Acute hospital-based services used by adults during the last year of life in New South Wales, Australia: A population-based retrospective cohort study

© 2015 Goldsbury et al. Background: There is limited information about health care utilisation at the end of life for people in Australia. We describe acute hospital-based services utilisation during the last year of life for all adults (aged 18+ years) who died in a 12-month period in Australia's most populous state, New South Wales (NSW). Methods: Linked administrative health data were analysed for all adults who died in NSW in 2007 (the most recent year for which cause of death information was available for linkage for this study). The data comprised linked death records (2007), hospital admissions and emergency department (ED) presentations (2006-2007) and cancer registrations (1994-2007). Measures of hospital-based service utilisation during the last year of life included: number and length of hospital episodes, ED presentations, admission to an intensive care unit (ICU), palliative-related admissions and place of death. Factors associated with these measures were examined using multivariable logistic regression. Results: Of the 45,749 adult decedents, 82 % were admitted to hospital during their last year of life: 24 % had >3 care episodes (median 2); 35 % stayed a total of >30 days in hospital (median 17); 42 % were admitted to 2 or more different hospitals. Twelve percent of decedents spent time in an ICU with median 3 days. In the metropolitan area, 80 % of decedents presented to an ED and 18 % had >3 presentations. Overall 55 % died in a hospital or inpatient hospice. Although we could not quantify the extent and type of palliative care, 24 % had mention of "palliative care" in their records. The very elderly and those dying from diseases of the circulatory system or living in the least disadvantaged areas generally had lower hospital service use. Conclusions: These population-wide health data collections give a highly informative description of NSWhospital-based end-of-life service utilisation. Use of hospital-based services during the last year of life was common, with substantial variation across sociodemographic groups, especially defined by age, cause of death and socioeconomic classification of the decedents' place of residence. Further research is now needed to identify the contributors to these findings. Gaps in data collection were identified - particularly for palliative care and patient-reported outcomes. Addressing these gaps should facilitate improved monitoring and assessment of service use and care

Patterns of care and emergency presentations for people with non-small cell lung cancer in New South Wales, Australia: A population-based study

Introduction Little is known about population-wide emergency presentations and patterns of care for people diagnosed with non-small cell lung cancer (NSCLC) in Australia. We examined patients’ characteristics associated with presenting to an emergency department around the time of diagnosis (“emergency presenters”), and receiving anti-cancer treatment within 12 months of diagnosis. Materials and Methods Participants in the 45 and Up Study who were newly diagnosed with NSCLC during 2006–2010 were included. We used linked data from population-wide health databases including Medicare and pharmaceutical claims, inpatient hospitalisations and emergency department presentations to follow participants to June 2014. Patients’ characteristics associated with being an emergency presenter and receiving any anti-cancer treatment were examined. Results A total of 647 NSCLC cases were included (58.6% male, median age 73 years). Emergency presenters (34.5% of cases) were more likely to have a high Charlson comorbidity index score, be an ex-smoker who had quit in the past 15 years and to be diagnosed with distant metastases. Almost all patients had visited their general practitioner ≥3 times in the 6 months prior to diagnosis. Nearly one-third (29.5%) of patients did not receive any anti-cancer treatment, however, there were no differences between emergency and non-emergency presenters in the likelihood of receiving treatment. Those less likely to be treated were older, had no private health insurance, and had unknown stage disease recorded. Conclusion Our results indicate the difficulties in diagnosing lung cancer at an early stage and inequities in NSCLC treatment. Future research should address opportunities to diagnose lung cancer earlier and to optimise treatment pathways

Health-services utilisation amongst older persons during the last year of life: A population-based study

© 2018 The Author(s). Background: Accurate population-based data regarding hospital-based care utilisation by older persons during their last year of life are important in health services planning. We investigated patterns of acute hospital-based service use at the end of life, amongst older decedents in New South Wales (NSW), Australia. Methods: Data from all persons aged ≥70 years who died in the state of NSW Australia in 2007 were included. Several measures of hospital-based service utilisation during the last year of life were assessed from retrospectively linked data comprising data for all registered deaths, cause of death, hospital care during the last year of life (NSW Admitted Patient Data Collection [APDC] and Emergency Department [ED] Data Collection [EDDC]), and the NSW Cancer Registry. Results: Amongst 34,556 decedents aged ≥70 years, 82% (n = 28,366) had ≥1 hospitalisation during the last year of life (median 2), and 21% > 3 hospitalisations. Twenty-five percent (n = 5485) of decedents attended ED during the last week of life. Overall, 21% had a hospitalisation > 30 days in the last year of life, and 7% spent > 3 months in hospital; 79% had ≥1 ED attendance, 17% > 3. Nine percent (n = 3239) spent time in an intensive care unit. Fifty-three percent (n = 18,437) died in an inpatient setting. Hospital records had referenced palliative care for a fifth (7169) of decedents. Adjusting for age group, sex, place of residence, area-level socioeconomic status, and cause of death, having > 3 hospitalisations during the last year of life was more likely for persons dying from cancer (35% versus 16% non-cancer deaths, adjusted odds ratio [aOR] 2.33), 'younger' old decedents (29% for age 70-79 and 20% for age 80-89 versus 11% for 90+, aOR 2.42 and 1.77 respectively) and males (25% versus 17% females, aOR 1.38). Patterns observed for other hospital-based service use were similar. Conclusions: This population-based study reveals high use of hospital care among older persons during their last year of life, although this decreased with increasing older age, providing important data to inform health services planning for this population, and highlighting aspects requiring further study

Health system costs and days in hospital for colorectal cancer patients in New South Wales, Australia.

IntroductionColorectal cancer (CRC) care costs the Australian healthcare system more than any other cancer. We estimated costs and days in hospital for CRC cases, stratified by site (colon/rectal cancer) and disease stage, to inform detailed analyses of CRC-related healthcare.MethodsIncident CRC patients were identified using the Australian 45 and Up Study cohort linked with cancer registry records. We analysed linked hospital admission records, emergency department records, and reimbursement records for government-subsidised medical services and prescription medicines. Cases' health system costs (2020 Australian dollars) and hospital days were compared with those for cancer-free controls (matched by age, sex, geography, smoking) to estimate excess resources by phase of care, analysed by sociodemographic, health, and disease characteristics.Results1200 colon and 546 rectal cancer cases were diagnosed 2006-2013, and followed up to June 2016. Eighty-nine percent of cases had surgery, chemotherapy or radiotherapy, and excess costs were predominantly for hospitalisations. Initial phase (12 months post-diagnosis) mean excess health system costs were $50,434 for colon and$60,877 for rectal cancer cases, with means of 16 and 18.5 excess hospital days, respectively. The annual continuing mean excess costs were $6,779 (colon) and$8,336 (rectal), with a mean of 2 excess hospital days each. Resources utilised (costs and days) in these phases increased with more advanced disease, comorbidities, and younger age. Mean excess costs in the year before death were $74,952 (colon) and$67,733 (rectal), with means of 34 and 30 excess hospital days, respectively-resources utilised were similar across all characteristics, apart from lower costs for cases aged ≥75 at diagnosis.ConclusionsHealth system costs and hospital utilisation for CRC care are greater for people with more advanced disease. These findings provide a benchmark, and will help inform future cost-effectiveness analyses of potential approaches to CRC screening and treatment

Quantifying the Universality of the Stellar Initial Mass Function in Old Star Clusters

We present a new technique to quantify cluster-to-cluster variations in the observed present-day stellar mass functions of a large sample of star clusters. Our method quantifies these differences as a function of both the stellar mass and the total cluster mass, and offers the advantage that it is insensitive to the precise functional form of the mass function. We applied our technique to data taken from the ACS Survey for Globular Clusters, from which we obtained completeness-corrected stellar mass functions in the mass range 0.25-0.75 M$_{\odot}$ for a sample of 27 clusters. The results of our observational analysis were then compared to Monte Carlo simulations for globular cluster evolution spanning a range of initial mass functions, total numbers of stars, concentrations, and virial radii. We show that the present-day mass functions of the clusters in our sample can be reproduced by assuming an universal initial mass function for all clusters, and that the cluster-to-cluster differences are consistent with what is expected from two-body relaxation. A more complete exploration of the initial cluster conditions will be needed in future studies to better constrain the precise functional form of the initial mass function. This study is a first step toward using our technique to constrain the dynamical histories of a large sample of old Galactic star clusters and, by extension, star formation in the early Universe.Comment: 11 pages, 4 figures, 4 tables, accepted for publication in MNRAS, proof corrections made in updated versio

The VMC survey - XI : Radial Stellar Population Gradients in the Galactic Globular Cluster 47 Tucanae

Copyright American Astronomical SocietyWe present a deep near-infrared color-magnitude diagram of the Galactic globular cluster 47 Tucanae, obtained with the Visible and Infrared Survey Telescope for Astronomy (VISTA) as part of the VISTA near-infrared Y, J, Ks survey of the Magellanic System (VMC). The cluster stars comprising both the subgiant and red giant branches exhibit apparent, continuous variations in color-magnitude space as a function of radius. Subgiant branch stars at larger radii are systematically brighter than their counterparts closer to the cluster core; similarly, red-giant-branch stars in the cluster's periphery are bluer than their more centrally located cousins. The observations can very well be described by adopting an age spread of ~0.5 Gyr as well as radial gradients in both the cluster's helium abundance (Y) and metallicity (Z), which change gradually from (Y = 0.28, Z = 0.005) in the cluster core to (Y = 0.25, Z = 0.003) in its periphery. We conclude that the cluster's inner regions host a significant fraction of second-generation stars, which decreases with increasing radius; the stellar population in the 47 Tuc periphery is well approximated by a simple stellar population.Peer reviewe

Dissecting the Colour-Magnitude Diagram: A Homogeneous Catalogue of Stellar Populations in Globular Clusters

We present a homogeneous catalogue for blue straggler, red giant branch, horizontal branch and main-sequence turn-off stars in a sample of 35 clusters taken from the ACS Survey for Globular Clusters. As a result of the superior photometry and relatively large field of view offered by the ACS data, this new catalogue is a significant improvement upon the one presented in Leigh, Sills & knigge (2007). Using our catalogue, we study and compare the radial distributions of the different stellar populations. We have confirmed our previous result (Knigge, Leigh & Sills 2009) that there is a clear, but sub-linear, correlation between the number of blue stragglers found in the cluster core and the total stellar mass contained within it. By considering a larger spatial extent than just the core, our results suggest that mass segregation is not the dominant effect contributing to the observed sub-linearity. We also investigate the radial distributions of the different stellar populations in our sample of clusters. Our results are consistent with a linear relationship between the number of stars in these populations and the total mass enclosed within the same radius. Therefore, we conclude that the cluster dynamics does not significantly affect the relative distributions of these populations in our sample.Comment: 14 pages, 5 figures, accepted for publication in MNRA

Central kinematics of the globular cluster NGC 2808: Upper limit on the mass of an intermediate-mass black hole

Globular clusters are an excellent laboratory for stellar population and dynamical research. Recent studies have shown that these stellar systems are not as simple as previously assumed. With multiple stellar populations as well as outer rotation and mass segregation they turn out to exhibit high complexity. This includes intermediate-mass black holes which are proposed to sit at the centers of some massive globular clusters. Today's high angular resolution ground based spectrographs allow velocity-dispersion measurements at a spatial resolution comparable to the radius of influence for plausible IMBH masses, and to detect changes in the inner velocity-dispersion profile. Together with high quality photometric data from HST, it is possible to constrain black-hole masses by their kinematic signatures. We determine the central velocity-dispersion profile of the globular cluster NGC 2808 using VLT/FLAMES spectroscopy. In combination with HST/ACS data our goal is to probe whether this massive cluster hosts an intermediate-mass black hole at its center and constrain the cluster mass to light ratio as well as its total mass. We derive a velocity-dispersion profile from integral field spectroscopy in the center and Fabry Perot data for larger radii. High resolution HST data are used to obtain the surface brightness profile. Together, these data sets are compared to dynamical models with varying parameters such as mass to light ratio profiles and black-hole masses. Using analytical Jeans models in combination with variable M/L profiles from N-body simulations we find that the best fit model is a no black hole solution. After applying various Monte Carlo simulations to estimate the uncertainties, we derive an upper limit of the back hole mass of M_BH < 1 x 10^4 M_SUN (with 95 % confidence limits) and a global mass-to-light ratio of M/L_V = (2.1 +- 0.2) M_SUN/L_SUN.Comment: 12 pages, 9 figures, 2 tables, accepted for publication in A&

Spatial Extent of Charge Repulsion Regulates Assembly Pathways for Lysozyme Amyloid Fibrils

Formation of large protein fibrils with a characteristic cross β-sheet architecture is the key indicator for a wide variety of systemic and neurodegenerative amyloid diseases. Recent experiments have strongly implicated oligomeric intermediates, transiently formed during fibril assembly, as critical contributors to cellular toxicity in amyloid diseases. At the same time, amyloid fibril assembly can proceed along different assembly pathways that might or might not involve such oligomeric intermediates. Elucidating the mechanisms that determine whether fibril formation proceeds along non-oligomeric or oligomeric pathways, therefore, is important not just for understanding amyloid fibril assembly at the molecular level but also for developing new targets for intervening with fibril formation. We have investigated fibril formation by hen egg white lysozyme, an enzyme for which human variants underlie non-neuropathic amyloidosis. Using a combination of static and dynamic light scattering, atomic force microscopy and circular dichroism, we find that amyloidogenic lysozyme monomers switch between three different assembly pathways: from monomeric to oligomeric fibril assembly and, eventually, disordered precipitation as the ionic strength of the solution increases. Fibril assembly only occurred under conditions of net repulsion among the amyloidogenic monomers while net attraction caused precipitation. The transition from monomeric to oligomeric fibril assembly, in turn, occurred as salt-mediated charge screening reduced repulsion among individual charged residues on the same monomer. We suggest a model of amyloid fibril formation in which repulsive charge interactions are a prerequisite for ordered fibril assembly. Furthermore, the spatial extent of non-specific charge screening selects between monomeric and oligomeric assembly pathways by affecting which subset of denatured states can form suitable intermolecular bonds and by altering the energetic and entropic requirements for the initial intermediates emerging along the monomeric vs. oligomeric assembly path

Rapid Changes in Phospho-MAP/Tau Epitopes during Neuronal Stress: Cofilin-Actin Rods Primarily Recruit Microtubule Binding Domain Epitopes

Abnormal mitochondrial function is a widely reported contributor to neurodegenerative disease including Alzheimer's disease (AD), however, a mechanistic link between mitochondrial dysfunction and the initiation of neuropathology remains elusive. In AD, one of the earliest hallmark pathologies is neuropil threads comprising accumulated hyperphosphorylated microtubule-associated protein (MAP) tau in neurites. Rod-like aggregates of actin and its associated protein cofilin (AC rods) also occur in AD. Using a series of antibodies - AT270, AT8, AT100, S214, AT180, 12E8, S396, S404 and S422 - raised against different phosphoepitopes on tau, we characterize the pattern of expression and re-distribution in neurites of these phosphoepitope labels during mitochondrial inhibition. Employing chick primary neuron cultures, we demonstrate that epitopes recognized by the monoclonal antibody 12E8, are the only species rapidly recruited into AC rods. These results were recapitulated with the actin depolymerizing drug Latrunculin B, which induces AC rods and a concomitant increase in the 12E8 signal measured on Western blot. This suggests that AC rods may be one way in which MAP redistribution and phosphorylation is influenced in neurons during mitochondrial stress and potentially in the early pathogenesis of AD