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St Leonards, Australia

Sambrook P.N.,University of Sydney | Sambrook P.N.,Institute of Bone and Joint Research | Cameron I.D.,University of Sydney | Chen J.S.,University of Sydney | And 11 more authors.
Osteoporosis International | Year: 2012

Summary: Sunlight exposure by improving vitamin D status could be a simple public health strategy in reducing falls among frail elder people. In a randomised controlled trial, adherence to sunlight exposure was low (median adherence, 26%) and no effect of increased UV exposure on falls risk was observed (incidence rate ratio (IRR) 1.06, P = 0.73). Introduction: This study aimed to determine whether increased sunlight exposure was effective to improve vitamin D status and reduce falls in the elderly. Methods: In a cluster randomised controlled trial (NCT00322166 at ClinicalTrials.gov), 602 residents aged 70 or more (mean age, 86.4 years; 71% female) were recruited from 51 aged care facilities in Northern Sydney, Australia. Participants were randomised by facility to receive either increased sunlight exposure (additional 30-40 min/day in the early morning) with (UV+) or without (UV) calcium supplementation (600 mg/day) or neither (control) for a year. The co-primary endpoints were change in serum 25 hydroxy vitamin D (25OHD) and falls incidence after 12 months. Results: Adherence to sunlight exposure was low (median adherence, 26%; IQR, 7%-45%). Serum 25OHD levels were low at baseline (median, 32.9 nmol/L) and increased only slightly depending on the number of sunlight sessions attended over 12 months (P = 0.04). During the study, 327 falls occurred in 111 (54%) subjects in the control group, 326 falls in 111 (58%) subjects in the UV only group and 335 falls in 108 (52%) subjects in the UV+ group. By intention-to-treat analysis, there was no significant effect of increased UV exposure on falls risk (IRR, 1.06; 95% CI, 0.76-1.48; P = 0.73). However, in 66 participants who attended ≥130 sessions per year (adherence, ≥50% of 260 sessions-five per week), falls were significantly reduced (IRR, 0.52; 95% CI, 0.31-0.88; P = 0.01) compared with the control group. Conclusions: Increased sunlight exposure did not reduce vitamin D deficiency or falls risk in frail older people. This public health strategy was not effective most likely due to poor adherence to the intervention. © 2011 International Osteoporosis Foundation and National Osteoporosis Foundation. Source

Wilson N.M.,Kolling Institute of Medical Research | Wilson N.M.,University of Sydney | Wilson N.M.,Institute of Bone and Joint Research | Hilmer S.N.,University of Sydney | And 11 more authors.
Journal of the American Geriatrics Society | Year: 2011

Objectives: To evaluate the association between the Drug Burden Index (DBI), a measure of a person's total exposure to anticholinergic and sedative medications that includes principles of dose-response and maximal effect and is associated with impaired physical function in community-dwelling older people, and falls in residents of residential aged care facilities (RACFs). Design: Data were drawn from participants in a randomized controlled trial that investigated falls and fractures. Setting: RACFs in Sydney, Australia. Participants: Study participants (N=602; 70.9% female) were recruited from 51 RACFs. Mean age was 85.7 ± 6.4, and mean DBI was 0.60 ± 0.66. Measurements: Medication history was obtained on each participant. Drugs were classified as anticholinergic or sedative and a DBI was calculated. Falls were measured over a 12-month period. Comorbidity, cognitive impairment (Mini-Mental State Examination) and depression (Geriatric Depression Scale) were determined. Results: There were 998 falls in 330 individuals during a follow-up period of 574.2 person-years, equating to an average rate of 1.74 falls per person-year. The univariate negative binomial regression model for falls showed incidence rate ratios of 1.69 (95% confidence interval (CI)=1.22-2.34) for low DBI (<1) and 2.11 (95% CI=1.47-3.04) for high DBI (≥1) when compared with those who had a DBI of 0. After adjusting for age, sex, history of falling, cognitive impairment, depression, use of a walking aid, comorbidities, polypharmacy, and incontinence, incident rate ratios of 1.61 (95% CI=1.17-2.23) for low DBI and 1.90 (95% CI=1.30-2.78) for high DBI were obtained. Conclusion: DBI is significantly and independently associated with falls in older people living in RACFs. Interventional studies designed for this population are needed to determine whether reducing DBI, through dose reduction or cessation of anticholinergic and sedative drugs, can prevent falls. © 2011, The American Geriatrics Society. Source

Brown S.,Keele University | Melrose J.,Institute of Bone and Joint Research | Caterson B.,University of Cardiff | Roughley P.,McGill University | And 2 more authors.
European Spine Journal | Year: 2012

Purpose: Proteoglycans are important to the functioning of the intervertebral disc. In addition to aggrecan there are the small leucine-rich proteoglycans (SLRPs). These are less common but in other locations their functions include collagen organisation, sequestering growth factors and stimulating inflammation. We have performed a comparative analysis of the SLRP core protein species present in intervertebral discs with various pathologies. Methods: Eighteen intervertebral discs from patients with scoliosis (n = 7, 19-53 years), degenerative disc disease (n = 6, 35-51 years) and herniations (n = 5, 33-58 years) were used in this study. Proteoglycans were dissociatively extracted from disc tissues and the SLRPs (biglycan, decorin, fibromodulin, keratocan and lumican) assessed by Western blotting following deglycosylation with chondro-itinase ABC and keratanase. Results: Intact SLRP core proteins and a number of core protein fragments were identified in most of the discs examined. Biglycan and fibromodulin were the most extensively fragmented. Keratocan generally occurred as two bands, one representing the intact core protein, the other a smaller fragment. The intact core protein of lumican was detected in all samples with fragmentation evident in only one of the older scoliotic discs. Decorin was less obvious in the disc samples and showed little fragmentation. Conclusion: In this cohort of pathological intervertebral discs, fragmentation of certain SLRP core proteins was common, indicating that some SLRPs are extensively processed during the pathological process. Identification of specific SLRP fragments which correlate with disc pathology may not only help understand their aetiopatho-geneses, but also provide biomarkers which can be used to monitor disease progression or to identify particular disc disorders. © Springer-Verlag 2012. Source

Goldschlager T.,Monash Immunology and Stem Cell Laboratories | Goldschlager T.,Monash University | Goldschlager T.,Monash Medical Center | Goldschlager T.,Gribbles Pathology Pty Ltd | And 6 more authors.
Neurosurgery | Year: 2011

BACKGROUND: Rapid, reliable fusion is the goal in anterior cervical diskectomy and fusion. Iliac crest autograft has a high rate of donor-site morbidity. Alternatives such as bone graft substitutes lack osteoinductivity, and recombinant bone morphogenetic proteins risk life-threatening complications. Both allogeneic mesenchymal precursor cells (MPCs) and amnion derived epithelial cells (AECs) have osteogenic potential. OBJECTIVE: To compare for the first time the capacity of MPCs and AECs to promote osteogenesis in an ovine model. METHODS: Five groups of 2-year-old ewes were subjected to C3-4 anterior cervical diskectomy and fusion with a Fidji interbody cage packed with iliac crest autograft alone (group A; n = 6), hydroxyapatite-tricalcium phosphate Mastergraft granules (HA/TCP) alone (group B; n = 6), HA/TCP containing 5 million MPCs (group C; n = 6), or HA/TCP containing 5 million AECs (group D; n = 5); group E was made up of age-matched nonoperative controls (n = 6). At 3 months, animals were euthanized and quantitative multislice computed tomography, functional radiography, biomechanics, histology, and histomorphometry were performed. RESULTS: No procedure- or cell-related adverse events were observed. There was significantly more fusion in the MPC group (C) than in group A, B, or D. Computed tomography scan at 3 months revealed that 5 of 6 MPC-treated animals (83%) had continuous bony bridging compared with 0 of 5 AEC-treated and only 1 of 6 autograft- and 2 of 6 HA/TCP-treated animals (P = .01). CONCLUSION: Implantation of allogeneic MPCs in combination with HA/TCP within an interbody spacer facilitates interbody fusion after diskectomy. The earlier, more robust fusion observed with MPCs relative to autograft and HA/TCP bone substitute indicates that this approach may offer a therapeutic benefit. © 2011 by the 2011 Congress of Neurological surgeons. Source

Shand A.W.,University of Sydney | Algert C.S.,University of Sydney | March L.,Institute of Bone and Joint Research | Roberts C.L.,University of Sydney
Annals of the Rheumatic Diseases | Year: 2013

Background: Systemic lupus erythematosus (SLE) is associated with adverse pregnancy outcomes overall. Objective To examine the outcomes for women with SLE in a pregnancy subsequent to a fi rst birth with an adverse outcome. Methods: A population-based cohort study was carried out of 794 577 deliveries to 532 612 women giving birth in New South Wales, Australia from 2001 to 2009. Data were obtained from longitudinally linked birth records and hospital records. Results: 675 women had a diagnosis of SLE in the study period (prevalence 127 per 100 000 childbearing women). Of 177 women who had a fi rst nulliparous birth and subsequent pregnancy, 10 (5.6%) had a perinatal death in the fi rst pregnancy, and of these women, 9 (90%) had a baby discharged home alive in the second pregnancy. Of the 167 women whose fi rst-birth infants survived, second pregnancy outcomes included: 18 (11%) admission for spontaneous abortion, 1 perinatal death (0.6%) and 148 (89%) infants discharged home. Two women had a thromboembolic event in their fi rst pregnancy but had no thromboembolic event in the second. Two women had thromboembolic events in second pregnancies only. Conclusion Women with SLE are at high risk of adverse pregnancy outcomes. However, those who have a perinatal death in their fi rst pregnancy can expect a live birth for a subsequent pregnancy. Source

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