Personal and societal costs of multiple sclerosis in the UK: A population-based MS Registry study.

OBJECTIVES: To investigate through survey and data linkage, healthcare resource use and costs (except drugs), including who bears the cost, of multiple sclerosis in the United Kingdom by disease severity and type. METHODS: The United Kingdom Multiple Sclerosis Register deployed a cost of illness survey, completed by people with multiple sclerosis and linked this with data within the United Kingdom Multiple Sclerosis Register and from their hospital records. Resource consumption was categorised as being medical or non-medical and costed by National Health Service and social services estimates for 2018. RESULTS: We calculated £509,003 in non-medical costs over a year and £435,488 in medical costs generated over 3 months. People with multiple sclerosis reported self-funding 75% of non-medical costs with non-medical interventions having long-term potential benefits. Costs increased with disability as measured by patient-reported Expanded Disability Status Score and Multiple Sclerosis Impact Scale, with Multiple Sclerosis Impact Scale physical being a more powerful predictor of costs than the patient-reported Expanded Disability Status Score. Two distinct groups were identified: medical and non-medical interventions (n = 138); and medical interventions only (n = 399). The medical and non-medical group reported increased disease severity and reduced employment but incurred 80% more medical costs per person than the medical-only group. CONCLUSIONS: The importance of disability in driving costs is illustrated with balance between medical and non-medical costs consistent with the United Kingdom health environment. People with multiple sclerosis and their families fund a considerable proportion of non-medical costs but non-medical interventions with longer term impact could affect future medical costs.

Effects and costs of implementing predictive risk stratification in primary care: a randomised stepped wedge trial.

AIM: We evaluated the introduction of a predictive risk stratification model (PRISM) into primary care. Contemporaneously National Health Service (NHS) Wales introduced Quality and Outcomes Framework payments to general practices to focus care on those at highest risk of emergency admission to hospital. The aim of this study was to evaluate the costs and effects of introducing PRISM into primary care. METHODS: Randomised stepped wedge trial with 32 general practices in one Welsh health board. The intervention comprised: PRISM software; practice-based training; clinical support through two 'general practitioner (GP) champions' and technical support. The primary outcome was emergency hospital admissions. RESULTS: Across 230 099 participants, PRISM implementation increased use of health services: emergency hospital admission rates by 1 % when untransformed (while change in log-transformed rate ΔL=0.011, 95% CI 0.010 to 0.013); emergency department (ED) attendance rates by untransformed 3 % (while ΔL=0.030, 95% CI 0.028 to 0.032); outpatient visit rates by untransformed 5 % (while ΔL=0.055, 95% CI 0.051 to 0.058); the proportion of days with recorded GP activity by untransformed 1 % (while ΔL=0.011, 95% CI 0.007 to 0.014) and time in hospital by untransformed 3 % (while ΔL=0.029, 95% CI 0.026 to 0.031). Thus NHS costs per participant increased by £76 (95% CI £46 to £106). CONCLUSIONS: Introduction of PRISM resulted in a statistically significant increase in emergency hospital admissions and use of other NHS services without evidence of benefits to patients or the NHS.

Impact of cystic fibrosis on birthweight: a population based study of children in Denmark and Wales.

BACKGROUND: Poor growth during infancy and childhood is a characteristic feature of cystic fibrosis (CF). However, the impact of CF on intrauterine growth is unclear. We studied the effect of CF on birth weight in Denmark and Wales, and assessed whether any associations are due to differences in gestational age at birth. METHODS: We conducted national registry linkage studies in two countries, using data for 2.2 million singletons born in Denmark (between 1980 and 2010) and Wales (between 1998 and 2015). We used hospital inpatient and outpatient data to identify 852 children with CF. Using causal mediation methods, we estimated the direct and indirect (via gestational age) effect of CF on birth weight after adjustment for sex, parity and socioeconomic background. We tested the robustness of our results by adjusting for additional factors such as maternal smoking during pregnancy in subpopulations where these data were available. RESULTS: Babies with CF were more likely to be born preterm and with low birth weight than babies with no CF (12.7% vs 5% and 9.4% vs 5.8% preterm; 11.9% vs 4.2% and 11% vs 5.4% low birth weight in Denmark and Wales, respectively). Using causal mediation methods, the total effect of CF on birth weight was estimated to be -178.8 g (95% CI -225.43 to -134.47 g) in the Danish population and -210.08 g (95% CI -281.97 to -141.5 g) in the Welsh population. About 40% of this effect of CF on birth weight was mediated through gestational age. CONCLUSIONS: CF significantly impacts on intrauterine growth and leads to lower birth weight in babies with CF, which is only partially explained by shorter gestation.

The epidemiology, healthcare and societal burden and costs of asthma in the UK and its member nations: analyses of standalone and linked national databases.

BACKGROUND: There are a lack of reliable data on the epidemiology and associated burden and costs of asthma. We sought to provide the first UK-wide estimates of the epidemiology, healthcare utilisation and costs of asthma. METHODS: We obtained and analysed asthma-relevant data from 27 datasets: these comprised national health surveys for 2010-11, and routine administrative, health and social care datasets for 2011-12; 2011-12 costs were estimated in pounds sterling using economic modelling. RESULTS: The prevalence of asthma depended on the definition and data source used. The UK lifetime prevalence of patient-reported symptoms suggestive of asthma was 29.5 % (95 % CI, 27.7-31.3; n = 18.5 million (m) people) and 15.6 % (14.3-16.9, n = 9.8 m) for patient-reported clinician-diagnosed asthma. The annual prevalence of patient-reported clinician-diagnosed-and-treated asthma was 9.6 % (8.9-10.3, n = 6.0 m) and of clinician-reported, diagnosed-and-treated asthma 5.7 % (5.7-5.7; n = 3.6 m). Asthma resulted in at least 6.3 m primary care consultations, 93,000 hospital in-patient episodes, 1800 intensive-care unit episodes and 36,800 disability living allowance claims. The costs of asthma were estimated at least £1.1 billion: 74 % of these costs were for provision of primary care services (60 % prescribing, 14 % consultations), 13 % for disability claims, and 12 % for hospital care. There were 1160 asthma deaths. CONCLUSIONS: Asthma is very common and is responsible for considerable morbidity, healthcare utilisation and financial costs to the UK public sector. Greater policy focus on primary care provision is needed to reduce the risk of asthma exacerbations, hospitalisations and deaths, and reduce costs.

Residential Moving and Preventable Hospitalizations.

OBJECTIVES: To investigate the association between moving home in the first year of life and subsequent emergency admissions for potentially preventable hospitalizations. METHODS: We undertook a cohort analysis of linked anonymized data on 237 842 children in the Welsh Electronic Cohort for Children. We included children born in Wales between April 1, 1999 and December 31, 2008. The exposure was the number of residential moves from birth up to 1 year. The main outcome was emergency admissions for potentially preventable hospitalizations (PPH) between the age of 1 and 5 years. RESULTS: After adjustment for confounders, we identified that moving home frequently in the first year of life was associated with an increased risk of emergency PPH between the ages of 1 and 5 when compared with not moving. We found significant differences associated with ≥2 moves for the following: ear, nose, and throat infections (incidence risk ratio [IRR], 1.44; 95% confidence interval [CI], 1.29-1.61); convulsions/epilepsy (IRR, 1.58; 95% CI, 1.23-2.04); injuries (IRR, 1.33; 95% CI, 1.18-1.51); dehydration/gastroenteritis (IRR, 1.51; 95% CI, 1.21-1.88); asthma (IRR, 1.61; 95% CI, 1.19-2.16); influenza/pneumonia (IRR, 1.15; 95% CI, 1.00-1.32); and dental conditions (IRR, 1.30; 95% CI, 1.03-1.64) for ≥1 moves. CONCLUSIONS: Children who move home in the first year of life are at substantially increased risk of emergency admissions for PPH in early childhood. Additional research that focuses on enhancing health and social support services for highly mobile families, educating parents about safety risks, and improving housing quality is warranted.

Data Safe Havens and Trust: Toward a Common Understanding of Trusted Research Platforms for Governing Secure and Ethical Health Research.

In parallel with the advances in big data-driven clinical research, the data safe haven concept has evolved over the last decade. It has led to the development of a framework to support the secure handling of health care information used for clinical research that balances compliance with legal and regulatory controls and ethical requirements while engaging with the public as a partner in its governance. We describe the evolution of 4 separately developed clinical research platforms into services throughout the United Kingdom-wide Farr Institute and their common deployment features in practice. The Farr Institute is a case study from which we propose a common definition of data safe havens as trusted platforms for clinical academic research. We use this common definition to discuss the challenges and dilemmas faced by the clinical academic research community, to help promote a consistent understanding of them and how they might best be handled in practice. We conclude by questioning whether the common definition represents a safe and trustworthy model for conducting clinical research that can stand the test of time and ongoing technical advances while paying heed to evolving public and professional concerns.

Estimating the incidence, prevalence and true cost of asthma in the UK: secondary analysis of national stand-alone and linked databases in England, Northern Ireland, Scotland and Wales-a study protocol.

INTRODUCTION: Asthma is now one of the most common long-term conditions in the UK. It is therefore important to develop a comprehensive appreciation of the healthcare and societal costs in order to inform decisions on care provision and planning. We plan to build on our earlier estimates of national prevalence and costs from asthma by filling the data gaps previously identified in relation to healthcare and broadening the field of enquiry to include societal costs. This work will provide the first UK-wide estimates of the costs of asthma. In the context of asthma for the UK and its member countries (ie, England, Northern Ireland, Scotland and Wales), we seek to: (1) produce a detailed overview of estimates of incidence, prevalence and healthcare utilisation; (2) estimate health and societal costs; (3) identify any remaining information gaps and explore the feasibility of filling these and (4) provide insights into future research that has the potential to inform changes in policy leading to the provision of more cost-effective care. METHODS AND ANALYSIS: Secondary analyses of data from national health surveys, primary care, prescribing, emergency care, hospital, mortality and administrative data sources will be undertaken to estimate prevalence, healthcare utilisation and outcomes from asthma. Data linkages and economic modelling will be undertaken in an attempt to populate data gaps and estimate costs. Separate prevalence and cost estimates will be calculated for each of the UK-member countries and these will then be aggregated to generate UK-wide estimates. ETHICS AND DISSEMINATION: Approvals have been obtained from the NHS Scotland Information Services Division's Privacy Advisory Committee, the Secure Anonymised Information Linkage Collaboration Review System, the NHS South-East Scotland Research Ethics Service and The University of Edinburgh's Centre for Population Health Sciences Research Ethics Committee. We will produce a report for Asthma-UK, submit papers to peer-reviewed journals and construct an interactive map.

A case study of the Secure Anonymous Information Linkage (SAIL) Gateway: a privacy-protecting remote access system for health-related research and evaluation.

With the current expansion of data linkage research, the challenge is to find the balance between preserving the privacy of person-level data whilst making these data accessible for use to their full potential. We describe a privacy-protecting safe haven and secure remote access system, referred to as the Secure Anonymised Information Linkage (SAIL) Gateway. The Gateway provides data users with a familiar Windows interface and their usual toolsets to access approved anonymously-linked datasets for research and evaluation. We outline the principles and operating model of the Gateway, the features provided to users within the secure environment, and how we are approaching the challenges of making data safely accessible to increasing numbers of research users. The Gateway represents a powerful analytical environment and has been designed to be scalable and adaptable to meet the needs of the rapidly growing data linkage community.

Cohort profile: the housing regeneration and health study.

A cohort comprising residents of a housing regeneration and health programme was created from routinely collected data using a system which allows us to anonymously link housing data to individuals and their health. The regeneration programme incorporating four rolling work packages runs from 2009 to 2014. The main intervention cohort we describe here contains the 18 312 residents of 9051 residences at baseline. The cohort will be followed continuously through routine health data (demographics, mortality, hospital admissions and general practitioner records including prescriptions) with periodic updates of housing regeneration intervention data. Here, we describe the baseline data for the primary health outcomes of emergency hospital admissions for cardiovascular and respiratory conditions and injuries for those aged ≥60 years. We will compare the health of residents within the homes before and after the housing regeneration work has taken place, and we will calculate the change in health service costs with use of hospital and General Practitioners (GP) services. We will also use a difference in differences approach to assess changes in comparison with comparator cohorts. These data will be accessible at the end of the study period in 2016. Further information about this study can be obtained from Ronan Lyons; r.a.lyons@swansea.ac.uk.

Predictive risk stratification model: a progressive cluster-randomised trial in chronic conditions management (PRISMATIC) research protocol.

BACKGROUND: An ageing population increases demand on health and social care. New approaches are needed to shift care from hospital to community and general practice. A predictive risk stratification tool (Prism) has been developed for general practice that estimates risk of an emergency hospital admission in the following year. We present a protocol for the evaluation of Prism. METHODS/DESIGN: We will undertake a mixed methods progressive cluster-randomised trial. Practices begin as controls, delivering usual care without Prism. Practices will receive Prism and training randomly, and thereafter be able to use Prism with clinical and technical support. We will compare costs, processes of care, satisfaction and patient outcomes at baseline, 6 and 18 months, using routine data and postal questionnaires. We will assess technical performance by comparing predicted against actual emergency admissions. Focus groups and interviews will be undertaken to understand how Prism is perceived and adopted by practitioners and policy makers. We will model data using generalised linear models and survival analysis techniques to determine whether any differences exist between intervention and control groups. We will take account of covariates and explanatory factors. In the economic evaluation we will carry out a cost-effectiveness analysis to examine incremental cost per emergency admission to hospital avoided and will examine costs versus changes in primary and secondary outcomes in a cost-consequence analysis. We will also examine changes in quality of life of patients across the risk spectrum. We will record and transcribe focus groups and interviews and analyse them thematically. We have received full ethical and R and D approvals for the study and Information Governance Review Panel (IGRP) permission for the use of routine data. We will comply with the CONSORT guidelines and will disseminate the findings at national and international conferences and in peer-reviewed journals. DISCUSSION: The proposed study will provide information on costs and effects of Prism; how it is used in practice, barriers and facilitators to its implementation; and its perceived value in supporting the management of patients with and at risk of developing chronic conditions. TRIAL REGISTRATION: Controlled Clinical Trials ISRCTN no. ISRCTN55538212.

Do children who move home and school frequently have poorer educational outcomes in their early years at school? An anonymised cohort study.

Frequent mobility has been linked to poorer educational attainment. We investigated the association between moving home and moving school frequently and the early childhood formal educational achievement. We carried out a cohort analysis of 121,422 children with anonymised linked records. Our exposure measures were: 1) the number of residential moves registered with a health care provider, and 2) number of school moves. Our outcome was the formal educational assessment at age 6-7. Binary regression modeling was used to examine residential moves within the three time periods: 0 - <1 year; 1 - <4 years and 4 - <6 years. School moves were examined from age 4 to age 6. We adjusted for demographics, residential moves at different times, school moves and birth related variables. Children who moved home frequently were more likely not to achieve in formal assessments compared with children not moving. Adjusted odds ratios were significant for 3 or more moves within the time period 1 -<4 years and for any number of residential moves within the time period 4-<6 years. There was a dose response relationship, with increased odds ratios with increased frequency of residential moves (2 or more moves at 4-<6 years, adjusted odds ratio 1.16 (1.03, 1.29). The most marked effect was seen with frequent school moves where 2 or more moves resulted in an adjusted odds ratio of 2.33 (1.82, 2.98). This is the first study to examine the relationship between residential and school moves in early childhood and the effect on educational attainment. Children experiencing frequent mobility may be disadvantaged and should be closely monitored. Additional educational support services should be afforded to children, particularly those who frequently change school, in order to help them achieve the expected educational standards.

Volunteer bias in recruitment, retention, and blood sample donation in a randomised controlled trial involving mothers and their children at six months and two years: a longitudinal analysis.

BACKGROUND: The vulnerability of clinical trials to volunteer bias is under-reported. Volunteer bias is systematic error due to differences between those who choose to participate in studies and those who do not. METHODS AND RESULTS: This paper extends the applications of the concept of volunteer bias by using data from a trial of probiotic supplementation for childhood atopy in healthy dyads to explore 1) differences between a) trial participants and aggregated data from publicly available databases b) participants and non-participants as the trial progressed 2) impact on trial findings of weighting data according to deprivation (Townsend) fifths in the sample and target populations. 1) a) Recruits (n = 454) were less deprived than the target population, matched for area of residence and delivery dates (n = 6,893) (mean [SD] deprivation scores 0.09[4.21] and 0.79[4.08], t = 3.44, df = 511, p<0.001). b) i) As the trial progressed, representation of the most deprived decreased. These participants and smokers were less likely to be retained at 6 months (n = 430[95%]) (OR 0.29,0.13-0.67 and 0.20,0.09-0.46), and 2 years (n = 380[84%]) (aOR 0.68,0.50-0.93 and 0.55,0.28-1.09), and consent to infant blood sample donation (n = 220[48%]) (aOR 0.72,0.57-0.92 and 0.43,0.22-0.83). ii) Mothers interested in probiotics or research or reporting infants' adverse events or rashes were more likely to attend research clinics and consent to skin-prick testing. Mothers participating to help children were more likely to consent to infant blood sample donation. 2) In one trial outcome, atopic eczema, the intervention had a positive effect only in the over-represented, least deprived group. Here, data weighting attenuated risk reduction from 6.9%(0.9-13.1%) to 4.6%(-1.4-+10.5%), and OR from 0.40(0.18-0.91) to 0.56(0.26-1.21). Other findings were unchanged. CONCLUSIONS: Potential for volunteer bias intensified during the trial, due to non-participation of the most deprived and smokers. However, these were not the only predictors of non-participation. Data weighting quantified volunteer bias and modified one important trial outcome. TRIAL REGISTRATION: This randomised, double blind, parallel group, placebo controlled trial is registered with the International Standard Randomised Controlled Trials Register, Number (ISRCTN) 26287422. Registered title: Probiotics in the prevention of atopy in infants and children.

The effect of gender, age, and geographical location on the incidence and prevalence of renal replacement therapy in Wales.

BACKGROUND: This study used a cross sectional survey to examine the effect of gender, age, and geographical location on the population prevalence of renal replacement therapy (RRT) provision in Wales. METHODS: Physicians in renal centres in Wales and in adjacent areas of England were asked to undertake a census of patients on renal replacement therapy on 30 June 2004 using an agreed protocol. Data were collated and analysed in anonymous form. RESULTS: 2434 patients were on RRT in Wales at the census date. Median age of patients on RRT was 56 years, peritoneal dialysis 58 years, haemodialysis 66 years and transplantation 50 years. The three treatment modalities had significantly different age-specific peak prevalence rates and distributions. RRT age-specific prevalence rates peaked at around 70 years (1790 pmp), transplantation at around 60 years (924 pmp), haemodialysis at around 80 years (1080 pmp) and peritoneal dialysis did not have a clear peak prevalence rate. Age-specific incidence of RRT peaked at a rate of 488 pmp at 79 years, as did incidence rates for haemodialysis, which peaked at the same age. Age had less effect on the initiation of peritoneal dialysis, which had a broad plateau between the early fifties and late seventies. Kidney transplantation rates were highest in the early fifties but were markedly absent in old age. CONCLUSION: Differences in the provision of RRT are evident, particularly in the very elderly, where the gender difference for haemodialysis is particularly marked. The study illustrates that grouping patients over 75 years into a single age-band may mask significant diversity within this age group. Significant numbers of very elderly patients who are currently not receiving RRT may wish to receive RRT as the elderly population increases, and as technology improves survival and quality of life on RRT. The study suggests that if technologies that are more effective were developed, and which had a lower impact on quality of life, there might be up to a 17% increase in demand for RRT in those aged over 75 years; around 90% of this increased demand would be for haemodialysis.