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JAMIA Open Jul 2024Anaphylaxis is a severe life-threatening allergic reaction, and its accurate identification in healthcare databases can harness the potential of "Big Data" for...
OBJECTIVES
Anaphylaxis is a severe life-threatening allergic reaction, and its accurate identification in healthcare databases can harness the potential of "Big Data" for healthcare or public health purposes.
MATERIALS AND METHODS
This study used claims data obtained between October 1, 2015 and February 28, 2019 from the CMS database to examine the utility of machine learning in identifying incident anaphylaxis cases. We created a feature selection pipeline to identify critical features between different datasets. Then a variety of unsupervised and supervised methods were used (eg, Sammon mapping and eXtreme Gradient Boosting) to train models on datasets of differing data quality, which reflects the varying availability and potential rarity of ground truth data in medical databases.
RESULTS
Resulting machine learning model accuracies ranged from 47.7% to 94.4% when tested on ground truth data. Finally, we found new features to help experts enhance existing case-finding algorithms.
DISCUSSION
Developing precise algorithms to detect medical outcomes in claims can be a laborious and expensive process, particularly for conditions presented and coded diversely. We found it beneficial to filter out highly potent codes used for data curation to identify underlying patterns and features. To improve rule-based algorithms where necessary, researchers could use model explainers to determine noteworthy features, which could then be shared with experts and included in the algorithm.
CONCLUSION
Our work suggests machine learning models can perform at similar levels as a previously published expert case-finding algorithm, while also having the potential to improve performance or streamline algorithm construction processes by identifying new relevant features for algorithm construction.
PubMed: 38911332
DOI: 10.1093/jamiaopen/ooae037 -
Allergy, Asthma & Immunology Research May 2024The diagnosis of anaphylaxis is based on the clinical history. The utility of tryptase measurements in clinical setting is limited. Mas-related G protein-coupled...
The diagnosis of anaphylaxis is based on the clinical history. The utility of tryptase measurements in clinical setting is limited. Mas-related G protein-coupled receptor-X2 (MRGPRX2) is expressed in mast cells and is involved in the degranulation of these cells. We evaluated the potential of MRGPRX2 as a diagnostic biomarker in patients with iodinated contrast media (ICM)-induced immediate hypersensitivity reactions (IHRs). A total of 173 patients with documented ICM-induced IHR within 4 months from registration were enrolled and skin tests for the culprit ICM were performed. The time interval was evaluated as the duration between the onset of ICM-induced IHR and the measurement of serum MRGPRX2 levels. Serum MRGPRX2 concentration was determined using an enzyme-linked immunosorbent assay kit. Of the 173 patients, 33 and 140 were included in the anaphylaxis and non-anaphylaxis groups, respectively. Serum MRGPRX2 levels were significantly higher in the anaphylaxis than in the non-anaphylaxis group (29.9 ± 24.1 vs. 20.7±17.5, = 0.044). Serum MRGPRX2 showed a moderate predictive ability for anaphylaxis, with an area under the curve of 0.61 ( = 0.058). When groups were classified based on the time interval, T1(0-2months) and T2 (2-4months), patients with anaphylaxis had higher MRGPRX2 levels compared to the non-anaphylaxis group in the T2 group (36.5±19.2 vs. 20.5±19.0, = 0.035). This pilot study shows that serum MRGPRX2 is a potential long-term biomarker for predicting anaphylaxis, particularly ICM-induced anaphylaxis. Further studies are needed to determine the role of MRGPRX2 in anaphylaxis in a larger population of patients with various drug-induced IHRs.
PubMed: 38910288
DOI: 10.4168/aair.2024.16.3.308 -
BMC Pediatrics Jun 2024Serum Sickness-Like Reaction (SSLR) is an immune response characterized by rash, polyarthralgias, inflammation, and fever. Serum sickness-like reaction is commonly...
BACKGROUND
Serum Sickness-Like Reaction (SSLR) is an immune response characterized by rash, polyarthralgias, inflammation, and fever. Serum sickness-like reaction is commonly attributed to antibiotics, anticonvulsants, and anti-inflammatory agents.
CASE PRESENTATION
A 16-year-old female with a history of overactive bladder and anemia presented with a diffuse urticarial rash, headaches, joint pain, and swelling for three days. Her medications included oral contraceptive pills, iron, mirabegron, UQora, and a probiotic. Physical examination revealed a diffuse urticarial rash, and her musculoskeletal exam revealed swelling and tenderness in her wrists. She was evaluated by her pediatrician and started on a 7-day course of prednisone, as well as antihistamines. Her CBC, basic metabolic panel, liver function panel, Lyme titers, and urinalysis were all within normal limits. With concern for hypersensitivity reaction to medication, all medications were discontinued. Nine days after symptom onset, the patient was evaluated by an allergist, who confirmed her presentation was consistent with serum sickness-like reaction. Her symptoms resolved, and her medications were re-introduced sequentially over several months. Restarting UQora, however, triggered a recurrence of her symptoms, and it was identified as the culprit medication. Consequently, UQora was permanently discontinued, and the patient has remained symptom-free.
CONCLUSIONS
This case report describes the first documented case of serum sickness-like reaction caused by UQora (active ingredient D-mannose). D-mannose is a monosaccharide, and it is frequently promoted to prevent urinary tract infections. While the clinical features and timeline in this case were typical of serum sickness-like reaction, UQora as the trigger was highly unusual. Clinicians should be aware of the diverse triggers of serum sickness-like reaction and the importance of prompt identification and management to enhance patient safety. Further research is necessary to better understand the potential therapeutic applications of D-mannose, as well as the potential risks and interactions.
Topics: Humans; Female; Serum Sickness; Adolescent
PubMed: 38909179
DOI: 10.1186/s12887-024-04753-8 -
European Journal of Dermatology : EJD Apr 2024
Topics: Humans; Drug Eruptions; Imidazoles; Pyridazines; Ichthyosis, Lamellar; Female; Antineoplastic Agents; Male
PubMed: 38907571
DOI: 10.1684/ejd.2024.4670 -
Drug Safety Jun 2024Pharmacovigilance (PV), or the ongoing safety monitoring after a medication has been licensed, plays a crucial role in pregnancy, as clinical trials often exclude... (Review)
Review
INTRODUCTION
Pharmacovigilance (PV), or the ongoing safety monitoring after a medication has been licensed, plays a crucial role in pregnancy, as clinical trials often exclude pregnant people. It is important to understand how pregnancy PV projects operate in low- and middle-income countries (LMICs), where there is a disproportionate lack of PV data yet a high burden of adverse pregnancy outcomes. We conducted a scoping review to assess how exposures and outcomes were measured in recently published pregnancy PV projects in LMICs.
METHODS
We utilized a search string, secondary review, and team knowledge to review publications focusing on therapeutic or vaccine exposures among pregnant people in LMICs. We screened abstracts for relevance before conducting a full text review, and documented measurements of exposures and outcomes (categorized as maternal, birth, or neonatal/infant) among other factors, including study topic, setting, and design, comparator groups, and funding sources.
RESULTS
We identified 31 PV publications spanning at least 24 LMICs, all focusing on therapeutics or vaccines for infectious diseases, including HIV (n = 17), tuberculosis (TB; n = 9), malaria (n = 7), pertussis, tetanus, and diphtheria (n = 1), and influenza (n = 3). As for outcomes, n = 15, n = 31, and n = 20 of the publications covered maternal, birth, and neonatal/infant outcomes, respectively. Among HIV-specific publications, the primary exposure-outcome relationship of focus was exposure to maternal antiretroviral therapy and adverse outcomes. For TB-specific publications, the main exposures of interest were second-line drug-resistant TB and isoniazid-based prevention therapeutics for pregnant people living with HIV. For malaria-specific publications, the primary exposure-outcome relationship of interest was antimalarial medication exposure during pregnancy and adverse outcomes. Among vaccine-focused publications, the exposure was assessed during a specific time during pregnancy, with an overall interest in vaccine safety and/or efficacy. The study settings were frequently from Africa, designs varied from cohort or cross-sectional studies to clinical trials, and funding sources were largely from high-income countries.
CONCLUSION
The published pregnancy PV projects were largely centered in Africa and concerned with infectious diseases. This may reflect the disease burden in LMICs but also funding priorities from high-income countries. As the prevalence of non-communicable diseases increases in LMICs, PV projects will have to broaden their scope. Birth and neonatal/infant outcomes were most reported, with fewer reporting on maternal outcomes and none on longer-term child outcomes; additionally, heterogeneity existed in definitions and ascertainment of specific measures. Notably, almost all projects covered a single therapeutic exposure, missing an opportunity to leverage their projects to cover additional exposures, add scientific rigor, create uniformity across health services, and bolster existing health systems. For many publications, the timing of exposure, specifically by trimester, was crucial to maternal and neonatal safety. While currently published pregnancy PV literature offer insights into the PV landscape in LMICs, further work is needed to standardize definitions and measurements, integrate PV projects across health services, and establish longer-term monitoring.
PubMed: 38907172
DOI: 10.1007/s40264-024-01445-1 -
The Journal of Allergy and Clinical... Jun 2024Asthma is a leading worldwide biomedical concern. Patients can experience life-threatening worsening episodes (exacerbations) usually controlled by anti-inflammatory and... (Review)
Review
Asthma is a leading worldwide biomedical concern. Patients can experience life-threatening worsening episodes (exacerbations) usually controlled by anti-inflammatory and bronchodilator drugs. However, substantial heterogeneity in treatment response exists and a subset of patients with unresolved asthma carry the major burden of this disease. The study of the epigenome and microbiome might bridge the gap between human genetics and environmental exposures to partially explain the heterogeneity in drug response. This review aims to provide a critical examination of the existing literature on the microbiome and epigenetic studies examining associations with asthma treatments and drug response, highlight convergent pathways, address current challenges, and offer future perspectives. Current epigenetic and microbiome studies have shown the bilateral relationship between asthma pharmacological interventions and the human epigenome and microbiome. These studies, focusing on corticosteroids and to a lesser extent on bronchodilators, azithromycin, immunotherapy, and mepolizumab, have improved the understanding of the molecular basis of treatment response and identified promising biomarkers for drug response prediction. Immune and inflammatory pathways (i.e., IL-2, TNF-α, NF-κB, and CEBPs) underlie microbiome-epigenetic associations with asthma treatment, representing potential therapeutic pathways to be targeted. A comprehensive evaluation of these omic biomarkers could significantly contribute to precision medicine and new therapeutic target discovery.
PubMed: 38906272
DOI: 10.1016/j.jaci.2024.06.010 -
International Journal of Clinical... Jun 2024Multidrug chemotherapy for Ewing sarcoma can lead to severe myelosuppression. We proposed two clinical questions (CQ): CQ #1, "Does primary prophylaxis with G-CSF...
Effectiveness and safety of primary prophylaxis with G-CSF for patients with Ewing sarcomas: a systematic review for the Clinical Practice Guidelines for the Use of G-CSF 2022 of the Japan Society of Clinical Oncology.
BACKGROUND
Multidrug chemotherapy for Ewing sarcoma can lead to severe myelosuppression. We proposed two clinical questions (CQ): CQ #1, "Does primary prophylaxis with G-CSF benefit chemotherapy for Ewing sarcoma?" and CQ #2, "Does G-CSF-based intensified chemotherapy improve Ewing sarcoma treatment outcomes?".
METHODS
A comprehensive literature search was conducted in PubMed, Cochrane Library, and Ichushi web databases, including English and Japanese articles published from 1990 to 2019. Two reviewers assessed the extracted papers and analyzed overall survival (OS), febrile neutropenia (FN) incidence, infection-related mortality, quality of life (QOL), and pain.
RESULTS
Twenty-five English and five Japanese articles were identified for CQ #1. After screening, a cohort study of vincristine, ifosfamide, doxorubicin, and etoposide chemotherapy with 851 patients was selected. Incidence of FN was 60.8% with G-CSF and 65.8% without; statistical tests were not conducted. Data on OS, infection-related mortality, QOL, or pain was unavailable. Consequently, CQ #1 was redefined as a future research question. As for CQ #2, we found two English and five Japanese papers, of which one high-quality randomized controlled trial on G-CSF use in intensified chemotherapy was included. This trial showed trends toward lower mortality and a significant increase in event-free survival for 2-week interval regimen with the G-CSF primary prophylactic use compared with 3-week interval.
CONCLUSION
This review indicated that G-CSF's efficacy as primary prophylaxis in Ewing sarcoma, except in children, is uncertain despite its common use. This review tentatively endorses intensified chemotherapy with G-CSF primary prophylaxis for Ewing sarcoma.
PubMed: 38904887
DOI: 10.1007/s10147-024-02572-6 -
Evidence-based Dentistry Jun 2024A critical review on the use of antimicrobials in dentistry.
DESIGN
A critical review on the use of antimicrobials in dentistry.
AIM
To provide a general overview of the use of antimicrobials in dentistry.
METHODS
The paper was divided into different topics, starting with an approach to understanding both commensal and pathogenic oral microbiota. Subsequently, emphasis was placed on the main categories of antibiotics used in dentistry (β-lactams, tetracyclines, macrolides, lincosamides, nitroimidazoles and quinolones), and the basis for their prescription. Finally, the implications between systemic diseases and the use of orally-administered antibiotics are presented.
RESULTS
The study suggests that an adequate medical history can minimize the risk of systemic adverse effects, unwanted drug interactions, and allergies related to the use of antibiotics. In this regard, when facing a potential history of allergy to a particular group of antibiotics, the prescription of a different group is mandatory. In most indications, β-lactam antibiotics represent the first-choice in dentistry. Moreover, a short-term prescription of antibiotics when treating acute oral infections is recommended. The use should be extended for 2 to 3 days following the resolution of the infection, with an average duration of 6 days in order to prevent the development of antibiotic resistance.
CONCLUSIONS
Oral infections should be managed with interventions aiming at the elimination/reduction of the associated pathogens. Furthermore, inadequate prescription of antibiotics can lead to potential risks to the patient such as allergy, adverse effects, and development of microbial resistance.
PubMed: 38902494
DOI: 10.1038/s41432-024-01031-5 -
The Journal of Allergy and Clinical... Jun 2024Ten % of the population is labeled as allergic to penicillin(s), when in fact 90% of these labels are inappropriate. Recent studies have shown that inpatient...
BACKGROUND
Ten % of the population is labeled as allergic to penicillin(s), when in fact 90% of these labels are inappropriate. Recent studies have shown that inpatient de-labelling by a direct drug challenge (dDC) is safe in low-risk patients. However, there is a need for outpatient and non-allergist de-labelling.
OBJECTIVE
To assess the safety of de-labelling low-risk adults by means of dDC in primary care.
METHODS
We searched MEDLINE, EMBASE and the Conchrane Library databases, from inception to March 15, 2022 (updated June 5, 2023) for studies performing dDC in adults in primary care or other outpatient settings. Two researchers independently screened studies for eligibility. The data extraction and critical appraisal was performed by one reviewer and we pooled the results in a meta-analysis.
RESULTS
Out of 2,138 results, 12 studies (1070 participants) were eligible for inclusion. Three studies evaluated de-labelling in primary care and 9 studies in an outpatient hospital setting. There were no critical adverse events during dDC. No reaction occurred in 97.13% of the 1070 patients, who previously labeled as penicillin-allergic, and were safely de-labelled. Ten patients (<1%) developed an immediate reaction: three had self-limiting reactions, and seven needed antihistaminics, steroids, epinephrine and/or salbutamol.
CONCLUSION
No serious allergic reactions are observed during direct amoxicillin challenge in adults in an outpatient setting. However, with the exception of one recent report, these studies are of low to moderate quality. Non-specialist de-labelling is promising but further research is required on correct risk stratification and safety assessment in large cohort studies evaluating dDC in primary care.
PubMed: 38901618
DOI: 10.1016/j.jaip.2024.06.017 -
Blood Jun 2024
Topics: Humans; Herpesvirus 6, Human; Lymphadenitis; Roseolovirus Infections; Drug Hypersensitivity Syndrome; Lymphoma; Diagnosis, Differential; Male; Female; Middle Aged
PubMed: 38900479
DOI: 10.1182/blood.2023023384