Medicine (Western Health) - Research Publications
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ItemUndercarboxylated osteocalcin and ibandronate combination ameliorates hindlimb immobilization-induced muscle wasting(WILEY, 2023-05)Immobilization leads to muscle wasting and insulin resistance, particularly during ageing. It has been suggested that undercarboxylated osteocalcin (ucOC) improves muscle mass and glucose metabolism. Bisphosphonates, an anti-osteoporosis treatment, might protect muscle wasting independent of ucOC. We hypothesize that the combination of ucOC and ibandronate (IBN) treatments has superior protective effects against immobilization-induced muscle wasting and insulin resistance than either treatment alone. C57BL/6J mice were hindlimb-immobilized for two weeks, with injections of vehicle, ucOC (90 ng/g daily) and/or IBN (2 Ī¼g/g weekly). Insulin/oral glucose tolerance tests (ITT/OGTT) were performed. Immediately after immobilization, muscles (extensor digitorum longus (EDL), soleus, tibialis anterior, gastrocnemius and quadriceps) were isolated and measured for muscle mass. Insulin-stimulated glucose uptake (EDL and soleus) was examined. Phosphorylation/expression of proteins in anabolic/catabolic pathways were examined in quadriceps. Primary human myotubes derived from older adult muscle biopsies were treated with ucOC and/or IBN, then signalling proteins were analysed. Combined treatment, but not individual treatments, significantly increased the muscle weight/body weight ratio in immobilized soleus (31.7%; P = 0.013) and quadriceps (20.0%; P = 0.0008) muscles, concomitant with elevated p-Akt (S473)/Akt ratio (P = 0.0047). Combined treatment also enhanced whole-body glucose tolerance (16.6%; P = 0.0011). In human myotubes, combined treatment stimulated greater activation of ERK1/2 (P = 0.0067 and 0.0072) and mTOR (P = 0.036), and led to a lesser expression of Fbx32 (P = 0.049) and MuRF1 (P = 0.048) than individual treatments. These findings suggest a potential therapeutic role for the ucOC and bisphosphonates combination in protecting against muscle wasting induced by immobilization and ageing. KEY POINTS: It has been suggested that undercarboxylated osteocalcin (ucOC) improves muscle mass and glucose metabolism. Bisphosphonates, an anti-osteoporosis treatment, might protect against muscle wasting independent of ucOC. The combination treatment of ucOC and ibandronate was shown to exert a greater therapeutic effect against immobilization-induced muscle wasting, and led to greater activation of anabolic pathway and less expression of catabolic signalling proteins in myotubes derived from older adults, compared with individual treatments. The combination treatment was found to improve whole-body glucose tolerance. Our findings suggest a potential therapeutic role for the ucOC and bisphosphonates combination in protecting against muscle wasting induced by immobilization and ageing.
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ItemNo Preview AvailableThe educational needs of people with bronchiectasis in a pulmonary rehabilitation setting(European Respiratory Society, 2020-09-07)
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ItemNo Preview AvailableIS QUALITY OF LIFE RECOVERY ASSOCIATED WITH LOWER MORTALITY 5 YEARS POST-FRACTURE IN COMMUNITY-DWELLING OLDER ADULTS?(SPRINGER LONDON LTD, 2022-04)
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ItemCOLD SNARE POLYPECTOMY OF COLORECTAL POLYPS ā¤10MM ON CLOPIDOGREL: AN AUSTRALIAN AND NEW ZEALAND RANDOMISED CONTROLLED TRIAL(MOSBY-ELSEVIER, 2020-06)Abstract Background and study aimsāOptimal peri-colonoscopic management of clopidogrel remains unclear. Cold snare polypectomy is safe and effective for removing polyps ā¤ā10āmm and clips can control intraprocedural bleeding. We conducted a randomized controlled trial to compare continuation of clopidogrel versus temporary replacement of clopidogrel with aspirin for routine colonoscopy using cold snare polypectomy for polyps ā¤ā10āmm. Patients and methodsāBetween August 2016 and August 2019, consenting participants at 12 centers were randomized to continuation of clopidogrel as a single or dual antiplatelet agent, or to temporarily take aspirin alone from 7 days prior to 2 days after routine colonoscopy. Endoscopists were blinded to group allocation. Cold snare polypectomy was used to remove polypsāā¤ā10āmm, with endoscopic clips applied if intraprocedural bleeding continued for >ā2 minutes. Follow-up was performed on Day 30. The trial was stopped early due to delayed patient enrollment. ResultsāTwo hundred seventy-six consecutive polypsāā¤ā10āmm were removed from 107 patients. Of the patients, 61.7ā% were male with a median age of 69 years (interquartile range [IQR] 63 to 76.75). Fifty-nine patients continued on clopidogrel and 48 temporarily took aspirin instead. One hundred thirty-four polyps were removed from 49 patients who continued on clopidogrel vs 142 from 43 patients temporarily took aspirin instead (Pā=ā0.33). Intraprocedural bleeding requiring clips occurred in 11 of 49 patients who continued on clopidogrel and in two of 43 patients who temporarily took replacing with aspirin instead (Pā=ā0.02). More post-procedural minor bleeding was seen in the aspirin arm (six of 43 vs one of 49; Pā=ā0.03). One patient in each arm had acute coronary syndrome, which was medically managed. None of the patients had clinically significant post-procedural bleeding. ConclusionsāContinuation of clopidogrel in patients undergoing cold snare polypectomy for colorectal polyps ā¤ā10āmm does not appear to increase the rate of clinically significant postpolypectomy bleeding. It is associated with an increase in intraprocedural bleeding, which can be successfully treated with clips.
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ItemSPUTUM PROCALCITONIN - A POTENTIAL BIOMARKER OF INFECTION IN STABLE BRONCHIECTASIS(WILEY, 2020-06)Sputum procalcitonin is elevated in exacerbations of bronchiectasis. The primary aim of this study was to investigate whether sputum procalcitonin levels are higher in patients with stable bronchiectasis than in healthy controls. We also assessed differences in procalcitonin levels in spontaneously expectorated and induced sputum samples and their repeatability 1ā week later. Participants included were aged over 18ā years and either had radiologically confirmed bronchiectasis or were healthy controls. Patients with bronchiectasis were clinically stable for at least 6ā weeks and had spontaneous and induced sputum collected at visit 1 and again 7ā days later. Only induced sputum samples were collected from healthy controls during visit 1. Sputum procalcitonin concentrations in sputum were measured. In total, 30 patients with bronchiectasis and 15 healthy controls were enrolled in this observational study. In the pooled data from visit 1 and 2, the geometric mean procalcitonin level in induced sputum was significantly higher in the bronchiectasis group than in the healthy control group (1.5ā ngĀ·mL-1, 95% CI 1.0-2.1 ngĀ·mL-1 versus 0.4ā ngĀ·mL-1, 95% CI 0.2-0.9ā ngĀ·mL-1; mean ratio 3.6, 95% CI 1.5-8.6; p=0.006). Mean procalcitonin level was higher in spontaneous sputum than in induced sputum at visit 1 (1.8ā ngĀ·mL-1, 95% CI 1.2-2.7 ngĀ·mL-1 versus 1.1ā ngĀ·mL-1, 95% CI 0.7-1.8ā ngĀ·mL-1) and visit 2 (1.5ā ngĀ·mL-1, 95% CI 1.0-2.5ā ngĀ·mL-1 versus 1.2ā ngĀ·mL-1, 95% CI 0.8-1.6ā ngĀ·mL-1; p=0.001). Repeating spontaneous and induced sputum procalcitonin levels 1ā week later produced similar concentrations (p=0.29, intraclass correlation coefficient (ICC)=0.76 and p=0.72, ICC=0.70, respectively). Sputum procalcitonin is increased in patients with stable bronchiectasis and has potential as a biomarker of airway inflammation and infection in bronchiectasis.
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ItemFrailty associations with socioeconomic status, healthcare utilisation and quality of life among older women residing in regional Australia(WILEY, 2021-05)OBJECTIVES: The health and well-being of older women may be influenced by frailty and low socioeconomic status (SES). This study examined the association between frailty and SES, healthcare utilisation and quality of life (QOL) among older women in regional Australia. METHODS: Cross-sectional analysis of the Geelong Osteoporosis Study was conducted on 360 women (ages ā„60yr) in the 15-year follow up. Frailty was identified using modified Fried's phenotype. Individual SES measures and healthcare utilisation were documented by questionnaire. Area-based SES was determined by cross-referencing residential addresses with the Australian Bureau of Statistics Index of Relative Socio-economic Advantage and Disadvantage (IRSAD). QOL was measured using the Australian World Health Organisation Quality of Life Instrument (WHOQoL-Bref). Multinomial logistic regression was conducted with frailty groupings as outcome. RESULTS: Sixty-two (17.2%) participants were frail, 199 (55.3%) pre-frail and 99 (27.5%) robust. Frail participants were older with higher body mass index. Frailty was associated with lower education but not marital status, occupation or IRSAD. Strong associations with frailty were demonstrated for all WHOQoL-Bref domains. Frailty was associated with more primary care doctor visits (p<0.001). CONCLUSIONS: This population-based study highlights the significant impact of frailty on older women, indicating reduced QOL and increased primary care doctor visits.
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ItemClinical outcomes following ST-elevation myocardial infarction secondary to stent thrombosis treated by percutaneous coronary intervention(WILEY, 2020-10-01)OBJECTIVES: To assess the clinical outcomes of patients presenting with ST-elevation myocardial infarction (STEMI) secondary to stent thrombosis (ST) compared to those presenting with STEMI secondary to a de novo culprit lesion and treated by percutaneous coronary intervention (PCI). BACKGROUND: ST is an infrequent but serious complication of PCI with substantial associated morbidity and mortality, however with limited data. METHODS: We studied consecutive patients who underwent PCI for STEMI from 2005 to 2013 enrolled prospectively in the Melbourne Interventional Group registry. Patients were divided into two groups: the ST group comprised patients where the STEMI was due to ST and the de novo group formed the remainder of the STEMI cohort and all patients were treated by PCI. The primary endpoint was 30-day all-cause mortality. RESULTS: Compared to the de novo group (n = 3,835), the ST group (n = 128; 3.2% of STEMI) had higher rates of diabetes, hypertension and dyslipidemia, established cardiovascular diseases, myocardial infarction, and peripheral vascular disease, all pā<ā.01. Within the ST group, very-late ST was the most common form of ST, followed by late and early ST (64, 19, and 17%, respectively). There was no significant difference in the primary outcome between the ST group and the de novo group (4.7 vs. 7.1%, p = .29). On multivariate analysis, ST was not an independent predictor of 30-day mortality (odds ratio: 0.62, 95% confidence interval: 0.07-1.09, p = .068). CONCLUSION: The short-term prognosis of patients with STEMI secondary to ST who were treated by PCI was comparable to that of patients with STEMI due to de novo lesions.