Optimization of the allergen classification of the International Classification Of Diseases, 11th Revision (ICD-11).

BACKGROUND: Accurate diagnosis of triggers or causative allergens is essential for appropriate risk assessment, providing correct advice to patients with allergy and their caregivers and personalized treatment. However, allergens have never been represented in the World Health Organization International Classification of Diseases (ICD). OBJECTIVE: In this article, we present the process of selection of allergens to better fit the ICD, 11th Revision (ICD-11) structure and the outcomes of this process. METHODS: The Logical Observation Identifiers Names and Codes database, containing 1444 allergens, was used as the basis for the selection process. Two independent experts were responsible for the first selection of the allergens according to specific technical criteria. The second step of the selection process was based on real-life relevance of the allergens according to the frequency of requests regarding each of them. RESULTS: We selected 1109 allergens (76.8%) from all 1444 present in the Logical Observation Identifiers Names and Codes database, with considerable agreement between experts (Cohen κ = 8.6). After assessment of real-life data, 297 additional relevant allergens worldwide were selected and grouped as plants (36.4%), drugs (32.6%), animal proteins (21%), mold and other microorganisms (1.5%), occupational allergens (0.4%), and miscellaneous allergens (0.5%). CONCLUSION: The stepwise approach allowed us to select the most relevant allergens in practice, which is the first step to building a classification of allergens for the WHO ICD-11. Aligned with the achievement in the construction of the pioneer section addressed to the allergic and hypersensitivity conditions in the ICD-11, the introduction of a classification for allergens can be considered timely and much needed in clinical practice.

Estimating diversity in networked ecological communities.

Comparing ecological communities across environmental gradients can be challenging, especially when the number of different taxonomic groups in the communities is large. In this setting, community-level summaries called diversity indices are widely used to detect changes in the community ecology. However, estimation of diversity indices has received relatively little attention from the statistical community. The most common estimates of diversity are the maximum likelihood estimates of the parameters of a multinomial model, even though the multinomial model implies strict assumptions about the sampling mechanism. In particular, the multinomial model prohibits ecological networks, where taxa positively and negatively co-occur. In this article, we leverage models from the compositional data literature that explicitly account for co-occurrence networks and use them to estimate diversity. Instead of proposing new diversity indices, we estimate popular diversity indices under these models. While the methodology is general, we illustrate the approach for the estimation of the Shannon, Simpson, Bray-Curtis, and Euclidean diversity indices. We contrast our method to multinomial, low-rank, and nonparametric methods for estimating diversity indices. Under simulation, we find that the greatest gains of the method are in strongly networked communities with many taxa. Therefore, to illustrate the method, we analyze the microbiome of seafloor basalts based on a 16S amplicon sequencing dataset with 1425 taxa and 12 communities.

Incorporating NOE-Derived Distances in Conformer Generation of Cyclic Peptides with Distance Geometry.

Nuclear magnetic resonance (NMR) data from NOESY (nuclear Overhauser enhancement spectroscopy) and ROESY (rotating frame Overhauser enhancement spectroscopy) experiments can easily be combined with distance geometry (DG) based conformer generators by modifying the molecular distance bounds matrix. In this work, we extend the modern DG based conformer generator ETKDG, which has been shown to reproduce experimental crystal structures from small molecules to large macrocycles well, to include NOE-derived interproton distances. In noeETKDG, the experimentally derived interproton distances are incorporated into the distance bounds matrix as loose upper (or lower) bounds to generate large conformer sets. Various subselection techniques can subsequently be applied to yield a conformer bundle that best reproduces the NOE data. The approach is benchmarked using a set of 24 (mostly) cyclic peptides for which NOE-derived distances as well as reference solution structures obtained by other software are available. With respect to other packages currently available, the advantages of noeETKDG are its speed and that no prior force-field parametrization is required, which is especially useful for peptides with unnatural amino acids. The resulting conformer bundles can be further processed with the use of structural refinement techniques to improve the modeling of the intramolecular nonbonded interactions. The noeETKDG code is released as a fully open-source software package available at www.github.com/rinikerlab/customETKDG.

OCRE Domains of Splicing Factors RBM5 and RBM10: Tyrosine Ring-Flip Frequencies Determined by Integrated Use of 1 H NMR Spectroscopy and Molecular Dynamics Simulations.

The 55-residue OCRE domains of the splicing factors RBM5 and RBM10 contain 15 tyrosines in compact, globular folds. At 25 °C, all 15 tyrosines show symmetric 1 H NMR spectra, with averaged signals for the pairs of δ- and ϵ-ring hydrogens. At 4 °C, two tyrosines were identified as showing 1 H NMR line-broadening due to lowered frequency of the ring-flipping. For the other 13 tyrosine rings, it was not evident, from the 1 H NMR data alone, whether they were either all flipping at high frequencies, or whether slowed flipping went undetected due to small chemical-shift differences between pairs of exchanging ring hydrogen atoms. Here, we integrate 1 H NMR spectroscopy and molecular dynamics (MD) simulations to determine the tyrosine ring-flip frequencies. In the RBM10-OCRE domain, we found that, for 11 of the 15 tyrosines, these frequencies are in the range 2.0×106 to 1.3×108  s-1 , and we established an upper limit of <1.0×106  s-1 for the remaining four residues. The experimental data and the MD simulation are mutually supportive, and their combined use extends the analysis of aromatic ring-flip events beyond the limitations of routine 1 H NMR line-shape analysis into the nanosecond frequency range.

Prospective Study of Plant-Based Dietary Patterns and Diabetes in Puerto Rican Adults.

BACKGROUND: Vegetarian-type dietary patterns have been associated with reducing the risk of developing diabetes and may function as an effective strategy for diabetes management. OBJECTIVES: We aimed to examine the associations between adherence to plant-based diet indices and the risk of developing diabetes in the Boston Puerto Rican Health Study. METHODS: Puerto Rican adults (n = 646), aged 45-75 y and free of diabetes at baseline, were included. Dietary intake was assessed via a validated FFQ. Three plant-based dietary indices were calculated: an overall plant-based diet index (PDI), a healthful plant-based diet index (hPDI), and an unhealthful plant-based diet index (uPDI). Incident diabetes was defined as fasting plasma glucose ≥ 126 mg/dL (7.0 mmol/L), glycated hemoglobin ≥ 6.5% (48 mmol/mol), or use of hypoglycemic agents during follow-up. Cox proportional hazards were used to evaluate associations between the dietary patterns and incidence of diabetes, adjusting for potential confounders, such as age, sex, socioeconomic status, lifestyle factors, obesity, total energy intake, depressive symptomatology, and plasma concentrations of lipids. RESULTS: During a mean of 4.2 y of follow-up, we identified 134 diabetes cases. After adjustment for covariates, higher hPDI was associated with lower risk of developing diabetes (adjusted HR for the highest compared with the lowest tertile: 0.54; 95% CI: 0.31, 0.94; P-trend = 0.03). In contrast, the PDI and uPDI were not significantly associated with the risk of diabetes (P-trend > 0.3 for both). CONCLUSIONS: The healthful plant-based dietary index, but not the total plant-based dietary index, was inversely associated with diabetes risk. These findings suggest that the quality of plant-based diets must be considered when recommending plant-based diets for the prevention of diabetes.This trial was registered at clinicaltrials.gov as NCT01231958.

Food-induced anaphylaxis morbidity: Emergency department and hospitalization data support preventive strategies.

BACKGROUND: Anaphylaxis is a recognized public health issue. There is no doubt that food-induced anaphylaxis (FIA) has tremendous impact on the quality of life of patients and their families and increases direct and indirect costs. FIA is associated with increasing rates of emergency department admissions and hospitalizations and implies the risk of death. Morbidity epidemiological data are a key to tailor public health actions to this non-communicable disease. The aim of this article was to review published morbidity epidemiological data relating to FIA and potential risk factors, in order to provide evidence-based recommendations to reduce the risk of severe adverse outcomes. METHODS: We identified published studies available in PUBMED/MEDLINE (1966-2020), EMBASE (1980-2020) and CINAHL (1982-2020). The systematic review was carried out using MeSH terms related to FIA ED admissions and hospitalizations. RESULTS: A total of 25 articles were selected, 80% published in the last 5 years. After critical analysis of methodological and clinical characteristics reported in the data selected, we were able to propose preventive strategies. CONCLUSION: Anaphylaxis is a recognized public health issue. FIA is associated with increasing rates of ED admissions and hospitalizations and imply in risk of death. More than reviewing and critically interpreting the key patterns related to FIA morbidity published data, we proposed strategies in order to promote quality care of patients suffering from FIA. Our World Health Organization Collaborative Center is deeply involved in this process, and we believe that the proposed strategies will inform future healthcare policies on anaphylaxis. The long-term objective would be to improve clinical care and quality of life of patients and their families, and develop risk-stratified, cost-effective preventive measures.

Global implementation of the world health organization's International Classification of Diseases (ICD)-11: The allergic and hypersensitivity conditions model.

The International Classification of Diseases (ICD) provides a common language for use worldwide as a diagnostic and classification tool for epidemiology, clinical purposes and health management. Since its first edition, the ICD has maintained a framework distributing conditions according to topography, with the result that some complex conditions, such as allergies and hypersensitivity disorders (A/H) including anaphylaxis, have been poorly represented. The change in hierarchy in ICD-11 permitted the construction of the pioneer section addressed to A/H, which may result in more accurate mortality and morbidity statistics, including more accurate accounting for mortality due to anaphylaxis, strengthen classification, terminology and definitions. The ICD-11 was presented and adopted by the 72nd World Health Assembly in May 2019, and the implementation is ongoing worldwide. We here present the outcomes from an online survey undertaken to reach out the allergy community worldwide in order to peer review the terminology, classification and definitions of A/H introduced into ICD-11 and to support their global implementation. Data are presented here for 406 respondents from 74 countries. All of the subsections of the new A/H section of the ICD-11 had been considered with good accuracy by the majority of respondents. We believe that, in addition to help during the implementation phase, all the comments provided will help to improve the A/H classification and to increase awareness by different disciplines of what actions are needed to ensure more accurate epidemiological data and better clinical management of A/H patients.

Changing the history of anaphylaxis mortality statistics through the World Health Organization's International Classification of Diseases-11.

We review the history of the classification and coding changes for anaphylaxis and provide current and perspective information in the field. In 2012, an analysis of Brazilian data demonstrated undernotification of anaphylaxis-related deaths because of the difficulties of coding using the International Classification of Diseases, 10th Revision. This work triggered strategic international actions supported by the Joint Allergy Academies and the International Classification of Diseases World Health Organization (WHO) leadership to update the classification of allergic disorders for the International Classification of Diseases, 11th Revision (ICD-11), which resulted in construction of the pioneer "Allergic and hypersensitivity conditions" chapter. The usability of the new framework has been tested by evaluating the same data published in 2012 from the ICD-11 perspective. Coding accuracy was much improved, reaching 95% for definite anaphylaxis. As the results were provided to the WHO Mortality Reference Group, coding rules have been changed, allowing anaphylaxis to be recorded as an underlying cause of death in official mortality statistics. The mandatory use of ICD-11 from January 2022 for documenting cause of death could have 2 immediate consequences: (1) the reported number of anaphylaxis-related deaths might increase because of more appropriate coding and (2) the cross-sectional and longitudinal mortality data generated might ultimately lead to a better understanding of anaphylaxis epidemiology and improved health policies directed at reducing anaphylaxis-related mortality.

Methods for Real-Time Prediction of the Mode of Travel Using Smartphone-Based GPS and Accelerometer Data.

We propose and compare combinations of several methods for classifying transportation activity data from smartphone GPS and accelerometer sensors. We have two main objectives. First, we aim to classify our data as accurately as possible. Second, we aim to reduce the dimensionality of the data as much as possible in order to reduce the computational burden of the classification. We combine dimension reduction and classification algorithms and compare them with a metric that balances accuracy and dimensionality. In doing so, we develop a classification algorithm that accurately classifies five different modes of transportation (i.e., walking, biking, car, bus and rail) while being computationally simple enough to run on a typical smartphone. Further, we use data that required no behavioral changes from the smartphone users to collect. Our best classification model uses the random forest algorithm to achieve 96.8% accuracy.

International Consensus on Allergen Immunotherapy II: Mechanisms, standardization, and pharmacoeconomics.

This article continues the comprehensive international consensus (ICON) statement on allergen immunotherapy (AIT). The initial article also recently appeared in the Journal. The conclusions below focus on key mechanisms of AIT-triggered tolerance, requirements in allergen standardization, AIT cost-effectiveness, and regulatory guidance. Potential barriers to and facilitators of the use of AIT are described in addition to future directions. International allergy specialists representing the European Academy of Allergy and Clinical Immunology; the American Academy of Allergy, Asthma & Immunology; the American College of Allergy, Asthma and Immunology; and the World Allergy Organization critically reviewed the existing literature and prepared this summary of recommendations for best AIT practice. The authors contributed equally and reached consensus on the statements presented herein.

Oncostatin M binds to extracellular matrix in a bioactive conformation: implications for inflammation and metastasis.

Oncostatin M (OSM) is an interleukin-6-like inflammatory cytokine reported to play a role in a number of pathological processes including cancer. Full-length OSM is expressed as a 26 kDa protein that can be proteolytically processed into 24 kDa and 22 kDa forms via removal of C-terminal peptides. In this study, we examined both the ability of OSM to bind to the extracellular matrix (ECM) and the activity of immobilized OSM on human breast carcinoma cells. OSM was observed to bind to ECM proteins collagen types I and XI, laminin, and fibronectin in a pH-dependent fashion, suggesting a role for electrostatic bonds that involves charged amino acids of both the ECM and OSM. The C-terminal extensions of 24 kDa and 26 kDa OSM, which contains six and thirteen basic amino acids, respectively, enhanced electrostatic binding to ECM at pH 6.5-7.5 when compared to 22 kDa OSM. The highest levels of OSM binding to ECM, though, were observed at acidic pH 5.5, where all forms of OSM bound to ECM proteins to a similar extent. This indicates additional electrostatic binding properties independent of the OSM C-terminal extensions. The reducing agent dithiothreitol also inhibited the binding of OSM to ECM suggesting a role for disulfide bonds in OSM immobilization. OSM immobilized to ECM was protected from cleavage by tumor-associated proteases and maintained activity following incubation at acidic pH for extended periods of time. Importantly, immobilized OSM remained biologically active and was able to induce and sustain the phosphorylation of STAT3 in T47D and ZR-75-1 human breast cancer cells over prolonged periods, as well as increase levels of STAT1 and STAT3 protein expression. Immobilized OSM also induced epithelial-mesenchymal transition-associated morphological changes in T47D cells. Taken together, these data indicate that OSM binds to ECM in a bioactive state that may have important implications for the development of chronic inflammation and tumor metastasis.

Bioproduction Platform to Generate Functionalized Disulfide-Constrained Peptide Analogues.

Disulfide-constrained peptides (DCPs) have gained increased attention as a drug modality due to their exceptional stability and combined advantages of large biologics and small molecules. Chemical synthesis, although widely used to produce DCPs, is associated with high cost, both economically and environmentally. To reduce the dependence on solid phase peptide synthesis and the negative environmental footprint associated with it, we present a highly versatile, low-cost, and environmentally friendly bioproduction platform to generate DCPs and their conjugates as well as chemically modified or isotope-labeled DCPs. Using the DCP against the E3 ubiquitin ligase Zinc and Ring Finger 3, MK1-3.6.10, as a model peptide, we have demonstrated the use of bacterial expression, combined with Ser ligation or transglutaminase-mediated XTEN ligation, to produce multivalent MK1-3.6.10 and MK1-3.6.10 with N-terminal functional groups. We have also developed a bioproduction method for the site-specific incorporation of unnatural amino acids into recombinant DCPs by the amber codon suppression system. Lastly, we produced 15N/13C-labeled MK1-3.6.10 with high yield and assessed the performance of a semiautomated resonance assignment workflow that could be used to accelerate binding studies and structural characterization of DCPs. This study provides a proof of concept to generate functionalized DCPs using bioproduction, providing a potential solution to alleviate the reliance on hazardous chemicals, reduce the cost, and expedite the timeline for DCP discovery.

Allergic and hypersensitivity condition in the International Patients' Summary (IPS) standard: The need of updates through the International Classification of Diseases (ICD)-11.

In 2010, the United States Human and Health Services (US HHS) and the European Union's (EU) Directorate General for Communications Networks, Content and Technology signed a memorandum of understanding to stimulate cooperation surrounding health-related information communications technology. The key project that emerged from this agreement is the International Patient Summary (IPS), intended to provide succinct clinically relevant patient summaries, which are generalizable and condition-independent, that can be readily used by all clinicians for the care of patients. Although allergies are included in the main information required by the IPS library and framework, it is misrepresented which leads to underdiagnosis or misdiagnosis of patients suffering from allergic and hypersensitivity conditions (A/H). The French and Montpellier World Health Organization (WHO) Collaborating Centres have provided arguments for supporting representation of A/H in the IPS. These are based on the relevance of the new classification of A/H in the WHO International Classification of Diseases 11th version (ICD-11), and the need for alignment of eHealth tools with harmonized health information. We first present the A/H in the IPS initiative with the mission of producing an international information system that can be used globally in electronic health records to standardize clinical diagnoses and facilitate communication between clinicians caring for patients with A/H diseases. It is believed this initiative will provide a strong voice for the allergy community and an effective process for improving the quality of health data that will optimize medical care for our patients worldwide.

Time to ACT-UP: Update on precautionary allergen labelling (PAL).

Background: Precautionary Allergen ("may contain") Labelling (PAL) is used by industry to communicate potential risk to food-allergic individuals posed by unintended allergen presence (UAP). In 2014, the World Allergy Organization (WAO) highlighted that PAL use was increasing, but often applied inconsistently and without regulation - which reduces its usefulness to consumers with food allergy and those purchasing food for them. WAO proposed the need for a regulated, international framework to underpin application of PAL. In 2019, the World Health Organization (WHO) and the Food and Agriculture Organization (FAO) of the United Nations convened an expert consultation to address the issue of PAL, the outputs of which are now being considered by the Codex Committee on Food Labelling (CCFL). Objectives: To summarise the latest data to inform the application of PAL in a more systematic way, for implementation into global food standards. Methods: A non-systematic review of issues surrounding precautionary labelling and food allergens in pre-packaged products. Results: Approximately, 100 countries around the world have legislation on the declaration of allergenic ingredients. Just a few have legislation on UAP. Given the risks that UAP entails, non-regulated PAL creates inconvenience in real life due to its unequal, difficult interpretation by patients. The attempts made so far to rationalize PAL present lights and shadows. Conclusions: At a time when CCFL is considering the results of the FAO/WHO Expert Consultation 2020-2023, we summarise the prospects to develop an effective and homogeneous legislation at a global level, and the areas of uncertainty that might hinder international agreement on a regulated framework for PAL of food allergens.

Global disparities in availability of epinephrine auto-injectors.

Background: Anaphylaxis is the most severe clinical presentation of acute systemic allergic reactions and can cause death. Given the prevalence of anaphylaxis within healthcare systems, it is a high priority public health issue. However, management of anaphylaxis - both acute and preventative - varies by region. Methods: The World Allergy Organization (WAO) Anaphylaxis Committee and the WAO Junior Members Steering Group undertook a global online survey to evaluate local practice in the diagnosis and management of anaphylaxis across regions. Results: Responses were received from WAO members in 66 countries. While intramuscular epinephrine (adrenaline) is first-line treatment for anaphylaxis, some countries continue to recommend alternative routes in contrast to guidelines. Epinephrine auto-injector (EAI) devices, prescribed to individuals at ongoing risk of anaphylaxis in the community setting, are only available in 60% of countries surveyed, mainly in high-income countries. Many countries in South America, Africa/Middle-East and Asian-Pacific regions do not have EAI available, or depend on individual importation. In countries where EAIs are commercially available, national policies regarding the availability of EAIs in public settings are limited to few countries (16%). There is no consensus regarding the time patients should be observed following emergency treatment of anaphylaxis. Conclusion: This survey provides a global snapshot view of the current management of anaphylaxis, and highlights key unmet needs including the global availability of epinephrine for self-injection as a key component of anaphylaxis management.

The ability of adults and children to visually identify peanuts and tree nuts.

BACKGROUND: Peanuts and tree nuts are common food allergens and are the leading cause of fatalities from food-induced anaphylaxis. Dietary avoidance is the primary management of these allergies and requires the ability to identify peanuts or tree nuts. OBJECTIVES: To investigate the ability of adults and children to visually identify peanuts and tree nuts. METHODS: A nut display was assembled that held peanuts and 9 tree nuts in a total of 19 different forms. Persons 6 years or older completed a worksheet to name the items. RESULTS: One-thousand one-hundred five subjects completed the study. The mean number of peanuts and tree nuts identified by all subjects was 8.4 (44.2%) out of a possible 19. The mean for children ages 6 to 18 was 4.6 (24.2%), compared with 11.1 (58.4%) for adults older than 18 (P < .001). The most commonly identified items were peanut in the shell and without the shell. The least identified was hazelnut (filbert) in the shell and without the shell. No difference was seen in the performance of peanut- or tree nut-allergic subjects compared with nonallergic subjects. Fifty percent of subjects with a peanut or tree nut allergy correctly identified all forms of peanuts or tree nuts to which they are allergic. Parents of peanut- or tree nut-allergic children did no better than parents of children without such allergy. CONCLUSIONS: Overall, both children and adults are unreliable at visually identifying most nuts. Treatment of nut allergies with dietary avoidance should include education for both adults and children on identification of peanuts and tree nuts.

New York City jails: COVID discharge policy, data transparency, and reform.

During the early stages of the COVID-19 pandemic in 2020, Mayor Bill de Blasio ordered the release of individuals incarcerated in New York City jails who were at high risk of contracting the disease and at low risk of committing criminal reoffense. Using public information, we construct and analyze a database of nearly 350,000 incarceration episodes in the city jail system from 2014-2020, paying special attention to what happened during the week of March 23-29, 2020, immediately following the mayor's order. In concordance with de Blasio's stated policy, we find that being discharged during this focus week is associated with a lower probability of readmission as compared to being discharged during the same calendar week in previous years. Furthermore, comparing the individuals discharged during the focus week of 2020 to those discharged during the same calendar week in previous years, we find that the former group was, on average, slightly older than the latter group, although the difference is not large. Additionally, the individuals in the former group had spent substantially longer in jail than those in the latter group. With the release of long-serving individuals demonstrated to be feasible, we also examine how the jail population would have looked over the past six years had caps in incarceration been in place. With a cap of one year, the system would experience a 15% decrease in incarceration. With a cap of 100 days, the reduction would be over 50%. Because our results are only as accurate as New York City's public-facing jail data, we discuss numerous challenges with this data and suggest improvements related to the incarcerated individual's age, gender, race, and more. Finally, we discuss the policy implications of our work, highlight some opportunities and challenges posed by incarceration caps, and suggest key areas for reform. One such reform might involve identifying and discharging low-risk individuals sooner in general, which might be feasible given the de Blasio administration's actions during the early stages of COVID-19.

Insights into urticaria in pediatric and adult populations and its management with fexofenadine hydrochloride.

OBJECTIVE: The present narrative review provides a comprehensive update of the current knowledge on urticaria, both in adult and pediatric populations, and on the safety and efficacy of fexofenadine hydrochloride (HCl) as a treatment option. DATA SOURCE: A literature search was conducted on Embase and Medline. STUDY SELECTION: Clinical studies published in English and published between 1999 and 2020 were selected. RESULTS: Although the exact pathogenesis of urticaria is not fully understood, multiple pathways of mast cell activation are discussed to explain the existence of phenotypically different clinical manifestations of urticaria. An overview of the worldwide prevalence of chronic urticaria, including disease burden and patient's quality of life is provided. The impact of urticaria on patient's life differs on the basis of whether its form is acute or chronic, but pharmacological approaches are most often needed to control the disabling symptoms. A summary of the current management of urticaria recommended by different guidelines across countries (Global; European; American; Australian; Asian; Japanese) is presented. Non-sedating, second-generation H1-antihistamines are the preferred choice of treatment across several guidelines worldwide. Herein, the efficacy and safety of fexofenadine HCl, a representative second-generation H1-antihistamine approved for the treatment of urticaria, is discussed. The occurrence of urticaria manifestations in COVID-19 patients is also briefly presented. CONCLUSION: The burden of acute and chronic urticaria is high for patients. Second generation anti-histamines such as fexofenadine HCl can help managing the symptoms.