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1.
Syst Rev ; 13(1): 154, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38858798

ABSTRACT

BACKGROUND: Frailty reduction and reversal have been addressed successfully among older populations within community settings. However, these findings may not be applicable to residential care settings, largely due to the complex and multidimensional nature of the condition. Relatively, few attempts at frailty prevention exist in residential settings. This review aims to identify and describe best practice models of care for addressing frailty among older populations in residential care settings. This research also sets out to explore the impact of multidisciplinary health service delivery models on health outcomes such as mortality, hospitalisations, quality of life, falls and frailty. METHODS: A scoping review of the literature was conducted to address the project objectives. Reference lists of included studies, bibliographic databases and the grey literature were systematically searched for literature reporting multidisciplinary, multidimensional models of care for frailty. RESULTS: The scoping review found no interventions that met the inclusion criteria. Of the 704 articles screened, 664 were excluded as not relevant. Forty articles were fully assessed, and while no eligible studies were found, relevant data were extracted from 10 near-eligible studies that reported single disciplines or single dimensions rather than a model of care. The physical, nutritional, medicinal, social and cognitive aspects of the near eligible studies have been discussed as playing a key role in frailty reduction or prevention care models. CONCLUSION: This review has identified a paucity of interventions for addressing and reducing frailty in residential care settings. High-quality studies investigating novel models of care for addressing frailty in residential care facilities are required to address this knowledge gap. Similarly, there is a need to develop and validate appropriate screening and assessment tools for frailty in residential care populations. Health service providers and policy-makers should also increase their awareness of frailty as a dynamic and reversible condition. While age is a non-modifiable predictor of frailty, addressing modifiable factors through comprehensive care models may help manage and prevent the physical, social and financial impacts of frailty in the ageing population.


Subject(s)
Frail Elderly , Frailty , Humans , Frailty/prevention & control , Aged , Residential Facilities , Quality of Life , Homes for the Aged
2.
BMC Cardiovasc Disord ; 22(1): 96, 2022 03 09.
Article in English | MEDLINE | ID: mdl-35264114

ABSTRACT

BACKGROUND: It is unclear whether genetic variants identified from single nucleotide polymorphisms (SNPs) strongly associated with coronary heart disease (CHD) in genome-wide association studies (GWAS), or a genetic risk score (GRS) derived from them, can help stratify risk of recurrent events in patients with CHD. METHODS: Study subjects were enrolled at the close-out of the LIPID randomised controlled trial of pravastatin vs placebo. Entry to the trial had required a history of acute coronary syndrome 3-36 months previously, and patients were in the trial for a mean of 36 months. Patients who consented to a blood sample were genotyped with a custom designed array chip with SNPs chosen from known CHD-associated loci identified in previous GWAS. We evaluated outcomes in these patients over the following 10 years. RESULTS: Over the 10-year follow-up of the cohort of 4932 patients, 1558 deaths, 898 cardiovascular deaths, 727 CHD deaths and 375 cancer deaths occurred. There were no significant associations between individual SNPs and outcomes before or after adjustment for confounding variables and for multiple testing. A previously validated 27 SNP GRS derived from SNPs with the strongest associations with CHD also did not show any independent association with recurrent major cardiovascular events. CONCLUSIONS: Genetic variants based on individual single nucleotide polymorphisms strongly associated with coronary heart disease in genome wide association studies or an abbreviated genetic risk score derived from them did not help risk profiling in this well-characterised cohort with 10-year follow-up. Other approaches will be needed to incorporate genetic profiling into clinically relevant stratification of long-term risk of recurrent events in CHD patients.


Subject(s)
Coronary Disease , Genome-Wide Association Study , Coronary Disease/diagnosis , Coronary Disease/genetics , Genetic Predisposition to Disease , Genotype , Humans , Polymorphism, Single Nucleotide , Risk Factors
4.
J Nutr Health Aging ; 24(6): 547-549, 2020.
Article in English | MEDLINE | ID: mdl-32510104
5.
Int J Med Inform ; 136: 104094, 2020 04.
Article in English | MEDLINE | ID: mdl-32058264

ABSTRACT

INTRODUCTION: Research has shown that frailty, a geriatric syndrome associated with an increased risk of negative outcomes for older people, is highly prevalent among residents of residential aged care facilities (also called long term care facilities or nursing homes). However, progress on effective identification of frailty within residential care remains at an early stage, necessitating the development of new methods for accurate and efficient screening. OBJECTIVES: We aimed to determine the effectiveness of artificial intelligence (AI) algorithms in accurately identifying frailty among residents aged 75 years and over in comparison with a calculated electronic Frailty Index (eFI) based on a routinely-collected residential aged care administrative data set drawn from 10 residential care facilities located in Queensland, Australia. A secondary objective included the identification of best-performing candidate algorithms. METHODS: We designed a frailty prediction system based on the eFI identification of frailty, allocating 84.5 % and 15.5 % of the data to training and test data sets respectively. We compared the performance of 18 specific scenarios to predict frailty against eFI based on unique combinations of three ML algorithms (support vector machines [SVM], decision trees [DT] and K-nearest neighbours [KNN]) and six cases (6, 10, 11, 14, 39 and 70 input variables). We calculated accuracy, percentage positive and negative agreement, sensitivity, specificity, Cohen's kappa and Prevalence- and Bias- Adjusted Kappa (PABAK), table frequencies and positive and negative predictive values. RESULTS: Of 592 eligible resident records, 500 were allocated to the training set and 92 to the test set. Three scenarios (10, 11 and 70 input variables), all based on SVM algorithm, returned overall accuracy above 75 %. CONCLUSIONS: There is some potential for AI techniques to contribute towards better frailty identification within residential care. However, potential benefits will need to be weighed against administrative burden, data quality concerns and presence of potential bias.


Subject(s)
Artificial Intelligence , Assisted Living Facilities/statistics & numerical data , Frailty/diagnosis , Geriatric Assessment/methods , Homes for the Aged/statistics & numerical data , Mass Screening/methods , Nursing Homes/statistics & numerical data , Aged , Aged, 80 and over , Australia , Cross-Sectional Studies , Delivery of Health Care , Female , Humans , Male , Queensland , Retrospective Studies
6.
Aging Clin Exp Res ; 32(9): 1849-1856, 2020 Sep.
Article in English | MEDLINE | ID: mdl-31686388

ABSTRACT

OBJECTIVES: Studies conducted among older people have shown that frailty is a common condition associated with an array of adverse outcomes. The aims of this study were to identify the prevalence and associations of frailty in older people residing in several aged care facilities located in Queensland, Australia. METHODS: The database used for this study was drawn from the Aged Care Funding Instrument (ACFI) database of an Australian aged care provider, and contained data from ten aged care facilities in Queensland, Australia. A modification of an eFI originally developed by Clegg and colleagues and based on Rockwood's Frailty Index (FI) of cumulative deficits was used to identify frailty. RESULTS: In total, 592 participants aged 75 years and over were included in the study (66.6% female). Median (IQR) age was 88.0 (9.0) years. Frailty prevalence among the sample was 43.6%, with 46.3% pre-frail and 10.1% not frail. In a multivariate logistic regression analysis incorporating three different models, frailty was significantly associated with three ACFI domains (Nutrition, Depression and Complex Health Care), along with facility size, consistently across two models. In the third model, frailty was also significantly associated with arthritis, diabetes, hypertension, osteoporosis and vision problems, along with male gender. CONCLUSION: There is a need to develop frailty identification and management programs as part of standard care pathways for older adults residing in aged care facilities. Aged care facilities should consider regular frailty screening in residential aged care residents, along with interventions addressing specific issues such as dysphagia and depression.


Subject(s)
Frailty , Aged , Aged, 80 and over , Australia/epidemiology , Female , Frail Elderly , Frailty/epidemiology , Geriatric Assessment , Humans , Male , Prevalence , Retrospective Studies
7.
J Nutr Health Aging ; 23(9): 771-787, 2019.
Article in English | MEDLINE | ID: mdl-31641726

ABSTRACT

OBJECTIVE: The task force of the International Conference of Frailty and Sarcopenia Research (ICFSR) developed these clinical practice guidelines to overview the current evidence-base and to provide recommendations for the identification and management of frailty in older adults. METHODS: These recommendations were formed using the GRADE approach, which ranked the strength and certainty (quality) of the supporting evidence behind each recommendation. Where the evidence-base was limited or of low quality, Consensus Based Recommendations (CBRs) were formulated. The recommendations focus on the clinical and practical aspects of care for older people with frailty, and promote person-centred care. Recommendations for Screening and Assessment: The task force recommends that health practitioners case identify/screen all older adults for frailty using a validated instrument suitable for the specific setting or context (strong recommendation). Ideally, the screening instrument should exclude disability as part of the screening process. For individuals screened as positive for frailty, a more comprehensive clinical assessment should be performed to identify signs and underlying mechanisms of frailty (strong recommendation). Recommendations for Management: A comprehensive care plan for frailty should address polypharmacy (whether rational or nonrational), the management of sarcopenia, the treatable causes of weight loss, and the causes of exhaustion (depression, anaemia, hypotension, hypothyroidism, and B12 deficiency) (strong recommendation). All persons with frailty should receive social support as needed to address unmet needs and encourage adherence to a comprehensive care plan (strong recommendation). First-line therapy for the management of frailty should include a multi-component physical activity programme with a resistance-based training component (strong recommendation). Protein/caloric supplementation is recommended when weight loss or undernutrition are present (conditional recommendation). No recommendation was given for systematic additional therapies such as cognitive therapy, problem-solving therapy, vitamin D supplementation, and hormone-based treatment. Pharmacological treatment as presently available is not recommended therapy for the treatment of frailty.


Subject(s)
Frailty/diagnosis , Frailty/therapy , Sarcopenia/diagnosis , Sarcopenia/therapy , Aged , Aged, 80 and over , Aging/physiology , Exercise/physiology , Humans , Mass Screening/methods
8.
J Frailty Aging ; 7(3): 193-195, 2018.
Article in English | MEDLINE | ID: mdl-30095151

ABSTRACT

Older frequent users of acute care can experience fragmented care. There is a need to understand the issues in a local context before attempting to address fragmented care. 0.5% (n=61) of the population in a defined local government area were identified as having ≥4 unplanned emergency department (ED) presentations/ admissions to an acute-care hospital over 13 months. A retrospective case-series study was conducted to examine detailed pathways of care for 17 patients within the identified population. The two dominant presentation reasons were clinical symptoms associated with a declining/significant loss of capacity in fundamental self-care activities and chronic cardiac/respiratory conditions. Of patients discharged home, 21% of discharge letters were delayed >7 days and only 19% received a written discharge plan. Half of community dwelling patients received home nursing and/or assistance. Frequent users of acute care can experience untimely hospital communication and may require more coordinated care provided in the community to assist self-care and manage chronic conditions.


Subject(s)
Critical Care/statistics & numerical data , Delivery of Health Care/organization & administration , Aged , Emergency Service, Hospital/statistics & numerical data , Hospitalization/statistics & numerical data , Humans , Independent Living , Patient Discharge/statistics & numerical data , Retrospective Studies
9.
J Frailty Aging ; 6(4): 212-215, 2017.
Article in English | MEDLINE | ID: mdl-29165539

ABSTRACT

With age, the prevalence of musculoskeletal conditions increases markedly. This rural-based study determined the benefits of two approaches for managing musculoskeletal conditions: a multiple-component 'Self-management Plus' intervention, and usual care. The intervention combined self-management education with physical activity and health professional support. 6-month outcomes included: Clinical Global Impression-Improvement Scale (CGI-IS) and Quality of Life (QoL). A total of 145 people were recruited; mean (SD) age was 66.1 (11.1) and 63.3 (10.9) years for intervention and control groups respectively. The intervention resulted in greater improvements in global functioning (CGI-IS mean (SD) = 3.2 (1.3)) than usual care (CGI-IS mean (SD) = 4.2 (1.5)). There was no difference in QoL improvement between study groups. A multiple-component 'Self-management Plus' intervention had a positive effect on physical functioning for older adults with musculoskeletal conditions. However, recruitment and retention of participants was problematic, which raises questions about the intervention's feasibility in its current form.


Subject(s)
Health Promotion/methods , Musculoskeletal Diseases/prevention & control , Patient Education as Topic/methods , Rural Population/statistics & numerical data , Self Care/methods , Aged , Exercise , Female , Humans , Male , Middle Aged , Musculoskeletal Pain/prevention & control , Quality of Life/psychology , South Australia
10.
Intern Med J ; 43(12): 1272-9, 2013 Dec.
Article in English | MEDLINE | ID: mdl-23654213

ABSTRACT

BACKGROUND: Controversies exist around predictive testing (PT) programmes in neurodegenerative disorders. AIMS: This study sets out to answer the following questions relating to Huntington disease (HD) and other neurodegenerative disorders: differences between these patients in their PT journeys, why and when individuals withdraw from PT, and decision-making processes regarding reproductive genetic testing. METHODS: A case series analysis of patients having PT from the multidisciplinary Western Australian centre for PT over the past 20 years was performed using internationally recognised guidelines for predictive gene testing in neurodegenerative disorders. RESULTS: Of 740 at-risk patients, 518 applied for PT: 466 at risk of HD, 52 at risk of other neurodegenerative disorders - spinocerebellar ataxias, hereditary prion disease and familial Alzheimer disease. Thirteen percent withdrew from PT - 80.32% of withdrawals occurred during counselling stages. Major withdrawal reasons related to timing in the patients' lives or unknown as the patient did not disclose the reason. Thirty-eight HD individuals had reproductive genetic testing: 34 initiated prenatal testing (of which eight withdrew from the process) and four initiated pre-implantation genetic diagnosis. There was no recorded or other evidence of major psychological reactions or suicides during PT. CONCLUSIONS: People withdrew from PT in relation to life stages and reasons that are unknown. Our findings emphasise the importance of: (i) adherence to internationally recommended guidelines for PT; (ii) the role of the multidisciplinary team in risk minimisation; and (iii) patient selection.


Subject(s)
Genetic Testing/methods , Genetic Testing/standards , Huntington Disease/diagnosis , Huntington Disease/genetics , Neurodegenerative Diseases/diagnosis , Neurodegenerative Diseases/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Decision Making , Female , Humans , Huntington Disease/epidemiology , Male , Middle Aged , Neurodegenerative Diseases/epidemiology , Predictive Value of Tests , Retrospective Studies , Western Australia/epidemiology , Young Adult
11.
Diabet Med ; 30(7): 855-63, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23600375

ABSTRACT

AIMS: To determine the cost-effectiveness of alternative models of practice nurse involvement in the management of type 2 diabetes within the primary care setting. METHODS: Linked routinely collected clinical data and resource use (general practitioner visits, hospital services and pharmaceuticals) were used to undertake a risk-adjusted cost-effectiveness analysis of alternative models of care for the management of diabetes patients. These models were based on the reported level of involvement of practice nurses in the provision of clinical-based activities. Potential confounders were controlled for by using propensity score-weighted regression analyses. The impact of alternative models of care on outcomes and costs was measured and incremental cost-effectiveness estimated. The uncertainty around the estimates of cost-effectiveness was illustrated through bootstrapping. RESULTS: Although the difference in total cost between two models of care was not statistically significant, the high-level model was associated with better outcomes (larger mean reductions in HbA(1c)). The upper 95% confidence intervals showed that the incremental cost per 1% decrease in HbA(1c) is only $454, and per one additional patient to achieve an HbA(1c) value of less than 53 mmol/mol (7.0%) is $323. Further analyses showed little uncertainty surrounding the decision to adopt the high-level model. CONCLUSIONS: The results provide a strong indication that the high-level model is a cost-effective way of managing diabetes patients. Our findings highlight the need for effective incentives to encourage general practices to better integrate practice nurses in the provision of clinical services.


Subject(s)
Diabetes Mellitus, Type 2/economics , Diabetes Mellitus, Type 2/therapy , Nurse Practitioners/economics , Aged , Australia , Cost-Benefit Analysis , Female , General Practice/economics , General Practice/methods , Glycated Hemoglobin/analysis , Humans , Male , Middle Aged , Primary Health Care/economics , Primary Health Care/methods , Regression Analysis , Treatment Outcome
12.
Obesity (Silver Spring) ; 21(3): 472-9, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23592655

ABSTRACT

OBJECTIVE: Controlled evaluations are subject to uncertainty regarding their replication in the real world, particularly around systems of service provision. Using routinely collected data, we undertook a risk adjusted cost-effectiveness (RAC-E) analysis of alternative applied models of primary health care for the management of obese adult patients. Models were based on the reported level of involvement of practice nurses (registered or enrolled nurses working in general practice) in the provision of clinical-based activities. DESIGN AND METHODS: Linked, routinely collected clinical data describing clinical outcomes (weight, BMI, and obesity-related complications) and resource use (primary care, pharmaceutical, and hospital resource use) were collected. Potential confounders were controlled for using propensity weighted regression analyses. RESULTS: Relative to low level involvement of practice nurses in the provision of clinical-based activities to obese patients, high level involvement was associated with lower costs and better outcomes (more patients losing weight, and larger mean reductions in BMI). Excluding hospital costs, high level practice nurse involvement was associated with slightly higher costs. Incrementally, the high level model gets one additional obese patient to lose weight at an additional cost of $6,741, and reduces mean BMI by an additional one point at an additional cost of $563 (upper 95% confidence interval $1,547). CONCLUSION: Converted to quality adjusted life year (QALY) gains, the results provide a strong indication that increased involvement of practice nurses in clinical activities is associated with additional health benefits that are achieved at reasonable additional cost. Dissemination activities and incentives are required to encourage general practices to better integrate practice nurses in the active provision of clinical services.


Subject(s)
Nurses/statistics & numerical data , Obesity/economics , Obesity/therapy , Primary Health Care/economics , Body Mass Index , Body Weight , Cost-Benefit Analysis , Databases, Factual , Female , Humans , Male , Middle Aged , Quality-Adjusted Life Years
13.
Aust J Prim Health ; 19(3): 184-9, 2013.
Article in English | MEDLINE | ID: mdl-22951281

ABSTRACT

There is evidence for a team-based approach in the management of chronic disease in primary health care. However, the standard of care is variable, probably reflecting the limited organisational capacity of health services to provide the necessary structured and organised care for this group of patients. This study aimed to evaluate the impact of a structured intervention involving non-GP staff in GP practices on the quality of care for patients with diabetes or cardiovascular disease. A cluster randomised trial was undertaken across 60 GP practices. The intervention was implemented in 30 practices with staff and patients interviewed at baseline and at 12-15 months follow up. The change in team roles was evaluated using a questionnaire completed by practice staff. The quality of care was evaluated using the Patient Assessment of Chronic Illness Care questionnaire. We found that although the team roles of staff improved in the intervention practices and there were significant differences between practices, there was no significant difference between those in the intervention and control groups in patient-assessed quality of care after adjusting for baseline-level score and covariates at the 12-month follow up. Practice team roles were not significantly associated with change in Patient Assessment of Chronic Illness Care scores. Patients with multiple conditions were more likely to assess their quality of care to be better. Thus, although previous research has shown a cross-sectional association between team work and quality of care, we were unable to replicate these findings in the present study. These results may be indicative of insufficient time for organisational change to result in improved patient-assessed quality of care, or because non-GP staff roles were not sufficiently focussed on the aspects of care assessed. The findings provide important information for researchers when designing similar studies.


Subject(s)
Allied Health Personnel/organization & administration , Chronic Disease/therapy , Disease Management , General Practice/organization & administration , Patient Care Team/organization & administration , Quality of Health Care/standards , Allied Health Personnel/standards , Australian Capital Territory , Diabetes Mellitus/therapy , Female , General Practice/methods , Humans , Hypertension/therapy , Linear Models , Male , Middle Aged , Models, Organizational , Myocardial Ischemia/therapy , New South Wales , Patient Care Team/standards , Patient Satisfaction , Program Evaluation , Standard of Care , Victoria , Workforce
14.
Osteoporos Int ; 23(2): 599-606, 2012 Feb.
Article in English | MEDLINE | ID: mdl-21359669

ABSTRACT

SUMMARY: In older men, both lower and higher total osteocalcin levels predict increased all-cause mortality, with comparable associations for cardiovascular and non-cardiovascular deaths. Differences in osteocalcin levels might influence glucose metabolism and thereby cardiovascular risk, or reflect changes in bone turnover thus representing a marker for poorer health outcomes. INTRODUCTION: Reduced levels of total osteocalcin (TOC) are associated with adiposity, insulin resistance and type 2 diabetes, implying this bone-derived peptide might modulate cardiovascular risk. However, there are few longitudinal data relating TOC levels to survival. We examined associations of TOC level with all-cause and cardiovascular mortality in older men. METHODS: We conducted a prospective cohort study of community-dwelling men aged 70-89 years. Aliquots of plasma collected at baseline (2001-2004) were assayed for TOC. Incidence and causes of death to 31 December 2008 were ascertained using data linkage. Cox regression analyses were performed with adjustment for conventional cardiovascular risk factors. RESULTS: From 3,542 men followed for median 5.2 years there were 572 deaths (16.1%). Mortality was lowest in men with TOC levels in the second quintile (12.6%). In multivariate analyses, men with TOC in the lowest and highest quintiles of values had increased all-cause mortality (Q1 vs Q2: hazard ratio [HR], 1.36; 95% confidence interval 1.02-1.80 and Q5 vs Q2: HR, 1.53, 95% CI 1.18-1.98). Men with low TOC levels had similar HR for cardiovascular and non-cardiovascular deaths (Q1 vs Q2: HR, 1.35 and 1.30 respectively). Higher TOC levels predicted cardiovascular disease (CVD)-related mortality (Q5 vs Q2, HR, 1.69, 95% CI 1.09-2.64). CONCLUSIONS: TOC predicts all-cause and CVD-related mortality in community-dwelling older men. However, the relationship is U shaped with men at both ends of the distribution at increased risk. Further investigation is required to clarify whether the underlying mechanisms involve altered bone turnover or relate specifically to the biological activity of osteocalcin.


Subject(s)
Cardiovascular Diseases/blood , Mortality , Osteocalcin/blood , Aged , Aged, 80 and over , Anthropometry/methods , Biomarkers/blood , Cardiovascular Diseases/etiology , Cardiovascular Diseases/mortality , Epidemiologic Methods , Humans , Male , Western Australia/epidemiology
15.
Eur Respir J ; 38(5): 1053-9, 2011 Nov.
Article in English | MEDLINE | ID: mdl-21565919

ABSTRACT

The aim of this study was to examine how objective measures related to lung function cluster in the general population and how the patterns relate to asthma and bronchitis as diagnosed by a doctor (DDA and DDB, respectively). A cross-sectional survey of an age-stratified random general population sample of 1,969 adults from the electoral register of Busselton (Australia) was performed in 2005-2007. Respiratory symptoms, DDA ever, DDB ever, recent wheezing and smoking history, together with anthropometric measurements, forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC), methacholine challenge or bronchodilator response, exhaled nitric oxide (eNO), skin-prick tests to common allergens, and blood eosinophil and neutrophil counts were studied. Cluster analysis (variables sex, age, atopy, FEV1 % predicted, FEV1/FVC, airway hyperresponsiveness, eNO, log eosinphil count, log neutrophil count and body mass index) was used to identify phenotypic patterns. Seven clusters (subjects with DDA and DDB, respectively) were identified: normal males (n=467; 7 and 13%), normal females (n=477; 12 and 18%), obese females (n=250; 16 and 28%), atopic younger adults (n=330; 21 and 17%), atopic adults with high eNO (n=130; 30 and 25%), atopic males with reduced FEV1 (n=103; 33 and 32%) and atopic adults with bronchial hyperreactivity (n=212; 40 and 26%). The clinical diagnosis of asthma (ever) and bronchitis (ever) is not specific for any of the clustering patterns of airway abnormality.


Subject(s)
Asthma/diagnosis , Bronchitis/diagnosis , Adult , Asthma/epidemiology , Asthma/immunology , Asthma/physiopathology , Body Mass Index , Bronchial Hyperreactivity , Bronchial Provocation Tests , Bronchitis/epidemiology , Bronchitis/immunology , Bronchitis/physiopathology , Female , Forced Expiratory Volume , Humans , Male , Middle Aged , Prevalence , Skin Tests , Vital Capacity , Western Australia/epidemiology
16.
Diabet Med ; 28(7): 849-55, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21231957

ABSTRACT

AIMS: To determine whether the reduction in urinary albumin excretion through renin-angiotensin-aldosterone system blockade found in intervention trials extends to community-based patients with Type 2 diabetes. METHODS: We analysed data from 302 participants in the longitudinal observational Fremantle Diabetes Study who commenced angiotensin-converting enzyme inhibitor or angiotensin receptor blocker therapy during follow-up and who had an annual assessment on either side of this therapeutic change. RESULTS: At baseline, the patients had a mean age of 63.8 years, a median diabetes duration of 4 years, a median HbA(1c) of 7.6% (60 mmol/mol) and a geometric mean (sd range) urinary albumin:creatinine ratio of 3.3 mg/mmol (0.8-13.1 mg/mmol). The percentages with normo-, micro- and macroalbuminuria were 49.0, 38.4 and 12.6%, respectively. During 6.1 ± 1.7 years of follow-up, initiation of renin-angiotensin-aldosterone system blockade was associated with a larger geometric mean (sd range) absolute albumin:creatinine ratio reduction in the patients with macroalbuminuria compared with those who had either normo- or microalbuminuria [-40.9 (-825.7 to 159.9) mg/mmol) vs. 1.7 (-1.6 to 20.0) mg/mmol and -0.5 (-23.0 to 39.5) mg/mmol, respectively; P < 0.001]. These changes remained significant after adjustment for changes in blood pressure and other potentially confounding variables, including drug dose and angiotensin-converting enzyme genotype. The post-treatment median albumin:creatinine ratios were 35.4 and 27.4% lower than before treatment in those with micro- or macroalbuminuria, respectively. CONCLUSIONS: Usual-care initiation of renin-angiotensin-aldosterone system blockade confers a quantitatively similar renal benefit to that in intervention trials in Type 2 diabetes.


Subject(s)
Albuminuria/metabolism , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Antihypertensive Agents/therapeutic use , Diabetes Mellitus, Type 2/drug therapy , Diabetic Nephropathies/drug therapy , Renin-Angiotensin System/drug effects , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/urine , Diabetic Nephropathies/metabolism , Diabetic Nephropathies/urine , Female , Humans , Longitudinal Studies , Male , Middle Aged
17.
Eur J Clin Nutr ; 64(10): 1235-8, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20683458

ABSTRACT

Previous studies relating increased serum levels of folate and fat-soluble vitamins to prostate cancer risk have variously shown null associations or to either decrease or increase the risk of developing prostate cancer. Prospective studies of serum folate levels have been reported to show a null association and increased serum levels to either decrease or increase the risk of subsequently developing prostate cancer. Similarly, serum ß-carotene and lycopene levels have either been reported to be inversely correlated or not associated with prostate cancer risk. Using a prospective nested case-control study design, which minimized the possibility of disease effects on serum-vitamin concentrations, we report null associations for serum concentrations of folate, lycopene, ß-carotene, vitamin A and vitamin E, and subsequent development of prostate cancer.


Subject(s)
Carotenoids/blood , Folic Acid/blood , Prostatic Neoplasms/blood , Prostatic Neoplasms/epidemiology , Vitamin A/blood , Vitamin E/blood , Aged , Case-Control Studies , Cohort Studies , Humans , Lycopene , Male , Middle Aged , Risk Factors , beta Carotene/blood
18.
Stat Med ; 29(12): 1298-311, 2010 May 30.
Article in English | MEDLINE | ID: mdl-20209660

ABSTRACT

Genetic markers can be used as instrumental variables, in an analogous way to randomization in a clinical trial, to estimate the causal relationship between a phenotype and an outcome variable. Our purpose is to extend the existing methods for such Mendelian randomization studies to the context of multiple genetic markers measured in multiple studies, based on the analysis of individual participant data. First, for a single genetic marker in one study, we show that the usual ratio of coefficients approach can be reformulated as a regression with heterogeneous error in the explanatory variable. This can be implemented using a Bayesian approach, which is next extended to include multiple genetic markers. We then propose a hierarchical model for undertaking a meta-analysis of multiple studies, in which it is not necessary that the same genetic markers are measured in each study. This provides an overall estimate of the causal relationship between the phenotype and the outcome, and an assessment of its heterogeneity across studies. As an example, we estimate the causal relationship of blood concentrations of C-reactive protein on fibrinogen levels using data from 11 studies. These methods provide a flexible framework for efficient estimation of causal relationships derived from multiple studies. Issues discussed include weak instrument bias, analysis of binary outcome data such as disease risk, missing genetic data, and the use of haplotypes.


Subject(s)
Bayes Theorem , Meta-Analysis as Topic , Biostatistics , C-Reactive Protein/genetics , C-Reactive Protein/metabolism , Fibrinogen/metabolism , Genetic Markers , Humans , Models, Statistical , Phenotype , Polymorphism, Single Nucleotide
19.
Thorax ; 64(7): 620-5, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19386584

ABSTRACT

BACKGROUND: Numerous areas of the human genome have previously been associated with asthma and asthma-related phenotypes, but few positive findings have been successfully replicated in independent populations. Initial studies have reported strong associations of variants in the plant homeodomain zinc finger protein 11 (PHF11) gene with serum IgE levels, asthma, airway hyper-responsiveness and childhood atopic dermatitis. OBJECTIVES: To investigate the association of variants in the PHF11 gene with asthma and associated intermediate phenotypes in two independent Western Australian population-based samples. METHODS: A linkage-disequilibrium (LD)-tagging set of 20 single nucleotide polymorphisms (SNPs) was genotyped in PHF11 in two separate populations (total n = 2315), a family-based twin study consisting of 230 families (n = 992 subjects) and a population-based nested case-control study consisting of 617 asthma cases and 706 controls. Information regarding asthma, respiratory physiology, atopy and environmental exposures was collected. Transmission disequilibrium tests, variance components models and generalised linear models were used to test for association between PHF11 SNPs and selected asthma outcomes (including longitudinal change in lung function). RESULTS: After correction for multiple testing, no statistically significant (p < 0.05) associations were found between PHF11 and either asthma or total serum IgE levels in either population. No statistically significant associations were found with any other asthma-associated phenotypes in either population. CONCLUSIONS: Previously reported associations of PHF11 with asthma outcomes were not replicated in this study. This study suggests that PHF11 is unlikely to contain polymorphic loci that have a major impact on asthma susceptibility in our populations.


Subject(s)
Asthma/genetics , DNA-Binding Proteins/genetics , Transcription Factors/genetics , Adolescent , Adult , Aged , Asthma/immunology , Case-Control Studies , Child , Diseases in Twins/genetics , Female , Genetic Predisposition to Disease , Genotype , Humans , Immunoglobulin E/blood , Linkage Disequilibrium , Male , Middle Aged , Phenotype , Polymorphism, Single Nucleotide , Young Adult
20.
Diabetologia ; 52(1): 106-14, 2009 Jan.
Article in English | MEDLINE | ID: mdl-19018513

ABSTRACT

AIMS/HYPOTHESIS: Common genetic variants influence plasma triacylglycerol, HDL-cholesterol (HDL-C) and glucose levels in cross-sectional studies. However, the longitudinal effects of these established variants have not been studied. Our aim was to examine the longitudinal associations of four such variants in the apolipoprotein A-V (APOA5), lipoprotein lipase (LPL), and glucokinase (GCK) genes with fasting glucose or lipid levels. METHODS: The individuals analysed were participants in the Busselton Health Survey (n = 4,554). Cross-sectional analyses of family data used the total association test. Longitudinal association analyses of unrelated participant data (n = 2,864) used linear mixed-effects models. RESULTS: The findings of cross-sectional association analyses replicated those of previous studies. We observed associations of the G and C alleles at the APOA5 single nucleotide polymorphisms (SNPs) rs662799 and rs3135506 with raised triacylglycerol levels (p = 0.0003 and p < 0.0001, respectively), the 447X allele at the LPL SNP rs328 with reduced triacylglycerol levels (p = 0.0004) and raised HDL-C levels (p = 0.0004), and the A allele of the GCK SNP rs1799884 with raised fasting glucose level (p = 0.015). Longitudinal association analyses showed that most of these associations did not change in the same individuals over an average follow-up time of 17.4 years, though there was some evidence that the association of the 447X allele of rs328 with raised HDL-C level significantly increased with age (p = 0.01), and that the association of the C allele of rs3135506 with raised triacylglycerol level significantly increased over time (p = 0.0007). CONCLUSIONS/INTERPRETATION: The current study suggests that the effects of established gene variants on lipid and glucose traits do not tend to alter with age during adulthood or over time.


Subject(s)
Apolipoproteins A/genetics , Blood Glucose/analysis , Genetic Variation , Glucokinase/genetics , Lipids/blood , Lipoprotein Lipase/genetics , Polymorphism, Single Nucleotide , Adolescent , Adult , Apolipoprotein A-V , Australia , DNA/blood , DNA/genetics , DNA/isolation & purification , Health Surveys , Humans , Longitudinal Studies , Middle Aged , Triglycerides/blood , Young Adult
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