Compliance-Adjusted Estimates of Aspirin Effects Among Older Persons in the ASPREE Randomized Trial.

The Aspirin in Reducing Events in the Elderly (ASPREE) Trial recruited 19,114 participants across Australia and the United States during 2010-2014. Participants were randomized to receive either 100 mg of aspirin daily or matching placebo, with disability-free survival as the primary outcome. During a median 4.7 years of follow-up, 37% of participants in the aspirin group permanently ceased taking their study medication and 10% commenced open-label aspirin use. In the placebo group, 35% and 11% ceased using study medication and commenced open-label aspirin use, respectively. In order to estimate compliance-adjusted effects of aspirin, we applied rank-preserving structural failure time models. The results for disability-free survival and most secondary endpoints were similar in intention-to-treat and compliance-adjusted analyses. For major hemorrhage, cancer mortality, and all-cause mortality, compliance-adjusted effects of aspirin indicated greater risks than were seen in intention-to-treat analyses. These findings were robust in a range of sensitivity analyses. In accordance with the original trial analyses, compliance-adjusted results showed an absence of benefit with aspirin for primary prevention in older people, along with an elevated risk of clinically significant bleeding.

The relationship between long-term blood pressure variability and cortical thickness in older adults.

High blood pressure variability (BPV) is a risk factor for cognitive decline and dementia, but its association with cortical thickness is not well understood. Here we use a topographical approach, to assess links between long-term BPV and cortical thickness in 478 (54% men at baseline) community dwelling older adults (70-88 years) from the ASPirin in Reducing Events in the Elderly NEURO sub-study. BPV was measured as average real variability, based on annual visits across three years. Higher diastolic BPV was significantly associated with reduced cortical thickness in multiple areas, including temporal (banks of the superior temporal sulcus), parietal (supramarginal gyrus, post-central gyrus), and posterior frontal areas (pre-central gyrus, caudal middle frontal gyrus), while controlling for mean BP. Higher diastolic BPV was associated with faster progression of cortical thinning across the three years. Diastolic BPV is an important predictor of cortical thickness, and trajectory of cortical thickness, independent of mean blood pressure. This finding suggests an important biological link in the relationship between BPV and cognitive decline in older age.

Clinical risk prediction model for 30-day all-cause re-hospitalisation or mortality in patients hospitalised with heart failure.

BACKGROUND: This study aimed to develop a risk prediction model (AUS-HF model) for 30-day all-cause re-hospitalisation or death among patients admitted with acute heart failure (HF) to inform follow-up after hospitalisation. The model uses routinely collected measures at point of care. METHODS: We analyzed pooled individual-level data from two cohort studies on acute HF patients followed for 30-days after discharge in 17 hospitals in Victoria, Australia (2014-2017). A set of 58 candidate predictors, commonly recorded in electronic medical records (EMR) including demographic, medical and social measures were considered. We used backward stepwise selection and LASSO for model development, bootstrap for internal validation, C-statistic for discrimination, and calibration slopes and plots for model calibration. RESULTS: The analysis included 1380 patients, 42.1% female, median age 78.7 years (interquartile range = 16.2), 60.0% experienced previous hospitalisation for HF and 333 (24.1%) were re-hospitalised or died within 30 days post-discharge. The final risk model included 10 variables (admission: eGFR, and prescription of anticoagulants and thiazide diuretics; discharge: length of stay>3 days, systolic BP, heart rate, sodium level (<135 mmol/L), >10 prescribed medications, prescription of angiotensin converting enzyme inhibitors or angiotensin receptor blockers, and anticoagulants prescription. The discrimination of the model was moderate (C-statistic = 0.684, 95%CI 0.653, 0.716; optimism estimate = 0.062) with good calibration. CONCLUSIONS: The AUS-HF model incorporating routinely collected point-of-care data from EMRs enables real-time risk estimation and can be easily implemented by clinicians. It can predict with moderate accuracy risk of 30-day hospitalisation or mortality and inform decisions around the intensity of follow-up after hospital discharge.

Australasian ACPGBI risk prediction model for 30-day mortality after colorectal cancer surgery.

BACKGROUND: Postoperative mortality after colorectal cancer surgery varies across hospitals and countries. The aim of this study was to test the Association of Coloproctologists of Great Britain and Ireland (ACPGBI) models as predictors of 30-day mortality in an Australian cohort. METHODS: Data from patients who underwent surgery in six hospitals between 1996 and 2015 (CRC data set) were reviewed to test ACPGBI models, and patients from 79 hospitals in the Bi-National Colorectal Cancer Audit between 2007 and 2016 (BCCA data set) were analysed to validate model performance. Recalibrated models based on ACPGBI risk models were developed, tested and validated on a data set of Australasian patients. RESULTS: Of 18 752 patients observed during the study, 6727 (CRC data set) and 3814 (BCCA data set) were analysed. The 30-day mortality rate was 1·1 and 3·5 per cent in the CRC and BCCA data sets respectively. Both the original and revised ACPGBI models overestimated 30-day mortality for the CRC data set (observed to expected (O/E) ratio 0·17 and 0·21 respectively). Their ability to correctly predict mortality risk was poor (P < 0·001, Hosmer-Lemeshow test); however, the area under the curve for both models was 0·88 (95 per cent c.i. 0·85 to 0·92) showing good discriminatory power to classify 30-day mortality. The recalibrated original model performed well for calibration and discrimination, whereas the recalibrated revised model performed well for discrimination but not for calibration. Risk prediction was good for both recalibrated models. On external validation using the BCCA data set, the recalibrated models underestimated mortality risk (O/E ratio 3·06 and 2·98 respectively), whereas both original and revised ACPGBI models overestimated the risk (O/E ratio 0·48 and 0·69). All models showed similar good discrimination. CONCLUSION: The original and revised ACPGBI models overpredicted risk of 30-day mortality. The new Australasian calibrated ACPGBI model needs to be tested further in clinical practice.

ANTECEDENTES: La mortalidad postoperatoria tras la cirugía del cancer colorrectal (colorectal cáncer, CRC) varía entre hospitales y países. El objetivo de este estudio era evaluar los modelos de la Asociación de Coloproctólogos de Gran Bretaña e Irlanda (Association of Coloproctologists of Great Britain and Ireland, ACPGBI) como predictores de mortalidad a los 30 días en una cohorte de pacientes de Australia. MÉTODOS: Se revisaron los datos de pacientes sometidos a cirugía en seis hospitales entre 1996-2015 (datos CRC) para evaluar los modelos ACPGBI, mientras que los datos recogidos en 79 hospitales en la auditoría bi-nacional de cáncer colorrectal (Bi-National Colorectal Cancer Audit) entre 2007-2016 (datos BCCA) se analizaron para validar el comportamiento del modelo. Se desarrollaron modelos recalibrados basados en los modelos de riesgo ACPGBI que fueron aplicados y validados en un conjunto de datos multi-institucionales de pacientes australianos. La mortalidad observada y estimada (tasa 0/E) a 30 días se calculó en los modelos ACPGBI original y revisados usando el test de Hosmer-Lemeshow y los análisis de la curva de las características operador-receptor (ROC) para evaluar la calibración y discriminación de los modelos. RESULTADOS: De un total de 18,752 pacientes observados durante el periodo de estudio, se analizaron 6.727 (datos CRC) y 3.814 (datos BCCA). La mortalidad en los pacientes del grupo de datos CRC fue del 1,1% y en los del grupo de datos BCCA del 3,5%. Para el grupo de datos CRC, los modelos ACPGBI sobreestimaron significativamente la mortalidad a los 30 días, tanto en el modelo original como en el modelo revisado (O/E 0,17 y 0,21). La capacidad de los modelos para predecir correctamente el riesgo de mortalidad también fue limitada (test de Hosmer-Lemeshow 23,1 y 22.9); sin embargo, el área bajo la curva ROC de ambos modelos fue de 0,88 (i.c. del 95% 0,85-0,92) con una buena capacidad discriminatoria para clasificar a los pacientes que fallecían durante los primeros 30 días tras la cirugía. El modelo original ACPGBI recalibrado presentó un buen comportamiento para la predicción de riesgo (tasa O/E 1,06), pero no fue así en el caso del modelo revisado ACPGBI recalibrado (tasa O/E 0,99). En la validación externa con los datos BCCA, los modelos recalibrados subestimaron el riesgo de mortalidad a los 30 días (tasa O/E 3,06 y 2,98), mientras que los modelos ACPGBI original y revisado sobreestimaron el riesgo (tasa O/E 0,48 y 0,69, respectivamente). Todos los modelos mostraron una buena discriminación en las curvas ROC. CONCLUSIÓN: Los modelos ACPGBI original y revisado sobreestimaron el riesgo de mortalidad a los 30 días. Se desarrolló un nuevo modelo, denominado modelo ACPGBI calibrado australiano o modelo ACACPGBI, cuya utilidad en la práctica clínica debe ser evaluada.

Age and other perioperative risk factors for postoperative systemic inflammatory response syndrome after cardiac surgery.

BACKGROUND: The inflammatory response to surgery varies considerably between individual patients. Age might be a substantial factor in this variability. Our objective was to examine the association of patient age and other potential risk factors with the occurrence of a postoperative systemic inflammatory response syndrome, during the first 24 h after cardiac surgery. METHODS: This was a retrospective cohort study, using linked data from the Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) Database and the Australian and New Zealand Intensive Care Society (ANZICS) Adult Patient Database. Data from patients who underwent coronary artery bypass grafting and/or valve surgery were used. The association between age and postoperative SIRS was analysed using Poisson regression, and corrected for other risk factors. Restricted cubic splines were used to determine relevant age categories. Results are expressed as risk ratios (RR) with 95% confidence intervals (CI). RESULTS: Data from 28 513 patients were used. In both univariable and multivariable models, increased patient age was strongly associated with reduced postoperative SIRS prevalence. Using 73-83 yr as the reference category, the RRs (95% CI) for the age categories were 1.38 (1.28-1.49) for ≤43 yr, 1.15 (1.09-1.20) for 44-63 yr, 1.05 (1.00-1.09) for 64-72 yr, and 1.03 (0.94-1.12) for >83 yr, respectively. The predictive value for postoperative SIRS of the final model, however, was moderate (c-statistic: 0.61). CONCLUSIONS: We have demonstrated that advanced patient age is associated with a decreased risk of postoperative SIRS among cardiac surgery patients, where patients aged over 72 yr had the lowest risk.

The association between peri-operative acute risk change (ARC) and long-term survival after cardiac surgery.

Acute risk change has been described as the difference in calculated mortality risk between the pre-operative and postoperative periods of cardiac surgery. We aimed to assess whether this was associated with long-term survival after cardiac surgery. We retrospectively analysed 22,570 cardiac surgical patients, with minimum and maximum follow-up of 1.0 and 6.7 years. Acute risk change was calculated as the arithmetic difference between pre- and postoperative mortality risk. 'Rising risk' represented an increase in risk from pre- to postoperative phase. The primary outcome was one-year mortality. Secondary outcomes included mortality at 3 and 5 years and time to death. Univariable and multivariable analyses were undertaken to examine the relationship between acute risk change and outcomes. Rising risk was associated with higher mortality (5.6% vs. 3.5%, p < 0.001). After adjusting for baseline risk, rising risk was independently associated with increased 1-year mortality (OR 2.6, 95%CI 2.2-3.0, p < 0.001). The association of rising risk with long-term survival was greatest in patients with highest baseline risk. Cox regression confirmed rising risk was associated with shorter time to death (HR 1.86, 1.68-2.05, p < 0.001). Acute risk change may represent peri-operative clinical events in combination with unmeasured patient risk and noise. Measuring risk change could potentially identify patterns of events that may be amenable to investigation and intervention. Further work with case review, and risk scoring with shared variables, may identify mechanisms, including the interaction between miscalibration of risk and true differences in peri-operative care.

Standard vs. intensified management of heart failure to reduce healthcare costs: results of a multicentre, randomized controlled trial.

AIMS: To determine if an intensified form of heart failure management programme (INT-HF-MP) based on individual profiling is superior to standard management (SM) in reducing health care costs during 12-month follow-up (primary endpoint). METHODS AND RESULTS: A multicentre randomized trial involving 787 patients (full analysis set) discharged from four tertiary hospitals with chronic HF who were randomized to SM (n = 391) or INT-HF-MP (n = 396). Mean age was 74 ± 12 years, 65% had HF with a reduced ejection fraction (31.4 ± 8.9%) and 14% were remote-dwelling. Study groups were well matched. According to Green, Amber, Red Delineation of rIsk And Need in HF (GARDIAN-HF) profiling, regardless of location, patients in the INT-HF-MP received a combination of face-to-face (home visits) and structured telephone support (STS); only 9% (`low risk') were designated to receive the same level of management as the SM group. The median cost in 2017 Australian dollars (A$1 equivalent to ∼EUR €0.7) of applying INT-HF-MP was significantly greater than SM ($152 vs. $121 per patient per month; P < 0.001), However, at 12 months, there was no difference in total health care costs for the INT-HF-MP vs. SM group (median $1579, IQR $644 to $3717 vs. $1450, IQR $564 to $3615 per patient per month, respectively). This reflected minimal differences in all-cause mortality (17.7% vs. 18.4%; P = 0.848) and recurrent hospital stay (18.6 ± 26.5 vs. 16.6 ± 24.8 days; P = 0.199) between the INT-HF-MP and SM groups, respectively. CONCLUSION: During 12-months follow-up, an INT-HF-MP did not reduce healthcare costs or improve health outcomes relative to SM.

Incidence of chronic kidney disease among people with diabetes: a systematic review of observational studies.

AIMS: The aim was to systematically review published articles that reported the incidence of chronic kidney disease among people with diabetes. METHODS: A systematic literature search was performed using MEDLINE, Embase and CINAHL databases. The titles and abstracts of all publications identified by the search were reviewed and 10 047 studies were retrieved. RESULTS: A total of 71 studies from 30 different countries with sample sizes ranging from 505 to 211 132 met the inclusion criteria. The annual incidence of microalbuminuria and albuminuria ranged from 1.3% to 3.8% for Type 1 diabetes. For Type 2 diabetes and studies combining both diabetes types, the range was from 3.8% to 12.7%, with four of six studies reporting annual rates between 7.4% and 8.6%. In studies reporting the incidence of eGFR < 60 ml/min/1.73 m2 using the Modification of Diet on Renal Disease (MDRD) equation, apart from one study which reported an annual incidence of 8.9%, the annual incidence ranged from 1.9% to 4.3%. The annual incidence of end-stage renal disease ranged from 0.04% to 1.8%. CONCLUSIONS: The annual incidence of microalbuminuria and albuminuria is ~ 2-3% in Type 1 diabetes, and ~ 8% in Type 2 diabetes or mixed diabetes type. The incidence of developing eGFR < 60 ml/min/1.73 m2 is ~ 2-4% per year. Despite the wide variation in methods and study design, within a particular category of kidney disease, there was only modest variation in incidence rates. These findings may be useful in clinical settings to help understand the risk of developing kidney disease among those with diabetes.

ASPREE-D: Aspirin for the prevention of depression in the elderly.

BACKGROUND: Not only is depression associated with increased inflammation but inflammation is a risk factor for the genesis of depression. Many of the environmental risk factors for depression are transduced through inflammatory signaling. Anti-inflammatory agents show promise for the management of depression in preclinical, epidemiological, and early clinical studies. This opens the door to the potential for anti-inflammatory agents to treat and prevent depression. There are no evidence-based pharmacotherapies for depression prevention. METHOD: ASPREE-D, aspirin in the prevention of depression in the elderly, is a sub study of ASPREE, which explores the potential of aspirin to prevent a range of inflammation related disorders in the elderly. With a sample size of 19,114, and a duration of 5 years, this placebo controlled study will be one of the largest randomized controlled trials in psychiatry and will provide definitive evidence on the ability of aspirin to prevent depression. RESULTS: This paper presents the rationale for the study and presents a summary of the study design. CONCLUSIONS: ASPREE-D may not only define novel therapy but will provide mechanistic proof of concept of the role of inflammation in depression.

Acute risk change (ARC) identifies outlier institutions in perioperative cardiac surgical care when the standardized mortality ratio cannot.

BACKGROUND: With improvements in short-term mortality after cardiac surgery, the sensitivity of the standardized mortality ratio (SMR) as a performance-monitoring tool has declined. We assessed acute risk change (ARC) as a new and potentially more sensitive metric to differentiate overall cardiac surgical unit performance. METHODS: Retrospective analysis of the Australian and New Zealand Society of Cardiac and Thoracic Surgeons database and Australian and New Zealand Intensive Care Society Adult Patient Database was performed. The 16 656 patients who underwent coronary artery bypass grafting or cardiac valve procedures during a 4 yr period were included. The ARC was generated using the change between preoperative and postoperative probability of death. Outlier institutions were those with higher (outside 99.8% confidence intervals) ARC or SMR on annual and 4 yr funnel plots. Outliers were grouped and compared with non-outliers for baseline characteristics, intraoperative events, and postoperative morbidity. RESULTS: No outliers were identified using SMR. Two outliers were identified using ARC. Outliers had higher rates of new renal failure (5.7 vs 4.5%, P=0.017), stroke (1.6 vs 0.9%, P=0.001), reoperation (9 vs 6.0%, P<0.001), and prolonged ventilation (15.3 vs 9.5%, P<0.001). Outliers transfused more blood products (P<0.001) and had longer cardiopulmonary bypass times (P<0.001) and less senior surgeons operating (P<0.001). CONCLUSIONS: Acute risk change was able to discriminate between units where SMR could not. Outliers had more adverse events. Acute risk change can be calculated before mortality outcome and identifies outliers with lower patient numbers. This may allow early recognition and investigation of outlier units.

Clopidogrel, prasugrel or ticagrelor in patients with acute coronary syndromes undergoing percutaneous coronary intervention.

BACKGROUND: Guidelines recommend prasugrel or ticagrelor instead of clopidogrel in patients with acute coronary syndromes (ACS) undergoing percutaneous coronary interventions (PCI). AIM: We sought to describe the trends in uptake of the newer agents and analyse the clinical characteristics and short-term outcomes of patients treated with clopidogrel, prasugrel or ticagrelor. METHODS: We analysed the temporal trends of antiplatelet use since the availability of prasugrel (2009-2013) in patients with ACS from the Melbourne Interventional Group registry. To assess clinical characteristics and outcomes, we included 1850 patients from 2012 to 2013, corresponding to the time all three agents were available. The primary outcome was major adverse cardiovascular events (MACE). The safety end-point was in-hospital bleeding. RESULTS: For the period of 2009-2013, the majority of patients were treated with clopidogrel (72%) compared with prasugrel (14%) or ticagrelor (14%). There was a clear trend towards ticagrelor by the end of 2013. Patients treated with clopidogrel were more likely to present with non-ST-elevation ACS, be older, and have more comorbidities. There was no difference in unadjusted 30-day mortality (0.9 vs 0.5 vs 1.0%, P = 0.76), myocardial infarction (2 vs 1 vs 2%, P = 0.52) or MACE (3 vs 3 vs 4%, P = 0.57) between the three agents. There was no difference in in-hospital bleeding (3 vs 2 vs 2%, P = 0.64). CONCLUSION: Prasugrel and ticagrelor are increasingly used in ACS patients treated with PCI, predominantly in a younger cohort with less comorbidity. Although antiplatelet therapy should still be individualised based on the thrombotic and bleeding risk, our study highlights the safety of the new P2Y12 inhibitors in contemporary Australian practice.

Associations of hospital characteristics with nosocomial pneumonia after cardiac surgery can impact on standardized infection rates.

To identify hospital-level factors associated with post-cardiac surgical pneumonia for assessing their impact on standardized infection rates (SIRs), we studied 43 691 patients in a cardiac surgery registry (2001-2011) in 16 hospitals. In a logistic regression model for pneumonia following cardiac surgery, associations with hospital characteristics were quantified with adjustment for patient characteristics while allowing for clustering of patients by hospital. Pneumonia rates varied from 0·7% to 12·4% across hospitals. Seventy percent of variability in the pneumonia rate was attributable to differences in hospitals in their long-term rates with the remainder attributable to within-hospital differences in rates over time. After adjusting for patient characteristics, the pneumonia rate was found to be higher in hospitals with more registered nurses (RNs)/100 intensive-care unit (ICU) admissions [adjusted odds ratio (aOR) 1·2, P = 0·006] and more RNs/available ICU beds (aOR 1·4, P < 0·001). Other hospital characteristics had no significant association with pneumonia. SIRs calculated on the basis of patient characteristics alone differed substantially from the same rates calculated on the basis of patient characteristics and the hospital characteristic of RNs/100 ICU admissions. Since SIRs using patient case-mix information are important for comparing rates between hospitals, the additional allowance for hospital characteristics can impact significantly on how hospitals compare.

Slowing the progression of age-related hearing loss: Rationale and study design of the ASPIRIN in HEARING, retinal vessels imaging and neurocognition in older generations (ASPREE-HEARING) trial.

BACKGROUND: Age-related hearing loss (ARHL) is a leading cause of disability in the elderly. Low-grade inflammation and microvessel pathology may be responsible for initiating or exacerbating some of the hearing loss associated with aging. A growing body of evidence demonstrates an association of hearing loss with cognitive decline. A shared etiological pathway may include a role of inflammation, alongside vascular determinants. The ASPREE-HEARING study aims to determine whether low-dose aspirin decreases the progression of ARHL, and if so, whether this decrease in progression is also associated with retinal microvascular changes and/or greater preservation of cognitive function. DESIGN AND METHODS: A three year double-blind, randomized controlled trial of oral 100mg enteric-coated aspirin or matching placebo, enrolling 1262 Australians aged ≥70years with normal cognitive function and no overt cardiovascular disease. The primary outcome is the change in mean pure tone average hearing threshold (decibels) in the better ear, over a 3-year period. Secondary outcomes consist of changes in retinal microvascular indicators, and changes in cognitive function. Participants are recruited from a larger trial, ASPirin in Reducing Events in the Elderly (ASPREE), which is designed to assess whether daily low dose aspirin will extend disability-free life. DISCUSSION: ASPREE-HEARING will determine whether aspirin slows development or progression of ARHL, and will interrogate the relationship between inflammatory and microvascular mechanisms that may underlie the effects of aspirin on ARHL. This study will improve understanding of the patterns of comorbidity with, and the relationships between, aging and ARHL, alongside modeling the impacts of ARHL.

Trends in door-to-balloon time and outcomes following primary percutaneous coronary intervention for ST-elevation myocardial infarction: an Australian perspective.

BACKGROUND: Guidelines for patients with ST-elevation myocardial infarction include a door-to-balloon time (DTBT) of ≤90 min for primary percutaneous coronary intervention. AIM: The aim of this study was to assess temporal trends (2006-2010) in DTBT and determine if a reduction in DTBT was associated with improved clinical outcomes. METHODS: We compared annual median DTBT in 1926 STEMI patients undergoing primary percutaneous coronary intervention from the Melbourne Interventional Group registry. ST-elevation myocardial infarction presenting >12 h and rescue percutaneous coronary intervention was excluded. Major adverse cardiac events were analysed according to DTBT (dichotomised as ≤90 min vs >90 min). A multivariable analysis for predictors of mortality (including DTBT) was performed. RESULTS: Baseline demographics, clinical and procedural characteristics were similar in the STEMI cohort across the 5 years, apart from an increase in out-of-hospital cardiac arrest (3.6% in 2006 vs 9.4% in 2010, P < 0.0001) and cardiogenic shock (7.7-9.6%, P = 0.07). The median DTBT (interquartile range) was reduced from 95 (74-130) min in 2006 to 75 (51-100) min in 2010 (P < 0.01). In this period, the proportion of patients achieving a DTBT of ≤90 min increased from 45% to 67% (P < 0.01). Lower mortality and major adverse cardiac event rates were observed with DTBT ≤90 min (all P < 0.01). Multivariable analysis showed that a DTBT of ≤90 min was associated with improved clinical outcomes at 12 months (odds ratio 0.48; 95% confidence interval 0.33-0.73, P < 0.01). CONCLUSION: There has been a decline in median DTBT in the Melbourne Interventional Group registry over 5 years. DTBT of ≤90 min is associated with improved clinical outcomes at 12 months.

External validation and updating of a prediction model for nosocomial pneumonia after coronary artery bypass graft surgery.

The generalizability of a prediction model from North America for incident nosocomial pneumonia following coronary artery bypass graft surgery was assessed for 23247 patients on the Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) registry. The performance of the North American model was evaluated using measures of calibration and discrimination. The model had reasonable discrimination (area under the receiver-operating characteristic curve, AUC=0·69), but unsatisfactory calibration (Hosmer-Lemeshow test, P<0·001) in the ANZSCTS patients. An update of the model coefficients yielded a model with AUC=0·71 and good calibration (P=0·46).

Elderly man with rapidly enlarging axillary mass.

Melanoma has long been known to be a malignancy that can present in a plethora of forms. This often makes diagnosing it a challenge, but lends support to the concept of frequently keeping it in the clinician's differential. We present the unique case of a rapidly enlarging axillary mass in an elderly man that initially did not appear concerning for malignancy. Pathologic diagnosis was particularly difficult due to the cystic nature of the mass, and the uncommon histo-chemical staining pattern of this malignant melanoma. We discuss the variety of therapies directed at symptom relief and control when discovered in advanced stages. This was a rare presentation of a malignant melanoma that highlights the need to maintain a suspicion for the disease in uncertain clinical situations.

Barriers to achieving blood pressure treatment targets in elderly hypertensive individuals.

High blood pressure (BP) is highly prevalent among the elderly, and even with pharmacological therapy BP is difficult to control to guideline recommended levels. Although poor compliance to therapy is associated with less BP control, little is known regarding other barriers to attaining on-treatment target BP. This study examined factors associated with achieving on-treatment target BP in 6010 hypertensive participants aged 65-84 years from the Second Australian National Blood Pressure study. Participants were followed for a median of 4.1 years, with BP monitored every 6 months. 'Target BP' was defined as a reduction of systolic/diastolic BP of at least 20/10 mm Hg and BP <160/90 mm Hg from randomization in two consecutive follow-up visits. Cox regression was used to identify factors associated with achieving target BP from a number of baseline and in-study factors. Mean BP at randomization was 168/91 mm Hg and patients had a median of 9 (range: 2-20) study visits. Target BP was achieved in 50% of patients. Demographic factors associated with achieving target BP were male gender, living in a regional area; and clinical factors included history of antihypertensive therapy, increased plasma creatinine, lower pretreatment pulse pressure and in-study use of multiple BP-lowering drugs. Those aged >80 years and seeking care from multiple doctors (hazard ratio 0.40, 95% confidence interval 0.36-0.45, P<0.001) were less likely to achieve target BP. These findings identify clinical markers that can be targeted for intervention, but also demographic factors related to service delivery, which may provide further opportunity for achieving better BP control in hypertensive elderly.

Females do not have increased risk of early or late mortality after isolated aortic valve replacement: results from a multi-institutional Australian study.

AIM: There is controversy regarding whether isolated aortic valve replacement (AVR) in women is associated with an increased risk of early and late mortality. The current study evaluates the impact of gender as an independent risk factor for early and late mortality after isolated AVR. METHODS: Data obtained between June 2001 and December 2009 by the Australasian Society of Cardiac and Thoracic Surgeons Cardiac Surgery Database Program was retrospectively analysed. Demographic, operative data and postoperative complications were compared between male and female patients using χ(2) and t-tests. Long-term survival analysis was performed using Kaplan Meier survival curves and the log rank test. Independent risk factors for short term and long term mortality were identified using binary logistic and Cox regression, respectively. RESULTS: Isolated aortic valve replacement was undertaken for 2790 patients in 18 Australian institutions; 41.9% were female. Female patients were generally older (mean age 72 vs. 66 years (P<0.001) and presented more often with hypertension (P<0.001) and obesity (P<0.001). They were less likely to present with cerebrovascular disease (P=0.018), renal failure (P=0.017) and non-elective presentation (P=0.017). Women were observed to have a lower 30-day mortality (1.7% vs. 2.1%) but there was no difference on univariate (P=0.490) or multivariate analysis (P=0.983). There was no difference in the incidence of early complications but women were more likely to require red blood cell transfusion (P<0.001). Long-term survival was comparable between men and women (P=0.662). CONCLUSION: Female patients undergoing isolated AVR do not have an increased risk of early and late mortality. Further investigation is required to delineate the impact of gender on early and late outcomes following AVR.

Most individuals with treated blood pressures above target receive only one or two antihypertensive drug classes.

BACKGROUND: A significant proportion of individuals taking antihypertensive therapies fail to achieve blood pressures <140/90 mmHg. In order to develop strategies for improved treatment of blood pressure, we examined the association of blood pressure control with antihypertensive therapies and clinical and lifestyle factors in a cohort of adults at increased cardiovascular risk. METHODS: A cross-sectional study of 3994 adults from Melbourne and Shepparton, Australia enrolled in the SCReening Evaluation of the Evolution of New Heart Failure (SCREEN-HF) study. Inclusion criteria were age ≥60 years with one or more of self-reported ischaemic or other heart disease, atrial fibrillation, cerebrovascular disease, renal impairment or treatment for hypertension or diabetes for ≥2 years. Exclusion criteria were known heart failure or cardiac abnormality on echocardiography or other imaging. The main outcome measures were the proportion of participants receiving antihypertensive therapy with blood pressures ≥140/90 mmHg and the association of blood pressure control with antihypertensive therapies and clinical and lifestyle factors. RESULTS: Of 3623 participants (1975 men and 1648 women) receiving antihypertensive therapy, 1867 (52%) had blood pressures ≥140/90 mmHg. Of these 1867 participants, 1483 (79%) were receiving only one or two antihypertensive drug classes. Blood pressures ≥140/90 mmHg were associated with increased age, male sex, waist circumference and log amino-terminal-pro-B-type natriuretic peptide levels. CONCLUSIONS: Most individuals with treated blood pressures above target receive only one or two antihypertensive drug classes. Prescribing additional antihypertensive drug classes and lifestyle modification may improve blood pressure control in this population of individuals at increased cardiovascular risk.