Aspirin and cancer treatment: systematic reviews and meta-analyses of evidence: for and against.

Aspirin as a possible treatment of cancer has been of increasing interest for over 50 years, but the balance of the risks and benefits remains a point of contention. We summarise the valid published evidence 'for' and 'against' the use of aspirin as a cancer treatment and we present what we believe are relevant ethical implications. Reasons for aspirin include the benefits of aspirin taken by patients with cancer upon relevant biological cancer mechanisms. These explain the observed reductions in metastatic cancer and vascular complications in cancer patients. Meta-analyses of 118 observational studies of mortality in cancer patients give evidence consistent with reductions of about 20% in mortality associated with aspirin use. Reasons against aspirin use include increased risk of a gastrointestinal bleed though there appears to be no valid evidence that aspirin is responsible for fatal gastrointestinal bleeding. Few trials have been reported and there are inconsistencies in the results. In conclusion, given the relative safety and the favourable effects of aspirin, its use in cancer seems justified, and ethical implications of this imply that cancer patients should be informed of the present evidence and encouraged to raise the topic with their healthcare team.

Systematic review update of observational studies further supports aspirin role in cancer treatment: Time to share evidence and decision-making with patients?

BACKGROUND: Evidence is growing that low-dose aspirin used as an adjuvant treatment of cancer is associated with an increased survival and a reduction in metastatic spread. We therefore extended up to August 2017 an earlier systematic search and meta-analyses of published studies of low-dose aspirin taken by patients with a diagnosis of cancer. METHODS: Searches were completed in Medline and Embase to August 2017 using a pre-defined search strategy to identify reports of relevant studies. References in all the selected papers were scanned. Two reviewers independently applied pre-determined eligibility criteria and extracted data on cause-specific cancer deaths, overall mortality and the occurrence of metastatic spread. Meta-analyses were then conducted for different cancers and heterogeneity and publication bias assessed. Sensitivity analyses and attempts to reduce heterogeneity were conducted. RESULTS: Analyses of 29 studies reported since an earlier review up to April 2015 are presented in this report, and these are then pooled with the 42 studies in our earlier publication. Overall meta-analyses of the 71 studies are presented, based on a total of over 120 thousand patients taking aspirin. Ten of the studies also give evidence on the incidence of metastatic cancer spread. There are now twenty-nine observational studies describing colorectal cancer (CRC) and post-diagnostic aspirin. Pooling the estimates of reduction by aspirin which are reported as hazard ratios (HR), gives an overall HR for aspirin and CRC mortality 0.72 (95% CI 0.64-0.80). Fourteen observational studies have reported on aspirin and breast cancer mortality and pooling those that report the association with aspirin as a hazard ratio gives HR 0.69 (0.53-0.90). Sixteen studies report on aspirin and prostate cancer mortality and a pooled estimate yields an HR of 0.87 (95% CI 0.73-1.05). Data from 12 reports relating to other cancers are also listed. Ten studies give evidence of a reduction in metastatic spread; four give a pooled HR 0.31 (95% CI 0.18, 0.54) and five studies which reported odds ratio of metastatic spread give OR 0.79 (0.66 to 0.95). CONCLUSION: Being almost entirely from observational studies, the evidence of benefit from aspirin is limited. There is heterogeneity between studies and the results are subject to important biases, only some of which can be identified. Nevertheless, the evidence would seem to merit wide discussion regarding whether or not it is adequate to justify the recommendation of low-dose therapeutic aspirin, and if it is, for which cancers?

Healthy living and cancer: evidence from UK Biobank.

CONTEXT: UK Biobank is a prospective study of half a million subjects, almost all aged 40-69 years, identified in 22 centres across the UK during 2006-2010. OBJECTIVE: A healthy lifestyle has been described as 'better than any pill, and no side effects [5]. We therefore examined the relationships between healthy behaviours: low alcohol intake, non-smoking, healthy BMI, physical activity and a healthy diet, and the risk of all cancers, colon, breast and prostate cancers in a large dataset. METHOD: Data on lifestyle behaviours were provided by 343,150 subjects, and height and weight were measured at recruitment. 14,285 subjects were diagnosed with cancer during a median of 5.1 years of follow-up. RESULTS: Compared with subjects who followed none or a single healthy behaviour, a healthy lifestyle based on all five behaviours was associated with a reduction of about one-third in incident cancer (hazard ratio [HR] 0.68; 95% confidence intervals [CI] 0.63-0.74). Colorectal cancer was reduced in subjects following the five behaviours by about one-quarter (HR 0.75; 95% CI 0.58-0.97), and breast cancer by about one-third (HR 0.65; 95% CI 0.52-0.83). The association between a healthy lifestyle and prostate cancer suggested a significant increase in risk, but this can be attributed to bias consequent on inequalities in the uptake of the prostate specific antigen screening test. CONCLUSIONS: Taken together with reported reductions in diabetes, vascular disease and dementia, it is clearly important that every effort is taken to promote healthy lifestyles throughout the population, and it is pointed out that cancer and other screening clinics afford 'teachable moments' for the promotion of a healthy lifestyle.

From passive subject to active agent: the potential of Citizens' Juries for nursing research.

The nursing profession needs to have a greater appreciation of how techniques such as Citizens' Juries can be used in nursing research. This paper explains the concept of Citizens' Juries and how it is being used as a form of social research, that can simultaneously increase public participation in policy making. Participation has become a key component of the discourse in policy making, and public participation initiatives can be one way of bridging the democratic deficit. For nursing, Citizens' Juries offer a way of discovering lay people's considered judgment on key policy issues, while also providing a potentially powerful platform for citizens to express their concerns and priorities, thereby influencing the services they receive. A Citizens' Jury brings together a small group of people over a period of time and presents them with a policy question. The jurors listen to expert witnesses, examine the evidence, deliberate on the issues and arrive at a policy decision or set of recommendations. In this paper we argue that any ordinary person given the opportunity, enough time and the necessary resources can make decisions about complex policy matters. Key findings from two Citizens' Juries on genetics in Wales are offered as case studies.

Systematic Review and Meta-Analysis of Randomised Trials to Ascertain Fatal Gastrointestinal Bleeding Events Attributable to Preventive Low-Dose Aspirin: No Evidence of Increased Risk.

BACKGROUND: Aspirin has been shown to lower the incidence and the mortality of vascular disease and cancer but its wider adoption appears to be seriously impeded by concerns about gastrointestinal (GI) bleeding. Unlike heart attacks, stroke and cancer, GI bleeding is an acute event, usually followed by complete recovery. We propose therefore that a more appropriate evaluation of the risk-benefit balance would be based on fatal adverse events, rather than on the incidence of bleeding. We therefore present a literature search and meta-analysis to ascertain fatal events attributable to low-dose aspirin. METHODS: In a systematic literature review we identified reports of randomised controlled trials of aspirin in which both total GI bleeding events and bleeds that led to death had been reported. Principal investigators of studies in which fatal events had not been adequately described were contacted via email and asked for further details. A meta-analyses was then performed to estimate the risk of fatal gastrointestinal bleeding attributable to low-dose aspirin. RESULTS: Eleven randomised trials were identified in the literature search. In these the relative risk (RR) of 'major' incident GI bleeding in subjects who had been randomised to low-dose aspirin was 1.55 (95% CI 1.33, 1.83), and the risk of a bleed attributable to aspirin being fatal was 0.45 (95% CI 0.25, 0.80). In all the subjects randomised to aspirin, compared with those randomised not to receive aspirin, there was no significant increase in the risk of a fatal bleed (RR 0.77; 95% CI 0.41, 1.43). CONCLUSIONS: The majority of the adverse events caused by aspirin are GI bleeds, and there appears to be no valid evidence that the overall frequency of fatal GI bleeds is increased by aspirin. The substantive risk for prophylactic aspirin is therefore cerebral haemorrhage which can be fatal or severely disabling, with an estimated risk of one death and one disabling stroke for every 1,000 people taking aspirin for ten years. These adverse effects of aspirin should be weighed against the reductions in vascular disease and cancer.

United Kingdom: Health System Review.

This analysis of the United Kingdom health system reviews recent developments in organization and governance, health financing, health care provision, health reforms and health system performance. It provides an overview of how the national health services operate in the four nations that make up the United Kingdom, as responsibility for organizing health financing and services was devolved from 1997. With devolution, the health systems in the United Kingdom have diverged in the details of how services are organized and paid for, but all have maintained national health services which provide universal access to a comprehensive package of services that are mostly free at the point of use. These health services are predominantly financed from general taxation and 83.5% of total health expenditure in the United Kingdom came from public sources in 2013. Life expectancy has increased steadily across the United Kingdom, but health inequalities have proved stubbornly resistant to improvement, and the gap between the most deprived and the most privileged continues to widen, rather than close. The United Kingdom faces challenges going forward, including how to cope with the needs of an ageing population, how to manage populations with poor health behaviours and associated chronic conditions, how to meet patient expectations of access to the latest available medicines and technologies, and how to adapt a system that has limited resources to expand its workforce and infrastructural capacity so it can rise to these challenges.

Evaluating the role of Cardiac Genetics Nurses in inherited cardiac conditions services using a Maturity Matrix.

BACKGROUND: Cardiovascular disease is a leading cause of death worldwide and genetic risk factors play a role in nearly all such cases. In the UK, health service capacity to meet either current or future estimated needs of people affected by inherited cardiac conditions (ICCs) is inadequate. In 2008 the British Heart Foundation funded nine three-year Cardiac Genetics Nurse (CGN) posts across England and Wales to enhance ICC services. The CGNs were experienced cardiac nurses who had additional training in genetics and acted to coordinate cardiac and genetics service activities. AIM: To create and apply a framework against which progress in ICC service improvement could be measured over time following the CGN appointments. METHODS: A performance grid (Maturity Matrix, MM) articulating standards in five domains against stages of ICC service development was created by stakeholders through a consensus approach. The MM was used to guide staged self-assessments by the CGNs between 2009 and 2011. A six-point scale was used to locate progress from 'emerging' to 'established', represented graphically by spider diagrams. RESULTS: Progress in all domains was significant for new, emerging and established services. It was most notable for effective utilisation of care pathways and efficient running of clinics. Commitment to family-centred care was evident. CONCLUSION: The ICC-MM provided a comprehensive framework for assessing ICC services and has merit in providing guidance on development. CGNs can help integrate care across specialisms, facilitating the development of effective and sustainable ICC services at new, developing, and more established ICC service locations.

Healthy lifestyles reduce the incidence of chronic diseases and dementia: evidence from the Caerphilly cohort study.

BACKGROUND: Healthy lifestyles based on non-smoking, an acceptable BMI, a high fruit and vegetable intake, regular physical activity, and low/moderate alcohol intake, are associated with reductions in the incidence of certain chronic diseases, but to date there is limited evidence on cognitive function and dementia. METHODS: In 1979 healthy behaviours were recorded on 2,235 men aged 45-59 years in Caerphilly, UK. During the following 30 years incident diabetes, vascular disease, cancer and death were recorded, and in 2004 cognitive state was determined. FINDINGS: Men who followed four or five of the behaviours had an odds ratio (OR) and confidence intervals (CI) for diabetes, corrected for age and social class, of 0.50 (95% CI: 0.19, 1.31; P for trend with increasing numbers of healthy behaviours <0.0005). For vascular disease the OR was 0.50 (95% CI: 0.30, 0.84; P for trend <0.0005), and there was a delay in vascular disease events of up to 12 years. Cancer incidence was not significantly related to lifestyle although there was a reduction associated with non-smoking (OR: 0.65; 95% CI: 0.54, 0.79). All-cause mortality was reduced in men following four or five behaviours (OR 0.40; 95% CI: 0.24, 0.67; P for trend <0.005). After further adjustment for NART, the OR for men following four or five healthy behaviours was 0.36 (95% CI: 0.12, 1.09; P for trend <0.001) for cognitive impairment, and 0.36 (95% CI: 0.07, 1.99; P for trend <0.02) for dementia. The adoption of a healthy lifestyle by men was low and appears not to have changed during the subsequent 30 years, with under 1% of men following all five of the behaviours and 5% reporting four or more in 1979 and in 2009. INTERPRETATION: A healthy lifestyle is associated with increased disease-free survival and reduced cognitive impairment but the uptake remains low.

United Kingdom (Wales): Health system review.

Wales is situated to the west of England, with a population of approximately 3 million (5% of the total for the United Kingdom), and a land mass of just over 20 000 km2. For several decades, Wales had a health system largely administered through the United Kingdom Governments Welsh Office, but responsibility for most aspects of health policy was devolved to Wales in a process beginning in 1999. Since then, differences between the policy approach and framework in England and Wales have widened. The internal market introduced in the United Kingdom National Health Service (NHS) has been abandoned in Wales, and seven local health boards (LHBs; supported by three specialist NHS trusts) now plan and provide all health services for their resident populations. Wales currently has more than 120 hospitals as part of an overall estate valued at 2.3 billion pounds. Total spending on health services increased in the first decade of the 21st century, but Wales now faces a period of financial retrenchment greater than in other parts of the United Kingdom as a result of the Welsh Governments decision not to afford the same degree of protection to health spending as that granted elsewhere. The health system in Wales continues to face some structural weaknesses that have proved resistant to reform for some time. However, there has been substantial improvement in service quality and outcomes since the end of the 1990s, in large part facilitated by substantial real growth in health spending. Life expectancy has continued to increase, but health inequalities have proved stubbornly resistant to improvement.

A national health inequalities fund for Wales: concept, design and implementation.

OBJECTIVES: To evaluate the potential for a national innovation fund, in the context of devolved health policy, to stimulate local action to deliver national priorities, using as a case study the conception, design and implementation of the £30m Welsh Assembly Government's (WAG) Inequalities in Health Fund (IiHF) 2001-08. METHODS: Multi-method evaluation of the national and local conception, design and implementation of the Fund, using analysis of documentary evidence, interviews and focus groups with national (Wales) officials and more than 170 local managers and professionals. The field work was carried out between October 2004 and June 2007. RESULTS: Different approaches at the three stages (concept, design, implementation) can reduce or enhance the effectiveness of funds like this one as a tool for achieving national objectives, and these are described. CONCLUSIONS: National funds can be a useful lever for change, if appropriately conceived, designed and implemented. However, in the context of competing healthcare and other policy priorities, 'good practice' is often difficult to achieve, and somewhat simplistic incentives are often subverted locally, diluting the original purpose of the initiative.

My health: whose responsibility? A jury decides.

BACKGROUND: Medicines are likely to assume an increasingly important role in helping people to remain healthy. But there are few indications as to what information and other support people want when assessing the risks and benefits of medicines; what role they feel government and healthcare professionals should play in informing, advising and encouraging healthy people on the potential benefits and possible risks of prophylactic medicines; and, ultimately, where does the responsibility for maintaining a person's health lie? METHODS: A Citizens' Jury was convened in October 2006 to consider these issues against the background of healthy living in general. The Jury was a broadly representative group of 16 people drawn from the community. A number of experts in clinical medicine, pharmacology and public health gave evidence and were questioned by the jurors. Vascular prophylaxis by a daily low-dose of aspirin was used as a case study throughout the discussions. RESULTS: The judgements of the jury included a clear demand for more information on health issues in general and on prophylactic medicines in particular, together with a desire that the public be more closely and openly involved in decision-taking in all matters relevant to health. The jurors were generally receptive to the possible role of medicines in the maintenance of health and a majority argued that people should be presented with evidence on medicines with possible health benefits, even when there is disagreement between experts about efficacy. CONCLUSION: The strategy of the Citizens' Jury, alongside other deliberative methods, could clearly have an important and valuable role in the formulation of public health and social policy.

United Kingdom: health system review

This analysis of the United Kingdom health system reviews recent developments in organization and governance, health financing, health care provision, health reforms and health system performance. It provides an overview of how the national health services operate in the four nations that make up the United Kingdom, as responsibility for organizing health financing and services was devolved from 1997. With devolution, the health systems in the United Kingdom have diverged in the details of how services are organized and paid for, but all have maintained national health services which provide universal access to a comprehensive package of services that are mostly free at the point of use. These health services are predominantly financed from general taxation and 83.5% of total health expenditure in the United Kingdom came from public sources in 2013. Life expectancy has increased steadily across the United Kingdom, but health inequalities have proved stubbornly resistant to improvement, and the gap between the most deprived and the most privileged continues to widen, rather than close. The United Kingdom faces challenges going forward, including how to cope with the needs of an ageing population, how to manage populations with poor health behaviours and associated chronic conditions, how to meet patient expectations of access to the latest available medicines and technologies, and how to adapt a system that has limited resources to expand its workforce and infrastructural capacity so it can rise to these challenges.

United Kingdom (Wales): health system review

For several decades, Wales had a health system largely administered through the United Kingdom Government’s Welsh Office, but responsibility for most aspects of health policy was devolved to Wales in a process beginning in 1999. Since then, differences between the policy approach and framework in England and Wales have widened. The internal market introduced in the United Kingdom National Health Service (NHS) has been abandoned in Wales, and seven local health boards (supported by three specialist NHS trusts) now plan and provide all health services for their resident populations. Wales currently has more than120 hospitals as part of an overall estate valued at £2.3 billion. Total spending on health services increased in the first decade of the 21st century, but Wales now faces a period of financial retrenchment greater than in other parts of the United Kingdom as a result of the Welsh Government’s decision not to afford the same degree of protection to health spending as that granted elsewhere. The health system in Wales continues to face some structural weaknesses that have proved resistant to reform for some time. However, there has been substantial improvement in service quality and outcomes since the end of the 1990s, in large part facilitated by substantial real growth in health spending. Life expectancy has continued to increase, but health inequalities have proved stubbornly resistant to improvement.

My health: whose responsibility? Low-dose aspirin and older people.

The benefit of aspirin as a prophylactic after a thrombotic event was first observed 30 years ago. Its use after coronary or cerebral thrombosis, and in patients judged to be at increased risk of a thrombotic event, is now virtually mandatory, unless there are signs of intolerance. The present policy in the UK for cardiovascular protection by low-dose aspirin is dependent upon the identification of people at high vascular risk. The policy has had only very limited success, partly owing to the fact that only a relatively small proportion of people with levels of vascular risk factors that would justify aspirin prophylaxis are identified. In fact, it has been demonstrated that the application of accepted guidelines for aspirin prophylaxis to risk factor data in representative UK population samples gives a cost-effective evidence-base for a reasonable extension of prophylaxis to all people aged over approximately 50 years. It is possible that reductions in both dementia and cancer incidence could also follow the wider use of low-dose aspirin but further research on these outcomes is urgently required. The evidence on possible benefits and harm from low-dose aspirin should therefore be publicized widely, and everything possible should be done to stimulate discussion involving the general public. In the end, however, the preservation of health is one's own responsibility and, therefore, people should generally be encouraged to evaluate the evidence on health-promotion measures, including low-dose aspirin, and take responsibility for their own health.

What choices should we be able to make about designer babies? A Citizens' Jury of young people in South Wales.

BACKGROUND: Young people will increasingly have the option of using new technologies for reproductive decision making but their voices are rarely heard in debates about acceptable public policy in this area. Capturing the views of young people about potentially esoteric topics, such as genetics, is difficult and methodologically challenging. DESIGN: A Citizens' Jury is a deliberative process that presents a question to a group of ordinary people, allows them to examine evidence given by expert witnesses and personal testimonies and arrive at a verdict. This Citizens' Jury explored designer babies in relation to inherited conditions, saviour siblings and sex selection with young people. PARTICIPANTS: Fourteen young people aged 16-19 in Wales. RESULTS: Acceptance of designer baby technology was purpose-specific; it was perceived by participants to be acceptable for preventing inherited conditions and to create a child to save a sibling, but was not recommended for sex selection. Jurors stated that permission should not depend on parents' age, although some measure of suitability should be assessed. Preventing potential parents from going abroad was considered impractical. These young people felt the Human Fertilisation and Embryology Authority should have members under 20 and that the term 'designer baby' was not useful. CONCLUSIONS: Perspectives on the acceptability of this technology were nuanced, and based on implicit value judgements about the extent of individual benefit derived. Young people have valuable and interesting contributions to make to the debate about genetics and reproductive decision making and a variety of innovative methods must be used to secure their involvement in decision-making processes.