A third of deaths in the UK from ruptured abdominal aortic aneurysm (AAA) are in women. In men, national screening programmes reduce deaths from AAA and are cost-effective. The benefits, harms, and ...cost-effectiveness in offering a similar programme to women have not been formally assessed, and this was the aim of this study.
We developed a decision model to assess predefined outcomes of death caused by AAA, life years, quality-adjusted life years, costs, and the incremental cost-effectiveness ratio for a population of women invited to AAA screening versus a population who were not invited to screening. A discrete event simulation model was set up for AAA screening, surveillance, and intervention. Relevant women-specific parameters were obtained from sources including systematic literature reviews, national registry or administrative databases, major AAA surgery trials, and UK National Health Service reference costs.
AAA screening for women, as currently offered to UK men (at age 65 years, with an AAA diagnosis at an aortic diameter of ≥3·0 cm, and elective repair considered at ≥5·5cm) gave, over 30 years, an estimated incremental cost-effectiveness ratio of £30 000 (95% CI 12 000–87 000) per quality-adjusted life year gained, with 3900 invitations to screening required to prevent one AAA-related death and an overdiagnosis rate of 33%. A modified option for women (screening at age 70 years, diagnosis at 2·5 cm and repair at 5·0 cm) was estimated to have an incremental cost-effectiveness ratio of £23 000 (9500–71 000) per quality-adjusted life year and 1800 invitations to screening required to prevent one AAA-death, but an overdiagnosis rate of 55%. There was considerable uncertainty in the cost-effectiveness ratio, largely driven by uncertainty about AAA prevalence, the distribution of aortic sizes for women at different ages, and the effect of screening on quality of life.
By UK standards, an AAA screening programme for women, designed to be similar to that used to screen men, is unlikely to be cost-effective. Further research on the aortic diameter distribution in women and potential quality of life decrements associated with screening are needed to assess the full benefits and harms of modified options.
UK National Institute for Health Research Health Technology Assessment programme.
Aortic aneurysms are an important cause of cardiovascular death in elderly patients. At present, little is known of the pathobiology of aneurysmal disease and this limits the ability to develop ...non-surgical treatments to stabilise aneurysms. Both thoracic and abdominal aortic aneurysms (AAA) demonstrate a strong genetic component in their aetiology. Determination of the genetic variants associated with aneurysmal disease is one approach to increasing the understanding the pathways leading to aneurysmal degeneration of the aorta. In this review, we aim to summarise the current knowledge of the genetics underlying the two most common disease phenotypes, thoracic aortic aneurysm (TAA) and AAA. Genetically, AAA represent a multifactorial disease, with the likelihood that there are multiple variants of very low effect sizes contributing to the overall genetic disease risk. Non-syndromic TAA appears to be associated with a smaller number of risk loci with higher individual effect sizes at these loci. Candidate gene and genome-wide approaches have identified robust associations between AAA and variants in/nearby the SORT1, low-density lipoprotein receptor, DAB2IP, LRP1, ELN, CRP, TGFB and various matrix metallo-proteinase genes suggesting that aberrations of lipid metabolism and proteolytic pathways are the key contributors to disease. Some of these associations (eg, LRP1) are not associated with atherosclerosis, suggesting pathways unique to AAA. Genetic variants associated with non-syndromic TAA (ACTA2 and MYH11) are related to the TGFβ pathway, strongly implicated in syndromic TAA, thus suggesting a common pathway between syndromic and non-syndromic TAA.
Abstract Objective To assess the utility of funnel plots in assessing publication bias (PB) in meta-analyses of proportion studies. Study Design and Setting Meta-analysis simulation study and ...meta-analysis of published literature reporting peri-operative mortality after abdominal aortic aneurysm (AAA) repair. Data for the simulation study were stochastically generated. A literature search of Medline and Embase was performed to identify studies for inclusion in the published literature meta-analyses. Results The simulation study demonstrated that conventionally constructed funnel plots (log odds vs. 1/standard error 1/SE) for extreme proportional outcomes were asymmetric despite no PB. Alternative funnel plots constructed using study size rather than 1/SE showed no asymmetry for extreme proportional outcomes. When used in meta-analyses of the mortality of AAA repair, these alternative funnel plots highlighted the possibility for conventional funnel plots to demonstrate asymmetry when there was no evidence of PB. Conclusion Conventional funnel plots used to assess for potential PB in meta-analyses are inaccurate for meta-analyses of proportion studies with low proportion outcomes. Funnel plots of study size against log odds may be a more accurate way of assessing for PB in these studies.
Abstract Atherosclerosis and abdominal aortic aneurysms (AAAs) are multifactorial and polygenic diseases with known environmental and genetic risk factors that contribute towards disease development. ...Atherosclerosis represents an important independent risk factor for AAA, as people with AAA often have atherosclerosis. Studies have shown that co-morbidity is usually between~25–55%, but it is still not fully known whether this association is causal or a result of common shared risk profiles. Most recent epidemiological, clinical and biological evidence suggests that the two pathologies are more distinct than traditionally thought. For instance diabetes mellitus, hypercholesterolemia and obesity are high risk for atherosclerosis development but are not as pronounced in AAA, whereas smoking, gender and ethnicity are particularly high risk for AAA but less so for atherosclerosis. In addition genetic and epigenetic studies have identified independent risk loci involved in AAA susceptibility that are not associated with other cardiovascular diseases, and research on important common cardiovascular biomarkers has illustrated discrepancies in those with AAA.
Cardiovascular disease is a major contributor to poor health in the UK and the leading cause of death in England. Peripheral arterial disease and high blood pressure are conditions that identify ...individuals at high cardiovascular disease risk, likely to benefit from cardiovascular risk management. Both conditions remain considerably underdiagnosed and untreated. The National Health Service abdominal aortic aneurysm (AAA) screening programmes represent an opportunity to screen for these conditions with potentially minimal additional effort or cost. We explored AAA screening programme staff views on the proposed introduction of such additional screening within AAA screening.
Nine focus groups and seven follow-on interviews were undertaken with 38 AAA screening staff. Our study methods were oriented broadly towards a grounded theory methodology, and data were analysed using thematic analysis.
Three themes were identified: (i) 'Perceptions of patient experience and health-related outcomes', (ii) 'Opportunities and challenges for programme staff', and (iii) 'Maintaining and improving programme standards'. Staff talked about the high uptake of AAA screening, staff experience and skills in their role, and the programme's high quality standards as both opportunities and potential challenges linked to the proposed additions to AAA screening. While positive about the potential to improve patients' health outcomes, participants had questions about the practicalities of incorporating additional procedures within their time- and resource-constrained context, and how this may reconfigure work processes, roles and relationships.
The proposed additions to the programme require taking staff's views into account. Key areas that need to be addressed relate to ensuring follow-up support for patients, clarity around staff responsibilities, and availability of sufficient resources for the programme.
Celotno besedilo
Dostopno za:
CEKLJ, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
There is a clinical need for treatments that can slow or prevent the growth of an abdominal aortic aneurysm, not only to reduce the need for surgery, but to provide a means to treat those who cannot ...undergo surgery.
Analysis of the UK Aneurysm Growth Study (UKAGS) prospective cohort was conducted to test for an association between cardiometabolic medications and the growth of an abdominal aortic aneurysm above 30 mm in diameter, using linear mixed-effect models.
A total of 3670 male participants with data available on abdominal aortic aneurysm growth, smoking status, co-morbidities, and medication history were included. The mean age at recruitment was 69.5 years, the median number of surveillance scans was 6, and the mean(s.e.) unadjusted abdominal aortic aneurysm growth rate was 1.75(0.03) mm/year. In a multivariate linear mixed-effect model, smoking (mean(s.e.) +0.305(0.07) mm/year, P = 0.00003) and antiplatelet use (mean(s.e.) +0.235(0.06) mm/year, P = 0.00018) were found to be associated with more rapid abdominal aortic aneurysm growth, whilst metformin was strongly associated with slower abdominal aortic aneurysm growth (mean(s.e.) -0.38(0.1) mm/year, P = 0.00019), as were angiotensin-converting enzyme inhibitors (mean(s.e.) -0.243(0.07) mm/year, P = 0.0004), angiotensin II receptor antagonists (mean(s.e.) -0.253(0.08) mm/year, P = 0.00255), and thiazides/related diuretics (mean(s.e.) -0.307(0.09) mm/year, P = 0.00078).
The strong association of metformin with slower abdominal aortic aneurysm growth highlights the importance of the ongoing clinical trials assessing the effectiveness of metformin with regard to the prevention of abdominal aortic aneurysm growth and/or rupture. The association of angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists, and diuretics with slower abdominal aortic aneurysm growth points to the possibility that optimization of cardiovascular risk management as part of abdominal aortic aneurysm surveillance may have the secondary benefit of also reducing abdominal aortic aneurysm growth rates.
We conducted a systematic review and meta-analysis of studies reporting circulating IL-6 in AAA, and new investigations of the association between a common non-synonymous functional variant ...(Asp358Ala) in the IL-6R gene (IL6R) and AAA, followed the analysis of the variant both in vitro and in vivo. Inflammation may play a role in the development of abdominal aortic aneurysms (AAA). Interleukin-6 (IL-6) signalling through its receptor (IL-6R) is one pathway that could be exploited pharmacologically. We investigated this using a Mendelian randomization approach.
Up to October 2011, we identified seven studies (869 cases, 851 controls). Meta-analysis demonstrated that AAA cases had higher levels of IL-6 than controls standardized mean difference (SMD) = 0.46 SD, 95% CI = 0.25-0.66, I(2) = 70%, P = 1.1 × 10-5 random effects. Meta-analysis of five studies (4524 cases/15 710 controls) demonstrated that rs7529229 (which tags the non-synonymous variant Asp358Ala, rs2228145) was associated with a lower risk of AAA, per Ala358 allele odds ratio 0.84, 95% CI: 0.80-0.89, I(2) = 0%, P = 2.7 × 10-11). In vitro analyses in lymphoblastoid cell lines demonstrated a reduction in the expression of downstream targets (STAT3, MYC and ICAM1) in response to IL-6 stimulation in Ala358 carriers.
A Mendelian randomization approach provides robust evidence that signalling via the IL-6R is likely to be a causal pathway in AAA. Drugs that inhibit IL-6R may play a role in AAA management.
Abdominal aortic aneurysm (AAA) screening programmes have been established for men in the UK to reduce deaths from AAA rupture. Whether or not screening should be extended to women is uncertain.
To ...evaluate the cost-effectiveness of population screening for AAAs in women and compare a range of screening options.
A discrete event simulation (DES) model was developed to provide a clinically realistic model of screening, surveillance, and elective and emergency AAA repair operations. Input parameters specifically for women were employed. The model was run for 10 million women, with parameter uncertainty addressed by probabilistic and deterministic sensitivity analyses.
Population screening in the UK.
Women aged ≥ 65 years, followed up to the age of 95 years.
Invitation to ultrasound screening, followed by surveillance for small AAAs and elective surgical repair for large AAAs.
Number of operations undertaken, AAA-related mortality, quality-adjusted life-years (QALYs), NHS costs and cost-effectiveness with annual discounting.
AAA surveillance data, National Vascular Registry, Hospital Episode Statistics, trials of elective and emergency AAA surgery, and the NHS Abdominal Aortic Aneurysm Screening Programme (NAAASP).
Systematic reviews of AAA prevalence and, for elective operations, suitability for endovascular aneurysm repair, non-intervention rates, operative mortality and literature reviews for other parameters.
The prevalence of AAAs (aortic diameter of ≥ 3.0 cm) was estimated as 0.43% in women aged 65 years and 1.15% at age 75 years. The corresponding attendance rates following invitation to screening were estimated as 73% and 62%, respectively. The base-case model adopted the same age at screening (65 years), definition of an AAA (diameter of ≥ 3.0 cm), surveillance intervals (1 year for AAAs with diameter of 3.0-4.4 cm, 3 months for AAAs with diameter of 4.5-5.4 cm) and AAA diameter for consideration of surgery (5.5 cm) as in NAAASP for men. Per woman invited to screening, the estimated gain in QALYs was 0.00110, and the incremental cost was £33.99. This gave an incremental cost-effectiveness ratio (ICER) of £31,000 per QALY gained. The corresponding incremental net monetary benefit at a threshold of £20,000 per QALY gained was -£12.03 (95% uncertainty interval -£27.88 to £22.12). Almost no sensitivity analyses brought the ICER below £20,000 per QALY gained; an exception was doubling the AAA prevalence to 0.86%, which resulted in an ICER of £13,000. Alternative screening options (increasing the screening age to 70 years, lowering the threshold for considering surgery to diameters of 5.0 cm or 4.5 cm, lowering the diameter defining an AAA in women to 2.5 cm and lengthening the surveillance intervals for the smallest AAAs) did not bring the ICER below £20,000 per QALY gained when considered either singly or in combination.
The model for women was not directly validated against empirical data. Some parameters were poorly estimated, potentially lacking relevance or unavailable for women.
The accepted criteria for a population-based AAA screening programme in women are not currently met.
A large-scale study is needed of the exact aortic size distribution for women screened at relevant ages. The DES model can be adapted to evaluate screening options in men.
This study is registered as PROSPERO CRD42015020444 and CRD42016043227.
The National Institute for Health Research Health Technology Assessment programme.
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