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1.
J Bone Miner Res ; 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32176830

RESUMO

OBJECTIVES: Mutations in SQSTM1 are strongly associated with Paget's disease of bone (PDB) but little is known about the clinical characteristics of those with early disease. METHODS: Radionuclide bone scans, biochemical markers of bone turnover and clinical characteristics were analysed in SQSTM1 mutation carriers who took part in the Zoledronic acid in the Prevention of Paget's disease (ZiPP) study. RESULTS: We studied 222 individuals of whom 54.9% were female with average (± sem) age of 50.1± 0.6 years. Twelve SQSTM1 mutations were observed, including p.Pro392Leu which was present in 141/222 (63.5%) subjects. Bone scan examination revealed evidence of PDB in 20 subjects (9.0%) of which 9 (50%) had a single affected site. Participants with lesions were older than those without lesions but the difference was not significant (53.6 ± 9.1 vs. 49.8 ± 8.9, p=0.07). The mean age of participants with lesions was not significantly different from the age at which their parents were diagnosed with PDB (55 years vs. 59 years, p=0.25). All individuals with lesions were asymptomatic. Serum concentrations of total alkaline phosphatase (ALP) normalised to the upper limit of normal in each centre were higher in those with lesions (0.75 ± 0.69 vs 0.42 ± 0.29; p<0.0001). Similar findings were observed for other biochemical markers of bone turnover but the sensitivity of ALP and other markers in detecting lesions was poor. CONCLUSIONS: Asymptomatic PDB is present in about 9% of SQSTM1 mutation carriers by the fifth decade. Further follow up of this cohort will provide important information on the natural history of early PDB and its response to treatment. This article is protected by copyright. All rights reserved.

2.
BMJ Open ; 9(9): e030689, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31488492

RESUMO

INTRODUCTION: Paget's disease of bone (PDB) is characterised by increased and disorganised bone remodelling affecting one or more skeletal sites. Complications include bone pain, deformity, deafness and pathological fractures. Mutations in sequestosome-1 (SQSTM1) are strongly associated with the development of PDB. Bisphosphonate therapy can improve bone pain in PDB, but there is no evidence that treatment alters the natural history of PDB or prevents complications. The Zoledronate in the Prevention of Paget's disease trial (ZiPP) will determine if prophylactic therapy with the bisphosphonate zoledronic acid (ZA) can delay or prevent the development of PDB in people who carry SQSTM1 mutations. METHODS AND ANALYSIS: People with a family history of PDB aged >30 years who test positive for SQSTM1 mutations are eligible to take part. At the baseline visit, participants will be screened for the presence of bone lesions by radionuclide bone scan. Biochemical markers of bone turnover will be measured and questionnaires completed to assess pain, health-related quality of life (HRQoL), anxiety and depression. Participants will be randomised to receive a single intravenous infusion of 5 mg ZA or placebo and followed up annually for between 4 and 8 years at which point baseline assessments will be repeated. The primary endpoint will be new bone lesions assessed by radionuclide bone scan. Secondary endpoints will include changes in biochemical markers of bone turnover, pain, HRQoL, anxiety, depression and PDB-related skeletal events. ETHICS AND DISSEMINATION: The study was approved by the Fife and Forth Valley Research Ethics Committee on 22 December 2008 (08/S0501/84). Following completion of the trial, a manuscript will be submitted to a peer-reviewed journal. The results of this trial will inform clinical practice by determining if early intervention with ZA in presymptomatic individuals with SQSTM1 mutations can prevent or slow the development of bone lesions with an adverse event profile that is acceptable. TRIAL REGISTRATION NUMBER: ISRCTN11616770.

3.
Australas Psychiatry ; 27(4): 362-365, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31165642

RESUMO

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.


Assuntos
Competência Cultural , Entrevista Psicológica/métodos , Entrevista Psicológica/normas , Transtornos Mentais/diagnóstico , Grupo com Ancestrais Oceânicos/estatística & dados numéricos , Austrália/etnologia , Manual Diagnóstico e Estatístico de Transtornos Mentais , Retroalimentação , Serviços de Saúde do Indígena/organização & administração , Humanos , Transtornos Mentais/etnologia , Reprodutibilidade dos Testes , Inquéritos e Questionários
4.
J Psychiatr Res ; 111: 104-109, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30711770

RESUMO

OBJECTIVE: In the general population, people with mental disorders have increased mortality. This association, however, has not been explored in a population who at some time were inpatients of a public hospital. METHODS: The sampling frame was patients admitted to an Australian regional public hospital 1996-2010. Those with known mental disorder were compared with an equal number of randomly selected patients without known mental disorder, matched for age, sex, and year of admission. Mortality outcomes were determined by linkage of hospital data and the National Death Index. RESULTS: We identified 15,356 patients with mental disorder and 15,356 without known mental disorder, 25.2% of the former and 17.3% of the latter died during the study period. The odds ratio (OR) for death in those with mental disorder was 2.20 (95% confidence interval: 2.01-2.41) after adjusting for confounders, and their mean age at death was 4.6 years younger (p < 0.001). Other independent risk factors for mortality were being Indigenous (OR 1.72, 1.32-2.24), not partnered (OR 1.55, 1.36-1.76) or having multiple comorbidities (OR 1.65, 1.43-1.90). In the model that included multiple interactions, the ORs for death in Indigenous patients with mental disorder were markedly higher (6.6-9.5), regardless of other risk factors. DISCUSSION: Among patients with a history of public hospital admission, those with mental disorders have higher mortality than those without mental disorders. This gap in life expectancy mandates increased attention, by clinicians and health services alike, to preventable causes of death in people with mental illness.

5.
Gerontologist ; 2018 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-30500896

RESUMO

Background and Objectives: Traditional Elders are integral to the social structure of Australian Indigenous communities. Due to progressive loss of traditional way of life, however, the role of Elders has been eroding. This study aims to develop a conceptual model of the role of Elders in an Australian Indigenous community, with the goal of attaining strategies to strengthen the role of Elders. Research Design and Methods: The study, conducted in a regional Indigenous community in Australia, adopted a community-based participatory approach. Design and focus of the project were informed by a community forum (Yarning Circle). One-on-one semistructured interviews and focus groups with community members were conducted by Indigenous researchers. Group concept mapping (GCM) was applied to elicit major themes in qualitative data, from the point of view of community members, and to derive a conceptual model of the role of Elders. Results: Fifty members of the Indigenous community took part in interviews and focus groups. The participants' median age was 45 years (range 18-76 years); 31 (62%) were female. An additional 24 Indigenous community members took part in the data sorting task of GCM. GCM identified seven major aspects of the role of Elders, including Community relations, Passing down the knowledge, Dealing with racism and oppression, Building a better resourced community, Intergenerational connectedness, Safeguarding our identity, and Caring for our youth. Discussion and Implications: Elders fulfill many important roles in contemporary Indigenous communities. Our results can be used to assist the community to codesign a program to increase community wellbeing.

6.
BMJ Open ; 8(6): e020196, 2018 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-29961007

RESUMO

OBJECTIVE: To determine, using face-to-face diagnostic interviews, the prevalence of common mental disorders (CMD) in a cohort of adult Indigenous Australians, the cultural acceptability of the interviews, the rates of comorbid CMD and concordance with psychiatrists' diagnoses. DESIGN: Cross-sectional study July 2014-November 2016. Psychologists conducted Structured Clinical Interviews for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision Axis I Disorders (SCID-I) (n=544). Psychiatrists interviewed a subsample (n=78). SETTING: Four Aboriginal Medical Services and the general community located in urban, regional and remote areas of Southern Queensland and two Aboriginal Reserves located in New South Wales. PARTICIPANTS: Indigenous Australian adults. OUTCOME MEASURES: Cultural acceptability of SCID-I interviews, standardised rates of CMD, comorbid CMD and concordance with psychiatrist diagnoses. RESULTS: Participants reported that the SCID-I interviews were generally culturally acceptable. Standardised rates (95% CI) of current mood, anxiety, substance use and any mental disorder were 16.2% (12.2% to 20.2%), 29.2% (24.2% to 34.1%), 12.4% (8.8% to 16.1%) and 42.2% (38.8% to 47.7%), respectively-6.7-fold, 3.8-fold, 6.9-fold and 4.2-fold higher, respectively, than those of the Australian population. Differences between this Indigenous cohort and the Australian population were less marked for 12-month (2.4-fold) and lifetime prevalence (1.3-fold). Comorbid mental disorder was threefold to fourfold higher. In subgroups living on traditional lands in Indigenous reserves and in remote areas, the rate was half that of those living in mainstream communities. Moderate-to-good concordance with psychiatrist diagnoses was found. CONCLUSIONS: The prevalence of current CMD in this Indigenous population is substantially higher than previous estimates. The lower relative rates of non-current disorders are consistent with underdiagnosis of previous events. The lower rates among Reserve and remote area residents point to the importance of Indigenous peoples' connection to their traditional lands and culture, and a potentially important protective factor. A larger study with random sampling is required to determine the population prevalence of CMD in Indigenous Australians.


Assuntos
Transtornos Mentais/etnologia , Grupo com Ancestrais Oceânicos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , New South Wales/etnologia , Prevalência , Queensland/etnologia , População Rural , Adulto Jovem
7.
PLoS One ; 12(7): e0180394, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28686628

RESUMO

BACKGROUND: Rural medical workforce shortage contributes to health disadvantage experienced by rural communities worldwide. This study aimed to determine the regional results of an Australian Government sponsored national program to enhance the Australian rural medical workforce by recruiting rural background students and establishing rural clinical schools (RCS). In particular, we wished to determine predictors of graduates' longer-term rural practice and whether the predictors differ between general practitioners (GPs) and specialists. METHODS: A cross-sectional cohort study, conducted in 2012, of 729 medical graduates of The University of Queensland 2002-2011. The outcome of interest was primary place of graduates' practice categorised as rural for at least 50% of time since graduation ('Longer-term Rural Practice', LTRP) among GPs and medical specialists. The main exposures were rural background (RB) or metropolitan background (MB), and attendance at a metropolitan clinical school (MCS) or the Rural Clinical School for one year (RCS-1) or two years (RCS-2). RESULTS: Independent predictors of LTRP (odds ratio [95% confidence interval]) were RB (2.10 [1.37-3.20]), RCS-1 (2.85 [1.77-4.58]), RCS-2 (5.38 [3.15-9.20]), GP (3.40 [2.13-5.43]), and bonded scholarship (2.11 [1.19-3.76]). Compared to being single, having a metropolitan background partner was a negative predictor (0.34 [0.21-0.57]). The effects of RB and RCS were additive-compared to MB and MCS (Reference group): RB and RCS-1 (6.58[3.32-13.04]), RB and RCS-2 (10.36[4.89-21.93]). Although specialists were less likely than GPs to be in LTRP, the pattern of the effects of rural exposures was similar, although some significant differences in the effects of the duration of RCS attendance, bonded scholarships and partner's background were apparent. CONCLUSIONS: Among both specialists and GPs, rural background and rural clinical school attendance are independent, duration-dependent, and additive, predictors of longer-term rural practice. Metropolitan-based medical schools can enhance both specialist and GP rural medical workforce by enrolling rural background medical students and providing them with long-term rural undergraduate clinical training. Policy settings to achieve optimum rural workforce outcomes may differ between specialists and GPs.


Assuntos
Escolha da Profissão , Clínicos Gerais/psicologia , Área de Atuação Profissional/tendências , Faculdades de Medicina/provisão & distribução , Estudantes de Medicina/psicologia , Adulto , Atitude do Pessoal de Saúde , Austrália , Estudos Transversais , Feminino , Humanos , Masculino , Área Carente de Assistência Médica , Serviços de Saúde Rural/provisão & distribução , População Rural , Especialização/estatística & dados numéricos , Inquéritos e Questionários
8.
BMC Psychiatry ; 17(1): 219, 2017 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-28610603

RESUMO

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.


Assuntos
Serviços Comunitários de Saúde Mental , Encaminhamento e Consulta , Suicídio/prevenção & controle , Grupos Focais , Humanos , Entrevistas como Assunto , Grupo com Ancestrais Oceânicos , Avaliação de Programas e Projetos de Saúde , Queensland , Suicídio/etnologia
9.
BMC Psychiatry ; 16(1): 357, 2016 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-27769204

RESUMO

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.


Assuntos
Grupo com Ancestrais Nativos do Continente Americano/psicologia , Competência Cultural/educação , Assistência à Saúde Culturalmente Competente/métodos , Grupo com Ancestrais Oceânicos/psicologia , Suicídio/prevenção & controle , Adolescente , Austrália , Canadá , Feminino , Humanos
10.
Metabolism ; 65(5): 783-793, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27085785

RESUMO

AIMS: Reported associations between liver enzymes and mortality may not hold true in type 2 diabetes, owing to a high prevalence of non-alcoholic fatty liver disease, which has been linked to cardiovascular disease and mortality in its own right. Our study aimed to determine whether alanine aminotransferase (ALT) or γ-glutamyl transferase (GGT) levels predict mortality in type 2 diabetes, and to examine possible mechanisms. METHODS: Data from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study were analyzed to examine the relationship between liver enzymes and all-cause and cause-specific mortality over 5years. RESULTS: Over 5years, 679 (6.9%) individuals died. After adjustment, for every standard deviation increase in ALT (13.2U/L), the HR for death on study was 0.85 (95% CI 0.78-0.93), p<0.001. Conversely, GGT >70U/L, compared with GGT ≤70U/L, had HR 1.82 (1.48-2.24), p<0.001. For cause-specific mortality, lower ALT was associated with a higher risk of cardiovascular death only, whereas GGT >70U/L was associated with higher risks of death due to cardiovascular disease, cancer and non-cancer/non-cardiovascular causes. The relationship for ALT persisted after adjustment for indirect measures of frailty but was attenuated by elevated hsCRP. CONCLUSIONS: As in the general population, ALT has a negative, and GGT a positive, correlation with mortality in type 2 diabetes when ALT is less than two times the upper limit of normal. The relationship for ALT appears specific for death due to cardiovascular disease. Links of low ALT with frailty, as a potential mechanism for relationships seen, were neither supported nor conclusively refuted by our analysis and other factors are also likely to be important in those with type 2 diabetes.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/complicações , Angiopatias Diabéticas/prevenção & controle , Fenofibrato/uso terapêutico , Hipolipemiantes/uso terapêutico , Fígado/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Idoso , Alanina Transaminase/sangue , Austrália/epidemiologia , Biomarcadores/sangue , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/mortalidade , Diabetes Mellitus Tipo 2/fisiopatologia , Angiopatias Diabéticas/complicações , Angiopatias Diabéticas/epidemiologia , Cardiomiopatias Diabéticas/complicações , Cardiomiopatias Diabéticas/epidemiologia , Cardiomiopatias Diabéticas/prevenção & controle , Método Duplo-Cego , Feminino , Finlândia/epidemiologia , Humanos , Fígado/fisiopatologia , Masculino , Pessoa de Meia-Idade , Mortalidade , Nova Zelândia/epidemiologia , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Prevalência , gama-Glutamiltransferase/sangue
11.
J Bone Miner Res ; 31(2): 358-68, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26256109

RESUMO

Protein phosphorylation regulates a wide variety of cellular processes. Thus, we hypothesize that single-nucleotide polymorphisms (SNPs) that may modulate protein phosphorylation could affect osteoporosis risk. Based on a previous conventional genome-wide association (GWA) study, we conducted a three-stage meta-analysis targeting phosphorylation-related SNPs (phosSNPs) for femoral neck (FN)-bone mineral density (BMD), total hip (HIP)-BMD, and lumbar spine (LS)-BMD phenotypes. In stage 1, 9593 phosSNPs were meta-analyzed in 11,140 individuals of various ancestries. Genome-wide significance (GWS) and suggestive significance were defined by α = 5.21 × 10(-6) (0.05/9593) and 1.00 × 10(-4), respectively. In stage 2, nine stage 1-discovered phosSNPs (based on α = 1.00 × 10(-4)) were in silico meta-analyzed in Dutch, Korean, and Australian cohorts. In stage 3, four phosSNPs that replicated in stage 2 (based on α = 5.56 × 10(-3), 0.05/9) were de novo genotyped in two independent cohorts. IDUA rs3755955 and rs6831280, and WNT16 rs2707466 were associated with BMD phenotypes in each respective stage, and in three stages combined, achieving GWS for both FN-BMD (p = 8.36 × 10(-10), p = 5.26 × 10(-10), and p = 3.01 × 10(-10), respectively) and HIP-BMD (p = 3.26 × 10(-6), p = 1.97 × 10(-6), and p = 1.63 × 10(-12), respectively). Although in vitro studies demonstrated no differences in expressions of wild-type and mutant forms of IDUA and WNT16B proteins, in silico analyses predicts that WNT16 rs2707466 directly abolishes a phosphorylation site, which could cause a deleterious effect on WNT16 protein, and that IDUA phosSNPs rs3755955 and rs6831280 could exert indirect effects on nearby phosphorylation sites. Further studies will be required to determine the detailed and specific molecular effects of these BMD-associated non-synonymous variants.


Assuntos
Densidade Óssea/genética , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único , Proteínas Wnt/genética , Estudos de Coortes , Feminino , Colo do Fêmur/metabolismo , Humanos , Vértebras Lombares/metabolismo , Masculino , Fosforilação , Proteínas Wnt/metabolismo
12.
Hum Mol Genet ; 24(16): 4710-27, 2015 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-25941324

RESUMO

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.


Assuntos
Regiões 3' não Traduzidas , Densidade Óssea/genética , Loci Gênicos , MicroRNAs/genética , Polimorfismo Genético , Receptor Tipo 5 de Fator de Crescimento de Fibroblastos/genética , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino
14.
Aust N Z J Psychiatry ; 49(5): 412-29, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25690747

RESUMO

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.


Assuntos
Transtornos Mentais/classificação , Transtornos Mentais/epidemiologia , Grupo com Ancestrais Oceânicos/psicologia , Austrália , Humanos
15.
Med J Aust ; 202(1): 41-5, 2015 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-25588445

RESUMO

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.


Assuntos
Serviços de Saúde Rural , Estudos de Coortes , Educação Pré-Médica , Previsões , Modelos Estatísticos , Queensland , Estudos Retrospectivos , Inquéritos e Questionários
16.
Diabetes Care ; 37(11): 3121-3, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25125506

RESUMO

OBJECTIVE: To evaluate the safety and efficacy of methazolamide as a potential therapy for type 2 diabetes. RESEARCH DESIGN AND METHODS: This double-blind, placebo-controlled study randomized 76 patients to oral methazolamide (40 mg b.i.d.) or placebo for 24 weeks. The primary efficacy end point for methazolamide treatment was a placebo-corrected reduction in HbA1c from baseline after 24 weeks (ΔHbA1c). RESULTS: Mean ± SD baseline HbA1c was 7.1 ± 0.7% (54 ± 5 mmol/mol; n = 37) and 7.4 ± 0.6% (57 ± 5 mmol/mol; n = 39) in the methazolamide and placebo groups, respectively. Methazolamide treatment was associated with a ΔHbA1c of -0.39% (95% CI -0.82, 0.04; P < 0.05) (-4.3 mmol/mol [-9.0, 0.4]), an increase in the proportion of patients achieving HbA1c ≤6.5% (48 mmol/mol) from 8 to 33%, a rapid reduction in alanine aminotransferase (∼10 units/L), and weight loss (2%) in metformin-cotreated patients. CONCLUSIONS: Methazolamide is the archetype for a new intervention in type 2 diabetes with clinical benefits beyond glucose control.


Assuntos
Inibidores da Anidrase Carbônica/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Metazolamida/uso terapêutico , Idoso , Inibidores da Anidrase Carbônica/efeitos adversos , Método Duplo-Cego , Feminino , Hemoglobina A Glicada/análise , Humanos , Hipoglicemiantes/uso terapêutico , Masculino , Metformina/uso terapêutico , Metazolamida/efeitos adversos , Pessoa de Meia-Idade , Perda de Peso/efeitos dos fármacos
17.
Bone ; 64: 8-12, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24662619

RESUMO

We investigated the association between undercarboxylated osteocalcin (ucOC) and lower-limb muscle strength in women over the age of 70years. The study also aims to confirm the association between bone turnover markers and heel ultrasound measures. A post-hoc analysis using data collected as part of a randomized placebo-controlled trial of vitamin D supplementation. An immunoassay was used to quantify total OC (tOC), with hydroxyapatite pre-treatment for ucOC. We determined associations of absolute and relative (ucOC/tOC; ucOC%) measures of ucOC with lower-limb muscle strength, heel ultrasound measures of speed of sound (SOS) and broadband ultrasound attenuation (BUA), bone turnover markers (BTMs; P1NP and CTx) and the acute phase protein alpha-1-antichymotrypsin (α-ACT). ucOC%, but not absolute ucOC concentration, was positively associated with hip flexor, hip abductor and quadriceps muscle strength (all p<0.05). ucOC% was negatively associated with α-ACT (ß-coefficient=-0.24, p=0.02). tOC was positively associated with both P1NP and CTx (p<0.001). For each per unit increase in tOC (µg/L) there was a corresponding lower BUA, SOS and SI (ß-coefficient = -0.28; -0.23 and -0.23, respectively; all p<0.04). In conclusion, ucOC% is positively associated with muscle strength and negatively associated with α-ACT. These data support a role for ucOC in musculoskeletal interactions in humans. Whilst tOC is associated with bone health, ucOC% and ucOC may also be linked to falls and fracture risk by influencing muscle function.


Assuntos
Densidade Óssea , Osteocalcina/sangue , Idoso , Método Duplo-Cego , Feminino , Humanos , Placebos
18.
Calcif Tissue Int ; 94(4): 363-72, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24390582

RESUMO

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.


Assuntos
Composição Corporal , Músculo Esquelético/fisiologia , Absorciometria de Fóton , Adulto , Idoso , Idoso de 80 Anos ou mais , Antropometria , Austrália , Estudos Transversais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/patologia , Atrofia Muscular/fisiopatologia , Osteoporose/epidemiologia , Osteoporose/fisiopatologia , Prevalência , Valores de Referência , Análise de Regressão , Reprodutibilidade dos Testes , Sarcopenia/fisiopatologia , Adulto Jovem
19.
Hum Mol Genet ; 23(7): 1923-33, 2014 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-24249740

RESUMO

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.


Assuntos
Densidade Óssea/genética , Claudinas/genética , Osteonectina/genética , Osteoporose/genética , Idoso , Osso e Ossos/metabolismo , Feminino , Colo do Fêmur/fisiologia , Expressão Gênica , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Quadril/fisiologia , Humanos , Vértebras Lombares/fisiologia , Masculino , Pessoa de Meia-Idade , Osteoclastos/citologia , Osteogênese/genética , Osteoporose/terapia , Polimorfismo de Nucleotídeo Único
20.
PLoS One ; 8(9): e73266, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24069182

RESUMO

In bone, depletion of osteoclasts reduces bone formation in vivo, as does osteal macrophage depletion. How osteoclasts and macrophages promote the action of bone forming osteoblasts is, however, unclear. Since recruitment and differentiation of multi-potential stromal cells/mesenchymal stem cells (MSC) generates new active osteoblasts, we investigated whether human osteoclasts and macrophages (generated from cord blood-derived hematopoietic progenitors) induce osteoblastic maturation in adipose tissue-derived MSC. When treated with an osteogenic stimulus (ascorbate, dexamethasone and ß-glycerophosphate) these MSC form matrix-mineralising, alkaline phosphatase-expressing osteoblastic cells. Cord blood-derived progenitors were treated with macrophage colony stimulating factor (M-CSF) to form immature proliferating macrophages, or with M-CSF plus receptor activator of NFκB ligand (RANKL) to form osteoclasts; culture medium was conditioned for 3 days by these cells to study their production of osteoblastic factors. Both osteoclast- and macrophage-conditioned medium (CM) greatly enhanced MSC osteoblastic differentiation in both the presence and absence of osteogenic medium, evident by increased alkaline phosphatase levels within 4 days and increased mineralisation within 14 days. These CM effects were completely ablated by antibodies blocking gp130 or oncostatin M (OSM), and OSM was detectable in both CM. Recombinant OSM very potently stimulated osteoblastic maturation of these MSC and enhanced bone morphogenetic protein-2 (BMP-2) actions on MSC. To determine the influence of macrophage activation on this OSM-dependent activity, CM was collected from macrophage populations treated with M-CSF plus IL-4 (to induce alternative activation) or with GM-CSF, IFNγ and LPS to cause classical activation. CM from IL-4 treated macrophages stimulated osteoblastic maturation in MSC, while CM from classically-activated macrophages did not. Thus, macrophage-lineage cells, including osteoclasts but not classically activated macrophages, can strongly drive MSC-osteoblastic commitment in OSM-dependent manner. This supports the notion that eliciting gp130-dependent signals in human MSC would be a useful approach to increase bone formation.


Assuntos
Sangue Fetal/citologia , Glicoproteínas/metabolismo , Células-Tronco Mesenquimais/citologia , Osteoblastos/citologia , Células Cultivadas , Citometria de Fluxo , Glicoproteínas/genética , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Humanos , Macrófagos/citologia , Macrófagos/metabolismo , Células-Tronco Mesenquimais/metabolismo , Osteoblastos/metabolismo , Reação em Cadeia da Polimerase em Tempo Real
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