Estimating the returns to UK publicly funded cancer-related research in terms of the net value of improved health outcomes

© 2014 Glover et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background - Building on an approach developed to assess the economic returns to cardiovascular research, we estimated the economic returns from UK public and charitable funded cancer-related research that arise from the net value of the improved health outcomes. Methods - To assess these economic returns from cancer-related research in the UK we estimated: 1) public and charitable expenditure on cancer-related research in the UK from 1970 to 2009; 2) net monetary benefit (NMB), that is, the health benefit measured in quality adjusted life years (QALYs) valued in monetary terms (using a base-case value of a QALY of GB£25,000) minus the cost of delivering that benefit, for a prioritised list of interventions from 1991 to 2010; 3) the proportion of NMB attributable to UK research; 4) the elapsed time between research funding and health gain; and 5) the internal rate of return (IRR) from cancer-related research investments on health benefits. We analysed the uncertainties in the IRR estimate using sensitivity analyses to illustrate the effect of some key parameters. Results - In 2011/12 prices, total expenditure on cancer-related research from 1970 to 2009 was £15 billion. The NMB of the 5.9 million QALYs gained from the prioritised interventions from 1991 to 2010 was £124 billion. Calculation of the IRR incorporated an estimated elapsed time of 15 years. We related 17% of the annual NMB estimated to be attributable to UK research (for each of the 20 years 1991 to 2010) to 20 years of research investment 15 years earlier (that is, for 1976 to 1995). This produced a best-estimate IRR of 10%, compared with 9% previously estimated for cardiovascular disease research. The sensitivity analysis demonstrated the importance of smoking reduction as a major source of improved cancer-related health outcomes. Conclusions - We have demonstrated a substantive IRR from net health gain to public and charitable funding of cancer-related research in the UK, and further validated the approach that we originally used in assessing the returns from cardiovascular research. In doing so, we have highlighted a number of weaknesses and key assumptions that need strengthening in further investigations. Nevertheless, these cautious estimates demonstrate that the returns from past cancer research have been substantial, and justify the investments made during the period 1976 to 1995.Wellcome Trust, Cancer Research UK, the National Institute of Health Research, and the Academy of Medical Sciences

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Morphometrics as an Insight Into Processes Beyond Tooth Shape Variation in a Bank Vole Population

Phenotype variation is a key feature in evolution, being produced by development and the target of the screening by selection. We focus here on a variable morphological feature: the third upper molar (UM3) of the bank vole, aiming at identifying the sources of this variation. Size and shape of the UM3 occlusal surface was quantified in successive samples of a bank vole population. The first source of variation was the season of trapping, due to differences in the age structure of the population in turn affecting the wear of the teeth. The second direction of variation corresponded to the occurrence, or not, of an additional triangle on the tooth. This intra-specific variation was attributed to the space available at the posterior end of the UM3, allowing or not the addition of a further triangle.This size variation triggering the shape polymorphism is not controlled by the developmental cascade along the molar row. This suggests that other sources of size variation, possibly epigenetic, might be involved. They would trigger an important shape variation as side-effect by affecting the termination of the sequential addition of triangles on the tooth

Why Are There Social Gradients in Preventative Health Behavior? A Perspective from Behavioral Ecology

Background: Within affluent populations, there are marked socioeconomic gradients in health behavior, with people of lower socioeconomic position smoking more, exercising less, having poorer diets, complying less well with therapy, using medical services less, ignoring health and safety advice more, and being less health-conscious overall, than their more affluent peers. Whilst the proximate mechanisms underlying these behavioral differences have been investigated, the ultimate causes have not. Methodology/Principal Findings: This paper presents a theoretical model of why socioeconomic gradients in health behavior might be found. I conjecture that lower socioeconomic position is associated with greater exposure to extrinsic mortality risks (that is, risks that cannot be mitigated through behavior), and that health behavior competes for people’s time and energy against other activities which contribute to their fitness. Under these two assumptions, the model shows that the optimal amount of health behavior to perform is indeed less for people of lower socioeconomic position. Conclusions/Significance: The model predicts an exacerbatory dynamic of poverty, whereby the greater exposure of poor people to unavoidable harms engenders a disinvestment in health behavior, resulting in a final inequality in health outcomes which is greater than the initial inequality in material conditions. I discuss the assumptions of the model, and it

The role of cognitive emotion regulation on the vicarious emotional response

Perceiving another in need may provoke two possible emotional responses: empathic concern and personal distress. This research aims to test whether different emotion regulation strategies (i.e., reappraisal and rumination) may lead to different vicarious emotional responses (i.e., empathic concern and personal distress). In this sense, we hypothesized that reappraisal may lead to a greater feeling of empathic concern, whereas rumination may lead to a higher feeling of personal distress. To test the hypotheses we used experimental instructions (Study 1) and a priming procedure (Study 2) to manipulate the emotion regulation strategies. The results supported our hypotheses. Furthermore in the rumination condition the emotional experience was described as being more negative and more highly arousing than in the reappraisal condition. We discuss the effect of these two forms of cognitive emotion regulation on empathic concern and personal distress

A Tradeoff Drives the Evolution of Reduced Metal Resistance in Natural Populations of Yeast

Various types of genetic modification and selective forces have been implicated in the process of adaptation to novel or adverse environments. However, the underlying molecular mechanisms are not well understood in most natural populations. Here we report that a set of yeast strains collected from Evolution Canyon (EC), Israel, exhibit an extremely high tolerance to the heavy metal cadmium. We found that cadmium resistance is primarily caused by an enhanced function of a metal efflux pump, PCA1. Molecular analyses demonstrate that this enhancement can be largely attributed to mutations in the promoter sequence, while mutations in the coding region have a minor effect. Reconstruction experiments show that three single nucleotide substitutions in the PCA1 promoter quantitatively increase its activity and thus enhance the cells' cadmium resistance. Comparison among different yeast species shows that the critical nucleotides found in EC strains are conserved and functionally important for cadmium resistance in other species, suggesting that they represent an ancestral type. However, these nucleotides had diverged in most Saccharomyces cerevisiae populations, which gave cells growth advantages under conditions where cadmium is low or absent. Our results provide a rare example of a selective sweep in yeast populations driven by a tradeoff in metal resistance

Nonlinear gap junctions enable long-distance propagation of pulsating calcium waves in astrocyte networks

A new paradigm has recently emerged in brain science whereby communications between glial cells and neuron-glia interactions should be considered together with neurons and their networks to understand higher brain functions. In particular, astrocytes, the main type of glial cells in the cortex, have been shown to communicate with neurons and with each other. They are thought to form a gap-junction-coupled syncytium supporting cell-cell communication via propagating Ca2+ waves. An identified mode of propagation is based on cytoplasm-to-cytoplasm transport of inositol trisphosphate (IP3) through gap junctions that locally trigger Ca2+ pulses via IP3-dependent Ca2+-induced Ca2+ release. It is, however, currently unknown whether this intracellular route is able to support the propagation of long-distance regenerative Ca2+ waves or is restricted to short-distance signaling. Furthermore, the influence of the intracellular signaling dynamics on intercellular propagation remains to be understood. In this work, we propose a model of the gap-junctional route for intercellular Ca2+ wave propagation in astrocytes showing that: (1) long-distance regenerative signaling requires nonlinear coupling in the gap junctions, and (2) even with nonlinear gap junctions, long-distance regenerative signaling is favored when the internal Ca2+ dynamics implements frequency modulation-encoding oscillations with pulsating dynamics, while amplitude modulation-encoding dynamics tends to restrict the propagation range. As a result, spatially heterogeneous molecular properties and/or weak couplings are shown to give rise to rich spatiotemporal dynamics that support complex propagation behaviors. These results shed new light on the mechanisms implicated in the propagation of Ca2+ waves across astrocytes and precise the conditions under which glial cells may participate in information processing in the brain.Comment: Article: 30 pages, 7 figures. Supplementary Material: 11 pages, 6 figure

Children reading to dogs: a systematic review of the literature

Background Despite growing interest in the value of human-animal interactions (HAI) to human mental and physical health the quality of the evidence on which postulated benefits from animals to human psychological health are based is often unclear. To date there exist no systematic reviews on the effects of HAI in educational settings specifically focussing on the perceived benefits to children of reading to dogs. With rising popularity and implementation of these programmes in schools, it is essential that the evidence base exploring the pedagogic value of these initiatives is well documented. Methods Using PRISMA guidelines we systematically investigated the literature reporting the pedagogic effects of reading to dogs. Because research in this area is in the early stages of scientific enquiry we adopted broad inclusion criteria, accepting all reports which discussed measurable effects related to the topic that were written in English. Multiple online databases were searched during January-March 2015; grey literature searches were also conducted. The search results which met the inclusion criteria were evaluated, and discussed, in relation to the Oxford Centre for Evidence Based Medicine levels of evidence; 27 papers were classified as Level 5, 13 as Level 4, 7 as Level 2c and 1 as Level 2b. Conclusion The evidence suggests that reading to a dog may have a beneficial effect on a number of behavioural processes which contribute to a positive effect on the environment in which reading is practiced, leading to improved reading performance. However, the evidence base on which these inferences are made is of low quality. There is a clear need for the use of higher quality research methodologies and the inclusion of appropriate controls in order to draw causal inferences on whether or how reading to dogs may benefit children’s reading practices. The mechanisms for any effect remain a matter of conjectur

Comorbidity and dementia: a scoping review of the literature.

BACKGROUND: Evidence suggests that amongst people with dementia there is a high prevalence of comorbid medical conditions and related complaints. The presence of dementia may complicate clinical care for other conditions and undermine a patient's ability to manage a chronic condition. The aim of this study was to scope the extent, range and nature of research activity around dementia and comorbidity. METHODS: We undertook a scoping review including all types of research relating to the prevalence of comorbidities in people with dementia; current systems, structures and other issues relating to service organisation and delivery; patient and carer experiences; and the experiences and attitudes of service providers. We searched AMED, Cochrane Library, CINAHL, PubMed, NHS Evidence, Scopus, Google Scholar (searched 2012, Pubmed updated 2013), checked reference lists and performed citation searches on PubMed and Google Scholar (ongoing to February 2014). RESULTS: We included 54 primary studies, eight reviews and three guidelines. Much of the available literature relates to the prevalence of comorbidities in people with dementia or issues around quality of care. Less is known about service organisation and delivery or the views and experiences of people with dementia and their family carers. There is some evidence that people with dementia did not have the same access to treatment and monitoring for conditions such as visual impairment and diabetes as those with similar comorbidities but without dementia. CONCLUSIONS: The prevalence of comorbid conditions in people with dementia is high. Whilst current evidence suggests that people with dementia may have poorer access to services the reasons for this are not clear. There is a need for more research looking at the ways in which having dementia impacts on clinical care for other conditions and how the process of care and different services are adapting to the needs of people with dementia and comorbidity. People with dementia should be included in the debate about the management of comorbidities in older populations and there needs to be greater consideration given to including them in studies that focus on age-related healthcare issues