Decision-Making for Preventive Interventions in Asymptomatic Patients.

The decision to treat an incidental finding in an asymptomatic patient results from careful risk-benefit consideration and is often challenging. One of the main aspects is after how many years the group who underwent the intervention and faced the immediate treatment complications will gain a treatment benefit over the conservatively managed group, which maintains a lower but ongoing risk. We identify a common error in decision-making. We illustrate how a risk-based approach using the classical break-even point at the Kaplan-Meier curves can be misleading and advocate for using an outcome-based approach, counting the cumulative number of lost quality-adjusted life years instead. In clinical practice, we often add together the yearly risk of the natural course up to the time point where the number equals the risk of the intervention and assume that the patient will benefit from an intervention beyond this point in time. It corresponds to the crossing of the Kaplan-Meier curves. However, because treatment-related poor outcome occurs at the time of the intervention, while the poor outcome in the conservative group occurs over a given time period, the true benefit of retaining more quality-adjusted life years in the interventional group emerges at a much later time. To avoid overtreatment of patients with asymptomatic diseases, decision-making should be outcome-based with counting the cumulative loss of quality-adjusted life years, rather than risk-based, comparing the interventional risk with the ongoing yearly risk of the natural course.

Improving sleep after stroke: A randomised controlled trial of digital cognitive behavioural therapy for insomnia.

Stroke is frequently accompanied by long-term sleep disruption. We therefore aimed to assess the efficacy of digital cognitive behavioural therapy 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-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 old), and were randomised to digital cognitive behavioural therapy or control (sleep hygiene information). Follow-up was at post-intervention (mean 75 days after baseline) and 8 weeks later. The primary outcome was self-reported insomnia symptoms, as per the Sleep Condition Indicator-8 (range 0-32, lower numbers indicate more severe insomnia, reliable change 7 points) at post-intervention. There were significant improvements in Sleep Condition Indicator-8 for digital cognitive behavioural therapy compared with control (intention-to-treat, digital cognitive behavioural therapy n = 48, control n = 36, 5 imputed datasets, effect of group p ≤ 0.02, η p 2 = 0.07-0.12 [medium size effect], pooled mean difference = -3.35). Additionally, secondary outcomes showed shorter self-reported sleep-onset latencies and better mood for the digital cognitive behavioural therapy group, but no significant differences for self-efficacy, quality of life or actigraphy-derived sleep parameters. Cost-effectiveness analysis found that digital cognitive behavioural therapy dominates over control (non-significant cost savings and higher quality-adjusted life years). No related serious adverse events were reported to the researchers. Overall, digital cognitive behavioural therapy 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.gov NCT04272892.

Health-related quality of life and healthcare costs of symptoms and cardiovascular disease events in patients with atrial fibrillation: a longitudinal analysis of 27 countries from the EURObservational Research Programme on Atrial Fibrillation general long-term registry.

AIMS: We examine the effects of symptoms and cardiovascular disease (CVD) events on health-related quality of life (HRQOL) and healthcare costs in a European population with atrial fibrillation (AF). METHODS AND RESULTS: In the EURObservational Research Programme on AF long-term general registry, AF patients from 250 centres in 27 European countries were enrolled and followed for 2 years. We used fixed effects models to estimate the association of symptoms and CVD events on HRQOL and annual healthcare costs. We found significant decrements in HRQOL in AF patients in whom ST-segment elevation myocardial infarction (STEMI) [-0.075 (95% confidence interval -0.144, -0.006)], angina or non-ST-elevation myocardial infarction (NSTEMI) [-0.037 (-0.071, -0.003)], new-onset/worsening heart failure [-0.064 (-0.088, -0.039)], bleeding events [-0.031 (-0.059, -0.003)], thromboembolic events [-0.071 (-0.115, -0.027)], mild symptoms [0.037 (-0.048, -0.026)], or severe/disabling symptoms [-0.090 (-0.108, -0.072)] occurred during the follow-up. During follow-up, annual healthcare costs were associated with an increase of €11 718 (€8497, €14 939) in patients with STEMI, €5823 (€4757, €6889) in patients with angina/NSTEMI, €3689 (€3219, €4158) in patients with new-onset or worsening heart failure, €3792 (€3315, €4270) in patients with bleeding events, and €3182 (€2483, €3881) in patients with thromboembolic events, compared with AF patients without these events. Healthcare costs were primarily driven by inpatient costs. There were no significant differences in HRQOL or healthcare resource use between EU regions or by sex. CONCLUSION: Symptoms and CVD events are associated with a high burden on AF patients and healthcare systems throughout Europe.

Economic burden of cardiovascular diseases in the European Union: a population-based cost study.

BACKGROUND AND AIMS: Cardiovascular disease (CVD) impacts significantly health and social care systems as well as society through premature mortality and disability, with patients requiring care from relatives. Previous pan-European estimates of the economic burden of CVD are now outdated. This study aims to provide novel, up-to-date evidence on the economic burden across the 27 European Union (EU) countries in 2021. METHODS: Aggregate country-specific resource use data on morbidity, mortality, and health, social and informal care were obtained from international sources, such as the Statistical Office of the European Communities, enhanced by data from the European Society of Cardiology Atlas programme and patient-level data from the Survey of Health, Ageing and Retirement in Europe. Country-specific unit costs were used, with cost estimates reported on a per capita basis, after adjustment for price differentials. RESULTS: CVD is estimated to cost the EU €282 billion annually, with health and long-term care accounting for €155 billion (55%), equalling 11% of EU-health expenditure. Productivity losses accounted for 17% (€48 billion), whereas informal care costs were €79 billion (28%). CVD represented a cost of €630 per person, ranging from €381 in Cyprus to €903 in Germany. Coronary heart disease accounted for 27% (€77 billion) and cerebrovascular diseases for 27% (€76 billion) of CVD costs. CONCLUSIONS: This study provides contemporary estimates of the wide-ranging impact of CVD on all aspects of the economy. The data help inform evidence-based policies to reduce the impact of CVD, promoting care access and better health outcomes and economic sustainability.

Long-Term Impact of Urgent Secondary Prevention After Transient Ischemic Attack and Minor Stroke: Ten-Year Follow-Up of the EXPRESS Study.

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.

Cost-effectiveness of ambulatory care management of primary spontaneous pneumothorax: an open-label, randomised controlled trial.

BACKGROUND: Ambulatory 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. OBJECTIVES: A 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. METHODS: Patients 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. RESULTS: 236 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. CONCLUSION: Outpatient ambulatory management is highly likely to be a cost-effective option in the management of primary pneumothorax. TRIAL REGISTRATION NUMBER: ISRCTN79151659.

Cost-Effectiveness of Mechanical Thrombectomy for Treatment of Nonminor Ischemic Stroke Across Europe.

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.

Late functional improvement and 5-year poststroke outcomes: a population-based cohort study.

BACKGROUND: Late 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. METHODS: In 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. RESULTS: Among 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, p<0.001) and healthcare/social care costs (margin US$17 524, -24 763 to -10 284, p<0.001). These associations remained on excluding patients with recurrent strokes during follow-up (eg, 5-year mortality/institutionalisation: aHR 0.59, 0.44 to 0.79, p<0.001) and on examining late improvement per RMI and/or BI (eg, 5-year mortality/institutionalisation with RMI/BI: aHR 0.73, 0.58 to 0.92, p=0.008). CONCLUSION: Late 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.

Ten-year risks of recurrent stroke, disability, dementia and cost in relation to site of primary intracerebral haemorrhage: population-based study.

BACKGROUND: Patients 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. METHODS: In 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. RESULTS: Of 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). CONCLUSION: Compared 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.

Effect of Thoracoscopic Talc Poudrage vs Talc Slurry via Chest Tube on Pleurodesis Failure Rate Among Patients With Malignant Pleural Effusions: A Randomized Clinical Trial.

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.

Cost-effectiveness of intrapleural use of tissue plasminogen activator and DNase in pleural infection: evidence from the MIST2 randomised controlled trial.

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.

Long-Term Consequences of Worsened Poststroke Status in Patients With Premorbid Disability.

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<0.001) and costs (margin for ΔmRS ≥2 versus 0: $30 011, 95% CI, $4222-55 801; P=0.023). Results were similar on examining patients with premorbid mRS of 2, 3, and 4 separately (eg, 5-year mortality/institutionalization adjusted hazard ratio for premorbid mRS=3 with ΔmRS=1 versus 0: 1.60; 95% CI, 1.06-2.42; P=0.027; ΔmRS=2: 3.20; 95% CI, 1.85-5.54; P<0.001). Conclusions- Patients with stroke with premorbid disability have higher mortality, institutionalization, and costs if they accumulate additional disability because of the stroke. These findings highlight the long-term outcomes expected if acute interventions are routinely withheld in patients with mild-moderate premorbid disability and suggest that trials/registries should include such patients.

Hospital and Institutionalisation Care Costs after Limb and Visceral Ischaemia Benchmarked Against Stroke: Long-Term Results of a Population Based Cohort Study.

OBJECTIVE/BACKGROUND: There are few published data on the acute care or long-term costs after acute/critical limb or visceral ischaemia (ACLVI) events. Using data from patients with acute events in a population based incidence study (Oxford Vascular Study), the present study aimed to determine the long-term costs after an ACLVI event. METHODS: All patients with first ever incident ACLVI from 2002 to 2012 were included. Analysis was based on follow up until January 2017, with all patients having full 5 year follow up. Multivariate regressions were used to assess baseline and subsequent predictors of total 5 year hospital care costs. Overall costs after an ACLVI event were benchmarked against those after stroke in the same population, during the same period. RESULTS: Among 351 patients with an ACLVI event, mean 5 year total care costs were €35,211 (SD 50,500), of which €6443 (18%) were due to long-term institutionalisation. Costs differed by type of event (acute visceral ischaemia €16,476; acute limb ischaemia €24,437; critical limb ischaemia €46,281; p < 0.001). Results of the multivariate analyses showed that patients with diabetes and those undergoing above knee amputations incurred additional costs of €11,804 (p = 0.014) and €25,692 (p < 0.001), respectively. Five year hospital care costs after an ACLVI event were significantly higher than after stroke (€28,768 vs. €22,623; p = 0.004), but similar after including long-term costs of institutionalisation (€35,211 vs. €35,391; p = 0.957). CONCLUSION: Long-term care costs after an ACLVI event are considerable, especially after critical limb ischaemia. Hospital care costs were significantly higher than for stroke over the long term, and were similar after inclusion of costs of institutionalisation.

Cost-effectiveness of indwelling pleural catheter compared with talc in malignant pleural effusion.

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 <14 weeks, and was more costly when 2-h nursing time per week was assumed for catheter drainage. CONCLUSION: IPC is cost-effective when compared with talc, although substantial uncertainty exists around this estimate. IPC appears most cost-effective in patients with limited survival. If significant nursing time is required for catheter drainage, IPC becomes less likely to be cost-effective. Either therapy may be considered as a first-line option in treating malignant pleural effusion in patients without history of prior pleurodesis, with consideration for patient survival, support and preferences.

Age-specific incidence, outcome, cost, and projected future burden of atrial fibrillation-related embolic vascular events: a population-based study.

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.

Economic burden of cancer across the European Union: a population-based cost analysis.

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.

Infection, delirium, and risk of dementia in patients with and without white matter disease on previous brain imaging: a population-based study.

BACKGROUND: The increased risk of dementia after delirium and infection might be influenced by cerebral white matter disease (WMD). In patients with transient ischaemic attack (TIA) and minor stroke, we assessed associations between hospital admissions with delirium and 5-year dementia risk and between admissions with infection and dementia risk, stratified by WMD severity (moderate or severe vs absent or mild) on baseline brain imaging. METHODS: We included patients with TIA and minor stroke (National Institutes of Health Stroke Score <3) from the Oxford Vascular Study (OXVASC), a longitudinal population-based study of the incidence and outcomes of acute vascular events in a population of 94 567 individuals, with no age restrictions, attending eight general practices in Oxfordshire, UK. Hospitalisation data were obtained through linkage to the Oxford Cognitive Comorbidity, Frailty, and Ageing Research Database-Electronic Patient Records (ORCHARD-EPR). Brain imaging was done using CT and MRI, and WMD was prospectively graded according to the age-related white matter changes (ARWMC) scale and categorised into absent, mild, moderate, or severe WMD. Delirium and infection were defined by ICD-10 coding supplemented by hand-searching of hospital records. Dementia was diagnosed using clinical or cognitive assessment, medical records, and death certificates. Associations between hospitalisation with delirium and hospitalisation with infection, and post-event dementia were assessed using time-varying Cox analysis with multivariable adjustment, and all models were stratified by WMD severity. FINDINGS: From April 1, 2002, to March 31, 2012, 1369 individuals were prospectively recruited into the study. Of 1369 patients (655 with TIA and 714 with minor stroke, mean age 72 [SD 13] years, 674 female and 695 male, and 364 with moderate or severe WMD), 209 (15%) developed dementia. Hospitalisation during follow-up occurred in 891 (65%) patients of whom 103 (12%) had at least one delirium episode and 236 (26%) had at least one infection episode. Hospitalisation without delirium or infection did not predict subsequent dementia (HR 1·01, 95% CI 0·86-1·20). In contrast, hospitalisation with delirium predicted subsequent dementia independently of infection in patients with and without WMD (2·64, 1·47-4·74; p=0·0013 vs 3·41, 1·91-6·09; p<0·0001) especially in those with unimpaired baseline cognition (cognitive test score above cutoff; 4·01, 2·23-7·19 vs 3·94, 1·95-7·93; both p≤0·0001). However, hospitalisation with infection only predicted dementia in those with moderate or severe WMD (1·75, 1·04-2·94 vs 0·68, 0·39-1·20; pdiff=0·023). INTERPRETATION: The increased risk of dementia after delirium is unrelated to the presence of WMD, whereas infection increases risk only in patients with WMD, suggesting differences in underlying mechanisms and in potential preventive strategies. FUNDING: National Institute for Health and Care Research and Wellcome Trust.

Cardiovascular disease burden due to productivity losses in European Society of Cardiology countries.

OBJECTIVE: Cardiovascular disease (CVD) is the leading cause of death across Europe. We estimated lost earnings (productivity losses) associated with premature mortality due to CVD, and separately for its main sub-categories of coronary heart disease and cerebrovascular disease, across 54 country members of the European Society of Cardiology (ESC). METHODS AND RESULTS: We used a standardized approach to estimate working years and earnings lost due to premature death resulting from CVD across the 54 ESC member countries in 2018. Our population-based approach was based on national data on the number of deaths, employment rates, and earnings by age group and sex. We discounted future working years and earnings lost to present values using a 3.5% annual rate. In 2018, there were 4.4 million deaths due to CVD across the 54 countries, with 7.1 million working years lost. This represented productivity losses due to premature death of €62 billion in 2018. Deaths due to coronary heart disease accounted for 47% (€29 billion) of all CVD costs, and cerebrovascular disease accounted for 18% (€11 billion). Approximately 60% (€37 billion) of all productivity losses occurred in the 28 European Union member states, despite accounting for only 42% (1.8 million) of deaths and 21% (1.5 million) of working years lost across the 54 countries. CONCLUSION: Our study provides a snapshot of the economic consequences posed by premature mortality due to CVD across 54 countries in 2018. The considerable variation across countries highlights the potential gains from policies targeting prevention and care of cardiovascular diseases.

Association of multimorbidity with mortality after stroke stratified by age, severity, etiology, and prior disability.

BACKGROUND: Multimorbidity is common in patients with stroke and is associated with increased medium- to long-term mortality, but its value for clinical decision-making and case-mix adjustment will depend on other factors, such as age, stroke severity, etiological subtype, prior disability, and vascular risk factors. AIMS: In the absence of previous studies, we related multimorbidity to long-term post-stroke mortality with stratification by these factors. METHODS: In patients ascertained in a population-based stroke incidence study (Oxford Vascular Study; 2002-2017), we related pre-stroke multimorbidity (weighted/unweighted Charlson comorbidity index (CCI)) to all-cause/vascular/non-vascular mortality (1/5/10 years) using regression models adjusted/stratified by age, sex, predicted early outcome (THRIVE score), stroke severity (NIH stroke scale (NIHSS)), etiology (Trial of Org 10172 in Acute Stroke Treatment (TOAST)), premorbid disability (modified Rankin Scale (mRS)), and non-CCI risk factors (hypertension, hyperlipidemia, atrial fibrillation, smoking, deprivation, anxiety/depression). RESULTS: Among 2454 stroke patients (M/SD age: 74.1/13.9 years; 48.9% male; M/SD NIHSS: 5.7/7.0), 1375/56.0% had ⩾ 1 CCI comorbidity and 685/27.9% had ⩾ 2. After age/sex adjustment, multimorbidity (unweighted CCI ⩾ 2 vs 0) predicted (all ps < 0.001) mortality at 1 year (aHR = 1.57, 95% CI = 1.38-1.78), 5 years (aHR = 1.73, 95% CI = 1.53-1.96), and 10 years (aHR = 1.79, 95% CI = 1.58-2.03). Although multimorbidity was independently associated with premorbid disability (mRS > 2: aOR = 2.76, 2.13-3.60) and non-CCI risk factors (hypertension: 1.56, 1.25-1.95; hyperlipidemia: 2.58, 2.03-3.28; atrial fibrillation: 2.31; 1.78-2.98; smoking: 1.37, 1.01-1.86), it predicted death after adjustment for all measured confounders (10-year-aHR = 1.56, 1.37-1.78, p < 0.001), driven mainly by non-vascular death (aHR = 1.89, 1.55-2.29). Predictive value for 10-year all-cause death was greatest in patients with lower expected early mortality: lower THRIVE score (pint < 0.001), age < 75 years (aHR = 2.27, 1.71-3.00), NIHSS < 5 (1.84, 1.53-2.21), and lacunar stroke (3.56, 2.14-5.91). Results were similar using the weighted CCI. CONCLUSION: Pre-stroke multimorbidity is highly prevalent and is an independent predictor of death after stroke, supporting its inclusion in case-mix adjustment models and in informing decision-making by patients, families, and carers. Prediction in younger patients and after minor stroke, particularly for non-vascular death, suggests potential clinical utility in targeting interventions that require survival for 5-10 years to achieve a favorable risk/benefit ratio. DATA ACCESS STATEMENT: Data requests will be considered by the Oxford Vascular Study (OXVASC) Study Director (P.M.R.-peter.rothwell@ndcn.ox.ac.uk).

Population-based study of disability and institutionalization after transient ischemic attack and stroke: 10-year results of the Oxford Vascular Study.

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<0.001), with 39% (132 of 339) of survivors disabled 5 years after stroke. Five years postevent, 70% (483 of 690) of patients with stroke and 48% (179 of 375) of patients with TIA were either dead or disabled. The 5-year risk of care home institutionalization was 11% after TIA and 19% after stroke. The average 5-year cost per institutionalized patient was $99,831 (SD, 67 020) for TIA and $125,359 (SD, 91 121) for stroke. 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.