Gareth Morgan

Aspirin in the Treatment of Cancer: Reductions in Metastatic Spread and in Mortality: A Systematic Review and Meta-Analyses of Published Studies.

Background Low-dose aspirin has been shown to reduce the incidence of cancer, but its role in the treatment of cancer is uncertain. Objectives We conducted a systematic search of the scientific literature on aspirin taken by patients following a diagnosis of cancer, together with appropriate meta-analyses. Methods Searches were completed in Medline and Embase in December 2015 using a pre-defined search strategy. References and abstracts of all the selected papers were scanned and expert colleagues were contacted for additional studies. Two reviewers applied pre-determined eligibility criteria (cross-sectional, cohort and controlled studies, and aspirin taken after a diagnosis of cancer), assessed study quality and extracted data on cancer cause-specific deaths, overall mortality and incidence of metastases. Random effects meta-analyses and planned sub-group analyses were completed separately for observational and experimental studies. Heterogeneity and publication bias were assessed in sensitivity analyses and appropriate omissions made. Papers were examined for any reference to bleeding and authors of the papers were contacted and questioned. Results Five reports of randomised trials were identified, together with forty two observational studies: sixteen on colorectal cancer, ten on breast and ten on prostate cancer mortality. Pooling of eleven observational reports of the effect of aspirin on cause-specific mortality from colon cancer, after the omission of one report identified on the basis of sensitivity analyses, gave a hazard ratio (HR) of 0.76 (95% CI 0.66, 0.88) with reduced heterogeneity (P = 0.04). The cause specific mortality in five reports of patients with breast cancer showed significant heterogeneity (P<0.0005) but the omission of one outlying study reduced heterogeneity (P = 0.19) and led to an HR = 0.87 (95% CI 0.69, 1.09). Heterogeneity between nine studies of prostate cancer was significant, but again, the omission of one study led to acceptable homogeneity (P = 0.26) and an overall HR = 0.89 (95% CI 0.79–0.99). Six single studies of other cancers suggested reductions in cause specific mortality by aspirin, and in five the effect is statistically significant. There were no significant differences between the pooled HRs for the three main cancers and after the omission of three reports already identified in sensitivity analyses heterogeneity was removed and revealed an overall HR of 0.83 (95% CI 0.76–0.90). A mutation of PIK3CA was present in about 20% of patients, and appeared to explain most of the reduction in colon cancer mortality by aspirin. Data were not adequate to examine the importance of this or any other marker in the effect of aspirin in the other cancers. On bleeding attributable to aspirin two reports stated that there had been no side effect or bleeding attributable to aspirin. Authors on the other reports were written to and 21 replied stating that no data on bleeding were available. Conclusions and Implications The study highlights the need for randomised trials of aspirin treatment in a variety of cancers. While these are awaited there is an urgent need for evidence from observational studies of aspirin and the less common cancers, and for more evidence of the relevance of possible bio-markers of the aspirin effect on a wide variety of cancers. In the meantime it is urged that patients in whom a cancer is diagnosed should be given details of this research, together with its limitations, to enable each to make an informed decision as to whether or not to take low-dose aspirin. Systematic Review Protocol Number CRD42015014145

Aspirin for everyone older than 50

Current population screening for vascular disease is neither efficient nor effective. Peter Elwood and colleagues believe we should have a public information strategy highlighting the benefits (and risks) of aspirin for older people, but Colin Baigent argues that the evidence of benefit is not yet strong enough It is 30 years since the first randomised trial was published showing a link between aspirin and myocardial infarction.1 We believe that the evidence now supports more widespread use of aspirin prophylaxis, and there needs to be a strategy to inform the public and enable older people to make their own decision. The evidence focuses on a crucial question—namely, at what age does the balance between benefit and risk justify low dose aspirin prophylaxis? Of further relevance is a possible reduction of cancer and dementia by aspirin. Although several groups have recommended aspirin prophylaxis based on age alone, including a recommendation of daily aspirin for everyone over 50,2 3 cardioprotection is usually given only to people at vascular risk. Many formulas are available to assess risk, and one of these4 is the basis of the recommendation that prophylactic aspirin be considered if the five year risk of a vascular event is 3% or more.5 Application of the Framingham risk formula4 to the …

Evidence-Based Health Policy: A Preliminary Systematic Review

Objective: The development of evidence-based health policy is challenging. This study has attempted to identify some of the underpinning factors that promote the development of evidence based health policy.Methods: A preliminary systematic literature review of published reviews with ‘evidence based health policy’ in their title was conducted using PubMed as a search engine. The identified papers were critically analysed using a ‘realist review’ method, driven by the question ‘What works for whom in what circumstances and in what respects?’.Results: Eight published reviews met the search criteria. Following the ‘realist review’, six factors that underpin the development of evidence-based health policy were identified. They are: (i) the importance and value of having multi-disciplinary teams; (ii) the need to have a broad evidence base to draw upon; (iii) the circular relationship between research and policy; (iv) the need for policy implementation to be locally sensitive; (v) the benefit of stakeholder inv...

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.

Co-production within health and social care – the implications for Wales?

Purpose – It is well recognised that individuals have much to contribute to the care that they receive, with attendant benefits on outcomes and reduction in cost. The recognition of individuals who access care services as interdependent citizens embedded in both formal and informal support networks is a shift that acknowledges their active role as partners in management of their own care and in service innovation and development. The purpose of this paper is therefore to explore and illustrate some of the domains of co-production. Design/methodology/approach – In this paper, the authors review the literature, both peer-reviewed and professional, in order to provide a broad and contemporary commentary on this emergent approach. This literature is critically summarised and presented along with a narrative that discusses the context in Wales, where the authors are based. The approach to this paper is to bring together existing knowledge and also propose potential avenues for further research and practise dev...

Integration of health and social care – what can Wales learn … and contribute?

Purpose – This paper aims to present a review on health and social care service integration, drawing on experience from the United Kingdom, Europe and Canada.Design/methodology/approach – A review of the literature was undertaken and critical summaries of the findings are presented.Findings – It seems no country can put forward a universal set of principles that are applicable in all settings.Practical implications – Each country has their own challenges, so perhaps this encourages Welsh professionals to learn from their own experience.Originality/value – This paper adds value by drawing together the literature and providing a contribution from Wales.

On the potential contribution of aspirin to healthy ageing programmes

Following myocardial infarction or ischaemic stroke, aspirin is often part of a package of measures to reduce the risk of subsequent vascular events [1]. In this context, the use of aspirin is therapeutic as part of the ongoing treatment of underlying atherosclerotic disease. The ongoing treatment of existing disease, however, can be distinct to the preservation of health. The former is often provided by healthcare services while the latter includes personal responsibility for self-care. Perhaps a balance of access to healthcare and personal self-care may be needed as part of healthy ageing programmes. But what is healthy ageing? This is difficult to answer, not least because the term ‘health’ per se lacks a universally accepted definition [2]. Given this fundamental question, perhaps it is more helpful to consider healthy ageing, at least in part, as one natural consequence of reducing the risk of disease. There are many ways to reduce the risk of disease. For example, there are approaches that are delivered by healthcare staff, such as vaccination programmes. Lifestyle and behaviour are also important, such as the level of alcohol consumption. Sometimes, numerous approaches to a single disease risk factor can be employed, for example smoking cessation can, respectively, combine nicotine replacement therapy with personal motivation. So reducing the risk of disease, which in everyday parlance may be termed healthy ageing, can combine evidence-based interventions with lifestyle choices. However, although there is evidence on the relationship between disease risk factors and life expectancy [3], converting this and other evidence into effective policy remains a challenge [4]. It has been suggested that the prevention agenda might only be properly progressed when Government, policy makers, public health services and the people collaborate in a ‘fully engaged’ way [5]. A related consideration, which illustrates some of the complexity, is that there are different organisations with vested interests in the factors that influence disease risk. For example, in the case of alcohol this includes Governments, the brewery industry, individual consumers and agencies who offer services to those adversely affected from the problems associated with excess drinking. Such a range of stakeholders may lead to mixed messages being delivered. Many questions arise. What are the roles and responsibilities of the media in disseminating information?? Will there ever be an integrated and widely agreed approach to healthy ageing?? If so, is it affordable to deliver it? It is against this complex background, with many uncertainties, that the potential of aspirin may be considered. There is evidence relating to the use of the medicine on age grounds. The risk of vascular events increases with age and perhaps aspirin use could be considered by about the age of 50 [6, 7]. Reasonable objections to the use of aspirin on age grounds for the primary prevention of vascular events include concerns about undesirable effects, most notably bleeding [8]. Some of these effects may have a serious clinical impact, such as a significant increased risk of haemorrhagic stroke [9]. Another objection is that recent primary prevention trials, for example in patients with type 2 diabetes mellitus [10, 11], have failed to demonstrate a clear overall benefit from aspirin. Furthermore, some individuals might be resistant to the effects of aspirin. Therefore in primary prevention, the number of vascular events avoided and bleeds caused by aspirin might be equivocal, both in terms of numbers and clinical significance. Of course, the aspirin failures, namely those taking the medicine experiencing a vascular event or bleed, are visible. Such failure visibility may lead to negative perceptions. Of course, this invites the question of what constitutes a ‘failure’. A vascular event may have been delayed and in healthy ageing that is also important. The evidence that aspirin also reduces risk of several cancers is a further factor to be considered. Aspirin chemoprevention of cancer, however, may take many years of continuous use [12]. Whether individuals will adhere to such a long-term regime is unclear, especially given the concerns of visible failure. The potential contribution of aspirin to healthy ageing programmes raises both specific and general questions. To consider one specific question, how does the evidence on aspirin and cancer chemoprevention influence the overall benefit versus risk assessment? This is not an easy question to answer given that each individual judgement on the benefit versus risk may vary. In addition, uncertainties and questions remain about optimum dose, duration and frequency of aspirin prophylaxis [13] and the age to start use. For vascular disease, 75–15 mg per day is typically used, with higher doses having equal efficacy and more

Health promotion for older people in Wales: preliminary evaluation of the National Service Framework for Older People

Aim. In this preliminary study, the health promotion activities for older people in Wales were evaluated with a view to form initial conclusions and research areas. The study drew on a dataset that is collated on an all-Wales basis. Background. The National Service Framework for Older People is a 10-year strategy concerned with the effective delivery of health and social care for individuals over the age of 50 years. It has 10 standards and number 3 of these relates to health promotion. The health promotion standard covers a wide range of issues, including alcohol, smoking, exercise, diet and vaccination. Methods. Information was extracted from an all-Wales Self-Assessment Audit Tool. A ‘realist review’ methodology was used to further extract information, using a combination of note taking and a questionnaire protocol. A further analysis was undertaken using a theoretical framework of six policy factors. Results. Health promotion in Wales is being implemented in locally sensitive ways and this has strengths. Weaknesses include measurement and comparison. Conclusions. This study illustrates that the health promotion agenda has a considerable amount of activity in Wales. Future research might include detailed evaluations of some areas, perhaps with health economic analysis included.

Use of the internet in assessing service provision for older people

Purpose – The evaluation of primary and other care services for older people remains difficult due to the challenges of cost‐effective sampling and assessment of older peoples views. The internet is an increasingly attractive option for evaluation due to its low cost and flexibility of use. The purpose of this paper is to report on a pilot study into the use of a web‐platform with older people.Design/methodology/approach – A sample of 552 community dwelling men and women, aged at least 50 years, participated in an epidemiologic study conducted entirely remotely which included questions on the provision of services for older people.Findings – The sample was heterogeneous being 52 per cent male, an age range of 50‐95 years (x¯=64 years) and with 13 per cent being in the two most deprived categories of social deprivation. Awareness of the National Service Framework for older people was low (14 per cent). For areas covered by the policy satisfaction with the availability of services was generally high (>70 p...

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.