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Mixed plaque on coronary CT angiography predicts atherosclerotic events in asymptomatic intermediate-risk individuals.
Warren, J, Ellims, A, Bloom, J, Sutherland, N, Lew, P, Kavnoudias, H, Paleri, S, Stub, D, Taylor, A
Open heart. 2024;(1)
Abstract
OBJECTIVE Coronary CT angiography (CCTA) permits both qualitative and quantitative analysis of atherosclerotic plaque and may be a suitable risk modifier in assessing patients at intermediate risk of atherosclerotic cardiovascular disease. We sought to determine the association of plaque components with long-term major adverse cardiovascular events (MACEs) in asymptomatic intermediate-risk patients, compared with conventional coronary artery calcium (CAC) score. METHODS 100 intermediate-risk patients underwent double-blinded CCTA. Follow-up was conducted at 10 years and data were cross-referenced with the National Death Index. The primary outcome was MACE, which was a composite of death, acute coronary syndrome (ACS), revascularisation and stroke. RESULTS The median time from CCTA to follow-up was 9.5 years. 83 patients completed follow-up interview and mortality data were available on all 100 patients. MACE occurred in 17 (20.5%) patients, which included 2 (2%) deaths, 8 (10%) ACS, 3 (4%) strokes and 5 (6%) revascularisation procedures. 47 (57%) patients had mixed plaque, which was predictive of MACE (OR 4.68 (95% CI 1.19 to 18.5) p=0.028). The burden of non-calcified and mixed plaque, defined by non-calcified plaque segment stenosis score, was also a predictor of long-term MACE (OR 1.59 (95% CI 1.18 to 2.13) p=0.002). Neither calcified plaque (OR 3.92 (95% CI 0.80 to 19.3)) nor CAC score (OR 1.01 (95% CI 0.999 to 1.02)) was associated with long-term MACE. CONCLUSION The presence and burden of mixed plaque on CCTA is associated with an increased risk of long-term MACE among asymptomatic intermediate-risk patients and is a superior predictor to CAC score.
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Progressive exercise training improves cardiovascular psychophysiological outcomes in young adult women with a history of adverse childhood experiences.
Rogers, EM, Banks, NF, Tomko, PM, Sciarrillo, CM, Emerson, SR, Thomas, EBK, Taylor, A, Teague, TK, Jenkins, NDM
Journal of applied physiology (Bethesda, Md. : 1985). 2023;(3):742-752
Abstract
Adverse childhood experiences (ACEs) are early-life psychosocial stressors that are associated with poorer mental health and increased cardiovascular disease (CVD) risk in a dose-dependent manner. We examined the feasibility of an 8-wk combined aerobic and resistance exercise training program to improve systolic (SBP) and diastolic blood pressure (DBP), serum endothelin-1 (ET-1), resilience, hope agency, and hope pathways in young women with ACEs. Forty-two healthy women (21 ± 3 yr) with ≥4 (ACE+; n = 28) or 0 ACEs (ACE-; n = 14) participated in this study. Women with ACEs were randomly assigned to an exercise (ACE+EXT; n = 14) or nonexercise control (ACE+CON; n = 14) group, whereas all ACE- participants were assigned to a nonexercise control (n = 14) group. Hope agency and DBP did not change in any group (P ≥ 0.43), but hope pathways improved only in ACE+EXT (means ± SE change; +1.6 ± 0.74 au, P = 0.032, Hedges' g = 0.53). ET-1 decreased in ACE+EXT only (-0.31 ± 0.15 pg/mL, P = 0.043, g = 0.46). Although the interactions for resilience and SBP did not reach significance (P = 0.05-0.06), forced post hoc analyses indicated that resilience improved (+4.9 ± 1.9 au, P = 0.012, g = 0.64) and SBP tended to improve (-4.0 ± 2.0 mmHg, P = 0.053, g = 0.51) in ACE+EXT only. There were significant associations between changes in hope pathways and SBP (ρ = -0.43, P = 0.023) and ET-1 (ρ = -0.53, P = 0.005), and between changes in SBP and ET-1 (ρ = 0.49; P = 0.012) in the ACE+ group. In summary, structured exercise training reduces serum ET-1 levels, improves positive psychological coping, and may improve SBP in young women with ACEs. The relationships among the changes in hope pathways, SBP, and ET-1 suggest a cardiovascular psychophysiological relationship in young women with ACEs.NEW & NOTEWORTHY This randomized controlled pilot trial shows, for the first time, that 8 wk of structured, progressive exercise training lowers serum endothelin-1 (ET-1) and improves positive psychological coping in young women with significant early-life psychosocial stress. Furthermore, the observed associations among changes in psychological attributes, ET-1, and systolic blood pressure signify a potential interplay between positive psychology and cardiovascular disease risk among women with adverse childhood experiences.
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Associations between meeting 24-hour movement guidelines and quality of life among children and adolescents with autism spectrum disorder.
Kong, C, Chen, A, Ludyga, S, Herold, F, Healy, S, Zhao, M, Taylor, A, Müller, NG, Kramer, AF, Chen, S, et al
Journal of sport and health science. 2023;(1):73-86
Abstract
BACKGROUND The Canadian 24-hour movement behavior (24-HMB) guidelines suggest that a limited amount of screen time use, an adequate level of physical activity (PA), and sufficient sleep duration are beneficial for ensuring and optimizing the health and quality of life (QoL) of children and adolescents. However, this topic has yet to be examined for children and adolescents with autism spectrum disorder (ASD) specifically. The aim of this cross-sectional observational study was to examine the associations between meeting 24-HMB guidelines and several QoL-related indicators among a national sample of American children and adolescents with ASD. METHODS Data were taken from the 2020 U.S. National Survey of Children's Health dataset. Participants (n = 956) aged 6-17 years and currently diagnosed with ASD were included. The exposure of interest was adherence to the 24-HMB guidelines. Outcomes were QoL indicators, including learning interest/curiosity, repeating grades, adaptive ability, victimization by bullying, and behavioral problems. Categorical variables were described with unweighted sample counts and weighted percentages. Age, sex, race, preterm birth status, medication, behavioral treatment, household poverty level, and the educational level of the primary caregivers were included as covariates. Odds ratio (OR) and 95% confidence interval (95%CI) were used to present the strength of association between adherence to 24-HMB guidelines and QoL-related indicators. RESULTS Overall, 452 participants (45.34%) met 1 of the 3 recommendations, 216 (22.65%) met 2 recommendations, whereas only 39 participants (5.04%) met all 3 recommendations. Compared with meeting none of the recommendations, meeting both sleep duration and PA recommendations (OR = 3.92, 95%CI: 1.63-9.48, p < 0.001) or all 3 recommendations (OR = 2.11, 95%CI: 1.03-4.35, p = 0.04) was associated with higher odds of showing learning interest/curiosity. Meeting both screen time and PA recommendations (OR = 0.15, 95%CI: 0.04-0.61, p < 0.05) or both sleep duration and PA recommendations (OR = 0.24, 95%CI: 0.07-0.87, p < 0.05) was associated with lower odds of repeating any grades. With respect to adaptive ability, participants who met only the PA recommendation of the 24-HMB were less likely to have difficulties dressing or bathing (OR = 0.11, 95%CI: 0.02-0.66, p < 0.05) than those who did not. For participants who met all 3 recommendations (OR = 0.38, 95%CI: 0.15-0.99, p = 0.05), the odds of being victimized by bullying was lower. Participants who adhered to both sleep duration and PA recommendations were less likely to present with severe behavioral problems (OR = 0.17, 95%CI: 0.04-0.71, p < 0.05) than those who did not meet those guidelines. CONCLUSION Significant associations were found between adhering to 24-HMB guidelines and selected QoL indicators. These findings highlight the importance of maintaining a healthy lifestyle as a key factor in promoting and preserving the QoL of children with ASD.
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Proteostasis in aging-associated ocular disease.
Weinberg, J, Gaur, M, Swaroop, A, Taylor, A
Molecular aspects of medicine. 2022;:101157
Abstract
Vision impairment has devastating consequences for the quality of human life. The cells and tissues associated with the visual process must function throughout one's life span and maintain homeostasis despite exposure to a variety of insults. Maintenance of the proteome is termed proteostasis, and is vital for normal cellular functions, especially at an advanced age. Here we describe basic aspects of proteostasis, from protein synthesis and folding to degradation, and discuss the current status of the field with a particular focus on major age-related eye diseases: age-related macular degeneration, cataract, and glaucoma. Our intent is to allow vision scientists to determine where and how to harness the proteostatic machinery for extending functional homeostasis in the aging retina, lens, and trabecular meshwork. Several common themes have emerged despite these tissues having vastly different metabolisms. Continued exposure to insults, including chronic stress with advancing age, increases proteostatic burden and reduces the fidelity of the degradation machineries including the ubiquitin-proteasome and the autophagy-lysosome systems that recognize and remove damaged proteins. This "double jeopardy" results in an exponential accumulation of cytotoxic proteins with advancing age. We conclude with a discussion of the challenges in maintaining an appropriate balance of protein synthesis and degradation pathways, and suggest that harnessing proteostatic capacities should provide new opportunities to design interventions for attenuating age-related eye diseases before they limit sight.
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The EASL-Lancet Liver Commission: protecting the next generation of Europeans against liver disease complications and premature mortality.
Karlsen, TH, Sheron, N, Zelber-Sagi, S, Carrieri, P, Dusheiko, G, Bugianesi, E, Pryke, R, Hutchinson, SJ, Sangro, B, Martin, NK, et al
Lancet (London, England). 2022;(10319):61-116
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Liraglutide reduces attenuation coefficient as a measure of hepatic steatosis during 16 weeks' treatment in nondiabetic obese patients: A pilot trial.
Wang, XJ, Gong, P, Zhou, C, Huang, C, Lok, UW, Tang, S, Taylor, A, Eckert, D, Chen, S, Camilleri, M
JGH open : an open access journal of gastroenterology and hepatology. 2021;(2):193-198
Abstract
BACKGROUND AND AIM Liraglutide, a long-acting GLP-1 analog, is approved for the treatment of obesity with improvements in fasting blood glucose, hemoglobin A1c, and cardiovascular health. Our aim was to measure the impact of liraglutide dose for obesity on hepatic steatosis measured by ultrasound. METHODS A single-center, randomized, double-blind, placebo-controlled pilot trial was undertaken in nondiabetic obese, otherwise healthy patients aged 18-65 years. Participants were randomly assigned to receive subcutaneous liraglutide (3.0 mg) or placebo over 16 weeks with dose escalation following US Food and Drug Administration guidelines. Both groups received standardized nutritional and behavioral counseling during the 16 weeks. Hepatic fat content was measured by ultrasound at baseline, 8 weeks, and 16 weeks as an attenuation coefficient (ACE). Effects of treatment were assessed using t-test for the entire groups and for patient subgroup with baseline ACE >0.66 (indicating significant steatosis). RESULTS Among 30 patients (93% female) enrolled, 16 were randomized to placebo and 14 to liraglutide. Baseline body mass indices (BMIs) and average age were similar in the two groups. After 16 weeks, the liraglutide group had a significant improvement in steatosis ACE scores (-0.068 ± 0.02 vs -0.0077 ± 0.02 placebo, P = 0.05). Change in steatosis was positively correlated with change in BMI (R2 = 0.402, P = 0.0007). Within the liraglutide group, patients with baseline ACE >0.66 had improvement in ACE (-0.134 ± 0.03) compared to those without significant steatosis (-0.041 ± 0.02, P = 0.05). CONCLUSIONS In this pilot trial, liraglutide, 3.0 mg over 16 weeks, reduced hepatic steatosis; a reduction in hepatic steatosis is correlated with BMI reduction, and effects are particularly evident in those with a significant degree of steatosis by ultrasound imaging.
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Feasibility and Efficacy of the "FUNPALs Playgroup" Intervention to Improve Toddler Dietary and Activity Behaviors: A Pilot Randomized Controlled Trial.
Cepni, AB, Taylor, A, Crumbley, C, Thompson, D, Moran, NE, Olvera, N, O'Connor, DP, Arlinghaus, KR, Johnston, CA, Ledoux, TA
International journal of environmental research and public health. 2021;(15)
Abstract
This study evaluated the feasibility and effects of the Families Understanding Nutrition and Physically Active Lifestyles (FUNPALs) Playgroup on toddler (12-36-month-old) diet and activity behaviors. Parent-toddler dyads were recruited from disadvantaged communities and randomly assigned to receive 10-weekly sessions of the FUNPALs Playgroup (n = 24) or dose-matched health education control group (n = 26). FUNPALs Playgroups involved physical and snack activities, delivery of health information, and positive parenting coaching. The control group involved group health education for parents only. Process outcomes (e.g., retention rate, fidelity) and focus groups determined feasibility and perceived effects. To evaluate preliminary effects, validated measures of toddler diet (food frequency questionnaire and a carotenoid biomarker), physical activity (PA; accelerometers), general and feeding parenting (self-report surveys), and home environment (phone interview) were collected pre and post. The sample comprised parents (84% female) who self-identified as Hispanic/Latino (38%) and/or African American (32%). Retention was high (78%). Parents from both groups enjoyed the program and perceived improvements in their children's health behaviors. Objective measures demonstrated improvement with large effects (η2 = 0.29) in toddler diet (p < 0.001) but not PA (p = 0.099). In conclusion, the FUNPALs Playgroup is feasible and may improve toddler eating behaviors.
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Plasma Mucin-1 (CA15-3) Levels in Autosomal Dominant Tubulointerstitial Kidney Disease due to MUC1 Mutations.
Vylet'al, P, Kidd, K, Ainsworth, HC, Springer, D, Vrbacká, A, Přistoupilová, A, Hughey, RP, Alper, SL, Lennon, N, Harrison, S, et al
American journal of nephrology. 2021;(5):378-387
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Abstract
INTRODUCTION Patients with ADTKD-MUC1 have one allele producing normal mucin-1 (MUC1) and one allele producing mutant MUC1, which remains intracellular. We hypothesized that ADTKD-MUC1 patients, who have only 1 secretory-competent wild-type MUC1 allele, should exhibit decreased plasma mucin-1 (MUC1) levels. To test this hypothesis, we repurposed the serum CA15-3 assay used to measure MUC1 in breast cancer to measure plasma MUC1 levels in ADTKD-MUC1. METHODS This cross-sectional study analyzed CA15-3 levels in a reference population of 6,850 individuals, in 85 individuals with ADTKD-MUC1, and in a control population including 135 individuals with ADTKD-UMOD and 114 healthy individuals. RESULTS Plasma CA15-3 levels (mean ± standard deviation) were 8.6 ± 4.3 U/mL in individuals with ADTKD-MUC1 and 14.6 ± 5.6 U/mL in controls (p < 0.001). While there was a significant difference in mean CA15-3 levels, there was substantial overlap between the 2 groups. Plasma CA15-3 levels were <5 U/mL in 22% of ADTKD-MUC1 patients, in 0/249 controls, and in 1% of the reference population. Plasma CA15-3 levels were >20 U/mL in 1/85 ADTKD-MUC1 patients, in 18% of control individuals, and in 25% of the reference population. Segregation of plasma CA15-3 levels by the rs4072037 genotype did not significantly improve differentiation between affected and unaffected individuals. CA15-3 levels were minimally affected by gender and estimated glomerular filtration rate. DISCUSSION/CONCLUSIONS Plasma CA15-3 levels in ADTKD-MUC1 patients are approximately 40% lower than levels in healthy individuals, though there is significant overlap between groups. Further investigations need to be performed to see if plasma CA15-3 levels would be useful in diagnosis, prognosis, or assessing response to new therapies in this disorder.
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A proposed tailored investigational algorithm for women treated for gynaecological cancer with long-term gastrointestinal consequences.
Muls, A, Taylor, A, Lalondrelle, S, Kabir, M, Norton, C, Hart, A, Andreyev, HJ
Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer. 2020;(10):4881-4889
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Abstract
BACKGROUND AND AIM Long-term changes in gastrointestinal function impacting quality of life after treatment for cancer are common. Peer reviewed guidance to investigate and manage GI dysfunction following cancer treatment has been published. This study reviewed gastrointestinal symptoms of women previously treated for gynaecological cancer and considered whether suggested algorithms could be amended to optimise management for this cohort. METHODS Demographic and clinical data recorded for patients attending a specialist consequences of cancer treatment gastroenterology service prospectively are reported using median and range. The Wilcoxon signed rank test analysed changes in symptoms between initial assessment to discharge from the service. RESULTS Between April 2013 and March 2016, 220 women, with a median age of 57 years (range 24-83 years), treated for gynaecological cancer (cervical (50%)), endometrial (28%), ovarian (15%), vaginal or vulval (7%) attended. Twelve gastrointestinal symptoms were statistically significantly reduced by time of discharge from the specialist gastroenterology clinic including bowel frequency ≥ 4/day (88%), type 6 or 7 stool consistency (36%), urgency (31%) and incontinence (21%). General quality of life improved from a median score of 4 at first assessment to a median of 6 at discharge (p < 0.001). A median of four (range, 1-9) diagnoses were made. CONCLUSION Women with gastrointestinal symptoms after cancer treatment benefit from a systematic management approach. After excluding disease recurrence, a proposed investigational algorithm and the oncology team includes FBC, U&Es, LFTs, thyroid function test, vitamin B12, vitamin D, a hydrogen methane breath test and a SeHCAT scan. If rectal bleeding is present, iron studies, flexible sigmoidoscopy or colonoscopy should be performed. Patients with normal investigations or symptoms not responding to treatment require gastroenterology input.
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Prehospital opioid dose and myocardial injury in patients with ST elevation myocardial infarction.
Fernando, H, Nehme, Z, Peter, K, Bernard, S, Stephenson, M, Bray, J, Cameron, P, Ellims, A, Taylor, A, Kaye, DM, et al
Open heart. 2020;(2)
Abstract
OBJECTIVE To characterise the relationship between opioid dose and myocardial infarct size in patients with ST elevation myocardial infarction (STEMI). METHODS Patients given opioid treatment by emergency medical services with confirmed STEMI were included in this secondary, retrospective cohort analysis of the Air versus Oxygen in Myocardial Infarction (AVOID) study. Patients with cardiogenic shock were excluded. The primary endpoint was comparison of cardiac biomarkers as a measure of infarct size based on opioid dose (low ≤8.75 mg, intermediate 8.76-15 mg and high >15 mg of intravenous morphine equivalent dose). RESULTS 422 patients were included in the analysis. There was a significantly higher proportion of patients with Thrombolysis in Myocardial Infarction (TIMI) 0 or 1 flow pre-percutaneous coronary intervention (PCI) (94% vs 81%, p=0.005) and greater use of thrombus aspiration catheters (59% vs 30%, p<0.001) in the high compared with low-dose opioid group. After adjustment for potential confounders, every 1 mg of intravenous morphine equivalent dose was associated with a 1.4% (95% CI 0.2%, 2.7%, p=0.028) increase in peak creatine kinase; however, this was no longer significant after adjustment for TIMI flow pre-PCI. CONCLUSIONS Our study suggests no benefit of higher opioid dose and a dose-dependent signal between opioid dose and increased myocardial infarct size. Prospective randomised controlled trials are required to establish causality given that this may also be explained by patients with a greater ischaemic burden requiring higher opioid doses due to more severe pain. Future research also needs to focus on strategies to mitigate the opioid-P2Y12 inhibitor interaction and non-opioid analgesia to treat ischaemic chest pain.