Medicine (Austin & Northern Health) - Research Publications
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ItemRelationship between autonomic cardiovascular control and obstructive sleep apnoea in persons with spinal cord injury: a retrospective study.(Springer Science and Business Media LLC, 2018)STUDY DESIGN: Retrospective study. OBJECTIVE: To determine if there is an association between obstructive sleep apnoea (OSA) and blood pressure (BP) pattern or heart rate variability (HRV) in people with spinal cord injury (SCI). SETTING: A state-based spinal cord service in Victoria, Australia. METHODS: We identified 42 subjects who had ambulatory BP monitoring (ABPM) within 6 months of a diagnostic sleep study at Austin Hospital between 2009 and 2014. Markers for autonomic function, including circadian BP pattern and HRV were extracted from the ABPM study database. Apnoea/hypopnoea index (AHI), arousals/hour and oxygen desaturation index were extracted from the sleep study database. Subjects with a nocturnal systolic BP dipping more than 10% of daytime value were defined as dippers, between 10 and 0% were non-dippers and those with a higher night than day systolic BP were reverse dippers. Severity of OSA is classified as non-OSA (AHI < 5), mild (AHI 5-15), moderate (AHI 15-30) and severe (AHI > 30). RESULTS: Subjects (n = 42) were predominantly male (85.7%), aged 44 ± 15.4 (mean ± SD), with a BMI of 24.4 ± 5.7 (mean ± SD) and mainly tetraplegic (92.9%). There was no difference in AHI, oxygen desaturation index or arousals/hour between dippers, non-dippers and reverse dippers. None of the HRV parameters differed between dippers, non-dippers and reverse dippers. No differences were found in 24 h, night-time, daytime or nocturnal dip in BP between subjects with non-OSA, mild, moderate and severe OSA. CONCLUSION: We found no relationship between BP pattern or HRV and the severity of OSA in persons with SCI.
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ItemA genome-wide association study of corneal astigmatism: The CREAM Consortium(MOLECULAR VISION, 2018-02-05)PURPOSE: To identify genes and genetic markers associated with corneal astigmatism. METHODS: A meta-analysis of genome-wide association studies (GWASs) of corneal astigmatism undertaken for 14 European ancestry (n=22,250) and 8 Asian ancestry (n=9,120) cohorts was performed by the Consortium for Refractive Error and Myopia. Cases were defined as having >0.75 diopters of corneal astigmatism. Subsequent gene-based and gene-set analyses of the meta-analyzed results of European ancestry cohorts were performed using VEGAS2 and MAGMA software. Additionally, estimates of single nucleotide polymorphism (SNP)-based heritability for corneal and refractive astigmatism and the spherical equivalent were calculated for Europeans using LD score regression. RESULTS: The meta-analysis of all cohorts identified a genome-wide significant locus near the platelet-derived growth factor receptor alpha (PDGFRA) gene: top SNP: rs7673984, odds ratio=1.12 (95% CI:1.08-1.16), p=5.55×10-9. No other genome-wide significant loci were identified in the combined analysis or European/Asian ancestry-specific analyses. Gene-based analysis identified three novel candidate genes for corneal astigmatism in Europeans-claudin-7 (CLDN7), acid phosphatase 2, lysosomal (ACP2), and TNF alpha-induced protein 8 like 3 (TNFAIP8L3). CONCLUSIONS: In addition to replicating a previously identified genome-wide significant locus for corneal astigmatism near the PDGFRA gene, gene-based analysis identified three novel candidate genes, CLDN7, ACP2, and TNFAIP8L3, that warrant further investigation to understand their role in the pathogenesis of corneal astigmatism. The much lower number of genetic variants and genes demonstrating an association with corneal astigmatism compared to published spherical equivalent GWAS analyses suggest a greater influence of rare genetic variants, non-additive genetic effects, or environmental factors in the development of astigmatism.
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ItemNo Preview AvailableIntensive exercise program after spinal cord injury (SCIPA full-on): A randomized controlled trial(Elsevier, 2018-01-01)Introduction/Background: While upper body training is effective for improving aerobic fitness and muscle strength after spinal cord injury (SCI), activity-based therapies (ABT) intended to activate the paralysed extremities have been reported to promote neurological improvement. We investigated the effectiveness of intensive ABT compared with upper body training for people with SCI. Material and method: One hundred and sixteen participants (C2-T12, AIS A-D) were recruited from six SCI units in Australia and New Zealand, and randomised to experimental or control groups. Experimental participants received a 12-week ABT program including locomotor training, functional electrical stimulation-assisted leg cycling, and trunk and lower extremity exercises, while control group participants undertook upper body strength and aerobic fitness training. The primary outcome measure was the ASIA motor scores for upper and lower extremities. Results: One hundred and three participants completed the interventions and were included in the primary analysis. Mean (SD) upper extremity motor scores for experimental (n = 49) and control (n = 54) groups were 41.45 (12.11) and 39.39 (11.94), respectively, with an adjusted mean between-group difference of −0.039 (95% CI: −1.12 to 1.04). Mean (SD) lower extremity motor scores were 12.51 (17) and 10.24 (17.19) for experimental and control groups, with an adjusted mean between-group difference of 0.895 (95% CI: −0.48 to 2.27). There were 15 serious adverse events within each group, but only one of these was related to the experimental intervention (bilateral femoral condyle and tibial plateau subchondral fractures). Conclusion: Activity-based therapy did not lead to greater improvements in ASIA motor scores compared to upper body training
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ItemVery Low Calorie Diets for Weight Loss in Obese Older Adults-A Randomized Trial(OXFORD UNIV PRESS INC, 2018-01)BACKGROUND: Obesity contributes to disability in older adults, and this is offset by weight loss and exercise. Very Low Calorie Diets (VLCDs) achieve rapid weight loss; however, these have not been rigorously evaluated in older people. METHODS: A randomized trial was conducted from August 2012 through December 2015. The intervention was 12 weeks of thrice weekly exercise combined with either healthy eating advice (Ex/HE), hypocaloric diet (Ex/Diet), or VLCD (Ex/VLCD). Outcomes were physical function, measured by 6-minute walk test (6MWT) and De Morton Mobility Index (DEMMI). Other measures were body composition measured by Dual Energy X-Ray Absorptiometry, and nutritional parameters (albumin, vitamins B12 and D, ferritin and folate). RESULTS: 36, 40, and 41 participants were randomized to Ex/HE, Ex/Diet, and Ex/VLCD, respectively. At 12 weeks, weight was reduced by 3.7, 5.1, and 11.1% (p < .01), respectively. Ex/VLCD had significant reduction in fat (16.8%), lean mass (4.8%), and bone mineral density (1.2%), but increased relative lean mass (3.8%). DEMMI improved by 14.25, 14.25, and 13.75 points in Ex/HE, Ex/Diet, and Ex/VLCD, respectively; however, there was no between-group difference (p = .30). 6MWT improved by 53.1, 64.7, and 84.4 meters in Ex/HE, Ex/Diet, and Ex/VLCD (p = .18). Post hoc stratification for gender and adjustment for initial physical function and type 2 diabetes only revealed significant between-group differences for men in the 6MWT, with improvement by 57.8, 77.8, and 140.3 meters in Ex/HE, Ex/Diet, and Ex/VLCD, respectively (p = .01). Improvements in nutritional parameters were seen in Ex/VLCD, but not in Ex/HE and Ex/Diet. The VLCD was well tolerated. CONCLUSIONS: VLCDs have potential in the treatment of obesity in older persons; of particular benefit is improvement in nutritional status. The gait speed improvement observed in men warrants further investigation.
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ItemSCIPA Full-On: A Randomized Controlled Trial Comparing Intensive Whole-Body Exercise and Upper Body Exercise After Spinal Cord Injury(SAGE PUBLICATIONS INC, 2018-06)Background. While upper body training has been effective for improving aerobic fitness and muscle strength after spinal cord injury (SCI), activity-based therapies intended to activate the paralyzed extremities have been reported to promote neurological improvement. Objective. To compare the effectiveness of intensive whole-body exercise compared with upper body exercise for people with chronic SCI. Methods. A parallel-group randomized controlled trial was conducted. Participants with a range of SCI levels and severity were randomized to either full-body exercise (FBE) or upper body exercise (UBE) groups (3 sessions per week over 12 weeks). FBE participants underwent locomotor training, functional electrical stimulation-assisted leg cycling, and trunk and lower extremity exercises, while UBE participants undertook upper body strength and aerobic fitness training only. The primary outcome measure was the American Spinal Injury Association (ASIA) motor score for upper and lower extremities. Adverse events were systematically recorded. Results. A total of 116 participants were enrolled and included in the primary analysis. The adjusted mean between-group difference was -0.04 (95% CI -1.12 to 1.04) for upper extremity motor scores, and 0.90 (95% CI -0.48 to 2.27) for lower extremity motor scores. There were 15 serious adverse events in UBE and 16 in FBE, but only one of these was definitely related to the experimental intervention (bilateral femoral condyle and tibial plateau subchondral fractures). No significant between-group difference was found for adverse events, or functional or behavioral variables. Conclusions. Full-body training did not lead to improved ASIA motor scores compared with upper body training in people with chronic SCI.
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ItemMechanical Loading Differentially Affects Osteocytes in Fibulae from Lactating Mice Compared to Osteocytes in Virgin Mice: Possible Role for Lacuna Size(SPRINGER, 2018-12)Hormonal changes during lactation are associated with profound changes in bone cell biology, such as osteocytic osteolysis, resulting in larger lacunae. Larger lacuna shape theoretically enhances the transmission of mechanical signals to osteocytes. We aimed to provide experimental evidence supporting this theory by comparing the mechanoresponse of osteocytes in the bone of lactating mice, which have enlarged lacunae due to osteocytic osteolysis, with the response of osteocytes in bone from age-matched virgin mice. The osteocyte mechanoresponse was measured in excised fibulae that were cultured in hormone-free medium for 24 h and cyclically loaded for 10 min (sinusoidal compressive load, 3000 µε, 5 Hz) by quantifying loading-related changes in Sost mRNA expression (qPCR) and sclerostin and β-catenin protein expression (immunohistochemistry). Loading decreased Sost expression by ~ threefold in fibulae of lactating mice. The loading-induced decrease in sclerostin protein expression by osteocytes was larger in lactating mice (55% decrease ± 14 (± SD), n = 8) than virgin mice (33% decrease ± 15, n = 7). Mechanical loading upregulated β-catenin expression in osteocytes in lactating mice by 3.5-fold (± 0.2, n = 6) which is significantly (p < 0.01) higher than the 1.6-fold increase in β-catenin expression by osteocytes in fibulae from virgin mice (± 0.12, n = 4). These results suggest that osteocytes in fibulae from lactating mice with large lacunae may respond stronger to mechanical loading than those from virgin mice. This could indicate that osteocytes residing in larger lacuna show a stronger response to mechanical loading.
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ItemNo Preview AvailableRandomized Controlled Trial of Melatonin for Sleep Disturbance in Dravet Syndrome: The DREAMS Study(AMER ACAD SLEEP MEDICINE, 2018-01-01)Dravet syndrome is a severe developmental and epileptic encephalopathy, in which 75% of patients have sleep disturbance. Melatonin is often used for sleep problems in childhood; however, there is no quality evidence supporting its use in Dravet syndrome. We hypothesized that melatonin would increase total sleep and quality of life for patients with Dravet syndrome.Methods: A double-blind crossover randomized placebo-controlled trial was conducted, comparing 6 mg regular-release melatonin to placebo for patients with Dravet syndrome and sleep disturbance. The primary outcome measure was total sleep measured by actigraphy, with secondary outcomes including wakefulness after sleep onset (WASO), Sleep Disturbance Scale in Children and Quality of Life in Children with Epilepsy 55 questionnaires, caregiver reports of clinical change, seizure diary and serum antiepileptic drug levels. We also compared actigraphy data of patients with Dravet syndrome to an age-matched healthy control group.Results: A total of 13 patients completed the study. There was no difference in total sleep or WASO between melatonin and placebo. However, of the 11 patients for whom caregivers reported a clear clinical difference between treatments (blinded), 8 reported improvement on melatonin (P < .05). Interestingly, when compared to patients in the control group, patients with Dravet syndrome had significantly increased total sleep (P = .002).Conclusions: Melatonin did not increase total sleep; however, blinded caregiver reports indicate treatment with melatonin provided considerable clinical benefit for some patients with Dravet syndrome and sleep disturbance.
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ItemInfluence of ethnic background on left atrial markers of inflammation, endothelial function and tissue remodelling.(Elsevier BV, 2018)BACKGROUND: It has been suggested that ethnicity can make a significant difference to the likelihood of thromboembolic stroke related to atrial fibrillation. Ethnic differences have been shown to alter inflammatory and haemostatic factors; however, this may all be confounded by differences in cardiovascular risk factors between different ethnicity. The impact of different ethnicities on the thrombogenic profile is not known. The aim of this study was to investigate differences in markers of inflammation, endothelial function and tissue remodelling between Caucasian and Indian populations with supraventricular tachycardia (SVT). METHODS: Patients with structurally normal hearts undergoing catheter ablation for SVT were studied. This study included 23 Australian (Caucasian) patients from the Royal Adelaide Hospital, Adelaide, Australia and 24 Indian (Indian) patients from the Christian Medical College, Vellore, India. Blood samples were collected from the femoral vein, and right and left atria. Blood samples were analysed for the markers of endothelial function (ADMA, ET-1), inflammation (CD40L, VCAM-1, ICAM-1), and tissue remodelling (MMP-9, TIMP-1) using ELISA. RESULTS: The study populations were well matched for cardiovascular risk factors and the absence of structural heart disease. No difference in the echocardiographic measurements between the two ethnicities was found. In this context, there was no difference in markers of inflammation, endothelial function or tissue remodelling between the two SVT populations. CONCLUSION: Caucasian and Indian populations demonstrate similar inflammatory, endothelial function or tissue remodelling profiles. This study suggests a lack of an impact of different ethnicity in these populations in terms of thrombogenic risk.
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ItemRevision of the ARRIVE guidelines: rationale and scope.(Portico, 2018-06-12)In 2010, the NC3Rs published the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines to improve the reporting of animal research. Despite considerable levels of support from the scientific community, the impact on the quality of reporting in animal research publications has been limited. This position paper highlights the strategy of an expert working group established to revise the guidelines and facilitate their uptake. The group's initial work will focus on three main areas: prioritisation of the ARRIVE items into a tiered system, development of an explanation and elaboration document, and revision of specific items.