BackgroundPhysical exercise is an intervention that might protect against doxorubicin‐induced cardiotoxicity. In this meta‐analysis and systematic review, we aimed to estimate the effect of exercise on doxorubicin‐induced cardiotoxicity and to evaluate mechanisms underlying exercise‐mediated cardioprotection using (pre)clinical evidence.Methods and ResultsWe conducted a systematic search in PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases. Cochrane's and Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) risk‐of‐bias tools were used to assess the validity of human and animal studies, respectively. Cardiotoxicity outcomes reported by ≥3 studies were pooled and structured around the type of exercise intervention. Forty articles were included, of which 3 were clinical studies. Overall, in humans (sample sizes ranging from 24 to 61), results were indicative of exercise‐mediated cardioprotection, yet they were not sufficient to establish whether physical exercise protects against doxorubicin‐induced cardiotoxicity. In animal studies (n=37), a pooled analysis demonstrated that forced exercise interventions significantly mitigated in vivo and ex vivo doxorubicin‐induced cardiotoxicity compared with nonexercised controls. Similar yet slightly smaller effects were found for voluntary exercise interventions. We identified oxidative stress and related pathways, and less doxorubicin accumulation as mechanisms underlying exercise‐induced cardioprotection, of which the latter could act as an overarching mechanism.ConclusionsAnimal studies indicate that various exercise interventions can protect against doxorubicin‐induced cardiotoxicity in rodents. Less doxorubicin accumulation in cardiac tissue could be a key underlying mechanism. Given the preclinical evidence and limited availability of clinical data, larger and methodologically rigorous clinical studies are needed to clarify the role of physical exercise in preventing cardiotoxicity in patients with cancer.RegistrationURL: https://www.crd.york.ac.uk/prospero; Unique identifier: CRD42019118218.
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In recent years, disasters are increasing in numbers, location, intensity and impact; they have become more unpredictable due to climate change, raising questions about disaster preparedness and management. Attempts by government entities at limiting the impact of disasters are insufficient, awareness and action are urgently needed at the citizen level to create awareness, develop capacity, facilitate implementation of management plans and to coordinate local action at times of uncertainty. We need a cultural and behavioral change to create resilient citizens, communities, and environments. To develop and maintain new ways of thinking has to start by anticipating long-term bottom-up resilience and collaborations. We propose to develop a serious game on a physical tabletop that allows individuals and communities to work with a moderator and to simulate disasters and individual and collective action in their locality, to mimic real-world scenarios using game mechanics and to train trainers. Two companies–Stratsims, a company specialized in game development, and Society College, an organization that aims to strengthen society, combine their expertise as changemakers. They work with Professor Carola Hein (TU Delft), who has developed knowledge about questions of disaster and rebuilding worldwide and the conditions for meaningful and long-term disaster preparedness. The partners have already reached out to relevant communities in Amsterdam and the Netherlands, including UNUN, a network of Ukrainians in the Netherlands. Jaap de Goede, an experienced strategy simulation expert, will lead outreach activities in diverse communities to train trainers and moderate workshops. This game will be highly relevant for citizens to help grow awareness and capacity for preparing for and coping with disasters in a bottom-up fashion. The toolkit will be available for download and printing open access, and for purchase. The team will offer training and facilitate workshops working with local communities to initiate bottom-up change in policy making and planning.
