Evidence-based medication adherence among seniors in the first year after heart failure hospitalisation and subsequent long-term outcomes: a restricted cubic spline analysis of adherence-outcome relationships.

PURPOSE: Non-adherence to heart failure (HF) medications is associated with poor outcomes. We used restricted cubic splines (RCS) to assess the continuous relationship between adherence to renin-angiotensin system inhibitors (RASI) and ß-blockers and long-term outcomes in senior HF patients. METHODS: We identified a population-based cohort of 4234 patients, aged 65-84 years, 56% male, who were hospitalised for HF in Western Australia between 2003 and 2008 and survived to 1-year post-discharge (landmark date). Adherence was calculated using the proportion of days covered (PDC) in the first year post-discharge. RCS Cox proportional-hazards models were applied to determine the relationship between adherence and all-cause death and death/HF readmission at 1 and 3 years after the landmark date. RESULTS: RCS analysis showed a curvilinear adherence-outcome relationship for both RASI and ß-blockers which was linear above PDC 60%. For each 10% increase in RASI and ß-blocker adherence above this level, the adjusted hazard ratio for 1-year all-cause death fell by an average of 6.6% and 4.8% respectively (trend p < 0.05) and risk of all-cause death/HF readmission fell by 5.4% and 5.8% respectively (trend p < 0.005). Linear reductions in adjusted risk for these outcomes at PDC ≥ 60% were also seen at 3 years after landmark date (all trend p < 0.05). CONCLUSION: RCS analysis showed that for RASI and ß-blockers, there was no upper adherence level (threshold) above 60% where risk reduction did not continue to occur. Therefore, interventions should maximise adherence to these disease-modifying HF pharmacotherapies to improve long-term outcomes after hospitalised HF.

Validation of ICD-10-AM Coding for Myocardial Infarction Subtype in Hospitalisation Data.

BACKGROUND: International Classification of Disease (ICD) codes are central for identifying myocardial infarction (MI) in administrative hospitalisation data, however validation of MI subtype codes is limited. We measured the sensitivity and specificity of ICD-10-AM (Australian Modification) codes for ST-elevation MI (STEMI) and non-STEMI (NSTEMI). METHODS: A sample of MI admissions was obtained from a dataset containing all MI hospitalisations in Western Australia (WA) for 2003, 2008 and 2013. Clinical data were collected from hospital medical records (n=799 patients). Cases were classified by ICD-10-AM codes for STEMI, NSTEMI and unspecified MI, and compared to clinical classification from review of available electrocardiographs (ECGs) and cardiac biomarkers (n=660). Sensitivity and specificity for ICD-10-AM coding versus clinical classification was measured, stratified by calendar year of discharge. RESULTS: The majority of classifiable cases had MI recorded in the principal diagnosis field (STEMI n=293, 84.2%; NSTEMI n=202, 74.3%; unspecified MI n=20, 50.0%). Overall sensitivity of the ICD-10-AM STEMI code was 86.3% (95% CI 81.7-90.0%) and was higher when restricted to MI as a principal versus secondary diagnosis (88.8% vs 66.7%). Comparable values for NSTEMI were 66.7% (95% CI 61.5-71.6%), and 68.8% vs 61.4% respectively. Between 2003 and 2013, sensitivity for both MI subtypes increased: 80.2-89.5% for STEMI, and 51.2-73.8% for NSTEMI. Specificity was high for NSTEMI throughout (88.2% 95% CI 84.1-91.6%), although improving over time for STEMI (68.1-76.4%). CONCLUSIONS: The sensitivity and specificity of ICD-10-AM codes for MI subtypes in hospitalisation data are generally high, particularly for principal diagnosis cases. However, the temporal improvement in sensitivity in coding of MI subtypes, particularly NSTEMI, may necessitate modification to trend studies using administrative hospitalisation data.

Prevalence and patterns of multimorbidity in Australian baby boomers: the Busselton healthy ageing study.

BACKGROUND AND OBJECTIVE: Chronic medical conditions accumulate within individuals with age. However, knowledge concerning the trends, patterns and determinants of multimorbidity remains limited. This study assessed the prevalence and patterns of multimorbidity using extensive individual phenotyping in a general population of Australian middle-aged adults. METHODS: Participants (n = 5029, 55% female), born between 1946 and 1964 and attending the cross-sectional phase of the Busselton Healthy Ageing Study (BHAS) between 2010 and 2015, were studied. Prevalence of 21 chronic conditions was estimated using clinical measurement, validated instrument scores and/or self-reported doctor-diagnosis. Non-random patterns of multimorbidity were explored using observed/expected (O/E) prevalence ratios and latent class analysis (LCA). Variables associated with numbers of conditions and class of multimorbidity were investigated. RESULTS: The individual prevalence of 21 chronic conditions ranged from 2 to 54% and multimorbidity was common with 73% of the cohort having 2 or more chronic conditions. (mean ± SD 2.75 ± 1.84, median = 2.00, range 0-13). The prevalence of multimorbidity increased with age, obesity, physical inactivity, tobacco smoking and family history of asthma, diabetes, myocardial infarct or cancer. There were 13 pairs and 27 triplets of conditions identified with a prevalence > 1.5% and O/E > 1.5. Of the triplets, arthritis (> 50%), bowel disease (> 33%) and depression-anxiety (> 33%) were observed most commonly. LCA modelling identified 4 statistically and clinically distinct classes of multimorbidity labelled as: 1) "Healthy" (70%) with average of 1.95 conditions; 2) "Respiratory and Atopy" (11%, 3.65 conditions); 3) "Non-cardiometabolic" (14%, 4.77 conditions), and 4) "Cardiometabolic" (5%, 6.32 conditions). Predictors of multimorbidity class membership differed between classes and differed from predictors of number of co-occurring conditions. CONCLUSION: Multimorbidity is common among middle-aged adults from a general population. Some conditions associated with ageing such as arthritis, bowel disease and depression-anxiety co-occur in clinically distinct patterns and at higher prevalence than expected by chance. These findings may inform further studies into shared biological and environmental causes of co-occurring conditions of ageing. Recognition of distinct patterns of multimorbidity may aid in a holistic approach to care management in individuals presenting with multiple chronic conditions, while also guiding health resource allocation in ageing populations.

A comparison of obesity indices in relation to mortality in type 2 diabetes: the Fremantle Diabetes Study.

AIMS/HYPOTHESIS: This prospective association study aimed to compare the relationship between each of four obesity indices and mortality risk in people with type 2 diabetes. METHODS: The associations of BMI, waist circumference, WHR and A Body Shape Index (ABSI) with all-cause mortality were analysed in 1282 participants of the Fremantle Diabetes Study, followed for up to 20 years after baseline assessment. Models were adjusted for age and other confounders; assessments as continuous measures and by quintile were carried out for men and women separately. Sensitivity analyses were conducted to minimise reverse causality. RESULTS: When indices were assessed as continuous variables, there were significant bivariate associations with mortality for: ABSI, which was greater in both men and women who died (p < 0.001); WHR, which was greater in women only (p = 0.033); and BMI, which was lower in women only (p < 0.001). When assessed by quintile, there were significant bivariate associations with mortality for ABSI in men and women (p < 0.001) and BMI in women only (p = 0.002). In Cox models of time to death, adjusted for age, diabetes duration, ethnicity and smoking, ABSI quintiles showed a linear trend for both men (p = 0.003) and women (p = 0.035). Men in the fifth ABSI quintile had an increased mortality risk compared with those in the first quintile (HR [95% CI]: 1.74 [1.24, 2.44]) and women in the fifth ABSI quintile had an increased mortality risk that approached statistical significance (1.42 [0.97, 2.08], p = 0.08). Men in the fifth WHR quintile had an increased mortality risk (1.47 [1.05, 2.06]). There was no association between mortality and BMI or waist circumference in either sex. CONCLUSIONS/INTERPRETATION: ABSI was the obesity index most strongly associated with all-cause mortality in Australians with type 2 diabetes. There was no evidence for an obesity paradox with any of the assessed indices. ABSI may be a better index of central obesity than waist circumference, BMI or WHR when assessing mortality risk in type 2 diabetes.

The MAAPE score in intermediate and advanced hepatocellular carcinoma treated with Yttrium-90 resin microsphere radioembolization.

BACKGROUND AND AIM: Yttrium-90 resin microsphere radioembolization (RE) is not recommended for routine use in intermediate or advanced hepatocellular carcinoma (HCC) by recent guidelines. This study aims to establish pre-treatment variables which predict survival in HCC patients treated with RE to identify those who will benefit most from it, and to inform patient selection for future trials. METHODS: Single center, retrospective study of consecutive patients with HCC treated with RE from 2007 to 2018. Patients included if undergoing their first RE treatment for intermediate or advanced HCC; a Child-Pugh score of B7 or less; and a performance status of 1 or less. Multivariable Cox regression identified variables that were significantly associated with survival. A predictive score was developed based upon coefficients from the fitted Cox regression model, and cubic spline regression was used to identify prognostic groups. RESULTS: One hundred thirteen patients with intermediate (53.1%) and advanced HCC (45.1%) followed for a median of 13.2 months were included. Variables associated with superior survival used to derive the MAAPE score were lower Model for End-Stage Liver Disease score (≤ 7), lower Alpha-fetoprotein (≤ 150 IU/L), higher serum Albumin (> 37 g/L), absence of Portal vein tumor thrombus, and better performance status (Eastern Cooperative Oncology Group = 0). Three survival prognostic groups were identified: good (median overall survival 25.0 months), average (15.3 months), and poor (6.3 months) (overall log-rank test, P < 0.001). CONCLUSION: The MAAPE score accurately identifies HCC patients in whom RE is safe and effective. This will allow for optimal patient selection for future trials of RE versus systemic therapy.

Comparison of medication adherence measures derived from linked administrative data and associations with mortality using restricted cubic splines in heart failure patients.

PURPOSE: There is no gold standard method to calculate medication adherence using administrative drug data. We compared three common methods and their ability to predict subsequent mortality in patients with heart failure (HF). METHODS: Person-linked population-based datasets were used to identify 4234 patients (56% male, mean age of 76), who survived 1 year (landmark period) following hospitalization for HF in Western Australia from 2003 to 2008. Adherence was estimated by the medication possession ratio (MPR), MPR modified (MPRm), and proportion of days covered (PDC) in patients dispensed a renin-angiotensin system inhibitor (RASI) and/or ß-blocker within the landmark period. Adjusted Cox regression models that fitted restricted cubic splines (RCS) assessed the relationship between medication adherence and 1-year all-cause death postlandmark period. RESULTS: In the landmark period, 87% and 68% of the HF cohort were dispensed RASI and ß-blockers, respectively. Mean adherence estimates for RASI and ß-blockers were 90% and 79% for MPR, 96% and 86% for MPRm, and 82% and 73% for PDC, respectively. In RCS models, MPRm was not associated with subsequent 1-year death in either the RASI or ß-blocker group, while MPR was independently associated with death in the RASI group only (P ≤ .01). However, PDC as a binary variable (PDC <80% or ≥80%) or continuous variable was independently associated with 1-year death in both RASI and ß-blocker groups (all P ≤ .02). CONCLUSION: Proportion of days covered calculated from administrative drug data provides a more conservative estimate of adherence than MPR or MPRm and was the most consistent predictor of subsequent mortality in an HF cohort using RCS analysis.

The influence of the local food environment on diet following residential relocation: longitudinal results from RESIDential Environments (RESIDE).

OBJECTIVE: To examine the associations of changes in the local food environment, individual behaviours and perceptions with changes in dietary intake, following relocation from an established neighbourhood to a new residential development. DESIGN: Spatial food environment exposure measures were generated relative to each participant's home address using the locations of food outlets at baseline (before moving house) and follow-up (1-2 years after relocation). Self-reported data on socio-demographics, self-selection, usual dietary intake, individual behaviours and perceptions of the local food environment were sourced from the RESIDential Environments (RESIDE) Project. Changes in spatial exposure measures, individual behaviours and perceptions with changes in dietary outcomes were examined using mixed linear models. SETTING: Perth, Western Australia, 2003-2007. PARTICIPANTS: Adults (n 1200) from the RESIDE Project. RESULTS: Moving to a new residential development with more convenience stores and café restaurants around the home was significantly associated with an increase in unhealthy food intake (ß = 0·049, 95 % CI 0·010, 0·089; ß = 0·020, 95 % CI 0·007, 0·033) and was partially mediated by individual behaviours and perceptions. A greater percentage of healthy food outlets around the home following relocation was significantly associated with an increase in healthy food (ß = 0·003, 95 % CI 0·001, 0·005) and fruit/vegetable intake (ß = 0·002, 95 % CI 0·001, 0·004). CONCLUSIONS: Policy and planning may influence dietary intakes by restricting the number of convenience stores and other unhealthy food outlets and increasing the relative percentage of healthy food outlets.

U-shaped association of vigorous physical activity with risk of metabolic syndrome in men with low lean mass, and no interaction of physical activity and serum 25-hydroxyvitamin D with metabolic syndrome risk.

BACKGROUND: There is uncertainty over how lean mass, physical activity (PA) and 25-hydroxyvitamin D (25-OH-D) status interact on metabolic syndrome (MetS) risk in adults. AIMS: To test the hypothesis that these factors additively influence MetS risk. METHODS: Four thousand eight hundred and fifty-eight adults (54.6% female) mean ± SD age 58.0 ± 5.8 years, body mass index 28.1 ± 4.8 kg/m2 , resident in Busselton, Western Australia. PA assessed by questionnaire (all/total and vigorous), lean mass using dual energy X-ray absorptiometry (% total body mass), serum 25-OH-D via immunoassay, analysed using multivariable logistic regression. RESULTS: In men, lower total PA was associated with MetS (no vs >24 h/week odds ratio (OR) = 3.1; ≤8 vs >24 h/week OR = 1.8, both P < 0.001), as was lower lean mass (low vs high OR = 20.4; medium vs high OR = 7.4, both P < 0.001). Men with low lean mass exhibited a U-shaped relationship of vigorous PA with MetS risk (covariate-adjusted: 0 vs 4-8 h/week OR = 2.1, P = 0.037; >12 vs 4-8 h/week OR = 4.3, P = 0.002; interaction P = 0.039). In women, low PA (0 vs >24 h/week OR = 2.1, P = 0.003) and lean mass (low vs high OR = 13.1; medium vs high OR = 7.2, both P < 0.001) were associated with MetS risk. Low 25-OH-D status was associated with MetS in men (low vs high OR = 4.1; medium vs high OR = 2.3, both P < 0.001) and women (OR = 3.5 and 2.1 respectively, both P < 0.001) with no PA interaction. CONCLUSIONS: Men and women with high lean mass have low risk of MetS regardless of PA. Low lean mass identifies men who may benefit most from increasing PA, with an optimal level associated with lowest risk. 25-OH-D and PA do not interact on MetS risk.

Equalization of four cardiovascular risk algorithms after systematic recalibration: individual-participant meta-analysis of 86 prospective studies.

AIMS: There is debate about the optimum algorithm for cardiovascular disease (CVD) risk estimation. We conducted head-to-head comparisons of four algorithms recommended by primary prevention guidelines, before and after 'recalibration', a method that adapts risk algorithms to take account of differences in the risk characteristics of the populations being studied. METHODS AND RESULTS: Using individual-participant data on 360 737 participants without CVD at baseline in 86 prospective studies from 22 countries, we compared the Framingham risk score (FRS), Systematic COronary Risk Evaluation (SCORE), pooled cohort equations (PCE), and Reynolds risk score (RRS). We calculated measures of risk discrimination and calibration, and modelled clinical implications of initiating statin therapy in people judged to be at 'high' 10 year CVD risk. Original risk algorithms were recalibrated using the risk factor profile and CVD incidence of target populations. The four algorithms had similar risk discrimination. Before recalibration, FRS, SCORE, and PCE over-predicted CVD risk on average by 10%, 52%, and 41%, respectively, whereas RRS under-predicted by 10%. Original versions of algorithms classified 29-39% of individuals aged ≥40 years as high risk. By contrast, recalibration reduced this proportion to 22-24% for every algorithm. We estimated that to prevent one CVD event, it would be necessary to initiate statin therapy in 44-51 such individuals using original algorithms, in contrast to 37-39 individuals with recalibrated algorithms. CONCLUSION: Before recalibration, the clinical performance of four widely used CVD risk algorithms varied substantially. By contrast, simple recalibration nearly equalized their performance and improved modelled targeting of preventive action to clinical need.

A 5α-reductase (SRD5A2) polymorphism is associated with serum testosterone and sex hormone-binding globulin in men, while aromatase (CYP19A1) polymorphisms are associated with oestradiol and luteinizing hormone reciprocally.

CONTEXT: Pituitary luteinizing hormone (LH) stimulates testicular production of testosterone (T) which is metabolized to dihydrotestosterone (DHT) by 5α-reductase and to oestradiol (E2) by aromatase. How the activity of population variants in these enzymes impacts on gonadal function is unclear. We examined whether polymorphisms in 5α-reductase (SRD5A2) and aromatase (CYP19A1) genes predict circulating sex hormone concentrations. DESIGN: Cross-sectional analysis of 1865 community-dwelling men aged 50.4 ± 16.8 years. MEASUREMENTS: Early morning sera assayed for T, DHT and E2 (mass spectrometry), and SHBG and LH (immunoassay). Two SRD5A2 and eleven CYP19A1 polymorphisms were analysed by PCR. Regression models were adjusted for age and cardiometabolic risk factors. RESULTS: SRD5A2 polymorphism rs9282858 GA vs. GG was associated with higher serum T (+1.5 nmol/L, P < 0.001) and higher SHBG (+3.3 nmol/L, P = 0.001). CYP19A1 polymorphisms were associated with higher serum E2 and lower LH in reciprocal fashion, from which the two-copy haplotype rs10046 = T/rs2899470 = G/rs11575899 = I/rs700518 = G/rs17703883 = T was associated with higher E2 (63.4 vs. 56.5 pmol/L, P = 0.001) and lower LH (3.9 vs. 4.5 IU/L, P = 0.001) compared to null copies. Conversely, rs10046 = C/rs2899470 = T/rs11575899 = D/rs700518 = A/rs17703883 = C was associated with lower E2 (51.8 vs. 62.0 pmol/L, P = 0.001) and higher LH (5.7 vs. 3.9 IU/L, P < 0.001). These haplotypes were associated primarily with differences in E2 in men <65 years and LH in men ≥65 years. CONCLUSIONS: A 5α-reductase polymorphism predicts circulating T and SHBG, while aromatase polymorphisms predict E2 and LH in reciprocal fashion. Age and aromatase polymorphisms interact to affect E2 and LH. How these functional polymorphisms impact on male reproductive and general health outcomes requires further study.

Higher circulating androgens and higher physical activity levels are associated with less central adiposity and lower risk of cardiovascular death in older men.

OBJECTIVE: Low endogenous sex hormones and low physical activity (PA) levels have been associated with CVD risk. Whether these interact to influence CVD outcomes remains unclear. We assessed whether sex hormone concentrations and PA were additively associated with lower central adiposity and CVD risk. PATIENTS: 3351 community-dwelling men, mean age 77 years. MEASUREMENTS: Baseline testosterone (T), dihydrotestosterone (DHT) and oestradiol (E2) were assayed. Levels of PA were ascertained by questionnaire. Men were stratified using median splits into high hormone + high PA (H/H), high hormone + low PA (H/L); low hormone + high PA (L/H) and low hormone + low PA (L/L) groups. RESULTS: A total of 865 CVD events and 499 CVD deaths occurred during 10-year mean follow-up. Men with higher T, DHT or SHBG and higher PA had the lowest BMI, waist circumference and risk of metabolic syndrome. Men with higher T had the lowest risk of incident CVD events, irrespective of PA level. Men with higher T or DHT and higher PA had the lowest risk of dying from CVD (eg, hazard ratios for T/PA H/H 0.76 P = 0.031; H/L 0.85 P = 0.222; L/H 0.80 P = 0.075; L/L 1.00). CONCLUSION: Higher circulating androgens and higher PA were associated with less central adiposity at baseline and fewer CVD deaths during follow-up. These findings are consistent with a potential additive effect of androgens and PA on cardiometabolic outcomes in older men.

Cross-sectional associations of sex hormones with leucocyte telomere length, a marker of biological age, in a community-based cohort of older men.

CONTEXT: Telomeres protect chromosomes from damage, and shorter leucocyte telomere length (LTL) is a marker of advancing biological age. The association between testosterone (T) and its bioactive metabolites, dihydrotestosterone (DHT) and oestradiol (E2) with telomere length, particularly in older men, is uncertain. The study aimed to clarify associations of sex hormones with LTL in older men. PARTICIPANTS AND METHODS: We used cross-sectional data from 2913 men aged 76.7 ± 3.2 years with morning blood samples assayed for T, DHT, E2 (mass spectrometry), and sex hormone-binding globulin (SHBG, immunoassay), to correlate sex hormones with LTL measured using PCR and expressed as T/S ratio in multivariable linear regression models adjusted for age, cardiometabolic risk factors and cardiovascular disease history. RESULTS: Average difference per decade of age was T -0.46 nmol/L, DHT -0.11 nmol/L, E2 -7.5 pmol/L, SHBG +10.2 nmol/L and LTL (T/S ratio) -0.065. E2 correlated with T/S ratio (r = 0.038, P = 0.039) and SHBG was inversely correlated (r = -0.053, P = 0.004). After multivariable adjustment, E2 was associated with T/S ratio (per 1 SD increase E2: coefficient 0.011, P = 0.043), T and DHT were not associated. When E2 and SHBG were simultaneously included, E2 remained positively (coefficient 0.014, P = 0.014) and SHBG inversely (coefficient -0.013, P = 0.037) associated with T/S ratio. CONCLUSIONS: In older men, neither T nor DHT is associated with LTL while E2 is independently associated with LTL and SHBG is inversely associated, thus relating sex hormone exposure to lower biological age. Further research is needed to determine causality and clarify the role of sex hormones in male ageing.

Serum 25-hydroxyvitamin D as a predictor of mortality and cardiovascular events: A 20-year study of a community-based cohort.

OBJECTIVE: Prospective studies, mostly from Europe and North America, suggest that serum 25-hydroxyvitamin D (25(OH)D) is inversely associated with mortality and cardiovascular disease (CVD) risk. Data from other regions are limited, and threshold levels for adverse cardiovascular outcomes are uncertain. We examined serum 25(OH)D as a predictor of total mortality and cardiovascular outcomes in an Australian cohort. DESIGN: A 20-year, community-based cohort study. PATIENTS: Participants in the 1994/1995 Busselton Health Survey (n = 3946, baseline age 25-84 years). MEASUREMENTS: Baseline serum 25(OH)D and mortality and cardiovascular outcomes to 2014 obtained by record linkage. RESULTS: The mean serum 25(OH)D concentration was 60.6 ± 18.0 nmol/L. During 20-year follow-up (excluding the first 2 years), 889 participants died (including 363 from CVD) and 944 experienced a CVD event (including 242 with heart failure). In the full cohort, controlling for Framingham risk score variables, higher baseline 25(OH)D was associated with significantly reduced all-cause mortality (adjusted HR 0.83 per SD increment of 25(OH)D, 95% CI 0.77-0.90), CVD death (HR 0.85, 95% CI 0.74-0.96) and heart failure (HR 0.81, 95% CI 0.69-0.94), but not CVD events (HR 0.99, 0.92-1.07). In restricted cubic spline regression models, serum 25(OH)D below 65 and 55 nmol/L was associated with higher total mortality and higher CVD mortality/heart failure, respectively. In participants without CVD at baseline (n = 3220), results were similar, but hazard ratios were attenuated and associations with CVD mortality no longer significant. CONCLUSIONS: In an Australian community-based cohort, baseline vitamin D levels below 55-65 nmol/L are predictive of all-cause mortality, CVD death and heart failure.

A prospective cohort examination of haematological parameters in relation to cancer death and incidence: the Busselton Health Study.

BACKGROUND: Cancer risk is associated with serum iron levels. The aim of this study was to evaluate whether haematological parameters reflect serum iron levels and may also be associated with cancer risk. METHODS: We studied 1564 men and 1769 women who were enrolled in the Busselton Health Study, Western Australia. Haematological parameters evaluated included haemoglobin (Hb), mean cell volume (MCV), mean cell haemoglobin (MCH) and mean cell haemoglobin concentration (MCHC) and red cell distribution width (RCDW). Statistical analyses included t-tests for quantitative variables, chi-square tests for categorical variables and Cox proportional hazards regression modelling for cancer incidence and death. RESULTS: There was marginal evidence of an association between MCV (as a continuous variable) and non-skin cancer incidence in women (HR 1.15, 95% CI 1.013, 1.302; p = 0.030) but the hazard ratio was attenuated to non-significance after adjustment for serum ferritin (SF), iron and transferrin saturation (TS) (HR 1.11, 95% CI 0.972, 1.264; p = 0.126). There was strong evidence of an association between MCHC and prostate cancer incidence in men; the estimated hazard ratio for an increase of one SD (0.5) in MCHC was 1.27 (95% CI 1.064, 1.507; p = 0.008). These results remained significant after further adjustment for SF and iron; the estimated hazard ratio for an increase of one SD (0.5) in MCHC was 1.25 (p = 0.014, 95% CI 1.05 to 1.48). CONCLUSIONS: The MCHC and MCV were associated with cancer incidence in a Western Australian population, although only MCHC remained associated with prostate cancer after adjusting with serum iron and TS (circulating iron) and SF (storage iron). Haematological parameters are thus of limited utility in population profiling for future cancer risk.

Patterns of Medicare-funded primary health and specialist consultations in Aboriginal and non-Aboriginal Australians in the two years before hospitalisation for ischaemic heart disease.

BACKGROUND: Ischaemic heart disease (IHD) remains the leading cause of morbidity and mortality for both Aboriginal and non-Aboriginal Australians. Patterns of primary and specialist care in patients leading up to the first hospitalisation for IHD potentially impact on prevention and subsequent outcomes. We investigated the differences in general practice (GP), specialist and emergency department (ED) consultations, and associated resource use in Aboriginal and non-Aboriginal people in the two years preceding hospitalisation for IHD. METHODS: Linked-data were used to identify first IHD admissions for Western Australians aged 25-74 years in 2002-2007. Person-linked GP, specialist and ED consultations were obtained from the Medicare Benefits Schedule (MBS) and ED records to assess health care access and costs for the preceding 2 years. RESULTS: Aboriginal people constituted 4.7% of 27,230 IHD patients, 3.5% of 1,348,238 MBS records, and 14% of 33,170 ED presentations. Aboriginal (vs. non-Aboriginal) people were younger (mean 50.2 vs 60.5 years), more commonly women (45.2% vs 28.4%), had more comorbidities [Charlson index≥1, 35.2% vs 26.3%], were more likely to have had GP visits (adjusted rate-ratio 1.07, 95% CI 1.02-1.12), long/prolonged (16.0% vs 11.9%) consults and non-vocationally registered GP consults (17.1% vs 3.2%), but less likely to received specialist consults (mean 1.0 vs 4.1). Mean number of urgent/semi-urgent ED presentations in the year preceding the IHD admission was higher in Aboriginal people (2.9 vs 1.9). Aboriginal people incurred 2.7% of total associated MBS expenditure (estimated at $59.7 million). Mean total cost per person was 43.3% lower in Aboriginal patients, with cost differentials being greatest in diabetic and chronic kidney disease patients. CONCLUSIONS: Despite being over-represented in urgent/semi-urgent ED presentations and admissions for IHD, Aboriginal people were under-resourced compared with the rest of the population, particularly in terms of specialist care prior to first IHD hospitalisation. The findings underscore the need for better primary and specialist shared care delivery models particularly for Aboriginal people.

Obstructive airway disease in 46-65-year-old people in Busselton, Western Australia, 1966-2015.

OBJECTIVE: To document the changing levels of tobacco smoking, respiratory symptoms, doctor-diagnosed asthma, and lung function in Busselton adults aged 46-65 years over the past 50 years. DESIGN, SETTING, PARTICIPANTS: Repeated cross-sectional population surveys (1966 to 2010-2015) of adults registered to vote in the Busselton shire, Western Australia, including a modified version of the British Medical Research Council questionnaire on respiratory symptoms. MAIN OUTCOME MEASURES: History of doctor-diagnosed asthma and chronic obstructive pulmonary disease (COPD), tobacco smoking history, respiratory medications used, spirometry parameters (forced expiratory volume in one second [FEV1], forced vital capacity [FVC]). RESULTS: The prevalence of tobacco smoking among men declined from 53% in 1966 to 12% in 2010-2015, and from 26% to 9% among women. The prevalence of ever-smoking (ie, smokers and ex-smokers) decreased from 80% to 57% for men but increased from 33% to 50% for women. The prevalence of doctor-diagnosed asthma increased, as did the use of long-acting bronchodilator aerosol medications by people with asthma and COPD. There have been no consistent changes in the prevalence of specific respiratory symptoms, but measures of lung function have significantly improved. CONCLUSIONS: Smoking rates declined as a result of changes in pricing, prohibitions on smoking and the feedback of survey results to Busselton participants. Significant improvements in lung function were measured, and it can be anticipated that the prevalence of other smoking-related diseases will also decline.

The Prognostic Ability of Major Hepatocellular Carcinoma Staging Systems Is Improved by Including a Treatment Variable.

BACKGROUND AND AIMS: There has been significant debate regarding which hepatocellular carcinoma (HCC) staging system is best able to predict survival. We hypothesized that the prognostic ability of the Barcelona Clinic Liver Cancer (BCLC) and Hong Kong Liver Cancer (HKLC) systems would be improved with the addition of an explicit treatment variable. METHODS: We performed an analysis of a prospectively enrolled cohort of 292 patients undergoing 532 treatment episodes for HCC from 2006 to 2014. BCLC, standard nine-stage HKLC (HKLC9), and modified five-stage HKLC (HKLC5) for each treatment episode were assessed. Overall survival and time to disease progression were calculated for the initial treatment, re-treatment, and overall treatment cohorts. We compared the performance of various prognostic models including staging system alone, treatment alone, and staging system plus treatment using the corrected Akaike information criterion and Harrell's C statistic. RESULTS: The BCLC, HKLC5, and HKLC9 systems were significant predictors of survival and time to progression for all treatment cohorts (log rank test, p < 0.001). The addition of a treatment variable significantly improved (p < 0.01) the prognostic ability of the survival and time to progression models compared with those containing only the BCLC or HKLC stage across all treatment cohorts other than survival in re-treatment for BCLC (p = 0.094). CONCLUSIONS: Adding a treatment variable to major HCC staging systems improves their ability to predict survival and time to progression in initial treatment, re-treatment, and overall.

Vitamin D and respiratory health in the Busselton Healthy Ageing Study.

BACKGROUND AND OBJECTIVE: The relationship between vitamin D and respiratory disease was examined by cross-sectional analysis of a large community-based sample. METHODS: Serum 25-hydroxyvitamin D (25OHD) and history of respiratory disease, symptoms (recorded by questionnaire) and spirometry were measured in 5011 adults aged 45-69 years. Adjustments were made for age, sex, season and smoking (Model A), plus body mass index (BMI) and physical activity level (Model B), plus history of chronic diseases (Model C). RESULTS: Mean (SD) age was 58 (SD 6) years with 45% males, 10% current smokers and 12% taking vitamin D supplements. The prevalence of 25OHD level <50 nmol/L was 8.0%. In all the three models, 25OHD <50 nmol/L was significantly associated with asthma (Model C: odds ratio (OR): 1.32; 95% CI: 1.00, 1.73), bronchitis (1.54; 1.17, 2.01), wheeze (1.37; 1.10, 1.71) and chest tightness (1.42; 1.10, 1.83). Participants with vitamin D level > 100 nmol/L had higher forced vital capacity (FVC) in all the three models (1.17% higher, compared with the 50-100 nmol/L group in Model C). CONCLUSION: Low levels of serum 25OHD were independently associated with asthma, bronchitis, wheeze and chest tightness after three levels of adjustment for potential confounders. Higher vitamin D levels were associated with higher levels of lung function.

Food environments and dietary intakes among adults: does the type of spatial exposure measurement matter? A systematic review.

BACKGROUND: The relationships between food environments and dietary intake have been assessed via a range of methodologically diverse measures of spatial exposure to food outlets, resulting in a largely inconclusive body of evidence, limiting informed policy intervention. OBJECTIVE: This systematic review aims to evaluate the influence of methodological choice on study outcomes by examining the within-study effect of availability (e.g., counts) versus accessibility (e.g., proximity) spatial exposure measures on associations with diet. METHODS: (PROSPERO registration: CRD42018085250). PubMed, Web of Science, Scopus and ScienceDirect databases were searched for empirical studies from 1980 to 2017, in the English language, involving adults and reporting on the statistical association between a dietary outcome and spatial exposure measures of both availability and accessibility. Studies were appraised using an eight-point quality criteria with a narrative synthesis of results. RESULTS: A total of 205 associations and 44 relationships (i.e., multiple measures of spatial exposure relating to a particular food outlet type and dietary outcome) were extracted from 14 eligible articles. Comparative measures were dominated by counts (availability) and proximity (accessibility). Few studies compared more complex measures and all counts were derived from place-based measures of exposure. Sixteen of the 44 relationships had a significant effect involving an availability measure whilst only 8 had a significant effect from an accessibility measure. The largest effect sizes in relationships were mostly for availability measures. After stratification by scale, availability measure had the greatest effect size in 139 of the 176 pairwise comparisons. Of the 33% (68/205) of associations that reached significance, 53/68 (78%) were from availability measures. There was no relationship between study quality and reported study outcomes. CONCLUSIONS: The limited evidence suggests that availability measures may produce significant and greater effect sizes than accessibility measures. However, both availability and accessibility measures may be important concepts of spatial exposure depending on the food outlet type and dietary outcome examined. More studies reporting on multi-method effects are required to differentiate findings by the type of spatial exposure assessment and build an evidence base regarding the appropriateness and robustness of measures under different circumstances.

Use of Repeated Blood Pressure and Cholesterol Measurements to Improve Cardiovascular Disease Risk Prediction: An Individual-Participant-Data Meta-Analysis.

The added value of incorporating information from repeated blood pressure and cholesterol measurements to predict cardiovascular disease (CVD) risk has not been rigorously assessed. We used data on 191,445 adults from the Emerging Risk Factors Collaboration (38 cohorts from 17 countries with data encompassing 1962-2014) with more than 1 million measurements of systolic blood pressure, total cholesterol, and high-density lipoprotein cholesterol. Over a median 12 years of follow-up, 21,170 CVD events occurred. Risk prediction models using cumulative mean values of repeated measurements and summary measures from longitudinal modeling of the repeated measurements were compared with models using measurements from a single time point. Risk discrimination (C-index) and net reclassification were calculated, and changes in C-indices were meta-analyzed across studies. Compared with the single-time-point model, the cumulative means and longitudinal models increased the C-index by 0.0040 (95% confidence interval (CI): 0.0023, 0.0057) and 0.0023 (95% CI: 0.0005, 0.0042), respectively. Reclassification was also improved in both models; compared with the single-time-point model, overall net reclassification improvements were 0.0369 (95% CI: 0.0303, 0.0436) for the cumulative-means model and 0.0177 (95% CI: 0.0110, 0.0243) for the longitudinal model. In conclusion, incorporating repeated measurements of blood pressure and cholesterol into CVD risk prediction models slightly improves risk prediction.