropists, patients, and public participants expressed a desire for greater transparency with grant funding processes, and voiced concerns that current models fostered bias towards certain topics and researchers. Patients and donors felt that conventional processes at times seemed disconnected from their interests. Crowdfunding was identified as an alternative strategy that could facilitate democratization in terms of topics studied, exploration of new frontiers, integration of diverse methods, and capacity building for less established researchers/centers. However, participants emphasized the importance of expert review, as in current processes, in building trust in proposal quality. They noted that successful crowdfunding strategies would require innovative approaches from researchers to promote their work. Conclusions: Our findings revealed stakeholder concerns about transparency and equity with current research funding paradigms. Stakeholders recognize crowdfunding as a useful alternative approach, but incorporation of expert review will be important to engender trust.

Background: Patient engagement and knowledge translation are increasingly recognized as critical components of stroke research. However, it is unclear how these components are currently perceived by interested parties. Methods: The PERSPECT (Priorities and Expectations of Researchers, Donors, Patients, and the Public Regarding the Funding and Conduct of Stroke Research) qualitative study involved in-depth, semi-structured interviews with patients, members of the general public, researchers, and donors, including board members of funding organizations and philanthropists. Participants were asked to discuss their thoughts about the role of patient and public engagement in stroke research and on the translation/dissemination of research findings. Collected data were analyzed through constant comparison and theme identification, followed by grounded theory content analysis. Results: Forty-one interviews were completed (11 with researchers and 10 for each patients, public and donors). An important theme that emerged was a need to re-evaluate and broaden conventional definitions of “expertise” in the context of selecting grant application review panels, recognizing the value of lived experience alongside that of education and professional experience. Whereas participants identified an important role for patient voices in guiding research direction and design; concerns were raised about the limited public awareness and understanding of medical research, which may hinder meaningful, advantageous involvement in the research process, as well as trust in evidence-based recommendations. In this regard, lay participants highlighted media-driven misinformation and a lack of credible lay-language resources as impeding effective dissemination of research findings. Conclusions: All four participant groups recognized the importance of knowledge end-users being engaged in research from its early stages, including decision-making about funding allocation. Impactful involvement seems however hindered by knowledge and communication gaps between the research and lay communities. Our results underscore the importance of efforts to make ongoing research and study findings more visible, accessible, and comprehensible.

To evaluate agreement between National Institutes of Health Stroke Scale (NIHSS) assessed within 7-days follow-up and 90-day modified Rankin Scale (mRS) outcomes in randomized-controlled trials (RCTs).

BACKGROUND AND PURPOSE:Hemorrhagic transformation can occur as a complication of endovascular treatment for acute ischemic stroke. This study aimed to determine whether ischemia depth as measured by admission CTP metrics can predict the development of hemorrhagic transformation at 24 hours. MATERIALS AND METHODS:Patients with baseline CTP and 24-hour follow-up imaging from the ESCAPE-NA1 trial were included. RAPID software was used to generate CTP volume maps for relative CBF, CBV, and time-to-maximum at different thresholds. Hemorrhage on 24-hour imaging was classified according to the Heidelberg system, and volumes were calculated. Univariable and multivariable regression analyses assessed the association between CTP lesion volumes and hemorrhage/hemorrhage subtypes. RESULTS:Among 408 patients with baseline CTP, 142 (35%) had hemorrhagic transformation at 24-hour follow-up, with 89 (63%) classified as hemorrhagic infarction (HI1/HI2), and 53 (37%), as parenchymal hematoma (PH1/PH2). Patients with HI or PH had larger volumes of low relative CBF and CBV at each threshold compared with those without hemorrhage. After we adjustied for baseline and treatment variables, only increased relative CBF <30% lesion volume was associated with any hemorrhage (adjusted OR, 1.14; 95% CI, 1.02-1.27 per 10 mL), as well as parenchymal hematoma (adjusted OR, 1.23; 95% CI, 1.06-1.43 per 10 mL). No significant associations were observed for hemorrhagic infarction. CONCLUSIONS:Larger "core" volumes of relative CBF <30% were associated with an increased risk of PH following endovascular treatment. This particular metric, in conjunction with other clinical and imaging variables, may, therefore, help estimate the risk of post-endovascular treatment hemorrhagic complications.

BackgroundIncomplete reperfusion (IR) after mechanical thrombectomy (MT) can be a consequence of residual occlusion, no-reflow phenomenon, or collateral counterpressure. Data on the impact of these phenomena on clinical outcome are limited. MethodsPatients from the ESCAPE-NA1 trial with IR (expanded Thrombolysis In Cerebral Infarction (eTICI) 2b) were compared with those with complete or near-complete reperfusion (eTICI 2c-3) on the final angiography run. Final runs were assessed for (a) an MT-accessible occlusion, or (b) a non-MT-accessible occlusion pattern. The primary clinical outcome was modified Rankin Scale (mRS) 0-2 at 90 days. Our imaging outcome was infarction in IR territory on follow-up imaging. Unadjusted and adjusted incidence rate ratios (aIRR) with 95% confidence intervals (95% CI) were obtained. ResultsOf 1105 patients, 443 (40.1%) with IR and 506 (46.1%) with complete or near-complete reperfusion were included. An MT-accessible occlusion was identified in 147/443 patients (33.2%) and a non-MT-accessible occlusion in 296/443 (66.8%). As compared with patients with near-complete/complete reperfusion, patients with IR had significantly lower chances of achieving mRS 0-2 at 90 days (aIRR 0.82, 95% CI 0.74 to 0.91). Rates of mRS 0-2 were lower in the MT-accessible occlusion group as compared with the non-MT-accessible occlusion pattern group (aIRR 0.71, 95% CI 0.60 to 0.83, and aIRR 0.89, 95% CI 0.81 to 0.98, respectively). More patients with MT-accessible occlusion patterns developed infarcts in the non-reperfused territory as compared with patients with non-MT occlusion patterns (68.7% vs 46.3%). ConclusionIR was associated with worse clinical outcomes than near-complete/complete reperfusion. Two-thirds of our patients with IR had non-MT-accessible occlusion patterns which were associated with better clinical and imaging outcomes compared with those with MT-accessible occlusion patterns.

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.

Background and aims: Recent evidence from thrombolysis trials indicate the non-inferiority of the Tenecteplase (TNK) to the Alteplase (TPA) with respect to functional outcomes in acute stroke patients. This study examines the predictors of patient-reported health-related quality of life (HRQOL) in acute stroke patients who received thrombolysis therapy. Methods: Data were used from all acute stroke patients included in AcT, a pragmatic, registry-linked randomized trial comparing TNK with TPA. HRQOL at 90-day post-randomization was assessed using the EuroQol-5D-5L (EQ-5D) visual analogue scale (VAS). Based on the Canadian norms, health state utilities were estimated from the EQ-5D items using the EQ-5D time trade-off approach. Tobit regression model and linear mixed-effects regression were used to evaluate the adjusted effect of type of treatment on health utility scores and VAS score, respectively. Results: Of the 1262 patients included in this analysis, 647(51.3%) were administered the TNK, 584(46.3%) were female, and 380(30.1%) were greater than or equal to 80 years old. There was no significant adjusted effect of the type of thrombolysis on health utility scores (adjusted beta coefficient [95%CI] = 0.029 [-0.001, 0.062]), but patients who received TNK reported higher adjusted VAS scores than those that received TPA [adjusted beta coefficient [95%CI] = 2.1 [-0.29, 4.49]). Older age (p < 0.01), female sex (p = 0.01), higher NIHSS score (p < 0.01) were associated with lower health utilities and VAS scores. Conclusion: There is no differential effect of the type of thrombolysis on patient-reported global HRQOL and health state utilities of acute stroke patients. Disparities in HRQOL were mainly explained by sex, age, and disease severity.

Background and aims: Recent evidence from thrombolysis trials indicate the non-inferiority of the Tenecteplase (TNK) to the Alteplase (TPA) with respect to functional outcomes in acute stroke patients. This study examines the predictors of patient-reported health-related quality of life (HRQOL) in acute stroke patients who received thrombolysis therapy. Methods: Data were used from all acute stroke patients included in AcT, a pragmatic, registry-linked randomized trial comparing TNK with TPA. HRQOL at 90-day post-randomization was assessed using the EuroQol-5D-5L (EQ-5D) visual analogue scale (VAS). Based on the Canadian norms, health state utilities were estimated from the EQ-5D items using the EQ-5D time trade-off approach. Tobit regression model and linear mixed-effects regression were used to evaluate the adjusted effect of type of treatment on health utility scores and VAS score, respectively. Results: Of the 1262 patients included in this analysis, 647(51.3%) were administered the TNK, 584(46.3%) were female, and 380(30.1%) were greater than or equal to 80 years old. There was no significant adjusted effect of the type of thrombolysis on health utility scores (adjusted beta coefficient [95%CI] = 0.029 [-0.001, 0.062]), but patients who received TNK reported higher adjusted VAS scores than those that received TPA [adjusted beta coefficient [95%CI] = 2.1 [-0.29, 4.49]). Older age (p < 0.01), female sex (p = 0.01), higher NIHSS score (p < 0.01) were associated with lower health utilities and VAS scores. Conclusion: There is no differential effect of the type of thrombolysis on patient-reported global HRQOL and health state utilities of acute stroke patients. Disparities in HRQOL were mainly explained by sex, age, and disease severity.

BACKGROUND & PURPOSE:Neurovascular research is underfunded, imposing substantial challenges on clinical researchers in the field of neurovascular diseases. We explored what physicians perceive to be the greatest challenges with regard to neurovascular research funding, and how they think the funding crisis in neurovascular research could be overcome. METHODS:We performed an international, multi-disciplinary survey among physicians involved in the medical care of patients with neurovascular diseases. After providing their demographic data, physicians were asked closed-ended questions on their personal opinion regarding challenges in neurovascular research funding, and how these challenges could be overcome. Physicians also described in their own words what they perceived to be the biggest challenges in obtaining funding. Data were analyzed using descriptive statistics and response clustering. RESULTS:Of 233 participating physicians (70.4% male,82.8% senior staff) from 48 countries, 217(97.4%) perceived the discrepancy between required and available funding to be a problem;172(73.8%) considered it a major problem. High competitiveness (61/118 available free text responses[51.7%]), time-consuming application processes (28/118[23.7%]) and administrative requirements (25/118[21.1%]) were identified as key obstacles. Traditional big funding agencies were perceived to be most capable of closing the neurovascular research funding gap, followed by specialty-specific organizations and industry, while philanthropy and crowdfunding were perceived to be less important. CONCLUSION:The gap between required and available funding was perceived to be a major problem in neurovascular research, with high competitiveness, time-consuming funding processes and excessive administrative requirements being the key obstacles to obtaining funding. Traditional funding agencies were perceived to be most capable of closing this funding gap.

The regulation of erythropoiesis via hemodynamic stimuli such as reduced central blood volume (CBV) remains uncertain in women and elderly individuals. This study assessed the acute effects of lower body negative pressure (LBNP) on key endocrine biomarkers regulating erythropoiesis, that is, erythropoietin (EPO) and copeptin, in young and older women and men (n = 87). Transthoracic echocardiography and hemodynamics were assessed throughout incremental LBNP levels for 1 hour, or until presyncope, with established methods. Venous blood samples were collected at baseline and immediately after termination of the orthostatic tolerance (OT) test for subsequent hormone analyses. The average age of young women and men (33.1 ± 6.0 vs. 29.5 ± 6.9 yr) and older women and men (63.8 ± 8.0 vs. 65.3 ± 8.9 yr) as well as their physical activity levels were matched within each age and sex group. CBV, as determined by right atrial volume, was reduced in all individuals at the end of the OT test (p < 0.001). The average OT time ranged from 50.1 to 58.1 min in all individuals. LBNP increased circulating EPO in young women (p = 0.023) but not in young men or older individuals. Copeptin was increased in all individuals with LBNP but was exclusively associated with EPO in men (r = 0.39, p = 0.013). The present study indicates that the acute hemodynamic regulation of EPO production is both sex‐ and age‐dependent.

Whether average sex differences in cardiorespiratory fitness can be mainly explained by blood inequalities in the healthy circulatory system remains unresolved. This study evaluated the contribution of blood volume (BV) and oxygen (O2) carrying capacity to the sex gap in cardiac and aerobic capacities in healthy young individuals. Healthy young women and men (n = 28, age range = 20–43 years) were matched by age and physical activity. Echocardiography, blood pressures, and O2 uptake were measured during incremental exercise. Left ventricular end-diastolic volume (LVEDV), stroke volume (SV), cardiac output (Q), peak O2 uptake (VO2peak), and BV were assessed with precise methods. The test was repeated in men after blood withdrawal and reduction of O2 carrying capacity, reaching women’s levels. Before blood normalization, exercise cardiac volumes and output (LVEDV, SV, Q) adjusted by body size and VO2peak (42 ± 9 vs. 50 ± 11 ml⋅min–1⋅kg–1, P < 0.05) were lower in women relative to men. Blood normalization abolished sex differences in cardiac volumes and output during exercise (P ≥ 0.100). Likewise, VO2peak was similar between women and men after blood normalization (42 ± 9 vs. 40 ± 8 ml⋅min–1⋅kg–1, P = 0.416). In conclusion, sex differences in cardiac output and aerobic capacity are not present in experimental conditions matching BV and O2 carrying capacity between healthy young women and men.

Blood donation entails acute reductions of cardiorespiratory fitness in healthy men. Whether these effects can be extrapolated to blood donor populations comprising women remains uncertain. The purpose of this study was to comprehensively assess the acute impact of blood withdrawal on cardiac function, central hemodynamics and aerobic capacity in women throughout the mature adult lifespan. Transthoracic echocardiography and O2 uptake were assessed at rest and throughout incremental exercise (cycle ergometry) in healthy women (n = 30, age: 47-77 yr). Left ventricular end-diastolic volume (LVEDV), stroke volume (SV), cardiac output (Q̇) and peak O2 uptake (V̇O2peak), and blood volume (BV) were determined with established methods. Measurements were repeated following a 10% reduction of BV within a week period. Individuals were non-smokers, non-obese and moderately fit (V̇O2peak = 31.4 ± 7.3 mL·min-1·kg-1). Hematocrit and BV ranged from 38.0 to 44.8% and from 3.8 to 6.6 L, respectively. The standard 10% reduction in BV resulted in 0.5 ± 0.1 L withdrawal of blood, which did not alter hematocrit (P = 0.953). Blood withdrawal substantially reduced cardiac LVEDV and SV at rest as well as during incremental exercise (≥10% decrements, P ≤ 0.009). Peak Q̇ was proportionally decreased after blood withdrawal (P < 0.001). Blood withdrawal induced a 10% decrement in V̇O2peak (P < 0.001). In conclusion, blood withdrawal impairs cardiac filling, Q̇ and aerobic capacity in proportion to the magnitude of hypovolemia in healthy mature women. Novelty: The filling of the heart and therefore cardiac output are impaired by blood withdrawal in women. Oxygen delivery and aerobic capacity are reduced in proportion to blood withdrawal.

OBJECTIVES:. The reduced orthostatic tolerance (OT) that is characteristic of the female sex may be explained by multiple phenotypic differences between sexes. This study aimed to elucidate the mechanistic role of blood volume (BV) and oxygen carrying capacity on sex differences in OT. DESIGN:. Experimental intervention. SETTING:. University of Calgary, Main Campus, Calgary, AB, Canada. SUBJECTS:. Healthy women and men (n = 90) throughout the adult lifespan (20–89 yr) matched by age and physical activity. INTERVENTIONS:. Incremental lower body negative pressure (LBNP) in all individuals. Blood withdrawal and oxygen carrying capacity reduction in men to match with women’s levels. MEASUREMENTS AND MAIN RESULTS:. Transthoracic echocardiography and central blood pressures were assessed throughout incremental LBNP for 1 hour or until presyncope. Blood uniformization resulted in a precise sex match of BV and oxygen carrying capacity (p ≥ 0.598). A third of women (14/45) and two thirds of men (31/45) prior to blood uniformization completed the orthostatic test without presyncopal symptoms (p-for-sex < 0.001). After blood uniformization, seven out of 45 men completed the test (p-for-sex = 0.081). Left ventricular end-diastolic volume (LVEDV) and stroke volume (SV) were progressively reduced with LBNP in both sexes, with women showing markedly lower volumes than men (p < 0.001). Blood uniformization did not eliminate sex differences in LVEDV and SV. CONCLUSIONS:. Sex differences in OT are not present when BV and oxygen carrying capacity are experimentally matched between sexes throughout the adult lifespan.

Objectives: To investigate the effects of blood withdrawal on cardiac, hemodynamic, and pulmonary responses to submaximal exercise in females. Design and methods: 30 healthy females (63.8 +/- 8.3 years) were recruited for this experimental study. Transtho-racic echocardiography, non-invasive blood pressure monitoring, and oxygen uptake were assessed during a fixed submaximal workload (100 W) prior to (day 1) and immediately after (day 2) a 10% reduction of blood vol-ume. Main measurements included left ventricular end-diastolic volume, stroke volume, cardiac output, mean arterial pressure, systolic blood pressure, diastolic blood pressure, and oxygen uptake. Blood volume was deter-mined via carbon monoxide rebreathing. Results: Participant's blood volume ranged from 3.8 to 6.6 L. Following 10% reduction in blood volume (0.5 +/- 0.1 L), left ventricular end-diastolic volume (p <= 0.030) and stroke volume (p < 0.019) were reduced during submaximal exercise while cardiac output was unchanged (p = 0.139) due to increased heart rate (p < 0.026). Hemodynamic variables including mean arterial pressure (p < 0.015), systolic blood pressure (p < 0.005), and diastolic blood pres -sure (p < 0.038) were reduced while oxygen uptake was unaltered (p = 0.250). Conclusions: Blood withdrawal results in marked reductions in cardiac filling with compensatory chronotropic responses that preserve cardiac output at a moderate submaximal workload in healthy females. Thus, blood volume determines the relative exercise intensity, as typically determined by heart rate, of submaximal efforts in this population. (c) 2021 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Introduction The optimal anaesthesia approach for endovascular treatment (EVT) in acute ischaemic stroke is currently unknown. In stroke due to medium vessel occlusions (MeVO), the occluded vessels are particularly small and more difficult to access, especially in restless or uncooperative patients. In these patients, general anaesthesia (GA) may be preferred by physicians to prevent complications due to patient movement. We investigated physicians' approaches to anaesthesia during EVT for MeVO stroke. Methods In a worldwide, case-based, online survey, physicians' preferred anaesthesia approach during EVT for MeVO stroke was categorized as "initial GA", "initial GA if necessary" (depending on patient cooperation), "no initial GA, but conversion if necessary" (start with local anaesthesia or conscious sedation), and "no GA". Preferred anaesthesia approaches were reported overall and stratified by physician and patient characteristics. Results A total of 366 survey participants provided 1464 responses to 4 primary MeVO EVT case-scenarios. One-third of responses (489/1464 [33%]) favoured no initial GA, but conversion if necessary. Both initial GA and initial GA if necessary were preferred in 368/1464 (25%) of responses respectively. No GA was favoured in 244/1464 (17%). Occlusion location, respondent specialization (interventional neuroradiology), higher age, and female respondent sex were significantly associated with GA preference. GA was more often used in Europe than in other parts of the world (p < 0.001). Conclusions Anaesthesia approaches in MeVO EVT vary across world regions and patient and physician factors. Most physicians in this survey preferred to start with local anaesthesia or conscious sedation and convert to GA if necessary.

Humans are remarkably heterogeneous in their capacity to tolerate the upright posture.1 Nonetheless, a consistent average gap in orthostatic tolerance (OT) prevails between sexes.2 Women reach their OT limit well in advance than men.2 Importantly, limited OT may be a prominent factor underlying the 50% increased risk of falls in women throughout the adult lifespan.3 While most falls do not generally entail serious consequences for young women, fall-related mortality increases dramatically with advanced age.4 Previous research efforts have resolutely advanced our understanding of the aetiology of syncope, albeit the primary female-specific factor limiting OT remains to be ascertained.5 To date, the importance of gravity-dependent fluid extravasation and the subsequent cascade involving the reduction of circulating blood volume (BV), venous return, cardiac filling, and stroke volume (SV) is generally accepted.6 Yet, do women suffer a larger reduction in BV, for a specific orthostatic stimulus,...

Recent evidence points toward a link between lean body mass (LBM) and cardiovascular capacity in women. This study aimed at determining the sex-specific relationship of LBM with central and peripheral circulatory variables in healthy women and men ( n =70) matched by age (60±12 years versus 58±15 years), physical activity, and cardiovascular risk factors. Regional (legs, arms, and trunk) and whole-body (total) body composition were assessed via dual-energy x-ray absorptiometry. Cardiac structure, function, and central/peripheral hemodynamics were measured via transthoracic echocardiography and the volume-clamp method at rest and peak incremental exercise. Regression analyses determined sex-specific relationships between LBM and cardiovascular variables. Regional and total LBM were lower in women than men ( P <0.001), with little overlap between sexes. Leg and arm LBM positively associated with left ventricular (LV) internal resting dimensions in women ( r ≥0.53, P ≤0.002) but not men ( P ≥0.156). Leg, arm, and total LBM only associated with LV relaxation in women ( r ≥0.43, P ≤0.013). All LBM variables strongly associated with LV volumes at peak exercise in women ( r ≥0.54, P ≤0.001) but not men and negatively associated with total peripheral resistance at peak exercise in women ( r ≥0.43, P ≤0.023). Adjustment by adiposity-related or cardiovascular risk factors did not alter results. In conclusion, leg and arm LBM independently associate with internal cardiac dimensions, ventricular relaxation, and systemic vascular resistance in a sex-specific manner, with these relationships exclusively present in women.