Population-based Modelling Study Research Articles

Effect of recipient age on prioritisation for liver transplantation in the UK: a population-based modelling study

Following the introduction of an algorithm aiming to maximise life-years gained from liver transplantation in the UK (the transplant benefit score [TBS]), donor livers were redirected from younger to older patients, mortality rate equalised across the age range and short-term waiting list mortality reduced. Understanding age-related prioritisation has been challenging, especially for younger patients and clinicians allocating non-TBS-directed livers. We aimed to assess age-related prioritisation within the TBS algorithm by modelling liver transplantation prioritisation based on data from a UK transplant unit and comparing these data with other regions. In this population-based modelling study, serum parameters and age at liver transplantation assessment of patients attending the Scottish Liver Transplant Unit, Edinburgh, UK, between December, 2002, and November, 2023, were combined with representative synthetic data to model TBS survival predictions, which were compared according to age group (25-49 years vs ≥60 years), chronic liver disease severity, and disease cause. Models for end-stage liver disease (UKELD [UK], MELD [Eurotransplant region], and MELD 3.0 [USA]) were used as validated comparators of liver disease severity. Of 2093 patients with chronic liver disease, 1808 (86%) had complete datasets and liver disease parameters consistent with eligibility for the liver transplant waiting list in the UK (UKELD ≥49). Disease severity as assessed by UKELD, MELD, and MELD 3.0 did not differ by age (median UKELD scores of 56 for patients aged ≥60 years vs 56 for patients aged 25-49 years; MELD scores of 16 vs 16; and MELD 3.0 scores of 18 vs 18). TBS increased with advancing age (R=0·45, p<0·0001). TBS predicted that transplantation in patients aged 60 years or older would provide a two-fold greater net benefit at 5 years than in patients aged 25-49 years (median TBS 1317 [IQR 1116-1436] in older patients vs 706 [411-1095] in younger patients; p<0·0001). Older patients were predicted to have shorter survival without transplantation than younger patients (263 days [IQR 144-473] in older patients vs 861 days [448-1164] in younger patients; p<0·0001) but similar survival after transplantation (1599 days [1563-1628] vs 1573 days [1525-1614]; p<0·0001). Older patients could reach a TBS for which a liver offer was likely below minimum criteria for transplantation (UKELD <49), whereas many younger patients were required to have high-urgent disease (UKELD >60). US and Eurotransplant programmes did not prioritise according to age. The UK liver allocation algorithm prioritises older patients for transplantation by predicting that advancing age increases the benefit from liver transplantation. Restricted follow-up and biases in waiting list data might limit the accuracy of these benefit predictions. Measures beyond overall waiting list mortality are required to fully capture the benefits of liver transplantation. None.

Explaining declining hip fracture rates in Norway: a population-based modelling study.

Although age-standardised hip fracture incidence has declined in many countries during recent decades, the number of fractures is forecast to increase as the population ages. Understanding the drivers behind this decline is essential to inform policy for targeted preventive measures. We aimed to quantify how much of this decline could be explained by temporal trends in major risk factors and osteoporosis treatment. We developed a new modelling approach, Hip-IMPACT, based on the validated IMPACT coronary heart disease models. The model applied sex- and age stratified hip fracture numbers and prevalence of pharmacologic treatments and risk/preventive factors in 1999 and 2019, and best available evidence for independent relative risks of hip fracture associated with each treatment and risk/preventive factor. Hip-IMPACT explained 91% (2500/2756) of the declining hip fracture rates during 1999-2019. Two-thirds of the total decline was attributed to changes in risk/preventive factors and one-fifth to osteoporosis medication. Increased prevalence of total hip replacements explained 474/2756 (17%), increased body mass index 698/2756 (25%), and increased physical activity 434/2756 (16%). Reduced smoking explained 293/2756 (11%), and reduced benzodiazepine use explained (366/2756) 13%. Increased uptake of alendronate, zoledronic acid, and denosumab explained 307/2756 (11%), 104/2756 (4%) and 161/2756 (6%), respectively. The explained decline was partially offset by increased prevalence of type 2 diabetes and users of glucocorticoids, z-drugs, and opioids. Two-thirds of the decline in hip fractures from 1999 to 2019 was attributed to reductions in major risk factors and approximately one-fifth to osteoporosis medication. The Research Council of Norway.

Health service planning to assess the expected impact of centralising specialist cancer services on travel times, equity, and outcomes: a national population-based modelling study.

Centralisation of specialist cancer services is occurring in many countries, often without evaluating the potential impact before implementation. We developed a health service planning model that can estimate the expected impacts of different centralisation scenarios on travel time, equity in access to services, patient outcomes, and hospital workload, using rectal cancer surgery as an example. For this population-based modelling study, we used routinely collected individual patient-level data from the National Cancer Registration and Analysis Service (NCRAS) and linked to the NHS Hospital Episode Statistics (HES) database for 11 888 patients who had been diagnosed with rectal cancer between April 1, 2016, and Dec 31, 2018, and who subsequently underwent a major rectal cancer resection in 163 National Health Service (NHS) hospitals providing rectal cancer surgery in England. Five centralisation scenarios were considered: closure of lower-volume centres (scenario A); closure of non-comprehensive cancer centres (scenario B); closure of centres with a net loss of patients to other centres (scenario C); closure of centres meeting all three criteria in scenarios A, B, and C (scenario D); and closure of centres with high readmission rates (scenario E). We used conditional logistic regression to predict probabilities of affected patients moving to each of the remaining centres and the expected changes in travel time, multilevel logistic regression to predict 30-day emergency readmission rates, and linear regression to analyse associations between the expected extra travel time for patients whose centre is closed and five patient characteristics, including age, sex, socioeconomic deprivation, comorbidity, and rurality of the patients' residential areas (rural, urban [non-London], or London). We also quantified additional workload, defined as the number of extra patients reallocated to remaining centres. Of the 11 888 patients, 4130 (34·7%) were women, 5249 (44·2%) were aged 70 years and older, and 5005 (42·1%) had at least one comorbidity. Scenario A resulted in closures of 43 (26%) of the 163 rectal cancer surgery centres, affecting 1599 (13·5%) patients; scenario B resulted in closures of 112 (69%) centres, affecting 7029 (59·1%) patients; scenario C resulted in closures of 56 (34%) centres, affecting 3142 (26·4%) patients; scenario D resulted in closures of 24 (15%) centres, affecting 874 (7·4%) patients; and scenario E resulted in closures of 16 (10%) centres, affecting 1000 (8·4%) patients. For each scenario, there was at least a two-times increase in predicted travel time for re-allocated patients with a mean increase in travel time of 23 min; however, the extra travel time did not disproportionately affect vulnerable patient groups. All scenarios resulted in significant reductions in 30-day readmission rates (range 4-48%). Three hospitals in scenario A, 41 hospitals in in scenario B, 13 hospitals in scenario C, no hospitals in scenario D, and two hospitals in scenario E had to manage at least 20 extra patients annually. This health service planning model can be used to to guide complex decisions about the closure of centres and inform mitigation strategies. The approach could be applied across different country or regional health-care systems for patients with cancer and other complex health conditons. National Institute for Health Research.

The current and future incidence and mortality of gastric cancer in 185 countries, 2020–40: A population-based modelling study

SummaryBackgroundTo examine global patterns of gastric cancer in 2020 and the projected burden in 2040.MethodsData on primary gastric cancer were extracted from the GLOBOCAN database for the year 2020. Age-standardized incidence and mortality rates were calculated by sex, country, world region and level of human development index (HDI) for 185 countries. The predicted burden of incidence and mortality in 2040 was calculated based on demographic projections.FindingsIn total, ∼1.1 million new cases and 770,000 deaths of gastric cancer were estimated in 2020. Incidence rates were on average 2-fold higher in males than females (15.8 and 7.0 per 100,000, respectively) with variation across countries. Highest incidence rates were observed in Eastern Asia for both males and females (32.5 and 13.2, respectively); males residing in Japan (48.1), Mongolia (47.2) and Korea (39.7) had the highest rates in the world. Incidence was lowest in Africa with incidence rates < 5 per 100,000. Highest mortality rates were observed in Eastern Asia for both males (21.1) and females (8.8). A lower share of deaths was observed in very high HDI countries compared to medium and low HDI countries. The annual burden of gastric cancer is predicted to increase to ∼1.8 million new cases and ∼1.3 million deaths by 2040.InterpretationThese estimates of the global burden of gastric cancer pinpoint countries and regions of high incidence and mortality in need of cancer control initiatives. Primary prevention through eradication of H. pylori and behavioural changes such as reducing salt intake, smoking, obesity, and alcohol, remains key in stomach cancer control.FundingNo direct funding was received. All authors had access to the included study data and all authors agreed with the final decision to submit for publication.

IDF21-0481 The burden of inadequately controlled risk factors for type 2 diabetes in Hong Kong: A population-based modelling study

Background: The economic and clinical burden of diabetes is well-established, yet a substantial proportion of people with diabetes have inadequate control of risk factors. Adherence to glycaemic, blood pressure and LDL-cholesterol targets could reduce the disease burden and save medical costs. Aim: To estimate the clinical and economic burden of diabetes associated with inadequate control of type 2 diabetes risk factors in Hong Kong over the next 10 years. Method: Population-based data of 590,008 people diagnosed with type 2 diabetes from January to December 2017 was obtained from the Hong Kong Hospital Authority electronic health records. The Hospital Authority system provides care for 95% of people with diabetes in Hong Kong. Immediate control of blood glucose, blood pressure and LDL-cholesterol (separately and combined) was compared to constant baseline levels, with outcomes projected over 10 years using the validated Chinese Hong Kong Integrated Modelling and Evaluation (CHIME) Diabetes model. Risk factor control was defined by American Diabetes Association (ADA) guidelines as glycated haemoglobin (HbA1c) targets <7% (53 mmol/mol), blood pressure <130/80 mmHg, and LDL-cholesterol <2.6 mmol/L. Quality-adjusted life years (QALYs) were calculated based on a meta-analysis of Asia-specific utility weights for diabetes and related complications. Direct medical costs were estimated from a health care provider perspective. Results: Immediate control of blood glucose, blood pressure and LDL-cholesterol was associated with population-level increases of 36,939 QALYs and 23,921 life-years with medical cost savings of USD 5.4 billion over 10 years compared to constant baseline risk levels. On an individual-level, immediate control of individual risk factors was associated with small gains of 0.06 QALYs, 0.04 life-years, and cost savings of USD 9,114 at 10 years. Among the individual risk factors, glycaemic control was associated with the greatest QALY gains and blood pressure control with the greatest medical cost savings.Tabled 1IndividualPopulationCombinedHbA1cBPLDLCombinedHbA1cBPLDLQuality-adjusted life years5 years0.020.020.010.0112,26911,4686,3915,35610 years0.060.060.040.0336,93935,71422,89220,476Life expectancy, years5 years0.010.0200.017,5488,9001,7233,49810 years0.040.050.020.0223,92127,58910,52814,475Medical cost savings, USD5 years5,1973,9014,9762,9723.1bn2.3 bn2.9 bn1.8 bn10 years9,1146,6438,5975,0545.4bn3.9 bn5.1 bn3.0 bnAbbreviations: HbA1c, glycated haemoglobin; BP, blood pressure; LDL, LDL-cholesterol, bn, billion. Open table in a new tab Abbreviations: HbA1c, glycated haemoglobin; BP, blood pressure; LDL, LDL-cholesterol, bn, billion. Discussion: The clinical and economic burden from inadequate control of risk factors in Hong Kong is substantial, particularly on a population-level. This disease burden is potentially reducible by early intervention and adherence to risk factor targets.

The impact of the COVID-19 pandemic on urological care in Poland - Post-COVID resilience scenarios and recommendations for healthcare system: A national population-based modelling study.

IntroductionOur aim was to assess the time required to recover the hypothetical surgical capacity of urological procedures that were suspended due to lockdowns caused by the SARS-CoV-2 outbreak in 2020 and 2021 in Poland, to indicate the most affected procedures, and to estimate the recovery time after a likely fourth lockdown.Material and methodsThe data aggregates contained the number of patients who underwent specific urological procedures classified in the ICD-9, performed from January 2009 to October 2019, acquired in granulation per month and per single voivodeship, and obtained by healthcare providers such as hospitals, ambulatory units, and primary care facilities. Using the model, we obtained the time required to discharge the excessive load on the healthcare system and the median wait time in the post-lockdown period. We validated the model based on the data aggregates from March to October 2020.ResultsLeaving the capacity of the most affected procedures unaltered, or increasing it by 20%, would not reduce the backlog of patients waiting to receive care after the third lockdown. The consequences of a feasible fourth lockdown would cause the necessity of a post-lockdown increase in capacity by more than 50%.ConclusionsThe availability of the most affected procedures will never achieve the pre-pandemic state without increasing the hypothetical surgical capacity of urological procedures that were suspended due to lockdowns caused by the SARS-CoV-2 outbreak. These procedures require taking special steps to unblock the urological healthcare system and allow patients continuous access to treatment.

Smoking-related cancer death among men and women in an ageing society (China 2020–2040): a population-based modelling study

BackgroundChina is experiencing a postpeak smoking epidemic with accelerating population ageing. Understanding the impacts of these factors on the future cancer burden has widespread implications.MethodsWe developed predictive models to estimate...

The ophthalmic surgical backlog associated with the COVID-19 pandemic: a population-based and microsimulation modelling study.

Background:Jurisdictions worldwide ramped down ophthalmic surgeries to mitigate the effects of COVID-19, creating a global surgical backlog. We sought to predict the long-term impact of COVID-19 on the timely delivery of non-emergent ophthalmology sub-specialty surgical care in Ontario.Methods:This is a microsimulation modelling study. We used provincial population-based administrative data from the Wait Time Information System database in Ontario for January 2019 to May 2021 and facility-level data for March 2018 to May 2021 to estimate the backlog size and wait times associated with the COVID-19 pandemic. For the postpandemic recovery phase, we estimated the resources required to clear the backlog of patients accumulated on the wait-list during the pandemic. Outcomes were accrued over a time horizon of 3 years.Results:A total of 56 923 patients were on the wait-list in the province of Ontario awaiting non-emergency ophthalmic surgery as of Mar. 15, 2020. The number of non-emergency surgeries performed in the province decreased by 97% in May 2020 and by 80% in May 2021 compared with the same months in 2019. By 2 years and 3 years since the start of the pandemic, the overall estimated number of patients awaiting surgery grew by 129% and 150%, respectively. The estimated mean wait time for patients for all subspecialty surgeries increased to 282 (standard deviation [SD] 91) days in March 2023 compared with 94 (SD 97) days in 2019. The provincial monthly additional resources required to clear the backlog by March 2023 was estimated to be a 34% escalation from the prepandemic volumes (4626 additional surgeries).Interpretation:The estimates from this microsimulation modelling study suggest that the magnitude of the ophthalmic surgical backlog from the COVID-19 pandemic has important implications for the recovery phase. This model can be adapted to other jurisdictions to assist with recovery planning for vision-saving surgeries.

Identifying priority interventions for stroke in Ireland through stakeholder engagement to inform population-based modelling: a mixed methods protocol.

Introduction Improvements in stroke survival have resulted in increasing numbers of people living with stroke, and with a rapidly evolving evidence-base for stroke prevention and management, there is a need for robust data and evidence to inform future policy decision-making. Population-based modelling and economic evaluation of alternative policy options is a useful tool to support decision making. However, this process must be aligned to key stakeholder priorities. The aim of the proposed research is to engage with stakeholders in Ireland to identify their priorities for the development of stroke prevention and management strategies and policies. Methods The design is iterative, based on mixed methods. Phase 1 involves a qualitative approach for initial priority gathering, based on an open-ended online survey (target sample: 100-120) and interviews (target sample: 34-40). Stakeholders will include: 1) stroke survivors and family member/main carers, 2) healthcare professionals (HCPs) providing stroke care and 3) people working in stroke research, policy and advocacy. These data will be analysed qualitatively, with the aim of identifying a long-list of specific interventions. Phase 2 involves an interim priority-setting exercise, based on a quantitative online survey. Participants will be asked to rank the interventions on the initial long-list. These rankings will be used to inform a final priority-setting workshop (Phase 3), where a small stakeholder group will decide on the final set of priorities. Discussion The rich and detailed quantitative and qualitative data, based on the views of diverse stakeholders, will be directly relevant to policy makers and service planners involved in developing and improving stroke care in Ireland. The information provided will also be essential to inform the Scenario and Intervention Modelling in Ireland for Stroke (SIMI-Stroke) project, a population-based economic and epidemiological modelling study aimed at identifying cost-effective interventions for stroke across the prevention, acute and post-acute care continuum.

Economic impact of avoidable cancer deaths caused by diagnostic delay during the COVID-19 pandemic: A national population-based modelling study in England, UK

IntroductionDelays in cancer diagnosis arose from the commencement of non-pharmaceutical interventions (NPI) introduced in the UK in March 2020 in response to the COVID-19 pandemic. Our earlier work predicted this will lead to approximately 3620 avoidable deaths for four major tumour types (breast, bowel, lung, and oesophageal cancer) in the next 5 years. Here, using national population-based modelling, we estimate the health and economic losses resulting from these avoidable cancer deaths. We also compare these with the impact of an equivalent number of COVID-19 deaths to understand the welfare consequences of the different health conditions. MethodsWe estimate health losses using quality-adjusted life years (QALYs) and lost economic productivity using the human capital (HC) approach. The analysis uses linked English National Health Service (NHS) cancer registration and hospital administrative datasets for patients aged 15–84 years, diagnosed with breast, colorectal, and oesophageal cancer between 1st Jan to 31st Dec 2010, with follow-up data until 31st Dec 2014, and diagnosed with lung cancer between 1st Jan to 31st Dec 31 2012, with follow-up data until 31st Dec 2015. Productivity losses are based on the estimation of excess additional deaths due to cancer at 1, 3 and 5 years for the four cancer types, which were derived from a previous analysis using this dataset. A total of 500 random samples drawn from the total number of COVID-19 deaths reported by the Office for National Statistics, stratified by gender, were used to estimate productivity losses for an equivalent number of deaths (n = 3620) due to SARS-CoV-2 infection. ResultsWe collected data for 32,583 patients with breast cancer, 24,975 with colorectal cancer, 6744 with oesophageal cancer, and 29,305 with lung cancer. We estimate that across the four site-specific cancers combined in England alone, additional excess cancer deaths would amount to a loss of 32,700 QALYs (95% CI 31,300-34,100) and productivity losses of £103.8million GBP (73.2–132.2) in the next five years. For breast cancer, we estimate a loss of 4100 QALYS (3900–4400) and productivity losses of £23.2 m (18.2–28.6); for colorectal cancer, 15,000 QALYS (14,100–16,000) lost and productivity losses of £35.7 m (22.4–48.7); for lung cancer 10,900 QALYS (9,900–11,700) lost and productivity losses of £38.3 m (14.0–59.9) for lung cancer; and for oesophageal cancer, 2700 QALYS (2300–3,100) lost and productivity losses of £6.6 m (–6 to –17.6). In comparison, the equivalent number of COVID-19 deaths caused approximately 21,450 QALYs lost, as well as productivity losses amounting to £76.4 m (73.5–79.2). ConclusionPremature cancer deaths resulting from diagnostic delays during the first wave of the COVID-19 pandemic in the UK will result in significant economic losses. On a per-capita basis, this impact is, in fact, greater than that of deaths directly attributable to COVID-19. These results emphasise the importance of robust evaluation of the trade-offs of the wider health, welfare and economic effects of NPI to support both resource allocation and the prioritisation of time-critical health services directly impacted in a pandemic, such as cancer care.

Global demand for cancer surgery and an estimate of the optimal surgical and anaesthesia workforce between 2018 and 2040: a population-based modelling study.

The growing demand for cancer surgery has placed a global strain on health systems. In-depth analyses of the global demand for cancer surgery and optimal workforce requirements are needed to plan service provision. We estimated the global demand for cancer surgery and the requirements for an optimal surgical and anaesthesia workforce, using benchmarks based on clinical guidelines. Using models of benchmark surgical use based on clinical guidelines, we estimated the proportion of cancer cases with an indication for surgery across 183 countries, stratified by income group. These proportions were multiplied by age-adjusted national estimates of new cancer cases using GLOBOCAN 2018 data and then aggregated to obtain the estimated number of surgical procedures required globally. The numbers of cancer surgical procedures in 44 high-income countries were divided by the actual number of surgeons and anaesthetists in the respective countries to calculate cancer procedures per surgeon and anaesthetist ratios. Using the median (IQR) of these ratios as benchmarks, we developed a three-tiered optimal surgical and anaesthesia workforce matrix, and the predictions were extrapolated up to 2040. Our model estimates that the number of cancer cases globally with an indication for surgery will increase by 5 million procedures (52%) between 2018 (9 065 000) and 2040 (13 821 000). The greatest relative increase in surgical demand will occur in 34 low-income countries, where we also observed the largest gaps in workforce requirements. To match the median benchmark for high-income countries, the surgical workforce in these countries would need to increase by almost four times and the anaesthesia workforce by nearly 5·5 times. The greatest increase in optimal workforce requirements from 2018 to 2040 will occur in low-income countries (from 28 000 surgeons to 58 000 surgeons; 107% increase), followed by lower-middle-income countries (from 166 000 surgeons to 277 000 surgeons; 67% increase). The global demand for cancer surgery and the optimal workforce are predicted to increase over the next two decades and disproportionately affect low-income countries. These estimates provide an appropriate framework for planning the provision of surgical services for cancer worldwide. University of New South Wales Scientia Scholarship and UK Research and Innovation Global Challenges Research Fund.

Delayed access to lung cancer screening and treatment during the COVID-19 pandemic: Are we headed for a lung cancer pandemic?

Delayed access to lung cancer screening and treatment during the COVID-19 pandemic: Are we headed for a lung cancer pandemic?

The impact of the COVID-19 pandemic on cancer deaths due to delays in diagnosis in England, UK: a national, population-based, modelling study.

BackgroundSince a national lockdown was introduced across the UK in March, 2020, in response to the COVID-19 pandemic, cancer screening has been suspended, routine diagnostic work deferred, and only urgent symptomatic cases prioritised for diagnostic intervention. In this study, we estimated the impact of delays in diagnosis on cancer survival outcomes in four major tumour types.MethodsIn this national population-based modelling study, we used linked English National Health Service (NHS) cancer registration and hospital administrative datasets for patients aged 15–84 years, diagnosed with breast, colorectal, and oesophageal cancer between Jan 1, 2010, and Dec 31, 2010, with follow-up data until Dec 31, 2014, and diagnosed with lung cancer between Jan 1, 2012, and Dec 31, 2012, with follow-up data until Dec 31, 2015. We use a routes-to-diagnosis framework to estimate the impact of diagnostic delays over a 12-month period from the commencement of physical distancing measures, on March 16, 2020, up to 1, 3, and 5 years after diagnosis. To model the subsequent impact of diagnostic delays on survival, we reallocated patients who were on screening and routine referral pathways to urgent and emergency pathways that are associated with more advanced stage of disease at diagnosis. We considered three reallocation scenarios representing the best to worst case scenarios and reflect actual changes in the diagnostic pathway being seen in the NHS, as of March 16, 2020, and estimated the impact on net survival at 1, 3, and 5 years after diagnosis to calculate the additional deaths that can be attributed to cancer, and the total years of life lost (YLLs) compared with pre-pandemic data.FindingsWe collected data for 32 583 patients with breast cancer, 24 975 with colorectal cancer, 6744 with oesophageal cancer, and 29 305 with lung cancer. Across the three different scenarios, compared with pre-pandemic figures, we estimate a 7·9–9·6% increase in the number of deaths due to breast cancer up to year 5 after diagnosis, corresponding to between 281 (95% CI 266–295) and 344 (329–358) additional deaths. For colorectal cancer, we estimate 1445 (1392–1591) to 1563 (1534–1592) additional deaths, a 15·3–16·6% increase; for lung cancer, 1235 (1220–1254) to 1372 (1343–1401) additional deaths, a 4·8–5·3% increase; and for oesophageal cancer, 330 (324–335) to 342 (336–348) additional deaths, 5·8–6·0% increase up to 5 years after diagnosis. For these four tumour types, these data correspond with 3291–3621 additional deaths across the scenarios within 5 years. The total additional YLLs across these cancers is estimated to be 59 204–63 229 years.InterpretationSubstantial increases in the number of avoidable cancer deaths in England are to be expected as a result of diagnostic delays due to the COVID-19 pandemic in the UK. Urgent policy interventions are necessary, particularly the need to manage the backlog within routine diagnostic services to mitigate the expected impact of the COVID-19 pandemic on patients with cancer.FundingUK Research and Innovation Economic and Social Research Council.

The economic burden of cancer care for Syrian refugees: a population-based modelling study

Cancer represents a substantial health burden for refugees and host countries. However, no reliable data on the costs of cancer care for refugees are available, which limits the planning of official development assistance in humanitarian settings. We aimed to model the direct costs of cancer care among Syrian refugee populations residing in Jordan, Lebanon, and Turkey. In this population-based modelling study, direct cost per capita and per incident case for cancer care were estimated using generalised linear models, informed by a representative dataset of cancer costs drawn from 27 EU countries. A range of regression specifications were tested, in which cancer costs were modelled using different independent variables: gross domestic product (GDP) per capita, crude or age-standardised incidence, crude or age-standardised mortality, and total host country population size. Models were compared using the Akaike information criterion. Total cancer care costs for Syrian refugees in Jordan, Lebanon, and Turkey were calculated by multiplying the estimated direct cancer care costs (per capita) by the total number of Syrian refugees, or by multiplying the estimated direct cancer costs (per incident case [crude or age-standardised]) by the number of incident cancer cases in Syrian refugee populations. All costs are expressed in 2017 euros (€). Total cancer care costs for all 4·74 million Syrian refugees in Jordan, Lebanon, and Turkey in 2017 were estimated to be €140·23 million using the cost per capita approach, €79·02 million using the age-standardised incidence approach, and €33·68 million using the crude incidence approach. Under the lowest estimation, and with GDP and total country population as model predictors, the financial burden of cancer care was highest for Turkey (€25·18 million), followed by Lebanon (€6·40 million), and then Jordan (€2·09 million). Cancer among the Syrian refugee population represents a substantial financial burden for host countries and humanitarian agencies, such as the UN Refugee Agency. New ways to provide financial assistance need to be found and must be coupled with clear, prioritised pathways and models of care for refugees with cancer. UK Research and Innovation Global Challenges Research Fund: Research for Health in Conflict-Middle East and North Africa region (R4HC-MENA).

Attributable sources of community-acquired carriage of Escherichia coli containing β-lactam antibiotic resistance genes: a population-based modelling study

Extended-spectrum β-lactamase-producing Escherichia coli (ESBL-EC), plasmid-mediated AmpC-producing E coli (pAmpC-EC), and other bacteria are resistant to important β-lactam antibiotics. ESBL-EC and pAmpC-EC are increasingly reported in animals, food, the environment, and community-acquired and health-care-associated human infections. These infections are usually preceded by asymptomatic carriage, for which attributions to animal, food, environmental, and human sources remain unquantified. In this population-based modelling study, we collected ESBL and pAmpC gene data on the Netherlands population for 2005-17 from published datasets of gene occurrences in E coli isolates from different sources, and from partners of the ESBL Attribution Consortium and the Dutch National Antimicrobial Surveillance System. Using these data, we applied an established source attribution model based on ESBL-EC and pAmpC-EC prevalence and gene data for humans, including high-risk populations (ie, returning travellers, clinical patients, farmers), farm and companion animals, food, surface freshwater, and wild birds, and human exposure data, to quantify the overall and gene-specific attributable sources of community-acquired ESBL-EC and pAmpC-EC intestinal carriage. We also used a simple transmission model to determine the basic reproduction number (R0) in the open community. We identified 1220 occurrences of ESBL-EC and pAmpC-EC genes in humans, of which 478 were in clinical patients, 454 were from asymptomatic carriers in the open community, 103 were in poultry and pig farmers, and 185 were in people who had travelled out of the region. We also identified 6275 occurrences in non-human sources, including 479 in companion animals, 4026 in farm animals, 66 in wild birds, 1430 from food products, and 274 from surface freshwater. Most community-acquired ESBL-EC and pAmpC-EC carriage was attributed to human-to-human transmission within or between households in the open community (60·1%, 95% credible interval 40·0-73·5), and to secondary transmission from high-risk groups (6·9%, 4·1-9·2). Food accounted for 18·9% (7·0-38·3) of carriage, companion animals for 7·9% (1·4-19·9), farm animals (non-occupational contact) for 3·6% (0·6-9·9), and swimming in freshwater and wild birds (ie, environmental contact) for 2·6% (0·2-8·7). We derived an R0 of 0·63 (95% CI 0·42-0·77) for intracommunity transmission. Although humans are the main source of community-acquired ESBL-EC and pAmpC-EC carriage, the attributable non-human sources underpin the need for longitudinal studies and continuous monitoring, because intracommunity ESBL-EC and pAmpC-EC spread alone is unlikely to be self-maintaining without transmission to and from non-human sources. 1Health4Food, Dutch Ministry of Economic Affairs, and the EU's Horizon-2020 through One-Health European Joint Programme.

Attributable sources of community-acquired carriage of Escherichia coli containing β-lactam antibiotic resistance genes: a population-based modelling study

Attributable sources of community-acquired carriage of Escherichia coli containing β-lactam antibiotic resistance genes: a population-based modelling study

Long-term health benefits of stroke prevention with apixaban versus vitamin K antagonist warfarin in patients with non-valvular atrial fibrillation in Germany: a population-based modelling study

ABSTRACTBackground: Patients with non-valvular atrial fibrillation (NVAF) have a five times higher stroke risk. For more than 50 years, vitamin K antagonists (VKAs) have been the primary medication for stroke prevention. Apixaban, a non-vitamin K oral anticoagulant (NOAC), has demonstrated better efficacy and safety characteristics than the VKA warfarin in the ARISTOTLE trial. This study aims to quantify the potential societal effects of using apixaban instead of VKA in the German NVAF population from 2017 to 2030.Methods: Using an existing Markov model and a dynamic population approach, we modelled the health benefits of apixaban in patients with NVAF compared to VKA therapy in the German population from 2017 to 2030.Results: The results represent the extrapolated direct long-term health benefits of apixaban over VKA therapy for the German NVAF population. From 2017 until 2030, the use of apixaban instead of a VKA could avoid 52,185 major clinical events. This includes 15,383 non-fatal strokes or SEs, 22,483 non-fatal major bleeds, and 14,319 all-cause deaths, which correspond to 109,887 life years gained.Conclusion: This study demonstrated that using apixaban instead of VKA for stroke prevention can lead to considerable reduction in cardiovascular events.

Effects of tightening standards for indoor ozone levels on associated mortalities in urban China: a population-based modelling study

BackgroundPrevious studies have shown that exposure to ozone is associated with mortality. Reducing indoor ozone of outdoor origin may be an effective short-term method to reduce overall ozone exposure and the associated premature mortality. Here, we estimated (1) premature mortalities attributable to ozone for individuals aged 25 years and over in urban China, (2) the proportion of this mortality associated with time indoors, and (3) the mortality that might be achieved by meeting the current Chinese Indoor Air Quality Standard (IAQS) or Assessment Standard for Healthy Buildings (ASHB), as well as more stringent guidelines. MethodsOutdoor ozone concentrations were measured hourly at all 1497 government monitoring stations (as at 2015) located in 339 cities dispersed across China, and these data were used to estimate premature mortality in 2015 from circulatory and respiratory causes based on a concentration–response model derived from an extended analysis of the American Cancer Society Cancer Prevention Study II. We used estimated air exchange rates, ozone penetration factors, and ozone surface removal rates to estimate the corresponding indoor ozone concentrations for the hourly outdoor ozone measurements. Finally, we estimated mortality reductions that might be achieved in urban China by meeting different 1-h indoor ozone standards or guidelines. FindingsWe estimated that there were 61 000 premature deaths from respiratory and cardiovascular disease attributable to ozone among individuals aged 25 years or over in urban China in 2015. Indoor exposures accounted for 87% (53 000) of this total. If the current indoor ozone standards (IAQS 80 ppb; ASHB 56 ppb) were met, the reduction in total mortality would be indistinguishable from zero. To be meaningful, an indoor standard should be no higher than 30 ppb. InterpretationRegardless of whether a person is outdoors or indoors, the mortality risks associated with long-term ozone exposure are derived using data from outdoor ozone monitoring stations. Outdoor concentrations of ozone are substantially higher than the time-matched estimates of indoor ozone concentrations, reflecting the reactive chemistry of ozone indoors. Globally, guidelines for indoor ozone concentrations should be substantially lower than guidelines for outdoor ozone concentrations to account for both ozone and its indoor reaction products. FundingNatural Science Foundation of China (numbers 51420105010 and 51521005) and the National Key Research and Development Program of China (number 2017YFC0702700).

Phase of care prevalence for prostate cancer in New South Wales, Australia: A population-based modelling study.

ObjectiveTo develop a method for estimating the future numbers of prostate cancer survivors requiring different levels of care.Design, setting and participantsAnalysis of population-based cancer registry data for prostate cancer cases (aged 18–84 years) diagnosed in 1996–2007, and a linked dataset with hospital admission data for men with prostate cancer diagnosed during 2005–2007 in New South Wales (NSW), Australia.MethodsCancer registry data (1996–2007) were used to project complete prostate cancer prevalence in NSW, Australia for 2008–2017, and treatment information from hospital records (2005–2007) was used to estimate the inpatient care needs during the first year after diagnosis. The projected complete prevalence was divided into care needs-based groups. We first divided the cohort into two groups based on patient’s age (<75 and 75–84 years). The younger cohort was further divided into initial care and monitoring phases. Cause of death data were used as a proxy for patients requiring last year of life prostate cancer care. Finally, episode data were used to estimate the future number of cases with metastatic progression.ResultsOf the estimated total of 60,910 men with a previous diagnosis of prostate cancer in 2017, the largest groups will be older patients (52.0%) and younger men who require monitoring (42.5%). If current treatment patterns continue, in the first year post-diagnosis 41% (1380) of patients (<75 years) will have a radical prostatectomy, and 52.6% (1752) will be likely to have either active surveillance, external beam radiotherapy or androgen deprivation therapy. About 3% will require care for subsequent metastases, and 1288 men with prostate cancer are likely to die from the disease in 2017.ConclusionsThis method extends the application of routinely collected population-based data, and can contribute much to the knowledge of the number of men with prostate cancer and their health care requirements. This could be of significant use in planning future cancer care services and facilities in Australia.

Assessing potential population impact of statin treatment for primary prevention of atherosclerotic cardiovascular diseases in the USA: population-based modelling study

ObjectiveNew cholesterol treatment guidelines from American College of Cardiology/American Heart Association recommend statin treatment for more of US population to prevent atherosclerotic cardiovascular disease (ASCVD). It is important to assess...