Exercise As Adjunctive Therapy In Chronic Kidney Disease

Background. Exercise is a natural medicine that has been prescribed for the prevention and management of chronic diseases, to enhance quality of life, improve health status and promote longevity. Current efforts to implement exercise as routine practice in the conventional renal replacement therapy population have been hampered by a lack of randomised controlled data. The aim of this thesis was to investigate the effect of exercise as an adjunctive therapy to enhance outcomes pertaining to renal transplantation, vascular access, haemodialysis adequacy and muscle wasting in Stages four and five Chronic Kidney Disease patients. It was hypothesised that randomised controlled trials employing gold standard outcome measures would reveal significant beneficial effects of exercise that are strongly associated with quality of life, hospitalisation and survival in this patient population. Reports. The first report presents a systematic literature review of exercise in the kidney transplant population. The largest positive effects were noted on intermediate outcomes such as aerobic fitness and muscle strength. Presumably these adaptations contributed to the trends observed for improvement in quality of life. Whether exercise impacts on outcomes associated with longevity of life requires further study. The rest of the thesis focused on patients receiving the more popular form of renal replacement therapy, haemodialysis. The first empirical study of the thesis appertaining to vascular access investigated the feasibility of implementing a post-operative forearm exercise intervention for arteriovenous fistula maturation. Exercise had no effect on primary outcomes measures of arterial diameter (95% CI, -0.24 [-1.12; 0.51] mm) and venous diameter (95% CI, 0.16 [-1.84; 1.24] mm). It was concluded that future randomized controlled trials should investigate a similar protocol implemented before arteriovenous fistula creation to enhance surgery success and maturation. The second randomised controlled trial explored the effect of intradialytic exercise in comparison to the traditional prescription of increased dialysis time to enhance dialysis adequacy and solute removal. Increased haemodialysis time, but not exercise, increased equilibrated Kt/Vurea compared to control trials (Extra time vs. control: 95% CI, 0.15 [0.05; 0.26]; exercise vs. control: 95% CI, 0.03 [-0.05; 0.12]). Exercise, but not increased time, increased phosphate reduction ratio (exercise vs. control: 95% CI, 8.6 [0.5; 16.7] %; extra time vs. control: 95% CI, 5.0 [-1.0; 11.1] %). Thus intradialytic exercise cannot replace the traditional prescription of increased haemodialysis time, but may be a useful adjunctive therapy for serum phosphate control. The third study implemented a randomised controlled trial of intradialytic progressive resistance training for muscle wasting. The primary outcome measure of thigh muscle volume, as measured by magnetic resonance imaging, significantly increased following 12 weeks of training compared to a sham exercise control (95% CI, 193 [63; 324] cm3 ). Intradialytic resistance exercise elicited an anabolic and strength response in haemodialysis patients. However, a surprising lack of a change in functional capacity despite increased muscle mass warrants further investigation. Conclusion. The findings suggested that exercise had a beneficial effect on factors relating to outcomes in Stages 4 and 5 Chronic Kidney Disease patients. However, to ensure effectiveness of interventions and to maximize programme efficiency, careful consideration of basic exercise and physiological principles is required. Nevertheless, the observed benefits of exercising outweighed its risks thus supporting the initiative for exercise prescription as an adjunctive therapy for the management of this disease state

GPs’ Insights into Prostate Cancer Diagnosis and Care in Regional Victoria, Australia

The aim of this research was to ascertain General Practitioners’ (GPs) perceptions and experiences of prostate cancer (PCa) diagnosis, treatment, and care in metropolitan Melbourne and in a regional area of Victoria, Australia, associated with poorer PCa outcomes. Semi-structured qualitative interviews were conducted with GPs (N= 10) practising in the selected region and in metropolitan Melbourne, Australia. GPs thought that most men wanted PSA testing and were willing to undergo rectal examination. Some GPs were troubled by inconsistent screening guidelines from different professional bodies. They identified a need for resources to support them in educating patients about PCa. GPs thought it might be more difficult for young female GPs to care for patients in relation to PCa screening; differences were evident between younger female GPs and older male GPs in the approach they adopted in interviews. Regional GPs often referred patients to services in larger centres because no local specialists were available. GPs also found it hard to explain differences in PCa outcomes in regional and metropolitan areas. Potential age and gender differences in GPs in relation to prostate care warrant further examination. Although GPs were able to offer only limited insights into the poorer outcomes in regional areas, they identified ways in which they could be assisted to provide best-practice care. Multidisciplinary care, resources for patients, and consistent guidelines for the detection and treatment of PCa should contribute to better care in all areas

Validity of the Actigraph GT9X Accelerometer Step-Count Function in Adults with Heart Failure with Preserved Ejection Fraction

Low physical activity is associated with heart failure with preserved ejection fraction (HFpEF). Step-counts, a measure of physical activity, can be measured via accelerometry. To date, few studies have examined validity of accelerometer-derived step-counts in the adults with HFpEF. PURPOSE To assess criterion validity of the Actigraph GT9X accelerometer step-count function in adults with HFpEF via ankle, waist, and wrist placement, compared with manually counted, directly observed steps. METHODS Six adults with HFpEF (age: 57.2 ± 9.4 y; African American: 50%; females: 100%) completed a cardiopulmonary exercise test (CPET) on a treadmill while wearing synchronized GT9X accelerometers on the ankle, waist, and wrist. Steps during CPET were measured by using the step-count function on the GT9X at 60 Hz sampling and data were downloaded into 1-second and 10-second epochs. Hand-tallied, directly observed steps (OS) was the criterion measure. Criterion validity was assessed via paired t tests to determine whether mean total steps (TS) from the three devices were significantly different from the mean TS from OS, and Pearson correlations were used to determine associations between device-measured TS and the total OS. Simple linear regression models were used to assess the effect of walking speed on absolute percentage error of the devices compared to OS. Agreement of the devices throughout the duration of the CPET was examined using Pearson correlations. Alpha was set at 0.05 for all statistical analyses. RESULTS Mean TS from waist-worn (t = -5.29, p = .001) and wrist-worn (t = -12.50, p \u3c .001) devices were significantly lower than mean TS from OS. Only TS from the ankle GT9X was significantly associated with TS from OS (r = 0.974, p = .001). GT9X-estimate steps from the ankle (r = 0.869, p \u3c .001), waist (r = 0.550, p \u3c.001), and wrist (r = 0.429, p \u3c.001) were all significantly associated with OS-measured steps. Absolute percentage error was significantly and negatively associated with treadmill speed for devices on the ankle (b = - 10.70, p \u3c .001), waist (b = -32.49, p \u3c .001) and wrist (b = -10.08, p \u3c .001). CONCLUSION Our results suggest that accelerometer-derived TS may be a more accurate measure of TS when the device is worn on the ankle rather than waist or wrist, and that measurement error is higher at lower walking speed.https://scholarscompass.vcu.edu/gradposters/1153/thumbnail.jp

Abundance of Indo-Pacific bottlenose dolphins (Tursiops aduncus) along the south coast of South Africa

Coastally distributed dolphin species are vulnerable to a variety of anthropogenic pressures, yet a lack of abundance data often prevents data-driven conservation management strategies from being implemented. We investigated the abundance of Indo-Pacific bottlenose dolphins (Tursiops aduncus) along the south coast of South Africa, from the Goukamma Marine Protected Area (MPA) to the Tsitsikamma MPA, between 2014 and 2016. During this period, 662.3h of boat-based photo-identification survey effort was carried out during 189 surveys. The sighting histories of 817 identified individuals were used to estimate abundance using capture-recapture modelling. Using open population (POPAN) models, we estimated that 2,155 individuals (95% CI: 1,873–2,479) occurred in the study area, although many individuals appeared to be transients. We recorded smaller group sizes and an apparent decline in abundance in a subset of the study area (Plettenberg Bay) compared to estimates obtained in 2002–2003 at this location. We recorded declines of more than 70% in both abundance and group size for a subset of the study area (Plettenberg Bay), in relation to estimates obtained in 2002–2003 at this location. We discuss plausible hypotheses for causes of the declines, including anthropogenic pressure, ecosystem change, and methodological inconsistencies. Our study highlights the importance of assessing trends in abundance at other locations to inform data-driven conservation management strategies of T. aduncus in South Africa.Supporting information: Fig S1. Survey tracks along the study area. Table S1. Search effort per section of the study area, year and season. Table S2. Model selection and abundance estimates for T. aduncus obtained from POPAN open population Jolly-Seber models.http://www.plosone.orgpm2020Mammal Research InstituteZoology and Entomolog

Indian Ocean humpback dolphin (Sousa plumbea) movement patterns along the South African coast

1. The Indian Ocean humpback dolphin was recently uplisted to ‘Endangered’ in the recent South African National Red List assessment. Abundance estimates are available from a number of localized study sites, but knowledge of movement patterns and population linkage between these sites is poor. A national research collaboration, the SouSA project, was established in 2016 to address this key knowledge gap. Twenty identification catalogues collected between 2000 and 2016 in 13 different locations were collated and compared. 2. Photographs of 526 humpback dolphins (all catalogues and photos) were reduced to 337 individuals from 12 locations after data selection. Of these, 90 matches were found for 61 individuals over multiple sites, resulting in 247 uniquely, well‐marked humpback dolphins identified in South Africa. 3. Movements were observed along most of the coastline studied. Ranging distances had a median value of 120 km and varied from 30 km up to 500 km. Long‐term site fidelity was also evident in the data. Dolphins ranging along the south coast of South Africa seem to form one single population at the western end of the species' global range. 4. Current available photo‐identification data suggested national abundance may be well below previous estimates of 1000 individuals, with numbers possibly closer to 500. Bearing in mind the poor conservation status of the species in the country, the development of a national Biodiversity Management Plan aimed at ensuring the long‐term survival of the species in South Africa is strongly recommended. At the same time, increased research efforts are essential, particularly to allow for an in‐depth assessment of population numbers and drivers of changes therein. 5. The present study clearly indicates the importance of scientific collaboration when investigating highly mobile and endangered species.This collaborative research project was funded by the South African Network for Coastal and Oceanic Research (SANCOR), the National Research Foundation (NRF), and the University of Pretoria.http://wileyonlinelibrary.com/journal/aqc2019-02-01hj2018Mammal Research Institut

Exercise As Adjunctive Therapy In Chronic Kidney Disease

Background. Exercise is a natural medicine that has been prescribed for the prevention and management of chronic diseases, to enhance quality of life, improve health status and promote longevity. Current efforts to implement exercise as routine practice in the conventional renal replacement therapy population have been hampered by a lack of randomised controlled data. The aim of this thesis was to investigate the effect of exercise as an adjunctive therapy to enhance outcomes pertaining to renal transplantation, vascular access, haemodialysis adequacy and muscle wasting in Stages four and five Chronic Kidney Disease patients. It was hypothesised that randomised controlled trials employing gold standard outcome measures would reveal significant beneficial effects of exercise that are strongly associated with quality of life, hospitalisation and survival in this patient population. Reports. The first report presents a systematic literature review of exercise in the kidney transplant population. The largest positive effects were noted on intermediate outcomes such as aerobic fitness and muscle strength. Presumably these adaptations contributed to the trends observed for improvement in quality of life. Whether exercise impacts on outcomes associated with longevity of life requires further study. The rest of the thesis focused on patients receiving the more popular form of renal replacement therapy, haemodialysis. The first empirical study of the thesis appertaining to vascular access investigated the feasibility of implementing a post-operative forearm exercise intervention for arteriovenous fistula maturation. Exercise had no effect on primary outcomes measures of arterial diameter (95% CI, -0.24 [-1.12; 0.51] mm) and venous diameter (95% CI, 0.16 [-1.84; 1.24] mm). It was concluded that future randomized controlled trials should investigate a similar protocol implemented before arteriovenous fistula creation to enhance surgery success and maturation. The second randomised controlled trial explored the effect of intradialytic exercise in comparison to the traditional prescription of increased dialysis time to enhance dialysis adequacy and solute removal. Increased haemodialysis time, but not exercise, increased equilibrated Kt/Vurea compared to control trials (Extra time vs. control: 95% CI, 0.15 [0.05; 0.26]; exercise vs. control: 95% CI, 0.03 [-0.05; 0.12]). Exercise, but not increased time, increased phosphate reduction ratio (exercise vs. control: 95% CI, 8.6 [0.5; 16.7] %; extra time vs. control: 95% CI, 5.0 [-1.0; 11.1] %). Thus intradialytic exercise cannot replace the traditional prescription of increased haemodialysis time, but may be a useful adjunctive therapy for serum phosphate control. The third study implemented a randomised controlled trial of intradialytic progressive resistance training for muscle wasting. The primary outcome measure of thigh muscle volume, as measured by magnetic resonance imaging, significantly increased following 12 weeks of training compared to a sham exercise control (95% CI, 193 [63; 324] cm3 ). Intradialytic resistance exercise elicited an anabolic and strength response in haemodialysis patients. However, a surprising lack of a change in functional capacity despite increased muscle mass warrants further investigation. Conclusion. The findings suggested that exercise had a beneficial effect on factors relating to outcomes in Stages 4 and 5 Chronic Kidney Disease patients. However, to ensure effectiveness of interventions and to maximize programme efficiency, careful consideration of basic exercise and physiological principles is required. Nevertheless, the observed benefits of exercising outweighed its risks thus supporting the initiative for exercise prescription as an adjunctive therapy for the management of this disease state

Men’s perceptions of prostate cancer diagnosis and care: insights from qualitative interviews in Victoria, Australia

Abstract Background The Victorian Prostate Cancer Registry (Australia) revealed poorer rates of survival for men diagnosed with prostate cancer in one Victorian regional area than for men in metropolitan Melbourne. We sought to explore the perceptions and experiences of prostate cancer diagnosis, treatment, and care of men diagnosed with prostate cancer who lived in regional or metropolitan areas and of men who had not been so diagnosed. Our goal was to contribute to the evidence from which can be built continuing improvements in prostate health care. Methods Using the qualitative method of in-depth interviews to gain access to explanation and meaning, we interviewed 21 men: 10 recruited through the Prostate Cancer Outcome Registry-Victoria and 11 from the community. Transcripts were analysed thematically. Results We identified four main themes within which men discussed prostate cancer: Case-finding, Diagnosis, Treatment and Care, and Spreading the Word. Contrasts revealed between regional and metropolitan areas related mostly to the more limited supportive care in regional areas. Conclusions It is evident from the perspectives of these men that every aspect of prostate cancer care would benefit from attention: publicising the need to check prostate health, treatment, and supporting men in the years after treatment. Continuing to work on systemic improvements is an important goal for all those committed to men’s health

Altered vascular function in chronic kidney disease: evidence from passive leg movement

Abstract Chronic kidney disease (CKD) is an independent risk factor for the development of cardiovascular disease and is characterized by reduced nitric oxide (NO) bioavailability and vascular dysfunction, typically assessed using brachial artery flow‐mediated dilation (FMD). It has been previously reported that passive leg movement (PLM)‐induced hyperemia, an assessment of lower extremity vascular function, is highly dependent on NO, but has not yet been utilized to assess vascular function in patients with CKD. The purpose of this study was to comprehensively assess vascular function in patients with CKD using PLM, in addition to the traditional FMD technique. Assessment of vascular function via PLM and FMD was performed on 12 patients (CKD, 66 ± 3 years) and 16 age‐matched healthy controls (CON, 60 ± 2 years). Blood velocity and artery diameters during PLM and FMD were measured using duplex ultrasound of the femoral and brachial arteries, respectively. Habitual physical activity, assessed by accelerometry, was performed in a subset of each group. CKD patients had reduced peak leg blood flow (LBF) (384 ± 39 vs. 569 ± 77 mL/min, P < 0.05) and change in LBF from baseline to peak (∆peakLBF) (143 ± 22 vs. 249 ± 34 mL/min, P < 0.05) during PLM compared to CON. Additionally, PLM responses were significantly associated with kidney function and physical activity levels. As anticipated, FMD was significantly attenuated in CKD patients (5.2 ± 1.1 vs. 8.8 ± 1.2%, P < 0.05). In conclusion, both upper and lower extremity measures of vascular function indicate impairment in CKD patients when compared to controls. PLM appears to be a novel and feasible approach to assessing lower extremity vascular function in CKD

KIDNEY DYSFUNCTION IS ASSOCIATED WITH DIMINISHED SKELETAL MUSCLE MITOCHONDRIAL PLASTICITY IN LIVER TRANSPLANT RECIPIENTS

BACKGROUND: Liver transplant (LT) recipients experience severe weight gain after transplant. This weight gain is driven by myopenia and subsequent metabolic inflexibility that culminates in an exacerbated risk of cardiometabolic disease. The risk of cardiovascular disease is increased in LT recipients with impaired kidney function. We do not fully understand the underlying physiological mechanisms that link kidney dysfunction with cardiometabolic disease in this patient population. Therefore, the purpose of this study was to determine the relationship between renal dysfunction and skeletal muscle mitochondrial plasticity in LT patients. We hypothesized that worse kidney function would be associated with impaired skeletal muscle mitochondrial oxidative capacity. METHODS: LT recipients were recruited from Virginia Commonwealth University Health Systems outpatient clinic visits. Venous blood samples were analyzed as part of routine clinical labs including renal function reported as estimated glomerular filtration rate (eGFR) calculated using the race free CKD-EPI equation. Skeletal muscle mitochondrial capacity of the wrist flexor muscle group was determined using near-infrared spectroscopy coupled with repeated, transient arterial occlusions to measure the recovery kinetics of oxygen consumption following an acute bout of handgrip exercise. The metabolic recovery rate constant (Tc) of muscle metabolism was calculated and reported as an index of mitochondrial oxidative capacity. Statistical associations were conducted using Pearson’s correlation test. RESULTS: 21 LT recipients (11 Male/10 Female; 5 African American/1 Asian/15 Caucasian; Mean ± SD: Age 58±9 years; body mass index 36.5±5.9 kg/m2) were enrolled. Renal function measured by eGFR (54±19 mL/min/1.73m2) was negatively associated with skeletal muscle mitochondrial oxidative capacity (Tc: 79.73±26.47 seconds; r = -0.51, p = 0.02). CONCLUSIONS: Impaired kidney function was associated with diminished skeletal muscle mitochondrial oxidative capacity in LT recipients. Future studies are warranted to establish if the observed impairments in mitochondrial plasticity are the mechanistic underpinning of metabolic inflexibility and cardiometabolic sequelae that are increased in LT recipients with impaired kidney function. FUNDING: Supported by NIH UL1TR00264