Economics of asthma: estimating quality of life in people with asthma attacks

Asthma effects 5.4 million people in the United Kingdom. It is a chronic respiratory condition defined as frequent episodes of breathlessness, chest tightness and wheezing. An asthma attack is the progressive worsening of these symptoms, and can lead to increased healthcare resource use and reduced quality of life. It can be a costly disease, with over £1 billion of direct costs in England and Wales and over £130 million spent in Scotland. Patient reported outcome measures (PROMs) can be used to measure quality of life, but it is currently not clear which preference-based measures are more appropriate for asthma. In most studies, quality of life is measured by PROMs at particular time points, such as baseline and 12 months, however an asthmatic episode may occur in between these time points due to the unpredictable nature of these events. Therefore, the loss in quality of life associated with an episode may not be fully captured. Alternatively, an event could occur at 12 months. This may result in an underestimation of quality of life, measured by the area under the curve technique. Consequently, this thesis explored quality of life in acute asthmatics. Firstly, a systematic review explored the cost effectiveness of non-pharmacological asthma management interventions and the methodologies used to estimate costs and outcomes in the included studies. Secondly, a prospective cohort study estimated the loss in quality of life associated with an asthma-related crisis event (A&E attendance or hospital admission) using PROMs. Thirdly, the preference-based measures from the cohort study data set were compared using psychometric techniques. This thesis has indicated that largest decreases in quality of life occurred during the first four weeks from the crisis event for all PROMs considered. The EQ-5D-5L and the AQL-5D had better psychometric performance compared to the other preference-based measures

Estimating loss in quality of life associated with asthma-related crisis events (ESQUARE): a cohort, observational study

Background: Evidence of quality of life implications of asthma attacks are limited,particularly when measured on a utility scale, which enables calculating Quality-Adjusted Life-Years (QALYs) and comparisons with other health conditions andservices. Therefore, this study sought to estimate the utility loss associated with anasthma-related crisis event (accident and emergency (A&E) attendance or hospitaladmission).Methods: Participants were recruited in a cohort study from A&E and hospitaladmissions at three UK hospitals. They completed the EuroQol-5 Dimensions 5-Level(EQ-5D-5L), Asthma Quality of Life Questionnaire (AQLQ), Time trade-off (TTO), andpeak flow and symptom diary over 8 weeks, where three different methods (EQ-5D-5L,AQLQ, and TTO), were used to estimate utilities. The mean difference between twotime points were estimated using the Wilcoxon signed rank test.Results: From baseline to week 8, mean increases (95% CI) were estimated to be0.086 (0.019-0.153), 0.154 (0.112-0.196) and 0.132 (0.063-0.201) for EQ-5D-5L, AQL-5D (preference-based measure derived from AQLQ), and TTO respectively over 8weeks (p<0.01).Conclusion: Asthma crisis events are estimated to be associated with a mean utilityloss of between 0.086 and 0.132. The utility decrement can be used to assign valuesto asthma-related crisis events, which can enhance economic evaluations

The construct validity and responsiveness of the EQ-5D-5L, AQL-5D and a bespoke TTO in acute asthmatics

Purpose: Measuring quality of life in acute asthmatics is challenging, especially when asthma attacks can occur sporadically. Several questionnaires can be used to measure quality of life in this patient group; however, psychometric testing is limited on questionnaires that can be used to estimate Quality Adjusted Life years. The objective of this study is to assess the construct validity (convergent and discriminative validity) and responsiveness of the EuroQol-5-Dimensions 5-Level (EQ-5D-5L), Asthma Quality of Life Utility Index-5 Dimensions (AQL-5D) and Time Trade-Off (TTO) in acute asthma patients. Methods: Data from a prospective cohort study were used to test the validity and responsiveness of the EQ-5D-5L, AQL-5D and TTO in asthma patients who were recruited from UK accident & emergency departments or hospital wards. The spearman’s rank correlation coefficient, the Kruskal–Wallis test statistic and the standardized response mean were used to test for convergent validity, discriminative validity and responsiveness, respectively. Results: One hundred and twenty-one participants were included in the available case analysis. The EQ-5D-5L and AQL-5D showed moderate to strong correlations for convergent validity at baseline, week 4 and week 8. The AQL-5D and TTO showed moderate correlations at week 4 and week 8. No statistical significance was observed for discriminative validity at baseline. Both the EQ-5D-5L and the AQL-5D also showed that they were sensitive to change for the recovery responses. Conclusions: The EQ-5D-5L and AQL-5D showed stronger construct validity and responsiveness compared to the TTO. Therefore, both the EQ-5D-5L and AQL-5D should be considered for use in future economic evaluations

Biomarkers in adult asthma: a systematic review of 8-isoprostane in exhaled breath condensate

Objectives: We aimed to assess the evidence for the use of 8-isoprostane in exhaled breath condensate (EBC) as a biomarker in adult asthma. Design: A systematic review and meta-analysis of EBC 8-isoprostane. Methods: We searched a number of online databases (including PubMed, Embase and Scopus) in January 2016. We included studies of adult non-smokers with EBC collection and asthma diagnosis conducted according to recognised guidelines. We aimed to pool data using random effects meta-analysis and assess heterogeneity using I2. Results: We included twenty studies, the findings from which were inconsistent. Seven studies (n = 329) reported 8-isoprostane levels in asthma to be significantly higher than that of control groups, whilst six studies (n = 403) did not. Only four studies were appropriate for inclusion in a random effects meta-analysis of mean difference. This found a statistically significant between-groups difference of 22pg/ml. Confidence in the result is limited by the small number of studies and by substantial statistical heterogeneity (I2 = 94). Conclusion: The clinical value of EBC 8-isoprostane as a quantitative assessment of oxidative stress in asthma remains unclear due to variability in results and methodological heterogeneity. It is essential to develop a robust and standardised methodology if the use of EBC 8-isoprostane in asthma is to be properly evaluated

High-Expenditure Disease in the EU-28: Does Drug Spend Correspond to Clinical and Economic Burden in Oncology, Autoimmune Disease and Diabetes?

Greiner W, Patel K, Crossman-Barnes C-J, Rye-Andersen TV, Hvid C, Vandebrouck T. High-Expenditure Disease in the EU-28: Does Drug Spend Correspond to Clinical and Economic Burden in Oncology, Autoimmune Disease and Diabetes? PharmacoEconomics - open. 2021.BACKGROUND: Drug costs are increasing in Europe, and there is a heightened need to reduce pressure on healthcare systems. In 2017, oncology, autoimmune disease, and diabetes featured as the three highest therapy areas for drug spend in the EU-28. However, the absolute 1-year drug spend growth for diabetes did not feature within the ten fastest growing therapy areas.; OBJECTIVE: This study explores the association between drug spend and disease burden in oncology, autoimmune disease, and diabetes in the EU-28.; METHODS: Oncology, autoimmune disease and diabetes therapeutic areas were investigated using four methodologies. Historical and forecasted drug spend was analysed using the IQVIA MIDAS drug sales database. Clinical and economic burden was estimated from targeted literature reviews. Trend analyses compared changes in drug spend with clinical burden using the Global Burden of Disease tool as the epidemiological reference. Cost per quality-adjusted life-years (QALYs) from UK health technology assessments were compared to interpret the health economic value.; RESULTS: Oncology had the highest historical drug spend and growth compared with autoimmune disease and diabetes. Total drug spend and growth in oncology is forecasted to exceed diabetes by twofold. Increasing oncology drug spend historically did not correspond with reductions in mortality and morbidity. Diabetes had the lowest drug spend and greatest QALY/1000 spent benefit.; CONCLUSION: This study indicates that drug spend may not correlate to clinical burden across diseases. Future research could stimulate debate on whether more equitable drug funding may improve disease management

8-Isoprostane in Exhaled Breath Condensate: A Systematic Review in Adult Asthma

Background: The potential of exhaled breath condensate (EBC) as a non-invasive indicator of airways disease has been studied for over thirty years. 8-isoprostane is a product of lipid peroxidation detectable within EBC, and a potential objective indicator of oxidative stress in asthma. Aim: To assess the evidence for the use of 8-isoprostane in EBC as a biomarker in adult asthma. Methods: We searched a number of online databases (including PubMed, Embase and Scopus) in January 2016. We included studies of adult non-smokers with EBC collection and asthma diagnosis conducted according to recognised guidelines. We aimed to pool data using random effects meta-analysis and assess heterogeneity using I2. Study quality and risk of bias was assessed using QUADAS-2 and GRADE. Results: We included twenty studies, the findings from which were inconsistent. Seven studies (n = 329) reported 8-isoprostane concentrations in asthma to be significantly higher than that of control groups, whilst six studies (n = 403) did not. Only four studies had results appropriate for inclusion in a random effects meta-analysis of mean difference between asthma and controls. This found a statistically significant between-groups difference of +22pg/ml in asthma. Confidence in the result is limited by the small number of studies; substantial methodological and statistical heterogeneity; and inability to assess the risk of bias in key domains. Conclusion: The clinical value of EBC 8-isoprostane as a quantitative assessment of oxidative stress in asthma remains unclear due to variability in results and methodological heterogeneity. It will be essential to develop accurate, reliable and standardised methods of both EBC collection and 8-isoprostane analysis if its use as a biomarker in asthma is to be evaluated. Funding: University of East Anglia and the Asthma UK Centre for Applied Research

Measurement of the double-differential inclusive jet cross section in proton-proton collisions at s\sqrt{s} = 5.02 TeV

International audienceThe inclusive jet cross section is measured as a function of jet transverse momentum $p_\mathrm{T}$ and rapidity $y$. The measurement is performed using proton-proton collision data at $\sqrt{s}$ = 5.02 TeV, recorded by the CMS experiment at the LHC, corresponding to an integrated luminosity of 27.4 pb$^{-1}$. The jets are reconstructed with the anti-$k_\mathrm{T}$ algorithm using a distance parameter of $R$ = 0.4, within the rapidity interval $\lvert y\rvert$$\lt$ 2, and across the kinematic range 0.06 $\lt$$p_\mathrm{T}$$\lt$ 1 TeV. The jet cross section is unfolded from detector to particle level using the determined jet response and resolution. The results are compared to predictions of perturbative quantum chromodynamics, calculated at both next-to-leading order and next-to-next-to-leading order. The predictions are corrected for nonperturbative effects, and presented for a variety of parton distribution functions and choices of the renormalization/factorization scales and the strong coupling $\alpha_\mathrm{S}$

Two-particle Bose-Einstein correlations and their Lévy parameters in PbPb collisions at sNN\sqrt{s_\mathrm{NN}} = 5.02 TeV

Two-particle Bose-Einstein momentum correlation functions are studied for charged-hadron pairs in lead-lead collisions at a center-of-mass energy per nucleon pair of $\sqrt{s_\mathrm{NN}}$ = 5.02 TeV. The data sample, containing 4.27$\times10^{9}$ minimum bias events corresponding to an integrated luminosity of 0.607 nb$^{-1}$, was collected by the CMS experiment in 2018. The experimental results are discussed in terms of a L\'evy-type source distribution. The parameters of this distribution are extracted as functions of particle pair average transverse mass and collision centrality. These parameters include the L\'evy index or shape parameter ($\alpha$), the L\'evy scale parameter ($R$), and the correlation strength parameter ($\lambda$). The source shape, characterized by $\alpha$, is found to be neither Cauchy nor Gaussian, implying the need for a full L\'evy analysis. Similarly to what was previously found for systems characterized by Gaussian source radii, a hydrodynamical scaling is observed for the L\'evy $R$ parameter. The $\lambda$ parameter is studied in terms of the core-halo model.Comment: Submitted to Physical Review C. All figures and tables can be found at http://cms-results.web.cern.ch/cms-results/public-results/publications/HIN-21-011 (CMS Public Pages

Measurement of the double-differential inclusive jet cross section in proton-proton collisions at s= \sqrt{s} = 5.02 TeV

The inclusive jet cross section is measured as a function of jet transverse momentum $p_{\mathrm{T}}$ and rapidity $y$. The measurement is performed using proton-proton collision data at $\sqrt{s} =$ 5.02 TeV, recorded by the CMS experiment at the LHC, corresponding to an integrated luminosity of 27.4$\,\text{pb}^{-1}$. The jets are reconstructed with the anti-$k_{\mathrm{T}}$ algorithm using a distance parameter of $R=$ 0.4, within the rapidity interval $|y| <$ 2, and across the kinematic range 0.06 $< p_{\mathrm{T}} <$ 1 TeV. The jet cross section is unfolded from detector to particle level using the determined jet response and resolution. The results are compared to predictions of perturbative quantum chromodynamics, calculated at both next-to-leading order and next-to-next-to-leading order. The predictions are corrected for nonperturbative effects, and presented for a variety of parton distribution functions and choices of the renormalization/factorization scales and the strong coupling $\alpha_\mathrm{S}$.The inclusive jet cross section is measured as a function of jet transverse momentum $p_\mathrm{T}$ and rapidity $y$. The measurement is performed using proton-proton collision data at $\sqrt{s}$ = 5.02 TeV, recorded by the CMS experiment at the LHC, corresponding to an integrated luminosity of 27.4 pb$^{-1}$. The jets are reconstructed with the anti-$k_\mathrm{T}$ algorithm using a distance parameter of $R$ = 0.4, within the rapidity interval $\lvert y\rvert$$\lt$ 2, and across the kinematic range 0.06 $\lt$$p_\mathrm{T}$$\lt$ 1 TeV. The jet cross section is unfolded from detector to particle level using the determined jet response and resolution. The results are compared to predictions of perturbative quantum chromodynamics, calculated at both next-to-leading order and next-to-next-to-leading order. The predictions are corrected for nonperturbative effects, and presented for a variety of parton distribution functions and choices of the renormalization/factorization scales and the strong coupling $\alpha_\mathrm{S}$

Measurement of the double-differential inclusive jet cross section in proton-proton collisions at s\sqrt{s} = 5.02 TeV

International audienceThe inclusive jet cross section is measured as a function of jet transverse momentum $p_\mathrm{T}$ and rapidity $y$. The measurement is performed using proton-proton collision data at $\sqrt{s}$ = 5.02 TeV, recorded by the CMS experiment at the LHC, corresponding to an integrated luminosity of 27.4 pb$^{-1}$. The jets are reconstructed with the anti-$k_\mathrm{T}$ algorithm using a distance parameter of $R$ = 0.4, within the rapidity interval $\lvert y\rvert$$\lt$ 2, and across the kinematic range 0.06 $\lt$$p_\mathrm{T}$$\lt$ 1 TeV. The jet cross section is unfolded from detector to particle level using the determined jet response and resolution. The results are compared to predictions of perturbative quantum chromodynamics, calculated at both next-to-leading order and next-to-next-to-leading order. The predictions are corrected for nonperturbative effects, and presented for a variety of parton distribution functions and choices of the renormalization/factorization scales and the strong coupling $\alpha_\mathrm{S}$