Stevens-Johnson syndrome and toxic epidermal necrolysis: A systematic review of PubMed/MEDLINE case reports from 1980 to 2020.

Background: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare, life-threatening immunologic reactions. Prior studies using electronic health records, registries or reporting databases are often limited in sample size or lack clinical details. We reviewed diverse detailed case reports published over four decades. Methods: Stevens-Johnson syndrome and toxic epidermal necrolysis-related case reports were identified from the MEDLINE database between 1980 and 2020. Each report was classified by severity (i.e., SJS, TEN, or SJS-TEN overlap) after being considered a "probable" or "definite" SJS/TEN case. The demographics, preconditions, culprit agents, clinical course, and mortality of the cases were analyzed across the disease severity. Results: Among 1,059 "probable" or "definite" cases, there were 381 (36.0%) SJS, 602 (56.8%) TEN, and 76 (7.2%) SJS-TEN overlap cases, with a mortality rate of 6.3%, 24.4%, and 21.1%, respectively. Over one-third of cases had immunocompromised conditions preceding onset, including cancer (n = 194,18.3%), autoimmune diseases (n = 97, 9.2%), and human immunodeficiency virus (HIV) (n = 52, 4.9%). During the acute phase of the reaction, 843 (79.5%) cases reported mucous membrane involvement and 210 (19.8%) involved visceral organs. Most cases were drug-induced (n = 957, 90.3%). A total of 379 drug culprits were reported; the most frequently reported drug were antibiotics (n = 285, 26.9%), followed by anticonvulsants (n = 196, 18.5%), analgesics/anesthetics (n = 126, 11.9%), and antineoplastics (n = 120, 11.3%). 127 (12.0%) cases reported non-drug culprits, including infections (n = 68, 6.4%), of which 44 were associated with a mycoplasma pneumoniae infection and radiotherapy (n = 27, 2.5%). Conclusion: An expansive list of potential causative agents were identified from a large set of literature-reported SJS/TEN cases, which warrant future investigation to understand risk factors and clinical manifestations of SJS/TEN in different populations.

Reconciling Allergy Information in the Electronic Health Record After a Drug Challenge Using Natural Language Processing.

Background: Drug challenge tests serve to evaluate whether a patient is allergic to a medication. However, the allergy list in the electronic health record (EHR) is not consistently updated to reflect the results of the challenge, affecting clinicians' prescription decisions and contributing to inaccurate allergy labels, inappropriate drug-allergy alerts, and potentially ineffective, more toxic, and/or costly care. In this study, we used natural language processing (NLP) to automatically detect discrepancies between the EHR allergy list and drug challenge test results and to inform the clinical recommendations provided in a real-time allergy reconciliation module. Methods: This study included patients who received drug challenge tests at the Mass General Brigham (MGB) Healthcare System between June 9, 2015 and January 5, 2022. At MGB, drug challenge tests are performed in allergy/immunology encounters with routine clinical documentation in notes and flowsheets. We developed a rule-based NLP tool to analyze and interpret the challenge test results. We compared these results against EHR allergy lists to detect potential discrepancies in allergy documentation and form a recommendation for reconciliation if a discrepancy was identified. To evaluate the capability of our tool in identifying discrepancies, we calculated the percentage of challenge test results that were not updated and the precision of the NLP algorithm for 200 randomly sampled encounters. Results: Among 200 samples from 5,312 drug challenge tests, 59% challenged penicillin reactivity and 99% were negative. 42.0%, 61.5%, and 76.0% of the results were confirmed by flowsheets, NLP, or both, respectively. The precision of the NLP algorithm was 96.1%. Seven percent of patient allergy lists were not updated based on drug challenge test results. Flowsheets alone were used to identify 2.0% of these discrepancies, and NLP alone detected 5.0% of these discrepancies. Because challenge test results can be recorded in both flowsheets and clinical notes, the combined use of NLP and flowsheets can reliably detect 5.5% of discrepancies. Conclusion: This NLP-based tool may be able to advance global delabeling efforts and the effectiveness of drug allergy assessments. In the real-time EHR environment, it can be used to examine patient allergy lists and identify drug allergy label discrepancies, mitigating patient risks.

The Use of Electronic Health Records to Study Drug-Induced Hypersensitivity Reactions from 2000 to 2021: A Systematic Review.

Electronic health records (EHRs) have revolutionized the field of drug hypersensitivity reaction (DHR) research. In this systematic review, we assessed 140 articles from 2000-2021, classifying them under six themes: observational studies (n=61), clinical documentation (n=27), case management (n=22), clinical decision support (CDS) (n=18), case identification (n=9), and genetic studies (n=3). EHRs provide convenient access to millions of medical records, facilitating epidemiological studies of DHRs. Though the goal of CDS is to promote safe drug prescribing, allergy alerts must be designed and used in a way that supports this effort. Ultimately, accurate allergy documentation is essential for DHR prevention.

The α-ketoglutarate/Fe(II)-dependent dioxygenase VldW is responsible for the formation of validamycin B.

From A to B: Through detailed biochemical investigations, we discovered that VldW, an α-ketoglutarate/Fe(II)-dependent dioxygenase, regioselectively hydroxylates validamycin A to validamycin B. The results provide insights into the biosynthesis of hydroxylated validamycins and could be used to control the metabolic outcomes of the validamycin pathway.