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Abstract Background Aboriginal and Torres Strait Islander peoples are disproportionately impacted by type 2 diabetes. Continuous glucose monitoring (CGM) technology (such as Abbott Freestyle Libre 2, previously referred to as Flash Glucose Monitoring) offers real-time glucose monitoring that is convenient and easy to use compared to self-monitoring of blood glucose (SMBG). However, this technology’s use is neither widespread nor subsidised for Aboriginal and Torres Strait Islander peoples with type 2 diabetes. Building on existing collaborations with a national network of Aboriginal and Torres Strait Islander communities, this randomised controlled trial aims to assess the effect of CGM compared to SMBG on (i) haemoglobin A1c (HbA1c), (ii) achieving blood glucose targets, (iii) reducing hypoglycaemic episodes and (iv) cost-effective healthcare in an Aboriginal and Torres Strait Islander people health setting. Methods This is a non-masked, parallel-group, two-arm, individually randomised, controlled trial (ACTRN12621000753853). Aboriginal and Torres Strait Islander adults with type 2 diabetes on injectable therapy and HbA1c ≥ 7.5% (n = 350) will be randomised (1:1) to CGM or SMBG for 6 months. The primary outcome is change in HbA1c level from baseline to 6 months. Secondary outcomes include (i) CGM-derived metrics, (ii) frequency of hypoglycaemic episodes, (iii) health-related quality of life and (iv) incremental cost per quality-adjusted life year gained associated with the CGM compared to SMBG. Clinical trial sites include Aboriginal Community Controlled Organisations, Aboriginal Medical Services, primary care centres and tertiary hospitals across urban, rural, regional and remote Australia. Discussion The trial will assess the effect of CGM compared to SMBG on HbA1c for Aboriginal and Torres Strait Islander people with type 2 diabetes in Australia. This trial could have long-term benefits in improving diabetes management and providing evidence for funding of CGM in this population. Trial registration Australian and New Zealand Clinical Trials Registry ACTRN12621000753853. Registered on 15th June 2021.

Abstract Background The emergence of high-priced potential cures has sparked significant health policy discussions in South Korea, where the healthcare system is funded through a single-payer National Health Insurance model. We conducted focus group interviews (FGIs) and accompanying surveys with diverse stakeholders to comprehensively understand related issues and find better solutions to the challenges brought by these technologies. Methods From October to November 2022, 11 FGIs were conducted with stakeholders from various sectors, including government payers, policy and clinical experts, civic and patient organisations, and the pharmaceutical industry, involving a total of 25 participants. These qualitative discussions were supplemented by online surveys to effectively capture and synthesise stakeholder perspectives. Results Affordability was identified as a critical concern by 84% of stakeholders, followed by clinical uncertainty (76%) and limited value for money (72%). Stakeholders expressed a preference for both financial-based controls and outcome-based pricing strategies to mitigate these challenges. Despite the support for outcome-based refunds, payers raised concerns about the feasibility of instalment payment models, whether linked to outcomes or not, due to the specific challenges of the Korean reimbursement system and the potential risk of ‘cumulative liabilities’ from ongoing payments for previously administered treatments. In addition, the FGIs highlighted the need for clear budgetary limits for drugs with high uncertainties, with mixed opinions on the creation of special silo funds (64.0% agreement). Less than half (48%) endorsed the use of external reference pricing, currently applied to such essential drugs in South Korea. A significant majority (84%), predominantly non-pharma stakeholders, advocated for addressing cost-effectiveness uncertainty through re-assessment once long-term clinical data become available. Conclusions This study uncovers a broad agreement among stakeholders on the need for more effective value assessment methodologies for high-priced potential cures, stressing the importance of more robust and comprehensive re-assessment supported by long-term data collection, rather than primarily relying on external reference pricing. Each type of stakeholders exhibited a cautious approach to their specific uncertainties, suggesting that new funding strategies should accommodate these uncertainties with predefined guidelines and agreements prior to the initiation of managed entry agreements.

Abstract Background Recruitment of participants is crucial to the success of randomised control trials (RCTs) but can be challenging and expensive. Current research on trial efficiency is often focused at the patient-level with an emphasis on effective recruitment strategies. Less is known about selection of study sites to optimise recruitment. We examine site-level factors that are associated with patient recruitment and cost efficiency using data from an RCT conducted across 25 general practices (GP) in Victoria, Australia. Methods Data on number of participants screened, excluded, eligible, recruited, and randomised from each study site were extracted from a clinical trial. Details regarding site characteristics, recruitment practices, and staff time commitment were collected using a three-part survey. The key outcomes assessed were recruitment efficiency (ratio of screened to randomised), average time, and cost for each participant recruited and randomised. To identify practice-level factors associated with efficient recruitment and lower cost, outcomes were dichotomised (25th percentile vs others) and each practice-level factor assessed against the outcomes to determine its association. Results Across 25 GP study sites, 1968 participants were screened of which 299 (15.2%) were recruited and randomised. The mean recruitment efficiency was 7.2, varying from 1.4 to 19.8 across sites. The strongest factor associated with efficiency was assigning clinical staff to identify potential participants (57.14% vs. 22.2%). The more efficient sites were smaller practices and were more likely to be rural locations and in areas of lower socioeconomic status. The average time used for recruitment was 3.7 h (SD2.4) per patient randomised. The mean cost per patient randomised was $277 (SD161), and this varied from $74 to $797 across sites. The sites identified with the 25% lowest recruitment cost (n = 7) were more experienced in research participation and had high levels of nurse and/or administrative support. Conclusion Despite the small sample size, this study quantified the time and cost used to recruit patients and provides helpful indications of site-level characteristics that can help improve feasibility and efficiency of conducting RCT in GP settings. Characteristics indicative of high levels of support for research and rural practices, which often tends to be overlooked, were observed to be more efficient in recruiting.

The therapeutic efficacy of anticancer nanocarriers is highly dependent on their size, shape, targeting ability, and stimuli-responsiveness. Herein, we studied the in vivo therapeutic efficacy of Doxorubicin (Dox) loaded redox responsive micellar-like nanoparticles (MNPs)based on linear 2-hydroxypropyl methacrylamide (HPMA) via histopathological evaluations. The therapeutic efficacy of DOX-loaded micellar-like Nanoparticles significantly improved while the side effects reduced as confirmed by histopathological examinations. H&E and tunnel staining of tumor tissues indicated the higher population of apoptotic tumor cells in both treatment groups containing DOX. These redox responsive crosslinked HPMA-based micellar-like nanoparticles with acceptable therapeutic efficacy and apoptosis induction in cancerous cells proved to be promising nanomedicine for breast cancer chemotherapy.

During 2020 and 2021, Australia implemented relatively stringent government restrictions yet had few COVID-19 deaths. This provides an opportunity to understand the effects of lockdowns and quarantining restrictions on short-term mortality and to help provide evidence in understanding how such public health policies can impact on health. Our analysis is based on preliminary mortality data collected by the Australian Bureau of Statistics. Rates were estimated by disease and over time and compared with mortality statistics in the period 2015–2019. Comparing deaths in 2020-2021 with 2015–2019 show the annual mortality rate (per 100 000 people) fell by 5.9% from 528.4 in 2015–2019 to 497.0 in 2020–2021. Declines in mortality are across many disease categories including respiratory diseases (down 9.4 deaths per 100 000), cancer (down 7.5 deaths per 100 000) and heart disease (down 8.4 deaths per 100 000). During 2020 and 2021, Australian age-standardised mortality rates fell by 6%. This drop was similar for men and women, and was driven by a reduction in both communicable and non-communicable causes of death. Such evidence can help inform public health policies designed to both control COVID-19 and other infectious diseases.

Summary: Background: Myocardial infarction mortality has declined since the 1970s, but contemporary drivers of this trend remain unexplained. The aim of this study was to compare the contribution of trends in event rates and case fatality to declines in myocardial infarction mortality in four high-income jurisdictions from 2002–15. Methods: Linked hospitalisation and mortality data were obtained from New South Wales (NSW), Australia; Ontario, Canada; New Zealand; and England, UK. People aged between 30 years and 105 years were included in the study. Age-adjusted trends in myocardial infarction event rates and case fatality were estimated from Poisson and binomial regression models, and their relative contribution to trends in myocardial infarction mortality calculated. Findings: 1 947 895 myocardial infarction events from a population of 80·4 million people were identified in people aged 30 years or older. There were significant declines in myocardial infarction mortality, event rates, and case fatality in all jurisdictions. Age-standardised myocardial infarction event rates were highest in New Zealand (men 893/100 000 person-years in 2002, 536/100 000 person-years in 2015; women 482/100 000 person-years in 2002, 271/100 000 person-years in 2015) and lowest in England (men 513/100 000 person-years in 2002, 382/100 000 person-years in 2015; women 238/100 000 person-years in 2002, 173/100 000 person-years in 2015). Annual age-adjusted reductions in event rates ranged from –2·6% (95% CI –3·0 to –2·3) in men in England to –4·3% (–4·4 to –4·1) in women in Ontario. Age-standardised case fatality was highest in England in 2002 (48%), but declined at a greater rate than in the other jurisdictions (men –4·1%/year, 95% CI –4·2 to –4·0%; women –4·4%/year, –4·5 to –4·3%). Declines in myocardial infarction mortality rates ranged from –6·1%/year to –7·6%/year. Event rate declines were the greater contributor to myocardial infarction mortality reductions in Ontario (69·4% for men and women), New Zealand (men 68·4%; women 67·5%), and NSW women (60·1%), whereas reductions in case fatality were the greater contributor in England (60% in men and women) and for NSW men (54%). There were greater contributions from case fatality than event rate reductions in people younger than 55 years in all jurisdictions, with contributions to mortality declines varying by country in those aged 55–74 years. Event rate declines had a greater impact than changes in case fatality in those aged 75 years and older. Interpretation: While the mortality burden of myocardial infarction has continued to fall across these four populations, the relative contribution of trends in myocardial infarction event rates and case fatality to declining mortality varied between jurisdictions, including by age and sex. Understanding the causes of this variation will enable optimisation of prevention and treatment efforts. Funding: National Health and Medical Research Council, Australia; Australian Research Council; Health Research Council of New Zealand; Canadian Institutes of Health Research, Canada; National Institute for Health Research, UK.

Abstract Background The Health Research Council of New Zealand is the first major government funding agency to use a lottery to allocate research funding for their Explorer Grant scheme. This is a somewhat controversial approach because, despite the documented problems of peer review, many researchers believe that funding should be allocated solely using peer review, and peer review is used almost ubiquitously by funding agencies around the world. Given the rarity of alternative funding schemes, there is interest in hearing from the first cohort of researchers to ever experience a lottery. Additionally, the Health Research Council of New Zealand wanted to hear from applicants about the acceptability of the randomisation process and anonymity of applicants. Methods This paper presents the results of a survey of Health Research Council applicants from 2013 to 2019. The survey asked about the acceptability of using a lottery and if the lottery meant researchers took a different approach to their application. Results The overall response rate was 39% (126 of 325 invites), with 30% (76 of 251) from applicants in the years 2013 to 2018, and 68% (50 of 74) for those in the year 2019 who were not aware of the funding result. There was agreement that randomisation is an acceptable method for allocating Explorer Grant funds with 63% (n = 79) in favour and 25% (n = 32) against. There was less support for allocating funds randomly for other grant types with only 40% (n = 50) in favour and 37% (n = 46) against. Support for a lottery was higher amongst those that had won funding. Multiple respondents stated that they supported a lottery when ineligible applications had been excluded and outstanding applications funded, so that the remaining applications were truly equal. Most applicants reported that the lottery did not change the time they spent preparing their application. Conclusions The Health Research Council’s experience through the Explorer Grant scheme supports further uptake of a modified lottery.

Objective:. To investigate the factors underlying willingness to participate in a hypothetical trial among patients and surgeons, to inform the design of future placebo surgery controlled trials. Background:. Placebo surgery controlled trials are the gold standard for testing the efficacy of surgical procedures. However, these trials commonly fail to meet the target sample size and terminate underpowered. Methods:. From October 2019 to July 2020, eligible patients were identified from the orthopedic waiting list at a single tertiary hospital and surgeons were identified from orthopedic clinics at three tertiary hospitals in Australia. Qualitative interviews explored factors underlying willingness to participate in a hypothetical trial, including understanding of trial concepts; attitudes; and trial design preferences. Data collection and analysis were conducted in parallel. Recruitment ceased when no new concepts emerged. Interview data were analyzed using reflexive thematic analysis. Results:. The majority of surgeons and only a few patients indicated a willingness to participate in a placebo surgery controlled trial. Factors underlying willingness were captured in four themes: (1) Understanding and attitudes toward placebo; (2) Attitudes towards randomization/perception of equipoise; (3) Perception of risk; and (4) Ethical concerns. Conclusions:. To optimize recruitment in the future, trialists may consider embedding strategies into the recruitment process that validate patients’ symptoms, encourage an altruistic mindset, address surgeon biases, and involve surgeons in explaining trial concepts to patients. Trialists may also consider designing three arm trials that meet surgeons’ preferences for a “low” and “high” fidelity placebo.

BackgroundReducing disease can maintain personal individual income and improve societal economic productivity. However, estimates of income loss for multiple diseases simultaneously with thorough adjustment for confounding are lacking, to our knowledge. We estimate individual-level income loss for 40 conditions simultaneously by phase of diagnosis, and the total income loss at the population level (a function of how common the disease is and the individual-level income loss if one has the disease).Methods and findingsWe used linked health tax data for New Zealand as a high-income country case study, from 2006 to 2007 to 2015 to 2016 for 25- to 64-year-olds (22.5 million person-years). Fixed effects regression was used to estimate within-individual income loss by disease, and cause-deletion methods to estimate economic productivity loss at the population level. Income loss in the year of diagnosis was highest for dementia for both men (US$8,882; 95% CI $6,709 to $11,056) and women ($7,103; $5,499 to $8,707). Mental illness also had high income losses in the year of diagnosis (average of about $5,300 per year for males and $4,100 per year for females, for 4 subcategories of: depression and anxiety; alcohol related; schizophrenia; and other). Similar patterns were evident for prevalent years of diagnosis. For the last year of life, cancers tended to have the highest income losses, (e.g., colorectal cancer males: $17,786, 95% CI $15,555 to $20,018; females: $14,192, $12,357 to $16,026). The combined annual income loss from all diseases among 25- to 64-year-olds was US$2.72 billion or 4.3% of total income. Diseases contributing more than 4% of total disease-related income loss were mental illness (30.0%), cardiovascular disease (15.6%), musculoskeletal (13.7%), endocrine (8.9%), gastrointestinal (7.4%), neurological (6.5%), and cancer (4.5%). The limitations of this study include residual biases that may overestimate the effect of disease on income loss, such as unmeasured time-varying confounding (e.g., divorce leading to both depression and income loss) and reverse causation (e.g., income loss leading to depression). Conversely, there may also be offsetting underestimation biases, such as income loss in the prodromal phase before diagnosis that is misclassified to "healthy" person time.ConclusionsIn this longitudinal study, we found that income loss varies considerably by disease. Nevertheless, mental illness, cardiovascular, and musculoskeletal diseases stand out as likely major causes of economic productivity loss, suggesting that they should be prioritised in prevention programmes.

Abstract Background Income-related inequality measures such as the concentration index are often used to describe the unequal distribution of health, health care access, or expenditure in a single measure. This study demonstrates the use of such measures to evaluate the distributional impact of changes in health insurance coverage. We use the example of Medicare Part D in the United States, which increased access to prescription medications for Medicare beneficiaries from 2006. Methods Using pooled cross-sectional samples from the Medical Expenditure Panel Survey for 1997–2011, we estimated income-related inequality in drug expenditures over time using the concentration and generalised concentration indices. A difference-in-differences analysis investigated the change in inequality in drug expenditures, as measured using the concentration index and generalised concentration index, between the elderly (over 65 years) and near-elderly (54–63 years) pre- and post-implementation of Medicare Part D. Results Medicare Part D increased public drug expenditure while out-of-pocket and private spending fell. Public drug expenditures favoured the poor during all study periods, but the degree of pro-poorness declined in the years immediately following the implementation of Part D, with the poor gaining less than the rich in both relative and absolute terms. Part D also appeared to result in a fall in the pro-richness of private insurance drug expenditure in absolute terms but have minimal distributional impact on out-of-pocket expenditure. These effects appeared to be short lived, with a return to the prevailing trends in both concentration and generalised concentration indices several years following the start of Part D. Conclusions The implementation of Medicare Part D significantly reduced the degree of pro-poorness in public drug expenditure. The poor gained less of the increased public drug expenditure than the rich in both relative and absolute terms. This study demonstrates how income-related inequality measures can be used to estimate the impact of health system changes on inequalities in health expenditure and provides a guide for future evaluations.

A promotion to a more senior role brings an exciting yet challenging period in a leader's career. Using an interpretative phenomenological methodology, this study explores the experiences of six leaders who received coaching during recent transitions into C-suite roles (Chief Executive Officers (CEOs) and direct reports) within global corporate organisations. Leaders experienced significant change, challenge and emotional turmoil. They valued the coaching, which led to lasting benefits in terms of confidence, capabilities and strengthened identity. In a nascent research landscape, results advocate the benefits of coaching, highlighting aspects of value, success factors and areas where further research is needed.

Background To evaluate the cost‐effectiveness of combination pulmonary arterial hypertension specific therapy in systemic sclerosis–related PAH. Methods and Results Health outcomes and costs were captured through data linkage. Health utility was derived from Medical Outcomes Study Short Form‐36 scores. A probabilistic discrete‐time model was developed to simulate lifetime changes in costs and health utility. Mortality was predicted using a Gompertz parametric survival model. For both treatment arms, the simulations were started using the same cohort of 10 000 patients. Probabilistic sensitivity analysis was performed using the Monte Carlo simulation with 1000 sets of sampled parameter values. Of 143 patients with systemic sclerosis–related pulmonary arterial hypertension, 89 were on monotherapy and 54 on combination therapy. Mean simulated costs per patient per year in monotherapy and combination therapy groups were AU$23 411 (US$16 080) and AU$29 129 (US$19 982), respectively. Mean life years and quality‐adjusted life years from pulmonary arterial hypertension diagnosis to death of patients receiving monotherapy were 7.1 and 3.0, respectively, and of those receiving combination therapy were 9.2 and 3.9, respectively. Incremental costs per life year and quality‐adjusted life year gained of combination therapy compared with monotherapy were AU$47 989 (US$32 920) and AU$113 823 (US$78 082), respectively. At a willingness‐to‐pay threshold of AU$102 000 (US$69 972) per life year gained, and of AU$177 222 (US$121 574) per quality‐adjusted life year gained, the probability of combination therapy being cost‐effective was 0.95. Conclusions The incremental cost per quality‐adjusted life year gained of combination therapy compared with monotherapy was substantial in the base case analysis. Given the fatal prognosis of systemic sclerosis–related pulmonary arterial hypertension and the incremental cost per life year of AU$47 989 (US$32 920), combination therapy could be considered cost‐effective in systemic sclerosis–related pulmonary arterial hypertension.

Background Cancer patients are at significant risk of developing sepsis due to underlying malignancy and necessary treatments. Little is known about the economic burden of sepsis in this high-risk population. We estimate the short- and long-term healthcare costs of care of cancer patients with and without sepsis using individual-level linked-administrative data. Methods We conducted a population-based matched cohort study of cancer patients aged ≥18, diagnosed between 2010 and 2017. Cases were identified if diagnosed with sepsis during the study period, and were matched 1:1 by age, sex, cancer type and other variables to controls without sepsis. Mean costs (2018 Canadian dollars) for patients with and without sepsis up to 5 years were estimated adjusted using survival probabilities at partitioned intervals. We estimated excess cost associated with sepsis presented as a cost difference between the two cohorts. Haematological and solid cancers were analysed separately. Results 77,483 cancer patients with sepsis were identified and matched. 64.3% of the cohort were aged ≥65, 46.3% female and 17.8% with haematological malignancies. Among solid tumour patients, the excess cost of care among patients who developed sepsis was $29,081 (95%CI, $28,404-$29,757) in the first year, rising to $60,714 (95%CI, $59,729-$61,698) over 5 years. This was higher for haematology patients; $46,154 (95%CI, $45,505-$46,804) in year 1, increasing to $75,931 (95%CI, $74,895-$76,968). Conclusions Sepsis imposes substantial economic burden and can result in a doubling of cancer care costs, particularly during the first year of cancer diagnosis. These estimates are helpful in improving our understanding of burden of sepsis along the cancer pathway and to deploy targeted strategies to alleviate this burden.

IntroductionIn order to properly evaluate the efficacy of orthopaedic procedures, rigorous, randomised controlled sham surgery trial designs are necessary. However, randomised controlled trials (RCTs) for surgery involving a placebo are ethically debated and difficult to conduct with many failing to reach their desired sample size and power. A review of the literature on barriers and enablers to recruitment, and patient and surgeon attitudes and preferences towards sham surgery trials, will help to determine the characteristics necessary for successful recruitment.Methods and analysisThis review will scope the diverse literature surrounding sham surgery trials with the aim of informing a discrete choice experiment to empirically test patient and surgeon preferences for different sham surgery trial designs. The scoping review will be conducted in accordance with the methodological framework described in Arksey and O’Malley (2005) and reported using the Preferred Reporting Items for Systematic Reviews and Meta-analyses Protocols extension for Scoping Reviews. The review will be informed by a systematic search of Medline, Embase, PsycInfo, CINAHL and EconLit databases (from database inception to 21 June 2019), a Google Scholar search, and hand searching of reference lists of relevant studies or reviews. Studies or opinion pieces that involve patient, surgeon or trial characteristics, which influence the decision to participate in a trial, will be included. Study selection will be carried out independently by two authors with discrepancies resolved by consensus among three authors. Data will be charted using a standardised form, and results tabulated and narratively summarised with reference to the research questions of the review.Ethics and disseminationThe findings from this review will inform the design of a discrete choice experiment around willingness to participate in surgical trials, the outcomes of which can inform decision and cost-effectiveness models of sham surgery RCTs. The qualitative information from this review will also inform patient-centred outcomes research. The review will be published in a peer-reviewed journal.Trial registration numberCRD42019133296.

Over the past two decades, there has been a sharp rise in the use of prescription opioids. In several countries, most notably the United States, opioid-related harm has been deemed a public health crisis. As surgeons are among the most prolific prescribers of opioids, growing attention is now being paid to the role that opioids play in surgical care. While opioids may sometimes be necessary to provide patients with adequate relief from acute pain after major surgery, the impact of opioids on the quality and safety of surgical care calls for greater scrutiny. This narrative review summarizes the available evidence on rates of persistent postsurgical opioid use and highlights the need to target known risk factors for persistent postoperative use before patients present for surgery. We draw attention to the mounting evidence that preoperative opioid exposure places patients at risk of persistent postoperative use, while also contributing to an increased risk of several other adverse clinical outcomes. By discussing the prevalence of excess opioid prescribing following surgery and highlighting significant variations in prescribing practices between countries, we note that there is a pressing need to optimize postoperative prescribing practices. Guided by the available evidence, we call for specific actions to be taken to address important research gaps and alleviate the harms associated with opioid use among surgical patients.

The ability to perform under heightened levels of pressures is one of the largest discriminators of those who achieve success in competition and those who do not. There are several phenomena associated with breakdowns in an athlete’s performance in a high-pressure environment, collectively known as paradoxical performances. The two most prevalent and researched forms of paradoxical performance are the yips and choking. The aim of the current study is to investigate a range of psychological traits (fear of negative evaluation, individual differences, anxiety sensitivity, self-consciousness, perfectionistic self-presentation, and perfectionism) and their ability to predict susceptibility to choking and the yips in an experienced athlete sample. 155 athletes (Golfers n = 86; Archers n = 69) completed six trait measures and a self-report measure of yips or choking experience. The prevalence rate for choking and yips in both archers and golfers was 67.7 and 39.4%, respectively. A 2 × 2 × 2 MANOVA and discriminant function analysis revealed that a combination of 11 variables correctly classified 71% of choking and non-choking participants. Furthermore, analysis confirmed that a combination of four variables correctly classified 69% of the yips and non-yips affected participants. In this first study to examine both paradoxical performances simultaneously, these findings revealed that for the yips, all predictors stemmed from social sources (i.e., perfectionistic self-presentation), whereas choking was associated with anxiety and perfectionism, as well as social traits. This important distinction identified here should now be tested to understand the role of these traits as development or consequential factors of choking and the yips.

Abstract Background Winning funding for health and medical research usually involves a lengthy application process. With success rates under 20%, much of the time spent by 80% of applicants could have been better used on actual research. An alternative funding system that could save time is using democracy to award the most deserving researchers based on votes from the research community. We aimed to pilot how such a system could work and examine some potential biases. Methods We used an online survey with a convenience sample of Australian researchers. Researchers were asked to name the 10 scientists currently working in Australia that they thought most deserved funding for future research. For comparison, we used recent winners from large national fellowship schemes that used traditional peer review. Results Voting took a median of 5 min (inter-quartile range 3 to 10 min). Extrapolating to a national voting scheme, we estimate 599 working days of voting time (95% CI 490 to 728), compared with 827 working days for the current peer review system for fellowships. The gender ratio in the votes was a more equal 45:55 (female to male) compared with 34:66 in recent fellowship winners, although this could be explained by Simpson’s paradox. Voters were biased towards their own institution, with an additional 1.6 votes per ballot (inter-quartile range 0.8 to 2.2) above the expected number. Respondents raised many concerns about the idea of using democracy to fund research, including vote rigging, lobbying and it becoming a popularity contest. Conclusions This is a preliminary study of using voting that does not investigate many of the concerns about how a voting system would work. We were able to show that voting would take less time than traditional peer review and would spread the workload over many more reviewers. Further studies of alternative funding systems are needed as well as a wide discussion with the research community about potential changes.

BackgroundThere is little systematic assessment of how total health expenditure is distributed across diseases and comorbidities. The objective of this study was to use statistical methods to disaggregate all publicly funded health expenditure by disease and comorbidities in order to answer three research questions: (1) What is health expenditure by disease phase for noncommunicable diseases (NCDs) in New Zealand? (2) Is the cost of having two NCDs more or less than that expected given the independent costs of each NCD? (3) How is total health spending disaggregated by NCDs across age and by sex?Methods and findingsWe used linked data for all adult New Zealanders for publicly funded events, including hospitalisation, outpatient, pharmaceutical, laboratory testing, and primary care from 1 July 2007 to 30 June 2014. These data include 18.9 million person-years and $26.4 billion in spending (US$ 2016). We used case definition algorithms to identify if a person had any of six NCDs (cancer, cardiovascular disease [CVD], diabetes, musculoskeletal, neurological, and a chronic lung/liver/kidney [LLK] disease). Indicator variables were used to identify the presence of any of the 15 possible comorbidity pairings of these six NCDs. Regression was used to estimate excess annual health expenditure per person. Cause deletion methods were used to estimate total population expenditure by disease. A majority (59%) of health expenditure was attributable to NCDs. Expenditure due to diseases was generally highest in the year of diagnosis and year of death. A person having two diseases simultaneously generally had greater health expenditure than the expected sum of having the diseases separately, for all 15 comorbidity pairs except the CVD-cancer pair. For example, a 60-64-year-old female with none of the six NCDs had $633 per annum expenditure. If she had both CVD and chronic LLK, additional expenditure for CVD separately was $6,443/$839/$9,225 for the first year of diagnosis/prevalent years/last year of life if dying of CVD; additional expenditure for chronic LLK separately was $6,443/$1,291/$9,051; and the additional comorbidity expenditure of having both CVD and LLK was $2,456 (95% confidence interval [CI] $2,238-$2,674). The pattern was similar for males (e.g., additional comorbidity expenditure for a 60-64-year-old male with CVD and chronic LLK was $2,498 [95% CI $2,264-$2,632]). In addition to this, the excess comorbidity costs for a person with two diseases was greater at younger ages, e.g., excess expenditure for 45-49-year-old males with CVD and chronic LLK was 10 times higher than for 75-79-year-old males and six times higher for females. At the population level, 23.8% of total health expenditure was attributable to higher costs of having one of the 15 comorbidity pairs over and above the six NCDs separately; of the remaining expenditure, CVD accounted for 18.7%, followed by musculoskeletal (16.2%), neurological (14.4%), cancer (14.1%), chronic LLK disease (7.4%), and diabetes (5.5%). Major limitations included incomplete linkage to all costed events (although these were largely non-NCD events) and missing private expenditure.ConclusionsThe costs of having two NCDs simultaneously is typically superadditive, and more so for younger adults. Neurological and musculoskeletal diseases contributed the largest health system costs, in accord with burden of disease studies finding that they contribute large morbidity. Just as burden of disease methodology has advanced the understanding of disease burden, there is a need to create disease-based costing studies that facilitate the disaggregation of health budgets at a national level.

The updated national guidelines for cardiovascular risk assessment and lipid modification in the UK and US expand the indications for statin therapy in primary prevention to adults with moderate risk of cardiovascular disease (CVD) but many adults at high CVD risk remain untreated in both countries. We set out to identify treatment gaps in English and American adults at moderate and high risk of cardiovascular disease (CVD), and to estimate the number of CVD events that would be prevented from expanding statin therapy to those who are currently untreated.We used nationally representative samples of 10,375 English adults and 7,687 US adults aged 40-75 years and free of existing CVD from the Health Survey for England 2009-2013, and the National Health and Nutrition Examination Survey 2007-2012 in the US. We used the risk algorithms and the risk thresholds for statin therapy recommended by each country's national guideline to categorize the survey participants into moderate-risk (≥10% to

Background: Various lipid measurements in monitoring/screening programmes can be used, alone or in cardiovascular risk scores, to guide treatment for prevention of cardiovascular disease (CVD). Because some changes in lipids are due to variability rather than true change, the value of lipid-monitoring strategies needs evaluation. Objective: To determine clinical value and cost-effectiveness of different monitoring intervals and different lipid measures for primary and secondary prevention of CVD. Data sources: We searched databases and clinical trials registers from 2007 (including the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, the Clinical Trials Register, the Current Controlled Trials register, and the Cumulative Index to Nursing and Allied Health Literature) to update and extend previous systematic reviews. Patient-level data from the Clinical Practice Research Datalink and St Luke’s Hospital, Japan, were used in statistical modelling. Utilities and health-care costs were drawn from the literature. Methods: In two meta-analyses, we used prospective studies to examine associations of lipids with CVD and mortality, and randomised controlled trials to estimate lipid-lowering effects of atorvastatin doses. Patient-level data were used to estimate progression and variability of lipid measurements over time, and hence to model lipid-monitoring strategies. Results are expressed as rates of true-/false-positive and true-/false-negative tests for high lipid or high CVD risk. We estimated incremental costs per quality-adjusted life-year. Results: A total of 115 publications reported strength of association between different lipid measures and CVD events in 138 data sets. The summary adjusted hazard ratio per standard deviation of total cholesterol (TC) to high-density lipoprotein (HDL) cholesterol ratio was 1.25 (95% confidence interval 1.15 to 1.35) for CVD in a primary prevention population but heterogeneity was high (I2 = 98%); similar results were observed for non-HDL cholesterol, apolipoprotein B and other ratio measures. Associations were smaller for other single lipid measures. Across 10 trials, low-dose atorvastatin (10 and 20 mg) effects ranged from a TC reduction of 0.92 mmol/l to 2.07 mmol/l, and low-density lipoprotein reduction of between 0.88 mmol/l and 1.86 mmol/l. Effects of 40 mg and 80 mg were reported by one trial each. For primary prevention, over a 3-year period, we estimate annual monitoring would unnecessarily treat 9 per 1000 more men (28 vs. 19 per 1000) and 5 per 1000 more women (17 vs. 12 per 1000) than monitoring every 3 years. However, annual monitoring would also undertreat 9 per 1000 fewer men (7 vs. 16 per 1000) and 4 per 1000 fewer women (7 vs. 11 per 1000) than monitoring at 3-year intervals. For secondary prevention, over a 3-year period, annual monitoring would increase unnecessary treatment changes by 66 per 1000 men and 31 per 1000 women, and decrease undertreatment by 29 per 1000 men and 28 per 1000 men, compared with monitoring every 3 years. In cost-effectiveness, strategies with increased screening/monitoring dominate. Exploratory analyses found that any unknown harms of statins would need utility decrements as large as 0.08 (men) to 0.11 (women) per statin user to reverse this finding in primary prevention. Limitation: Heterogeneity in meta-analyses. Conclusions: While acknowledging known and potential unknown harms of statins, we find that more frequent monitoring strategies are cost-effective compared with others. Regular lipid monitoring in those with and without CVD is likely to be beneficial to patients and to the health service. Future research should include trials of the benefits and harms of atorvastatin 40 and 80 mg, large-scale surveillance of statin safety, and investigation of the effect of monitoring on medication adherence. Study registration: This study is registered as PROSPERO CRD42013003727. Funding: The National Institute for Health Research Health Technology Assessment programme.

Background: Erythropoiesis stimulating agent (ESA)-resistant anemia is common in chronic kidney disease (CKD). Objectives: To evaluate the determinants of severity of ESA resistance in patients with CKD and primary ESA-resistance. Design: Secondary analysis of a randomized controlled trial (the Handling Erythropoietin Resistance with Oxpentifylline, HERO) Setting and patients: 53 adult patients with CKD stage 4 or 5 and primary ESA-resistant anemia (hemoglobin ≤120 g/L, ESA resistance index [ERI] ≥1.0 IU/kg/week/gHb for erythropoietin or ≥0.005 μg/kg/week/gHb for darbepoeitin, no cause for ESA-resistance identified). Measurements: Iron studies, parathyroid hormone, albumin, liver enzymes, phosphate or markers of oxidative stress and inflammation. Methods: Participants were divided into tertiles of ERI. Multinomial logistic regression was used to analyse the determinants of ERI tertiles. Results: All patients, except one, were receiving dialysis for end-stage kidney disease. The mean ± SD ERI values in the low ( n = 18), medium ( n = 18) and high ( n = 17) ERI tertiles were 1.4 ± 0.3, 2.3 ± 0.2 and 3.5 ± 0.8 IU/kg/week/gHb, respectively ( P < 0.001). There were no significant differences observed in age, gender, ethnicity, cause of kidney disease, diabetes, iron studies, parathyroid hormone, albumin, liver enzymes, phosphate or markers of oxidative stress and inflammation between the ERI tertiles. The median [inter-quartile range] serum alkaline phosphatase concentrations in the low, medium and high ERI tertiles were 89 [64,121], 99 [76,134 and 148 [87,175] U/L, respectively ( P = 0.054). There was a weak but statistically significant association between ERI and serum alkaline phosphatase (R 2 = 0.06, P = 0.03). Using multinomial logistic regression, the risk of being in the high ERI tertile relative to the low ERI tertile increased with increasing serum alkaline phosphatase levels ( P = 0.02). No other variables were significantly associated with ERI. Limitations: Small sample size; bone-specific alkaline phosphatase, other markers of bone turnover and bone biopsies not evaluated. Conclusions: Serum alkaline phosphatase was associated with severity of ESA resistance in ESA-resistant patients with CKD. Large prospective studies are required to confirm this association. (Trial registration: Australian New Zealand Clinical Trials Registry 12608000199314)

Background: Annual screening for adults with type 2 diabetes to detect the early onset of kidney disease is widely recommended, but the recommendations are based on a limited methodological approach. In addition, there are continuing uncertainties about underlying rates of progression of the condition and the benefits of treatments with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. Objectives: We aimed to estimate the clinical value and cost-effectiveness of different screening intervals to diagnose early diabetic kidney disease. Data sources: We used the following databases for the literature review (searched January 2005 to August 2010): MEDLINE, EMBASE and the Cochrane Database of Systematic Reviews. Individual patient data were obtained from the Oxford Regional Prospective Diabetes Study and the Collaborative Atorvastatin Diabetes Study. Methods: Data from systematically identified randomised trials reporting the impact on renal outcomes of angiotensin-converting enzyme inhibitors and angiotensin 2 receptor blockers for type 1 and type 2 diabetes patients with normoalbuminuria and microalbuminuria were pooled to derive estimates of effect. Individual patient data for type 1 and type 2 diabetes patients were used to obtain parameters describing progression and variability of measurement over time for the albumin-to-creatinine ratio (ACR) and estimated glomerular filtration rate. Based on accepted diagnostic thresholds, we modelled whether these tests accurately identified patients who were developing early diabetic kidney disease and required intensification of treatment. Cost-effectiveness analyses were carried out using simulation outcome models to estimate the incremental costs per quality-adjusted life-year (QALY) for different screening intervals. Results: In total, 49 trials (n = 34,082 patients) were eligible for inclusion in the systematic review. For type 1 diabetes, pooled estimates of urinary albumin excretion (UAE) for treated patients with microalbuminuria were on average 67% [95% confidence interval (CI) 54% to 77%] lower at the end of the trial than for untreated patients. There was no significant treatment effect for patients with normoalbuminuria (p interaction = 0.006). For treated patients with type 2 diabetes and normoalbuminuria or microalbuminuria, UAE was lower by, on average, 21% (95% CI 97% to 32%) or 27% (95% CI 15% to 38%), respectively. The proportion (95% CI) of men and women with type 1 diabetes screened annually for microalbuminuria over 6 years and inaccurately identified as having microalbuminuria would be 48% (43% to 53%) and 55% (48% to 61%), respectively. The corresponding proportions for type 2 diabetes are 36% (32% to 42%) and 48% (41% to 55%). Decreasing the screening interval to 3-yearly would reduce this for men with type 1 diabetes to 38% (33% to 44%), with an increase in those not identified over 6 years from 1.5% (95% CI 1% to 2%) to 4% (95% CI 3% to 5%). For type 1 diabetes, incremental cost per QALY [standard deviation (SD)] of a 5-yearly compared with a 4-yearly screening interval was £3612 (£6586), increasing to £9601 (£34,112) for annual compared with 2-yearly screening. The probability that the intervention is cost saving is around 25%, and it has around an 80% chance of being below a cost-effectiveness threshold of £30,000. For type 2 diabetes, incremental cost per QALY (SD) of a yearly compared with a 2-yearly screening interval was £606 (£1782). The intervention is almost certainly below a cost-effectiveness threshold of £5000. Conclusions: These results support current UK guidance, which recommends annual screening with ACR to identify early kidney disease in patients with diabetes, despite a high false-positive rate leading to, at worst, unnecessary or, at best, early therapeutic intervention. For type 1 diabetes, screening costs for annual compared with 2-yearly screening are well within the bounds of accepted cost-effectiveness. Annual screening is even more cost-effective in type 2 diabetes than in type 1 diabetes. Identification of alternative markers for developing diabetic nephropathy may improve targeting of treatment for those at high risk. Funding: The National Institute for Health Research Health Technology Assessment programme.