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Under-representation of female researchers tends to create under-representation of issues that are relevant to women in research — in our current situation this may create important gaps in our understanding of COVID-19. [...]we investigated whether gender differences existed in authorship of COVID-19 research since the onset of the pandemic. [...]although we employed a widely used and validated software, it is still possible that it may have misclassified the gender of some authors. [...]COVID-19 is a high-profile and dynamic topic where women may either be overtly or covertly denied access to COVID-19 research, because of its anticipated high impact.6 Third, women may have less time to commit to research during the pandemic.7 Fourth, COVID-19-related papers are likely to be affected as much as other papers by gender bias in the peer-review process.8 Fifth, a relatively large amount of the early COVID-19 publications are commissioned articles, which are, in general, more likely to be published by men.9 There is a pressing need to reduce these gender inequalities because women’s participation in research is associated with a higher likelihood of reporting gender and sex-disaggregated data,4 which in turn improve our understanding of the clinical and epidemiological dimensions of COVID-19. A further step would be to consider gender quotas, as these have shown to help rectify women’s under-representation in prominent positions, for instance, in political, economic and academic systems.12 Conclusion Women have been under-represented in COVID-19 research since the beginning of the outbreak.

Physical inactivity, a modifiable risk factor for cardiovascular disease, is independently associated with stroke. Though some prior data have suggested sex differences in levels of physical activity, whether there are sex differences in the role of physical activity in primary stroke prevention is largely unknown. This systematic review identifies and describes recent findings on sex differences in the association between physical activity and incident (first-ever) stroke. This review also describes the current evidence on the strength of the association between physical activity and a reduced stroke risk in women in particular. Using a prespecified strategy, PubMed/MEDLINE and Cochrane Central were searched to identify observational studies or trials published from 2000 to 2020 and reporting sex differences in physical activity and incident stroke. To be included, among other criteria, studies had to include sex-specific effect estimates from women, men, or both. Titles, abstracts, and full-text articles were screened to identify studies meeting the inclusion criteria, and adjusted sex-specific estimates of the association between physical activity and incident stroke for total stroke (ischemic plus hemorrhagic) or ischemic stroke were abstracted. Thirty-seven studies met the inclusion criteria. Of 17 studies that included data on total incident stroke (ischemic and hemorrhagic combined) in both women and men, 7 (41%) showed similar associations between physical activity and incident stroke between women and men, 6 (35%) suggested a significant effect in women but not in men, and 3 (18%) showed a significant effect in men but not in women. Of 10 studies that included data on ischemic stroke in women and men, 5 (50%) suggested similar effects in women and men, 4 (40%) suggested a significant effect in women but not in men, and 1 (10%) showed an effect in men but not women. In women specifically, the majority of included studies demonstrated a reduced risk for incident stroke with physical activity, with relative risk reductions ranging from 11% to 72%, though most estimates fell between 20% and 40%. The majority of studies indicated a clear association between physical activity and a reduction in stroke risk. Studies were split as to the potential for sex differences in this association. Future prospective investigations should identify strategies for the use of increased physical activity for primary stroke prevention, with sex-specific considerations as warranted. The data on sex-specific dose–response relationship between physical activity and stroke risk are inconclusive and warrant more research.

ObjectiveTo evaluate the impact of the Coronavirus disease of 2019 (COVID‐19) pandemic on patients with migraine.MethodsSelf-reported data from a migraine tracking smartphone application, Migraine Buddy, were used. Data were collected from users who reported at least one attack in the Jan, Feb, Mar and Apr of 2018, 2019 and 2020. In addition, a survey was conducted to evaluate the impact of COVID‐19 on migraine management.ResultsOn average, data from 124,717 users per month (mean age 36.3 ± 10.9 years and 89% female) were collected. Overall, the mean frequency of migraine headache was higher in 2020 than in 2019 and higher in 2019 than in 2018. The four commonest headache triggers in 2018, 2019 and 2020 were stress in 39.7, 38.4 and 36.1%, lack of sleep in 25, 25 and 22.8%, neck pain, 20, 20.4 and 19.3 and anxiety in 19, 18.4 and 18.4% of participants, respectively. 1689 users participated in the survey and they reported that they preferred face-to-face (54.29%) to telehealth (11.9%) consultations.ConclusionAn increase in migraine frequency from 2018 to 2020 was reported by the users of the mobile phone. This could reflect a real increase or change in reporting habits. Stress, lack of sleep, neck pain and anxiety were the commonest attack triggers. The frequency of these triggers decreased slightly in 2020 compared to 2019 and 2018. An increase in telehealth consultations with specialists was reported in the survey but migraine patients preferred face-to-face consultations.

Women with peripheral artery disease (PAD) often have atypical symptoms, late hospital presentations, and worse prognosis. Risk factor identification and management are important. We assessed sex differences in associations of risk factors with PAD. 500,207 UK Biobank participants (54.5% women, mean age 56.5 years) without prior hospitalisation of PAD at baseline were included. Examined risk factors included blood pressure, smoking, diabetes, lipids, adiposity, history of stroke or myocardial infarction (MI), socioeconomic status, kidney function, C-reactive protein, and alcohol consumption. Poisson and Cox regressions were used to estimate sex-specific incidence of PAD hospitalisation or death, hazard ratios (HRs), and women-to-men ratios of HRs (RHR) with confidence intervals (CIs). Over a median of 12.6 years, 2658 women and 5002 men had a documented PAD. Age-adjusted incidence rates were higher in men. Most risk factors were associated with a higher risk of PAD in both sexes. Compared with men, women who were smokers or had a history of stroke or MI had a greater excess risk of PAD (relative to those who never smoked or had no history of stroke or MI): RHR 1.18 (95%CI 1.04, 1.34), 1.26 (1.02, 1.55), and 1.50 (1.25, 1.81), respectively. Higher high-density lipoprotein cholesterol (HDL-C) was more strongly associated with a lower risk of PAD in women than men, RHR 0.81 (0.68, 0.96). Compared to HDL-C at 40 to 60 mg/dL, the lowest level of HDL-C ([less than or equal to]40 mg/dL) was related to greater excess risk in women, RHR 1.20 (1.02, 1.41), whereas the highest level of HDL-C (>80 mg/dL) was associated with lower risk of PAD in women, but higher risk in men, RHR 0.50 (0.38, 0.65). While the incidence of PAD was higher in men, smoking and a history of stroke or MI were more strongly associated with a higher risk of PAD in women than men. HDL-C was more strongly associated with a lower risk of PAD in women than men.

BackgroundLack of progress in finding disease-modifying treatments for dementia may be due to heterogeneity in treatment effects among subgroups, such as by sex. Therefore, we investigated the characteristics of dementia trials completed in the last decade, with a focus on women’s representation and sex-disaggregated outcomes.MethodsClinical trials on dementia completed since 2010 were identified from ClinicalTrials.gov. Randomised, phase III/IV trials with ≥100 participants were selected to quantify women’s representation among participants, by computing the participation to prevalence ratio (PPR) and investigate whether sex-disaggregated analyses had been performed.ResultsA total of 1351 trials were identified between January 2010 and August 2021 (429 520 participants), of which 118 were eligible for analysis of women’s representation and sex-stratified analysis. Only 113 reported the sex of participants and were included in the analysis of women’s representation. Of the 110 469 participants in these 113 trials, 58% were women, lower than their estimated representation in the global dementia population of 64%. The mean PPR was 0.90 (95% CI 0.86 to 0.94). Women’s participation tended to be higher when the first or last authors of the trial report were women. Eight out of the 118 trials reported sex-disaggregated outcomes, and three of those found significant sex differences in efficacy outcomes. None of the trials reported screening failures or adverse events stratified by sex.ConclusionsOverall, women and men were equally represented in dementia trials carried out over the past decade, but women’s representation was lower than in the underlying dementia population. Sex-disaggregated efficacy and safety outcomes were rarely reported.

ObjectiveTo test the hypothesis that imaging signs of ‘brain frailty’ and acute ischaemia predict clinical outcomes and symptomatic intracranial haemorrhage (sICH) after thrombolysis for acute ischaemic stroke (AIS) in the alteplase dose arm of ENhanced Control of Hypertension ANd Thrombolysis strokE stuDy (ENCHANTED).MethodsBlinded assessors coded baseline images for acute ischaemic signs (presence, extent, swelling and attenuation of acute lesions; and hyperattenuated arteries) and pre-existing changes (atrophy, leucoaraiosis and old ischaemic lesions). Logistic regression models assessed associations between imaging features and death at 7 and 90 days; good recovery (modified Rankin Scale scores 0–2 at 90 days) and sICH. Data are reported with adjusted ORs and 95% CIs.Results2916 patients (67±13 years, National Institutes of Health Stroke Scale 8 (5–14)) were included. Visible ischaemic lesions, severe hypoattenuation, large ischaemic lesion, swelling and hyperattenuated arteries were associated with 7-day death (OR (95% CI): 1.52 (1.06 to 2.18); 1.51 (1.01 to 2.18); 2.67 (1.52 to 4.71); 1.49 (1.03 to 2.14) and 2.17 (1.48 to 3.18)) and inversely with good outcome. Severe atrophy was inversely associated with 7-day death (0.52 (0.29 to 0.96)). Atrophy (1.52 (1.08 to 2.15)) and severe leucoaraiosis (1.74 (1.20 to 2.54)) were associated with 90-day death. Hyperattenuated arteries were associated with sICH (1.71 (1.01 to 2.89)). No imaging features modified the effect of alteplase dose.ConclusionsNon-expert-defined brain imaging signs of brain frailty and acute ischaemia contribute to the prognosis of thrombolysis-treated AIS patients for sICH and mortality. However, these imaging features showed no interaction with alteplase dose.

Decompressive hemicraniectomy (DHC) can improve outcomes for patients with severe forms of acute ischemic stroke (AIS), but the evidence is mainly derived from non-thrombolyzed patients. We aimed to determine the characteristics and outcomes of early DHC in thrombolyzed AIS participants of the international Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). Post-hoc analyses of ENCHANTED, an international, partial-factorial, open, blinded outcome-assessed, controlled trial in 4557 thrombolysis-eligible AIS patients randomized to low- versus standard-dose intravenous alteplase (Arm A, n = 2350), intensive versus guideline-recommended blood pressure control (Arm B, n = 1280), or both (Arms A + B, n = 947). Logistic regression models were used to identify baseline variables associated with DHC, with inverse probability of treatment weights employed to eliminate baseline imbalances between those with and without DHC. Logistic regression was also used to determine associations of DHC and clinical outcomes of death/disability, major disability, and death (defined by scores 2–6, 3–5, and 6, respectively, on the modified Rankin scale) at 90 days post-randomization. There were 95 (2.1%) thrombolyzed AIS patients who underwent DHC, who were significantly younger, of non-Asian ethnicity, and more likely to have had prior lipid-lowering treatment and severe neurological impairment from large vessel occlusion than other patients. DHC patients were more likely to receive other management interventions and have poor functional outcomes than non-DHC patients, with no relation to different doses of intravenous alteplase. Compared to other thrombolyzed AIS patients, those who received DHC had a poor prognosis from more severe disease despite intensive in-hospital management.

Sex and gender are inadequately considered in health and medical research, policy and practice, leading to preventable disparities in health and wellbeing. Several global institutions, journals, and funding bodies have developed policies and guidelines to improve the inclusion of diverse participants and consideration of sex and gender in research design and reporting and the delivery of clinical care. However, according to recent evaluations, these policies have had limited impact on the inclusion of diverse research participants, adequate reporting of sex and gender data and reducing preventable inequities in access to, and quality provision of, healthcare. In Australia, the Sex and Gender Policies in Medical Research (SGPMR) project aims to address sex and gender bias in health and medical research by (i) examining how sex and gender are currently considered in Australian research policy and practice; (ii) working with stakeholders to develop policy interventions; and (iii) understanding the wider impacts, including economic, of improved sex and gender consideration in Australian health and medical research. In this paper we describe the development of a theory of change (ToC) for the SGPMR project. The ToC evolved from a two-stage process consisting of key stakeholder interviews and a consultation event. The ToC aims to identify the pathways to impact from improved consideration of sex and gender in health and medical research, policy and practice, and highlight how key activities and policy levers can lead to improvements in clinical practice and health outcomes. In describing the development of the ToC, we present an entirely novel framework for outlining how sex and gender can be appropriately considered within the confines of health and medical research, policy and practice.

IntroductionLife expectancy (LE) depends on the wider determinants of health, which have different impact in women and men. Therefore, this study aimed to investigate whether gender equality was correlated with LE in women and men.MethodsGender equality in the 27 European Union (EU) member states between 2010 and 2019 was estimated using a modified Gender Equality Index (mGEI), based on the index developed by the European Institute for Gender Equality. The correlation between this mGEI and LE and the gender gap in LE was calculated using the Spearman correlation coefficient.ResultsBetween 2010 and 2019, LE increased more for men than women, which resulted in a narrowing of the gender gap in LE in the EU. During the same period, there was an increase in gender equality, as measured by the mGEI, although with substantial heterogeneity between countries. There was a strong correlation between the mGEI and the gender gap in LE (−0.880), which was explained by a stronger correlation between the mGEI and longer LE in men than in women (0.655 vs 0.629, respectively). The domains of the mGEI most strongly associated with a narrowing of the gender gap in LE were health, money and knowledge, while power was the domain with the weakest association.ConclusionsGender equality appears to be at least as beneficial to men as women with regard to LE, thus reinforcing the key role gender equality plays in improving population health and longevity.

Studies of sex differences in the use and outcomes of endovascular treatment (EVT) for acute ischemic stroke report inconsistent results. We systematically searched PubMed and Embase databases for studies examining sex-specific utilization of EVT for acute ischemic stroke published before 31 December 2021. Estimates were compared by study type: randomized clinical trials (RCTs) and non-RCTs (hospital-based, registry-based or administrative data). Random effects odds ratios (ORs) were generated to quantify sex differences in EVT use. To estimate sex differences in functional outcome on the modified Rankin scale after EVT, the female:male ratio of ORs and 95% confidence intervals (CIs) were obtained from ordinal or binary analysis. 6,396 studies were identified through database searching, of which 594 qualified for a full review. A total of 51 studies (36 non-RCT and 15 RCTs) reporting on sex-specific utilization of EVT were included, and of those 10 estimated the sex differences of EVT on functional outcomes. EVT use was similar in women and men both in non-RCTs (OR: 1.03, 95% CI: 0.96-1.11) and RCTs (1.02, 95% CI: 0.89-1.16), with consistent results across years of publication and regions of study, except that in Europe EVT treatment was higher in women than men (1.15, 95% CI: 1.13-1.16). No sex differences were found in the functional outcome by either ordinal and binary analyses (ORs 0.95, 95% CI: 0.68-1.32] and 0.90, 95% CI: 0.65-1.25, respectively). No sex differences in EVT utilization or on functional outcomes were evident after acute ischemic stroke from large-vessel occlusion. Further research may be required to examine sex differences in long-term outcomes, social domains, and quality of life. https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=226100, identifier: CRD42021226100.