International Variation in Severe Exacerbation Rates in Patients With Severe Asthma.

BACKGROUND: Exacerbation frequency strongly influences treatment choices in patients with severe asthma. RESEARCH QUESTION: What is the extent of the variability of exacerbations rate across countries and its implications in disease management? STUDY DESIGN AND METHODS: We retrieved data from the International Severe Asthma Registry, an international observational cohort of patients with a clinical diagnosis of severe asthma. We identified patients ≥ 18 years of age who did not initiate any biologics prior to baseline visit. A severe exacerbation was defined as the use of oral corticosteroids for ≥ 3 days or asthma-related hospitalization/ED visit. A series of negative binomial models were applied to estimate country-specific severe exacerbation rates during 365 days of follow-up, starting from a naïve model with country as the only variable to an adjusted model with country as a random-effect term and patient and disease characteristics as independent variables. RESULTS: The final sample included 7,510 patients from 17 countries (56% from the United States), contributing to 1,939 severe exacerbations (0.27/person-year). There was large between-country variation in observed severe exacerbation rate (minimum, 0.04 [Argentina]; maximum, 0.88 [Saudi Arabia]; interquartile range, 0.13-0.54), which remained substantial after adjusting for patient characteristics and sampling variability (interquartile range, 0.16-0.39). INTERPRETATION: Individuals with similar patient characteristics but coming from different jurisdictions have varied severe exacerbation risks, even after controlling for patient and disease characteristics. This suggests unknown patient factors or system-level variations at play. Disease management guidelines should recognize such between-country variability. Risk prediction models that are calibrated for each jurisdiction will be needed to optimize treatment strategies.

Individualised risk prediction model for exacerbations in patients with severe asthma: protocol for a multicentre real-world risk modelling study.

INTRODUCTION: Severe 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 ANALYSIS: The 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 DISSEMINATION: This 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 NUMBER: European Union electronic Register of Post-Authorisation Studies, EU PAS Register (EUPAS46088).

Bioaugmentation of soil with Enterobacter cloacae AKS7 enhances soil nitrogen content and boosts soil microbial functional-diversity.

Biofertilizer happens to be a promising alternative of chemical fertilizer in the establishment of sustainable agricultural practices. Following this observation, several nitrogen-fixing bacteria were isolated from the soil in which an isolate (AKS7) was selected for further studies as AKS7 showed considerable competence in growth on nitrogen-free growth medium. Acetylene reduction assay confirmed that AKS7 can fix atmospheric nitrogen efficiently. The result of Kjeldahl assay revealed that the organism (AKS7) could fix nitrogen up to 12 mg in 8 days. A strong positive correlation (r = 0.987) was observed between microbial cell biomass and the amount of nitrogen fixed by AKS7 over a period of 8 days. The organism was identified as Enterobacter cloacae through molecular and biochemical tests. To investigate the in situ nitrogen fixation by E. cloacae AKS7, naturally attenuated (AKS7 not-inoculated) and bioaugmented (AKS7-inoculated) soil microcosms were prepared. The bioaugmented microcosm showed higher level of soil nitrogen content than naturally attenuated microcosm. A large number of heterotrophic as well as nitrogen-fixing microorganisms were counted in bioaugmented microcosm than naturally attenuated microcosm. Results of the carbon source utilization patterns of BiOLOG ECO plate revealed that bioaugmented microcosm exhibited higher level of functional richness and evenness that lead to the exhibition of higher level of microbial functional-diversity in bioaugmented microcosm than the naturally attenuated microcosm. Taken together, the results indicated that augmentation of E. cloacae AKS7 into soil enhanced the nitrogen content and soil microbial functional-diversity considerably.

A Ti(III) reduction method for one-step conversion of seawater and freshwater nitrate into N2 O for stable isotopic analysis of 15 N/14 N, 18 O/16 O and 17 O/16 O.

RATIONALE: The nitrogen and oxygen (δ15 N, δ18 O, and δ17 O values) isotopic compositions of nitrate (NO3 - ) are crucial tracers of nutrient nitrogen (N) sources and dynamics in aquatic systems. Current methods such as bacterial denitrification or Cd-azide reduction require laborious multi-step conversions or toxic chemicals to reduce NO3 - to N2 O for 15 N and 18 O isotopic analyses by isotope ratio mass spectrometry (IRMS). Furthermore, the 17 O composition of N2 O cannot be directly disentangled using IRMS because 17 O contributes to mass 45 (15 N). METHODS: We describe a new one-step chemical conversion method that employs Ti(III) chloride to reduce nitrate to N2 O gas in septum sample vials. Sample preparation takes only a few minutes followed by a 24-h reaction producing N2 O gas (65-75% recovery) which partitions into the headspace. The N2 O headspace was measured for 15 N, 18 O and 17 O by IRMS or laser spectrometry. RESULTS: IRMS and laser spectrometric analyses gave accurate and reproducible N and O isotopic results down to 50 ppb (3.5 µM) NO3 -N, similar in precision to the denitrifier and Cd-azide methods. The uncertainties for dissolved nitrate reference materials (USGS32, USGS34, USGS35, IAEA-NO3 ) were ±0.2‰ for δ15 N values and ±0.3‰ for δ18 O values using IRMS. For laser-based N2 O isotope analyses the results were similar, with an δ17 O uncertainty of ±0.9‰ without any need for 15 N correction. CONCLUSIONS: Advantages of the Ti(III) reduction method are simplicity, low cost, and no requirement for toxic chemicals or anaerobic bacterial cultures. Minor corrections may be required to account for sample nitrate concentration variance and potential chemical interferences. The Ti(III) method is easily implemented into laboratories currently using N2 O headspace sampling apparatus. We expect that the Ti(III) method will promulgate the use of N and O isotopes of nitrate in important studies of nutrient dynamics and pollution in a wide range of aquatic ecosystems.