Rationale and protocol for a prospective cohort study of respiratory viral infections in patients admitted from emergency departments of community hospitals: Effect of respiratory Virus infection on EmeRgencY admission (EVERY) study.

INTRODUCTION: Respiratory syncytial virus (RSV) is a causative virus for the common cold worldwide and can result in hospitalisations and even death in patients with high-risk conditions and older adults. However, the relationship between RSV or other incidental respiratory infections and acute exacerbations of underlying conditions has not been well investigated. The primary objective of this study is to estimate RSV prevalence, risk factors for adverse outcomes or hospitalisation and their effect on the hospital course of patients with acute respiratory symptoms admitted from emergency departments. Furthermore, we evaluate the prevalence of other respiratory viruses associated with respiratory symptoms. METHODS AND ANALYSIS: We are conducting a multicentre prospective cohort study in Japan. We plan to enrol 3000 consecutive patients admitted from emergency departments with acute respiratory symptoms or signs from 1 July 2023 to 30 June 2024. A nasopharyngeal swab is obtained within 24 hours of admission and the prevalence of RSV and other respiratory viruses is measured using the FilmArray Respiratory 2.1 panel. Paired serum samples are collected from patients with suspected lower respiratory infections to measure RSV antibodies at admission and 30 days later. Information on patients' hospital course is retrieved from the electronic medical records at discharge, death or 30 days after admission. Furthermore, information on readmission to the hospital and all-cause mortality is collected 180 days after admission. We assess the differences in clinical outcomes between patients with RSV or other respiratory viruses and those without, adjusting for baseline characteristics. Clinical outcomes include in-hospital mortality, length of hospital stay, disease progression, laboratory tests and management of respiratory symptoms or underlying conditions. ETHICS AND DISSEMINATION: The study protocol was approved by the institutional review boards of participating hospitals. Our study reports will be published in academic journals as well as international meetings. TRIAL REGISTRATION NUMBER: NCT05913700.

The potential public health impact of the respiratory syncytial virus prefusion F protein vaccine in people aged ≥60 years in Japan: results of a Markov model analysis.

BACKGROUND: Respiratory syncytial virus (RSV), a common respiratory pathogen, can lead to severe symptoms, especially in older adults (OA). A recently developed RSV prefusion F protein (RSVPreF3 OA) vaccine confers high protection against RSV lower respiratory tract disease (LRTD) over two full RSV seasons. The aim of this study was to assess the potential public health impact of RSVPreF3 OA vaccination in the Japanese OA population. RESEARCH DESIGN AND METHODS: A static Markov model was used to estimate the number of symptomatic RSV cases, hospitalizations and deaths in the Japanese population aged ≥ 60 years over a 3-year time horizon. Japan-specific RSV epidemiology and healthcare resource use parameters were used; vaccine efficacy was derived from a phase 3 randomized study (AReSVi-006, NCT04886596). Vaccination coverage was set to 50%. RESULTS: Without vaccination, >5 million RSV acute respiratory illness (ARI) would occur (2.5 million LRTD and 2.8 million upper respiratory tract infections) leading to ~ 3.5 million outpatient visits, >534,000 hospitalizations and ~ 25,500 RSV-related deaths over 3 years. Vaccination could prevent > 1 million RSV-ARI cases, 728,000 outpatient visits, 143,000 hospitalizations and 6,840 RSV-related deaths. CONCLUSIONS: RSVPreF3 OA vaccination is projected to have a substantial public health impact by reducing RSV-related morbidity and mortality in the OA population.

Respiratory syncytial virus (RSV) is one of the most frequent disease-causing agents that leads to common cold symptoms. In older adults, infection with RSV can result in severe complications including bronchitis/bronchiolitis, lung infection (pneumonia) and in rare cases death. Older people and people with chronic heart or lung disease are more likely to experience complications. We estimated that more than 5 million RSV cases occur in older adults (≥60 years) over a three-year period (1.8 million over one year). Many older adults (≥60 years) will see their treating physician because of an acute RSV infection or will be hospitalized.Recently, a vaccine has been registered which protects older adults against RSV disease: the RSV prefusion F protein Older Adult (RSVPreF3 OA) vaccine. Vaccination with RSVPreF3 OA could prevent RSV infection in the older adult population and reduce the number of outpatient visits and hospitalizations; the impact is particularly high in Japan, where 35% of people are 60 years or older. We used a public health impact model to estimate how many RSV cases, hospitalizations and deaths could be prevented if 50% of people aged ≥ 60 years received the RSVPreF3 OA vaccine: We found that the vaccine could prevent about 1 million RSV infections, more than 728,000 outpatient visits, approximately 143,000 hospitalizations and 6,840 RSV-related deaths over a three-year period.Adding RSVPreF3 OA vaccine to the national immunization program in Japan could protect older adults against RSV disease and reduce the burden on patients and the healthcare system.

Epidemiological, clinical and economic burden of severe eosinophilic asthma in Taiwan: Results from a large tertiary care hospital.

BACKGROUND: Burden of severe eosinophilic asthma (SEA) data in Asia are limited. OBJECTIVE: This retrospective, observational study characterized SEA epidemiology, healthcare resource use (HCRU) and costs for adult patients in Taiwan. METHODS: Data from Taichung Veterans General Hospital electronic medical record database, between 2013 to 2016, were extracted. Eligible general asthma patients were ≥ 18 years at index date, with ≥ 1 medical claim with an asthma diagnosis after the index date. Patients with SEA (meeting additional criteria: Global Initiative for Asthma Step 4/5 treatment guidelines [within 3 months preceding index date], ≥ 2 clinically significant exacerbations, and eosinophil counts ≥ 300 cells/µL [within 12 months preceding index date] or ≥ 150 cells/µL [on index date]) and SEA patients using high-dose inhaled corticosteroids (HD ICS) were also identified. Twelve months' pre-index data were used to evaluate exacerbation frequency, treatment patterns, HCRU, and costs (2016 US Dollars). RESULTS: Of 2,601 eligible general asthmatic patients, 162 (6.2%) met predefined criteria for SEA; of SEA patients, 72/162 (44.4%) had used HD ICS. SEA and HD ICS SEA patients experienced more clinically significant exacerbations than general asthma patients (1.6 ± 3.3 and 1.5 ± 2.6 vs 0.6 ± 2.0, p < 0.01). HD ICS SEA and SEA patients incurred at least 2-2.5-fold higher total asthma-related and all-cause costs than general asthma patients and had significantly greater HCRU. CONCLUSIONS: Of eligible Taiwanese general asthma patients, 6.2% met predefined SEA criteria. Compared with general asthma patients, SEA and HD ICS SEA patients used more respiratory medications, experienced more exacerbations, and incurred greater HCRU and higher costs.

Long-Term Effectiveness and Safety of Dutasteride versus Finasteride in Patients with Male Androgenic Alopecia in South Korea: A Multicentre Chart Review Study.

BACKGROUND: Dutasteride improves hair growth compared with finasteride in male androgenic alopecia (AGA) and is well tolerated. However, real-world evidence for long-term dutasteride use in AGA is lacking. OBJECTIVE: To describe baseline characteristics, treatment patterns and long-term safety and effectiveness of dutasteride versus finasteride. METHODS: This was a multicentre, retrospective medical chart review study conducted in South Korea. The index date was the first prescription of dutasteride or finasteride. Baseline characteristics were assessed 6 months prior to index. Safety and effectiveness (improvements in basic and specific [BASP] classification) data were collected from index throughout the observation period. RESULTS: Overall, 600 male adult patients were included (dutasteride, n=295; finasteride, n=305). Dutasteride-treated patients were older (p<0.001) and more likely to have moderate/severe BASP classification at baseline (p=0.010) compared with finasteride-treated patients. Among patients treated with recommended, on-label dosing exclusively (n=535: dutasteride, n=250; finasteride, n=285), dutasteride-treated patients showed greater improvement in hair growth than finasteride-treated patients, as measured by the BASP basic M classification (adjusted incidence rate ratio [95% confidence interval]: 2.06 [1.08, 3.95]; p=0.029). Among this same subset, overall occurrence of adverse events (AEs) during the observation period were not statistically equivalent between groups (dutasteride 7.6%, finasteride 10.5%; p=0.201), although reports of AEs of special interest were equivalent (p<0.001). CONCLUSION: Dutasteride showed greater effectiveness than finasteride in improving BASP classification in treating male AGA and had a similar or possibly lower occurrence of overall AEs. Dutasteride may provide an effective and safe treatment option for male patients with AGA.

Modeling the Health and Economic Burden of Chronic Obstructive Pulmonary Disease in China From 2020 to 2039: A Simulation Study.

OBJECTIVES: Despite a growing prevalence of respiratory diseases in recent decades in China, limited evidence is available on the health and economic burden of chronic obstructive pulmonary disease (COPD). We estimated the 20-year health and economic burden of COPD in China from 2020 to 2039. METHODS: We created a probabilistic dynamic open-cohort Markov model of COPD for the Chinese population aged ≥40 years. Projections of population growth and urbanization rates were obtained from the United Nations Population Division. Other parameter inputs including smoking prevalence, COPD prevalence and severity distributions, disease-related costs, and utility weights were obtained from the most recent published literature. We modeled number of COPD patients, excess mortality due to COPD, exacerbations, COPD-attributable losses of quality-adjusted life-years, and direct and indirect COPD costs over the 20 years. RESULTS: The number of COPD patients was projected to increase from 88.3 million in 2020 to 103.3 million in 2039. The projected total losses of quality-adjusted life-years and the excess mortality due to COPD were, respectively, estimated to be 253.6 million and 3.9 million over the 20 years. The projected 20-year total discounted direct and indirect costs of COPD were, respectively, $3.1 trillion and $360.5 billion. The projected health and economic burden was higher in males and urban areas. CONCLUSIONS: COPD is projected to inflict a substantial burden to the society and the health care system in China. Effective strategies for prevention and early management of COPD are needed to mitigate the forthcoming disease burden.

Pneumococcal conjugate vaccines in Taiwan: optimizing health gains in children and older adults through constrained optimization modeling: Pneumococcal conjugate vaccines optimization in Taiwan.

OBJECTIVES: Budgetary constraints force healthcare authorities to set priorities for optimal vaccine interventions. A comprehensive decision-making tool would help inform the best combination and sequence of introduction of vaccines within constrained budgets. METHODS: Looking at available vaccines against pneumococcal infections in Taiwan (10/13-valent pneumococcal conjugate vaccines [PCV10, PCV13] and 23-valent pneumococcal polysaccharide vaccine [PPV23]), a constrained optimization (CO) model was used to assess the optimal combination of vaccines in children and older adults that would maximize the quality-adjusted life years under predefined budget constraints. Scenario analyses were carried out to evaluate the impact of vaccine efficacy (VE) on the optimized solution. RESULTS: The CO model demonstrated that the optimal sequence of vaccine introduction was PPV23 in older adults and PCV10 in children. The optimal solution was mostly driven by the potential to reduce disease burden in the older adult population. The VE of PPV23 in older adults and the VE of PCV vaccines against serotype 19A invasive pneumococcal disease had little impact on the optimal solution. CONCLUSIONS: The CO approach can be used to set priorities for introducing new vaccines while maximizing health gains per age group within the constrained National Vaccine Fund for the prevention of pneumococcal disease in Taiwan.

Burden of illness in blood eosinophilic phenotype COPD patients in New Zealand.

BACKGROUND: Real-world data on eosinophilic chronic obstructive pulmonary disease (COPD)'s clinical burden, in exacerbating/stable states, and the stability of blood eosinophil count (BEC) measurements are limited. We described measured BEC distributions among general practice COPD patients in New Zealand (NZ). METHODS: This retrospective cohort study utilized the NZ-HealthStat primary care database. Participants were aged ≥40 years, with ≥1 BEC 6 months following a COPD diagnosis code during 2011-2012. Descriptive analyses included examinations of BEC stability and association with COPD exacerbations/treatments/comorbidities. RESULTS: The most frequent COPD comorbidity was asthma (n = 1180/2909, 40.56%). Among COPD patients: 65% had BECs >150 cells/µL; 35% had BECs >300 cells/µL (non-mutually exclusive threshold categories). Treatment patterns were similar, except for more frequent inhaled corticosteroid (ICS)/long-acting beta2-agonist use in COPD patients with asthma history (51%) than those without (31%). Factors associated with BECs >150 cells/µL in participants without ICS treatment included Maori/Pacific ethnicity, obesity, oral corticosteroid (OCS) use, and exacerbation history. When stratified by asthma history, ICS treatment, and neutrophil count above/below 5000 cells/µL, geometric mean BECs ranged from 136.70 to 398.52 cells/µL. Exploratory analyses showed a fair-good COPD/BEC measurement stability over 12 months. CONCLUSIONS: Asthma was a common COPD comorbidity in NZ, particularly in Maori/Pacific patients. No overall relationship was observed between BEC/COPD exacerbations, which may reflect background ICS confounding. However, analyses in non-ICS treated participants suggested that Maori/Pacific patients with obesity and COPD, OCS treatment, exacerbation history, and/or elevated BECs are at the highest risk of COPD exacerbations. One BEC measurement appears a good indicator of a patient's BECs over time.

Characterization and burden of severe eosinophilic asthma in New Zealand: Results from the HealthStat Database.

BACKGROUND: This retrospective cohort study aimed to characterize epidemiology, medication use and healthcare resource utilization (HCRU) of patients diagnosed with severe eosinophilic asthma (SEA) compared to other patients with asthma in New Zealand. METHODS: Adult patients with asthma with no concurrent diagnosis of Chronic Obstructive Lung Disease (COPD) were identified from the HealthStat primary care database and the National Minimum Dataset using asthma diagnosis, hospital codes and prescriptions. Patients with SEA were identified using a 1-year baseline period (2011) and were those with: inhaled corticosteroid prescription above medium dose (including high dose) plus controller medication, ≥2 exacerbations, and eosinophils ≥300 cells/µl (or ≥150 in 6 weeks prior to index date); patients were followed for 1 year (2012). RESULTS: 160/3,276 (4.9%) asthmatics with available eosinophil counts met SEA criteria. Patients with SEA were more likely to be Maori, former smokers, have more comorbidities, higher mean BMI and higher neutrophil counts compared with other patients with asthma. In the follow up period, SEA patients had over 4 times as many exacerbations; incidence of exacerbations of the same frequency was highest in Maori patients. CONCLUSIONS: Compared with other patients with asthma, SEA patients had over 1.5 times as many respiratory treatment prescriptions and higher all-cause HCRU and total healthcare costs; asthma-related healthcare costs were 3.6 times greater.

Structure of polyelectrolyte brushes subject to normal electric fields.

Molecular dynamic simulations of salt-free polyelectrolyte brushes subject to external fields applied normal to the grafting substrate reveal the three-dimensional monomer and counterion distributions. It is found that below a critical electric field, local electroneutrality holds for densely grafted brushes and the brush height remains independent of field intensity. Above this critical field (which scales as 1/3 with grafting density) brush height increases smoothly, and the fraction of condensed counterions decreases. The brush bifurcates into two subpopulations of stretched and collapsed chains when the grafting density is not low. At intermediate grafting densities, the majority of chains are stretched and the minority are nonstretched. At high grafting densities bifurcation and brush height growth occur consecutively. The majority of the chains are nonstretched at high grafting densities. Although not observed prior to overstretching of the chain model, it is predicted that the two subpopulations will re-merge to a single highly stretched phase when field intensity reaches a third critical value. The ability to control subpopulations of chains suggests that utilizing electric fields normal to polyelectrolyte brushes holds potential as controllable gates in microfluidic devices.