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Showing papers by "University of Ottawa published in 2020"


Journal ArticleDOI
TL;DR: New WHO 2020 guidelines on physical activity and sedentary behaviour reaffirm messages that some physical activity is better than none, that more physical Activity is better for optimal health outcomes and provide a new recommendation on reducing sedentary behaviours.
Abstract: Objectives To describe new WHO 2020 guidelines on physical activity and sedentary behaviour. Methods The guidelines were developed in accordance with WHO protocols. An expert Guideline Development Group reviewed evidence to assess associations between physical activity and sedentary behaviour for an agreed set of health outcomes and population groups. The assessment used and systematically updated recent relevant systematic reviews; new primary reviews addressed additional health outcomes or subpopulations. Results The new guidelines address children, adolescents, adults, older adults and include new specific recommendations for pregnant and postpartum women and people living with chronic conditions or disability. All adults should undertake 150-300 min of moderate-intensity, or 75-150 min of vigorous-intensity physical activity, or some equivalent combination of moderate-intensity and vigorous-intensity aerobic physical activity, per week. Among children and adolescents, an average of 60 min/day of moderate-to-vigorous intensity aerobic physical activity across the week provides health benefits. The guidelines recommend regular muscle-strengthening activity for all age groups. Additionally, reducing sedentary behaviours is recommended across all age groups and abilities, although evidence was insufficient to quantify a sedentary behaviour threshold. Conclusion These 2020 WHO guidelines update previous WHO recommendations released in 2010. They reaffirm messages that some physical activity is better than none, that more physical activity is better for optimal health outcomes and provide a new recommendation on reducing sedentary behaviours. These guidelines highlight the importance of regularly undertaking both aerobic and muscle strengthening activities and for the first time, there are specific recommendations for specific populations including for pregnant and postpartum women and people living with chronic conditions or disability. These guidelines should be used to inform national health policies aligned with the WHO Global Action Plan on Physical Activity 2018-2030 and to strengthen surveillance systems that track progress towards national and global targets.

3,218 citations


Journal ArticleDOI
Peter J. Campbell1, Gad Getz2, Jan O. Korbel3, Joshua M. Stuart4  +1329 moreInstitutions (238)
06 Feb 2020-Nature
TL;DR: The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.
Abstract: Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1,2,3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10,11,12,13,14,15,16,17,18.

1,600 citations


Journal ArticleDOI
TL;DR: Among hospitalized patients with COVID-19 and coexisting hypertension, inpatient use of ACEI/ARB was associated with lower risk of all-cause mortality compared with ACEi/ARB nonusers, and it is unlikely that in-hospital use ofACEI/ARB wasassociated with an increased mortality risk.
Abstract: Rationale: Use of ACEIs (angiotensin-converting enzyme inhibitors) and ARBs (angiotensin II receptor blockers) is a major concern for clinicians treating coronavirus disease 2019 (COVID-19) in pati...

938 citations


Journal ArticleDOI
TL;DR: A minimum set of common outcome measures for studies of COVID-19, which includes a measure of viral burden, patient survival, and patient progression through the health-care system by use of the WHO Clinical Progression Scale are urged.
Abstract: Summary Clinical research is necessary for an effective response to an emerging infectious disease outbreak. However, research efforts are often hastily organised and done using various research tools, with the result that pooling data across studies is challenging. In response to the needs of the rapidly evolving COVID-19 outbreak, the Clinical Characterisation and Management Working Group of the WHO Research and Development Blueprint programme, the International Forum for Acute Care Trialists, and the International Severe Acute Respiratory and Emerging Infections Consortium have developed a minimum set of common outcome measures for studies of COVID-19. This set includes three elements: a measure of viral burden (quantitative PCR or cycle threshold), a measure of patient survival (mortality at hospital discharge or at 60 days), and a measure of patient progression through the health-care system by use of the WHO Clinical Progression Scale, which reflects patient trajectory and resource use over the course of clinical illness. We urge investigators to include these key data elements in ongoing and future studies to expedite the pooling of data during this immediate threat, and to hone a tool for future needs.

882 citations


Journal ArticleDOI
TL;DR: The dominant mechanism of nanoparticle entry into solid tumours has now been shown to be an active trans- endothelial pathway rather than the currently established passive transport via inter-endothelial gaps.
Abstract: The concept of nanoparticle transport through gaps between endothelial cells (inter-endothelial gaps) in the tumour blood vessel is a central paradigm in cancer nanomedicine. The size of these gaps was found to be up to 2,000 nm. This justified the development of nanoparticles to treat solid tumours as their size is small enough to extravasate and access the tumour microenvironment. Here we show that these inter-endothelial gaps are not responsible for the transport of nanoparticles into solid tumours. Instead, we found that up to 97% of nanoparticles enter tumours using an active process through endothelial cells. This result is derived from analysis of four different mouse models, three different types of human tumours, mathematical simulation and modelling, and two different types of imaging techniques. These results challenge our current rationale for developing cancer nanomedicine and suggest that understanding these active pathways will unlock strategies to enhance tumour accumulation. The dominant mechanism of nanoparticle entry into solid tumours has now been shown to be an active trans-endothelial pathway rather than the currently established passive transport via inter-endothelial gaps.

879 citations


Journal ArticleDOI
Joan B. Soriano1, Parkes J Kendrick2, Katherine R. Paulson2, Vinay Gupta2  +311 moreInstitutions (178)
TL;DR: It is shown that chronic respiratory diseases remain a leading cause of death and disability worldwide, with growth in absolute numbers but sharp declines in several age-standardised estimators since 1990.

829 citations


Journal ArticleDOI
TL;DR: The prevalence, hazard ratios, and population-attributable fractions (PAFs) for cardiovascular disease and mortality associated with a cluster of behavioural factors, metabolic factors, socioeconomic and psychosocial factors, and household and ambient pollution are described.

772 citations


Journal ArticleDOI
TL;DR: Persistent immune activation in predisposed patients, such as the elderly and those with CV risk, can lead to hemophagocytosis like syndrome, with uncontrolled amplification of cytokine production, leading to multi-organ failure and death.
Abstract: The coronavirus disease 2019 (COVID-19) pandemic has affected health and economy worldwide on an unprecedented scale. Patients have diverse clinical outcomes, but those with preexisting cardiovascular disease, hypertension, and related conditions incur disproportionately worse outcome. The high infectivity of severe acute respiratory syndrome coronavirus 2 is in part related to new mutations in the receptor binding domain, and acquisition of a furin cleavage site in the S-spike protein. The continued viral shedding in the asymptomatic and presymptomatic individuals enhances its community transmission. The virus uses the angiotensin converting enzyme 2 receptor for internalization, aided by transmembrane protease serine 2 protease. The tissue localization of the receptors correlates with COVID-19 presenting symptoms and organ dysfunction. Virus-induced angiotensin converting enzyme 2 downregulation may attenuate its function, diminish its anti-inflammatory role, and heighten angiotensin II effects in the predisposed patients. Lymphopenia occurs early and is prognostic, potentially associated with reduction of the CD4+ and some CD8+ T cells. This leads to imbalance of the innate/acquired immune response, delayed viral clearance, and hyperstimulated macrophages and neutrophils. Appropriate type I interferon pathway activation is critical for virus attenuation and balanced immune response. Persistent immune activation in predisposed patients, such as elderly adults and those with cardiovascular risk, can lead to hemophagocytosis-like syndrome, with uncontrolled amplification of cytokine production, leading to multiorgan failure and death. In addition to the airways and lungs, the cardiovascular system is often involved in COVID-19 early, reflected in the release of highly sensitive troponin and natriuretic peptides, which are all extremely prognostic, in particular, in those showing continued rise, along with cytokines such as interleukin-6. Inflammation in the vascular system can result in diffuse microangiopathy with thrombosis. Inflammation in the myocardium can result in myocarditis, heart failure, cardiac arrhythmias, acute coronary syndrome, rapid deterioration, and sudden death. Aggressive support based on early prognostic indicators with expectant management can potentially improve recovery. Appropriate treatment for heart failure, arrhythmias, acute coronary syndrome, and thrombosis remain important. Specific evidence-based treatment strategies for COVID-19 will emerge with ongoing global collaboration on multiple approaches being evaluated. To protect the wider population, antibody testing and effective vaccine will be needed to make COVID-19 history.

647 citations


Journal ArticleDOI
TL;DR: Findings can guide efforts to preserve and promote child health during the COVID-19 outbreak and crisis recovery period, and to inform strategies to mitigate potential harm during future pandemics.
Abstract: Healthy childhood development is fostered through sufficient physical activity (PA; including time outdoors), limiting sedentary behaviours (SB), and adequate sleep; collectively known as movement behaviours. Though the COVID-19 virus outbreak has changed the daily lives of children and youth, it is unknown to what extent related restrictions may compromise the ability to play and meet movement behaviour recommendations. This secondary data analysis examined the immediate impacts of COVID-19 restrictions on movement and play behaviours in children and youth. A national sample of Canadian parents (n = 1472) of children (5–11 years) or youth (12–17 years) (54% girls) completed an online survey that assessed immediate changes in child movement and play behaviours during the COVID-19 outbreak. Behaviours included PA and play, SB, and sleep. Family demographics and parental factors that may influence movement behaviours were assessed. Correlations between behaviours and demographic and parental factors were determined. For open-ended questions, word frequency distributions were reported. Only 4.8% (2.8% girls, 6.5% boys) of children and 0.6% (0.8% girls, 0.5% boys) of youth were meeting combined movement behaviour guidelines during COVID-19 restrictions. Children and youth had lower PA levels, less outside time, higher SB (including leisure screen time), and more sleep during the outbreak. Parental encouragement and support, parental engagement in PA, and family dog ownership were positively associated with healthy movement behaviours. Although families spent less time in PA and more time in SB, several parents reported adopting new hobbies or accessing new resources. This study provides evidence of immediate collateral consequences of the COVID-19 outbreak, demonstrating an adverse impact on the movement and play behaviours of Canadian children and youth. These findings can guide efforts to preserve and promote child health during the COVID-19 outbreak and crisis recovery period, and to inform strategies to mitigate potential harm during future pandemics.

644 citations


Journal ArticleDOI
TL;DR: The COVID-19 pandemic quickly led to the closure of universities and colleges around the world, in hopes that public health officials’ advice of social distancing could help to flatten the infectio...
Abstract: The COVID-19 pandemic quickly led to the closure of universities and colleges around the world, in hopes that public health officials’ advice of social distancing could help to flatten the infectio...

554 citations


Journal ArticleDOI
TL;DR: It is important to develop new strategies to address loneliness and social isolation among older adults for the post-pandemic era and to maintain social connections with each other, especially with older persons.
Abstract: Loneliness and social isolation are associated with adverse physical and psychological consequences which are particularly prevalent in older persons. During this unprecedented time of the COVID-19 pandemic, we must follow social distancing guidelines to protect ourselves and to reduce the spread of coronavirus. At the same time, it is crucial to maintain social connections with each other, especially with older persons, to help cope and reduce the negative consequences of loneliness and social isolation. It is important to develop new strategies (e.g. virtual health care and new government policy) to address loneliness and social isolation among older adults for the post-pandemic era.

Journal ArticleDOI
TL;DR: This work presents a novel and scalable approach to regenerative medicine that combines traditional and regenerative approaches to treat central giant cell granuloma, a leading cause of cancer in women.
Abstract: 1Northwestern University Feinberg School of Medicine, Division of Nephrology and Hypertension, Chicago, Illinois 2Hospital Universitari Vall d’Hebron, Division of Nephrology Autonomous University of Barcelona, Barcelona, Spain 3Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina 4Renal Section, Durham Veterans Affairs Health Care System, Durham, North Carolina 5Division of Nephrology, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada 6Department of Pediatrics, Section of Nephrology, Wake Forest School of Medicine, Winston Salem, North Carolina 7School of Medicine, Departments of Medicine and Physiology, Johns Hopkins University, Baltimore, Maryland 8Division of Nephrology, and Center for Immunity, Inflammation and Regenerative Medicine, University of Virginia, Charlottesville, Virginia

Journal ArticleDOI
TL;DR: Obesity is a complex chronic disease in which abnormal or excess body fat (adiposity) impairs health, increases the risk of long-term medical complications and reduces lifespan.
Abstract: KEY POINTS Obesity is a complex chronic disease in which abnormal or excess body fat (adiposity) impairs health, increases the risk of long-term medical complications and reduces lifespan.[1][1] Epidemiologic studies define obesity using the body mass index (BMI; weight/height2), which can stratify

Journal ArticleDOI
TL;DR: Ass associations of daily average temperature (AT) and relative humidity (ARH) with the daily count of COVID-19 cases in 30 Chinese provinces were examined to examine the influence of meteorological factors on the transmission and spread of the pandemic.

Journal ArticleDOI
TL;DR: This analysis assesses the incidence of events in 162 534 participants who were enrolled in the first two phases of the PURE core study, finding a pattern of the highest mortality in LICs and the lowest in HICs was observed for all causes of death except cancer, where mortality was similar across country income levels.

Journal ArticleDOI
TL;DR: A retrospective study on 13,981 patients with COVID-19 in Hubei Province, China found that the risk for 28-day all-cause mortality was 5.2% and 9.4% in the matched statin and non-statin groups, respectively, with a hazard ratio 0.58, implying the potential benefits of statin therapy in hospitalized subjects with CO VID-19.

Journal ArticleDOI
TL;DR: An empirical account of how one research team developed and employed strategies to detect and limit social desirability bias in rural Ethiopia is provided.
Abstract: Many qualitative research studies acknowledge the possibility of social desirability bias (a tendency to present reality to align with what is perceived to be socially acceptable) as a limitation t...

Journal ArticleDOI
TL;DR: It is demonstrated that platelets release their alpha- and dense-granule contents in both nonsevere and severe forms of COVID-19, as they release various sets of molecules through the different stages of the disease.
Abstract: Rationale: In addition to the overwhelming lung inflammation that prevails in COVID-19, hypercoagulation and thrombosis contribute to the lethality of subjects infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Platelets are chiefly implicated in thrombosis. Moreover, they can interact with viruses and are an important source of inflammatory mediators. While a lower platelet count is associated with severity and mortality, little is known about platelet function during COVID-19. Objective: To evaluate the contribution of platelets to inflammation and thrombosis in COVID-19 patients. Methods and Results: Blood was collected from 115 consecutive COVID-19 patients presenting non-severe (n=71) and severe (n=44) respiratory symptoms. We document the presence of SARS-CoV-2 RNA associated with platelets of COVID-19 patients. Exhaustive assessment of cytokines in plasma and in platelets revealed the modulation of platelet-associated cytokine levels in both non-severe and severe COVID-19 patients, pointing to a direct contribution of platelets to the plasmatic cytokine load. Moreover, we demonstrate that platelets release their alpha- and dense-granule contents in both non-severe and severe forms of COVID-19. In comparison to concentrations measured in healthy volunteers, phosphatidylserine-exposing platelet extracellular vesicles were increased in non-severe, but not in severe cases of COVID-19. Levels of D-dimers, a marker of thrombosis, failed to correlate with any measured indicators of platelet activation. Functionally, platelets were hyperactivated in COVID-19 subjects presenting non-severe and severe symptoms, with aggregation occurring at suboptimal thrombin concentrations. Furthermore, platelets adhered more efficiently onto collagen-coated surfaces under flow conditions. Conclusions: Taken together, the data suggest that platelets are at the frontline of COVID-19 pathogenesis, as they release various sets of molecules through the different stages of the disease. Platelets may thus have the potential to contribute to the overwhelming thrombo-inflammation in COVID-19, and the inhibition of pathways related to platelet activation may improve the outcomes during COVID-19.

Journal ArticleDOI
TL;DR: Over one-quarter of the most viewed YouTube videos on COVID-19 contained misleading information, reaching millions of viewers worldwide, highlighting the need to better use YouTube to deliver timely and accurate information and to minimise the spread of misinformation.
Abstract: Introduction The COVID-19 pandemic is this century’s largest public health emergency and its successful management relies on the effective dissemination of factual information. As a social media platform with billions of daily views, YouTube has tremendous potential to both support and hinder public health efforts. However, the usefulness and accuracy of most viewed YouTube videos on COVID-19 have not been investigated. Methods A YouTube search was performed on 21 March 2020 using keywords ‘coronavirus’ and ‘COVID-19’, and the top 75 viewed videos from each search were analysed. Videos that were duplicates, non-English, non-audio and non-visual, exceeding 1 hour in duration, live and unrelated to COVID-19 were excluded. Two reviewers coded the source, content and characteristics of included videos. The primary outcome was usability and reliability of videos, analysed using the novel COVID-19 Specific Score (CSS), modified DISCERN (mDISCERN) and modified JAMA (mJAMA) scores. Results Of 150 videos screened, 69 (46%) were included, totalling 257 804 146 views. Nineteen (27.5%) videos contained non-factual information, totalling 62 042 609 views. Government and professional videos contained only factual information and had higher CSS than consumer videos (mean difference (MD) 2.21, 95% CI 0.10 to 4.32, p=0.037); mDISCERN scores than consumer videos (MD 2.46, 95% CI 0.50 to 4.42, p=0.008), internet news videos (MD 2.20, 95% CI 0.19 to 4.21, p=0.027) and entertainment news videos (MD 2.57, 95% CI 0.66 to 4.49, p=0.004); and mJAMA scores than entertainment news videos (MD 1.21, 95% CI 0.07 to 2.36, p=0.033) and consumer videos (MD 1.27, 95% CI 0.10 to 2.44, p=0.028). However, they only accounted for 11% of videos and 10% of views. Conclusion Over one-quarter of the most viewed YouTube videos on COVID-19 contained misleading information, reaching millions of viewers worldwide. As the current COVID-19 pandemic worsens, public health agencies must better use YouTube to deliver timely and accurate information and to minimise the spread of misinformation. This may play a significant role in successfully managing the COVID-19 pandemic.

Journal ArticleDOI
TL;DR: In vitro and in vivo experiments have demonstrated that NPs have the potential to penetrate different biological barriers including the gastrointestinal barrier and the brain blood barrier and have been detected in many important organs such as brains, the circulation system and livers of sampled animals.

Journal ArticleDOI
TL;DR: There was sufficient evidence to support recommendations on limiting sedentary behaviours, which was not addressed in the 2010 WHO guidelines, but there is still insufficient evidence available to fully describe the dose-response relationships between physical activity or sedentary behaviour and health outcomes.
Abstract: The World Health Organization (WHO) released in 2020 updated global guidelines on physical activity and sedentary behaviour for children, adolescents, adults, older adults and sub-populations such as pregnant and postpartum women and those living with chronic conditions or disabilities. To summarize the evidence on the associations between physical activity, sedentary behaviour, and health-related outcomes used to inform the 2020 WHO guidelines on physical activity and sedentary behaviour for children and adolescents aged 5–17 years. The update of the WHO guideline recommendations for children and adolescents utilized and systematically updated the evidence syntheses on physical activity and sedentary behaviour conducted for the 2016 Canadian 24-Hour Movement Guidelines for Children and Youth, the 2019 Australian 24-Hour Movement Guidelines for Children and Young People (5–17 years), and the 2018 Physical Activity Guidelines for Americans, Second Edition. Systematic reviews published from 2017 up to July 2019 that addressed the key questions were identified, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework was used to rate the certainty of the evidence for the entire body of evidence. The updated literature search yielded 21 relevant systematic reviews. The evidence base reviewed (i.e., existing and new systematic reviews) provided evidence that greater amounts and higher intensities of physical activity as well as different types of physical activity (i.e., aerobic and muscle and bone strengthening activities) are associated with improved health outcomes (primarily intermediate outcomes). There was sufficient evidence to support recommendations on limiting sedentary behaviours, which was not addressed in the 2010 WHO guidelines. However, there is still insufficient evidence available to fully describe the dose-response relationships between physical activity or sedentary behaviour and health outcomes, and whether the associations vary by type or domain of physical activity or sedentary behaviour. Addressing the identified research gaps will better inform guideline recommendations in children and adolescents, and future work should aim to prioritize these areas of research. In the meantime, investment and leadership is needed to scale up known effective policies and programs aimed at increasing activity in children and adolescents.

Journal ArticleDOI
07 Feb 2020-Science
TL;DR: The method developed in this study permits spatially explicit predictions of climate change–related population extinction-colonization dynamics within species that explains observed patterns of geographical range loss and expansion across continents.
Abstract: Climate change could increase species' extinction risk as temperatures and precipitation begin to exceed species' historically observed tolerances. Using long-term data for 66 bumble bee species across North America and Europe, we tested whether this mechanism altered likelihoods of bumble bee species' extinction or colonization. Increasing frequency of hotter temperatures predicts species' local extinction risk, chances of colonizing a new area, and changing species richness. Effects are independent of changing land uses. The method developed in this study permits spatially explicit predictions of climate change-related population extinction-colonization dynamics within species that explains observed patterns of geographical range loss and expansion across continents. Increasing frequencies of temperatures that exceed historically observed tolerances help explain widespread bumble bee species decline. This mechanism may also contribute to biodiversity loss more generally.

Journal ArticleDOI
19 Jan 2020-Energies
TL;DR: The existing literature on the application of IoT in in energy systems, in general, and in the context of smart grids particularly is reviewed, and challenges of deploying IoT in the energy sector are reviewed, including privacy and security.
Abstract: Integration of renewable energy and optimization of energy use are key enablers of sustainable energy transitions and mitigating climate change. Modern technologies such the Internet of Things (IoT) offer a wide number of applications in the energy sector, i.e, in energy supply, transmission and distribution, and demand. IoT can be employed for improving energy efficiency, increasing the share of renewable energy, and reducing environmental impacts of the energy use. This paper reviews the existing literature on the application of IoT in in energy systems, in general, and in the context of smart grids particularly. Furthermore, we discuss enabling technologies of IoT, including cloud computing and different platforms for data analysis. Furthermore, we review challenges of deploying IoT in the energy sector, including privacy and security, with some solutions to these challenges such as blockchain technology. This survey provides energy policy-makers, energy economists, and managers with an overview of the role of IoT in optimization of energy systems.

Journal ArticleDOI
Michael D. Hill1, Mayank Goyal1, Bijoy K Menon1, Raul G. Nogueira2  +773 moreInstitutions (39)
TL;DR: Nerinetide did not improve the proportion of patients achieving good clinical outcomes after endovascular thrombectomy compared with patients receiving placebo, and this trial is registered with ClinicalTrials.gov, NCT02930018.

Journal ArticleDOI
Rafael Lozano1, Nancy Fullman1, John Everett Mumford1, Megan Knight1  +902 moreInstitutions (380)
TL;DR: To assess current trajectories towards the GPW13 UHC billion target—1 billion more people benefiting from UHC by 2023—the authors estimated additional population equivalents with UHC effective coverage from 2018 to 2023, and quantified frontiers of U HC effective coverage performance on the basis of pooled health spending per capita.

Journal ArticleDOI
TL;DR: The Consort-AI (Consolidated Standards of Reporting Trials-Artificial Intelligence) extension as mentioned in this paper is a new reporting guideline for clinical trials evaluating interventions with an AI component.
Abstract: The CONSORT 2010 statement provides minimum guidelines for reporting randomized trials. Its widespread use has been instrumental in ensuring transparency in the evaluation of new interventions. More recently, there has been a growing recognition that interventions involving artificial intelligence (AI) need to undergo rigorous, prospective evaluation to demonstrate impact on health outcomes. The CONSORT-AI (Consolidated Standards of Reporting Trials-Artificial Intelligence) extension is a new reporting guideline for clinical trials evaluating interventions with an AI component. It was developed in parallel with its companion statement for clinical trial protocols: SPIRIT-AI (Standard Protocol Items: Recommendations for Interventional Trials-Artificial Intelligence). Both guidelines were developed through a staged consensus process involving literature review and expert consultation to generate 29 candidate items, which were assessed by an international multi-stakeholder group in a two-stage Delphi survey (103 stakeholders), agreed upon in a two-day consensus meeting (31 stakeholders) and refined through a checklist pilot (34 participants). The CONSORT-AI extension includes 14 new items that were considered sufficiently important for AI interventions that they should be routinely reported in addition to the core CONSORT 2010 items. CONSORT-AI recommends that investigators provide clear descriptions of the AI intervention, including instructions and skills required for use, the setting in which the AI intervention is integrated, the handling of inputs and outputs of the AI intervention, the human-AI interaction and provision of an analysis of error cases. CONSORT-AI will help promote transparency and completeness in reporting clinical trials for AI interventions. It will assist editors and peer reviewers, as well as the general readership, to understand, interpret and critically appraise the quality of clinical trial design and risk of bias in the reported outcomes.

Journal ArticleDOI
09 Sep 2020-BMJ
TL;DR: The CONSORT-AI (Consolidated Standards of Reporting Trials–Artificial Intelligence) extension is a new reporting guideline for clinical trials evaluating interventions with an AI component that will assist editors and peer reviewers to understand, interpret and critically appraise the quality of clinical trial design and risk of bias in the reported outcomes.
Abstract: The CONSORT 2010 (Consolidated Standards of Reporting Trials) statement provides minimum guidelines for reporting randomised trials. Its widespread use has been instrumental in ensuring transparency when evaluating new interventions. More recently, there has been a growing recognition that interventions involving artificial intelligence (AI) need to undergo rigorous, prospective evaluation to demonstrate impact on health outcomes.The CONSORT-AI extension is a new reporting guideline for clinical trials evaluating interventions with an AI component. It was developed in parallel with its companion statement for clinical trial protocols: SPIRIT-AI. Both guidelines were developed through a staged consensus process, involving a literature review and expert consultation to generate 29 candidate items, which were assessed by an international multi-stakeholder group in a two-stage Delphi survey (103 stakeholders), agreed on in a two-day consensus meeting (31 stakeholders) and refined through a checklist pilot (34 participants).The CONSORT-AI extension includes 14 new items, which were considered sufficiently important for AI interventions, that they should be routinely reported in addition to the core CONSORT 2010 items. CONSORT-AI recommends that investigators provide clear descriptions of the AI intervention, including instructions and skills required for use, the setting in which the AI intervention is integrated, the handling of inputs and outputs of the AI intervention, the human-AI interaction and providing analysis of error cases.CONSORT-AI will help promote transparency and completeness in reporting clinical trials for AI interventions. It will assist editors and peer-reviewers, as well as the general readership, to understand, interpret and critically appraise the quality of clinical trial design and risk of bias in the reported outcomes.

Journal ArticleDOI
Doreen M. Rabi1, Kerry McBrien1, Ruth Sapir-Pichhadze2, Meranda Nakhla2, Sofia B. Ahmed3, Sandra M. Dumanski3, Sonia Butalia4, Alexander A. Leung1, Kevin C. Harris5, Lyne Cloutier6, Kelly B. Zarnke1, Marcel Ruzicka7, Swapnil Hiremath8, Ross D. Feldman9, Sheldon W. Tobe10, Tavis S. Campbell1, Simon L. Bacon11, Kara Nerenberg1, George K. Dresser12, Anne Fournier13, Ellen Burgess1, Patrice Lindsay14, Simon W. Rabkin5, Ally P.H. Prebtani15, Steven A. Grover16, George Honos17, Jeffrey E. Alfonsi12, JoAnne Arcand18, François Audibert17, Geneviève Benoit13, Jesse Bittman5, Peter Bolli15, Anne-Marie Côté19, Janis M. Dionne5, Andrew C. Don-Wauchope15, Cedric Edwards7, Tabassum Firoz20, Jonathan Y. Gabor, Richard E. Gilbert21, Jean Grégoire22, Steven E. Gryn12, Milan Gupta15, Fady Hannah-Shmouni23, Robert A. Hegele12, Robert J. Herman1, Michael D. Hill1, Jonathan G. Howlett1, Gregory L. Hundemer7, Charlotte Jones5, Janusz Kaczorowski17, Nadia A. Khan5, Laura M. Kuyper5, Maxime Lamarre-Cliche17, Kim L. Lavoie24, Lawrence A. Leiter25, Richard Lewanczuk26, Alexander G. Logan27, Laura A. Magee28, Birinder K. Mangat5, Philip A. McFarlane25, Donna McLean29, André Michaud19, Alain Milot30, Gordon W. Moe25, S. Brian Penner31, Andrew L. Pipe7, Alexandre Y Poppe17, Evelyne Rey17, Michael Roerecke32, Ernesto L. Schiffrin16, Peter Selby32, Mike Sharma33, Ashkan Shoamanesh33, Praveena Sivapalan34, Raymond R. Townsend35, Karen Tran5, Luc Trudeau16, Ross T. Tsuyuki26, Michel Vallée36, Vincent Woo31, Alan Bell25, Stella S. Daskalopoulou2 
TL;DR: The 2020 guidelines include new guidance on themanagement of resistant hypertension and the management of hypertension in women planning pregnancy.

Journal ArticleDOI
TL;DR: This research presents a novel probabilistic approach that allows us to assess the importance of knowing the carrier and removal status of canine coronavirus, as a source of infection for other animals.
Abstract: Myocarditis is an inflammatory disease of the heart that may occur because of infections, immune system activation, or exposure to drugs. The diagnosis of myocarditis has changed due to the introduction of cardiac magnetic resonance imaging. We present an expert consensus document aimed to summarize the common terminology related to myocarditis meanwhile highlighting some areas of controversies and uncertainties and the unmet clinical needs. In fact, controversies persist regarding mechanisms that determine the transition from the initial trigger to myocardial inflammation and from acute myocardial damage to chronic ventricular dysfunction. It is still uncertain which viruses (besides enteroviruses) cause direct tissue damage, act as triggers for immune-mediated damage, or both. Regarding terminology, myocarditis can be characterized according to etiology, phase, and severity of the disease, predominant symptoms, and pathological findings. Clinically, acute myocarditis (AM) implies a short time elapsed from the onset of symptoms and diagnosis (generally <1 month). In contrast, chronic inflammatory cardiomyopathy indicates myocardial inflammation with established dilated cardiomyopathy or hypokinetic nondilated phenotype, which in the advanced stages evolves into fibrosis without detectable inflammation. Suggested diagnostic and treatment recommendations for AM and chronic inflammatory cardiomyopathy are mainly based on expert opinion given the lack of well-designed contemporary clinical studies in the field. We will provide a shared and practical approach to patient diagnosis and management, underlying differences between the European and US scientific statements on this topic. We explain the role of histology that defines subtypes of myocarditis and its prognostic and therapeutic implications.

Journal ArticleDOI
TL;DR: This work identifies the mechanism by which BH4 acts as an endogenous antioxidant and provides a compendium of metabolic modifiers of lipid peroxidation, and identifies tetrahydrobiopterin (BH4) biosynthesis as an essential metabolic pathway upon GPX4 inhibition.
Abstract: Cancer cells rewire their metabolism and rely on endogenous antioxidants to mitigate lethal oxidative damage to lipids. However, the metabolic processes that modulate the response to lipid peroxidation are poorly defined. Using genetic screens, we compared metabolic genes essential for proliferation upon inhibition of cystine uptake or glutathione peroxidase-4 (GPX4). Interestingly, very few genes were commonly required under both conditions, suggesting that cystine limitation and GPX4 inhibition may impair proliferation via distinct mechanisms. Our screens also identify tetrahydrobiopterin (BH4) biosynthesis as an essential metabolic pathway upon GPX4 inhibition. Mechanistically, BH4 is a potent radical-trapping antioxidant that protects lipid membranes from autoxidation, alone and in synergy with vitamin E. Dihydrofolate reductase catalyzes the regeneration of BH4, and its inhibition by methotrexate synergizes with GPX4 inhibition. Altogether, our work identifies the mechanism by which BH4 acts as an endogenous antioxidant and provides a compendium of metabolic modifiers of lipid peroxidation.