The role of major and minor determinants in penicillin allergy testing: Time to revisit an old friend?

Background: Skin testing is an important step in evaluation of penicillin allergic reactions. It includes testing to the following: amoxicillin, benzyl penicillin, and products generated in vivo after penicillin administration, the major determinant hapten penicilloyl-polylysine (PPL) and the minor determinant mixture (MDM). Although PPL and MDM are available as a commercial kit, their supply and cost remain problematic. Objective: We aimed to evaluate the performance and utility of PPL and MDM in penicillin allergy testing. Methods: A retrospective audit over a 5-year period was undertaken for those with penicillin testing in a tertiary immunology unit. Results: In all, 214 patients were identified. Of those patients, 151 (70.6%) were female and the average age was 58 years. Unspecified penicillin was the most common index drug (n = 127 [59.3%]), followed by amoxicillin (n =3 [24.8%]) and amoxicillin-clavulanic acid (n = 21 [9.7%]). The result of skin testing was positive in 23 patients (10.7%); skin prick testing was positive in 10 patients (4.7%), and intradermal testing (IDT) was positive in 13 patients (6.1%), the majority of whom had identified amoxicillin or amoxicillin-clavulanic acid as the index drug (n = 22 [95.7%]). The result of testing to PPL and/or MDM was positive with IDT only (n=5 [23.8%]). PPL and MDM positivity coexisted with a positive reaction to amoxicillin IDT in 2 patients, 1 of whom passed an amoxicillin challenge. Additionally, 2 positive tests to PPL were present with a negative result for MDM; of these 2 positive results, 1 was positive to amoxicillin IDT. In only 1 case were the results of testing for MDM and PPL both positive, with negative results to all native ß-lactams tested; the patient tolerated an amoxicillin challenge. Overall, the negative predictive value for both skin prick testing and IDT was 89.5%. Conclusion: Benzyl penicillin and amoxicillin alone may be sufficient for in vivo testing in suspected individuals with penicillin allergy.

Forages and pastures symposium: an update on in vitro and in situ experimental techniques for approximation of ruminal fiber degradation.

Static quantification measures of chemical components are commonly used to make certain assumptions about forage or feed nutritive value and quality. In order for modern nutrient requirement models to estimate intake and digestibility more accurately, kinetic measures of ruminal fiber degradation are necessary. Compared to in vivo experiments, in vitro (IV) and in situ (IS) experimental techniques are relatively simple and inexpensive methods to determine the extent and rate of ruminal fiber degradation. This paper summarizes limitations of these techniques and statistical analyses of the resulting data, highlights key updates to these techniques in the last 30 yr, and presents opportunities for further improvements to these techniques regarding ruminal fiber degradation. The principle biological component of these techniques, ruminal fluid, is still highly variable because it is influenced by ruminally fistulated animal diet type and timing of feeding, and in the case of the IV technique by collection and transport procedures. Commercialization has contributed to the standardization, mechanization, and automation of the IV true digestibility technique, for example, the well-known DaisyII Incubator. There has been limited commercialization of supplies for the IS technique and several review papers focused on standardization in the last 30 yr; however, the IS experimental technique is not standardized and there remains variation within and among laboratories. Regardless of improved precision resulting from enhancements of these techniques, the accuracy and precision of determining the indigestible fraction are fundamental to modeling digestion kinetics and the use of these estimates in more complex dynamic nutritional modeling. Opportunities for focused research and development are additional commercialization and standardization, methods to improve the precision and accuracy of indigestible fiber fraction, data science applications, and statistical analyses of results, especially for IS data. In situ data is typically fitted to one of a few first-order kinetic models, and parameters are estimated without determining if the selected model has the best fit. Animal experimentation will be fundamental to the future of ruminant nutrition and IV and IS techniques will remain vital to bring together nutritive value with forage quality. It is feasible and important to focus efforts on improving the precision and accuracy of IV and IS results.

In vitro and in situ techniques are important to studying ruminant nutrition because these procedures go beyond measures of components of a feedstuff in a laboratory by fermenting a sample in ruminal fluid. The in situ procedure was first described regarding ruminant nutrition in 1938 and in vitro in 1966 and both techniques have been refined over time to improve the reliability of results. This review focused on the state of knowledge 30 yr ago and significant discoveries that have impacted these techniques in the last 30 yr and shared a vision for future opportunities to refine these methods further. Commercialization of equipment and supplies has resulted in increased standardization of these methods; however, efforts should be made to continue to improve the standardization, and reliability of the results, of these procedures. Statistical analyses and data science applications are opportunities to expand these techniques to modern nutritional models and/or forecasting animal performance. The amount and kinetics of ruminal degradation estimate that in vitro and in situ techniques provide continue to be crucial to advance the efficiency and sustainability of ruminant animal production.

A multicenter chart review of patient characteristics, treatment, and outcomes in hereditary angioedema: unmet need for more effective long-term prophylaxis.

BACKGROUND: Hereditary angioedema (HAE) is a rare disease characterized by unpredictable, recurring subcutaneous or submucosal swelling. Without effective therapy, HAE can negatively impact patients' quality of life. Management of HAE includes on-demand treatment of attacks and short- and long-term prophylaxis (LTP) to prevent attacks. Newer therapies may be more tolerable and effective in managing HAE; however, therapies such as androgens are still widely used in some countries owing to their relative ease of access and adequate disease control for some patients. This study evaluated the characteristics, treatment patterns, clinical outcomes, and healthcare resource utilization of a multinational cohort of patients with HAE, with a focus on understanding reasons for recommending or discontinuing available therapies. METHODS: A retrospective chart review was conducted at 12 centers in six countries and included data from patients with HAE type 1 or 2 who were ≥ 12 years of age at their first clinical visit. The relationship between LTP use and attack rates was evaluated using a multivariable Poisson regression model. Data were collected between March 2018 and July 2019. RESULTS: Data from 225 patients were collected (62.7% female, 86.2% White, 90.2% type 1); 64.4% of patients had their first HAE-related visit to the center prior to or during 2014. Treatment patterns varied between countries. Overall, 85.8% of patients were prescribed on-demand treatment and 53.8% were prescribed LTP, most commonly the androgen danazol (53.7% of patients who used LTP). Plasma-derived C1 inhibitor (Cinryze®) was used by 29.8% of patients for LTP. Patients who received LTP had a significantly lower rate of HAE attacks than patients who did not receive any LTP (incidence rate ratio (95% confidence interval) 0.90 (0.84-0.96)). Androgens were the most commonly discontinued therapy (51.3%), with low tolerability cited as the most frequent reason for discontinuation (50.0%). CONCLUSIONS: Overall, findings from this study support the use of LTP in the prevention of HAE attacks; a lower rate of attacks was observed with LTP compared with no LTP. However, the type of LTP used varied between countries, with tolerability and accessibility to specific treatments playing important roles in management decision-making.

Effects in air-exposed corn silage of medium chain fatty acids on select spoilage microbes, zoonotic pathogens, and in vitro rumen fermentation.

Medium chain fatty acid (MCFA) treatment (0.75% C6, hexanoic; C8, octanoic; C10, decanoic; or equal proportion mixtures of C6:C8:C10:C12 or C8:C10/g; C12 = dodecanoic acid) of aerobically-exposed corn silage on spoilage and pathogenic microbes and rumen fermentation were evaluated in vitro. After 24 h aerobic incubation (37 °C), microbial enumeration revealed 3 log10 colony-forming units (CFU)/g fewer (P = 0.03) wild-type yeast and molds in C8:C10-treated silage than controls. Compared with controls, wild-type enterococci decreased (P < 0.01) in all treatments except the C6:C8:C10:C12 mixture; lactic acid bacteria were decreased (P < 0.01) in all treatments except C6 and the C6:C8:C10:C12 mixture. Total aerobes and inoculated Staphylococcus aureus or Listeria monocytogenes were unaffected by treatment (P > 0.05). Anaerobic incubation (24 h at 39 °C) of ruminal fluid (10 mL) with 0.02 g overnight air-exposed MCFA-treated corn silage revealed higher hydrogen accumulations (P = 0.03) with the C8:C10 mixture than controls. Methane, acetate, propionate, butyrate, or estimates of fermented hexose were unaffected. Acetate:propionate ratios were higher (P < 0.01) and fermentation efficiencies were marginally lower (P < 0.01) with C8- or C8:C10-treated silage than controls. Further research is warranted to optimize treatments to target unwanted microbes without adversely affecting beneficial microbes.

Study protocol: Australasian Registry of Severe Cutaneous Adverse Reactions (AUS-SCAR).

INTRODUCTION: Severe cutaneous adverse reactions (SCAR) are a group of T cell-mediated hypersensitivities associated with significant morbidity, mortality and hospital costs. Clinical phenotypes include Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalised exanthematous pustulosis (AGEP). In this Australasian, multicentre, prospective registry, we plan to examine the clinical presentation, drug causality, genomic predictors, potential diagnostic approaches, treatments and long-term outcomes of SCAR in Australia and New Zealand. METHODS AND ANALYSIS: Adult and adolescent patients with SCAR including SJS, TEN, DRESS, AGEP and another T cell-mediated hypersensitivity, generalised bullous fixed drug eruption, will be prospectively recruited. A waiver of consent has been granted for some sites to retrospectively include cases which result in early mortality. DNA will be collected for all prospective cases. Blood, blister fluid and skin biopsy sampling is optional and subject to patient consent and site capacity. To develop culprit drug identification and prevention, genomic testing will be performed to confirm human leukocyte antigen (HLA) type and ex vivo testing will be performed via interferon-γ release enzyme linked immunospot assay using collected peripheral blood mononuclear cells. The long-term outcomes of SCAR will be investigated with a 12-month quality of life survey and examination of prescribing and mortality data. ETHICS AND DISSEMINATION: This study was reviewed and approved by the Austin Health Human Research Ethics Committee (HREC/50791/Austin-19). Results will be published in peer-reviewed journals and presented at relevant conferences. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (ACTRN12619000241134).

Safety and Pharmacokinetics of Taniborbactam (VNRX-5133) with Cefepime in Subjects with Various Degrees of Renal Impairment.

Taniborbactam, an investigational ß-lactamase inhibitor that is active against both serine- and metallo-ß-lactamases, is being developed in combination with cefepime to treat serious infections caused by multidrug-resistant Gram-negative bacteria. Anticipating the use of cefepime-taniborbactam in patients with impaired renal function, an open-label, single-dose clinical study was performed to examine the pharmacokinetics of both drugs in subjects with various degrees of renal function. Hemodialysis-dependent subjects were also studied to examine the amounts of cefepime and taniborbactam dialyzed. Single intravenous infusions of 2 g cefepime and 0.5 g taniborbactam coadministered over 2 h were examined, with hemodialysis-dependent subjects receiving doses both on- and off-dialysis. No subjects experienced serious adverse events or discontinued treatment due to adverse events. The majority of adverse events observed were mild in severity, and there were no trends in the safety of cefepime-taniborbactam related to declining renal function or the timing of hemodialysis. Clinically significant and similar decreases in drug clearance with declining renal function were observed for both cefepime and taniborbactam. The respective decreases in geometric mean clearance for subjects with mild, moderate, and severe renal impairment compared to subjects with normal renal function were 18%, 63%, and 78% for cefepime and 15%, 63%, and 81% for taniborbactam, respectively. Decreases in clearance were similar for both drugs and were shown to be proportional to decreases in renal function. Both cefepime and taniborbactam were dialyzable, with similar amounts removed during 4 h of hemodialysis. This study is registered at ClinicalTrials.gov as NCT03690362.

Licogliflozin for nonalcoholic steatohepatitis: a randomized, double-blind, placebo-controlled, phase 2a study.

Nonalcoholic steatohepatitis (NASH) is a common chronic liver disease that may advance to fibrosis and lead to mortality; however, no pharmacotherapy is currently available. We tested the hypothesis that inhibition of both the sodium-glucose cotransporters 1 and 2 with licogliflozin would lead to improvement in NASH. A total of 107 patients with phenotypic or histologic NASH were randomized (1:2:2) to receive oral administration of either placebo (n = 21), licogliflozin 30 mg (n = 43) or 150 mg (n = 43) once daily for 12 weeks. Licogliflozin 150 mg showed a significant 32% (80% confidence interval (CI): 21-43%; P = 0.002) placebo-adjusted reduction in serum alanine aminotransferase after 12 weeks of treatment, the primary endpoint of the study. However, the 30 mg dose of licogliflozin did not meet the primary endpoint (placebo-adjusted reduction 21% (80% CI: 7-32%; P = 0.061)). Diarrhea occurred in 77% (33 of 43), 49% (21 of 43) and 43% (9 of 21) of patients treated with licogliflozin 150 mg, 30 mg and placebo, respectively, which was mostly mild in severity. No other major safety concerns were identified. Treatment with 150 mg licogliflozin led to reductions in serum alanine aminotransferase in patients with NASH. Studies of longer duration and in combination with drugs that have different mechanisms of action are needed to validate these findings and to define a role of licogliflozin as a therapeutic option for NASH. ClinicalTrials.gov identifier: NCT03205150.

The international WAO/EAACI guideline for the management of hereditary angioedema - The 2021 revision and update.

Hereditary Angioedema (HAE) is a rare and disabling disease for which early diagnosis and effective therapy are critical. This revision and update of the global WAO/EAACI guideline on the diagnosis and management of HAE provides up-to-date guidance for the management of HAE. For this update and revision of the guideline, an international panel of experts reviewed the existing evidence, developed 28 recommendations, and established consensus by an online DELPHI process. The goal of these recommendations and guideline is to help physicians and their patients in making rational decisions in the management of HAE with deficient C1-inhibitor (type 1) and HAE with dysfunctional C1-inhibitor (type 2), by providing guidance on common and important clinical issues, such as: 1) How should HAE be diagnosed? 2) When should HAE patients receive prophylactic on top of on-demand treatment and what treatments should be used? 3) What are the goals of treatment? 4) Should HAE management be different for special HAE patient groups such as children or pregnant/breast feeding women? 5) How should HAE patients monitor their disease activity, impact, and control? It is also the intention of this guideline to help establish global standards for the management of HAE and to encourage and facilitate the use of recommended diagnostics and therapies for all patients.

A Systematic Review of Physical Examination Components Adapted for Telemedicine.

Introduction: The COVID-19 pandemic ushered in a rapid, transformative adoption of telemedicine to maintain patient access to care. As clinicians made the shift from in-person to virtual practice, they faced a paucity of established and reliable clinical examination standards for virtual care settings. In this systematic review, we summarize the accuracy and reliability of virtual assessments compared with traditional in-person examination tools. Methods: We searched PubMed, Embase, Web of Science, and CINAHL from inception through September 2019 and included additional studies from handsearching of reference lists. We included studies that compared synchronous video (except allowing for audio-only modality for cardiopulmonary exams) with in-person clinical assessments of patients in various settings. We excluded behavioral health and dermatological assessments. Two investigators abstracted data using a predefined protocol. Results: A total of 64 studies were included and categorized into 5 clinical domains: neurological (N = 41), HEENT (head, eyes, ears, nose, and throat; N = 5), cardiopulmonary (N = 5), musculoskeletal (N = 8), and assessment of critically ill patients (N = 5). The cognitive assessment within the neurological exam was by far the most studied (N = 19) with the Mini-Mental Status Exam found to be highly reliable in multiple settings. Most studies showed relatively good reliability of the virtual assessment, although sample sizes were often small (<50 participants). Conclusions: Overall, virtual assessments performed similarly to in-person exam components for diagnostic accuracy but had a wide range of interrater reliability. The high heterogeneity in population, setting, and outcomes reported across studies render it difficult to draw broad conclusions on the most effective exam components to adopt into clinical practice. Further work is needed to identify virtual exam components that improve diagnostic accuracy.

The international WAO/EAACI guideline for the management of hereditary angioedema-The 2021 revision and update.

Hereditary angioedema (HAE) is a rare and disabling disease for which early diagnosis and effective therapy are critical. This revision and update of the global WAO/EAACI guideline on the diagnosis and management of HAE provides up-to-date guidance for the management of HAE. For this update and revision of the guideline, an international panel of experts reviewed the existing evidence, developed 28 recommendations, and established consensus by an online DELPHI process. The goal of these recommendations and guideline is to help physicians and their patients in making rational decisions in the management of HAE with deficient C1 inhibitor (type 1) and HAE with dysfunctional C1 inhibitor (type 2), by providing guidance on common and important clinical issues, such as: (1) How should HAE be diagnosed? (2) When should HAE patients receive prophylactic on top of on-demand treatment and what treatments should be used? (3) What are the goals of treatment? (4) Should HAE management be different for special HAE patient groups such as children or pregnant/breast-feeding women? and (5) How should HAE patients monitor their disease activity, impact, and control? It is also the intention of this guideline to help establish global standards for the management of HAE and to encourage and facilitate the use of recommended diagnostics and therapies for all patients.

Effects on weight loss and glycemic control with SAR441255, a potent unimolecular peptide GLP-1/GIP/GCG receptor triagonist.

Unimolecular triple incretins, combining the activity of glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and glucagon (GCG), have demonstrated reduction in body weight and improved glucose control in rodent models. We developed SAR441255, a synthetic peptide agonist of the GLP-1, GCG, and GIP receptors, structurally based on the exendin-4 sequence. SAR441255 displays high potency with balanced activation of all three target receptors. In animal models, metabolic outcomes were superior to results with a dual GLP-1/GCG receptor agonist. Preclinical in vivo positron emission tomography imaging demonstrated SAR441255 binding to GLP-1 and GCG receptors. In healthy subjects, SAR441255 improved glycemic control during a mixed-meal tolerance test and impacted biomarkers for GCG and GIP receptor activation. Single doses of SAR441255 were well tolerated. The results demonstrate that integrating GIP activity into dual GLP-1 and GCG receptor agonism provides improved effects on weight loss and glycemic control while buffering the diabetogenic risk of chronic GCG receptor agonism.

Antibody semorinemab reduces tau pathology in a transgenic mouse model and engages tau in patients with Alzheimer's disease.

Tau has become an attractive alternative target for passive immunotherapy efforts for Alzheimer's disease (AD). The anatomical distribution and extent of tau pathology correlate with disease course and severity better than other disease markers to date. We describe here the generation, preclinical characterization, and phase 1 clinical characterization of semorinemab, a humanized anti-tau monoclonal antibody with an immunoglobulin G4 (igG4) isotype backbone. Semorinemab binds all six human tau isoforms and protects neurons against tau oligomer neurotoxicity in cocultures of neurons and microglia. In addition, when administered intraperitoneally once weekly for 13 weeks, murine versions of semorinemab reduced the accumulation of tau pathology in a transgenic mouse model of tauopathy, independent of antibody effector function status. Semorinemab also showed clear evidence of target engagement in vivo, with increases in systemic tau concentrations observed in tau transgenic mice, nonhuman primates, and humans. Higher concentrations of systemic tau were observed after dosing in AD participants compared to healthy control participants. No concerning safety signals were observed in the phase 1 clinical trial at single doses up to 16,800 mg and multiple doses totaling 33,600 mg in a month.

Understanding intake on pastures: how, why, and a way forward.

An assessment of dietary intake is a critical component of animal nutrition. Consumption of feed resources is the basis upon which feeding strategies and grazing management are based. Yet, as far back as 1948, researchers have lauded the trials and tribulations of estimation of the phenomenon, especially when focused on grazing animals and pasture resources. The grazing environment presents a unique situation in which the feed resource is not provided to the animal but, rather, the animal operates as the mechanism of harvest. Therefore, tools for estimation must be developed, validated, and applied to the scenario. There are a plethora of methods currently in use for the estimation of intake, ranging from manual measurement of herbage disappearance to digital technologies and sensors, each of which come with its share of advantages and disadvantages. In order to more firmly grasp these concepts and provide a discussion on the future of this estimation, the Forages and Pastures Symposium at the 2020 ASAS-CSAS-WSASAS Annual Meeting was dedicated to this topic. This review summarizes the presentations in that symposium and offers further insight into where we have come from and where we are going in the estimation of intake for grazing livestock.

Impact of Longitudinal Virtual Primary Care on Diabetes Quality of Care.

BACKGROUND: Lack of healthcare access to due to physician shortages is a significant driver of telemedicine expansion in rural areas. Telemedicine is effective for management of chronic conditions such as diabetes but its effectiveness in primary care settings is unknown. OBJECTIVE: To evaluate differences in diabetes care before and after implementation of a longitudinal virtual primary care program. DESIGN: Propensity score-matched cohort study utilizing difference-in-differences analysis. PARTICIPANTS: Patients with diabetes who received care at VA primary care clinics between January 2018 and December 2019 where the Virtual Integrated Multisite Patient Aligned Care Teams (V-IMPACT) program was implemented. EXPOSURE: Patient participation in at least one V-IMPACT visit while usual care patients did not participate in V-IMPACT. MAIN MEASURES: The primary outcome was change in hemoglobin A1C (HbA1C) and secondary outcomes included change in the proportion of patients meeting diabetes quality indicators: blood pressure control, statin use, angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers (ACEi/ARB) use, and annual microalbuminuria testing. KEY RESULTS: Our propensity-matched cohort included 9010 patients split evenly between those who participated in V-IMPACT and those who remained in usual in-person care. Among individuals with diabetes who participated in V-IMPACT, the change in mean HbA1C was - 0.055% (95% CI - 0.088 to - 0.022%) while those in usual care had a - 0.047% (95% CI - 0.080 to - 0.014%) change before and after program implementation. We observed a 5.1% (95% CI 2.4 to 7.7%) absolute increase in the proportion prescribed statins in the V-IMPACT group, a 5.3% (95% CI 2.5 to 8.2%) increase prescribed ACE/ARBs, and a 4.6% (95% 1.7 to 7.5%) increase in completed yearly microalbuminuria testing. V-IMPACT was not associated with a significant difference in the proportion with controlled blood pressure at < 140/90 or < 130/90 mmHg thresholds. CONCLUSIONS: Quality of diabetes care delivered by a longitudinal virtual primary care model was similar if not better than traditional in-person care.

Pharmacokinetics and tolerability of fedratinib, an oral, selective Janus kinase 2 inhibitor, in subjects with renal or hepatic impairment.

PURPOSE: Fedratinib is an oral, selective Janus kinase 2 inhibitor that is approved in the United States for the treatment of patients with intermediate-2 or high-risk myelofibrosis. Pharmacokinetics and tolerability of fedratinib in subjects with renal impairment (RI) and hepatic impairment (HI) were evaluated in two separate studies. METHODS: In the renal study, male and female subjects with stable, chronic mild, moderate, and severe RI, as well as those with end-stage renal disease, were included. The hepatic study included subjects with stable, chronic mild HI. Both were phase 1, multicenter, open-label, single-dose studies, and included matched healthy subjects. Subjects received a single oral dose of fedratinib 300 mg on day 1, were discharged on day 4, returned for clinical visits on days 5-12, and had their end-of-study visit between days 14 and 16. RESULTS: Thirty-six and 17 subjects were included in the renal and hepatic studies, respectively. In the renal study, fedratinib area under the plasma concentration-time curve from time 0 to infinity (AUCinf) was 1.9- and 1.5-fold higher in subjects with severe and moderate RI, respectively, than in matched healthy subjects. In the hepatic study, fedratinib AUCinf did not appreciably differ between subjects with mild HI and matched healthy subjects. Overall, most treatment-emergent adverse events were gastrointestinal and mild. CONCLUSION: Mild RI and HI do not necessitate fedratinib dosage adjustments. Subjects with moderate RI should be monitored (with dosage adjustments made as necessary), whereas those with severe RI should receive a daily dose of 200 mg, reduced from the indicated dose of 400 mg.

Categorization of adverse drug reactions in electronic health records.

The purpose of this study was to evaluate the quality of adverse drug reaction (ADR) documentation in a state-wide electronic health record (EHR), and to assess the impact of the interface design on documentation accuracy and ability to provide decision support. Data were extracted from 43 011 unique records in a state-wide electronic health record in South Australia, Australia. Information obtained included ADR coding as allergy or intolerance, allergen name, reaction, and occupation of those entering data. Categorization into drug allergy or intolerance was assessed for accuracy. Reactions were entered predominantly by nurses (60.1%), also by doctors (31.0%) and pharmacists (6.1%). Of 27 314 reactions, 86.5% were coded as allergy and 13.5% as intolerance. The majority (78.2%) described reactions to drugs (as opposed to food, environmental or contact allergens), predominantly chosen from the drug database (96.4%). Many entries used free text for the reaction description (27.4%). Terms found in the predefined list under the allergy heading were more likely to be categorized as allergy, even when the mechanism was pharmacological intolerance. Only 45.1% (n = 1671/3705) of reactions consistent with intolerance (eg, "nausea," "diarrhea") were correctly categorized as such, although categorization by pharmacists was more accurate (P < .0001). These data suggest that ADR categorization as allergy or intolerance is influenced by the EHR design. The obligatory classification of ADRs into allergy or intolerance was not well understood and does not appear to have practical benefit.

Biogeographical variation in specific IgE recognition of temperate and subtropical grass pollen allergens in allergic rhinitis patients.

OBJECTIVE: Globally, grass pollens (GP) are major aeroallergen triggers of allergic rhinitis (AR) and asthma. However, patterns of allergic sensitisation to pollen of temperate (Pooideae: Lolium perenne) and subtropical (Chloridoideae: Cynodon dactylon and Panicoideae: Paspalum notatum) subfamilies in diverse climates remain unclear. This study aims to evaluate the level of allergic sensitisation and IgE specificity for major GP allergens representing the three subfamilies in biogeographically distinct regions. METHODS: Participants (GP-allergic with AR, 330; non-atopic, 29; other allergies, 54) were recruited in subtropical: Queensland, and temperate: New South Wales, Western and South Australia, regions. Clinical history, skin prick test (SPT), total and specific IgE to GP and purified allergens (ImmunoCAP) were evaluated. Cross-inhibition of sIgE with Pas n 1, Cyn d 1 and Lol p 1 by GP extracts was investigated. RESULTS: Queensland participants showed higher sensitisation to P. notatum and C. dactylon than L. perenne GP. sIgE was higher to Pas n 1 and Cyn d 1, and sIgE to Pas n 1 and Cyn d 1 was inhibited more by Panicoideae and Chloridoideae, respectively, than Pooideae GP. Conversely, participants from temperate regions showed highest sensitisation levels to L. perenne GP and Lol p 1, and sIgE to Lol p 1 was inhibited more by Pooideae than other GP. CONCLUSION: Levels and patterns of sensitisation to subtropical and temperate GP in AR patients depended on biogeography. Knowledge of the specificity of sensitisation to local allergens is important for optimal diagnosis and choice of allergen-specific immunotherapy to maximise benefit.