Bernhard Sehm1,2*
Kristian Barlinn3
Eduardo Candelario-Jalil4
Krishna Kumar Veeravalli5
Chunping Ni6
Jun Yao7Editorial on the Research Topic
Reviews in: stroke
Stroke constitutes a significant global health challenge, with 12.2 million new strokes per year worldwide, a mortality of 6.5 million, and a cumulative disability of 143 million disability-adjusted life years [DALYs; (1)]. To confront this challenge, the clinical and scientific community is dedicated to addressing various aspects, including primary and secondary prevention, acute stroke care, biomarkers, patient stratification, and neuroplasticity and rehabilitation. The approaches involved encompass both clinical randomized trials and hypothesis-driven or exploratory research.
The global efforts in stroke research result in a substantial number of publications per year, as evidenced by a swift exploration of the PubMed database using the search term “stroke,” which yielded over 34,000 references in the year 2022 only. This deluge of literature highlights the necessity for meta-analyses and systematic reviews, which aggregate and synthesize a large body of evidence from multiple studies using comprehensive and systematic approaches. We, therefore, have collaborated to curate this Research Topic, with the following objectives: (i) increasing the statistical power by combining data from multiple clinical and preclinical studies and thereby helping to estimate the robustness of an effect; (ii) enhancing the generalizability of findings and fostering the application of preclinical research insights into broader clinical applications; and (iii) exploring subgroups or moderating factors for an observed effect and thus help to personalize treatment strategies.
The Research Topic “Reviews in: stroke” includes 25 articles that cover a variety of topics around stroke. One of the major emphases is on acute stroke diagnostics and treatment. We capture current topics like the impact of COVID-19 on acute ischemic stroke care (Stuckart et al.) or the use of telemedicine in acute stroke and its diagnostic accuracy (Poongkunran et al.). Several articles provide insight into neuroimaging (Zheng et al.; Huang et al.; Yoshimoto; Cheng et al.) and serum markers (Liu Y. et al.) that might help with patient selection and treatment monitoring in acute stroke. Other articles look at new treatment options for both ischemic and hemorrhagic stroke [(2); Zheng et al.; Fu et al.].
A further focus of this Research Topic is on risk factors and stroke etiology and addresses questions such as: what is the impact of inflammatory processes on the risk for atherosclerosis and stroke (Wang L. et al.; Jia et al.; Xie et al.; Pinzon et al.)? Can we identify risk factors for in-stent stenosis after intracranial stenting (Wang N. et al.)? And what do we know about perioperative stroke, an entity that is clinically relevant but only marginally addressed in the literature (Ji et al.), and the etiology of cervical artery dissection (Gunduz et al.)?
The third emphasis is on stroke rehabilitation and covers therapeutic interventions such as constrained-induced movement therapy (Cui et al.), balance training (Zhang et al.), and interventions in post-stroke dysphagia (Liu J. et al.). A further article covers the use of AI for the prediction of post-stroke cognitive deficits (Li et al.).
Taken together, this Research Topic provides a variety of topics related to clinical and preclinical stroke research with the common aim of synthesizing the evidence using systematic reviews and meta-analyses. We hope that it will help clinicians and scientists in the field of stroke and foster translational progress.
But work must be done to ensure that patients feel accepted by the research community.
27 July 2021 Dalmeet Singh Chawla
RLT_Images/Getty Images
Most editors-in-chiefs of scholarly journals have no objection to patients being included as co-authors of research papers when they actively participate in the work, a new survey has found.
The study, published last month in Research Involvement and Engagement (RIE), asked 74 editors-in-chief of medical journals whether they agreed, in principle, with patients co-authoring research manuscripts.
The question of co-authorship has arisen amid growing recognition of the added value gained by engaging patients as part of the research team. For example, it can help avoid the risk of research that is not relevant to meeting patients’ needs or improving their quality of life.
While hundreds of medical journals have adopted recommendations of the International Committee of Medical Journal Editors (ICMJE) on authorship, the study authors sought editors’ views on whether the recommendations regarding patient contributions were appropriate.
More than two-thirds (69%) of those surveyed said they were in favour of patients being listed as co-authors on biomedical research articles, but the remainder thought this wouldn’t be appropriate. Nearly three-quarters of the editors thought patients should not be required to have an academic affiliation to be listed as co-authors, while 16.7% thought they should, and the rest were unsure.
The editors were equally divided on whether the ICMJE authorship criteria should be revised to become more inclusive of patients, at just under 36% on both sides, with the rest undecided.
Kelly Cobey, who studies research methods at the Ottawa Hospital Research Institute in Canada and who co-authored the new study, says it was prompted by her observations of systemic barriers to patients’ involvement in research other than as subjects.
“Not all aspects of the research process were really inclusive to the patients’ participation," she says.
Cobey says it’s particularly important for patients to be involved in selecting which areas of research are worth exploring. She points to a 2015 study that used patients to identify priority areas in kidney dialysis research.
“Ultimately we’re doing research to create interventions, [and] cure diseases for patients. So the patient perspective is of utmost importance and certainly adds value.”
Holly Witteman, a health informatics researcher at Laval University in Quebec, Canada, has had run-ins with peer-reviewers of her diabetes manuscripts who have argued that patients should not be listed as co-authors. They have expressed concern about breaching confidentiality of patient health information and argued that under Canadian policy, patients are in any case compensated financially for their time on projects.
“Having these kinds of delays because of lack of understanding of patient partner co authorship is really frustrating,” Witteman says.
Karen Woolley, a consultant on patient partnerships and a professor of health sciences at the University of Queensland in Australia, says she wonders if editors who reject the inclusion of patients as co-authors “would actually be supporting the unethical practice of ghost-authorship.”
“As more patient-led research is encouraged, funded, approved and conducted, surely patients have to author the resulting publications?” she queries.
Richard Stephens, co-editor-in-chief of RIE and a well-known patient advocate in the United Kingdom, argues that to be recognized as authors, patients should fulfill the current ICMJE rules on what constitutes one.
“If you are going to be a patient, you do actually have to contribute something to the study,” he says. “Patients should be co-authors on an absolutely equal basis to all the other co-authors.”
Woolley agrees. “Supporting patient authorship supports the principles of diversity, equity and inclusion in medical publishing,” she says. “However, we must not allow tokenistic and unethical authorship practices, such as guest authorship.”
The British Medical Journal (BMJ) published guidelines for patient peer-reviewers on its website. RIE, which launched in 2015, insists that at least one peer-reviewer of every paper it publishes is a patient. The journal also has patients on its editorial board.
The biggest obstacle, however, is that most journals don’t have any clear policies around whether patients are allowed to be co-authors or peer-reviewers, which makes it difficult to get them involved, Cobey says.
Some studies have suggested that even when academics do partner up with stakeholders in new ways, university structures and incentives work against these alternative models of knowledge production.
Laurie Proulx, volunteer vice-president with the Canadian Arthritis Patient Alliance in Ottawa, was the patient partner in the RIE co-authorship study, and has served as a peer-reviewer for both the BMJ and RIE.
She says patients face various hurdles to participating and being credited for their input, such as her experience of being required to add details about her education when submitting manuscripts. “Things like that just make you feel like you don’t fit into the research world,” she says.
But deeper patient participation in research is “a huge opportunity really to make science meaningful or make healthcare meaningful to society at large,” Proulx adds. “The lived experience is likely something that’s never captured in [the] scientific process.”
PACIFIC-Stroke is a randomized, placebo controlled, double-blind, parallel group, dose-finding Phase 2 study to evaluate efficacy and safety of BAY 2433334 in patients following an acute non-cardioembolic ischemic stroke.
Primary outcome measures:
Background
Cardiovascular events (CVEs) occur more often in winter than in summer; however, the dependence of strokes on various meteorological factors remains unclear .
Aims
The purpose of this meta-analysis was to determine the dependence of the circannual dynamics of hospitalizations for hemorrhagic stroke (HS) and ischemic stroke (IS) on seasonal fluctuations in meteorological factors.
Summary of review and conclusions
For our meta-analysis, we selected 20 and 26 publications examining the seasonal dynamics of HS and IS, respectively . The meta-analysis showed that HS occurs more often in winter than in other seasons and does not depend on a region’s climate. The seasonal dynamics of IS are not clearly expressed and are determined by the characteristics of a region’s climate. In a climate without pronounced seasonal dynamics of atmospheric pressure and in wet winters, the vector of IS incidents will not be expressed or slightly shifted toward winter. Low atmospheric pressure in summer is associated with an increased likelihood of IS during this season compared to winter. There was also a relation between IS risk with high relative humidity and a significant decrease in ÏO2 in summer, but there is not enough evidence regarding this association. We did not reveal dependence of the seasonal dynamics of strokes on the amplitude of annual fluctuations in air temperature.
Keywords: ischemic stroke, hemorrhagic stroke, season, meteorological factors, climate
Edited by Margaret Gatz, University of Southern California, Los Angeles, CA, and accepted by Editorial Board Member Renée Baillargeon November 20, 2020 (received for review May 23, 2020)
We followed a population-representative cohort of children from birth to their mid-forties. As adults, children with better self-control aged more slowly in their bodies; showed fewer signs of brain aging; and were more equipped to manage later-life health, financial, and social demands. The effects of children’s self-control were separable from their socioeconomic origins and intelligence. Children changed in their rank order of self-control across age, suggesting the hypothesis that it is a malleable intervention target. Adults’ self-control was associated with their aging outcomes independently of their childhood self-control, indicating that midlife might offer another intervention window. Programs that are successful in increasing self-control might extend both the length (life span) and quality (health span) of life.
The ability to control one’s own emotions, thoughts, and behaviors in early life predicts a range of positive outcomes in later life, including longevity. Does it also predict how well people age? We studied the association between self-control and midlife aging in a population-representative cohort of children followed from birth to age 45 y, the Dunedin Study. We measured children’s self-control across their first decade of life using a multi-occasion/multi-informant strategy. We measured their pace of aging and aging preparedness in midlife using measures derived from biological and physiological assessments, structural brain-imaging scans, observer ratings, self-reports, informant reports, and administrative records. As adults, children with better self-control aged more slowly in their bodies and showed fewer signs of aging in their brains. By midlife, these children were also better equipped to manage a range of later-life health, financial, and social demands. Associations with children’s self-control could be separated from their social class origins and intelligence, indicating that self-control might be an active ingredient in healthy aging. Children also shifted naturally in their level of self-control across adult life, suggesting the possibility that self-control may be a malleable target for intervention. Furthermore, individuals’ self-control in adulthood was associated with their aging outcomes after accounting for their self-control in childhood, indicating that midlife might offer another window of opportunity to promote healthy aging.
The ability to control one’s own emotions, thoughts, and behaviors in early life sets the stage for many positive outcomes in later life. These include educational attainment, career success, healthy lifestyles (1⇓⇓–4), and, in particular, longevity (5⇓⇓–8). Prospective studies of children, adolescents, and adults have shown that individuals with better self-control—often measured as higher conscientiousness or lower impulsivity—live longer lives (5⇓⇓–8). But, do they also exhibit better midlife aging? Answering this question could reveal opportunities to extend not only life span (how long we live) but also health span [how long we live free of disease and disability (9)]. Here, we used data collected across five decades to connect children’s self-control to their pace of aging in midlife. We also linked children’s self-control with their midlife aging preparedness: the health, financial, and social reserves that may help prepare individuals for longer life span and better health span.
Midlife represents a useful window during which to measure individual differences in aging and their relation to childhood self-control. Meaningful variation between individuals in the speed of both physiological and cognitive aging can be detected already at this life stage (10, 11), and prior work has established that individual differences in midlife health are linked to early-life factors (12⇓–14). Furthermore, midlife is a critical period for preparing for the demands of older age (15). Now past their healthy young adult years, individuals must devote greater attention to preventing age-related diseases, increasing their financial reserves for retirement, and building the social networks that will provide practical and emotional supports in old age. Signs of one’s own aging emerge at this life stage, reminding us that multiple health, financial, and social demands are approaching: menopause and presbyopia set in, we start paying attention to our savings accounts, and we see our own futures in our parents’ decline.
If outcomes of self-control extend as far as midlife, then it could be a key intervention target. It would also suggest the hypothesis that there may be opportunities to build aging preparedness while individuals are still in their robust forties (15, 16). Much emphasis has been placed on the importance of intervening early in development, and there is vigorous debate over the optimal timing for implementing early-years programs (17⇓–19). Midlife, however, remains a largely unexplored potential window of opportunity for self-control intervention.
We tested associations between childhood self-control and midlife aging using data from the Dunedin Longitudinal Study, a prospective study of a complete birth cohort of 1,037 individuals followed from birth to age 45 with 94% retention. As previously reported in this journal, we measured study members’ self-control across their first decade of life using a multi-occasion/multi-informant strategy (2, 20). We measured their pace of aging as well as their aging preparedness in midlife using a range of prespecified measures known to be associated with life span and/or health span (Fig. 1 and SI Appendix, Table S1), which were derived from biological and physiological assessments, structural brain-imaging scans, observer ratings, self-reports, informant reports, and administrative records. We used these data to test two hypotheses. First, we tested the hypothesis that individuals with better self-control in childhood exhibit slower aging of the body and fewer signs of brain aging in midlife. Second, we tested the hypothesis that individuals with better self-control in childhood exhibit better preparedness for the health, financial, and social demands that emerge in later life. Research has shown that self-control predicts health behaviors such as diet, smoking, alcohol consumption, and exercise (4, 21⇓⇓–24). Here, we extend the reach of this research by testing whether self-control predicts outcomes beyond health behaviors, including individuals’ practical health knowledge, their attitudes toward and expectancies about aging, their practical financial knowledge and financial behavior, their social integration, and their satisfaction with life.
Aging domains and measures assessed in the current study. Column three indicates reference numbers for prior studies documenting associations between the given measure and life span and/or health span. The complete reference list is included in SI Appendix, Table S1.
Children’s self-control is correlated with their socioeconomic circumstances (25, 26) and their intelligence (27, 28). Both social class and intelligence have been implicated in life span and health span (29, 30); in fact, both social class and intelligence have been called “fundamental causes” of later-life health (31⇓–33). Social class has been proposed as a fundamental cause because it influences multiple disease outcomes through multiple mechanisms, it embodies access to important resources, and its associations with health outcomes are maintained even when intervening mechanisms change (31). Intelligence has been conceptualized as a fundamental cause for similar reasons (32). For childhood self-control to be implicated as an active ingredient in healthy aging, it is important to show that its effects are independent of these two fundamental influences on children’s futures. We therefore tested whether associations between self-control and aging survived after accounting for children’s social class and intelligence quotient (IQ) [assessing each, like self-control, using repeated measurements across childhood (Methods)].
Because all children lack self-control on occasion, we defined a child’s sustained self-control style using an omnibus measure of self-control that comprised reports collected at ages 3, 5, 7, 9, and 11 y. These reports by researcher-observers, parents, teachers, and the children themselves assessed capacities including lack of control, impulsive aggression, hyperactivity, lack of persistence, inattention, and impulsivity (SI Appendix, SI Methods 1). They were combined into a highly reliable composite measure for each study child [α = 0.86 (2)]. Children with better self-control tended to come from more socioeconomically advantaged families (r = 0.27, P < 0.0001) and had higher tested IQs (r = 0.45, P < 0.0001).
From ages 26 to 45 y, we measured the pace of study members’ physiological decline across multiple organ systems. At age 45 y, we also collected structural MRI measures to derive estimates of brain aging as well as the volume of white matter hyperintensities, a clinical index of microlesions that accrue across the life span and predict accelerated cognitive decline and dementia risk. In addition, we conducted assessments of study members’ functional capacity and asked several independent raters to judge each study member’s apparent age from facial photographs (Fig. 1 and SI Appendix, SI Methods 2). These outcomes were correlated with each other (Table 1) and were therefore combined to form a composite measure of accelerated aging using principal components analysis. Children with better self-control displayed slower aging in later life, as assessed by this composite (β = −0.35, 95% CI [−0.42, −0.29], P < 0.0001; Table 2 and Fig. 2). This remained the case even after controlling for their social class origins and IQ (β = −0.20 [−0.26, −0.13], P < 0.0001; Table 2). Self-control was also associated with each constituent measure individually. As adults, children with better self-control aged more slowly across different organ systems, had lower brain age scores, had a smaller volume of white matter hyperintensities, walked more quickly, and appeared younger in facial photographs shown to independent raters (Table 2). Associations with brain age and white matter hyperintensities became nonsignificant when we controlled for childhood social class and childhood IQ, but the remainder of associations were independent of these fundamental causes (Table 2).
Stroke research is underfunded in compared with other major chronic conditions and spend on stroke care is unclear across Europe.
In the Economic Impact of Stroke in Europe, SAFE set out to identify the full costs of stroke, including economic, societal and social costs. This will enable SAFE and our members to develop a robust case for investment in stroke prevention, care and rehabilitation.
The research was undertaken by the Health Economics Research Centre, University of Oxford and investigates the full current and full costs of stroke across the European Union plus Iceland, Israel, Norway, Switzerland and the UK.
At What Cost – the Economic Impact of Stroke in Europe report adds to the existing evidence that shows stroke care is woefully underfunded. The research shows that the total cost (health care, social care, informal care and productivity losses) of stroke care was €60 billion in 2017. Future costs of stroke care in Europe could increase to €86 billion in 2040 if we fail to invest in stroke prevention, treatments and rehabilitation.
The research was completed before COVID-19. Since the start of the pandemic, services have been diverted away from non-infectious conditions, including stroke care, therefore the projected costs in our report are likely to be even higher.
The report covers:
The report concludes that no matter at which point in the stroke pathway you intervene – prevention, treatment, long-term care – there’s likely to be gains to be had in terms of patient outcomes and cost savings.
The full report, summary, factsheet and supplementary data are available to download.
SAFE’s recommendations
In 2017, nearly 1.5 million people suffered a stroke, nine million Europeans lived with a stroke, and more than 430,000 people died due to a stroke in the 32 countries under this study. The total cost of stroke in 2017 was a €60 billion.
The number of new strokes and the number of people living with stroke is set to rise due to ageing population in Europe, as age is the biggest, non-modifiable risk factor for stroke. The costs of stroke are projected to increase by 44% between 2017 and 2040, with some countries seeing rises in stroke-related costs of nearly 100%.
At What Cost – the Economic Impact of Stroke offers solutions to help reduce the burden of stroke and future proof healthcare services at the time when COVID-19 has amplified the problem and exposed already overstretched and failing healthcare systems. SAFE calls on the EU and national governments to make stroke care a priority and ensure it is fit for the future.
European countries should:
The EU should:
