Inclusion of People With Aphasia in Stroke Trials: A Systematic Search and Review.

BACKGROUND: Although people with aphasia (PwA) represent 30% of stroke survivors, they are frequently excluded from stroke research, or their inclusion is unclear. Such practice significantly limits the generalizability of stroke research, increases the need to duplicate research in aphasia-specific populations, and raises important ethical and human rights issues. OBJECTIVE: To detail the extent and nature of inclusion of PwA in contemporary stroke randomized controlled trials (RCTs). METHODS: We conducted a systematic search to identify completed stroke RCTs and RCT protocols published in 2019. Web of Science was searched using terms "stroke" and "randomized controlled trial". These articles were reviewed by extracting rates of PwA inclusion/exclusion, whether "aphasia" or related terms were referred to in the article or supplemental files, eligibility criteria, consent procedures, adaptations made to support the inclusion of PwA, and attrition rates of PwA. Data were summarized, and descriptive statistics applied when appropriate. RESULTS: 271 studies comprising 215 completed RCTs and 56 protocols were included. 36.2% of included studies referred to aphasia/dysphasia. Of completed RCTs, only 6.5% explicitly included PwA, 4.7% explicitly excluded PwA, and inclusion was unclear in the remaining 88.8%. Among RCT protocols, 28.6% of studies intended inclusion, 10.7% intended excluding PwA, and in 60.7%, inclusion was unclear. In 45.8% of included studies, sub-groups of PwA were excluded, either explicitly (ie, particular types/severities of aphasia, eg, global aphasia) or implicitly, by way of ambiguous eligibility criteria which could potentially relate to a sub-group of PwA. Little rationale for exclusion was provided. 71.2% of completed RCTs did not report any adaptations that could support the inclusion of PwA, and minimal information was provided about consent procedures. Where it could be determined, attrition of PwA averaged 10% (range 0%-20%). CONCLUSION: This paper details the extent of inclusion of PwA in stroke research and highlights opportunities for improvement.

Towards the Consistent Inclusion of People With Aphasia in Stroke Research Irrespective of Discipline.

People with aphasia have been systematically excluded from stroke research or included without the necessary modifications, threatening external study validity. In this paper, we propose that 1) the inclusion of people with aphasia should be considered as standard in stroke research irrespective of discipline and that 2) modifications should be made to stroke research procedures to support people with aphasia to achieve meaningful and valid inclusion. We argue that outright exclusion of this heterogenous population from stroke research based purely on a diagnosis of aphasia is rarely required and present a rationale for deliberate inclusion of people with aphasia in stroke research. The purpose of this paper is fourfold: 1) to highlight the issue and implications of excluding people with aphasia from stroke research; 2) to acknowledge the current barriers to including people with aphasia in stroke research; 3) to provide stroke researchers with methods to enable inclusion, including recommendations, resources, and guidance; and 4) to consider research needed to develop aphasia inclusive practices in stroke research.

French legal approach to clinical research.

Since 1988, France has been committed to drafting laws regulating clinical research. These laws must both reflect general legal standards relating to personal data protection and patient information and comply with EU regulations, which are supra-national norms. The 2012 legislation known as "Jardé law" came into force in 2016 and distinguishes between 3 different types of research involving human subjects: category 1:interventional research implying an intervention on the patient which is not justified by their usual treatment. Category 2: interventional research, which does not focus on medicinal products and only entails minimal risks and constraints. Category 3: non-interventional research implying one or multiple acts or proceedings devoid of listed risks. These studies require preliminary favourable opinions from the French Ethical Research Committees (CPP), who are appointed by the State, and must ensure the protection of personal data. For the other types of studies (retrospective data, practice surveys), French legislation only requires that the protection of personal data is ensured. However, it is highly recommended to submit these studies to an Institutional Review Board (IRB) in order to confirm that human subjects are not involved and to obtain an ethical opinion in the event of a scientific journal submission. These laws are constantly evolving in order to comply with the various international recommendations and European regulations, which are binding in France.

Connexin37 is the major connexin expressed in the media of caudal artery.

OBJECTIVE: To determine the connexins (Cxs) involved in intercellular coupling within vascular muscle, the present study has quantified mRNA and protein expression for Cx37, Cx40, Cx43, and Cx45 in the caudal artery (CA) and thoracic aorta (ThA) of the rat. METHODS AND RESULTS: Real-time polymerase chain reaction and immunohistochemistry identified Cx37 as the most abundantly expressed Cx in the CA, with fine punctate staining observed in the media. Conversely, mRNA for Cx43 was 40-fold greater in the ThA than in the CA, with punctate staining in the endothelium and media of the ThA but confined to the endothelium in the CA. Western blotting confirmed the differences in the relative amounts of Cx43 between the 2 vessels. For both arteries, Cx45 was expressed to a lesser degree in the media but not in the endothelium, whereas Cx40 was found only in the endothelium. Cx37, Cx40, and Cx43 were expressed in the endothelium of both vessels, although the density of Cx40 plaques was significantly greater in the CA. CONCLUSIONS: The demonstration of Cx37 as the dominant Cx in the media of the CA highlights the potential heterogeneity in Cx involvement in vascular smooth muscle.