IntroductionSevere asthma is associated with a disproportionally high disease burden, including the risk of severe exacerbations. Accurate prediction of the risk of severe exacerbations may enable ...clinicians to tailor treatment plans to an individual patient. This study aims to develop and validate a novel risk prediction model for severe exacerbations in patients with severe asthma, and to examine the potential clinical utility of this tool.Methods and analysisThe target population is patients aged 18 years or older with severe asthma. Based on the data from the International Severe Asthma Registry (n=8925), a prediction model will be developed using a penalised, zero-inflated count model that predicts the rate or risk of exacerbation in the next 12 months. The risk prediction tool will be externally validated among patients with physician-assessed severe asthma in an international observational cohort, the NOVEL observational longiTudinal studY (n=1652). Validation will include examining model calibration (ie, the agreement between observed and predicted rates), model discrimination (ie, the extent to which the model can distinguish between high-risk and low-risk individuals) and the clinical utility at a range of risk thresholds.Ethics and disseminationThis study has obtained ethics approval from the Institutional Review Board of National University of Singapore (NUS-IRB-2021-877), the Anonymised Data Ethics and Protocol Transparency Committee (ADEPT1924) and the University of British Columbia (H22-01737). Results will be published in an international peer-reviewed journal.Trial registration numberEuropean Union electronic Register of Post-Authorisation Studies, EU PAS Register (EUPAS46088).
In order to deal with the volatility caused by the high proportion of renewable energy, Europe has established a cross-regional balancing market. The European experience and practices in the ...cross-regional balancing market can bring reference for the construction of China’s power market. To this end, this article conducts an in-depth study on the operation mode and settlement of the unified European balance market, and reviews the key issues and the corresponding solutions faced by the settlement level in the European integration of the balancing markets of various countries. Finally, founded on the actual situation of China’s inter-regional power market, the European balancing market is proposed for the construction of China’s inter-regional market.
IntroductionPrecision medicine (PM) involves gene testing to identify disease risk, enable early diagnosis or guide therapeutic choice, and targeted gene therapy. We aim to perform a systematic ...review and meta-analysis to quantify the cost-effectiveness profile of PM stratified by intervention type, identify sources of heterogeneity in the value-for-money of PM.Methods and analysisWe will perform a systematic search in Embase, MEDLINE, EconLit and CRD databases for studies published in English language or with translation in English between 1 January 2011 and 8 July 2021 on the topic of cost-effectiveness analysis of PM interventions. The focus will be on studies that reported health and economic outcomes. Study quality will be assessed using the Biases in Economic Studies checklist. The incremental net benefit of PM screening, diagnostic, treatment-targeting and therapeutic interventions over conventional strategies will be respectively pooled across studies using a random-effect model if heterogeneity is present, otherwise a fixed-effect model. Subgroup analyses will be performed based on disease area, WHO region and World Bank country-income level. Additionally, we will identify the potential sources of heterogeneity with random-effect meta-regressions. Finally, biases will be detected using jackknife sensitivity analysis, funnel plot assessment and Egger’s tests.Ethics and disseminationFor this type of study ethics approval or formal consent is not required. The results will be disseminated at various presentations and feedback sessions, in conference abstracts and manuscripts that will be submitted to peer-reviewed journals.PROSPERO registration numberCRD42021272956.
In this study, the start time of teleconsultations is optimized for the clinical departments of class A tertiary hospitals to improve service quality and efficiency. For this purpose, first, a ...general teleconsultation scheduling model is formulated. In the formulation, the number of services (NS) is one of the objectives because of demand intermittency and service mobility. Demand intermittency means that demand has zero size in several periods. Service mobility means that specialists move between clinical departments and the National Telemedicine Center of China to provide the service. For problem-solving, the general model is converted into a Markov decision process (MDP) by elaborately defining the state, action, and reward. To solve the MDP, deep reinforcement learning (DRL) is applied to overcome the problem of inaccurate transition probability. To reduce the dimensions of the state–action space, a semi-fixed policy is developed and applied to the deep Q network (DQN) to construct an algorithm of the DQN with a semi-fixed policy (DQN-S). For efficient fitting, an early stop strategy is applied in DQN-S training. To verify the effectiveness of the proposed scheduling model and the model solving method DQN-S, scheduling experiments are carried out based on actual data of teleconsultation demand arrivals and service arrangements. The results show that DQN-S can improve the quality and efficiency of teleconsultations by reducing 9%–41% of the demand average waiting time, 3%–42% of the number of services, and 3%–33% of the total cost of services.
•Start time is optimized to improve the quality and efficiency of teleconsultations.•The scheduling problem is modeled and solved from a data-driven perspective.•A deep reinforcement learning approach is developed for efficient solutions.
Abstract Background The recent Global Initiative for Asthma management strategy recommends achieving symptom control and minimizing the future risk of poor outcomes as priorities for asthma ...management. Objective The objective was to quantify the association between symptom control and health-related quality of life in asthma. Methods In a prospectively recruited random sample of adults with asthma, we ascertained symptom control and measured health-related quality of life using a generic (EuroQol five-dimensional questionnaire EQ-5D) and a disease-specific (Asthma Quality of Life Questionnaire) instrument, to estimate EQ-5D and five-dimensional Asthma Quality of Life Questionnaire (AQL-5D) utilities, respectively. We measured the adjusted difference in utilities across symptom control levels and calculated the loss of predictive efficiency due to aggregating multiple symptoms into one symptom control variable. Results The final sample included 958 observations from 494 individuals (mean age at baseline 52.2 ± 14.5 years; 67.0% women). Asthma was symptomatically controlled, partially controlled, and uncontrolled in 269 (28.1%), 367 (38.3%), and 322 (33.6%) observations, respectively. A person with symptomatically uncontrolled asthma would gain 0.0512 (95% CI 0.0339–0.0686) in EQ-5D or 0.0802 (95% CI 0.0693–0.0910) in AQL-5D utilities by achieving symptom control. The loss of predictive efficiency was 55.4% and 27.6% for EQ-5D and AQL-5D utilities, respectively. Conclusions Asthma symptom control status corresponds well with both generic and disease-specific quality-of-life measures. The trade-off, however, between ease of use and predictive power should be reconsidered in developing simplified measures of control. Our results have direct relevance in informing decision-analytic models of asthma and deducing the effect of interventions on quality of life through their impact on asthma control.
To date, studies investigating the association between pre-biologic biomarker levels and post-biologic outcomes have been limited to single biomarkers and assessment of biologic efficacy from ...structured clinical trials.
To elucidate the associations of pre-biologic individual biomarker levels or their combinations with pre-to-post biologic changes in asthma outcomes in real-life.
This was a registry-based, cohort study using data from 23 countries, which shared data with the International Severe Asthma Registry (May 2017-February 2023). The investigated biomarkers (highest pre-biologic levels) were immunoglobulin E (IgE), blood eosinophil count (BEC) and fractional exhaled nitric oxide (FeNO). Pre- to approximately 12-month post-biologic change for each of three asthma outcome domains (i.e. exacerbation rate, symptom control and lung function), and the association of this change with pre-biologic biomarkers was investigated for individual and combined biomarkers.
Overall, 3751 patients initiated biologics and were included in the analysis. No association was found between pre-biologic BEC and pre-to-post biologic change in exacerbation rate for any biologic class. However, higher pre-biologic BEC and FeNO were both associated with greater post-biologic improvement in FEV
for both anti-IgE and anti-IL5/5R, with a trend for anti-IL4Rα. Mean FEV
improved by 27-178 mL post-anti-IgE as pre-biologic BEC increased (250 to 1000 cells/µL), and by 43-216 mL and 129-250 mL post-anti-IL5/5R and -anti-IL4Rα, respectively along the same BEC gradient. Corresponding improvements along a FeNO gradient (25-100 ppb) were 41-274 mL, 69-207 mL and 148-224 mL for anti-IgE, anti-IL5/5R, and anti-IL4Rα, respectively. Higher baseline BEC was also associated with lower probability of uncontrolled asthma (OR 0.392; p=0.001) post-biologic for anti-IL5/5R. Pre-biologic IgE was a poor predictor of subsequent pre-to-post-biologic change for all outcomes assessed for all biologics. The combination of BEC + FeNO marginally improved the prediction of post-biologic FEV
increase (adjusted R
: 0.751), compared to BEC (adjusted R
: 0.747) or FeNO alone (adjusted R
: 0.743) (p=0.005 and <0.001, respectively); however, this prediction was not improved by the addition of IgE.
The ability of higher baseline BEC, FeNO and their combination to predict biologic-associated lung function improvement may encourage earlier intervention in patients with impaired lung function or at risk of accelerated lung function decline.
Current therapies for hepatitis B virus (HBV) cannot completely eliminate the HBV genome because of the stable population of covalently closed circular DNA (cccDNA) and so on. FIT-039, which is a ...cyclin-dependent kinase (CDK) 9 inhibitor, is known to suppress the replication of several DNA viruses including HSV, HPV and human adenovirus. In this study, we investigated the antiviral effect of FIT-039 on HBV infection. HepG2 cells expressing human sodium taurocholate cotransporting polypeptide (HepG2/NTCP cells) were infected with HBV in the presence of FIT-039. FIT-039 dose-dependently reduced intracellular viral RNA, nucleocapsid-associated viral DNA, and supernatant viral antigens without cytotoxicity in the infected cells (IC50 = 0.33 μM, CC50 > 50 μM). The antiviral activity of FIT-039 was prominent at an early phase of viral infection, although the compound did not inhibit preS1-binding to HepG2/NTCP cells. FIT-039 reduced cccDNA in HBV-replicating or HBV-infected cells. Furthermore, the antiviral activity of entecavir was significantly enhanced by the combination with FIT-039 in the chimeric mice having human hepatocytes infected with HBV. None of the mice had significant drug-related body weight or serum human-albumin concentration changes. These data suggest that CDK9 inhibitor FIT-039 is a promising antiviral candidate for HBV infection.
•CDK9 inhibitor FIT-039 inhibited HBV propagation irrespective of toxicity.•FIT-039 targeted HBV replication, but not viral attachment.•Treatment with FIT-039 significantly reduced HBV cccDNA in vitro.•The antiviral activity of entecavir was improved in cooperation with FIT-039 in vivo.
This study intends to examine influences of online information search on the use of aspirin in cardiovascular diseases (CVDs) prevention among the applicable adult population in the United States.
We ...used data of 2018 National Health Interview Survey (NHIS). Our study sample is limited to adults age 40 or older to be consistent with the American Heart Association/American College of Cardiology Foundation (AHA/ACCF) guidelines for aspirin use. Linear probability models were used to test the association between patient's aspirin use behaviors and the variables of interest in four separate models.
Our results show that the use of aspirin for CVD prevention was associated with online health information seeking in different ways. When patients received doctors' advice to use aspirin, online information seeking has a negative influence, depending on whether the individual has CVD risk factors. However, for patients without recommendations from providers, the effects of online information seeking on self-initiated aspirin use depend on the different types of preventions (primary vs. secondary) and CVD risk factors.
Overall, online health information might lead to both overuse and underuse of aspirin in CVD preventions. Findings in this study may lead to decision-making that is not consistent with advice from healthcare professionals and/or established clinical guidelines.
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