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Alexander Fisher,1–3 Wichat Srikusalanukul,1 Leon Fisher,4 Paul N Smith2,3 1Department of Geriatric Medicine, The Canberra Hospital, ACT Health, Canberra, Australia; 2Department of Orthopaedic Surgery, The Canberra Hospital, ACT Health, Canberra, Australia; 3Australian National University Medical School, Canberra, ACT, Australia; 4Department of Gastroenterology, Frankston Hospital, Peninsula Health, Melbourne, Australia Purpose: To estimate the discriminative value of serum P1NP/βCTX ratio and albumin levels in hospitalized orthogeriatric patients with and without nonvertebral fractures. Methods: In 1,239 orthogeriatric patients (mean age 78.1±9.52 years, 69.1% women) including 854 (68.9%) with osteoporotic nonvertebral fractures (455 [36.7%] with hip fracture [HF]) and 385 (31.1%) without fractures, markers of bone formation (procollagen type 1 N-terminal propeptide [P1NP], osteocalcin [OC], and bone resorption (beta-C-terminal cross-linking telopeptide of type 1 collagen [βCTX]), indices of mineral metabolism, and parameters of liver and renal functions were assessed; data on clinical and laboratory characteristics were collected prospectively. Results: Both lower serum P1NP/βCTX ratio and albumin concentration (as continuous or categorical variables) were independently associated with fracture presence in multivariate logistic regressions. Compared with the highest P1NP/βCTX tertile, the prevalence of HF, after adjustment for multiple covariates, was 3-fold higher in the lowest tertile and 1.5 times higher in the middle tertile; presence of any fracture was 2.3- and 1.6-fold higher, respectively; patients with albumin levels in the lowest tertile had multivariate odds ratio (OR) of 4.6 for HF and 2.8 for any fracture, in the middle tertile the ORs were 2.2 and 1.3, respectively. The P1NP/βCTX <100.0 (median) and hypoalbuminemia (<33 g/L) demonstrated area under the curve values for HF

Aim: To investigate the association of the neutrophil to lymphocyte ratio (NLR) at admission with presence of fracture, comorbid conditions, and its prognostic value for short-term outcomes in orthogeriatric patients. Methods: On 415 consecutive patients (mean age 78.8 ±8.7[SD] years, 281 women, 255 with a non-vertebral bone fracture, including 167 with a hip fracture, HF) admitted to the Department of Orthopaedic Surgery at the Canberra hospital (2010 - 2011) data on clinical and laboratory characteristics were collected prospectively. The validation dataset included 294 consecutive patients (mean age 82.1 ± 8.0 years, 72.1% women) with HF. Results: Multivariate regression revealed four variables, presence of HF, hypoalbuminaemia (<33g/L), anaemia (<120g/L) and hyperparathyroidism (PTH>6.8 pmol/L), as independent determinants of admission NLR≥5.1. There was a dose-graded relationship between presence of fracture, especially HF, postoperative complications and levels of NLR categorized as tertiles. Compared to patients with NLR<5.1(first tertile), patients with NLR 5.1-8.5 (second tertile) had a 1.8-, 3.1-, 2.6-, and 2.5-fold higher risk for presence of any fracture, HF, developing postoperative myocardial injury (troponin I rise) and a high inflammatory response/infection (CRP>100mg/L after the 3rd postoperative day), respectively, while in subjects with NLR>8.5 (third tertile) these risks were 2.6-, 4.9-, 5.9- and 4.5-times higher, respectively; subjects with NLR>8.5 had a 9.7 times higher chance of dying in the hospital compared to patients with NLR 5.1-8.5; the NLR retained its significance on multivariate analyses. The NLR ≥5.1 predicted postoperative myocardial injury with an area under the curve (AUC) of 0.626, CRP>100mg/L with AUC of 0.631 and the NLR >8.5 predicted in-hospital mortality with an AUC of 0.793, showing moderately high sensitivity (86.7%, 80% and 90%, respectively) and negative predictive value (92.9%, 71.2%, 99.6%, respectively), but low speci

AIMS: To estimate age- and sex-specific incidence rates and time trends of post-stroke hip fracture (HF) in the Australian Capital Territory (ACT) and to present projections of future post-stroke HF incidence in Australia until 2051.METHODS: Analysis of annual age- and sex-specific standardized (to 2006 Australian population) post-stroke HF incidence rates in older stroke survi-vors (aged ≥60 years) over an 11 year period (between 1999/2000 and 2009/2010). Projections of number of post-stroke HF in 2021 and 2051 are based on demographic predictors obtained from the Australian Bureau of Statistics.RESULTS: Over the study period among 1784 stroke survivors HF was recorded in 61 (3.42%) subjects (40 women and 21 men), indicating a HF incidence rate of 6.31 per 1000 stroke person-years. The standardized annual post-stroke HF incidence rate (per 100,000 person-years) in women was 1.7 times higher than in men (18.9 vs. 11.1 per, p = 0.008), and in the oldest group (>80 years) compared to aged 60-69 years was 10 times higher for women (47.54 vs. 4.73) and 4 times higher for men (26.65 vs. 6.50). Post-stroke HF occurred on average within the first 2.3 years, about 2 times more often in women aged ≥75 years (p = 0.033) and in survivors after an ischaemic stroke (p = 0.052), but age per se did not affect the time to HF. During the 11-year period the incidence rates of post-stroke HF decreased annually in total by 17.9%.CONCLUSIONS: Post-stroke HF is relatively common, prevalent in women and occurs on average within 2.3 years after the stroke. The incidence of post-stroke HF in elderly people is decreasing. However, because of population ageing and increasing number of stroke survivors, the absolute number of post-stroke patients sustaining a HF and their proportion among the total HF population could be expected to increase.

Aims The objective of this study is (i) to evaluate trends in the incidence rates of stroke survivors aged 60 years and older over a 11-year period in the Australian Capital Territory (ACT) and (ii) to forecast future trends in Australia until 2051. Methods Analysis of age- and sex-specific standardized incidence rates of older first-ever stroke survivors in ACT from 1999-2000 to 2009-2010 and projections of number of stroke survivors (NSS) in 2021 and 2051 using 2 models based only on (i) demographic changes and (ii) assuming changing of both incidence rates and demography. Results In the ACT in the first decade of the 21st century, the absolute numbers and age-adjusted standardized incidence rates of stroke survivors (measured as a function of age and period) increased among both men and women aged 60 years or older. The trend toward increased survival rates in both sexes was driven mainly by population aging, whereas the effect of stroke year was more pronounced in men compared with women. The absolute NSS (and the financial burden to the society) in Australia is predicted to increase by 35.5%-59.3% in 2021 compared with 2011 and by 1.6- to 4.6-fold in 2051 if current only demographic (first number) or both demographic and incidence trends (second number) continue. Conclusions Our study demonstrates favorable trends in stroke survivor rates in Australia in the first decade of the new millennium and projects in the foreseeable future significant increases in the absolute numbers of older stroke survivors, especially among those aged 70 years or older and men.

Objective. To assess the prevalence, clinical and laboratory characteristics, and short-term outcomes of poststroke hip fracture (HF). Methods. A cross-sectional study of 761 consecutive patients aged ≥60 years (82.3±8.8 years; 75% females) with osteop

A Fisher,1,3 W Srikusalanukul,1 M Davis,1,3 P Smith2,31Departments of Geriatric Medicine, 2Orthopaedic Surgery, The Canberra Hospital, 3Australian National University Medical School, Canberra, ACT, AustraliaBackground: Considerable controversy exists regarding the contribution of mineral/bone metabolism abnormalities to the association between cardiovascular diseases (CVDs) and osteoporotic fractures.Aims and methods: To determine the relationships between mineral/bone metabolism biomarkers and CVD in 746 older patients with hip fracture, clinical data were recorded and serum concentrations of parathyroid hormone (PTH), 25-hydroxyvitamin D, calcium, phosphate, magnesium, troponin I, parameters of bone turnover, and renal, liver, and thyroid functions were measured.Results: CVDs were diagnosed in 472 (63.3%) patients. Vitamin D deficiency was similarly prevalent in patients with (78.0%) and without (82.1%) CVD. The CVD group had significantly higher mean PTH concentrations (7.6 vs 6.0 pmol/L, P < 0.001), a higher prevalence of secondary hyperparathyroidism (SPTH) (PTH > 6.8 pmol/L, 43.0% vs 23.3%, P < 0.001), and excess bone resorption (urinary deoxypyridinoline corrected by creatinine [DPD/Cr] > 7.5 nmol/µmol, 87.9% vs 74.8%, P < 0.001). In multivariate regression analysis, SHPT (odds ratio [OR] 2.6, P = 0.007) and high DPD/Cr (OR 2.8, P = 0.016) were independent indictors of CVD. Compared to those with both PTH and DPD/Cr in the normal range, multivariate-adjusted ORs for the presence of CVD were 17.3 (P = 0.004) in subjects with SHPT and 9.7 (P < 0.001) in patients with high DPD/Cr. CVD was an independent predicator of SHPT (OR 2.8, P = 0.007) and excess DPD/Cr (OR 2.5, P = 0.031). CVD was predictive of postoperative myocardial injury, while SHPT was also an independent predictor of prolonged hospital stay and in-hospital death.Conclusion: SHPT and excess bone resorption are independent pathophysiological mediato

Naive T lymphocytes exhibit extensive antigen-independent recirculation between blood and lymph nodes, where they may encounter dendritic cells carrying cognate antigen. We examine how long different T cells may spend in an individual lymph node by examining data from long term cannulation of blood and efferent lymphatics of a single lymph node in the sheep. We determine empirically the distribution of transit times of migrating T cells by applying the Least Absolute Shrinkage & Selection Operator (LASSO) or regularised S-LASSO to fit experimental data describing the proportion of labelled infused cells in blood and efferent lymphatics over time. The optimal inferred solution reveals a distribution with high variance and strong skew. The mode transit time is typically between 10 and 20 hours, but a significant number of cells spend more than 70 hours before exiting. We complement the empirical machine learning based approach by modelling lymphocyte passage through the lymph node insilico. On the basis of previous two photon analysis of lymphocyte movement, we optimised distributions which describe the transit times (first passage times) of discrete one dimensional and continuous (Brownian) three dimensional random walks with drift. The optimal fit is obtained when drift is small, i.e. the ratio of probabilities of migrating forward and backward within the node is close to one. These distributions are qualitatively similar to the inferred empirical distribution, with high variance and strong skew. In contrast, an optimised normal distribution of transit times (symmetrical around mean) fitted the data poorly. The results demonstrate that the rapid recirculation of lymphocytes observed at a macro level is compatible with predominantly randomised movement within lymph nodes, and significant probabilities of long transit times. We discuss how this pattern of migration may contribute to facilitating interactions between low frequency T cells and antigen presenting cells c

Introduction. Experiments on genetically modified animals have discovered a complex cross-regulation between adipokines (leptin, adiponectin) and osteocalcin. The relationships between these molecules in human osteoporosis are still unclear. We evaluated

Objectives: To determine the relationship of serum resistin concentrations to biochemical determinants of bone metabolism, comorbidity and outcomes in patients with hip fracture (HF). Methods: In 256 consecutive patients (mean age 81.9 ± 7.8. years; 71.1

Objective: To investigate whether clinical and laboratory characteristics, including serum 25-hydroxyvitamin D (25(OH) D), PTH and parameters of mineral and bone metabolism, differ by hip fracture (HF) type. Patients and methods: We studied prospectively

Alex Fisher1, Jodie Martin2, Wichat Srikusalanukul2, Michael Davis11Department of Geriatric Medicine, The Canberra Hospital, Canberra, ACT, Australia; 2Australian National University Medical School, Canberra, ACT, AustraliaAim: The objective of this article is to evaluate the relationship between the changes in prescriptions of antiosteoporotic drugs (mainly the rapid fall in the use of bisphosphonates [BPs]) and standardized hip fracture (HF) rates over the period 2005–2008 in the Australian Capital Territory (ACT).Methods: Annual sex- and age-specific HF rates (per 100,000 population) were determined and standardized using the Australian 2006 population census. Data on the annual prescriptions of BPs (mainly alendronate and risedronate), strontium ranelate, and hormone replacement therapy were obtained from the Australian Pharmaceutical Benefits Scheme (PBS) and Repatriation Australian Pharmaceutical Benefits Scheme (RPBS) databases.Results: In the ACT, the peak annual number of prescriptions for BPs was observed in 2006. Following reports linking osteonecrosis of the jaw with BP use, the number of BP prescriptions dropped by 14% in 2007–2008 compared with 2005, when the lowest HF rates were recorded. The reduction in BP prescriptions coincided with increased HF rates in females in 2007 (+22.6%) and in 2008 (+25.2%) compared with 2005; in males, HF incidence declined by 6.6% and 16.7%, respectively. The proportion of filled prescriptions for strontium ranelate, risedronate, and alendronate in 2007–2008 was 1:8.4:15.5, indicating that BPs were the dominant antiosteoporotic drugs. There was an inverse statistically significant relationship between the total annual number of BP prescriptions and standardized HF incidence rates for the 10-year period 1999–2008.Conclusion: Although currently there is no clear understanding of factors contributing to changing HF epidemiology, the available evidence suggests that much of the declin

This methods paper outlines the overall design of a community-based multidisciplinary longitudinal study with the intent to stimulate interest and communication from scientists and practitioners studying the role of physical activity in preventive medicine. In adults, lack of regular exercise is a major risk factor in the development of chronic degenerative diseases and is a major contributor to obesity, and now we have evidence that many of our children are not sufficiently active to prevent early symptoms of chronic disease. The lifestyle of our kids (LOOK) study investigates how early physical activity contributes to health and development, utilizing a longitudinal design and a cohort of eight hundred and thirty 7-8-year-old (grade 2) school children followed to age 11-12 years (grade 6), their average family income being very close to that of Australia. We will test two hypotheses, that (a) the quantity and quality of physical activity undertaken by primary school children will influence their psychological and physical health and development; (b) compared with existing practices in primary schools, a physical education program administered by visiting specialists will enhance health and development, and lead to a more positive perception of physical activity. To test the first hypothesis we will monitor all children longitudinally over the 4 years. To test the second we will involve an intervention group of 430 children who receive two 50 min physical education classes every week from visiting specialists and a control group of 400 who continue with their usual primary school physical education with their class-room teachers. At the end of grades 2, 4, and 6 we will measure several areas of health and development including blood risk factors for chronic disease, cardiovascular structure and function, physical fitness, psychological characteristics and perceptions of physical activity, bone structure and strength, motor control, body composition, nutritional int

To evaluate whether there is a relationship between admission serum leptin concentrations and peri-operative myocardial injury, 238 consecutive older patients (mean age 81.9+/-7.9 years; 172 women) with low-trauma hip fracture were assessed. Myocardial injury as defined by elevated serum cardiac troponin I was associated with lower leptin levels analyzed as continuous or categorical variables. Patients with serum leptin concentrations <12ng/ml (medium value) had a two-fold greater increased risk for such complications compared with those with higher leptin levels (odd ratio 2.13, 95% confidence interval 1.06-4.28; p=0.033). This association remained significant after adjustments for age, gender, clinical (history of coronary artery disease [CAD], stroke, hypertension, diabetes, dementia), hematological (red, white, and lymphocyte count, hemoglobin, hematocrit), metabolic (parathyroid hormone [PTH], albumin), renal(creatinine, urea, glomerular filtration rate [GFR]), and inflammatory (C-reactive protein [CRP], ferritin) factors. The predictive value of lower leptin levels increased significantly when used in combination with traditional risk factors for myocardial injury.

To determine whether serum 25(OH)D and/or PTH levels in older patients with hip fracture (HF) could predict short-term clinical outcomes, we conducted a prospective observational study of 287 consecutive HF patients (mean age 81.9 ± 7.5 [SD] years, 72% f

Childhood obesity is increasingly prevalent in the community and is related to adverse cardiovascular outcomes during adulthood. In this study of healthy children, we evaluated the influence of adiposity and physical activity on carotid-femoral pulse wave velocity (PWV), an index of arterial stiffness and a marker of cardiovascular risk in adults. In 573 community-based children (mean age: 10.1±0.3 years; 51% boys), we measured body mass index and waist circumference. Percentage body fat was quantitated by dual-energy x-ray absorptiometry. Cardiorespiratory fitness (CRF) and physical activity levels were assessed using a 20-m shuttle run and 7-day pedometer count, respectively. PWV was estimated by applanation tonometry. In univariate analysis, PWV was positively correlated with body mass index (r=0.34), waist circumference (r=0.32), and percentage body fat (r=0.32; P<0.001 for all) and negatively correlated with CRF (r= -0.23; P<0.001) and pedometer count (r= -0.08; P=0.046). In separate multivariable linear regression models, body mass index, waist circumference, and percentage of body fat were independently and positively associated with PWV (P<0.01 for all) after adjusting for age, sex, systolic blood pressure, mean arterial pressure, heart rate, and CRF (P<0.01 for all). The influence of CRF on PWV was attenuated after adjusting for adiposity. In conclusion, increased body mass and adiposity and decreased CRF are associated with arterial stiffening in healthy prepubescent children. (Hypertension. 2009;53:611-616.)

OBJECTIVE: An age-dependent relationship between aortic and left ventricular (LV) stiffening has been observed in community-based adults. Our aim was to compare the performances of wave reflection-dependent (pulse pressure) and independent [carotid-femoral pulse wave velocity (PWV)] indexes of aortic stiffness to detect preclinical LV diastolic dysfunction. METHODS: In this case-control study, a stratified subsample of participants of a population-based echocardiographic survey with LV ejection fraction higher than 45% and without overt heart failure was randomly selected to undergo assessment of brachial blood pressure, LV diastolic function by Doppler echocardiography, and estimation of central aortic pressures and PWV by applanation tonometry. RESULTS: Of the 233 subjects (mean age 73 ± 6 years, 54% men), 84 had normal diastolic function, 99 had mild diastolic dysfunction, and 50 had moderate or severe diastolic dysfunction. Brachial pulse pressure, central pulse pressure, and PWV progressively increased according to the severity of diastolic dysfunction, independent of age and sex. The overall performance of PWV was superior to brachial pulse pressure [area under receiver operating characteristic curve (AUC): 0.70 versus 0.59, respectively; P = 0.005] and central pulse pressure (AUC: 0.70 versus 0.56, respectively; P = 0.001) for the detection of any diastolic dysfunction. CONCLUSION: PWV appeared to be superior to central and brachial pulse pressure for the detection of diastolic dysfunction in older adults with 'preserved' LV ejection fraction.

To determine whether abnormalities in heart rate (HR) were associated with long-term mortality in older, low-level care residents, 179 randomly selected persons aged 65 and older (mean, 83.2+/-7.0 [SD] years; 80% women) were prospectively assessed. At baseline, duplicate measurements of HR and blood pressure were recorded in the supine position and after standing. During the 5-year follow-up period, 97 (54%) participants died. Cox survival analysis revealed no association with total mortality when resting HR was analyzed as a continuous or categoric variable (< or = 60, 61-89, and > 90 bpm). However, HR > or = 90 bpm was associated with increased risk of dying in residents who used a walking aid (relative risk, 3.48; 95% confidence interval, 1.07-11.30; p=0.038). Postural HR change was not associated with mortality risk. The authors concluded that resting HR and postural change in HR are not significant predictors of 5-year mortality in older, low-level care residents, except in persons using a walking aid.

OBJECTIVES: To evaluate which indices of blood pressure (BP) homeostasis are the strongest predictors of mortality in older low-level-care residents in long-term health facilities. DESIGN: Prospective cohort study. SETTING: Eight long-term healthcare facilities in Canberra, Australia. PARTICIPANTS: A total of 179 randomly selected semi-independent residents aged 65 and older (mean age it standard deviation 83.2 ± 7.0; 80% women). MEASUREMENTS: Baseline BP levels taken while lying, after standing for 1 and 3 minutes, and sitting before and 1 hour after meal intake were recorded, as well as demographic information, chronic medical conditions, medications, and all-cause mortality during follow-up. Postprandial hypotension (PPH) was defined as a fall in systolic BP (SBP) of 20 mmHg or more 1 hour postmeal while sitting. Orthostatic hypotension (OH) was defined as a fall in SBP of 20 mmHg or more or in diastolic BP (DBP) of 10 mmHg or more within 3 minutes of standing from a supine position. Hypertension was defined as BP greater than 160/90 mmHg at commencement of the study. Mean arterial pressure (MAP) and pulse pressure (PP) were calculated. RESULTS: At baseline, 47% of participants had hypertension, 38% PPH, and 23% OH; PP was 70 mmHg or greater in 54%, and DBP was 65 mmHg or lower in 6%. Over 4.7 years, 97 (54%) participants died. Those who died were significantly older and more likely to have PPH (47% vs 28%) and atrial fibrillation (35% vs 17%) and a significantly greater decrease in BP after meal intake. Mortality rates in those with and without PPH were 145.0 and 98.5 per 1,000 person-years, respectively. Using multivariate Cox proportional hazards models after adjustment for age, sex, presence of atrial fibrillation, Parkinson's disease, and use of diuretics, PPH was the only BP parameter that significantly and independently predicted 4.7-year all-cause mortality (relative risk (RR) = 1.79; 95% confidence interval (CI) = 1.19-2.68; P = .005). Further adjustment

Lymphocyte recirculation between lymphatic and blood vessels and migration through tissues are essential mechanisms underlying immunological surveillance. However, the kinetics of lymphocyte migration through lymphoid tissues remains poorly understood. The present study of lymphocyte migration, based on a sheep model and entailing the long term cannulation of blood vessels and lymphatic vessels efferent from lymph nodes, represents the first attempt to apply control engineering based models to overcome some of the experimental impediments to understanding the complex phenomena involved in lymphocyte migration. An output error model order (1,2,nk) was systematically selected under given criteria from four classes of Linear Time-Invariant Single-Input Single-Output (LTI-SISO) systems to represent the peripheral lymph node system. The unit impulse responses were simulated under noise free conditions and their features were extracted to describe the dynamics of the system. The findings from this study revealed novel information about several aspects of the dynamics of lymphocyte migration.

This is the first application of the prediction error method (PEM) of system identification to modelling lymphocyte migration through peripheral lymphoid tissue. The PEM was applied to the emergence of labelled lymphocytes from the efferent lymphatic of a lymph node following their intravenous administration. Advantages of PEM included the capacity to calculate the response to a unit impulse stimulus, unavailable to direct observation, and to allow for the return to the node of labelled cells that had already recirculated once. Calculation of the system delay (time between introduction of cells into the blood and their first appearance in lymph) indicated 4.67 ± 1.05 h for the total lymphocyte population. The peak in efferent lymph occurred at 11.91 ± 4.68 h, much earlier than previous reports, which were affected by cells that had already recirculated. While 75% of labelled cells had emerged in efferent lymph by 20.77 ± 5.62 h, 86.38 ± 29.44 h was required for 100% emergence. The considerable heterogeneity in migratory behaviour is likely to reflect frequency and duration of binding of lymphocytes by dendritic cells in paracortical cord corridors. It is proposed that differences in the speed with which lymphocytes pass along corridors depend on their functional status, in particular whether they are naive or memory cells.