Projected Health and Economic Burden of Comorbid Gout and Chronic Kidney Disease in a Virtual US Population: A Microsimulation Study.

INTRODUCTION: Gout, a common comorbidity of chronic kidney disease (CKD), is associated with high morbidity and healthcare utilization. However, a large proportion of gout remains undermanaged or untreated which may lead to worse patient outcomes and greater healthcare costs. This study estimates the present and future health and economic burden of controlled and uncontrolled gout in a virtual United States (US) CKD population. METHODS: A validated microsimulation model was used to project the burden of gout in patients with CKD in the USA through 2035. Databases were utilized to build a virtual CKD population of "individuals" with controlled or uncontrolled gout. Modelling assumptions were made on the basis of the literature, which was sparse in some cases. Health and economic outcomes with the current care (baseline) scenario were evaluated, along with potential benefits of urate-lowering intervention scenarios. RESULTS: The prevalence of comorbid gout and CKD in the USA was projected to increase by 29%, from 7.9 million in 2023 to 9.6 million in 2035 in the baseline scenario. Gout flares, tophi, and comorbidity development were also projected to increase markedly through 2035, with the economic burden of gout in the CKD population subsequently increasing from $38.9 billion in 2023 to $47.3 billion in 2035. An increased use of oral urate-lowering therapies in undermanaged patients, and pegloticase use in patients refractory to oral urate-lowering therapies were also project to result in 744,000 and 353,000 fewer uncontrolled gout cases, respectively, by 2035. Marked reductions in complications and costs ensued. CONCLUSIONS: This study projected a substantial increase in comorbid gout and CKD. However, improved use of urate-lowering interventions could mitigate this growth and reduce the health and economic burdens of gout.

Preventing liver disease with policy measures to tackle alcohol consumption and obesity: The HEPAHEALTH II study.

BACKGROUND & AIMS: Chronic liver disease (CLD) causes 1.8% of all deaths in Europe, many of them from liver cancer. We estimated the impact of several policy interventions in France, the Netherlands, and Romania. METHODS: We used a validated microsimulation model to assess seven different policy scenarios in 2022-2030: a minimum unit price (MUP) of alcohol of €0.70 or €1, a volumetric alcohol tax, a sugar-sweetened beverage (SSB) tax, food marketing restrictions, plus two different combinations of these policies compared against current policies (the 'inaction' scenario). RESULTS: All policies reduced the burden of CLD and liver cancer. The largest impact was observed for a MUP of €1, which by 2030 would reduce the cumulative incidence of CLD by between 7.1% to 7.3% in France, the Netherlands, and Romania compared with inaction. For liver cancer, the corresponding reductions in cumulative incidence were between 4.8% to 5.8%. Implementing a package containing a MUP of €0.70, a volumetric alcohol tax, and an SSB tax would reduce the cumulative incidence of CLD by between 4.29% to 4.71% and of liver cancer by between 3.47% to 3.95% in France, the Netherlands, and Romania. The total predicted reduction in healthcare costs by 2030 was greatest with the €1 MUP scenario, with a reduction for liver cancer costs of €8.18M and €612.49M in the Netherlands and France, respectively. CONCLUSIONS: Policy measures tackling primary risk factors for CLD and liver cancer, such as the implementation of a MUP of €1 and/or a MUP of €0.70 plus SSB tax could markedly reduce the number of Europeans with CLD or liver cancer. IMPACT AND IMPLICATIONS: Policymakers must be aware that alcohol and obesity are the two leading risk factors for chronic liver disease and liver cancer in Europe and both are expected to increase in the future if no policy interventions are made. This study assessed the potential of different public health policy measures to mitigate the impact of alcohol consumption and obesity on the general population in three European countries: France, the Netherlands, and Romania. The findings support introducing a €1 minimum unit price for alcohol to reduce the burden of chronic liver disease. In addition, the study shows the importance of targeting multiple drivers of alcohol consumption and obesogenic products simultaneously via a harmonized fiscal policy framework, to complement efforts being made within health systems. These findings should encourage policymakers to introduce such policy measures across Europe to reduce the burden of liver disease. The modeling methods used in this study can assist in structuring similar modeling in other regions to expand on this study's findings.

How Could Different Obesity Scenarios Alter the Burden of Type 2 Diabetes and Liver Disease in Saudi Arabia?

INTRODUCTION: Obesity is a major risk factor for type 2 diabetes (T2DM) and liver disease, and obesity-attributable liver disease is a common indication for liver transplant. Obesity prevalence in Saudi Arabia (SA) has increased in recent decades. SA has committed to the WHO "halt obesity" target to shift prevalence to 2010 levels by 2025. We estimated the future benefits of reducing obesity in SA on incidence and costs of T2DM and liver disease under two policy scenarios: (1) SA meets the "halt obesity" target; (2) population body mass index (BMI) is reduced by 1% annually from 2020 to 2040. METHODS: We developed a dynamic microsimulation of working-age people (20-59 years) in SA between 2010 and 2040. Model inputs included population demographic, disease and healthcare cost data, and relative risks of diseases associated with obesity. In our two policy scenarios, we manipulated population BMI and compared predicted disease incidence and associated healthcare costs to a baseline "no change" scenario. RESULTS: Adults <35 years are expected to meet the "halt obesity" target, but those ≥35 years are not. Obesity is set to decline for females, but to increase amongst males 35-59 years. If SA's working-age population achieved either scenario, >1.15 million combined cases of T2DM, liver disease, and liver cancer could be avoided by 2040. Healthcare cost savings for the "halt obesity" and 1% reduction scenarios are 46.7 and 32.8 billion USD, respectively. CONCLUSION: SA's younger working-age population is set to meet the "halt obesity" target, but those aged 35-59 are off track. Even a modest annual 1% BMI reduction could result in substantial future health and economic benefits. Our findings strongly support universal initiatives to reduce population-level obesity, with targeted initiatives for working-age people ≥35 years of age.

The COVID-19 hangover: why we need to take harm caused by alcohol seriously as an indirect effect of the pandemic.

In the UK, harm caused by alcohol has worsened since 2020. A recent report from the Institute of Alcohol Studies projecting future rates of major alcohol-related diseases highlights what this means for health and healthcare. The authors argue that this additional burden is not inevitable if effective policies are introduced.

The future health and economic burden of obesity-attributable type 2 diabetes and liver disease among the working-age population in Saudi Arabia.

BACKGROUND: Obesity and type 2 diabetes (T2DM) are increasing in Saudi Arabia (SA). Among other conditions, these risk factors increase the likelihood of non-alcoholic fatty liver disease (NAFLD), which in turn increases risks for advanced liver diseases, such as non-alcoholic steatohepatitis (NASH), cirrhosis and cancer. The goal of this study was to quantify the health and economic burden of obesity-attributable T2DM and liver disease in SA. METHODS: We developed a microsimulation of the SA population to quantify the future incidence and direct health care costs of obesity-attributable T2DM and liver disease, including liver cancer. Model inputs included population demographics, body mass index, incidence, mortality and direct health care costs of T2DM and liver disease and relative risks of each condition as a function of BMI category. Model outputs included age- and sex-disaggregated incidence of obesity-attributable T2DM and liver disease and their direct health care costs for SA's working-age population (20-59 years) between 2020 and 2040. RESULTS: Between 2020 and 2040, the available data predicts 1,976,593 [± 1834] new cases of T2DM, 285,346 [±874] new cases of chronic liver diseases, and 2,101 [± 150] new cases of liver cancer attributable to obesity, amongst working-age people. By 2040, the direct health care costs of these obesity-attributable diseases are predicted to be 127,956,508,540 [± 51,882,446] USD. CONCLUSIONS: The increase in obesity-associated T2DM and liver disease emphasises the urgent need for obesity interventions and strategies to meaningfully reduce the future health and economic burden of T2DM, chronic liver diseases and liver cancer in SA.

Modelling the size, cost and health impacts of universal basic income: What can be done in advance of a trial?

Opposition to Universal Basic Income (UBI) is encapsulated by Martinelli's claim that 'an affordable basic income would be inadequate, and an adequate basic income would be unaffordable'. In this article, we present a model of health impact that transforms that assumption. We argue that UBI can affect higher level social determinants of health down to individual determinants of health and on to improvements in public health that lead to a number of economic returns on investment. Given that no trial has been designed and deployed with that impact in mind, we present a methodological framework for assessing prospective costs and returns on investment through modelling to make the case for that trial. We begin by outlining the pathways to health in our model of change in order to present criteria for establishing the size of transfer capable of promoting health. We then consider approaches to calculating cost in a UK context to estimate budgetary burdens that need to be met by the state. Next, we suggest means of modelling the prospective impact of UBI on health before asserting means of costing that impact, using a microsimulation approach. We then outline a set of fiscal options for funding any shortfall in returns. Finally, we suggest that fiscal strategy can be designed specifically with health impact in mind by modelling the impact of reform on health and feeding that data cyclically back into tax transfer module of the microsimulation.

Mitigating social and economic sources of trauma: The need for universal basic income during the coronavirus pandemic.

The COVID-19 pandemic is projected to cause an economic shock larger than the global financial crisis of 2007-2008 and a recession as great as anything seen since the Great Depression in 1930s. The social and economic consequences of lockdowns and social distancing measures, such as unemployment, broken relationships and homelessness, create potential for intergenerational trauma extending decades into the future. In this article, we argue that, in the absence of a vaccine, governments need to introduce universal basic income as a means of mitigating this trauma. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Future trends in social inequalities in obesity in England, Wales and Scotland.

BACKGROUND: Previous studies have shown persistent or increasing socioeconomic inequalities in obesity in many European countries. The aim of this study was to project trends in social inequalities in obesity to 2035 in male and female adults (aged 16+) in the UK to ascertain if the gap is widening or narrowing. METHODOLOGY: BMI data for the UK were extracted from the Health Survey for England (2004-14), Scottish Health Survey (2008-14) and the Welsh Health Survey (2004-14), respectively. A non-linear multivariate regression model was fitted to cross-sectional risk factor data to create longitudinal projections to 2035 stratified by sex, and occupational status or education level. RESULTS: Individuals in routine and manual jobs are projected to have the highest prevalence of obesity by 2035 and to experience the highest increases in obesity prevalence to 2035. Social inequalities based on occupation are projected to widen (except in English females). Social inequalities based on education are projected to decrease (except in Welsh females). DISCUSSION: A population strategy of prevention focused on the structural determinants of obesity is needed to change the trajectory of obesity prevalence trends and to tackle health inequalities.

Morbid obesity in the UK: A modelling projection study to 2035.

Background: Morbid obesity (body mass index ⩾40 kg/m2) carries a higher risk of non-communicable disease and is associated with more complex health issues and challenges than obesity body mass index ≥30kg/m2 and <40kg/m2, resulting in much higher financial implications for health systems. Although obesity trends have previously been projected to 2035, these projections do not separate morbid obesity from obesity. This study therefore complements these projections and looks at the prevalence and development of morbid obesity in the UK. Methods: Individual level body mass index data for people aged >15 years in England, Wales (2004-2014) and Scotland (2008-2014) were collated from national surveys and stratified by sex and five-year age groups (e.g. 15-19 years), then aggregated to calculate the annual distribution of healthy weight, overweight, obesity and morbid obesity for each age and sex group. A categorical multi-variate non-linear regression model was fitted to these distributions to project trends to 2035. Results: The prevalence of morbid obesity was predicted to increase to 5, 8 and 11% in Scotland, England and Wales, respectively, by 2035. Welsh women aged 55-64 years had the highest projected prevalence of 20%. In total, almost five million people are forecast to be classified as morbidly obese across the three countries in 2035. Conclusions: The prevalence of morbid obesity is predicted to increase by 2035 across the three UK countries, with Wales projected to have the highest rates. This is likely to have serious health and financial implications for society and the UK health system.

Screening and brief intervention for obesity in primary care: cost-effectiveness analysis in the BWeL trial.

BACKGROUND: The Brief Intervention for Weight Loss Trial enrolled 1882 consecutively attending primary care patients who were obese and participants were randomised to physicians opportunistically endorsing, offering, and facilitating a referral to a weight loss programme (support) or recommending weight loss (advice). After one year, the support group lost 1.4 kg more (95%CI 0.9 to 2.0): 2.4 kg versus 1.0 kg. We use a cohort simulation to predict effects on disease incidence, quality of life, and healthcare costs over 20 years. METHODS: Randomly sampling from the trial population, we created a virtual cohort of 20 million adults and assigned baseline morbidity. We applied the weight loss observed in the trial and assumed weight regain over four years. Using epidemiological data, we assigned the incidence of 12 weight-related diseases depending on baseline disease status, age, gender, body mass index. From a healthcare perspective, we calculated the quality adjusted life years (QALYs) accruing and calculated the incremental difference between trial arms in costs expended in delivering the intervention and healthcare costs accruing. We discounted future costs and benefits at 1.5% over 20 years. RESULTS: Compared with advice, the support intervention reduced the cumulative incidence of weight-related disease by 722/100,000 people, 0.33% of all weight-related disease. The incremental cost of support over advice was £2.01million/100,000. However, the support intervention reduced health service costs by £5.86 million/100,000 leading to a net saving of £3.85 million/100,000. The support intervention produced 992 QALYs/100,000 people relative to advice. CONCLUSIONS: A brief intervention in which physicians opportunistically endorse, offer, and facilitate a referral to a behavioural weight management service to patients with a BMI of at least 30 kg/m2 reduces healthcare costs and improves health more than advising weight loss.

Bariatric surgery, lifestyle interventions and orlistat for severe obesity: the REBALANCE mixed-methods systematic review and economic evaluation.

BACKGROUND: Adults with severe obesity [body mass index (BMI) of ≥ 35 kg/m2] have an increased risk of comorbidities and psychological, social and economic consequences. OBJECTIVES: Systematically review bariatric surgery, weight-management programmes (WMPs) and orlistat pharmacotherapy for adults with severe obesity, and evaluate the feasibility, acceptability, clinical effectiveness and cost-effectiveness of treatment. DATA SOURCES: Electronic databases including MEDLINE, EMBASE, PsycINFO, the Cochrane Central Register of Controlled Trials and the NHS Economic Evaluation Database were searched (last searched in May 2017). REVIEW METHODS: Four systematic reviews evaluated clinical effectiveness, cost-effectiveness and qualitative evidence for adults with a BMI of ≥ 35 kg/m2. Data from meta-analyses populated a microsimulation model predicting costs, outcomes and cost-effectiveness of Roux-en-Y gastric bypass (RYGB) surgery and the most effective lifestyle WMPs over a 30-year time horizon from a NHS perspective, compared with current UK population obesity trends. Interventions were cost-effective if the additional cost of achieving a quality-adjusted life-year is < £20,000-30,000. RESULTS: A total of 131 randomised controlled trials (RCTs), 26 UK studies, 33 qualitative studies and 46 cost-effectiveness studies were included. From RCTs, RYGB produced the greatest long-term weight change [-20.23 kg, 95% confidence interval (CI) -23.75 to -16.71 kg, at 60 months]. WMPs with very low-calorie diets (VLCDs) produced the greatest weight loss at 12 months compared with no WMPs. Adding a VLCD to a WMP gave an additional mean weight change of -4.41 kg (95% CI -5.93 to -2.88 kg) at 12 months. The intensive Look AHEAD WMP produced mean long-term weight loss of 6% in people with type 2 diabetes mellitus (at a median of 9.6 years). The microsimulation model found that WMPs were generally cost-effective compared with population obesity trends. Long-term WMP weight regain was very uncertain, apart from Look AHEAD. The addition of a VLCD to a WMP was not cost-effective compared with a WMP alone. RYGB was cost-effective compared with no surgery and WMPs, but the model did not replicate long-term cost savings found in previous studies. Qualitative data suggested that participants could be attracted to take part in WMPs through endorsement by their health-care provider or through perceiving innovative activities, with WMPs being delivered to groups. Features improving long-term weight loss included having group support, additional behavioural support, a physical activity programme to attend, a prescribed calorie diet or a calorie deficit. LIMITATIONS: Reviewed studies often lacked generalisability to UK settings in terms of participants and resources for implementation, and usually lacked long-term follow-up (particularly for complications for surgery), leading to unrealistic weight regain assumptions. The views of potential and actual users of services were rarely reported to contribute to service design. This study may have failed to identify unpublished UK evaluations. Dual, blinded numerical data extraction was not undertaken. CONCLUSIONS: Roux-en-Y gastric bypass was costly to deliver, but it was the most cost-effective intervention. Adding a VLCD to a WMP was not cost-effective compared with a WMP alone. Most WMPs were cost-effective compared with current population obesity trends. FUTURE WORK: Improved reporting of WMPs is needed to allow replication, translation and further research. Qualitative research is needed with adults who are potential users of, or who fail to engage with or drop out from, WMPs. RCTs and economic evaluations in UK settings (e.g. Tier 3, commercial programmes or primary care) should evaluate VLCDs with long-term follow-up (≥ 5 years). Decision models should incorporate relevant costs, disease states and evidence-based weight regain assumptions. STUDY REGISTRATION: This study is registered as PROSPERO CRD42016040190. FUNDING: The National Institute for Health Research Health Technology Assessment programme. The Health Services Research Unit and Health Economics Research Unit are core funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorate.

Forecasting Future Trends in Obesity across Europe: The Value of Improving Surveillance.

OBJECTIVE: To project the prevalence of obesity across the WHO European region and examine whether the WHO target of halting obesity at 2010 levels by 2025 is achievable. METHODS: BMI data were collected from online databases and the literature. Past and present BMI trends were extrapolated to 2025 using a non-linear categorical regression model fitted to nationally representative survey data. Where only 1 year of data was available, a flat trend was assumed. Where no data were available, proxy country data was used adjusted for demographics. RESULTS: By 2025, obesity is projected to increase in 44 countries. If present trends continue, 33 of the 53 countries are projected to have an obesity prevalence of 20% or more. The highest prevalence is projected for Ireland (43%, 95% confidence interval (CI): 28-58%). Lithuania, Finland, and the Netherlands were each estimated to have an absolute increase of 2 percentage points in the prevalence of obesity between 2015 and 2025. DISCUSSION: The quality of BMI data across Europe is highly variable, with fewer than 50% of the 53 countries having measured nationally representative data and often not enough data to interpret projections meaningfully. Nevertheless, the prevalence of obesity in the European Region appears to be increasing in most countries and, with it, the health and economic burden of its associated diseases. This paints a concerning picture of the future burden of obesity-related noncommunicable diseases across the region. Greater and continued effort for the implementation of effective preventive policies and interventions is required from governments.

Estimating the costs of air pollution to the National Health Service and social care: An assessment and forecast up to 2035.

BACKGROUND: Air pollution damages health by promoting the onset of some non-communicable diseases (NCDs), putting additional strain on the National Health Service (NHS) and social care. This study quantifies the total health and related NHS and social care cost burden due to fine particulate matter (PM2.5) and nitrogen dioxide (NO2) in England. METHOD AND FINDINGS: Air pollutant concentration surfaces from land use regression models and cost data from hospital admissions data and a literature review were fed into a microsimulation model, that was run from 2015 to 2035. Different scenarios were modelled: (1) baseline 'no change' scenario; (2) individuals' pollutant exposure is reduced to natural (non-anthropogenic) levels to compute the disease cases attributable to PM2.5 and NO2; (3) PM2.5 and NO2 concentrations reduced by 1 µg/m3; and (4) NO2 annual European Union limit values reached (40 µg/m3). For the 18 years after baseline, the total cumulative cost to the NHS and social care is estimated at £5.37 billion for PM2.5 and NO2 combined, rising to £18.57 billion when costs for diseases for which there is less robust evidence are included. These costs are due to the cumulative incidence of air-pollution-related NCDs, such as 348,878 coronary heart disease cases estimated to be attributable to PM2.5 and 573,363 diabetes cases estimated to be attributable to NO2 by 2035. Findings from modelling studies are limited by the conceptual model, assumptions, and the availability and quality of input data. CONCLUSIONS: Approximately 2.5 million cases of NCDs attributable to air pollution are predicted by 2035 if PM2.5 and NO2 stay at current levels, making air pollution an important public health priority. In future work, the modelling framework should be updated to include multi-pollutant exposure-response functions, as well as to disaggregate results by socioeconomic status.

Burden of liver disease in Europe: Epidemiology and analysis of risk factors to identify prevention policies.

The burden of liver disease in Europe continues to grow. We aimed to describe the epidemiology of liver diseases and their risk factors in European countries, identifying public health interventions that could impact on these risk factors to reduce the burden of liver disease. As part of the HEPAHEALTH project we extracted information on historical and current prevalence and mortality from national and international literature and databases on liver disease in 35 countries in the World Health Organization European region, as well as historical and recent prevalence data on their main determinants; alcohol consumption, obesity and hepatitis B and C virus infections. We extracted information from peer-reviewed and grey literature to identify public health interventions targeting these risk factors. The epidemiology of liver disease is diverse, with variations in the exact composition of diseases and the trends in risk factors which drive them. Prevalence and mortality data indicate that increasing cirrhosis and liver cancer may be linked to dramatic increases in harmful alcohol consumption in Northern European countries, and viral hepatitis epidemics in Eastern and Southern European countries. Countries with historically low levels of liver disease may experience an increase in non-alcoholic fatty liver disease in the future, given the rise of obesity across most European countries. Liver disease in Europe is a serious issue, with increasing cirrhosis and liver cancer. The public health and hepatology communities are uniquely placed to implement measures aimed at reducing their causes: harmful alcohol consumption, child and adult obesity, and chronic infection with hepatitis viruses, which will in turn reduce the burden of liver disease.

Inequalities in smoking and obesity in Europe predicted to 2050: Findings from the EConDA project.

AIMS: The aim of this study was to project educational inequalities in obesity and smoking prevalence to 2050 based on past obesity and smoking trends by education level. METHODS: Data on obesity (body mass index ≥ 30) and smoking prevalence (current smokers) by education level (tertiary education and less than tertiary) from nationally representative cross-sectional surveys were collected for the following six countries participating in the Economics of Chronic Diseases project (EConDA): England, Finland, Lithuania, the Netherlands, Poland (obesity only) and Portugal (obesity only). A nonlinear multivariate regression model was fitted to the data to create longitudinal projections to 2050. Inequalities were measured with a prevalence ratio and a prevalence difference using projected obesity/smoking prevalence. RESULTS: Educational inequalities in obesity prevalence are projected to increase in Finland, Lithuania and England for men, and in Lithuania and Poland for women, by 2050. Obesity prevalence is projected to increase faster among the more advantaged groups in England, Portugal, Finland and the Netherlands among women, and Portugal and the Netherlands among men, narrowing inequalities. In contrast to obesity, smoking prevalence is projected to continue declining in most of the countries studied. The decline is projected to be faster in relative terms among more advantaged groups; therefore, relative educational inequalities in smoking prevalence are projected to increase in all countries. CONCLUSIONS: Widening educational inequalities in obesity and smoking prevalence are expected in several European countries if current trends in obesity and smoking prevalence are unaltered. This will impact on inequalities in morbidity and mortality of associated diseases such as diabetes, coronary heart disease and chronic obstructive pulmonary disease.

Modelling the implications of reducing smoking prevalence: the benefits of increasing the UK tobacco duty escalator to public health and economic outcomes.

INTRODUCTION: Taxing tobacco is one of the most effective ways to reduce smoking prevalence, mitigate its devastating consequential health harms and progress towards a tobacco-free society. This study modelled the health and economic impacts of increasing the existing cigarette tobacco duty escalator (TDE) in the UK from the current 2% above consumer price inflation to 5%. METHODS: A two-stage modelling process was used. First, a non-linear multivariate regression model was fitted to cross-sectional smoking data, creating longitudinal projections from 2015 to 2035. Second, these projections were used to predict the future incidence, prevalence and cost of 17 smoking-related diseases using a Monte Carlo microsimulation approach. A sustained increase in the duty escalator was evaluated against a baseline of continuing historical smoking trends and the existing duty escalator. RESULTS: A sustained increase in the TDE is projected to reduce adult smoking prevalence to 6% in 2035, from 10% in a baseline scenario. After increasing the TDE, only 65% of female and 60% of male would-be smokers would actually be smoking in 2035. The intervention is projected to avoid around 75 200 new cases of smoking-related diseases between 2015 and 2035. In 2035 alone, £49 m in National Health Service and social care costs and £192 m in societal premature mortality and morbidity costs are projected to be avoided. CONCLUSION: Increasing the UK TDE to 5% above inflation could effectively reduce smoking prevalence, prevent diseases and avoid healthcare costs. It would deliver substantial progress towards a tobacco-free society and should be implemented by the UK Government with urgency.

Modelling the implications of reducing smoking prevalence: the public health and economic benefits of achieving a 'tobacco-free' UK.

INTRODUCTION: Smoking is still the most preventable cause of cancer, and a leading cause of premature mortality and health inequalities in the UK. This study modelled the health and economic impacts of achieving a 'tobacco-free' ambition (TFA) where, by 2035, less than 5% of the population smoke tobacco across all socioeconomic groups. METHODS: A non-linear multivariate regression model was fitted to cross-sectional smoking data to create projections to 2035. These projections were used to predict the future incidence and costs of 17 smoking-related diseases using a microsimulation approach. The health and economic impacts of achieving a TFA were evaluated against a predicted baseline scenario, where current smoking trends continue. RESULTS: If trends continue, the prevalence of smoking in the UK was projected to be 10% by 2035-well above a TFA. If this ambition were achieved by 2035, it could mean 97 300 +/- 5 300 new cases of smoking-related diseases are avoided by 2035 (tobacco-related cancers: 35 900+/- 4 100; chronic obstructive pulmonary disease: 29 000 +/- 2 700; stroke: 24 900 +/- 2 700; coronary heart disease: 7600 +/- 2 700), including around 12 350 diseases avoided in 2035 alone. The consequence of this health improvement is predicted to avoid £67 +/- 8 million in direct National Health Service and social care costs, and £548 million in non-health costs, in 2035 alone. CONCLUSION: These findings strengthen the case to set bold targets on long-term declines in smoking prevalence to achieve a tobacco 'endgame'. Results demonstrate the health and economic benefits that meeting a TFA can achieve over just 20 years. Effective ambitions and policy interventions are needed to reduce the disease and economic burden of smoking.