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BACKGROUND: Immunocompromised individuals are known to respond inadequately to SARS-CoV-2 vaccines, placing them at high risk of severe or fatal COVID-19. Thus, immunocompromised individuals and their caregivers may still practice varying degrees of social or physical distancing to avoid COVID-19. However, the association between physical distancing to avoid COVID-19 and quality of life has not been comprehensively evaluated in any study. OBJECTIVE: We aim to measure physical distancing behaviors among immunocompromised individuals and the association between those behaviors and person-centric outcomes, including health-related quality of life (HRQoL) measures, health state utilities, anxiety and depression, and work and school productivity impairment. METHODS: A patient-informed protocol was developed to conduct the EAGLE Study, a large cross-sectional, observational study, and this paper describes that protocol. EAGLE is designed to measure distancing behaviors and outcomes in immunocompromised individuals, including children (aged ≥6 mo) and their caregivers, and nonimmunocompromised adults in the United States and United Kingdom who report no receipt of passive immunization against COVID-19. We previously developed a novel self- and observer-reported instrument, the Physical Distancing Scale for COVID-19 Avoidance (PDS-C19), to measure physical distancing behavior levels cross-sectionally and retrospectively. Using an interim or a randomly selected subset of the study population, the PDS-C19 psychometric properties will be assessed, including structural validity, internal consistency, known-group validity, and convergent validity. Associations (correlations) will be assessed between the PDS-C19 and validated HRQoL-related measures and utilities. Structural equation modeling and regression will be used to assess these associations, adjusting for potential confounders. Participant recruitment and data collection took place from December 2022 to June 2023 using direct-to-patient channels, including panels, clinician referral, patient advocacy groups, and social media, with immunocompromising diagnosis confirmation collected and assessed for a randomly selected 25% of immunocompromised participants. The planned total sample size is 3718 participants and participant-caregiver pairs. Results will be reported by immunocompromised status, immunocompromising condition category, country, age group, and other subgroups. RESULTS: All data analyses and reporting were planned to be completed by December 2023. Results are planned to be submitted for publication in peer-reviewed journals in 2024-2025. CONCLUSIONS: This study will quantify immunocompromised individuals' physical distancing behaviors to avoid COVID-19 and their association with HRQoL as well as health state utilities. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/52643.
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COVID-19 , Hospedeiro Imunocomprometido , Distanciamento Físico , Qualidade de Vida , Humanos , COVID-19/prevenção & controle , COVID-19/epidemiologia , Estudos Transversais , Hospedeiro Imunocomprometido/imunologia , Adulto , Masculino , Feminino , Estados Unidos/epidemiologia , Reino Unido/epidemiologia , CriançaRESUMO
Background: Immunocompromised individuals are not optimally protected by COVID-19 vaccines and potentially require additional preventive interventions to mitigate the risk of severe COVID-19. We aimed to characterise and describe the risk of severe COVID-19 across immunocompromised groups as the pandemic began to transition to an endemic phase. Methods: COVID-19-related hospitalisations, intensive care unit (ICU) admissions, and deaths (01/01/2022-31/12/2022) were compared among different groups of immunocompromised individuals vs the general population, using a retrospective cohort design and electronic health data from a random 25% sample of the English population aged ≥12 years (Registration number: ISRCTN53375662). Findings: Overall, immunocompromised individuals accounted for 3.9% of the study population, but 22% (4585/20,910) of COVID-19 hospitalisations, 28% (125/440) of COVID-19 ICU admissions, and 24% (1145/4810) of COVID-19 deaths in 2022. Restricting to those vaccinated with ≥3 doses of COVID-19 vaccine (â¼84% of immunocompromised and 51% of the general population), all immunocompromised groups remained at increased risk of severe COVID-19 outcomes, with adjusted incidence rate ratios (aIRR) for hospitalisation ranging from 1.3 to 13.1. At highest risk for COVID-19 hospitalisation were individuals with: solid organ transplant (aIRR 13.1, 95% confidence interval [95% CI] 11.2-15.3), moderate to severe primary immunodeficiency (aIRR 9.7, 95% CI 6.3-14.9), stem cell transplant (aIRR 11.0, 95% CI 6.8-17.6), and recent treatment for haematological malignancy (aIRR 10.6, 95% CI 9.5-11.9). Results were similar for COVID-19 ICU admissions and deaths. Interpretation: Immunocompromised individuals continue to be impacted disproportionately by COVID-19 and have an urgent need for additional preventive measures beyond current vaccination programmes. These data can help determine the immunocompromised groups for which targeted prevention strategies may have the highest impact. Funding: This study was funded by AstraZeneca UK.
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BACKGROUND: Poor asthma control is associated with high short-acting ß2-agonist (SABA) use. AIM: To assess asthma-related healthcare resource utilisation (HCRU) and medication costs associated with high versus low SABA prescriptions in the UK. DESIGN & SETTING: Analysis of SABINA I (SABA use IN Asthma I), a retrospective longitudinal study using UK electronic health records (Clinical Practice Research Datalink GOLD 2008-2019 and Hospital Episode Statistics database). METHOD: Eligible patients were ≥12 years old with SABA prescriptions in the past year. SABA prescriptions (number of canisters per year) were defined as high (≥3) or low (1-2). Association of SABA prescriptions with HCRU was assessed by negative binominal model adjusted for covariates. The UK unit costs from the NHS were applied to estimate total healthcare costs (2020). Medication costs were based on the annual average number of canisters per year per patient. RESULTS: Overall, 186 061 patients with SABA prescriptions were included, of whom 51% were prescribed high SABA. Total annual average costs (HCRU and medication) were 52% higher in the high SABA group versus the low SABA group (£2 256 091 per 1000 patients/year versus £1 480 640 per 1000 patients/year). Medication costs accounted for the majority of asthma-related costs. Across both groups, most HCRU costs were for non-exacerbation-related primary care or hospital outpatient visits. The annual average HCRU cost difference for high SABA versus low SABA was the greatest for hospitalisations (+230%; £15 521 per 1000 patients/year versus £4697 per 1000 patients/year) and exacerbation-related primary care visits (+162%; £18 770 per 1000 patients/year versus £7160 per 1000 patients/year). Asthma-related HCRU extrapolated to the broader UK asthma population was £108.5 million per year higher with high SABA versus low SABA. CONCLUSION: High SABA versus low SABA prescriptions are associated with higher asthma-related HCRU costs.
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Healthcare decision-makers face difficult decisions regarding COVID-19 booster selection given limited budgets and the need to maximize healthcare gain. A constrained optimization (CO) model was developed to identify booster allocation strategies that minimize bed-days by varying the proportion of the eligible population receiving different boosters, stratified by age, and given limited healthcare expenditure. Three booster options were included: B1, costing US $1 per dose, B2, costing US $2, and no booster (NB), costing US $0. B1 and B2 were assumed to be 55%/75% effective against mild/moderate COVID-19, respectively, and 90% effective against severe/critical COVID-19. Healthcare expenditure was limited to US$2.10 per person; the minimum expected expense using B1, B2, or NB for all. Brazil was the base-case country. The model demonstrated that B1 for those aged <70 years and B2 for those ≥70 years were optimal for minimizing bed-days. Compared with NB, bed-days were reduced by 75%, hospital admissions by 68%, and intensive care unit admissions by 90%. Total costs were reduced by 60% with medical resource use reduced by 81%. This illustrates that the CO model can be used by healthcare decision-makers to implement vaccine booster allocation strategies that provide the best healthcare outcomes in a broad range of contexts.
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The objectives of this research were to produce a macro-level overview of the global COVID-19 burden and estimate the value of access to COVID-19 vaccines. A targeted literature review collated evidence of the burden. Linear modelling and data analysis estimated the health and economic effects of COVID-19 vaccines delivered in 2021, and whether additional value could have been achieved with broader and more equitable access. By 1 December 2020, there had been an estimated 17 million excess deaths due to COVID-19. Low-income countries allocated more than 30% of their healthcare budgets to COVID-19, compared to 8% in high-income countries. All country income groups experienced gross domestic product (GDP) growth lower than predicted in 2020. If all 92 countries eligible for COVAX Advance Market Committee (AMC), access had reached 40% vaccination coverage in 2021, 120% more excess deaths would have been averted, equivalent to USD 5 billion (109) in savings to healthcare systems. Every USD spent by advanced economies on vaccinations for less advanced economies averted USD 28 of economic losses in advanced economies and USD 29 in less advanced economies. The cost to high-income countries when not all countries are vaccinated far outweighs the cost of manufacturing and distributing vaccines globally.
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BACKGROUND: Expert national/global asthma management recommendations raise the issue whether a safe threshold of short-acting beta-2 agonist (SABA) use without concomitant inhaled corticosteroids (ICS) exists. OBJECTIVE: To examine SABA and maintenance therapy associations with severe asthma exacerbations across North America and Europe. METHODS: Observational analyses of 10 SABa use IN Asthma (SABINA) datasets involving 1,033,564 patients (≥12 y) from Canada, France, the Netherlands, Poland, Spain, the United Kingdom, and the United States. Negative binomial models (incidence rate ratio [IRR] [95% CI adjusted for prespecified-covariates]) evaluated associations between SABA and exacerbations. RESULTS: Across severities, 40.2% of patients were prescribed/possessed 3 or more SABA canisters/y. Per the Global Initiative for Asthma (GINA) 2018 definitions, steps 3 to 5-treated patients prescribed/possessing 3 or more versus 1 or 2 SABAs experienced more severe exacerbations (IRR 1.08 [95% CI 1.04â1.13], U.S. Medicare; IRR 2.11 [95% CI 1.96â2.27], Poland). This association was not observed in all step 1 or 2-treated patients (the Netherlands, IRR 1.25 [95% CI 0.91â1.71]; U.S. commercial, IRR 0.92 [95% CI 0.91â0.93]; U.S. Medicare, IRR 0.74 [95% CI 0.71â0.76]). We hypothesize that this inverse association between SABA and severe exacerbations in the U.S. datasets was attributable to the large patient population possessing fewer than 3 SABA and no maintenance therapy and receiving oral corticosteroid bursts without face-to-face health care provider encounters. In U.S. SABA monotherapy-treated patients, 3 or more SABAs were associated with more emergency/outpatient visits and hospitalizations (IRR 1.31 [95% CI 1.29â1.34]). Most GINA 2 to 5-treated study patients (60.6%) did not have maintenance therapy for up to 50% of the time; however, the association of 3 or more SABAs and severe exacerbations persisted (IRR 1.32 [95% CI 1.18â1.49]) after excluding these patients and the independent effect was further confirmed when U.K. SABA data were analyzed as a continuous variable in patients with up to 100% annual coverage for ICS-containing medications. CONCLUSIONS: Increasing SABA exposure is associated with severe exacerbation risk, independent of maintenance therapy. As addressed by GINA, based on studies across asthma severities where as-needed fast-acting bronchodilators with concomitant ICS decrease severe exacerbations compared with SABA, our findings highlight the importance of avoiding a rescue/reliever paradigm utilizing SABA monotherapy.
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Antiasmáticos , Asma , Administração por Inalação , Corticosteroides/uso terapêutico , Idoso , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Asma/epidemiologia , Broncodilatadores/uso terapêutico , Combinação Budesonida e Fumarato de Formoterol/uso terapêutico , Humanos , Programas Nacionais de SaúdeRESUMO
BACKGROUND: As-needed budesonide/formoterol is effective in patients with mild asthma for whom low-dose inhaled corticosteroid (ICS) maintenance therapy is appropriate. We assessed the cost-effectiveness of this regimen versus maintenance low-dose ICS plus as-needed short-acting ß2-agonist (SABA). METHODS: A probabilistic Markov cohort model was developed that simulated time within/outside severe asthma exacerbations, conducted from a UK NHS perspective with a 70-year time horizon. Clinical efficacy inputs were derived from the SYGMA 2 trial. Patients with mild asthma eligible for low-dose maintenance ICS therapy received as-needed budesonide/formoterol 200/6 µg or twice-daily budesonide 200 µg maintenance therapy plus as-needed terbutaline 0.5 mg. A severe exacerbation was defined as worsening asthma requiring systemic corticosteroid use alone/in combination with an emergency department visit, or hospitalisation for acute asthma. Utility values were derived from SYGMA 2 EQ-5D-5L data, and all-cause- and asthma-related mortality, reduction in utility of an exacerbation, and costs were based on published data. The base-case analysis discount rate was 3.5%. Model robustness was evaluated with one-way sensitivity, probabilistic sensitivity, and two scenario analyses. RESULTS: On average, as-needed budesonide/formoterol was associated with a £292.99 cost saving and quality-adjusted life year (QALY) gains of 0.001 versus ICS + SABA. At a willingness-to-pay of £20,000/QALY, as-needed budesonide/formoterol had >85% probability of being cost-effective versus ICS + SABA. Key drivers were budesonide/formoterol and budesonide maintenance annual exacerbation rates, mean daily budesonide/formoterol inhalations, and costs and outcomes discount rates. CONCLUSIONS: From a UK healthcare payer perspective, as-needed budesonide/formoterol is a cost-effective option for the treatment of mild asthma versus regular ICS.
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Corticosteroides/administração & dosagem , Corticosteroides/economia , Antiasmáticos/administração & dosagem , Antiasmáticos/economia , Asma/tratamento farmacológico , Asma/economia , Combinação Budesonida e Fumarato de Formoterol/administração & dosagem , Combinação Budesonida e Fumarato de Formoterol/economia , Análise Custo-Benefício , Quimioterapia de Manutenção/economia , Administração por Inalação , Adolescente , Adulto , Criança , Feminino , Humanos , Quimioterapia de Manutenção/métodos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Resultado do Tratamento , Reino Unido , Adulto JovemRESUMO
INTRODUCTION: Patients with asthma typically increase short-acting ß2-agonists (SABA) use with worsening symptoms. Excessive SABA use may lead to a higher risk of adverse outcomes. We evaluated, in a large population cohort, an association between SABA inhaler use and asthma exacerbations and healthcare utilization. METHODS: As part of the SABINA (SABA use IN Asthma) global program, we conducted a retrospective longitudinal observational study (SABINA I) using UK primary care electronic healthcare records (Clinical Practice Research Datalink; 2007-2017) from asthma patients aged ≥ 12 years. SABA inhaler use was classified as 'high use', ≥ 3 canisters/year versus 'low use', 0-2 canisters/year. Taking into consideration all their asthma prescriptions, patients were categorized into a treatment step according to 2016 British Thoracic Society (BTS) asthma management guidelines. Multivariable regression assessed the association of SABA inhaler use by BTS treatment steps (grouped as BTS steps 1/2 and 3-5), separately, and with outcomes of exacerbations or asthma-related healthcare utilization (primary care and hospital outpatient consultations); only patients with linked hospital data were included in this analysis. RESULTS: Of the 574,913 patients included, 218,365 (38%) had high SABA inhaler use. Overall, 336,412 patients had linked hospital data. High SABA inhaler use was significantly associated with an increased risk of exacerbations [adjusted hazard ratio, 95% confidence interval (CI): BTS steps 1/2 = 1.20, 1.16-1.24; BTS steps 3-5 = 1.24, 1.20-1.28], asthma-related primary care consultations [adjusted incidence rate ratio (IRR), 95% CI: BTS steps 1/2 = 1.24, 1.23-1.26; BTS steps 3-5 = 1.13, 1.11-1.15], and asthma-related hospital outpatient consultations (adjusted IRR, 95% CI: BTS steps 1/2 = 1.19, 1.12-1.27; BTS steps 3-5 = 1.19, 1.13-1.26). CONCLUSION: High SABA inhaler use was frequent across BTS steps and was associated with a significant increase in exacerbations and asthma-related healthcare utilization.
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Asma , Administração por Inalação , Adolescente , Asma/tratamento farmacológico , Asma/epidemiologia , Criança , Humanos , Nebulizadores e Vaporizadores , Avaliação de Resultados em Cuidados de Saúde , Estudos Retrospectivos , Reino Unido/epidemiologiaRESUMO
OBJECTIVE: Assess the cost effectiveness of budesonide/formoterol (BUD/FORM) Turbuhaler(®)+tiotropium (TIO) HandiHaler(®) vs. placebo (PBO)+TIO in patients with chronic obstructive pulmonary disease (COPD) eligible for inhaled corticosteroids/long-acting ß2-agonists (ICS/LABA). METHODS: The cost-effectiveness analysis was based on the 12-week, randomised, double-blind CLIMB trial. The study included 659 patients with pre-bronchodilator forced expiratory volume in 1 s ≤ 50% and ≥1 exacerbation requiring systemic glucocorticosteroids or antibiotics the preceding year. Patients received BUD/FORM 320/9 µg bid + TIO 18 µg qd or PBO bid + TIO 18 µg qd. Effectiveness was defined as the number of severe exacerbations (hospitalisation/emergency room visit/systemic glucocorticosteroids) avoided. A sub-analysis included antibiotics in the definition of an exacerbation. Resource use from CLIMB was combined with Danish (DKK), Finnish (), Norwegian (NOK) and Swedish (SEK) unit costs (2010). The incremental cost-effectiveness ratios (ICERs) for BUD/FORM + TIO vs. PBO + TIO were estimated using descriptive statistics and uncertainty around estimates using bootstrapping. Analyses were conducted from the societal and healthcare perspectives in Denmark, Finland, Norway and Sweden. RESULTS: From a societal perspective, the ICER was estimated at 174/severe exacerbation avoided in Finland while BUD/FORM + TIO was dominant in the other countries. From the healthcare perspective, ICERs were DKK 1580 (212), 307 and SEK 1573 (165) per severe exacerbation avoided for Denmark, Finland and Sweden, respectively, while BUD/FORM + TIO was dominant in Norway. Including antibiotics decreased ICERs by 8-15%. Sensitivity analyses showed that results were overall robust. CONCLUSION: BUD/FORM + TIO represents a clinical and economic benefit to health systems and society for the treatment of COPD in the Nordic countries. (ClinicalTrials.gov Identifier: NCT00496470).