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Stroke is frequently accompanied by long-term sleep disruption. We therefore aimed to assess the efficacy of digital cognitive behavioural therapy (dCBT) for insomnia to improve sleep after stroke. A parallel group randomised controlled trial was conducted remotely in participant’s homes/online. Randomisation was online with minimisation of between-group differences in age and baseline Sleep Condition Indicator (SCI-8) score. In total, 86 community dwelling stroke survivors consented, of whom 84 completed baseline assessments (39 female, mean 5.5 years post-stroke, mean 59 years of age) and were randomised to dCBT or control (sleep hygiene information). Follow-up was completed at post-intervention (mean 75 days after baseline) and 8-weeks later. The primary outcome was self-reported insomnia symptoms, as per the SCI-8 (range 0-32, lower numbers indicate more severe insomnia, reliable change 7-points) at post-intervention. There were significant improvements in SCI-8 for dCBT compared to control (intention-to-treat, dCBT n=48, control n=36, 5 imputed datasets, effect of group p≤0.02, ηp2=0.07–0.12, pooled mean difference=-3.35). Additionally, secondary outcomes showed shorter self-reported sleep onset latencies and better mood for the dCBT group, but no significant differences for self-efficacy, quality of life, or actigraphy-derived sleep parameters. Cost-effectiveness analysis found that dCBT dominates over control (non-significant cost savings and higher quality adjusted life years). No related serious adverse events were reported to the researchers. Overall, dCBT for insomnia effectively improves sleep after stroke. Future research is needed to assess earlier stages post-stroke, with a longer follow-up period to determine whether it should be included as part of routine post-stroke care.Clinicaltrials.govNCT04272892

Supplemental Digital Content is available in the text., Background and Purpose: Urgent assessment aimed at reducing stroke risk after transient ischemic attack or minor stroke is cost-effective over the short-term. However, it is unclear if the short-term impact is lost on long-term follow-up, with recurrent events being delayed rather than prevented. By 10-year follow-up of the EXPRESS study (Early Use of Existing Preventive Strategies for Stroke), previously showing urgent assessment reduced 90-day stroke risk by 80%, we determined whether that early benefit was still evident long-term for stroke risk, disability, and costs. Methods: EXPRESS was a prospective population-based before (phase 1: April 2002–September 2004; n=310) versus after (phase 2: October 2004–March 2007; n=281) study of the effect of early assessment and treatment of transient ischemic attack/minor stroke on early recurrent stroke risk, with an external control. This report assesses the effect on 10-year recurrent stroke risk, functional outcomes, quality-of-life, and costs. Results: A reduction in stroke risk in phase 2 was still evident at 10 years (55/23.3% versus 82/31.6%; hazard ratio=0.68 [95% CI, 0.48–0.95]; P=0.024), as was the impact on risk of disabling or fatal stroke (17/7.7% versus 32/13.1%; hazard ratio=0.54 [0.30–0.97]; P=0.036). These effects were due to maintenance of the early reduction in stroke risk, with neither additional benefit nor rebound catch-up after 90 days (post-90 days hazard ratio=0.88 [0.65–1.44], P=0.88; and hazard ratio=0.83 [0.42–1.65], P=0.59, respectively). Disability-free life expectancy was 0.59 (0.03–1.15; P=0.043) years higher in patients in phase 2, as was quality-adjusted life expectancy (0.49 [0.03–0.95]; P=0.036). Overall, 10-year costs were nonsignificantly higher in patients attending the phase 2 clinic ($1022 [-3865–5907]; P=0.66). The additional cost per quality-adjusted life year gained in phase 2 versus phase 1 was $2103, well below current cost-effectiveness thresholds. Conclusions: Urgent assessment and treatment of patients with transient ischemic attack or minor stroke resulted in a long-term reduction in recurrent strokes and improved outcomes, with little atrophy of the early benefit over time, representing good value for money even with a 10-year time horizon. Our results suggest that other effective acute treatments in transient ischemic attack/minor stroke in the short-term will also have the potential to have long-term benefit.

Background and Purpose: Mechanical thrombectomy (MT) has been recommended for the treatment of nonminor ischemic stroke by national and international guidelines, but cost-effectiveness evidence has been generated for only a few countries using heterogeneous evaluation methods. We estimate the cost-effectiveness of MT across 32 European countries. Methods: A Markov model was developed to estimate the cost-effectiveness of MT compared with standard care over a 5-year time horizon. Patients with ischemic stroke eligible for MT were identified from 2017 country-specific incidence data. A societal perspective was adopted, including health, social, and informal care costs, and productivity losses. Model outcomes were expressed as quality-adjusted life years. Sensitivity analyses were conducted to test the robustness of findings. Results: We identified 267 514 ischemic stroke cases that were eligible for MT treatment across 32 European countries. MT was found to be more effective and cheaper than standard care in two-thirds of the countries (21/32) and cost-effective in all but one country (Bulgaria). Across Europe, the intervention was estimated to produce over 101 327 additional quality-adjusted life years (95% uncertainty interval, 65 180–149 085) and cost savings of $981 million (€868 million, 95% uncertainty interval, −1544 to 2564) and of $1.7 billion (€1.5 billion, 95% uncertainty interval, −1.2 to 3.6) in health and social care and societal costs, respectively. Conclusions: MT is highly likely to be cost-effective compared with standard care across Europe as a whole and in the vast majority of European countries.

BackgroundPatients with primary intracerebral haemorrhage (ICH) are at increased long-term risks of recurrent stroke and other comorbidities. However, available estimates come predominantly from hospital-based studies with relatively short follow-up. Moreover, there are also uncertainties about the influence of ICH location on risks of recurrent stroke, disability, dementia and quality of life.MethodsIn a population-based study (Oxford Vascular Study/2002–2018) of patients with a first ICH with follow-up to 10 years, we determined the long-term risks of recurrent stroke, disability, quality of life, dementia and hospital care costs stratified by haematoma location.ResultsOf 255 cases with primary ICH (mean/SD age 75.5/13.1), 109 (42.7%) had lobar ICH, 144 (56.5%) non-lobar ICH and 2 (0.8%) had uncertain location. Annual rates of recurrent ICH were higher after lobar versus non-lobar ICH (lobar=4.0%, 2.7–7.2 vs 1.1%, 0.3–2.8; p=0.02). Moreover, cumulative rate of dementia was also higher for lobar versus non-lobar ICH (n/% lobar=20/36.4% vs 16/20.8%, p=0.047), and there was a higher proportion of disability at 5 years in survivors (15/60.0% vs 9/31.0%, p=0.03). The 10-year quality-adjusted life years (QALYs) were also lower after lobar versus non-lobar ICH (2.9 vs 3.8 for non-lobar, p=0.04). Overall, the mean 10-year censor-adjusted costs were £19 292, with over 80% of costs due to inpatient hospital admission costs, which did not vary by haematoma location (p=0.90).ConclusionCompared with non-lobar ICH, the substantially higher 10-year risks of recurrent stroke, dementia and lower QALYs after lobar ICH highlight the need for more effective prevention for this patient group.

The aim of this study was to explore the cost-effectiveness of home-based versus centre-based rehabilitation in stroke patients across Europe. A state-transition cohort model was developed to simulate the impact of the intervention in 32 European countries. A cost-utility analysis was conducted from a societal perspective including healthcare, social care and informal care costs, and productivity losses. Health outcomes were expressed as QALYs. Sensitivity analyses were conducted concerning model input values and structural assumptions. Data were obtained from a population-based cohort and previously published studies. Across Europe, over 855,000 patients with stroke would be eligible for rehabilitation in 2017. Europe-wide implementation of home-based rehabilitation was estimated to produce 61,888 additional QALYs (95% CI: 3,609 to 118,679) and cost savings of €237 million (95% CI: -237 to 1,764) and of €352 million (95% CI: -340 to 2,237) in health- and social-care and societal costs, respectively. Under base case assumptions, home-based rehabilitation was found highly likely to be cost-effective (>90%), compared to centre-based rehabilitation, in most European countries (29 out of 32). Evidence from this study suggests that a shift from a centre-based to a home-based approach to stroke rehabilitation is likely to be good value for money in most European countries. Further research should be conducted to assess the generalisability of these findings to local settings.

Background Pleurodesis is done as an in-patient procedure to control symptomatic recurrent malignant pleural effusion (MPE) and has a success rate of 75–80%. Thoracic ultrasonography has been shown in a small study to predict pleurodesis success early by demonstrating cessation of lung sliding (a normal sign seen in healthy patients, lung sliding indicates normal movement of the lung inside the thorax). We aimed to investigate whether the use of thoracic ultrasonography in pleurodesis pathways could shorten hospital stay in patients with MPE undergoing pleurodesis. Methods The Efficacy of Sonographic and Biological Pleurodesis Indicators of Malignant Pleural Effusion (SIMPLE) trial was an open-label, randomised controlled trial done in ten respiratory centres in the UK and one respiratory centre in the Netherlands. Adult patients (aged ≥18 years) with confirmed MPE who required talc pleurodesis via either a chest tube or as poudrage during medical thorascopy were eligible. Patients were randomly assigned (1:1) to thoracic ultrasonography-guided care or standard care via an online platform using a minimisation algorithm. In the intervention group, daily thoracic ultrasonography examination for lung sliding in nine regions was done to derive an adherence score: present (1 point), questionable (2 points), or absent (3 points), with a lowest possible score of 9 (preserved sliding) and a highest possible score of 27 (complete absence of sliding); the chest tube was removed if the score was more than 20. In the standard care group, tube removal was based on daily output volume (per British Thoracic Society Guidelines). The primary outcome was length of hospital stay, and secondary outcomes were pleurodesis failure at 3 months, time to tube removal, all-cause mortality, symptoms and quality-of-life scores, and cost-effectiveness of thoracic ultrasonography-guided care. All outcomes were assessed in the modified intention-to-treat population (patients with missing data excluded), and a non-inferiority analysis of pleurodesis failure was done in the per-protocol population. This trial was registered with ISRCTN, ISRCTN16441661. Findings Between Dec 31, 2015, and Dec 17, 2019, 778 patients were assessed for eligibility and 313 participants (165 [53%] male) were recruited and randomly assigned to thoracic ultrasonography-guided care (n=159) or standard care (n=154). In the modified intention-to-treat population, the median length of hospital stay was significantly shorter in the intervention group (2 days [IQR 2–4]) than in the standard care group (3 days [2–5]; difference 1 day [95% CI 1–1]; pInterpretation Thoracic ultrasonography-guided care for pleurodesis in patients with MPE results in shorter hospital stay (compared with the British Thoracic Society recommendation for pleurodesis) without reducing the success rate of the procedure at 3 months. The data support consideration of standard use of thoracic ultrasonography in patients undergoing MPE-related pleurodesis. Funding Marie Curie Cancer Care Committee

BackgroundAmbulatory management of primary spontaneous pneumothorax has been shown to reduce initial hospitalisation, but at the expense of increase adverse events. As a result, questions remain about the cost-effectiveness of this option.ObjectivesA within-trial economic evaluation alongside a randomised controlled trial was performed to assess the cost-effectiveness of ambulatory care when compared with standard guideline-based management.MethodsPatients were randomly assigned to treatment with either an ambulatory device or standard guideline-based management (aspiration, standard chest tube insertion or both). Follow-up was 12 months. Outcomes included healthcare resource use and costs, quality of life, quality-adjusted life-years (QALYs) and cost-effectiveness.Results236 patients were recruited and randomly assigned to ambulatory care (n=117) and standard care (n=119). After multiple imputation for missing data, patients in the ambulatory care group had significantly lower National Health Service healthcare costs (−£788, 95% CI difference: −1527 to −50; p=0.037) than those in the standard care group. There were no differences in the number of QALYs gained (mean difference: −0.001, 95% CI difference: −0.032 to 0.030; p=0.95). When standard care was compared with ambulatory care, the incremental cost-effectiveness ratio was £799 066 per QALY gained, well above current thresholds of cost-effectiveness. As a result, the probability of ambulatory care being cost-effective was 0.93.ConclusionOutpatient ambulatory management is highly likely to be a cost-effective option in the management of primary pneumothorax.Trial registration numberISRCTN79151659.

Background Long-term antiplatelet treatment is associated with major bleeding. Aims To determine the costs associated with major bleeding in patients treated with aspirin-based antiplatelet treatment for secondary prevention of vascular events without routine prescription of proton-pump inhibitors and to estimate the likely long-term savings from routine co-prescription. Methods In a prospective population-based cohort study of TIA, ischemic stroke, and MI treated with antiplatelet drugs, we evaluated hospital care costs associated with bleed management during 10-year follow-up. Bleeding-associated costs were averaged across all patients. For upper GI-bleeds, mean costs were compared with the cost of routine co-prescription of proton-pump inhibitor. Results Among 3166 patients on antiplatelet therapy with 405 first bleeding events, the average cost of major bleeding was $13,093 (S.D. 20,501), with similar costs for upper GI bleeds and intracranial bleeds ( p = 0.235). However, total costs among the 3166 patients were higher for upper GI bleeds ($1,158,385 vs. $740,123). Averaged across all patients, the 10-year cost of major bleeding was $838 (95%CI: 680–1007), $411 due to upper GI bleeding, the cost of which increased from $175 in those aged Conclusions In secondary prevention with aspirin-based antiplatelet treatment without routine proton-pump inhibitor use, the long-term costs of upper-GI bleeding at age ≥75 years are much higher than at younger age groups, and are at least 10-fold greater than the drug cost of routine co-prescription of proton-pump inhibitor.

BackgroundLate functional improvement between 3 and 12 months poststroke occurs in about one in four patients with ischaemic stroke, more commonly in lacunar strokes. It is unknown whether this late improvement is associated with better long-term clinical or health economic outcomes.MethodsIn a prospective, population-based cohort of 1-year ischaemic stroke survivors (Oxford Vascular Study; 2002–2014), we examined changes in functional status (modified Rankin Scale (mRS), Rivermead Mobility Index (RMI), Barthel Index (BI)) from 3 to 12 months poststroke. We used Cox regressions adjusted for age, sex, 3-month disability and stroke subtype (lacunar vs non-lacunar) to examine the association of late improvement (by ≥1 mRS grades, ≥1 RMI points and/or ≥2 BI points between 3 and 12 months) with 5-year mortality and institutionalisation. We used similarly adjusted generalised linear models to examine association with 5-year healthcare/social-care costs.ResultsAmong 1288 one-year survivors, 1135 (88.1%) had 3-month mRS >0, of whom 319 (28.1%) demonstrated late functional improvement between 3 and 12 months poststroke. Late improvers had lower 5-year mortality (aHR per mRS=0.68, 95% CI 0.51 to 0.91, p=0.009), institutionalisation (aHR 0.48, 0.33 to 0.72, pConclusionLate functional improvement poststroke is associated with lower 5-year mortality, institutionalisation rates and healthcare/social care costs. These findings should motivate patients and clinicians to maximise late recovery in routine practice, and to consider extending access to proven rehabilitative therapies during the first year poststroke.

Introduction: In 2017, 1.5 million people were diagnosed with stroke, 9 million were living with stroke and 0.4 million died because of stroke in 32 European countries. We estimate the economic burden of stroke across these countries in 2017. Patients and methods: In a population-based cost analysis, we evaluated the cost of stroke. We estimated overall health and social care costs from expenditure on care in the primary, outpatient, emergency, inpatient and nursing/residential care settings, and pharmaceuticals. Additionally, we estimated the costs of unpaid care provided by relatives or friends of patients, lost earnings due to premature death and costs associated with individuals who temporarily or permanently left employment because of illness. Results: In 2017 stroke cost the 32 European countries under analysis €60 billion, with health care accounting for €27 billion (45%), representing 1.7% of health expenditure. Adding the costs of social care (€5 billion), annual stroke-related care costs were equivalent to €59 per citizen, varying from €11 in Bulgaria to €140 in Finland. Productivity losses cost €12 billion, equally split between early death and lost working days. A total of €1.3 billion hours of informal care were provided to stroke survivors, costing Europe €16 billion. Conclusion: Our study provides a snapshot of the economic consequences posed by stroke to 32 European countries in 2017. It also strengthens and updates the evidence we have gathered over the last 15 years, indicating that the costs of stroke are rising, partly due to an ageing population.

Supplemental Digital Content is available in the text., Background and Purpose— Patients with premorbid disability, generally defined as modified Rankin Scale (mRS) score ≥2, are often excluded from trials of acute stroke therapies. However, increased disability in such patients will adversely affect long-term outcomes if treatments are withheld in routine practice. We assessed the extent to which increased disability poststroke influences 5-year mortality, institutionalization, and costs in premorbidly disabled patients. Methods— In a population-based, prospective cohort of patients with ischemic stroke (OXVASC [Oxford Vascular Study], 2002–2014), we tracked mortality, institutionalization, and healthcare/social-care costs during follow-up. We compared 5-year mortality and poststroke institutionalization (Cox regressions) and 5-year healthcare/social-care costs (generalized linear model) in 3-month survivors with premorbid mRS of 2 to 4 (excluding extreme disability, mRS=5), based on the degree of change in mRS(ΔmRS) from prestroke to 3 months poststroke, adjusting analyses for age/sex/initial National Institutes of Health Stroke Scale. Results— Among 1607 patients, 530 (33.0%) had premorbid mRS of 2 to 4. Only 2 premorbidly disabled patients received thrombolysis, but 421 (79.4%) were alive at 3 months. ΔmRS was independently associated with 5-year mortality/institutionalization (adjusted hazard ratio for ΔmRS=1 versus 0: 1.59; 95% CI, 1.20–2.11; ΔmRS=2: 2.39; 95% CI, 1.62–3.53; ΔmRS=3: 4.12; 95% CI, 1.98–8.60; P

Importance Malignant pleural effusion (MPE) is challenging to manage. Talc pleurodesis is a common and effective treatment. There are no reliable data, however, regarding the optimal method for talc delivery, leading to differences in practice and recommendations. Objective To test the hypothesis that administration of talc poudrage during thoracoscopy with local anesthesia is more effective than talc slurry delivered via chest tube in successfully inducing pleurodesis. Design, Setting, and Participants Open-label, randomized clinical trial conducted at 17 UK hospitals. A total of 330 participants were enrolled from August 2012 to April 2018 and followed up until October 2018. Patients were eligible if they were older than 18 years, had a confirmed diagnosis of MPE, and could undergo thoracoscopy with local anesthesia. Patients were excluded if they required a thoracoscopy for diagnostic purposes or had evidence of nonexpandable lung. Interventions Patients randomized to the talc poudrage group (n = 166) received 4 g of talc poudrage during thoracoscopy while under moderate sedation, while patients randomized to the control group (n = 164) underwent bedside chest tube insertion with local anesthesia followed by administration of 4 g of sterile talc slurry. Main Outcomes and Measures The primary outcome was pleurodesis failure up to 90 days after randomization. Secondary outcomes included pleurodesis failure at 30 and 180 days; time to pleurodesis failure; number of nights spent in the hospital over 90 days; patient-reported thoracic pain and dyspnea at 7, 30, 90, and 180 days; health-related quality of life at 30, 90, and 180 days; all-cause mortality; and percentage of opacification on chest radiograph at drain removal and at 30, 90, and 180 days. Results Among 330 patients who were randomized (mean age, 68 years; 181 [55%] women), 320 (97%) were included in the primary outcome analysis. At 90 days, the pleurodesis failure rate was 36 of 161 patients (22%) in the talc poudrage group and 38 of 159 (24%) in the talc slurry group (adjusted odds ratio, 0.91 [95% CI, 0.54-1.55]; P = .74; difference, –1.8% [95% CI, –10.7% to 7.2%]). No statistically significant differences were noted in any of the 24 prespecified secondary outcomes. Conclusions and Relevance Among patients with malignant pleural effusion, thoracoscopic talc poudrage, compared with talc slurry delivered via chest tube, resulted in no significant difference in the rate of pleurodesis failure at 90 days. However, the study may have been underpowered to detect small but potentially important differences. Trial Registration ISRCTN Identifier: ISRCTN47845793

Introduction The economic cost of osteoarthritis (OA) is high. At least 4.4 million people have hand OA in the UK. Symptomatic thumb base OA affects 20% of people over 55 years, causing more pain, work and functional disability than OA elsewhere in the hand. Most evidence-based guidelines recommend splinting for hand OA. Splints that support or immobilise the thumb base are routinely used despite there being limited evidence on their effectiveness. The potential effects of placebo interventions in OA are acknowledged, but few studies investigate the clinical efficacy of rehabilitation interventions nor the impact of any placebo effects associated with splints. Methods and analysis Participants aged 30 years and over with symptomatic thumb base OA will be recruited into the trial from secondary care occupational therapy and physiotherapy centres. Following informed consent, participants will complete a baseline questionnaire and then be randomised into one of three treatment arms: a self-management programme, a self-management programme plus a verum thumb splint or a self-management programme plus a placebo thumb splint. The primary outcome is the Australian Canadian Osteoarthritis Hand Index (AUSCAN) hand pain scale. The study endpoint is 8 weeks after baseline. Baseline assessments will be carried out prior to randomisation and outcomes collected at 4, 8 and 12 weeks. Cost-effectiveness analysis will be conducted and individual qualitative interviews conducted with up to 40 participants after 8 weeks to explore perceptions and outcome expectations of verum and placebo splints and exercise. Ethics and dissemination South Central—Oxford C Research Ethics Committee approved this study (16/SC/0188). The findings will be disseminated to health professional conferences, journals and lay publications for patient organisations. The research will contribute to improving the management of thumb base OA and help clinicians and patients make informed decisions about the value of different interventions. Trial registration number ISRCTN54744256.

We thank Dr. Bruno for the comment on our article.1 Although our focus was on how the ordinal and dichotomous forms of the 3-month modified Rankin Scale (mRS) relate to long-term outcomes and costs, we did exclude patients with prestroke mRS >1 and >2 to verify our findings in additional analyses. We agree that there is a need to establish more uniform methods for ascertainment of prestroke disability, which currently relies on measures like the mRS that were not originally designed for this purpose and may be vulnerable to confounding factors, such as sex differences in premorbid mRS ratings.

Introduction: Administrative hospital diagnostic coding data are increasingly being used in identifying incident and prevalent stroke cases, for outcome audit and for ‘big data’ research. Validity of administrative coding has varied in previous studies, but little is known about the temporal trends of coding accuracy, which could bias analyses. Patients and Methods: Using all incident and recurrent strokes in a population-based cohort (Oxford Vascular Study/OXVASC) with multiple sources of ascertainment as the reference, we determined the temporal trends in sensitivity and positive predictive value of hospital diagnostic codes for identifying acute stroke from 2002 to 2017. Results: Of 1883 hospitalised strokes, 1341 (71.2%) were correctly identified by coding. Sensitivity of coding improved over time for all strokes (ptrend = 0.005) and for incident cases (ptrend = 0.002). Of 1995 apparent stroke admissions identified by International Classification of Disease-10 stroke codes (I60–I68), 1588 (79.6%) used the stroke-specific codes (I60–I61/I63–I64). Positive predictive value was higher with the use of specific codes (83.2% vs. 69.2% for all codes) and highest if combined with the first admission only (88.5%), particularly during more recent time periods (2014–2017 = 90.3%). Of 2254 OXVASC incident strokes, 833 (37.0%) were not hospitalised. Sensitivity of coding increased over time for non-disabling stroke (ptrend = 0.001), but not for disabling/fatal stroke (ptrend = 0.40). Conclusions: Although accuracy of hospital diagnostic coding for identifying acute strokes improved over the last 15 years, residual insensitivity supports linkage to other sources in large epidemiological studies. Moreover, differences in the time trends of coding sensitivity in relation to stroke severity might bias studies of trends in stroke outcome if only administrative coding is used.

The MIST2 (Second Multicentre Intrapleural Sepsis Trial) trial showed that combined intrapleural use of tissue plasminogen activator (t-PA) and recombinant human DNase was effective when compared with single agents or placebo. However, the treatment costs are significant and overall cost-effectiveness of combined therapy remains unclear.An economic evaluation of the MIST2 trial was performed to assess the cost-effectiveness of combined therapy. Costs included were those related to study medications, initial hospital stay and subsequent hospitalisations. Outcomes were measured in terms of life-years gained. All costs were reported in euro and in 2016 prices.Mean annual costs were lowest in the t-PA–DNase group (EUR 10 605 for t-PA, EUR 17 856 for DNase, EUR 13 483 for placebo and EUR 7248 for t-PA–DNase; p=0.209). Mean 1-year life expectancy was 0.988 for t-PA, 0.923 for DNase, and 0.969 for both placebo and t-PA–DNase (p=0.296). Both DNase and placebo were less effective, in terms of life-years gained, and more costly than t-PA. When placebo was compared with t-PA–DNase, the incremental cost per life-year gained of placebo was EUR 1.6 billion, with a probability of 0.85 of t-PA–DNase being cost-effective.This study demonstrates that combined t-PA–DNase is likely to be highly cost-effective. In light of this evidence, a definitive trial designed to facilitate a thorough economic evaluation is warranted to provide further evidence on the cost-effectiveness of this promising combined intervention.

BACKGROUND AND OBJECTIVE: Malignant pleural effusion is associated with morbidity and mortality. A randomized controlled trial previously compared clinical outcomes and resource use with indwelling pleural catheter (IPC) and talc pleurodesis in this population. Using unpublished quality of life data, we estimate the cost-effectiveness of IPC compared with talc pleurodesis. METHODS: Healthcare utilization and costs were captured during the trial. Utility weights produced by the EuroQol Group five-dimensional three-level questionnaire and survival were used to determine quality-adjusted life-years (QALYs) gained. The incremental cost-effectiveness ratio (ICER) was calculated over the 1-year trial period. Sensitivity analysis used patient survival data and modelled additional nursing time required per week for catheter drainage. RESULTS: Utility scores, cost and QALYs gained did not differ significantly between groups. The ICER for IPC compared with talc was favorable at $US10 870 per QALY gained. IPC was less costly with a probability exceeding 95% of being cost-effective when survival was

Background: We recently demonstrated that late functional improvement between 3-12 months post-stroke occurs in about one in four patients with ischaemic stroke, more commonly in lacunar strokes. It is unknown whether this late improvement is associated with better long-term clinical or health economic outcomes. Methods: In 1-year ischaemic stroke survivors of the Oxford Vascular Study (OXVASC; 2002-2014), we examined changes in functional status (modified Rankin Scale[mRS], Rivermead Mobility Index[RMI], Barthel Index[BI]) from 3-12 months post-stroke. We used Cox regressions adjusted for age, sex, 3-month disability, and stroke subtype (lacunar vs non-lacunar) to examine the association of late functional improvement (by ≥1 mRS grades, ≥1 RMI points, and/or ≥2 BI points between 3-12 months) with 5-year mortality and institutionalization (admission to nursing or residential care home). We used similarly adjusted generalized linear models to examine the association with 5-year health/social-care costs. Analyses were restricted to patients capable of showing improvement per the relevant scale (mRS>0, RMI Results: Among 1,288 1-year survivors, 1,135 had 3-month mRS>0, of whom 319 (28.1%) demonstrated late functional improvement between 3-12 months post-stroke. 1-year survivors who demonstrated late functional improvement between 3-12 months per the mRS had lower 5-year mortality (aHR 0.68, 95%CI 0.51-0.91, p=0.009), were less likely to be institutionalized at 5-years (aHR 0.48, 0.33-0.72, p Conclusions: Late functional improvement post-stroke is associated with lower 5-year mortality, institutionalization rates, and health/social-care costs. These findings should motivate patients and clinicians to maximize late recovery in routine practice, and consider access to rehabilitative services for at least 1-year post-stroke.

Background: Patients with pre-morbid disability – generally defined as modified Rankin Scale score (mRS)≥2 – are often excluded from trials of acute stroke therapies. However, increased disability in such patients will adversely affect long-term outcomes if treatments are withheld in routine practice. We assessed the extent to which increased disability post-stroke influences 5-year mortality, institutionalization, and costs in pre-morbidly disabled patients. Methods: In a population-based, prospective cohort of ischaemic stroke patients (Oxford Vascular Study, 2002-2014), we tracked mortality, institutionalization, and health/social-care costs during follow-up. We compared 5-year mortality and/or post-stroke institutionalization (Cox regressions), and 5-year health/social-care costs (generalized linear model) in 3-month survivors with pre-morbid mRS 2-4 (excluding extreme disability, mRS=5), based on degree of change in mRS(ΔmRS) from pre-stroke to 3-months post-stroke, adjusting analyses for age/sex/initial NIHSS. Results: Among 1,607 patients, 530(33.0%) had pre-morbid mRS=2-4. Only 2 pre-morbidly disabled patients received thrombolysis, but 421(79.4%) were alive at 3-months. ΔmRS was independently associated with 5-year mortality/institutionalization (aHR for ΔmRS=1 vs 0: 1.59,1.20-2.11; ΔmRS=2: 2.39,1.62-3.53; ΔmRS=3: 4.12,1.98-8.60,p Conclusions: Stroke patients with pre-morbid disability have higher mortality, institutionalization, and costs if they accumulate additional disability due to the stroke. These findings highlight the long-term outcomes expected if acute interventions are routinely withheld in patients with mild-moderate pre-morbid disability, and suggest that trials/registries should include such patients.

Background: Dementia and institutionalization are known long-term complications of stroke, but the extent to which post-stroke disability – as captured by the modified Rankin Scale (mRS) in trials – predicts these outcomes remains unclear. Quantifying this relationship can inform prognostication and cost-effectiveness analyses. Methods: In consecutive 3-month survivors of ischaemic stroke in a population-based prospective cohort (Oxford Vascular Study;2002-2014), we established post-stroke dementia (excluding pre-stroke dementia) and tracked institutionalization (admission to nursing or residential care home) through overlapping methods of cognitive testing and interview-based assessments of patients and carers, and ongoing searches of primary care and hospital records. We related 3-month mRS to 5-year dementia and institutionalization using age/sex-adjusted Cox and logistic regressions (repeated excluding premorbid mRS>2), and compared the area under the receiver operating characteristics curves (AUC) for logistic models versus age/sex alone. Results: Among 1,425 survivors, 3-month mRS independently predicted 5-year dementia and institutionalization whether or not those with premorbid disability were excluded, with mRS of 3-5 carrying higher hazards of each outcome than mRS 0-2; aHR(dementia)=3.37, 95%CI 2.63-4.32, aHR(institutionalization)=6.33, 4.53-8.85, p Conclusions: 3-month mRS strongly predicts post-stroke dementia and institutionalization, both of which should be considered in cost-effectiveness analyses of acute treatments. The incremental rise in hazard with each step up the mRS ladder further supports using ordinal analysis of the mRS in trials.

Background: Outcome in acute stroke trials is often based on short-term mRS, but there are few data from prospective population-based studies on how this measure translates into long-term outcomes. We evaluated the relationship between 1-month mRS and 5-year disability, death, quality of life, and healthcare cost in a population-based cohort study. Methods: In 3-month survivors of ischaemic stroke in the Oxford Vascular Study (2002-2014), we used logistic regression to determine predictors of 5-year death/disability, including mRS score at 1 month, age, and sex. The analyses were repeated for different subgroups, including thrombectomy-eligible, atrial fibrillation-related, and lacunar strokes. Hospital resource use and institutionalization data up to 31 August 2015 were collected, and mean censor-adjusted costs were reported with 95% CIs from 1000 bootstrap estimates. A general gamma linear model was used with 1-month mRS controlling for age, sex, and comorbidities. 5-year quality-adjusted life expectancies (QALE) generated from survival data and EQ-5D-derived utility scores were stratified by 1-month mRS. Results: Among 1,425 survivors, mRS score was a strong independent predictor of 5-year death/disability, with a step-change from mRS 2 to 3: adjusted odds ratio for mRS 3-5 vs 0-2: 35.57, 95%CI 17.40-72.71, p Conclusions: Our results reaffirm the practice in acute stroke trials of using short-term mRS as the primary outcome measure. The step change between mRS 2 and 3 for both death/disability and healthcare costs supports the traditional dichotomous outcome, but the incremental drop in QALE with each mRS grade shows that ordinal analysis is also valid.

OBJECTIVE: To evaluate the 5-year impact of stroke and TIA on utility and quality-adjusted survival. METHODS: TIA and stroke patients from a UK population-based study (Oxford Vascular Study) were recruited from 2002 to 2007, and followed up until 2012. Quality of life was assessed over 5 years using the EQ-5D (EuroQol-5 Dimensions), with responses converted into utilities ranging from -0.59 (worse than death) to 1 (perfect health), using UK population valuations. Utilities for stroke and TIA patients were compared with those in matched controls obtained from the 2006 Health Survey for England. Five-year quality-adjusted life years were estimated by combining utility and survival information. RESULTS: Four hundred forty TIA and 748 stroke patients were ascertained and included. Utility remained constant at approximately 0.78 over the 5 years after TIA. Utility improved from 0.64 one month after stroke to 0.70 at 6 months (p = 0.006), remaining at approximately 0.70 thereafter. Matched controls had considerably higher utility levels than stroke/TIA patients (0.85, p < 0.001). Event severity and recurrent stroke were significant predictors of decreased long-term utility. Five-year quality-adjusted life expectancy was 3.32 (95% confidence interval: 3.22-3.48) quality-adjusted life years after TIA and 2.21 (2.15-2.37) after stroke, varying considerably by severity (minor: 2.94; moderate: 1.65; and severe: 0.70). CONCLUSION: Quality-adjusted survival is low over the 5 years after stroke and TIA, with severity and recurrent stroke being major predictors. There remains considerable scope for improvements in acute treatment and secondary prevention to improve the quality of life after TIA and stroke.

Background and Purpose— Long-term outcome information after transient ischemic attack (TIA) and stroke is required to help plan and allocate care services. We evaluated the impact of TIA and stroke on disability and institutionalization over 5 years using data from a population-based study. Methods— Patients from a UK population-based cohort study (Oxford Vascular Study) were recruited from 2002 to 2007 and followed up to 2012. Patients were followed up at 1, 6, 12, 24, and 60 months postevent and assessed using the modified Rankin scale. A multivariate regression analysis was performed to assess the predictors of disability postevent. Results— A total of 748 index stroke and 440 TIA cases were studied. For patients with TIA, disability levels increased from 14% (63 of 440) premorbidly to 23% (60 of 256) at 5 years ( P =0.002), with occurrence of subsequent stroke being a major predictor of disability. For stroke survivors, the proportion disabled (modified Rankin scale >2) increased from 21% (154 of 748) premorbidly to 43% (273 of 634) at 1 month ( P Conclusions— Our results show that 70% of patients with stroke are either dead or disabled 5 years after the event. Thus, there remains considerable scope for improvements in acute treatment and secondary prevention to reduce postevent disability and institutionalization.

Background and Purpose— Few studies have evaluated long-term costs after stroke onset, with almost no cost data for transient ischemic attack (TIA). We studied hospital costs during the 5 years after TIA or stroke in a population-based study. Methods— Patients from a United Kingdom population-based cohort study (Oxford Vascular Study) were recruited from 2002 to 2007. Analysis was based on follow-up until 2010. Hospital resource usage was obtained from patient hospital records and valued using 2008/2009 unit costs. Because not all patients had full 5-year follow-up, we used nonparametric censoring techniques. Results— Among 485 TIA and 729 stroke patients ascertained and included, mean censor-adjusted 5-year hospital costs after index stroke were $25741 (95% confidence interval, 23659–27914), with costs varying considerably by severity: $21134 after minor stroke; $33119 after moderate stroke; and $28552 after severe stroke. For the 239 surviving stroke patients who had reached final follow-up, mean costs were $24383 (95% confidence interval, 20156–28595), with more than half of costs ($12972) being incurred in the first year after the event. After index TIA, the mean censor-adjusted 5-year costs were $18091 (95% confidence interval, 15947–20258). A multivariate analysis showed that event severity, recurrent stroke, and coronary events after the index event were independent predictors of 5-year costs. Differences by stroke subtype were mostly explained by stroke severity and subsequent events. Conclusions— Long-term hospital costs after TIA and stroke are considerable, but they are mainly incurred during the first year after the index event. Event severity and experiencing subsequent stroke and coronary events after the index event accounted for much of the increase in costs.

In this two-part series on the economic evaluation of different health interventions, the methods for measuring costs and valuing benefits have been outlined and the methods by which the costs and benefits are collated within an economic evaluation framework have been described. Economic evaluation should be seen as a decision-making framework that renders the costs and benefits of any intervention or service explicit. In doing so, informed decisions can be made about the allocation of resources to various programmes. The outcome or benefit measure chosen will decide the actual 'type' of economic evaluation carried out. If a number of outcome measures are chosen, a variety of economic evaluations may be performed and the results used as an aid to decision making. By ensuring that the opportunity costs of programmes are minimised, this should ensure the maximisation of well-being to society given limited resources.

Objective: To estimate the economic burden of cardiovascular disease (CVD) in the United Kingdom, including health and non-healthcare costs, and the proportion of total CVD cost due to coronary heart disease (CHD) and cerebrovascular disease. Design and setting: Prevalence-based approach to assess CVD-related costs from a societal perspective. Patients: All UK residents in 2004 with CVD ( International classification of diseases , 10th revision (ICD-10) codes I00–I99) and subgroups with CHD (ICD-10 codes I20–I25) or cerebrovascular disease (ICD-10 codes I60–I69). Main outcome measures: Healthcare costs were estimated from expenditure on community health and social services, accident and emergency care, hospital care, rehabilitation and drugs. Non-healthcare costs were estimated from data on informal care and from productivity losses arising from morbidity and premature death. Results: CVD cost the UK economy £29.1 billion in 2004, with CHD and cerebrovascular disease accounting for 29% (£8.5 billion) and 27% (£8.0 billion) of the total, respectively. The major cost component of CVD was health care, which accounted for 60% of the cost, followed by productivity losses due to mortality and morbidity, accounting for 23%, with the remaining 17% due to informal care-related costs. Conclusions: CVD is a leading public health problem in the UK measured by the economic burden of disease. This study identified the size and main components of that burden, and will help to inform decisions about research priorities and to monitor the impact of policy initiatives.

Background and purpose: A UK government review recommended that the impact of disease on the population and economy should be assessed to inform health research priorities. This study aims to quantify UK governmental and charity research funding for dementia, cancer, coronary heart disease (CHD) and stroke in 2007/08 and assess whether the levels of research expenditure are aligned with disease and economic burden. Methods: We identified UK governmental agencies and charities providing health research funding and determined their levels of funding for dementia, cancer, CHD and stroke. Research funding levels were compared to the number of cases, disability-adjusted life years (DALYs) and economic burden. Economic costs were estimated using data on morbidity, mortality, health and social care use, private costs and other related indicators. Results: Research funding to the four diseases was £833 million, of which £590 million (71%) was devoted to cancer, £169 million (20%) to CHD, £50 million (6%) to dementia and £23 million (4%) to stroke. Cancer received £482 in research funding per 1000 DALYs lost, CHD received £266, dementia received £166, with stroke receiving £71. In terms of economic burden, for every £1 million of health and social care costs attributable to each disease, cancer received £129 269 in research funding, CHD received £73 153, stroke received £8745 and dementia received £4882. Conclusions: Most health research funding in the UK is currently directed towards cancer. When compared to their burden, our analysis suggests that research spending on dementia and stroke is severely underfunded in comparison with cancer and CHD.

Background. Mapping disease-specific instruments into generic health outcomes or utility values is an expanding field of interest in health economics. This article constructs an algorithm to translate the modified Rankin scale (mRS) into EQ-5D utility values. Methods. mRS and EQ-5D information was derived from stroke or transient ischemic attack (TIA) patients identified as part of the Oxford Vascular study (OXVASC). Ordinary least squares (OLS) regression was used to predict UK EQ-5D tariffs from mRS scores. An alternative method, using multinomial logistic regression with a Monte Carlo simulation approach (MLogit) to predict responses to each EQ-5D question, was also explored. The performance of the models was compared according to the magnitude of their predicted-to-actual mean EQ-5D tariff difference, their mean absolute and mean squared errors (MAE and MSE), and associated 95% confidence intervals (CIs). Out-of-sample validation was carried out in a subset of coronary disease and peripheral vascular disease (PVD) patients also identified as part of OXVASC but not used in the original estimation. Results. The OLS and MLogit yielded similar MAE and MSE in the internal and external validation data sets. Both approaches also underestimated the uncertainty around the actual mean EQ-5D tariff producing tighter 95% CIs in both data sets. Conclusions. The choice of algorithm will be dependent on the study aim. Individuals outside the United Kingdom may find it more useful to use the multinomial results, which can be used with different country-specific tariff valuations. However, these algorithms should not replace prospective collection of utility data.

BACKGROUND: The International Carotid Stenting Study was a multicenter randomized trial in which patients with symptomatic carotid artery stenosis were randomly allocated to treatment by carotid stenting or endarterectomy. Economic evidence comparing these treatments is limited and inconsistent. AIMS:We compared the cost-effectiveness of stenting versus endarterectomy using International Carotid Stenting Study data. METHODS:We performed a cost-utility analysis estimating mean costs and quality-adjusted life years per patient for both treatments over a five-year time horizon based on resource use data and utility values collected in the trial. Costs of managing stroke events were estimated using individual patient data from a UK population-based study (Oxford Vascular Study). RESULTS:Mean costs per patient (95% CI) were USD10,477 (USD9669 to USD11,285) in the stenting group (N = 853) and USD9669 (USD8835 to USD10,504) in the endarterectomy group (N = 857). There were no differences in mean quality-adjusted life years per patient (3.247 (3.160 to 3.333) and 3.228 (3.150 to 3.306), respectively). There were no differences in adjusted costs between groups (mean incremental costs for stenting versus endarterectomy $736 (95% CI -USD353 to USD1826)) or adjusted outcomes (mean quality-adjusted life years gained -0.010 (95% CI -0.117 to 0.097)). The incremental net monetary benefit for stenting versus endarterectomy was not significantly different from zero at the maximum willingness to pay for a quality-adjusted life year commonly used in the UK. Sensitivity analyses showed little uncertainty in these findings. CONCLUSIONS:Economic considerations should not affect whether patients with symptomatic carotid stenosis undergo stenting or endarterectomy.

BackgroundAsthma affects more than 5 million patients in the United Kingdom. Nearly 500,000 of these patients have severe asthma with severe symptoms and frequent exacerbations that are inadequately controlled with available treatments. The burden of severe asthma on the NHS is enormous, accounting for 80 % of the total asthma cost (£1 billion), with frequent exacerbations and expensive medications generating much of this cost.Of those patients with severe asthma, 70 % are sensitised to indoor aeroallergens, and the level of exposure to allergens determines the symptoms; patients exposed to high levels are therefore most at risk of exacerbations and hospital admissions.The LASER trial aims to assess whether a new treatment, temperature controlled laminar airflow (TLA) delivered by the Airsonett™ device, can reduce the frequency of exacerbations in patients with severe allergic asthma by reducing exposure to aeroallergens overnight.MethodsThis multicentre study is a placebo-controlled, blinded, randomised controlled, parallel group trial. A total of 222 patients with a new or current diagnosis of severe allergic asthma will be assigned with a random element in a 1:1 ratio to receive either an active device for one year or a placebo device. The primary outcome is the frequency of severe asthma exacerbations occurring over a 12-month period, defined in accordance with the American Thoracic Society/European Respiratory Society (ATS/ERS) guidelines. Secondary outcomes include changes in asthma control, lung function, asthma-specific and global quality of life for participants and their carers, adherence to intervention, healthcare resource use and costs, and cost-effectiveness. Qualitative interviews will be conducted to elicit participant’s and their partner’s perceptions of the treatment.DiscussionEffective measures of allergen avoidance have, to date, proved elusive. The LASER trial aims to address this. The study will ascertain whether home-based nocturnal TLA usage over a 12-month period can reduce the frequency of exacerbations and improve asthma control and quality of life as compared to placebo, whilst being cost-effective and acceptable to adults with poorly controlled, severe allergic asthma. The results of this study will be widely applicable to the many patients with allergic asthma both in the UK and internationally.Trial registrationCurrent controlled trials ISRCTN46346208 (Date assigned 22 January 2014).

Summary Background Blood disorders comprise a wide range of diseases including anaemia, malignant blood disorders, and haemorrhagic disorders. Although they are a common cause of disease, no systematic cost-of-illness studies have been done to assess the economic effect of non-malignant blood disorders in Europe. We aimed to assess the economic burden of non-malignant blood disorders across the 28 countries of the European Union (EU), Iceland, Norway, and Switzerland. Methods Non-malignant blood disorder-related costs (WHO International Classification of Diseases, 10th revision [ICD] D50–89) were estimated for 28 EU countries, Iceland, Norway, and Switzerland for 2012. Country-specific costs were estimated with aggregate data on morbidity, mortality, and health-care resource use obtained from international and national sources. Health-care costs were estimated from expenditure on primary care, outpatient care, emergency care, hospital inpatient care, and drugs. Costs of informal care and productivity losses due to morbidity and early death were also included. To these costs we added those due to malignant blood disorders (ICD-10 C81–96 and D47) as estimated in a Burns and colleagues' companion Article to obtain the total costs of blood disorders. Findings Non-malignant disorders of the blood cost the 31 European countries €11 billion in 2012. Health-care costs accounted for €8 billion (75% of total costs), productivity losses for €2 billion (19%), and informal care for less than €1 billion (6%). Averaged across the European population studied, non-malignant disorders of the blood represented an annual health-care cost of €159 per ten citizens. Combining malignant and non-malignant blood disorders, the total cost of blood disorders was €23 billion in 2012. Interpretation Our study highlights the economic burden that non-malignant blood disorders place on European health-care systems and societies. Our study also shows that blood disorder costs were evenly distributed between malignant and non-malignant blood disorders. Our results should be of use to decision makers and research-funding authorities charged with allocating health-care resources and research funds. Funding European Hematology Association.

BackgroundThe English NHS Diabetic Eye Screening Programme was established in 2003. Eligible people are invited annually for digital retinal photography screening. Those found to have potentially sight-threatening diabetic retinopathy (STDR) are referred to surveillance clinics or to Hospital Eye Services.ObjectivesTo determine whether personalised screening intervals are cost-effective.DesignRisk factors were identified in Gloucestershire, UK using survival modelling. A probabilistic decision hidden (unobserved) Markov model with a misgrading matrix was developed. This informed estimation of lifetime costs and quality-adjusted life-years (QALYs) in patients without STDR. Two personalised risk stratification models were employed: two screening episodes (SEs) (low, medium or high risk) or one SE with clinical information (low, medium–low, medium–high or high risk). The risk factor models were validated in other populations.SettingGloucestershire, Nottinghamshire, South London and East Anglia (all UK).ParticipantsPeople with diabetes in Gloucestershire with risk stratification model validation using data from Nottinghamshire, South London and East Anglia.Main outcome measuresPersonalised risk-based algorithm for screening interval; cost-effectiveness of different screening intervals.ResultsData were obtained in Gloucestershire from 12,790 people with diabetes with known risk factors to derive the risk estimation models, from 15,877 people to inform the uptake of screening and from 17,043 people to inform the health-care resource-usage costs. Two stratification models were developed: one using only results from previous screening events and one using previous screening and some commonly available GP data. Both models were capable of differentiating groups at low and high risk of development of STDR. The rate of progression to STDR was 5 per 1000 person-years (PYs) in the lowest decile of risk and 75 per 1000 PYs in the highest decile. In the absence of personalised risk stratification, the most cost-effective screening interval was to screen all patients every 3 years, with a 46% probability of this being cost-effective at a £30,000 per QALY threshold. Using either risk stratification models, screening patients at low risk every 5 years was the most cost-effective option, with a probability of 99-100% at a £30,000 per QALY threshold. For the medium-risk groups screening every 3 years had a probability of 43 –48% while screening high-risk groups every 2 years was cost-effective with a probability of 55–59%.ConclusionsThe study found that annual screening of all patients for STDR was not cost-effective. Screening this entire cohort every 3 years was most likely to be cost-effective. When personalised intervals are applied, screening those in our low-risk groups every 5 years was found to be cost-effective. Screening high-risk groups every 2 years further improved the cost-effectiveness of the programme. There was considerable uncertainty in the estimated incremental costs and in the incremental QALYs, particularly with regard to implications of an increasing proportion of maculopathy cases receiving intravitreal injection rather than laser treatment. Future work should focus on improving the understanding of risk, validating in further populations and investigating quality issues in imaging and assessment including the potential for automated image grading.Study registrationIntegrated Research Application System project number 118959.Funding detailsThe National Institute for Health Research Health Technology Assessment programme.

Background More than 120 000 people are diagnosed annually with bladder cancer in the 28 countries of the European Union (EU). With >40 000 people dying of it each year, it is the sixth leading cause of cancer. However, to date, no systematic cost-of-illness study has assessed the economic impact of bladder cancer in the EU. Objective To estimate the annual economic costs of bladder cancer in the EU for 2012. Design, setting, and participants Country-specific cancer cost data were estimated using aggregate data on morbidity, mortality, and health care resource use, obtained from numerous international and national sources. Outcome measurements and statistical analysis Health care costs were estimated from expenditures on primary, outpatient, emergency, and inpatient care, as well as medications. Costs of unpaid care and lost earnings due to morbidity and early death were estimated. Results and limitations Bladder cancer cost the EU €4.9 billion in 2012, with health care accounting for €2.9 billion (59%) and representing 5% of total health care cancer costs. Bladder cancer accounted for 3% of all cancer costs in the EU (€143 billion) in 2012 and represented an annual health care cost of €57 per 10 EU citizens, with costs varying >10 times between the country with the lowest cost, Bulgaria (€8 for every 10 citizens), and highest cost, Luxembourg (€93). Productivity losses and informal care represented 23% and 18% of bladder cancer costs, respectively. The quality and availability of comparable cancer-related data across the EU need further improvement. Conclusions Our results add to essential public health and policy intelligence for delivering affordable bladder cancer care systems and prioritising the allocation of public research funds. Patient summary We looked at the economic costs of bladder cancer across the European Union (EU). We found bladder cancer to cost €4.9 billion in 2012, with health care accounting for €2.9 billion. Our study provides data that can be used to inform affordable cancer care in the EU.

AIMS: Cardiovascular disease (CVD), together with its main components, coronary heart disease (CHD), and cerebrovascular diseases, is the main source of morbidity and mortality in the European Union (EU), but to date, there has not been any systematic cost-of-illness study to assess the economic impact of CVD in the EU. METHODS AND RESULTS: CVD-related expenditure was estimated using aggregate data on morbidity, mortality, and healthcare resource use. Healthcare costs were estimated from expenditure on primary, outpatient, emergency, and inpatient care, as well as medications. Costs of unpaid care and lost earnings due to morbidity and premature death were included in the study. CVD was estimated to cost the EU Euro 169 billion annually, with healthcare accounting for 62% of costs. Productivity losses and informal care represented 21% and 17% of costs, respectively. CHD represented 27% and cerebrovascular diseases 20% of overall CVD costs. CONCLUSION: CVD is a leading public health problem. Our study is the first to assess the economic burden of CVD across the EU, and our results should help policy makers evaluate policy impact and prioritize research expenditures. However, because of data unavailability, our study has important limitations, which highlight the need for more accurate and comparable CVD-specific information.

Background— Prevalence of atrial fibrillation (AF) is >10% at age ≥80 years, but the impact of population aging on rates of AF-related ischemic events is uncertain. Methods and Results— We studied age-specific incidence, outcome, and cost of all AF-related incident strokes and systemic emboli from 2002 to 2012 in the Oxford Vascular Study (OXVASC). We determined time trends in incidence of AF-related stroke in comparison with a sister study in 1981 to 1986, extrapolated numbers to the UK population and projected future numbers. Of 3096 acute cerebral or peripheral vascular events in the 92 728 study population, 383 incident ischemic strokes and 71 systemic emboli were related to AF, of which 272 (59.9%) occurred at ≥80 years. Of 597 fatal or disabling incident ischemic strokes, 262 (43.9%) were AF-related. Numbers of AF-related ischemic strokes at age ≥80 years increased nearly 3-fold from 1981–1986 to 2002–2012 (extrapolated to the United Kingdom: 6621 to 18 176 per year), due partly to increased age-specific incidence (relative rate 1.52, 95% confidence interval 1.31-1.77, P =0.001), with potentially preventable AF-related events at age ≥80 years costing the United Kingdom £374 million per year. At current incidence rates, numbers of AF-related embolic events at age ≥80 years will treble again by 2050 (72 974/year), with 83.5% of all events occurring in this age group. Conclusions— Numbers of AF-related incident ischemic strokes at age ≥80 years have trebled over the last 25 years, despite the introduction of anticoagulants, and are projected to treble again by 2050, along with the numbers of systemic emboli. Improved prevention in older people with AF should be a major public health priority.

Background: In 2008, 2·45 million people were diagnosed with cancer and 1·23 million died because of cancer in the 27 countries of the European Union (EU). We aimed to estimate the economic burden of cancer in the EU. Methods: In a population-based cost analysis, we evaluated the cost of all cancers and also those associated with breast, colorectal, lung, and prostate cancers. We obtained country-specific aggregate data for morbidity, mortality, and health-care resource use from international and national sources. We estimated health-care costs from expenditure on care in the primary, outpatient, emergency, and inpatient settings, and also drugs. Additionally, we estimated the costs of unpaid care provided by relatives or friends of patients (ie, informal care), lost earnings after premature death, and costs associated with individuals who temporarily or permanently left employment because of illness. Findings: Cancer cost the EU €126 billion in 2009, with health care accounting for €51·0 billion (40%). Across the EU, the health-care costs of cancer were equivalent to €102 per citizen, but varied substantially from €16 per person in Bulgaria to €184 per person in Luxembourg. Productivity losses because of early death cost €42·6 billion and lost working days €9·43 billion. Informal care cost €23·2 billion. Lung cancer had the highest economic cost (€18·8 billion, 15% of overall cancer costs), followed by breast cancer (€15·0 billion, 12%), colorectal cancer (€13·1 billion, 10%), and prostate cancer (€8·43 billion, 7%). Interpretation: Our results show wide differences between countries, the reasons for which need further investigation. These data contribute to public health and policy intelligence, which is required to deliver affordable cancer care systems and inform effective public research funds allocation. Funding: Pfizer. © 2013 Elsevier Ltd.

Background New treatments for atrial fibrillation patients have been shown to be effective at reducing subsequent vascular event recurrence. However, there are few data on stroke costs in atrial fibrillation patients to allow the cost-effectiveness of these treatments to be assessed. Aims Using data from a population-based study, we assessed the acute and long-term costs of stroke in atrial fibrillation patients. Methods Health-care costs one-year before and five-years after stroke were obtained from a large population-based study (Oxford Vascular study). Costs were assessed for the three-months poststroke (acute period) and annually thereafter (postacute period). Annual postacute costs were compared with annual baseline costs. Based on patients' living arrangements, costs of institutionalization after the event were included. Results A total of 191 strokes occurred in 153 patients with known prior atrial fibrillation. Mean health-care costs after stroke were £10 413 (standard deviation 15 105) in the acute phase, with annual postacute health-care costs nonsignificantly smaller than those incurred before the event (£2400 vs. £3356, respectively; P = 0·198). However, for the 136 strokes surviving past the 90-day acute period, costs were nonsignificantly higher than those incurred in the year before the event (£3370 vs. £2566, respectively; P = 0·333). After stroke, 25 (13%) patients were newly admitted into long-term warden, nursing, or residential care, resulting in annual costs of £6880 (standard deviation 15 600) averaged across the 136 stroke cases surviving past the acute period. Conclusions Although annual post acute phase hospital and primary health-care costs in stroke patients with prior atrial fibrillation were not significantly different to those incurred before the stroke, long-term nursing/residential care costs were substantial.