Cost-effectiveness of the National Health Service Abdominal Aortic Aneurysm Screening Programme in England.

BACKGROUND: Implementation of the National Health Service abdominal aortic aneurysm (AAA) screening programme (NAAASP) for men aged 65 years began in England in 2009. An important element of the evidence base supporting its introduction was the economic modelling of the long-term cost-effectiveness of screening, which was based mainly on 4-year follow-up data from the Multicentre Aneurysm Screening Study (MASS) randomized trial. Concern has been expressed about whether this conclusion of cost-effectiveness still holds, given the early performance parameters, particularly the lower prevalence of AAA observed in NAAASP. METHODS: The existing published model was adjusted and updated to reflect the current best evidence. It was recalibrated to mirror the 10-year follow-up data from MASS; the main cost parameters were re-estimated to reflect current practice; and more robust estimates of AAA growth and rupture rates from recent meta-analyses were incorporated, as were key parameters as observed in NAAASP (attendance rates, AAA prevalence and size distributions). RESULTS: The revised and updated model produced estimates of the long-term incremental cost-effectiveness of £5758 (95 per cent confidence interval £4285 to £7410) per life-year gained, or £7370 (£5467 to £9443) per quality-adjusted life-year (QALY) gained. CONCLUSION: Although the updated parameters, particularly the increased costs and lower AAA prevalence, have increased the cost per QALY, the latest modelling provides evidence that AAA screening as now being implemented in England is still highly cost-effective.

Systematic review and meta-analysis of the growth and rupture rates of small abdominal aortic aneurysms: implications for surveillance intervals and their cost-effectiveness.

BACKGROUND: Small abdominal aortic aneurysms (AAAs; 3.0-5.4 cm in diameter) are usually asymptomatic and managed by regular ultrasound surveillance until they grow to a diameter threshold (commonly 5.5 cm) at which surgical intervention is considered. The choice of appropriate surveillance intervals is governed by the growth and rupture rates of small AAAs, as well as their relative cost-effectiveness. OBJECTIVES: The aim of this series of studies was to inform the evidence base for small AAA surveillance strategies. This was achieved by literature review, collation and analysis of individual patient data, a focus group and health economic modelling. DATA SOURCES: We undertook systematic literature reviews of growth rates and rupture rates of small AAAs. The databases MEDLINE, EMBASE on OvidSP, Cochrane Central Register of Controlled Trials 2009 Issue 4, ClinicalTrials.gov, and controlled-trials.com were searched from inception up until the end of 2009. We also obtained individual data on 15,475 patients from 18 surveillance studies. REVIEW METHODS: Systematic reviews of publications identified 15 studies providing small AAA growth rates, and 14 studies with small AAA rupture rates, up to December 2009 (later updated to September 2012). We developed statistical methods to analyse individual surveillance data, including the effects of patient characteristics, to inform the choice of surveillance intervals and provide inputs for health economic modelling. We updated an existing health economic model of AAA screening to address the cost-effectiveness of different surveillance intervals. RESULTS: In the literature reviews, the mean growth rate was 2.3 mm/year and the reported rupture rates varied between 0 and 1.6 ruptures per 100 person-years. Growth rates increased markedly with aneurysm diameter, but insufficient detail was available to guide surveillance intervals. Based on individual surveillance data, for each 0.5-cm increase in AAA diameter, growth rates increased by about 0.5 mm/year and rupture rates doubled. To control the risk of exceeding 5.5 cm to below 10% in men, on average a 7-year surveillance interval is sufficient for a 3.0-cm aneurysm, whereas an 8-month interval is necessary for a 5.0-cm aneurysm. To control the risk of rupture to below 1%, the corresponding estimated surveillance intervals are 9 years and 17 months. Average growth rates were higher in smokers (by 0.35 mm/year) and lower in patients with diabetes (by 0.51 mm/year). Rupture rates were almost fourfold higher in women than men, doubled in current smokers and increased with higher blood pressure. Increasing the surveillance interval from 1 to 2 years for the smallest aneurysms (3.0-4.4 cm) decreased costs and led to a positive net benefit. For the larger aneurysms (4.5-5.4 cm), increasing surveillance intervals from 3 to 6 months led to equivalent cost-effectiveness. LIMITATIONS: There were no clear reasons why the growth rates varied substantially between studies. Uniform diagnostic criteria for rupture were not available. The long-term cost-effectiveness results may be susceptible to the modelling assumptions made. CONCLUSIONS: Surveillance intervals of several years are clinically acceptable for men with AAAs in the range 3.0-4.0 cm. Intervals of around 1 year are suitable for 4.0-4.9-cm AAAs, whereas intervals of 6 months would be acceptable for 5.0-5.4-cm AAAs. These intervals are longer than those currently employed in the UK AAA screening programmes. Lengthening surveillance intervals for the smallest aneurysms was also shown to be cost-effective. Future work should focus on optimising surveillance intervals for women, studying whether or not the threshold for surgery should depend on patient characteristics, evaluating the usefulness of surveillance for those with aortic diameters of 2.5-2.9 cm, and developing interventions that may reduce the growth or rupture rates of small AAAs. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Acceleration of cortical thinning in familial Alzheimer's disease.

BACKGROUND: MRI in presymptomatic autosomal dominant Alzheimer's disease mutation carriers (MC) provides an opportunity to detect changes that pre-date symptoms or clinical diagnosis. We used automated cortical thickness (CTh) measurement to compare the grey matter of such a group with cognitively normal controls. METHODS: 9 presymptomatic mutation carriers (4 PSEN1, 5 APP) and 25 healthy, age and sex-matched controls underwent longitudinal volumetric MRI brain imaging. CTh measurement was performed across the whole brain using a validated, automated technique. Four regions of interest (ROI) (entorhinal cortex (ERC), parahippocampal gyrus (PHG), posterior cingulate cortex and precuneus) and two control regions (paracentral and pericalcarine) were selected on the basis of imaging data in existing Alzheimer's disease (AD) literature. Linear mixed models were used to describe normal ageing in controls and the extent to which mean CTh in cases differed from controls according to time since clinical diagnosis, adjusting for normal ageing. RESULTS: An accelerating decline in CTh was observed across all ROI in the MC group. No such decline was demonstrated in the control regions for the MC group. Relative to controls, and adjusting for normal ageing, there was evidence (p=0.05, one-sided test) of lower CTh in the posterior cingulate up to 1.8 years prior to diagnosis and in the precuneus up to 4.1 years prior to diagnosis in the MC group. DISCUSSION: Automated CTh analysis is a relatively practical, rapid and effective technique for assessing subtle structural change in AD. There is evidence that cortical thickness is reduced in mutation carriers a number of years prior to clinical diagnosis.

Measuring disease progression in frontotemporal lobar degeneration: a clinical and MRI study.

OBJECTIVES: There is currently much interest in biomarkers of disease activity in frontotemporal lobar degeneration (FTLD). We assessed MRI and behavioral measures of progression in a longitudinal FTLD cohort. METHODS: Thirty-two patients with FTLD (11 behavioral variant frontotemporal dementia [bvFTD], 11 semantic dementia [SemD], 10 progressive nonfluent aphasia [PNFA]) and 24 age-matched healthy controls were assessed using volumetric brain MRI and standard behavioral measures (Mini-Mental State Examination, Frontal Assessment Battery, Clinical Dementia Rating Scale, Neuropsychiatric Inventory with Caregiver Distress scale) at baseline and 1 year later. A semi-automated image registration protocol was used to calculate annualized rates of brain atrophy (brain boundary shift integral [BBSI]) and ventricular expansion (ventricular boundary shift integral [VBSI]). Associations between these rates and changes in behavioral indices were investigated. RESULTS: Rates of whole brain atrophy were greater in the entire FTLD cohort and in each subgroup compared with controls (all p < or = 0.004). Rates of ventricular expansion were greater in the entire cohort (p < 0.001) and the SemD (p = 0.002) and PNFA (p = 0.05) subgroups compared with controls. Changes in Mini-Mental State Examination, Frontal Assessment Battery, and Clinical Dementia Rating Scale scores were associated with MRI measures of progression, though not uniformly across FTLD subgroups. Both BBSI and VBSI yielded feasible sample size estimates for detecting meaningful treatment effects in SemD and PNFA language subgroups. Sample sizes were substantially larger using MRI biomarkers for the bvFTD subgroup, and using behavioral biomarkers in general. CONCLUSIONS: Semi-automated MRI atrophy measures are potentially useful objective biomarkers of progression in frontotemporal lobar degeneration (FTLD); however, careful stratification of FTLD subtypes will be important in future clinical trials of disease-modifying therapies.

Fifteen-year follow-up of a randomized clinical trial of ultrasonographic screening for abdominal aortic aneurysms.

BACKGROUND: Long-term benefits of screening for abdominal aortic aneurysm (AAA) are uncertain. These are the final results of a randomized controlled screening trial for AAA in men, updating those reported previously. Benefit and compliance over a median 15-year interval were examined. METHODS: One group of men were invited for ultrasonographic AAA screening, and another group, who received standard care, acted as controls. A total of 6040 men aged 65-80 years were randomized to one of the two groups. Outcome was monitored in terms of AAA-related events (surgery or death). RESULTS: In the group invited for screening, AAA-related mortality was reduced by 11 per cent (from 1.8 to 1.6 per cent, hazard ratio 0.89) over the follow-up interval. Screening detected an AAA in 170 patients; 17 of these died from an AAA-related cause, seven of which might have been preventable. The incidence of AAA rupture after an initially normal scan increased after 10 years of follow-up, but was still low overall (0.56 per 1000 person-years). CONCLUSION: Screening with a single ultrasonography scan still conferred a benefit at 15 years, although the results were not significant for this population size. Fewer than half of the AAA-related deaths in those screened positive could be prevented. REGISTRATION NUMBER: ISRCTN 00079388 (http://www.controlled-trials.com).

How cost-effective is screening for abdominal aortic aneurysms?

OBJECTIVE: To provide reliable estimates of the long-term cost-effectiveness of abdominal aortic aneurysm screening in men. METHODS: A Markov health economic decision model for screening is described and extrapolated to 30 years. The strategy modelled involves a one-off scan at age 65 years, with annual and three-monthly follow-up scans for small and medium aneurysms, respectively. Referral for elective surgery occurs at an aortic diameter of 5.5 cm. Model parameters are estimated from patient-level data from the UK Multi-centre Aneurysm Screening Study. Model structure is validated on this trial's data, and input parameter uncertainty is addressed by probabilistic sensitivity analysis. Costs and life-years gained are obtained for both screening and no systematic screening strategies. RESULTS: Cost-effectiveness improves dramatically when considered over longer timescales. Taking a 30-year perspective, screening for abdominal aortic aneurysms in men is highly cost-effective at 2320 pounds per life-year gained (95% uncertainty interval: 1600 pounds to 4240 pounds). Adjusting life-years for the age-specific health-related quality of life experienced in this population gave a figure of 2970 pounds (95% uncertainty interval: 2030 pounds to 5430 pounds) per quality-adjusted life-year gained. The additional cost of screening the UK male population is estimated to be 19 m pounds per year. CONCLUSIONS: The long-term cost-effectiveness of screening for abdominal aortic aneurysms in men is highly attractive and this evidence provides further support for a national screening programme in the UK.

Implications of screening for abdominal aortic aneurysms on surgical workload.

BACKGROUND: The Multicentre Aneurysm Screening Study (MASS) provided strong evidence for both the clinical benefit and the cost-effectiveness of a screening programme for abdominal aortic aneurysms (AAAs) in men. If a national screening programme for AAA were adopted in the UK, it would be expected to increase the elective and decrease the emergency surgical workload. METHODS: The MASS trial randomized 67,800 men aged 65-74 years to be invited to attend for ultrasonographic screening for AAA or to a control group that received no invitation. Predictions of elective and emergency surgical workload were made for a 20-year interval after the introduction of a screening programme for 65-year-old men, based on surgical rates observed in the MASS trial and national mortality statistics. RESULTS: For a district general hospital serving a population of 400,000, there was an estimated reduction from nine emergency operations per year before introduction of the screening programme to three emergency operations annually in men aged 65 years and over by the end of the 20-year interval, and an increase from 24 to 43 AAA operations overall. The corresponding estimated annual costs for all AAA surgery increased by 47 per cent, from pound 209,000 to pound 308,000. These results were not affected by changes in the underlying assumptions. CONCLUSION: The results support the expectation of very few emergency operations, and principally elective operations, being performed following the introduction of a screening programme. For a typical district general hospital, a screening programme would be expected to lead to two additional elective AAA operations per month, and to save 11 AAA-related deaths per year.

Screening for abdominal aortic aneurysms: the effects of age and social deprivation on screening uptake, prevalence and attendance at follow-up in the MASS trial.

UNLABELLED: OBJECTIVES/SETTING: The effectiveness of screening programmes may be improved by knowledge of factors affecting screening uptake, disease prevalence and attendance for follow-up. Data from the Multicentre Aneurysm Screening Study (MASS) are used to examine the influences of age and social deprivation in the context of screening for abdominal aortic aneurysms (AAAs). METHODS: In the MASS trial, a population-based sample of 34,000 men aged 65 to 74 received an invitation to screening. The associations of attendance at screening with age, social deprivation and season of the year when invited to attend were investigated using logistic regression analysis. Similar analyses were performed for AAA prevalence and attendance at recall scans. RESULTS: Compared with men aged 65-69, those aged 70-74 were less likely to attend screening (79% vs 81%), had increased prevalence of AAA (6% vs 4%) and were less likely to attend for follow-up (79% vs 84%). Compared with those in the least deprived quartile, those in the most deprived quartile also were less likely to attend (75% vs 85%), had increased prevalence (6% vs 4%) and were less likely to attend for follow-up (80% vs 83%). Season showed no significant association with attendance at initial screening. CONCLUSIONS: Higher age and social deprivation are associated with both poorer attendance at screening and follow-up, and having an AAA. This highlights the importance of promoting screening programmes, particularly to the more deprived populations.

The Multicentre Aneurysm Screening Study (MASS) into the effect of abdominal aortic aneurysm screening on mortality in men: a randomised controlled trial.

BACKGROUND: Opposing views have been published on the importance of ultrasound screening for abdominal aortic aneurysms. The Multicentre Aneurysm Screening Study was designed to assess whether or not such screening is beneficial. METHODS: A population-based sample of men (n=67800) aged 65-74 years was enrolled, and each individual randomly allocated to either receive an invitation for an abdominal ultrasound scan (invited group, n=33839) or not (control group, n=33961). Men in whom abdominal aortic aneurysms (> or =3 cm in diameter) were detected were followed-up with repeat ultrasound scans for a mean of 4.1 years. Surgery was considered on specific criteria (diameter > or =5.5 cm, expansion > or =1 cm per year, symptoms). Mortality data were obtained from the Office of National Statistics, and an intention-to-treat analysis was based on cause of death. Quality of life was assessed with four standardised scales. The primary outcome measure was mortality related to abdominal aortic aneurysm. FINDINGS: 27147 of 33839 (80%) men in the invited group accepted the invitation to screening, and 1333 aneurysms were detected. There were 65 aneurysm-related deaths (absolute risk 0.19%) in the invited group, and 113 (0.33%) in the control group (risk reduction 42%, 95% CI 22-58; p=0.0002), with a 53% reduction (95% CI 30-64) in those who attended screening. 30-day mortality was 6% (24 of 414) after elective surgery for an aneurysm, and 37% (30 of 81) after emergency surgery. INTERPRETATION: Our results provide reliable evidence of benefit from screening for abdominal aortic aneurysms.

Monitoring adolescent gambling in Minnesota.

Youth gambling was investigated in a prospective sample of 532 Minnesota adolescents and young adults. Of particular interest was the possible impact among the study sample of a recent state lottery and of reaching the legal age for gambling on changes in the rate and type of gambling. Overall rates of gambling involvement and pathological gambling did not change across the 1.5 year interval. However, a preference for certain types of gambling activities (e.g., lottery, casino machines) significantly increased, whereas more informal and unregulated games (e.g., betting on games of personal skill) significantly decreased. Also, access to gambling activities by underage youths was high, suggesting the need for tighter controls of legalized games and greater awareness of this problem by the gaming industry and public health officials.