Gianluca Baio

Inequalities in participation in an organized national colorectal cancer screening programme: results from the first 2.6 million invitations in England

BACKGROUND An organized, population-based, colorectal cancer screening programme was initiated in England in 2006 offering biennial faecal occult blood testing (FOBT) to adults aged 60-69 years. Organized screening programmes with no associated financial costs to the individual should minimize barriers to access for lower socio-economic status (SES) groups. However, SES differences in uptake were observed in the pilot centres of the UK programme, so the aim of this analysis was to identify the extent of inequalities in uptake by SES, ethnic diversity, gender and age in the first 28 months of the programme. Design Cross-sectional analysis of colorectal cancer screening uptake data. METHODS Between October 2006 and January 2009, over 2.6 million adults aged 60-69 years were mailed a first FOBT kit by the five regional screening hubs. Uptake was defined as return of a test kit within 13 weeks. We used multivariate generalized linear regression to examine variation by area-based socioeconomic deprivation, area-based ethnicity, gender and age. RESULTS Uptake was 54%, but showed a gradient across quintiles of deprivation, ranging from 35% in the most deprived quintile to 61% in the least deprived. Multivariate analyses confirmed an independent effect of deprivation, with stronger effects in women and older people. The most ethnically diverse areas also had lower uptake (38%) than other areas (52-58%) independent of SES, age, gender and regional screening hub. Ethnic disparities were more pronounced in men but equivalent across age groups. More women than men returned a kit (56 vs 51%), but there was also an interaction with age, with uptake increasing with age in men (49% at 60-64 years; 53% at 65-69 years) but not women (57 vs 56%). CONCLUSIONS Overall uptake rates in this organized screening programme were encouraging, but nonetheless there was low uptake in the most ethnically diverse areas and a striking gradient by SES. Action to promote equality of uptake is needed to avoid widening inequalities in cancer mortality.

Spatial and spatio-temporal models with R-INLA.

During the last three decades, Bayesian methods have developed greatly in the field of epidemiology. Their main challenge focusses around computation, but the advent of Markov Chain Monte Carlo methods (MCMC) and in particular of the WinBUGS software has opened the doors of Bayesian modelling to the wide research community. However model complexity and database dimension still remain a constraint. Recently the use of Gaussian random fields has become increasingly popular in epidemiology as very often epidemiological data are characterised by a spatial and/or temporal structure which needs to be taken into account in the inferential process. The Integrated Nested Laplace Approximation (INLA) approach has been developed as a computationally efficient alternative to MCMC and the availability of an R package (R-INLA) allows researchers to easily apply this method. In this paper we review the INLA approach and present some applications on spatial and spatio-temporal data.

Long-term persistence with antihypertensive drugs in new patients

The objective of this study was to investigate stay-on-therapy patterns over 3 years among patients prescribed different classes of antihypertensive drugs for the first time. A retrospective analysis of information recorded in the drugs database of the Local Health Unit of Ravenna (Italy) was carried out on 7312 subjects receiving a first prescription for diuretics, beta-blockers, calcium channel blockers, angiotensin-converting enzyme (ACE) inhibitors or angiotensin II antagonists between 1 January and 31 December 1997. Patients were followed up for 3 years. All prescriptions of antihypertensive drugs filled during the follow-up periods were considered. The patients continuing or discontinuing the initial treatment, the duration of treatment, and the doses taken were all calculated, as well as main factors influencing the persistence rate. The drugs prescribed were predominantly ACE-inhibitors, followed by calcium channel blockers, diuretics, beta-blockers and angiotensin II antagonists. A total of 57.9% of patients continued their initial treatment during the 3-year follow-up period, 34.5% discontinued the treatment, whilst 7.6% were restarted on a treatment in the third year. Persistence with treatment was influenced by: age of patient (persistence rate increasing proportionately with advancing years), type of drug first prescribed (persistence rate higher with angiotensin II antagonists, progressively lower with ACE-inhibitors, beta-blockers, calcium channel blockers and diuretics), gender of patient (persistence was better in males), age of general practitioner (GP) (the younger the GP, the better the persistence rate) and gender of GP (better stay-on-therapy rate with male GP prescribing). In the case of patients treated continuously, mean daily dose increased progressively over the 3 years. With adequate markers, helpful data can be collected from prescription claims databases for the purpose of monitoring the persistence of patients in continuing their medication, and the quality of antihypertensive treatment in a general practice setting.

Non-pharmacological interventions for agitation in dementia: systematic review of randomised controlled trials

BACKGROUND Agitation in dementia is common, persistent and distressing and can lead to care breakdown. Medication is often ineffective and harmful. AIMS To systematically review randomised controlled trial evidence regarding non-pharmacological interventions. Method We reviewed 33 studies fitting predetermined criteria, assessed their validity and calculated standardised effect sizes (SES). RESULTS Person-centred care, communication skills training and adapted dementia care mapping decreased symptomatic and severe agitation in care homes immediately (SES range 0.3-1.8) and for up to 6 months afterwards (SES range 0.2-2.2). Activities and music therapy by protocol (SES range 0.5-0.6) decreased overall agitation and sensory intervention decreased clinically significant agitation immediately. Aromatherapy and light therapy did not demonstrate efficacy. CONCLUSIONS There are evidence-based strategies for care homes. Future interventions should focus on consistent and long-term implementation through staff training. Further research is needed for people living in their own homes.

The prevalence of primary angle closure glaucoma in European derived populations: a systematic review

Aim To estimate the prevalence of primary angle closure glaucoma (PACG) in European derived populations. Method Systematic review and modelling of PACG prevalence data from population studies. PACG was defined according to the ISGEO definition requiring structural and/or functional evidence of glaucomatous optic neuropathy. Prevalence estimates were applied to the 2010 United Nations projected population figures to estimate case numbers. Results The prevalence of PACG in those 40 years or more is 0.4% (95% CI 0.3% to 0.5%). Age-specific prevalence values are 0.02% (CI 0.00 to 0.08) for those 40–49 years, 0.60% (0.27 to 1.00) for those 50–59 years, 0.20% (0.06 to 0.42) for those 60–69 years and 0.94% (0.63 to 1.35) for those 70 years and older. Three-quarters of all cases occur in female subjects (3.25 female to 1 male; CI 1.76 to 5.94). Conclusion This analysis provides a current evidence-based estimate of PACG prevalence in European derived populations and suggests there are 130 000 people in the UK, 1.60 million people in Europe and 581 000 people in the USA with PACG today. Accounting for ageing population structures, cases are predicted to increase by 19% in the UK, 9% in Europe and 18% in the USA within the next decade. PACG is more common than previously thought, and all primary glaucoma cases should be considered to be PACG until the anterior chamber angle is shown to be open on gonioscopy.

Bayesian hierarchical model for the prediction of football results

The problem of modelling football data has become increasingly popular in the last few years and many different models have been proposed with the aim of estimating the characteristics that bring a team to lose or win a game, or to predict the score of a particular match. We propose a Bayesian hierarchical model to fulfil both these aims and test its predictive strength based on data about the Italian Serie A 1991–1992 championship. To overcome the issue of overshrinkage produced by the Bayesian hierarchical model, we specify a more complex mixture model that results in a better fit to the observed data. We test its performance using an example of the Italian Serie A 2007–2008 championship.

Bayesian Methods in Health Economics

Introduction to Health Economic Evaluation Introduction Health economic evaluation Cost components Outcomes Discounting Types of economic evaluations Comparing health interventions Introduction to Bayesian Inference Introduction Subjective probability and Bayes theorem Bayesian (parametric) modelling Choosing prior distributions and Bayesian computation Statistical Cost-Effectiveness Analysis Introduction Decision theory and expected utility Decision-making in health economics Probabilistic sensitivity analysis to parameter uncertainty Reporting the results of probabilistic sensitivity analysis Probabilistic sensitivity analysis to structural uncertainty Advanced issues in cost-effectiveness analysis Bayesian Analysis in Practice Introduction Software configuration An Example of analysis in JAGS/BUGS Logical nodes For loops and node transformations Predictive distributions Modelling the cost-effectiveness of a new chemotherapy drug in R/JAGS Health Economic Evaluation in Practice Cost-effectiveness analysis alongside clinical trials Evidence synthesis and hierarchical models Markov models

Economic burden of human papillomavirus-related diseases in Italy

Introduction Human papilloma virus (HPV) genotypes 6, 11, 16, and 18 impose a substantial burden of direct costs on the Italian National Health Service that has never been quantified fully. The main objective of the present study was to address this gap: (1) by estimating the total direct medical costs associated with nine major HPV-related diseases, namely invasive cervical cancer, cervical dysplasia, cancer of the vulva, vagina, anus, penis, and head and neck, anogenital warts, and recurrent respiratory papillomatosis, and (2) by providing an aggregate measure of the total economic burden attributable to HPV 6, 11, 16, and 18 infection. Methods For each of the nine conditions, we used available Italian secondary data to estimate the lifetime cost per case, the number of incident cases of each disease, the total economic burden, and the relative prevalence of HPV types 6, 11, 16, and 18, in order to estimate the aggregate fraction of the total economic burden attributable to HPV infection. Results The total direct costs (expressed in 2011 Euro) associated with the annual incident cases of the nine HPV-related conditions included in the analysis were estimated to be €528.6 million, with a plausible range of €480.1–686.2 million. The fraction attributable to HPV 6, 11, 16, and 18 was €291.0 (range €274.5–315.7 million), accounting for approximately 55% of the total annual burden of HPV-related disease in Italy. Conclusions The results provided a plausible estimate of the significant economic burden imposed by the most prevalent HPV-related diseases on the Italian welfare system. The fraction of the total direct lifetime costs attributable to HPV 6, 11, 16, and 18 infections, and the economic burden of noncervical HPV-related diseases carried by men, were found to be cost drivers relevant to the making of informed decisions about future investments in programmes of HPV prevention.

Inequalities in the provision of cardiovascular screening to people with severe mental illnesses in primary care: Cohort study in the United Kingdom THIN Primary Care Database 2000–2007

BACKGROUND People with severe mental illnesses (SMI), including schizophrenia, are at increased risk of cardiovascular disease (CVD). Guidelines recommend regular CVD screening and in the United Kingdom, since 2004, General Practitioners are remunerated for annual reviews. OBJECTIVES To compare annual rates of CVD screening provision in people with and without SMI between 2000 and 2008. METHOD We identified 18,696 people with SMI and 95,512 people without SMI in the UK The Health Improvement Network (THIN) primary care database. We compared the rates of measurement of blood pressure (BP), glucose, cholesterol and body mass index (BMI). RESULTS Prior to 2004, all people with SMI, were significantly less likely to receive each measurement, (including people above and below 60 years of age). In 2003; adjusted incidence rate ratios (95% CI) for screening in people with SMI under 60 years compared to people without SMI were: BMI: 0.62 (0.58-0.65); BP: 0.59 (0.56-0.62); glucose: 0.66 (0.61-0.70) and cholesterol: 0.54 (0.49-0.59). By 2007 people with SMI under 60 were equally likely receive a measurement of BMI: 1.00 (0.96-1.04), glucose: 1.00 (0.96-1.05) and cholesterol: 0.95 (0.90-1.0); the gap in screening for BP had narrowed 0.87 (0.83-0.90). However people with SMI over 60 years of age remained significantly less likely to be screened. There was little difference in screening according to social deprivation. CONCLUSIONS In UK primary care, people with SMI over 60 years of age remain less likely than the general population to receive annual CVD screening despite higher risk of developing CVD.

Sample size calculation for a stepped wedge trial

BackgroundStepped wedge trials (SWTs) can be considered as a variant of a clustered randomised trial, although in many ways they embed additional complications from the point of view of statistical design and analysis. While the literature is rich for standard parallel or clustered randomised clinical trials (CRTs), it is much less so for SWTs. The specific features of SWTs need to be addressed properly in the sample size calculations to ensure valid estimates of the intervention effect.MethodsWe critically review the available literature on analytical methods to perform sample size and power calculations in a SWT. In particular, we highlight the specific assumptions underlying currently used methods and comment on their validity and potential for extensions. Finally, we propose the use of simulation-based methods to overcome some of the limitations of analytical formulae. We performed a simulation exercise in which we compared simulation-based sample size computations with analytical methods and assessed the impact of varying the basic parameters to the resulting sample size/power, in the case of continuous and binary outcomes and assuming both cross-sectional data and the closed cohort design.ResultsWe compared the sample size requirements for a SWT in comparison to CRTs based on comparable number of measurements in each cluster. In line with the existing literature, we found that when the level of correlation within the clusters is relatively high (for example, greater than 0.1), the SWT requires a smaller number of clusters. For low values of the intracluster correlation, the two designs produce more similar requirements in terms of total number of clusters. We validated our simulation-based approach and compared the results of sample size calculations to analytical methods; the simulation-based procedures perform well, producing results that are extremely similar to the analytical methods. We found that usually the SWT is relatively insensitive to variations in the intracluster correlation, and that failure to account for a potential time effect will artificially and grossly overestimate the power of a study.ConclusionsWe provide a framework for handling the sample size and power calculations of a SWT and suggest that simulation-based procedures may be more effective, especially in dealing with the specific features of the study at hand. In selected situations and depending on the level of intracluster correlation and the cluster size, SWTs may be more efficient than comparable CRTs. However, the decision about the design to be implemented will be based on a wide range of considerations, including the cost associated with the number of clusters, number of measurements and the trial duration.