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Showing 201–220 of 2058 publications.
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Zhao, Emma; Bloomfield, Jacqueline G.; Lowres, Nicole; Gallagher, Robyn D.Background: Cognitive impairment and cardiovascular disease often coexist, and nurses are ideally positioned to detect and manage cognitive impairment in cardiac patients. Objectives: This study explored nurses' perspectives on understanding, detecting, and acting on cognitive impairment in cardiac patients. Design and Methods: Using an exploratory descriptive design, nurses from acute and outpatient cardiac units were interviewed. Data were thematically analyzed. Results: Sixteen nurses were interviewed, working in acute cardiology (n=7), cardiothoracic and intensive care (n=4), and cardiac rehabilitation (n=5). Three themes emerged: (1) Cognitive screening was not routine, with no clear protocols on who, when, and how to screen; (2) Nurses had varying understanding of cognitive impairment, dementia, and delirium; (3) Nurses acted on suspected cognitive changes to ensure patient safety, including referrals and care modifications. Conclusions: Cognitive screening was inconsistent, with barriers, such as workload and lack of education. Guidelines for feasible screening across settings are needed. 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
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Ball, Jocasta C.; Neumann, Johannes Tobias; Tonkin, Andrew Maxwell; Kirchhof, Paulus F.; Freedman, Ben; Brodtmann, Amy G.; Reid, Christopher M.; Nelson, Mark Raymond; Beilin, Lawerence Joseph; Fitzgerald, Sharyn M.; Stub, Dion A.; Woods, R. L.; McNeil, John J.[No abstract available]
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Lin, Alexander; Brittan, M.; Baker, Andrew H.; Dimmeler, Stefanie; Fisher, Edward A.; Sluimer, Judith C.; Misra, Ashish K.Clonal expansion refers to the proliferation and selection of advantageous clones that are better suited for survival in a Darwinian manner. In recent years, we have greatly enhanced our understanding of cell clonality in the cardiovascular context. However, our knowledge of the underlying mechanisms behind this clonal selection is still severely limited. There is a transpiring pattern of clonal expansion of smooth muscle cells and endothelial cellsand, in some cases, macrophagesin numerous cardiovascular diseases irrespective of their differing microenvironments. These findings indirectly suggest the possible existence of stem-like vascular cells which are primed to respond during disease. Subsequent clones may undergo further phenotypic changes to adopt either protective or detrimental roles. By investigating these clone-forming vascular cells, we may be able to harness this inherent clonal nature for future therapeutic intervention. This review comprehensively discusses what is currently known about clonal expansion across the cardiovascular field. Comparisons of the clonal nature of vascular cells in atherosclerosis (including clonal hematopoiesis of indeterminate potential), pulmonary hypertension, aneurysm, blood vessel injury, ischemia- and tumor-induced angiogenesis, and cerebral cavernous malformations are evaluated. Finally, we discuss the potential clinical implications of these findings and propose that proper understanding and specific targeting of these clonal cells may provide unique therapeutic options for the treatment of these cardiovascular conditions. 2024 The Authors
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Parter, Carmen; Gwynn, Josephine Diana; Wilson, Shawn; Skinner, John C.; Rix, Elizabeth F.; Hartz, Donna L.The inclusion of Indigenous cultures, known as the cultural determinants of health, in healthcare policy and health professional education accreditation and registration requirements, is increasingly being recognised as imperative for improving the appalling health and well-being of Indigenous Australians. These inclusions are a strengths-based response to tackling the inequities in Indigenous Australians health relative to the general population. However, conceptualising the cultural determinants of health in healthcare practice has its contextual challenges, and gaps in implementation evidence are apparent. In this paper, we provide a case example, namely the Katherine Hospital, of how healthcare services can implement the cultural determinants of health into clinical practice. However, to be effective, health professionals must concede that Australias Indigenous peoples knowledges involving cultural ways of being, knowing and doing must co-exist with western and biomedical knowledges of health practice. We use the Katherine Hospital ABC Radio National Background Briefing interview, which was mentioned by two research participants in a 2020 study, as an example of good practice that we can learn from. Additionally, the six Aboriginal and Torres Strait Islander Health actions contained in the 2nd Edition of the Australian National Safety and Quality Health Service Standards provide governance and accountability examples of how to enable Indigenous peoples cultures and their knowledges in the provision of services. The role of non-Indigenous clinical allies and accomplices is imperative when embedding and enacting Indigenous Australians cultures in service systems of health. When Indigenous Peoples access mainstream hospitals, deep self-reflection by allies and accomplices is necessary to enable safe, quality care, and treatment that is culturally safe and free from racism. Doing so can increase cultural responsiveness free of racism, thereby reducing the inherent power imbalances embedded within mainstream health services. 2023 by the authors.
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Lloyd, Larissa K.; Nicholson, Calum; Strange, G. A.; Celermajer, David S.Objective. Data linkage is a very powerful research tool in epidemiology, however, establishing this can be a lengthy and intensive process. This paper reports on the complex landscape of conducting data linkage projects in Australia. Methods. We reviewed the processes, required documentation, and applications required to conduct multi-jurisdictional data linkage across Australia, in 2023. Results. Obtaining the necessary approvals to conduct linkage will likely take nearly 2 years (estimated 730 days, including 605 days from initial submission to obtaining all ethical approvals and an estimated further 125 days for the issuance of unexpected additionally required approvals). Ethical review for linkage projects ranged from 51 to 128 days from submission to ethical approval, and applications consisted of 9-25 documents. Conclusions. Major obstacles to conducting multi-jurisdictional data linkage included the complexity of the process, and substantial time and financial costs. The process was characterised by inefficiencies at several levels, reduplication, and a lack of any key accountabilities for timely performance of processes. Data linkage is an invaluable resource for epidemiological research. Further streamlining, establishing accountability, and greater collaboration between jurisdictions is needed to ensure data linkage is both accessible and feasible to researchers. 2024 CSIRO. All rights reserved.
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Chung, Roger Yat Nork; Freedman, BenThe increasing integration of artificial intelligence (AI) in clinical and health care aims to enhance diagnosis, prognosis prediction, phenotype identification, treatment selection, and health system efficiency. However, the utilization of AI machine learning can inadvertently contribute to health inequalities. This chapter provides an overview of biases present in AI machine learning processes within traditional healthcare settings and explores how these biases can perpetuate and exacerbate existing healthcare inequalities. Specifically, four types of bias are examined: biases in (1) model design, (2) model training and prediction, (3) model deployment, and (4) model evaluation. Although these biases have received significant attention in the literature on AI machine learning and health equity, they represent only a subset of the challenges related to achieving health equity. Therefore, the second part of this chapter highlights the less explored dimension of AI's potential impact on social environments in the real world, which can act as social determinants of health and healthcare inequalities. 2024 Elsevier Inc. All rights reserved.
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Raeside, Rebecca; Todd, Allyson R.; Sim, Kyra A.; Kang, Melissa S.L.; Mihrshahi, Seema; Gardner, Lauren A.; Champion, Katrina Elizabeth; Skinner, John C.; Laranjo, Liliana; Steinbeck, Katharine S.; Redfern, Julie; Partridge, Stephanie R.Background: Chronic disease risk factors are increasing amongst adolescents, globally. Digital health prevention programs, which provide education and information to reduce chronic disease risk factors need to be equitable and accessible for all. For their success, multiple highly engaged stakeholders should be involved in development and implementation. This study aimed to evaluate stakeholders support for, and perspectives on potential public health impact of digital health prevention programs for adolescents and potential pathways for future implementation. Methods: Qualitative semi-structured online interviews with stakeholders. Stakeholder mapping identified key individuals, groups and organizations across Australia that may influence the implementation of digital health prevention programs for adolescents. Recorded and transcribed interviews were analyzed within the Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) Framework, using deductive content analysis. Findings: Nineteen interviews were conducted in 2023 with stakeholders from government, health, non-government organizations, youth services, education, community settings and others. Four overarching themes were identified: (i) existing digital health initiatives are not fit for purpose; (ii) the co-creation of digital health prevention programs is critical for successful implementation; (iii) digital health prevention programs must address equity and the unique challenges raised by technology and; (iv) system level factors must be addressed. Interpretation: Stakeholders broadly supported digital health prevention programs, yet raised unique insights to ensure that future programs create public health impact by improving chronic disease risk factors among adolescents. These insights can be applied in future development of digital health prevention programs for adolescents to strengthen widespread implementation. 2024 Raeside, Todd, Sim, Kang, Mihrshahi, Gardner, Champion, Skinner, Laranjo, Steinbeck, Redfern and Partridge.
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Role of inflammation and evidence for the use of colchicine in patients with acute coronary syndromeBulnes, Juan Francisco; Gonzez, Leticia; Velquez, Leonardo; Orellana, Mar Paz; Venturelli, Paula Muz; Martez, Gonzalo J.Acute Coronary Syndrome (ACS) significantly contributes to cardiovascular death worldwide. ACS may arise from the disruption of an atherosclerotic plaque, ultimately leading to acute ischemia and myocardial infarction. In the pathogenesis of atherosclerosis, inflammation assumes a pivotal role, not solely in the initiation and complications of atherosclerotic plaque formation, but also in the myocardial response to ischemic insult. Acute inflammatory processes, coupled with time to reperfusion, orchestrate ischemic and reperfusion injuries, dictating infarct magnitude and acute left ventricular (LV) remodeling. Conversely, chronic inflammation, alongside neurohumoral activation, governs persistent LV remodeling. The interplay between chronic LV remodeling and recurrent ischemic episodes delineates the progression of the disease toward heart failure and cardiovascular death. Colchicine exerts anti-inflammatory properties affecting both the myocardium and atherosclerotic plaque by modulating the activity of monocyte/macrophages, neutrophils, and platelets. This modulation can potentially result in a more favorable LV remodeling and forestalls the recurrence of ACS. This narrative review aims to delineate the role of inflammation across the different phases of ACS pathophysiology and describe the mechanistic underpinnings of colchicine, exploring its purported role in modulating each of these stages. 2024 Bulnes, Gonzez, Velquez, Orellana, Venturelli and Martez.
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Henson, Connie; Freedman, Ben; Rambaldini, Boe; Carlson, Bronwyn; Parter, Carmen; Nalliah, Chrishan Joseph; Chapman, Felicity; Shepherd, Gina; Orchard, Jessica Joan; Skinner, John C.; Gwynn, Josephine Diana; Macniven, Rona; Ramsden, Robyn L.; Speier, Sophia Nala ?ixsisa? Las; Nahdi, Suud Mohamed; Christie, Vita; Huang, Yansong; Ward, Katrina D.; Gwynne, Kylie G.Objective: Health programs for Indigenous people are most effective, acceptable, and sustainable when Indigenous perspectives are prioritized. Codesign builds on Indigenous people's creativity and propensity to experiment with new technologies and ensures research is designed and implemented in a culturally safe and respectful manner. Limited research has focused on older Indigenous people as partners in digital health. No research has focused on the acceptability and feasibility of older Indigenous people using wearables for heart health monitoring. This study provides insights into the acceptability and feasibility for ?55-year-old Indigenous people living in remote locations to use wearables (watches and patches) to detect atrial fibrillation (AF) and high blood pressure. Methods: This mixed methods study was codesigned and coimplemented with the local Aboriginal Controlled Health Service in a remote area of New South Wales, Australia. It included active involvement and codesign with the participants. The devices used in this study included a Withings Scan watch and a Biobeat patch. Results: Despite challenging conditions (>36C) and variable internet connectivity, 11 Indigenous older adults participated in a five-day wearables program in a remote location. Participants indicated that using digital health devices was acceptable and feasible for older Indigenous users. They described high levels of comfort, safety and convenience when using wearables (patches and watches) to detect AF. They were active participants in codesigning the program. Conclusion: Older Indigenous Australians are motivated to use wearable health devices. They are keen to participate in codesign innovative health tech programs to ensure new health technologies are acceptable to Indigenous people and feasible for remote locations. The Author(s) 2024.
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Sack, Fabian; Irwin, Amanda; van der Zalm, Raymond; Ho, Loraine; Celermajer, Danielle D.; Celermajer, David S.Healthcare is a major generator of greenhouse gases, so consideration of this contribution to climate change needs to be quantified in ways that can inform models of care. Given the availability of activity-based financial data, environmentally-extended inputoutput (EEIO) analysis can be employed to calculate systemic carbon footprints for healthcare activities, allowing comparison of different patient care pathways. We thus quantified and compared the carbon footprint of two common care pathways for patients with stable coronary artery disease, with similar clinical outcomes: coronary stenting and coronary artery bypass surgery (CABG). Healthcare cost data for these two pathways were disaggregated and the carbon footprint associated with this expenditure was calculated by connecting the flow of money within the economy to the greenhouse gases emitted to support the full range of associated activities. The systemic carbon footprint associated with an average stable patient CABG pathway, at a large tertiary referral hospital in Sydney, Australia in 202122, was 11.5 tonnes CO<inf>2</inf>-e, 4.9 times greater than the 2.4 tonnes CO<inf>2</inf>-e footprint of an average comparable stenting pathway. These data suggest that a stenting pathway for stable coronary disease should be preferred on environmental grounds and introduces EEIO analysis as a practical tool to assist in health-care related carbon footprinting. 2024 Sack, Irwin, van der Zalm, Ho, Celermajer and Celermajer.
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Brienesse, Stephen C.; Passman, Rod Stuart; Freedman, Ben[No abstract available]
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Misra, Ashish K.; Psaltis, Peter James; Nidorf, Stefan Mark[No abstract available]
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Eid, Stephanie; Giskes, Katrina; Jeong, Donna; Jennings, Luke; Dababneh, Edward; Woods, Margot; Hespe, Charlotte MaryBackground and objective Familial hypercholesterolaemia (FH) is a genetic condition contributing to premature cardiovascular disease. Currently, general practitioners (GPs) do not proactively screen for the condition. This study implemented and evaluated a digital FH self-screening questionnaire administered in general practice. Methods Patients aged 1860 years in four general practices were sent an FH screening questionnaire via SMS prior to their GP appointment. The survey identified at-risk patients, and results were exported to the patients electronic medical record. Results In all, 1258 patients were sent the survey; 234 (18.6%) interacted with it, 137 completed self-screening and nine patients were identified as high risk. Self-screening took 3.5 minutes (on average) and was positively evaluated by patients. Discussion This proof-of-concept study identified that FH self-screening can be implemented, but further refinements to the self-screening method and interface might be required for greater patient engagement. FH self-screening has the potential to increase FH detection and reduce preventable cardiovascular disease. (2024), (Royal Australian College of General Practitioners). All rights reserved.
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Raeside, Rebecca; Todd, Allyson R.; Barakat, Sarah; Rom, Sean; Boulet, Stephanie; Maguire, Sarah L.; Williams, Kathryn Helen; Mihrshahi, Seema; Hackett, Maree L.; Redfern, Julie; Partridge, Stephanie R.; Steinbeck, Katharine S.; Figtree, Gemma A.; Gallagher, Robyn D.; Kang, Melissa S.L.; Hyun, Karice K.; Spielman, Karen; Sim, Kyra A.; Usherwood, Tim; Hepse, Charlotte; Laranjo, Liliana; Skinner, John C.; Castles, Danielle; Champion, Katrina Elizabeth; Gardner, Lauren A.Background: Preventive interventions are needed to provide targeted health support to adolescents to improve health behaviors. Engaging adolescents in preventive interventions remains a challenge, highlighting the need for innovative recruitment strategies. Given adolescents' lives are intertwined with digital technologies, attention should be focused on these avenues for recruitment. The evolving nature of clinical trials, including the emergence of virtual clinical trials, requires new recruitment approaches, which must be evaluated. Objective: This study aimed to examine the effectiveness and cost of various digital recruitment strategies for recruiting adolescents to a virtual clinical trial, evaluate the progression of participants from screening to enrollment, and explore factors associated with nonparticipation. This was conducted using data from the Health4Me Study, a preventive digital health intervention to improve physical activity and nutrition behaviors among adolescents aged 12 to 18 years. Methods: Participants were recruited into the Health4Me Study via social media advertisements on various contemporary platforms, emails to schools, emails to contacts within known networks, and emails to relevant youth organizations. Data were collected from social media advertisements, screening, and recruitment logs. Data analysis included summary and descriptive statistics, as well as chi-square tests to explore factors associated with nonparticipation. Results: From 2369 expressions of interest, 390 (16.4%) participants were enrolled. A total of 19 advertisements were placed on social media, and 385 promotional emails were sent to schools, contacts within known networks, and relevant youth organizations. Social media advertisements reached 408,077 unique accounts. Advertisements mostly reached those living in populous states in Australia (306,489/408,077, 75.11% of unique accounts) and those identifying as female (177,698/408,077, 43.55% of unique accounts). A total of 24.97% (101,907/408,077) of advertisements were delivered to accounts with uncategorized genders. The total cost per participant enrolled was Aus $3.89 (approximately US $2.58). Most participants (1980/2305, 85.90%) found out about this study through Instagram. Differences in screening characteristics between eligible participants who did and did not enroll were found to be statistically significant for gender (P = .02), with fewer males and more individuals reporting their gender as other enrolling than expected by chance alone. The recruitment method also differed (P < .001), with fewer participants enrolling through Instagram and more enrolling through other methods (eg, known networks or word of mouth) than expected by chance alone. Conclusions: This study found that virtual clinical trial recruitment was found to be low-cost, with the potential to increase trial participation. Social media was the most effective recruitment method, reaching all states and territories, including hard-to-reach populations. Future action is needed to explore recruitment methods that are more effective for males and to build trust among adolescents regarding clinical trial recruitment via social media. Trial Registration: Australia New Zealand Clinical Trials Registry ACTRN12622000949785; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=383576&isReview=true. Rebecca Raeside, Allyson R Todd, Sarah Barakat, Sean Rom, Stephanie Boulet, Sarah Maguire, Kathryn Williams, Seema Mihrshahi, Maree L Hackett, Julie Redfern, Stephanie R Partridge, The Health4Me Team.
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Henson, Connie; Rambaldini, Boe; Freedman, Ben; Carlson, Bronwyn; Parter, Carmen; Christie, Vita; Skinner, John C.; Meharg, David P.; Kirwan, Morwenna; Ward, Katrina D.; Speier, Sophia Nala ?ixsisa? Las; Gwynne, Kylie G.Introduction Digital health technologies have the potential to provide cost-effective care to remote and underserved populations. To realise this potential, research must involve people not traditionally included. No research focuses on the acceptability and feasibility of older Indigenous people using wearables for early atrial fibrillation (AF) detection. This protocol compares digital augmentation against standard practice to detect AF, evaluate heart health self-efficacy and health literacy changes and identify barriers in collaboration with Aboriginal Community Controlled Health Organisations. It will establish a framework for implementing culturally safe and acceptable wearable programmes for detecting and managing AF in Indigenous adults ?55 years and older. Methods This mixed-methods research will use the Rambaldini model of collective impact, a user-centred, co-design methodology and yarning circles, a recognised Indigenous research methodology to assess the cultural safety, acceptability, feasibility and efficacy of incorporating wearables into standard care for early AF detection. Analysis Qualitative data will be analysed to create composite descriptions of participants' experiences and perspectives related to comfort, cultural safety, convenience, confidence, family reactions and concerns. Quantitative device data will be extracted and analysed via Statistical Product and Service Solutions (SPSS). Conclusion Prioritising perspectives of older Indigenous adults on using wearables for detecting and monitoring cardiovascular disease will ensure that the findings are effective, relevant and acceptable to those impacted. Ethics and dissemination Findings will be published in open-source peer-reviewed journals, shared at professional conferences, described in lay terms and made available to the public. The AHMRC HREC Reference Number approved 1135/15. 2024 Author(s). Published by BMJ.
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Naito, Tateaki; Wakabayashi, Hidetaka; Aso, Sakiko; Konishi, Masaaki; Saitoh, Masakazu; Baracos, V. Elaine; Coats, Andrew J.S.; Anker, Stefan D.; Sherman, Lawrence; Klompenhouwer, Tatiana; Shirotani, Noriyasu; Inui, Akio; Arai, HidenoriBackground: Cancer cachexia is a severe complication of advanced malignancy, with few therapeutic options. To promote interprofessional care for cancer cachexia, healthcare providers' needs should be addressed in detail. This pre-planned subgroup analysis of the Global Educational Needs Evaluation: a systemic interprofessional study in cancer cachexia (GENESIS-CC) survey aimed to identify barriers to interprofessional care of cancer cachexia in Japan. Methods: A nationwide survey was electronically conducted for healthcare providers in oncological or general healthcare facilities from January to March 2021 in Japan. The Japanese Regional Advisory Board developed a barrier scoring system with 33 from the 58 original survey items to quantify six domains of barriers: (1) lack of confidence, (2) lack of knowledge, (3) barriers in personal practice, (4) barriers in perception, (5) barriers in team practice and (6) barriers in education. The largest possible barrier score was set at 100 points. We compared the scores by profession. Results: A total of 1227 valid responses were obtained from 302 (24.6%) physicians, 252 (20.5%) pharmacists, 236 (19.2%) nurses, 218 (17.8%) dietitians, 193 (15.7%) rehabilitation therapists and 26 (2.0%) other professionals. Overall, 460 (37.5%) were not very or at all confident about cancer cachexia care, 791 (84.1%) agreed or strongly agreed that care was influenced by reimbursement availability and 774 (81.9%) did not have cancer cachexia as a mandatory curriculum. The largest mean barrier score (standard deviation) was 63.731.3 for education, followed by 55.621.8 for team practice, 43.732.5 for knowledge, 42.817.7 for perception and 36.516.7 for personal practice. There were statistically significant interprofessional differences in all domains (P<0.05), especially for pharmacists and nurses with the highest or second highest scores in most domains. Conclusions: There is a need to improve the educational system and team practices of cancer cachexia for most Japanese healthcare providers, especially pharmacists and nurses. Our study suggests the need to reform the mandatory educational curriculum and reimbursement system on cancer cachexia to promote interprofessional care for cancer cachexia in Japan. 2023 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.
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Coats, Andrew J.S.; Butler, Javed J.; Tsutsui, Hiroyuki; Doehner, Wolfram; Filippatos, Gerasimos S.; Ferreira, Jo Pedro; Bm, Michael; Chopra, Vijay Kumar; Verma, Subodh G.; Nordaby, Mats; Iwata, Tomoko; Nitta, Daisuke; Ponikowski, Piotr P.; Zannad, Faiez; Packer, Milton P.; Anker, Stefan D.Background: Frailty is a severe, common co-morbidity associated with heart failure (HF) with preserved ejection fraction (HFpEF). The impact of frailty on HFpEF outcomes may affect treatment choices in HFpEF. The impact of frailty on HFpEF patients and any impact on the clinical benefits of sodium glucose co-transporter 2 (SGLT2) inhibition in HFpEF have been described in only a limited number of trials. Whether the SGLT2 inhibitor empagliflozin would improve or worsen frailty status when given to HFpEF patients is also not known. The aims of this study were, therefore, to evaluate, in HFpEF patients enrolled in the EMPEROR-Preserved trial (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction), the impact of frailty on clinical outcomes, and on the effects of empagliflozin, as well as the effect of empagliflozin on frailty status during treatment period. Methods: We calculated a cumulative deficit-derived frailty index (FI) using 44 variables including clinical, laboratory and quality of life parameters recorded in EMPEROR-Preserved. Patients were classified into four groups: non-frail (FI<0.21), mild frailty (0.21 to <0.30), moderate frailty (0.30 to <0.40) and severe frailty (?0.40). Clinical outcomes and health-related quality of life were evaluated according to baseline FI along with the effect of empagliflozin on chronological changes in FI (at 12, 32 and 52weeks). Results: The patient distribution was 1514 (25.3%), 2100 (35.1%), 1501 (25.1%) and 873 (14.6%) in non-frail, mild frailty, moderate frailty and severe frailty, respectively. Severe frailty patients tended to be female and have low Kansas City Cardiomyopathy Questionnaire (KCCQ) scores, more co-morbidities and more polypharmacy. Incidence rates of the primary outcome of cardiovascular death or HF hospitalization increased as frailty worsened (hazard ratio [HR] of each FI category compared with the non-frail group: 1.10 [95% confidence interval, CI, 0.891.35], 2.00 [1.632.47] and 2.61 [2.083.27] in the mild frailty, moderate frailty and severe frailty groups, respectively; P trend<0.001). Compared with placebo, empagliflozin reduced the risk for the primary outcome across the four FI categories, HR: 0.59 [95% CI 0.420.83], 0.79 [0.611.01], 0.77 [0.610.96] and 0.90 [0.691.16] in non-frail to severe frailty categories, respectively (P value for trend=0.097). Empagliflozin also improved other clinical outcomes and KCCQ score across frailty categories. Compared with placebo, empagliflozin-treated patients had a higher likelihood of being in a lower FI category at Weeks 12, 32 and 52 (P<0.05), odds ratio: 1.12 [95% CI 1.011.24] at Week 12, 1.21 [1.091.34] at Week 32 and 1.20 [1.091.33] at Week 52. Conclusions: Empagliflozin improved key efficacy outcomes with a possible diminution of effect in very frail patients. Empagliflozin also improved frailty status during follow-up. 2023 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.
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Smith, Cassandra; Sim, Marc P.; Dalla Via, Jack; Gebre, Abadi Kahsu; Zhu, Kun; Lim, Waihon; Teh, Ryan; Kiel, Douglas P.; Schousboe, John T.; Levinger, Itamar; von Haehling, Stephan; Woodman, R. J.; Coats, Andrew J.S.; Prince, Richard L.; Lewis, Joshua R.BACKGROUND: Abdominal aortic calcification (AAC), a marker of vascular disease, is associated with disease in other vascular beds including gastrointestinal arteries. We investigated whether AAC is related to rapid weight loss over 5 years and whether rapid weight loss is associated with 9.5-year all-cause mortality in community-dwelling older women. METHODS: Lateral spine images from dual-energy x-ray absorptiometry (1998/1999) were used to assess AAC (24-point AAC scoring method) in 929 older women. Over 5 years, body weight was assessed at 12-month intervals. Rapid weight loss was defined as >5% decrease in body weight within any 12-month interval. Multivariable-adjusted logistic regression was used to assess AAC and rapid weight loss and Cox regression to assess the relationship between rapid weight loss and 9.5-year all-cause mortality. RESULTS: MeanSD age of women was 75.02.6 years. During the initial 5 years, 366 (39%) women presented with rapid weight loss. Compared with women with low AAC (24-point AAC score 0-1), those with moderate (24-point AAC score 2-5: odds ratio, 1.36 [95% CI, 1.00-1.85]) and extensive (24-point AAC score 6+: odds ratio, 1.59 [95% CI, 1.10-2.31]) AAC had higher odds for presenting with rapid weight loss. Results remained similar after further adjustment for dietary factors (alcohol, protein, fat, and carbohydrates), diet quality, blood pressure, and cholesterol measures. The estimates were similar in subgroups of women who met protein intake (n=599) and physical activity (n=735) recommendations (extensive AAC: odds ratios, 1.81 [95% CI, 1.12-2.92] and 1.58 [95% CI, 1.02-2.44], respectively). Rapid weight loss was associated with all-cause mortality over the next 9.5 years (hazard ratio, 1.49 [95% CI, 1.17-1.89]; P=0.001). CONCLUSIONS: AAC extent was associated with greater risk for rapid weight loss over 5 years in older women, a risk for all-cause mortality. Since the association was unchanged after taking nutritional intakes into account, these data support the possibility that vascular disease may play a role in the maintenance of body weight. 2024 Lippincott Williams and Wilkins. All rights reserved.
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Houlahan, Callum B.; Kong, Yvonne X.; Johnston, Bede; Cielesh, Michelle E.; Chau, The Huong; Fenwick, Jemma C.L.; Coleman, Paul R.; Hao, Huilin; Haltiwanger, Robert S.; Thaysen-Andersen, Morten; Passam, Freda H.; Larance, MarkPlatelet activation induces the secretion of proteins that promote platelet aggregation and inflammation. However, detailed analysis of the released platelet proteome is hampered by platelets' tendency to preactivate during their isolation and a lack of sensitive protocols for low abundance releasate analysis. Here, we detail the most sensitive analysis to date of the platelet releasate proteome with the detection of >1300 proteins. Unbiased scanning for posttranslational modifications within releasate proteins highlighted O-glycosylation as being a major component. For the first time, we detected Ofucosylation on previously uncharacterized sites including multimerin-1 (MMRN1), a major alpha granule protein that supports platelet adhesion to collagen and is a carrier for platelet factor V. The N-terminal elastin microfibril interface (EMI) domain of MMRN1, a key site for protein-protein interaction, was O-fucosylated at a conserved threonine within a new domain context. Our data suggest that either protein O-fucosyltransferase 1, or a novel protein O-fucosyltransferase, may be responsible for this modification. Mutating this O-fucose site on the EMI domain led to a >50% reduction of MMRN1 secretion, supporting a key role of EMI O-fucosylation in MMRN1 secretion. By comparing releasates from resting and thrombin-treated platelets, 202 proteins were found to be significantly released after high-dose thrombin stimulation. Complementary quantification of the platelet lysates identified >3800 proteins, which confirmed the platelet origin of releasate proteins by anticorrelation analysis. Low-dose thrombin treatment yielded a smaller subset of significantly regulated proteins with fewer secretory pathway enzymes. The extensive platelet proteome resource provided here (larancelab.com/plateletproteome) allows identification of novel regulatory mechanisms for drug targeting to address platelet dysfunction and thrombosis. 2024 THE AUTHORS.
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Celermajer, David S.[No abstract available]
