A Person-Centred Approach to Performance Measurement in the Health Svstem

Health systems strive to improve health outcomes in the populations they serve. In Australia, a national health system performance framework supports this aim. Review of performance measures showed a focus on organisational activity rather than outcomes for people. South Australia (SA) also set strategic targets for improved healthy life expectancy as influenced by: premature mortality; health related quality of life (HRQoL); and, potentially preventable hospitalisation (PPH). There are unmet information needs and capacity for improvement in the application of each of these measures. Aims This thesis aims to help inform system improvement by reorienting performance measurement toward outcomes of importance to people receiving healthcare – so called ‘person-centred’ measures. The thesis aims to provide empirical examples that help: i. Reframe premature mortality measures to account for survival time from disease detection until death; ii. Extend morbidity measurement to describe a person’s self-reported state of health; and, iii. Enhance enumeration of people experiencing PPH in emergency departments (EDs) and as admitted inpatients. Methods Four studies stem from the candidate’s projects in SA: monitoring summary population health; piloting an advanced cancer data system; steering the first Aboriginal specific population survey; and, quantifying individuals experiencing PPH. Study one introduces a new method that quantifies mortality related cancer burden using an example based on cancer registrations among Aboriginal and non-Aboriginal cohorts matched one-to-one on sex, year of birth, primary cancer site and year of diagnosis. Cancer burden is expressed as the PREmature Mortality to IncidencE Ratio (PREMIER), the ratio of years of life expectancy lost due to cancer against life expectancy years at risk at time of cancer diagnosis for each person. Study two presents the first, self-reported HRQoL utility results by Aboriginal South Australians. Population weighted HRQoL was measured using SF-6D and SF-12 version 2 in face-to-face interviews. Analyses describe relationships between HRQoL and respondent characteristics, and the characteristics of interviewees completing HRQoL questions. Studies three and four consider ED and inpatient PPH respectively. Those studies extend current reporting practices by shifting analyses from PPH as a proportion of activity, to a person-centred approach counting individuals experiencing PPH and the frequency of their events. Both studies draw on person-linked public hospital records within a period prevalence study design. Study three compares ED presentations among Refugee and Asylum Seeker Countries of birth (RASC); Aboriginal; those aged 75 years or more and all other adults. Study four determines disparities in rates, length of stay (LOS) and hospital costs of PPH for chronic conditions among Aboriginal and non-Aboriginal people. Results Study one included records for 777 Aboriginal people diagnosed with cancer from 1990 to 2010. Aboriginal people (n=777) had 57% (95%CI 52%-60%) more scope for improved cancer mortality outcomes two years after diagnosis compared to non-Aboriginal people of equivalent age, sex, diagnosis year and cancer site. PREMIER informs interventions by identifying people with greatest capacity to benefit from earlier detection, treatment and reduced premature mortality. Study two showed substantial variation in self-reported HRQoL among 399 Aboriginal people in 2010/11. For example, average SF-6D results varied from 0.82 (95%CIs 0.81-0.83) among those with no chronic conditions to 0.63 (95%CIs 0.59-0.67) where 3 or more conditions were reported. Comparatively less responding to HRQoL questions was evident among people speaking Aboriginal languages, in non-urban settings, and with multi-morbidities. Further developing culturally safe, self-reporting HRQoL instruments may improve participation by vulnerable and health compromised community members. Study three’s comparisons among adult residents attending EDs in 2005–2006 to 2010–2011 showed greatest disparities in GP-Type presentations among people from RASC compared to non-Aboriginal residents aged less than 75 years (423.7 and 240.1 persons per 1,000 population respectively). Study four’s inpatient PPH for chronic conditions showed Aboriginal people experienced more first-time events compared to others (11.5 and 6.2 per 1,000 persons per year respectively) and substantially longer, total length of stay (11.7 versus 9.0 days). Improved understanding of peoples’ PPH informs tailored services addressing primary healthcare needs. Conclusion The studies assembled in this thesis help align performance measurement with outcomes for people and provide support for system improvement and health reform. While the labour-intensive collaborations necessary may limit development, current opportunities for advancing research within government agencies are discussed. Australia’s health system performance measures remain underdeveloped. This thesis contributes to addressing that need by focussing attention on the people the system exists to serve – effectively, efficiently and equitably.Thesis (Ph.D.) -- University of Adelaide, School of Public Health, 202

Healthy life gains in South Australia 1999-2008: analysis of a local Burden of Disease series

BACKGROUND: The analysis describes trends in the levels and social distribution of total life expectancy and healthy life expectancy in South Australia from 1999 to 2008. METHODS: South Australian Burden of Disease series for the period 1999-2001 to 2006-2008 and across statistical local areas according to relative socioeconomic disadvantage were analyzed for changes in total life expectancy and healthy life expectancy by sex and area level disadvantage, with further decomposition of healthy life expectancy change by age, cause of death, and illness. RESULTS: Total life expectancy at birth increased in South Australia for both sexes (2.0 years [2.6%] among males; 1.5 years [1.8%] among females). Healthy life expectancy also increased (1.4 years [2.1%] among males; 1.2 years [1.5%] among females). Total life and healthy life expectancy gains were apparent in all socioeconomic groups, with the largest increases in areas of most and least disadvantage. While the least disadvantaged areas consistently had the best health outcomes, they also experienced the largest increase in the amount of life expectancy lived with disease and injury-related illness. CONCLUSIONS: While overall gains in both total life and healthy life expectancy were apparent in South Australia, gains were greater for total life expectancy. Additionally, the proportion of expected life lived with disease and injury-related illness increased as disadvantage decreased. This expansion of morbidity occurred in both sexes and across all socio-economic groups. This analysis outlines the continuing improvements to population health outcomes within South Australia. It also highlights the challenge of reducing population morbidity so that gains to healthy life match those of total life expectancy.David Banham, Tony Woollacott and John Lync

Elevated expression of the adhesion GPCR ADGRL4/ELTD1 promotes endothelial sprouting angiogenesis without activating canonical GPCR signalling.

Funder: Rhodes Scholarships; doi: http://dx.doi.org/10.13039/501100000697Funder: Clarendon ScholarshipFunder: Ernest Oppenheimer Memorial Trust; doi: http://dx.doi.org/10.13039/501100009978Funder: European Union (European Social Fund)Funder: Free State of SaxonyFunder: Cancer Research UK; doi: http://dx.doi.org/10.13039/501100000289Funder: Breast Cancer Research Foundation; doi: http://dx.doi.org/10.13039/100001006ADGRL4/ELTD1 is an orphan adhesion GPCR (aGPCR) expressed in endothelial cells that regulates tumour angiogenesis. The majority of aGPCRs are orphan receptors. The Stachel Hypothesis proposes a mechanism for aGPCR activation, in which aGPCRs contain a tethered agonist (termed Stachel) C-terminal to the GPCR-proteolytic site (GPS) cleavage point which, when exposed, initiates canonical GPCR signalling. This has been shown in a growing number of aGPCRs. We tested this hypothesis on ADGRL4/ELTD1 by designing full length (FL) and C-terminal fragment (CTF) ADGRL4/ELTD1 constructs, and a range of potential Stachel peptides. Constructs were transfected into HEK293T cells and HTRF FRET, luciferase-reporter and Alphascreen GPCR signalling assays were performed. A stable ADGRL4/ELTD1 overexpressing HUVEC line was additionally generated and angiogenesis assays, signalling assays and transcriptional profiling were performed. ADGRL4/ELTD1 has the lowest GC content in the aGPCR family and codon optimisation significantly increased its expression. FL and CTF ADGRL4/ELTD1 constructs, as well as Stachel peptides, did not activate canonical GPCR signalling. Furthermore, stable overexpression of ADGRL4/ELTD1 in HUVECs induced sprouting angiogenesis, lowered in vitro anastomoses, and decreased proliferation, without activating canonical GPCR signalling or MAPK/ERK, PI3K/AKT, JNK, JAK/HIF-1α, beta catenin or STAT3 pathways. Overexpression upregulated ANTXR1, SLC39A6, HBB, CHRNA, ELMOD1, JAG1 and downregulated DLL4, KIT, CCL15, CYP26B1. ADGRL4/ELTD1 specifically regulates the endothelial tip-cell phenotype through yet undefined signalling pathways

Repurposed immunomodulatory drugs for Covid-19 in pre-ICu patients - mulTi-Arm Therapeutic study in pre-ICu patients admitted with Covid-19 – Repurposed Drugs (TACTIC-R): A structured summary of a study protocol for a randomised controlled trial

Abstract: Objectives: To determine if a specific immunomodulatory intervention reduces progression of COVID-19-related disease to organ failure or death, compared to standard of care (SoC). Trial design: Randomised, parallel 3-arm (1:1:1 ratio), open-label, Phase IV platform trial of immunomodulatory therapies in patients with late stage 1 or stage 2 COVID-19-related disease, with a diagnosis based either on a positive assay or high suspicion of COVID-19 infection by clinical and/or radiological assessment. Participants: Patients aged 18 and over, with a clinical picture strongly suggestive of COVID-19-related disease (with/without a positive COVID-19 test) AND a Risk count (as defined below) >3 OR ≥3 if risk count includes “Radiographic severity score >3”. A risk count is calculated by the following features on admission (1 point for each): radiographic severity score >3, male gender, non-white ethnicity, diabetes, hypertension, neutrophils >8.0 x109/L, age >40 years and CRP >40 mg/L. Patients should be considered an appropriate subject for intervention with immunomodulatory therapies in the opinion of the investigator and be able to be maintained on venous thromboembolism prophylaxis during the inpatient dosing period, according to local guidelines. The complete inclusion and exclusion criteria as detailed in the additional file 1 should be fulfilled. Patients will be enrolled prior to the need for invasive mechanical ventilation, cardiac or renal support. Participants will be recruited across multiple centres including initially at Cambridge University Hospitals NHS Foundation Trust, King’s College Hospital NHS Foundation Trust, Guy’s and St Thomas’ NHS Foundation Trust, University Hospital of Wales, Gloucestershire Royal Hospitals NHS Foundation Trust and The Royal Wolverhampton NHS Trust. Intervention and comparator: Each active comparator arm will be compared against standard of care (SoC). The immunomodulatory drugs were selected from a panel of licenced candidates by a drug evaluation committee, which considered potential efficacy, potential toxicity, scalability and novelty of each strategy. The initial active arms comprise baricitinib and ravulizumab. Baricitinib will be given 4 mg orally (once daily (OD)) on days 1-14 or until day of discharge. The dose will be reduced to 2 mg OD for patients aged > 75 years and those with an estimated Cockcroft Gault creatinine clearance of 30-60 ml/min. Ravulizumab will be administered intravenously once according to the licensed weight-based dosing regimen (see Additional file 1). Each active arm will be compared with standard of care alone. No comparisons will be made between active arms in this platform trial. Main outcomes: The primary outcome is the incidence (from baseline up to Day 14) of any one of the events (whichever comes first): death, invasive mechanical ventilation, extra corporeal membrane oxygenation, cardiovascular organ support (inotropes or balloon pump), or renal failure (estimated Cockcroft Gault creatinine clearance <15ml/min). Randomisation: Eligible patients will be randomised using a central web-based randomisation service (Sealed Envelope) in a 1:1:1 ratio, stratified by site to one of the treatment arms or SoC. Blinding (masking): This is an open-label trial. Data analysis will not be blinded. Numbers to be randomised (sample size): There is no fixed sample size for this study. Serial interim analyses will be triggered by an Independent Data Monitoring Committee (IDMC), including analysis after 125 patients are recruited to each arm, 375 in total assuming 3 arms. Additional interim analyses are projected after 229 patients per arm, and potentially then after 469 per arm, but additional analyses may be triggered by the IDMC. Trial Status: TACTIC-R Protocol version number 2.0 date May 20, 2020, recruitment began May 7, 2020 and the end trial will be the date 18 months after the last patient’s last visit. The recruitment end date cannot yet be accurately predicted. Trial registration: Registered on EU Clinical Trials Register EudraCT Number: 2020-001354-22 Registered: 6 May 2020 It was registered on ClinicalTrials.gov (NCT04390464) and on ISRCTN (ISRCTN11188345) Full protocol: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol

Collision, Collusion and Coincidence: Pop Art’s Fairground Parallel

This article looks at parallel methods, motivations and modes of consumption between formative British pop art and British fairground art. I focus on two strands, the emergent critical work of the Independent Group and the school of artists based at the Royal College of Art under the nominal leadership of Peter Blake. I use iconographical and iconological methods to compare the content of the art, and then examine how pop art tried to create both a critical and playful distancing from established rules and practices of the artistic canon. I focus on non-institutional cultural groupings and diffuse production and consumption models

muLTi-Arm Therapeutic study in pre-ICu patients admitted with Covid-19-Experimental drugs and mechanisms (TACTIC-E): A structured summary of a study protocol for a randomized controlled trial

Abstract: Objectives: To determine if a specific intervention reduces the composite of progression of patients with COVID-19-related disease to organ failure or death as measured by time to incidence of any one of the following: death, invasive mechanical ventilation, ECMO, cardiovascular organ support (inotropes or balloon pump), or renal failure (estimated Cockcroft Gault creatinine clearance 3 OR ≥3 if risk count includes “Radiographic severity score >3”. A risk count is calculated by the following features on admission (1 point for each): radiographic severity score >3, male gender, non-white ethnicity, diabetes, hypertension, neutrophils >8.0 x109/L, age >40 years and CRP >40 mg/L. Patients should be considered an appropriate subject for intervention with immunomodulatory or other disease modifying agents in the opinion of the investigator and are able to swallow capsules or tablets. The complete inclusion and exclusion criteria as detailed in the Additional file 1 should be fulfilled. Drug specific inclusion and exclusion criteria will also be applied to the active arms. Patients will be enrolled prior to the need for invasive mechanical ventilation, cardiac or renal support. Participants will be recruited across multiple centres in the UK including initially at Cambridge University Hospitals NHS Foundation Trust and St George’s University NHS Foundation Trust. Other centres will be approached internationally in view of the evolving pandemic. Intervention and comparator: There is increasing evidence of the role of immunomodulation in altering the course of COVID-19. Additionally, various groups have demonstrated the presence of pulmonary shunting in patients with COVID-19 as well as other cardiovascular complications. TACTIC-E will assess the efficacy of the novel immunomodulatory agent EDP1815 versus the approved cardio-pulmonary drugs, Dapagliflozin in combination with Ambrisentan versus the prevailing standard of care. EDP1815 will be given as 2 capsules twice daily (1.6 x 1011 cells) for up to 7 days with the option to extend up to 14 days at the discretion of the principal investigator or their delegate, if the patient is felt to be clinically responding to treatment, is tolerating treatment, and is judged to be likely to benefit from a longer treatment course. Ambrisentan 5mg and Dapagliflozin 10mg will be given in combination once daily orally for up to maximum of 14 days. Patients will be randomised in a 1:1:1 ratio across treatments. Each active arm will be compared with standard of care alone. Additional arms may be added as the trial progresses. No comparisons will be made between active arms in this platform trial. Main outcomes: The primary outcome is the incidence (from baseline up to Day 14) to the occurrence of the any one of the following events: death, invasive mechanical ventilation, extra corporeal membrane oxygenation, cardiovascular organ support (inotropes or balloon pump), or renal failure (estimated Cockcroft Gault creatinine clearance <15ml/min). Randomisation: Eligible patients will be randomised using a central web-based randomisation service (Sealed Envelope) in a 1:1:1 ratio, stratified by site to one of the treatment arms or standard of care. Blinding (masking): This is an open-label trial. Data analysis will not be blinded. Numbers to be randomised (sample size): There is no fixed sample size for this study. There will be an early biomarker-based futility analysis performed at a point during the study. If this biomarker futility analysis is not conclusive, then a second futility analysis based on clinical endpoints will be performed after approximately 125 patients have been recruited per arm. Provisionally, further analyses of clinical endpoints will be performed after 229 patients per active arm and later 469 patients per arm have been recruited. Further additional analyses may be triggered by the independent data monitoring committee. Trial Status: TACTIC-E Protocol version number 1.0 date May 27th, 2020. Recruitment starts on the 3rd of July 2020. The end trial date will be 18 months after the last patient’s last visit and cannot be accurately predicted at this time. Trial registration: Registered on EU Clinical Trials Register EudraCT Number: 2020-002229-27 registered: 9 June 2020. The trial was also registered on ClinicalTrials.gov (NCT04393246) on 19 May 2020. Full protocol: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol

Aboriginal premature mortality within South Australia 1999-2006: a cross-sectional analysis of small area results

<p>Abstract</p> <p>Background</p> <p>This paper initially describes premature mortality by Aboriginality in South Australia during 1999 to 2006. It then examines how these outcomes vary across area level socio-economic disadvantage and geographic remoteness.</p> <p>Methods</p> <p>The retrospective, cross-sectional analysis uses estimated resident population by sex, age and small areas based on the 2006 Census, and Unit Record mortality data. Premature mortality outcomes are measured using years of life lost (YLL). Subsequent intrastate comparisons are based on indirect sex and age adjusted YLL results. A multivariate model uses area level socio-economic disadvantage rank, geographic remoteness, and an interaction between the two variables to predict premature mortality outcomes.</p> <p>Results</p> <p>Aboriginal people experienced 1.1% of total deaths but 2.2% of YLL and Aboriginal premature mortality rates were 2.65 times greater than the South Australian average. Premature mortality for Aboriginal and non-Aboriginal people increased significantly as area disadvantage increased. Among Aboriginal people though, a significant main effect for area remoteness was also observed, together with an interaction between disadvantage and remoteness. The synergistic effect shows the social gradient between area disadvantage and premature mortality increased as remoteness increased.</p> <p>Conclusions</p> <p>While confirming the gap in premature mortality rates between Aboriginal South Australians and the rest of the community, the study also found a heterogeneity of outcomes within the Aboriginal community underlie this difference. The results support the existence of relationship between area level socio-economic deprivation, remoteness and premature mortality in the midst of an affluent society. The study concludes that vertically equitable resourcing according to population need is an important response to the stark mortality gap and its exacerbation by area socio-economic position and remoteness.</p