Medicine (Western Health) - Research Publications

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    Quantifying sex, race, and age specific differences in bone microstructure requires measurement of anatomically equivalent regions
    Ghasem-Zadeh, A ; Burghardt, A ; Wang, X-F ; Iuliano, S ; Bonaretti, S ; Bui, M ; Zebaze, R ; Seeman, E (Elsevier, 2017-08-01)
    INTRODUCTION: Individuals differ in forearm length. As microstructure differs along the radius, we hypothesized that errors may occur when sexual and racial dimorphisms are quantified at a fixed distance from the radio-carpal joint. METHODS: Microstructure was quantified ex vivo in 18 cadaveric radii using high resolution peripheral quantitative computed tomography and in vivo in 158 Asian and Caucasian women and men at a fixed region of interest (ROI), a corrected ROI positioned at 4.5-6% of forearm length and using the fixed ROI adjusted for cross sectional area (CSA), forearm length or height. Secular effects of age were assessed by comparing 38 younger and 33 older women. RESULTS: Ex vivo, similar amounts of bone mass fashioned adjacent cross sections. Larger distal cross sections had thinner porous cortices of lower matrix mineral density (MMD), a larger medullary CSA and higher trabecular density. Smaller proximal cross-sections had thicker less porous cortices of higher MMD, a small medullary canal with little trabecular bone. Taller persons had more distally positioned fixed ROIs which moved proximally when corrected. Shorter persons had more proximally positioned fixed ROIs which moved distally when corrected, so dimorphisms lessened. In the corrected ROIs, in Caucasians, women had 0.6 SD higher porosity and 0.6 SD lower trabecular density than men (p<0.01). In Asians, women had 0.25 SD higher porosity (NS) and 0.5 SD lower trabecular density than men (p<0.05). In women, Asians had 0.8 SD lower porosity and 0.3 SD higher trabecular density than Caucasians (p<0.01). In men, Asians and Caucasians had similar porosity and trabecular density. Results were similar using an adjusted fixed ROI. Adjusting for secular effects of age on forearm length resulted in the age-related increment in porosity increasing from 2.08 SD to 2.48 SD (p<0.05). CONCLUSION: Assessment of sex, race and age related differences in microstructure requires measurement of anatomically equivalent regions.
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    Very early mobilization following acute stroke: Controversies, the unknowns, and a way forward
    Bernhardt, J (WOLTERS KLUWER MEDKNOW PUBLICATIONS, 2008-01)
    UNLABELLED: Evidence that organized stroke-unit care results in better outcome has led to positive changes in stroke service delivery around the world. It is well accepted that stroke rehabilitation should commence as early as possible for optimal recovery to be achieved. Exactly how early rehabilitation should start is controversial. Early mobilization (getting up out of bed within 24 h of stroke onset) is a wellestablished feature of acute stroke care in many Scandinavian hospitals. Elsewhere in the world, stroke protocols enforce bed rest for the first few days or foster long periods of bed rest after stroke. This paper aims to provide an overview of the topic of very early mobilization (VEM). It is divided into three sections: section 1 reviews the effects of bed rest and outlines arguments both for and against enforced bed rest after stroke; in section 2, VEM as a treatment for stroke and the limitations of existing literature in the field are described; and section 3 outlines the systematic approach that has been taken by our team of clinical researchers to the study the effect of VEM after stroke. CONCLUSION: VEM represents a simple, easy-to-deliver intervention, requiring little or no equipment. It is potentially deliverable to 85% of the acute stroke population and, if proven to be effective, may help reduce the significant personal and community burden of stroke. As current opinion about when mobilization should begin is divided, one way to move forward is through the conduct of a large high-quality clinical trial (such as A Very Early Rehabilitation Trial (AVERT)). Although some inroads have been made, further research in this field is clearly warranted.
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    Comparison of incidence, rate and length of all-cause hospital admissions between adults with normoglycaemia, impaired fasting glucose and diabetes: a retrospective cohort study in Geelong, Australia
    Sajjad, MA ; Holloway, KL ; de Abreu, LLF ; Mohebbi, M ; Kotowicz, MA ; Pedler, D ; Pasco, JA (BMJ PUBLISHING GROUP, 2018-03)
    OBJECTIVE: To determine whether adults with normoglycaemia, impaired fasting glucose (IFG) and diabetes differed according to the incidence, rate, length and primary reasons for hospital admission. DESIGN: Retrospective cohort study. SETTING: Barwon Statistical Division, Geelong, Australia. PARTICIPANTS: Cohort included 971 men and 924 women, aged 20+ years, participating in the Geelong Osteoporosis Study. Glycaemic status was assessed at cohort entry using fasting plasma glucose, use of antihyperglycaemic medication and/or self-report. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome measure was any admission to the major tertiary public hospital in the study region over the follow-up period. Secondary outcome measures were admission rate and length (days). RESULTS: Over a median follow-up of 7.4 years (IQR 5.3-9.6), participants with diabetes, compared with those with normoglycaemia, were two times as likely to be hospitalised (OR 2.07, 95% CI 1.42 to 3.02), had a higher admission rate (incidence rate ratio 1.61, 95% CI 1.17 to 2.23) and longer hospital stay (third quartile difference 7.7, 95% CI 1.3 to 14.1 and ninth decile difference 16.2, 95% CI 4.2 to 28.3). IFG group was similar to normoglycaemia for the incidence, rate and length of admission. Cardiovascular disease-related diagnoses were the most common primary reasons for hospitalisation across all glycaemic categories. CONCLUSIONS: Our results show increased incidence, rate and length of all-cause hospital admission in adults with diabetes as compared with normoglycaemia; however, we did not detect any associations for IFG. Interventions should focus on preventing IFG-to-diabetes progression and reducing cardiovascular risk in IFG and diabetes.
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    The association between major depressive disorder, use of antidepressants and bone mineral density (BMD) in men
    Rauma, PH ; Pasco, JA ; Berk, M ; Stuart, AL ; Koivumaa-Honkanen, H ; Honkanen, RJ ; Hodge, JM ; Williams, LJ (JMNI, 2015-06)
    OBJECTIVE: Both depression and use of antidepressants have been negatively associated with bone mineral density (BMD) but mainly in studies among postmenopausal women. Therefore, the aim of this study was to investigate these relationships in men. METHODS: Between 2006 and 2011, 928 men (aged 24-98 years) from the Geelong Osteoporosis Study completed a comprehensive questionnaire, clinical measurements and had BMD assessments at the forearm, spine, total hip and total body. Major depressive disorder (MDD) was identified using a structured clinical interview (SCID-I/NP). The cross-sectional associations between BMD and both MDD and antidepressant use were analyzed using multivariable linear regression. RESULTS: Of the study population, 84 (9.1%) men had a single MDD episode, 50 (5.4%) had recurrent episodes and 65 (7.0%) were using antidepressants at the time of assessment. Following adjustments, recurrent MDD was associated with lower BMD at the forearm and total body (-6.5%, P=0.033 and -2.5%, P=0.033, respectively compared to men with no history of MDD), while single MDD episodes were associated with higher BMD at the total hip (+3.4%, P=0.030). Antidepressant use was associated with lower BMD only in lower-weight men (<75-110 kg depending on bone site). CONCLUSIONS: Both depression and use of antidepressants should be taken into account as possible risk factors for osteoporosis in men.
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    Carotid artery stenosis and inflammatory biomarkers: the role of inflammation-induced immunological responses affecting the vascular systems
    Wijeratne, T ; Menon, R ; Sales, C ; Karimi, L ; Crewther, S (AME PUBLISHING COMPANY, 2020-10)
    The death, disability and economic cost of stroke are enormous. Indeed, among the 16 million people worldwide who suffer a stroke' annually, nearly six million die, and another five million are left permanently disabled making prevention of stroke one of the most important priorities in healthcare. Currently carotid artery stenosis (CS) or narrowing of the common carotid artery (CCA) or internal carotid artery (ICA) due to atherosclerotic plaque, accounts for 20-30% of all ischemic strokes. Atherosclerosis is now regarded as a chronic inflammatory disease in response to vascular compromise especially from hypertension. This has long been known to lead to inflammation and atherosclerotic plaque formation in the blood vessels. This mini-review aims to highlight the role of inflammation and neuro-immunological processes in carotid artery disease. Various cellular elements of inflammation and advanced imaging techniques have been identified as potential markers of plaque progression. Therapies related to decreasing and modulating immune-responsive inflammation in the carotid vessels have been shown to translate into decreased occurrence of acute neurologic events and improvement of clinical outcomes.
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    Evaluation of an Algorithm to Guide Patients With Type 1 Diabetes Treated With Continuous Subcutaneous Insulin Infusion on How to Respond to Real-Time Continuous Glucose Levels A randomized controlled trial
    Jenkins, AJ ; Krishnamurthy, B ; Best, JD ; Cameron, F ; Colman, PG ; Farish, S ; Hamblin, PS ; O'Connell, MA ; Rodda, C ; Rowley, K ; Teede, H ; O'Neal, DN (AMER DIABETES ASSOC, 2010-06)
    OBJECTIVE: To evaluate an algorithm guiding responses of continuous subcutaneous insulin infusion (CSII)-treated type 1 diabetic patients using real-time continuous glucose monitoring (RT-CGM). RESEARCH DESIGN AND METHODS: Sixty CSII-treated type 1 diabetic participants (aged 13-70 years, including adult and adolescent subgroups, with A1C
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    Depression: An Important Comorbidity With Metabolic Syndrome in a General Population
    Dunbar, JA ; Reddy, P ; Davis-Lameloise, N ; Philpot, B ; Laatikainen, T ; Kilkkinen, A ; Bunker, SJ ; Best, JD ; Vartiainen, E ; Lo, SK ; Janus, ED (AMER DIABETES ASSOC, 2008-12)
    OBJECTIVE: There is a recognized association among depression, diabetes, and cardiovascular disease. The aim of this study was to examine in a sample representative of the general population whether depression, anxiety, and psychological distress are associated with metabolic syndrome and its components. RESEARCH DESIGN AND METHODS: Three cross-sectional surveys including clinical health measures were completed in rural regions of Australia during 2004-2006. A stratified random sample (n = 1,690, response rate 48%) of men and women aged 25-84 years was selected from the electoral roll. Metabolic syndrome was defined by the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, Adult Treatment Panel III (NCEP ATP III), and International Diabetes Federation (IDF) criteria. Anxiety and depression were assessed by the Hospital Anxiety and Depression Scale and psychological distress by the Kessler 10 measure. RESULTS: Metabolic syndrome was associated with depression but not psychological distress or anxiety. Participants with the metabolic syndrome had higher scores for depression (n = 409, mean score 3.41, 95% CI 3.12-3.70) than individuals without the metabolic syndrome (n = 936, mean 2.95, 95% CI 2.76-3.13). This association was also present in 338 participants with the metabolic syndrome and without diabetes (mean score 3.37, 95% CI 3.06-3.68). Large waist circumference and low HDL cholesterol showed significant and independent associations with depression. CONCLUSIONS: Our results show an association between metabolic syndrome and depression in a heterogeneous sample. The presence of depression in individuals with the metabolic syndrome has implications for clinical management.
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    Detailed protocol for optimised expression and purification of functional monomeric human Heat Shock Factor 1
    Polidano, J ; Vankadari, N ; Price, JT ; Wilce, JA (ACADEMIC PRESS INC ELSEVIER SCIENCE, 2020-12)
    Heat Shock Factor 1 (HSF1) is the master regulator of the heat shock response, a universal survival mechanism throughout eukaryotic species used to buffer potentially lethal proteotoxic conditions. HSF1's function in vivo is regulated by several factors, including post translational modifications and elevated temperatures, whereupon it forms trimers to bind with heat shock elements in DNA. Unsurprisingly, HSF1 is also extremely sensitive to elevated temperatures in vitro, which poses specific technical challenges when producing HSF1 using a recombinant expression system. Although there are several useful publications which outline steps taken for HSF1 expression and purification, studies that describe specific strategies and detailed protocols to overcome HSF1 trimerisation and degradation are currently lacking. Herein, we have reported our detailed experimental protocol for the expression and purification of monomeric human HSF1 (HsHSF1) as a major species. We also propose a refined method of inducing HsHSF1 activation in vitro, that we consider more accurately mimics HsHSF1 activation in vivo and is therefore more physiologically relevant.
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    Informed, tailored, and targeted pharmacy support for nurses administering medicines in care homes
    Gilmartin, JF-M (DOVE MEDICAL PRESS LTD, 2015)
    Care home nurses could benefit from more informed, tailored, and targeted pharmacy support when undertaking medicine administration. Pharmacists could use the principles of ethnographic research methods to inform, tailor, and target the medicine administration support they provide. It should be determined if existing pharmacy support has been informed following comprehensive observations of care home medicine administration.
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    Depressive Symptoms Are Associated with Analgesic Use in People with Alzheimer's Disease: Kuopio ALSOVA Study
    Gilmartin, JF-M ; Vaatainen, S ; Tormalehto, S ; Bell, JS ; Lonnroos, E ; Salo, L ; Hallikainen, I ; Martikainen, J ; Koivisto, AM (PUBLIC LIBRARY SCIENCE, 2015-02-17)
    Neuropsychiatric symptoms of Alzheimer's disease (AD) such as depression may be associated with pain, which according to the literature may be inadequately recognized and managed in this population. This study aimed to identify the factors associated with analgesic use in persons with AD; in particular, how AD severity, functional status, neuropsychiatric symptoms of AD, co-morbidities and somatic symptoms are associated with analgesic use. 236 community-dwelling persons with very mild or mild AD at baseline, and their caregivers, were interviewed over five years as part of the prospective ALSOVA study. Generalized Estimating Equations (GEEs) were used to estimate unadjusted and adjusted odds ratios (ORs) for the factors associated with analgesic use over a five year follow-up. The proportion of persons with AD using any analgesic was low (13.6%) at baseline and remained relatively constant during the follow-up (15.3% at Year 5). Over time, the most prevalent analgesic changed from non-steroidal anti-inflammatories (8.1% of persons with AD at Year 1) to acetaminophen (11.1% at Year 5). Depressive symptoms (measured by the Beck Depression Inventory, BDI) were independently associated with analgesic use, after effects of age, gender, education, AD severity, comorbidities and somatic symptoms were taken into account. For every one unit increase in BDI, the odds of analgesic use increased by 4% (OR = 1.04, 95% confidence interval CI = 1.02-1.07). Caregiver depressive symptoms were not statistically significantly associated with analgesic use of the person with AD. Depressive symptoms were significantly associated with analgesic use during the five year follow-up period. Possible explanations warranting investigation are that persons with AD may express depressive symptoms as painful somatic complaints, or untreated pain may cause depressive symptoms. Greater awareness of the association between depressive symptoms and analgesic use may lead to safer and more effective prescribing for these conditions.