Randomised trial of genetic testing and targeted intervention to prevent the development and progression of Paget's disease of bone.

INTRODUCTION: Paget's disease of bone (PDB) frequently presents at an advanced stage with irreversible skeletal damage. Clinical outcomes might be improved by earlier diagnosis and prophylactic treatment. METHODS: We randomised 222 individuals at increased risk of PDB because of pathogenic SQSTM1 variants to receive 5 mg zoledronic acid (ZA) or placebo. The primary outcome was new bone lesions assessed by radionuclide bone scan. Secondary outcomes included change in existing lesions, biochemical markers of bone turnover and skeletal events related to PDB. RESULTS: The median duration of follow-up was 84 months (range 0-127) and 180 participants (81%) completed the study. At baseline, 9 (8.1%) of the ZA group had PDB lesions vs 12 (10.8%) of the placebo group. Two of the placebo group developed new lesions versus none in the ZA group (OR 0.41, 95% CI 0.00 to 3.43, p=0.25). Eight of the placebo group had a poor outcome (lesions which were new, unchanged or progressing) compared with none of the ZA group (OR 0.08, 95% CI 0.00 to 0.42, p=0.003). At the study end, 1 participant in the ZA group had lesions compared with 11 in the placebo group. Biochemical markers of bone turnover were significantly reduced in the ZA group. One participant allocated to placebo required rescue therapy with ZA because of symptomatic disease. The number and severity of adverse events did not differ between groups. CONCLUSIONS: Genetic testing for pathogenic SQSTM1 variants coupled with intervention with ZA is well tolerated and has favourable effects on the progression of early PDB. TRIAL REGISTRATION NUMBER: ISRCTN11616770.

Translating research into action: The design and development of an Indigenous specific suicide intervention skills training program (I-ASIST).

Note: We respectfully refer to Aboriginal and Torres Strait Islander people as Indigenous in this study. OBJECTIVE: To design and develop an Indigenous specific suicide intervention skills program that focuses on education and intervention training as an effective suicide prevention strategy. METHOD: Using a co-designed wrap-around framework, we developed a program in collaboration with >90 communities, stakeholders and service providers across Australia to understand knowledge, awareness and sense of connectedness between at-risk groups and health services or support groups. RESULTS: The I-ASIST training provides participants with the necessary skills and knowledge to apply a suicide intervention model. The framework behind the intervention model provides caregivers the awareness to recognise when someone may be at risk of suicide. It then gives them the skills to connect with a person at risk of suicide and to understand and clarify that risk, steps to keep that person safe for a specific period and then provide them with the resources or links required for further help. The program enables the development of knowledge through interactive strategies through cultural recognition and empowerment of participants. Based on a social-enterprise model, I-ASIST has been translated into a certified program supported by LivingWorks Australia. CONCLUSION: Based on a strengths-based and self-determination model of co-design, this grass roots innovative framework creates suicide safer communities.

Cultural validation of the structured clinical interview for diagnostic and statistical manual of mental disorders in Indigenous Australians.

OBJECTIVE: This study determined the cultural appropriateness of the Structured Clinical Interview for the DSM-IV Axis I Disorders (SCID-I) as an acceptable tool for diagnosing mental illness among Indigenous people. METHODS: De-identified qualitative feedback from participants and psychologists regarding the cultural appropriateness of the SCID-I for Indigenous people using open-ended anonymous questionnaires was gathered. Aboriginal Medial Service staff and Indigenous Support Workers participated in a focus group. RESULTS: A total of 95.6% of participants felt comfortable during the 498 questionnaires completed. Psychologists also provided qualitative feedback for 502 (92.3%) interviews, of whom 40.4% established a good rapport with participants. Of the participants, 77.7% understood the SCID-I questions well, while 72.5% did not require any cultural allowances to reach a clinical diagnosis. CONCLUSION: When administered by a culturally safe trained psychologist, SCID-I is well tolerated in this group.

Identification of a novel FGFRL1 MicroRNA target site polymorphism for bone mineral density in meta-analyses of genome-wide association studies.

MicroRNAs (miRNAs) are critical post-transcriptional regulators. Based on a previous genome-wide association (GWA) scan, we conducted a polymorphism in microRNA target sites (poly-miRTS)-centric multistage meta-analysis for lumbar spine (LS)-, total hip (HIP)- and femoral neck (FN)-bone mineral density (BMD). In stage I, 41 102 poly-miRTSs were meta-analyzed in seven cohorts with a genome-wide significance (GWS) α = 0.05/41 102 = 1.22 × 10(-6). By applying α = 5 × 10(-5) (suggestive significance), 11 poly-miRTSs were selected, with FGFRL1 rs4647940 and PRR5 rs3213550 as top signals for FN-BMD (P = 7.67 × 10(-6) and 1.58 × 10(-5)) in gender-combined sample. In stage II in silico replication (two cohorts), FGFRL1 rs4647940 was the only signal marginally replicated for FN-BMD (P = 5.08 × 10(-3)) at α = 0.10/11 = 9.09 × 10(-3). PRR5 rs3213550 was also selected based on biological significance. In stage III de novo genotyping replication (two cohorts), FGFRL1 rs4647940 was the only signal significantly replicated for FN-BMD (P = 7.55 × 10(-6)) at α = 0.05/2 = 0.025 in gender-combined sample. Aggregating three stages, FGFRL1 rs4647940 was the single stage I-discovered and stages II- and III-replicated signal attaining GWS for FN-BMD (P = 8.87 × 10(-12)). Dual-luciferase reporter assays demonstrated that FGFRL1 3' untranslated region harboring rs4647940 appears to be hsa-miR-140-5p's target site. In a zebrafish microinjection experiment, dre-miR-140-5p is shown to exert a dramatic impact on craniofacial skeleton formation. Taken together, we provided functional evidence for a novel FGFRL1 poly-miRTS rs4647940 in a previously known 4p16.3 locus, and experimental and clinical genetics studies have shown both FGFRL1 and hsa-miR-140-5p are important for bone formation.

An Australian Indigenous community-led suicide intervention skills training program: community consultation findings.

BACKGROUND: Little is known of the appropriateness of existing gatekeeper suicide prevention programs for Indigenous communities. Despite the high rates of Indigenous suicide in Australia, especially among Indigenous youth, it is unclear how effective existing suicide prevention programs are in providing appropriate management of Indigenous people at risk of suicide. METHODS: In-depth, semi-structured interviews and focus groups were conducted with Indigenous communities in rural and regional areas of Southern Queensland. Thematic analysis was performed on the gathered information. RESULTS: Existing programs were time-intensive and included content irrelevant to Indigenous people. There was inconsistency in the content and delivery of gatekeeper training. Programs were also not sustainable for rural and regional Indigenous communities. CONCLUSIONS: Appropriate programs should be practical, relevant, and sustainable across all Indigenous communities, with a focus on the social, emotional, cultural and spiritual underpinnings of community wellbeing. Programs need to be developed in thorough consultation with Indigenous communities. Indigenous-led suicide intervention training programs are needed to mitigate the increasing rates of suicide experienced by Indigenous peoples living in rural and remote locations.

Multistage genome-wide association meta-analyses identified two new loci for bone mineral density.

Aiming to identify novel genetic variants and to confirm previously identified genetic variants associated with bone mineral density (BMD), we conducted a three-stage genome-wide association (GWA) meta-analysis in 27 061 study subjects. Stage 1 meta-analyzed seven GWA samples and 11 140 subjects for BMDs at the lumbar spine, hip and femoral neck, followed by a Stage 2 in silico replication of 33 SNPs in 9258 subjects, and by a Stage 3 de novo validation of three SNPs in 6663 subjects. Combining evidence from all the stages, we have identified two novel loci that have not been reported previously at the genome-wide significance (GWS; 5.0 × 10(-8)) level: 14q24.2 (rs227425, P-value 3.98 × 10(-13), SMOC1) in the combined sample of males and females and 21q22.13 (rs170183, P-value 4.15 × 10(-9), CLDN14) in the female-specific sample. The two newly identified SNPs were also significant in the GEnetic Factors for OSteoporosis consortium (GEFOS, n = 32 960) summary results. We have also independently confirmed 13 previously reported loci at the GWS level: 1p36.12 (ZBTB40), 1p31.3 (GPR177), 4p16.3 (FGFRL1), 4q22.1 (MEPE), 5q14.3 (MEF2C), 6q25.1 (C6orf97, ESR1), 7q21.3 (FLJ42280, SHFM1), 7q31.31 (FAM3C, WNT16), 8q24.12 (TNFRSF11B), 11p15.3 (SOX6), 11q13.4 (LRP5), 13q14.11 (AKAP11) and 16q24 (FOXL1). Gene expression analysis in osteogenic cells implied potential functional association of the two candidate genes (SMOC1 and CLDN14) in bone metabolism. Our findings independently confirm previously identified biological pathways underlying bone metabolism and contribute to the discovery of novel pathways, thus providing valuable insights into the intervention and treatment of osteoporosis.

The need for a culturally-tailored gatekeeper training intervention program in preventing suicide among Indigenous peoples: a systematic review.

BACKGROUND: Suicide is a leading cause of death among Indigenous youth worldwide. The aim of this literature review was to determine the cultural appropriateness and identify evidence for the effectiveness of current gatekeeper suicide prevention training programs within the international Indigenous community. METHOD: Using a systematic strategy, relevant databases and targeted resources were searched using the following terms: 'suicide', 'gatekeeper', 'training', 'suicide prevention training', 'suicide intervention training' and 'Indigenous'. Other internationally relevant descriptors for the keyword "Indigenous" (e.g. "Maori", "First Nations", "Native American", "Inuit", "Metis" and "Aboriginal") were also used. RESULTS: Six articles, comprising five studies, met criteria for inclusion; two Australian, two from USA and one Canadian. While pre and post follow up studies reported positive outcomes, this was not confirmed in the single randomised controlled trial identified. However, the randomised controlled trial may have been underpowered and contained participants who were at higher risk of suicide pre-training. CONCLUSION: Uncontrolled evidence suggests that gatekeeper training may be a promising suicide intervention in Indigenous communities but needs to be culturally tailored to the target population. Further RCT evidence is required.

Determinants of rural practice: positive interaction between rural background and rural undergraduate training.

OBJECTIVE: To determine the role of rural background and years of rural clinical school training on subsequent rural clinical practice. DESIGN, SETTING AND PARTICIPANTS: Retrospective cohort study of University of Queensland (UQ) medical graduates who graduated during the period 2002-2011 (contacted via internet, telephone and mail, using information obtained from UQ, the Australian Health Practitioner Regulation Agency, and telephone directory and internet searches) who completed an online or hard copy questionnaire during the period December 2012 to October 2013. MAIN OUTCOME MEASURE: Current clinical practice in a rural location. RESULTS: Of 1572 graduates to whom the questionnaire was sent, 754 (48.0%) completed the questionnaire. Of the respondents, 236 (31.3%) had a rural background and 276 (36.6%) had attended the University of Queensland Rural Clinical School (UQRCS). Clinical practice location was rural for 18.8% (90/478) of UQ metropolitan clinical school attendees and 41.7% (115/276) of UQRCS attendees (P < 0.001). In the multivariate model with main effects, independent predictors of rural practice were (OR [95% CI]): UQRCS attendance for 1 year (1.84 [1.21-2.82]) or 2 years (2.71 [1.65-4.45]), rural background (2.30 [1.57-3.36]), partner with rural background (3.08 [1.96-4.84]), being single (1.98 [1.28-3.06]) and having a bonded scholarship (2.34 [1.37-3.98]). In the model with interaction between UQRCS attendance and rural background, independent predictors of rural practice were rural background and UQRCS attendance for 1 year (4.44 [2.38-8.29]) or 2 years (7.09 [3.57-14.10]), partner with rural background (3.14 [1.99-4.96]), being single (2.02 [1.30-3.12]) and bonded scholarship (2.27 [1.32-3.90]). The effects of rural background and UQRCS attendance were duration dependent. CONCLUSIONS: This study strengthens evidence that, after adjusting for multiple confounders, a number of exposures are independent predictors of rural medical practice. The strong positive interaction between rural background and rural clinical school exposure, and the duration-dependent relationships, could help inform policy changes aimed at enhancing the efficacy of Australia's rural clinical school program.

A systematic review: Identifying the prevalence rates of psychiatric disorder in Australia's Indigenous populations.

OBJECTIVE: This review aimed to draw on published literature to identify the prevalence rates of psychiatric disorders in Australia's Indigenous populations, Aboriginal and Torres Strait Islander peoples. METHOD: A systematic review following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) model was conducted using the following electronic databases: PubMed, Scopus, Web of Science, MEDLINE, PsycINFO, PsycARTICLES, and Informit Indigenous and Health Collections. Studies were included for analysis if they were empirical quantitative studies reporting prevalence rates for any psychiatric disorder in Indigenous people. RESULTS: Of the 1584 papers extracted by the search strategy, 17 articles met the eligibility criteria and were reviewed in detail. Methodology, sampling strategy and study design varied greatly across these 17 studies. Prevalence rates varied by disorder and are as follows: major depressive disorder (4.3-51%); mood disorders (7.7-43.1%); post-traumatic stress disorder (14.2-55.2%); anxiety disorders (17.2-58.6%); substance dependence (5.9%-66.2%); alcohol dependence (21.4-55.4%); and psychotic disorders (1.68-25%). While the number of studies on community-based Indigenous populations was limited, available evidence suggested that prevalence rates are higher in prison populations compared with community-based studies. CONCLUSIONS: It was identified that there is limited evidence on the occurrence of psychiatric disorders for Indigenous people in the general community. More research in this area is essential to provide accurate and reliable estimates and to provide a baseline for evaluating the effectiveness of programs aimed at reducing the high mental health burden experienced by Indigenous Australians. Future research needs to ensure that standardised and validated methods are used to accurately estimate the prevalence of psychiatric disorders among Indigenous Australians.

WNT16 influences bone mineral density, cortical bone thickness, bone strength, and osteoporotic fracture risk.

We aimed to identify genetic variants associated with cortical bone thickness (CBT) and bone mineral density (BMD) by performing two separate genome-wide association study (GWAS) meta-analyses for CBT in 3 cohorts comprising 5,878 European subjects and for BMD in 5 cohorts comprising 5,672 individuals. We then assessed selected single-nucleotide polymorphisms (SNPs) for osteoporotic fracture in 2,023 cases and 3,740 controls. Association with CBT and forearm BMD was tested for ∼2.5 million SNPs in each cohort separately, and results were meta-analyzed using fixed effect meta-analysis. We identified a missense SNP (Thr>Ile; rs2707466) located in the WNT16 gene (7q31), associated with CBT (effect size of -0.11 standard deviations [SD] per C allele, P = 6.2 × 10(-9)). This SNP, as well as another nonsynonymous SNP rs2908004 (Gly>Arg), also had genome-wide significant association with forearm BMD (-0.14 SD per C allele, P = 2.3 × 10(-12), and -0.16 SD per G allele, P = 1.2 × 10(-15), respectively). Four genome-wide significant SNPs arising from BMD meta-analysis were tested for association with forearm fracture. SNP rs7776725 in FAM3C, a gene adjacent to WNT16, was associated with a genome-wide significant increased risk of forearm fracture (OR = 1.33, P = 7.3 × 10(-9)), with genome-wide suggestive signals from the two missense variants in WNT16 (rs2908004: OR = 1.22, P = 4.9 × 10(-6) and rs2707466: OR = 1.22, P = 7.2 × 10(-6)). We next generated a homozygous mouse with targeted disruption of Wnt16. Female Wnt16(-/-) mice had 27% (P<0.001) thinner cortical bones at the femur midshaft, and bone strength measures were reduced between 43%-61% (6.5 × 10(-13)

Total and appendicular lean mass reference ranges for Australian men and women: the Geelong osteoporosis study.

The aim of this study was to develop reference ranges for total and appendicular lean mass measured using dual-energy X-ray absorptiometry (DXA) from a randomly selected population-based sample of men and women residing in southeastern Australia. Men (n = 1,411) and women (n = 960) aged 20-93 years, enrolled in the Geelong Osteoporosis Study, were randomly selected from the Barwon Statistical Division using the electoral roll as a sampling frame in 2001-2006 (67 % participation) and 1993-1997 (77 % participation), respectively. Using DXA (Lunar DPX-L or Prodigy Pro) at baseline for men and at the 10-year follow-up for women (2004-2008), total and appendicular lean mass were measured. Means and standard deviations for each lean mass measure (absolute and relative to height squared) were generated for each age decade, and cutpoints equivalent to T scores of -2.0 and -1.0 were calculated using data from young adult men and women aged 20-39 years. Young adult reference data were derived from 374 men and 308 women. Cutpoints for relative appendicular lean mass equal to T scores of -2.0 and -1.0 were 6.94 and 7.87 kg/m(2) for men and 5.30 and 6.07 kg/m(2) for women. The proportions of men and women aged ≥80 years with a T score less than -2.0 were 16.0 and 6.2 %, respectively. These reference ranges may be useful for identifying lean mass deficits in the assessment of muscle wasting and sarcopenia.

Genome-wide association study using extreme truncate selection identifies novel genes affecting bone mineral density and fracture risk.

Osteoporotic fracture is a major cause of morbidity and mortality worldwide. Low bone mineral density (BMD) is a major predisposing factor to fracture and is known to be highly heritable. Site-, gender-, and age-specific genetic effects on BMD are thought to be significant, but have largely not been considered in the design of genome-wide association studies (GWAS) of BMD to date. We report here a GWAS using a novel study design focusing on women of a specific age (postmenopausal women, age 55-85 years), with either extreme high or low hip BMD (age- and gender-adjusted BMD z-scores of +1.5 to +4.0, n = 1055, or -4.0 to -1.5, n = 900), with replication in cohorts of women drawn from the general population (n = 20,898). The study replicates 21 of 26 known BMD-associated genes. Additionally, we report suggestive association of a further six new genetic associations in or around the genes CLCN7, GALNT3, IBSP, LTBP3, RSPO3, and SOX4, with replication in two independent datasets. A novel mouse model with a loss-of-function mutation in GALNT3 is also reported, which has high bone mass, supporting the involvement of this gene in BMD determination. In addition to identifying further genes associated with BMD, this study confirms the efficiency of extreme-truncate selection designs for quantitative trait association studies.

A novel serogenetic approach determines the community prevalence of celiac disease and informs improved diagnostic pathways.

BACKGROUND: Changing perspectives on the natural history of celiac disease (CD), new serology and genetic tests, and amended histological criteria for diagnosis cast doubt on past prevalence estimates for CD. We set out to establish a more accurate prevalence estimate for CD using a novel serogenetic approach. METHODS: The human leukocyte antigen (HLA)-DQ genotype was determined in 356 patients with 'biopsy-confirmed' CD, and in two age-stratified, randomly selected community cohorts of 1,390 women and 1,158 men. Sera were screened for CD-specific serology. RESULTS: Only five 'biopsy-confirmed' patients with CD did not possess the susceptibility alleles HLA-DQ2.5, DQ8, or DQ2.2, and four of these were misdiagnoses. HLA-DQ2.5, DQ8, or DQ2.2 was present in 56% of all women and men in the community cohorts. Transglutaminase (TG)-2 IgA and composite TG2/deamidated gliadin peptide (DGP) IgA/IgG were abnormal in 4.6% and 5.6%, respectively, of the community women and 6.9% and 6.9%, respectively, of the community men, but in the screen-positive group, only 71% and 75%, respectively, of women and 65% and 63%, respectively, of men possessed HLA-DQ2.5, DQ8, or DQ2.2. Medical review was possible for 41% of seropositive women and 50% of seropositive men, and led to biopsy-confirmed CD in 10 women (0.7%) and 6 men (0.5%), but based on relative risk for HLA-DQ2.5, DQ8, or DQ2.2 in all TG2 IgA or TG2/DGP IgA/IgG screen-positive subjects, CD affected 1.3% or 1.9%, respectively, of females and 1.3% or 1.2%, respectively, of men. Serogenetic data from these community cohorts indicated that testing screen positives for HLA-DQ, or carrying out HLA-DQ and further serology, could have reduced unnecessary gastroscopies due to false-positive serology by at least 40% and by over 70%, respectively. CONCLUSIONS: Screening with TG2 IgA serology and requiring biopsy confirmation caused the community prevalence of CD to be substantially underestimated. Testing for HLA-DQ genes and confirmatory serology could reduce the numbers of unnecessary gastroscopies.

Is high dose vitamin D harmful?

With the potential to minimize the risk of many chronic diseases and the apparent biochemical safety of ingesting doses of oral vitamin D several-fold higher than the current recommended intakes, recent research has focussed on supplementing individuals with intermittent, high-dose vitamin D. However, two recent randomized controlled trials (RCTs) both using annual high-dose vitamin D reported an increase, rather than a decrease, in the primary outcome of fractures. This review summarises the results from studies that have used intermittent, high doses of vitamin D, with particular attention to those finding evidence of adverse effects. Results from observational, population-based studies with evidence of a U- or J-shaped curve are also presented as these findings suggest an increased risk in those with the highest serum 25D levels. Speculative mechanisms are discussed and biochemical results from studies using high-dose vitamin D are also presented. Emerging evidence from both observational studies and RCTs suggests there should be a degree of caution about recommending high serum 25D concentrations for the entire population. Furthermore, benefit of the higher doses commonly used in clinical practice on falls risk reduction needs to be demonstrated. The safety of loading doses of vitamin D should be demonstrated before these regimens become recommended as routine clinical practice. The current dilemma of defining vitamin D insufficiency and identifying safe and efficacious repletion regimens needs to be resolved.

Social determinants of bone densitometry uptake for osteoporosis risk in patients aged 50yr and older: a systematic review.

The World Health Organization identifies that osteoporosis is one of the leading health problems in the Western world. An increased risk of fragility fracture is observed in more socially disadvantaged individuals in most Western countries. Dual-energy X-ray absorptiometry (DXA) is currently the procedure of choice to diagnose osteoporosis and assess fracture risk. We systematically reviewed the literature regarding social determinants of DXA utilization for osteoporosis detection in patients aged 50yr and older using a computer-aided search of MEDLINE, EMBASE, CINAHL, and PsychINFO from January 1994 to December 2010. Five cross-sectional studies, incorporating 16 separate analyses, were identified for inclusion in this review. The best evidence analysis identified limited evidence for a positive association between either income or education with DXA utilization; furthermore, the best evidence analysis found no evidence for an association between either marital status or working status and DXA utilization. Further research is required to identify whether a relationship exists and elucidate reasons for disparities in DXA utilization between different social groups, such as choice and referral processes, as a necessary precursor in identifying modifiable determinants and appropriate strategies to promote preventive screening to identify fracture risk.

Cross-sectional analysis of association between socioeconomic status and utilization of primary total hip joint replacements 2006-7: Australian Orthopaedic Association National Joint Replacement Registry.

BACKGROUND: The utilization of total hip replacement (THR) surgery is rapidly increasing, however few data examine whether these procedures are associated with socioeconomic status (SES) within Australia. This study examined primary THR across SES for both genders for the Barwon Statistical Division (BSD) of Victoria, Australia. METHODS: Using the Australian Orthopaedic Association National Joint Replacement Registry data for 2006-7, primary THR with a diagnosis of osteoarthritis (OA) among residents of the BSD was ascertained. The Index of Relative Socioeconomic Disadvantage was used to measure SES; determined by matching residential addresses with Australian Bureau of Statistics census data. The data were categorised into quintiles; quintile 1 indicating the most disadvantaged. Age- and sex-specific rates of primary THR per 1,000 person years were reported for 10-year age bands using the total population at risk. RESULTS: Females accounted for 46.9% of the 642 primary THR performed during 2006-7. THR utilization per 1,000 person years was 1.9 for males and 1.5 for females. The highest utilization of primary THR was observed in those aged 70-79 years (males 6.1, and females 5.4 per 1,000 person years). Overall, the U-shaped pattern of THR across SES gave the appearance of bimodality for both males and females, whereby rates were greater for both the most disadvantaged and least disadvantaged groups. CONCLUSIONS: Further work on a larger scale is required to determine whether relationships between SES and THR utilization for the diagnosis of OA is attributable to lifestyle factors related to SES, or alternatively reflects geographic and health system biases. Identifying contributing factors associated with SES may enhance resource planning and enable more effective and focussed preventive strategies for hip OA.

The Path to Eldership: Results From a Contemporary Indigenous Australian Community.

BACKGROUND AND OBJECTIVES: Traditionally, Elders have held a unique social position within Indigenous Australian communities. This study aimed to identify the characteristics of Indigenous Elders that distinguish them from other people in their community. RESEARCH DESIGN AND METHODS: Using a community-based participatory research approach, the study was conducted in a regional Indigenous community in Southeast Queensland. The design and data collection methods were informed through a community forum, known as a "Yarning Circle." One-on-one semistructured interviews and focus groups with community members were carried out by Indigenous researchers. Data were analyzed in NVivo software, using thematic analysis (TA), with themes derived directly from data. RESULTS: Fifty individuals participated in the study. The participants' median age was 45 years (range 18-76 years) and 31 (62%) were female. TA identified 3 overarching themes related to Elders' attributes: (a) distinguishing characteristics of Elders (subthemes of respect, leadership, reciprocity, life experience, approachability, connection to traditional culture, and transmitting knowledge through generations); (b) how one becomes an Elder (earnt eldership, permanency of eldership, mentors and role models, age); and (c) threats to Elders' influence (intergenerational gap, community disconnect, and cultural trauma). DISCUSSION AND IMPLICATIONS: Our results build a greater understanding of the contemporary role of Indigenous Australian Elders, which will inform the development of future interventions directed at strengthening Elders' role in their communities.

Fracture risk score and absolute risk of fracture.

PURPOSE: To report the 5- and 10-year absolute risk of fracture associated with the previously reported fracture risk (FRISK) score. MATERIALS AND METHODS: All participants gave written, informed consent, and the Barwon Health Human Research Ethics Committee approved the study. An age-stratified population-based sample of women aged 60 years and older (n = 600) was recruited during 1994-1996. FRISK scores of 0-10 incorporating bone mineral density (BMD) at two sites (hip and spine), falls scores in the previous 12 months of 1-4, weight, and number of fractures as an adult were calculated. Fractures of the hip, spine, humerus, and wrist were ascertained during a median follow-up period of 9.6 years (interquartile range, 6.6-10.5). The cumulative probability of fracture at 5 and 10 years after baseline measurements was calculated by using actuarial methods. The utility of this model was compared with other FRISK algorithms, including the World Health Organization FRISK assessment tool FRAX designed for United Kingdom and that designed for the United States and the Garvan nomogram (Australia). RESULTS: This study supplies the 5- and 10-year absolute risk of fracture associated with all levels of the FRISK score. While there are modest differences in absolute risk of fracture seen for different numbers of prior fractures, the more marked differences occur across the different categories of falls scores and different categories of BMD. The receiver operating characteristic curves showed no significant difference in area under the curve for all four absolute risk of fracture algorithms. CONCLUSION: Absolute risk of fracture can be determined by using readily obtainable clinical information that may aid treatment decisions.

Habitual physical activity and the risk for depressive and anxiety disorders among older men and women.

BACKGROUND: Regular physical activity is generally associated with psychological well-being, although there are relatively few prospective studies in older adults. We investigated habitual physical activity as a risk factor for de novo depressive and anxiety disorders in older men and women from the general population. METHODS: In this nested case-control study, subjects aged 60 years or more were identified from randomly selected cohorts being followed prospectively in the Geelong Osteoporosis Study. Cases were individuals with incident depressive or anxiety disorders, diagnosed using the Structured Clinical Interview for DSM-IV-TR (SCID-I/NP); controls had no history of these disorders. Habitual physical activity, measured using a validated questionnaire, and other exposures were documented at baseline, approximately four years prior to psychiatric interviews. Those with depressive or anxiety disorders that pre-dated baseline were excluded. RESULTS: Of 547 eligible subjects, 14 developed de novo depressive or anxiety disorders and were classified as cases; 533 controls remained free of disease. Physical activity was protective against the likelihood of depressive and anxiety disorders; OR = 0.55 (95% CI 0.32-0.94), p = 0.03; each standard deviation increase in the transformed physical activity score was associated with an approximate halving in the likelihood of developing depressive or anxiety disorders. Leisure-time physical activity contributed substantially to the overall physical activity score. Age, gender, smoking, alcohol consumption, weight and socioeconomic status did not substantially confound the association. CONCLUSION: This study provides evidence consistent with the notion that higher levels of habitual physical activity are protective against the subsequent risk of development of de novo depressive and anxiety disorders.

Association of high-sensitivity C-reactive protein with de novo major depression.

BACKGROUND: Although there is cross-sectional evidence that changes in the immune system contribute to the pathophysiology of depression, longitudinal data capable of elucidating cause and effect relationships are lacking. AIMS: We aimed to determine whether subclinical systemic inflammation, as measured by serum high-sensitivity C-reactive protein (hsCRP) concentration, is associated with an increased risk of de novo major depressive disorder. METHOD: Major depressive disorder was diagnosed using a clinical interview (SCID-I/NP). This is a retrospective cohort study; from a population-based sample of 1494 randomly selected women recruited at baseline during the period 1994-7, 822 were followed for a decade and provided measures of both exposure and outcome. Of these women, 644 (aged 20-84 years) had no prior history of depression at baseline and were eligible for analysis. RESULTS: During 5827 person-years of follow-up, 48 cases of de novo major depressive disorder were identified. The hazard ratio (HR) for depression increased by 44% for each standard deviation increase in log-transformed hsCRP (ln-hsCRP) (HR = 1.44, 95% CI 1.04-1.99), after adjusting for weight, smoking and use of non-steroidal anti-inflammatory drugs. Further adjustment for other lifestyle factors, medications and comorbidity failed to explain the observed increased risk for depression. CONCLUSIONS: Serum hsCRP is an independent risk marker for de novo major depressive disorder in women. This supports an aetiological role for inflammatory activity in the pathophysiology of depression.