Medicine (Western Health) - Research Publications

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    The Effects of Acute High-Intensity Interval Exercise and Hyperinsulinemic-Euglycemic Clamp on Osteoglycin Levels in Young and Middle-Aged Men.
    Bauer, C ; Tacey, A ; Garnham, A ; Smith, C ; Woessner, MN ; Lin, X ; Zarekookandeh, N ; Hare, DL ; Lewis, JR ; Parker, L ; Levinger, I (Oxford University Press (OUP), 2022-11)
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    Glucocorticoid-Induced Insulin Resistance in Men Is Associated With Suppressed Undercarboxylated Osteocalcin
    Parker, L ; Lin, X ; Garnham, A ; McConell, G ; Stepto, NK ; Hare, DL ; Byrnes, E ; Ebeling, PR ; Seeman, E ; Brennan-Speranza, TC ; Levinger, I (WILEY, 2019-01)
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    Moving From Heart Failure Guidelines to Clinical Practice: Gaps Contributing to Readmissions in Patients With Multiple Comorbidities and Older Age
    Iyngkaran, P ; Liew, D ; Neil, C ; Driscoll, A ; Marwick, TH ; Hare, DL (SAGE PUBLICATIONS LTD, 2018-12-04)
    This feature article for the thematic series on congestive heart failure (CHF) readmissions aims to outline important gaps in guidelines for patients with multiple comorbidities and the elderly. Congestive heart failure diagnosis manifests as a 3-phase journey between the hospital and community, during acute, chronic stable, and end-of-life (palliative) phases. This journey requires in variable intensities a combination of multidisciplinary care within tertiary hospital or ambulatory care from hospital outpatients or primary health services, within the general community. Management goals are uniform, ie, to achieve the lowest New York Heart Association class possible, with improvement in ejection fraction, by delivering gold standard therapies within a CHF program. Comorbidities are an important common denominator that influences outcomes. Comorbidities include diabetes mellitus, chronic obstructive airways disease, chronic renal impairment, hypertension, obesity, sleep apnea, and advancing age. Geriatric care includes the latter as well as syndromes such as frailty, falls, incontinence, and confusion. Many systems still fail to comprehensively achieve all aspects of such programs. This review explores these factors.
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    Acute exercise alters skeletal muscle mitochondrial respiration and H2O2 emission in response to hyperinsulinemic-euglycemic clamp in middle-aged obese men
    Trewin, AJ ; Levinger, I ; Parker, L ; Shaw, CS ; Serpiello, FR ; Anderson, MJ ; McConell, GK ; Hare, DL ; Stepto, NK ; Philp, A (PUBLIC LIBRARY SCIENCE, 2017-11-21)
    Obesity, sedentary lifestyle and aging are associated with mitochondrial dysfunction and impaired insulin sensitivity. Acute exercise increases insulin sensitivity in skeletal muscle; however, whether mitochondria are involved in these processes remains unclear. The aim of this study was to investigate the effects of insulin stimulation at rest and after acute exercise on skeletal muscle mitochondrial respiratory function (JO2) and hydrogen peroxide emission (JH2O2), and the associations with insulin sensitivity in obese, sedentary men. Nine men (means ± SD: 57 ± 6 years; BMI 33 ± 5 kg.m2) underwent hyperinsulinemic-euglycemic clamps in two separate trials 1-3 weeks apart: one under resting conditions, and another 1 hour after high-intensity exercise (4x4 min cycling at 95% HRpeak). Muscle biopsies were obtained at baseline, and pre/post clamp to measure JO2 with high-resolution respirometry and JH2O2 via Amplex UltraRed from permeabilized fibers. Post-exercise, both JO2 and JH2O2 during ADP stimulated state-3/OXPHOS respiration were lower compared to baseline (P<0.05), but not after subsequent insulin stimulation. JH2O2 was lower post-exercise and after subsequent insulin stimulation compared to insulin stimulation in the rest trial during succinate supported state-4/leak respiration (P<0.05). In contrast, JH2O2 increased during complex-I supported leak respiration with insulin after exercise compared with resting conditions (P<0.05). Resting insulin sensitivity and JH2O2 during complex-I leak respiration were positively correlated (r = 0.77, P<0.05). We conclude that in obese, older and sedentary men, acute exercise modifies skeletal muscle mitochondrial respiration and H2O2 emission responses to hyperinsulinemia in a respiratory state-specific manner, which may have implications for metabolic diseases involving insulin resistance.
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    Assessing the Value of BMI and Aerobic Capacity as Surrogate Markers for the Severity of Left Ventricular Diastolic Dysfunction in Patients with Type 2 Diabetes Who Are Obese
    Smith, C ; ul Haq, MA ; Jerums, G ; Hanson, E ; Hayes, A ; Allen, JD ; Sbaraglia, M ; Selig, S ; Wong, C ; Hare, DL ; Levinger, I (SAGE PUBLICATIONS LTD, 2016-05-12)
    Left ventricular diastolic dysfunction (LVDD) is one of the earliest signs for abnormal cardiac function in patients with type 2 diabetes (T2DM). It is important to explore the risk factors that will assist in identifying the severity of the LVDD in this population. We examined the influences of fitness and fatness on the level of left ventricular (LV) impairment in patients with T2DM. Twenty-five patients (age: 64.0 ± 2.5 years, body mass index [BMI] = 36.0 ± 1.5 kg/m(2), mean ± standard error of measurement) with T2DM and preserved systolic function, but impaired diastolic function, mitral valve (MV) E/e', participated in the study. LV function was assessed using a stress echocardiograph, aerobic power was assessed with a sign- and symptom-limited graded exercise test, and the fatness level was assessed using Dual-energy X-ray absorptiometry and BMI. Patients in the higher 50% of BMI had higher lateral and septal MV E/e' (∼34% and ∼25%, respectively, both P < 0.001), compared to those in the lower 50% of BMI, with no difference in LV ejection fraction (LVEF) (P > 0.05). In addition, a higher BMI correlated with a higher lateral (r = 0.62, P < 0.001) and septal (r = 0.56, P < 0.01) E/e'. There was no such relationship for VO2peak. BMI and VO2peak were not correlated with LV systolic function (ejection fraction). In individuals with T2DM and diastolic dysfunction, a higher BMI was associated with worsening diastolic function independent of their aerobic capacity. The data provide a simple and practical approach for clinicians to assist in the early identification and diagnostics of functional changes in the heart diastolic function in this population.
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    Effect of Exercise Training on Left Ventricular Remodeling in Diabetic Patients with Diastolic Dysfunction: Rationale and Design
    ul Haq, MA ; Wong, C ; Levinger, I ; Srivastava, PM ; Sbaraglia, M ; Toia, D ; Jerums, G ; Selig, S ; Hare, DL (SAGE PUBLICATIONS LTD, 2014)
    INTRODUCTION: This study will examine the effects of combined aerobic and resistance training on left ventricular remodeling in diabetic patients with diastolic dysfunction. This is the first randomized controlled trial to look for effects of combined strength training and aerobic exercise on myocardial function as well as other clinical, functional, or psychological parameters in diabetic patients with isolated diastolic dysfunction, and will provide important insights into the potential management strategies for heart failure with preserved ejection fraction. METHODS AND ANALYSIS: This is a prospective, randomized controlled investigator initiated single center trial. Diabetic patients with LV diastolic dysfunction suitable for exercise training intervention will be randomized to three months of a supervised combination of aerobic and strength training exercises, or supervised light stretching (control arm). Pre and post intervention assessment will include stress echocardiography, peak aerobic power with 12-lead ECG, dual-energy X-ray absorptiometry, muscle strength, the capacity to perform activities of daily living (ADLs), and questionnaires to assess self-perceived quality of life and symptoms of depression. The primary endpoint is to compare any change in tissue Doppler-derived LV systolic and early diastolic velocities. ETHICS AND DISSEMINATION: The current trial protocol has been approved by the Human Research Ethics Committee of Austin Health and the University of Melbourne, Melbourne. The study will be performed in accordance with the Declaration of Helsinki. The investigator, regardless of the outcome, will publish the results of the study. AUSTRALIAN NEW ZEALAND CLINICAL TRIALS REGISTRY: ACTRN12610000943044.
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    What is the impact of systems of care for heart failure on patients diagnosed with heart failure: a systematic review
    Driscoll, A ; Meagher, S ; Kennedy, R ; Hay, M ; Banerji, J ; Campbell, D ; Cox, N ; Gascard, D ; Hare, D ; Page, K ; Nadurata, V ; Sanders, R ; Patsamanis, H (BMC, 2016-10-11)
    BACKGROUND: Hospital admissions for heart failure are predicted to rise substantially over the next decade placing increasing pressure on the health care system. There is an urgent need to redesign systems of care for heart failure to improve evidence-based practice and create seamless transitions through the continuum of care. The aim of the review was to examine systems of care for heart failure that reduce hospital readmissions and/or mortality. METHOD: Electronic databases searched were: Ovid MEDLINE, EMBASE, CINAHL, grey literature, reviewed bibliographies and Cochrane Central Register of Controlled Trials for randomised controlled trials, non-randomised trials and cohort studies from 1st January 2008 to 4th August 2015. Inclusion criteria for studies were: English language, randomised controlled trials, non-randomised trials and cohort studies of systems of care for patients diagnosed with heart failure and aimed at reducing hospital readmissions and/or mortality. Three reviewer authors independently assessed articles for eligibility based on title and abstract and then full-text. Quality of evidence was assessed using Newcastle-Ottawa Scale for non-randomised trials and GRADE rating tool for randomised controlled trials. RESULTS: We included 29 articles reporting on systems of care in the workforce, primary care, in-hospital, transitional care, outpatients and telemonitoring. Several studies found that access to a specialist heart failure team/service reduced hospital readmissions and mortality. In primary care, a collaborative model of care where the primary physician shared the care with a cardiologist, improved patient outcomes compared to a primary physician only. During hospitalisation, quality improvement programs improved the quality of inpatient care resulting in reduced hospital readmissions and mortality. In the transitional care phase, heart failure programs, nurse-led clinics, and early outpatient follow-up reduced hospital readmissions. There was a lack of evidence as to the efficacy of telemonitoring with many studies finding conflicting evidence. CONCLUSION: Redesigning systems of care aimed at improving the translation of evidence into clinical practice and transitional care can potentially improve patient outcomes in a cohort of patients known for high readmission rates and mortality.
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    Acute High-Intensity Interval Exercise-Induced Redox Signaling Is Associated with Enhanced Insulin Sensitivity in Obese Middle-Aged Men
    Parker, L ; Stepto, NK ; Shaw, CS ; Serpiello, PR ; Anderson, M ; Hare, DL ; Levinger, I (FRONTIERS MEDIA SA, 2016-09-16)
    Background: Obesity and aging are associated with increased oxidative stress, activation of stress and mitogen activated protein kinases (SAPK), and the development of insulin resistance and metabolic disease. In contrast, acute exercise also increases oxidative stress and SAPK signaling, yet is reported to enhance insulin sensitivity and reduce the risk of metabolic disease. This study explored this paradox by investigating the effect of a single session of high-intensity interval-exercise (HIIE) on redox status, muscle SAPK and insulin protein signaling in eleven middle-aged obese men. Methods: Participants completed a 2 h hyperinsulinaemic-euglycaemic clamp at rest, and 60 min after HIIE (4 × 4 mins at 95% HRpeak; 2 min recovery periods), separated by 1-3 weeks. Results: Irrespective of exercise-induced changes to redox status, insulin stimulation both at rest and after HIIE similarly increased plasma superoxide dismutase activity, plasma catalase activity, and skeletal muscle 4-HNE; and significantly decreased plasma TBARS and hydrogen peroxide. The SAPK signaling pathways of p38 MAPK, NF-κB p65, and JNK, and the distal insulin signaling protein AS160Ser588, were activated with insulin stimulation at rest and to a greater extent with insulin stimulation after a prior bout of HIIE. Higher insulin sensitivity after HIIE was associated with higher insulin-stimulated SOD activity, JNK, p38 MAPK and NF-κB phosphorylation (r = 0.63, r = 0.71, r = 0.72, r = 0.71; p < 0.05, respectively). Conclusion:These findings support a role for redox homeostasis and SAPK signaling in insulin-stimulated glucose uptake which may contribute to the enhancement of insulin sensitivity in obese men 3 h after HIIE.
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    Single dose prednisolone alters endocrine and haematologic responses and exercise performance in men.
    Levinger, I ; Tacey, A ; Parker, L ; Yeap, BB ; Joseph, J ; Lim, EM ; Garnham, A ; Hare, DL ; Brennan-Speranza, T (BioScientifica, 2019-02-01)
    The aim of this study was to investigate the effect of a single dose of prednisolone on (A) high-intensity interval cycling performance and (B) post-exercise metabolic, hormonal and haematological responses. Nine young men participated in this double-blind, randomised, cross-over study. The participants completed exercise sessions (4 × 4 min cycling bouts at 90–95% of peak heart rate), 12 h after ingesting prednisolone (20 mg) or placebo. Work load was adjusted to maintain the same relative heart rate between the sessions. Exercise performance was measured as total work performed. Blood samples were taken at rest, immediately post exercise and up to 3 h post exercise. Prednisolone ingestion decreased total work performed by 5% (P < 0.05). Baseline blood glucose was elevated following prednisolone compared to placebo (P < 0.001). Three hours post exercise, blood glucose in the prednisolone trial was reduced to a level equivalent to the baseline concentration in the placebo trial (P > 0.05). Prednisolone suppressed the increase in blood lactate immediately post exercise (P < 0.05). Total white blood cell count was elevated at all time-points with prednisolone (P < 0.01). Androgens and sex hormone-binding globulin were elevated immediately after exercise, irrespective of prednisolone or placebo. In contrast, prednisolone significantly reduced the ratio of testosterone/luteinizing hormone (P < 0.01). Acute prednisolone treatment impairs high-intensity interval cycling performance and alters metabolic and haematological parameters in healthy young men. Exercise may be an effective tool to minimise the effect of prednisolone on blood glucose levels.
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    A Review of Randomized Controlled Trials Utilizing Telemedicine for Improving Heart Failure Readmission: Can a Realist Approach Bridge the Translational Divide?
    Garcia, MG ; Fatehi, F ; Bashi, N ; Varnfield, M ; Iyngkaran, P ; Driscoll, A ; Neil, C ; Hare, DL ; Oldenburg, B (SAGE PUBLICATIONS LTD, 2019-07-10)
    BACKGROUND: Telemedicine and digital health technologies hold great promise for improving clinical care of heart failure. However, inconsistent and contradictory findings from randomized controlled trials have so far discouraged widespread adoption of digital health in routine clinical practice. We undertook this review study to summarize the study outcomes of the use of exploring the evidence for telemedicine in the clinical care of patients with heart failure and readmissions. METHODS: We inspected the references of guidelines and searched PubMed for randomized controlled trials published over the past 10 years on the use of telemedicine for reducing readmission in heart failure. We utilized a modified realist review approach to identify the underlying contextual mechanisms for the intervention(s) in each randomized controlled trial, evaluating outcomes of the intervention and understanding how and under what conditions they worked. To provide uniformity, all extracted data were synthesized using adapted domains from the taxonomy for disease management created by the Disease Management Taxonomy Writing Group. RESULTS: A total of 12 papers were eligible, 6 of them supporting and 6 others undermining the use of telemedicine for improving heart failure readmission. In general terms, those studies not supporting the use of telemedicine were multicentre, publicly funded, with large amount of participants, and long duration. The patients had also better rates of treatment with angiotensin-converting enzyme inhibitors/angiotensin II receptor blocker and beta-blockers, and telemonitoring and automatic transmission of vital signs were less utilized, in comparison with the studies in which telemedicine use was supported. The analysis of the environment, intensity, content of interventions, method of communication, quality of the underlying model of care and the ability, capability, and interest from health workers can help us to envisage probabilities of success of telemedicine use. CONCLUSIONS: A realist lens may aid to understand whom and in which circumstances the use of telemedicine can add any substantial value to traditional models of care. Wider outcome criteria beyond major adverse cardiovascular events, for example, cost efficacy, should also be considered as appropriate for effecting guidelines on care delivery when robust prognostic therapeutics already exist.