Defining myocardial tissue abnormalities in end-stage renal failure with cardiac magnetic resonance imaging using native T1 mapping

Noninvasive quantification of myocardial fibrosis in end-stage renal disease is challenging. Gadolinium contrast agents previously used for cardiac magnetic resonance imaging (MRI) are contraindicated because of an association with nephrogenic systemic fibrosis. In other populations, increased myocardial native T1 times on cardiac MRI have been shown to be a surrogate marker of myocardial fibrosis. We applied this method to 33 incident hemodialysis patients and 28 age- and sex-matched healthy volunteers who underwent MRI at 3.0T. Native T1 relaxation times and feature tracking–derived global longitudinal strain as potential markers of fibrosis were compared and associated with cardiac biomarkers. Left ventricular mass indices were higher in the hemodialysis than the control group. Global, Septal and midseptal T1 times were all significantly higher in the hemodialysis group (global T1 hemodialysis 1171 ± 27 ms vs. 1154 ± 32 ms; septal T1 hemodialysis 1184 ± 29 ms vs. 1163 ± 30 ms; and midseptal T1 hemodialysis 1184 ± 34 ms vs. 1161 ± 29 ms). In the hemodialysis group, T1 times correlated with left ventricular mass indices. Septal T1 times correlated with troponin and electrocardiogram-corrected QT interval. The peak global longitudinal strain was significantly reduced in the hemodialysis group (hemodialysis -17.7±5.3% vs. -21.8±6.2%). For hemodialysis patients, the peak global longitudinal strain significantly correlated with left ventricular mass indices (R = 0.426), and a trend was seen for correlation with galectin-3, a biomarker of cardiac fibrosis. Thus, cardiac tissue properties of hemodialysis patients consistent with myocardial fibrosis can be determined noninvasively and associated with multiple structural and functional abnormalities

Social support and social structure

The burgeoning study of social support in relation to social stress and health would benefit from increased attention to issues of social structure. Three aspects of social relationships, all often referred to as social support, must be more clearly distinguished—(1) their existence or quantity (i.e., social integration), (2) their formal structure (i.e., social networks), and (3) their functional or behavioral content (i.e., the most precise meaning of “social support”)—and the causal relationships between the structure of social relationships (social integration and networks) and their functional content (social support) must be more clearly understood. Research and theory are needed on the determinants of social integration, networks, and support as well as their consequences for stress and health. Among potential determinants, macrosocial structures and processes particularly merit attention.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45658/1/11206_2005_Article_BF01107897.pd

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Efficacy and safety of baricitinib or ravulizumab in adult patients with severe COVID-19 (TACTIC-R): a randomised, parallel-arm, open-label, phase 4 trial

Background From early in the COVID-19 pandemic, evidence suggested a role for cytokine dysregulation and complement activation in severe disease. In the TACTIC-R trial, we evaluated the efficacy and safety of baricitinib, an inhibitor of Janus kinase 1 (JAK1) and JAK2, and ravulizumab, a monoclonal inhibitor of complement C5 activation, as an adjunct to standard of care for the treatment of adult patients hospitalised with COVID-19. Methods TACTIC-R was a phase 4, randomised, parallel-arm, open-label platform trial that was undertaken in the UK with urgent public health designation to assess the potential of repurposing immunosuppressants for the treatment of severe COVID-19, stratified by a risk score. Adult participants (aged ≥18 years) were enrolled from 22 hospitals across the UK. Patients with a risk score indicating a 40% risk of admission to an intensive care unit or death were randomly assigned 1:1:1 to standard of care alone, standard of care with baricitinib, or standard of care with ravulizumab. The composite primary outcome was the time from randomisation to incidence (up to and including day 14) of the first event of death, invasive mechanical ventilation, extracorporeal membrane oxygenation, cardiovascular organ support, or renal failure. The primary interim analysis was triggered when 125 patient datasets were available up to day 14 in each study group and we included in the analysis all participants who were randomly assigned. The trial was registered on ClinicalTrials.gov (NCT04390464). Findings Between May 8, 2020, and May 7, 2021, 417 participants were recruited and randomly assigned to standard of care alone (145 patients), baricitinib (137 patients), or ravulizumab (135 patients). Only 54 (39%) of 137 patients in the baricitinib group received the maximum 14-day course, whereas 132 (98%) of 135 patients in the ravulizumab group received the intended dose. The trial was stopped after the primary interim analysis on grounds of futility. The estimated hazard ratio (HR) for reaching the composite primary endpoint was 1·11 (95% CI 0·62–1·99) for patients on baricitinib compared with standard of care alone, and 1·53 (0·88–2·67) for ravulizumab compared with standard of care alone. 45 serious adverse events (21 deaths) were reported in the standard-of-care group, 57 (24 deaths) in the baricitinib group, and 60 (18 deaths) in the ravulizumab group. Interpretation Neither baricitinib nor ravulizumab, as administered in this study, was effective in reducing disease severity in patients selected for severe COVID-19. Safety was similar between treatments and standard of care. The short period of dosing with baricitinib might explain the discrepancy between our findings and those of other trials. The therapeutic potential of targeting complement C5 activation product C5a, rather than the cleavage of C5, warrants further evaluation

An examination of nurses’ practical judgments about the cognitive function of hospitalized older people

Nurses’ understandings of older patients’ cognitive function are central to how they determine and enact nursing care of older people in hospital, however, it remains unclear how nurses develop these understandings. The nursing literature concerned with how nurses determine actions in practice has begun to shift from instrumental views of reasoning to recognition that judgments are based on complex knowledge and are embedded in the particular context of nurses’ work. This study aimed to make explicit the complex, situated practical judgments of nurses about the cognitive function of older people in hospitals. The conceptual foundation of the study was informed by an integration of Aristotle’s notion of phronesis and Foucault’s understanding of power. A focused ethnographic study was conducted on two units in an urban general hospital over one year. Data were collected from 21 nurse informants through observations and interviews, and an analysis of documents used in their practice. Data analysis was guided by an analytic framework reflective of the conceptual framework. The findings showed that practical judgments about the cognitive function of older patients in hospital were structured through social relations, and nurses worked within that structure toward a complex understanding of patients’ cognitive function that would enable them to improve the situation of patients. Furthermore, ensuring safety and physiological stability emerged as the goals of nursing care related to the cognitive function of older patients and provided direction for practical judgments, including what evidence was sought and how it was used in deliberations about action. This articulation of nurses’ practical judgments about the cognitive function of older patients in hospital is a foundation for further inquiry into the context of nursing practice, educating new nurses on the complexity of nursing judgments and examining policy related to the structures guiding acute care nursing.Applied Science, Faculty ofNursing, School ofGraduat

The experience of community for seniors involved in community-engaged arts

Social isolation is a concern for the health of older adults in Canada. Community-engaged arts (CEA) programs are thought to support social inclusion but how such programs contribute to building community connections for older adults at risk of social isolation is poorly understood. This study, therefore, is aimed to explore the experience of community for this population in the context of a CEA program as well as the role the program plays in that experience. A qualitative study using ethnographic methods was conducted to answer two research questions: (1) What does community mean to seniors in the Arts, Health and Seniors program? (2) What is the role of the Arts, Health and Seniors program in the participants’ experience of community? Data were collected over a six week period using participant observation, semi-structured interviews and document analysis. The sample was a group of 20 urban-dwelling seniors at risk for social isolation who participated in a CEA program once a week. Regular group art sessions were observed by the researcher and extensive field notes were recorded. Interviews were conducted with five senior participants and four other key informants (including two artists, a senior worker, and an administrators), and documents related to the community were reviewed. Data were analyzed throughout the data collection process and interpretations were noted. Through immersion in the data and a movement between the data and interpretations, themes were developed. Connections between themes were explored and taken back to the data. Findings were presented as a detailed description of the participants’ experience of community. Community for the participants focused around the Seniors Centre where the program was held. The participants expressed that the meaningful relationships at the centre made it ‘another home’ and was a place they could find resources to adapt to challenges. The CEA program provided a unique experience of community through working together as a group and making new social connections. For health professionals working with older people at risk for social isolation, this research will add to the understanding of how community is experienced by older adults and how community is supported by CEA programs.Applied Science, Faculty ofNursing, School ofGraduat

BACKGROUND

It is estimated that by the year 2005, the majority of healthcare facilities will have implemented some type of electronic health records (EHR) and electronic documentatio