Arrhythmias induced by dextrose-insulin challenge test in nondiagnostic Brugada ECG patterns.

INTRODUCTION: Dynamic ECG changes in Brugada syndrome (BrS) are influenced by several factors, may not be apparent, and can be unmasked by a drug test. METHODS AND RESULTS: Four of six patients with nondiagnostic Brugada ECG index patterns underwent a dextrose-insulin challenge test that resulted in J-ST segment elevation and triggered arrhythmias. CONCLUSION: Insulin action may be due in part to an outward shift in the K+ current at the end of action potential phase 1 and the dispersion of repolarization, leading to local re-entry with arrhythmogenicity. This effect is likely a phenomenon-specific to BrS.

Use, misuse, and pitfalls of the drug challenge test in the diagnosis of the Brugada syndrome.

The diagnosis of Brugada syndrome (BrS) requires the presence of a coved (Type 1) ST segment elevation in the right precordial leads of the electrocardiogram (ECG). The dynamic nature of the ECG is well known, and in patients with suspected BrS but non-diagnostic ECG at baseline, a sodium channel blocker test (SCBT) is routinely used to unmask BrS. There is little doubt, however, that in asymptomatic patients, a drug-induced Brugada pattern is associated with a much better prognosis compared to a spontaneous Type 1 ECG. The SCBT is also increasingly used to delineate the arrhythmogenic substrate during ablation studies. In the absence of a "gold standard" for the diagnosis of BrS, sensitivity and specificity of the SCBT remain elusive. By studying patient groups with different underlying diseases, it has become clear that the specificity of the test may not be optimal. This review aims to discuss the pitfalls of the SCBT and provides some directions in whom and when to perform the test. It is concluded that because of the debated specificity and the overall very low risk for future events in asymptomatic individuals, patients should be properly selected and counseled before SCBT is performed and that SCBT should not be performed in asymptomatic patients with a Type 2 Brugada pattern and no family history of BrS or sudden death.

Meropenem allergy testing performed at the bedside of hospitalized patients labelled with a penicillin allergy.

BACKGROUND: Meropenem is a widely prescribed beta-lactam for hospitalized patients. There are few data on meropenem allergy assessments in inpatients with a reported history of penicillin allergy who require a treatment with meropenem. This can lead to the use of less effective second-line antibiotics that may increase antibiotic resistances. We aimed to evaluate the clinical outcomes of a meropenem allergy assessment in admitted patients with a reported history of penicillin allergy that required meropenem for the treatment of an acute infection. METHODS: A retrospective analysis was performed on 182 inpatients labelled with a penicillin-allergy who received meropenem after an allergy assessment. The allergy study was performed bedside if meropenem was required urgently. The study included skin prick tests (SPTs) followed by an intradermal skin test (IDT) to meropenem, and a meropenem drug challenge test (DCT). If a non-immediate reaction to a beta-lactam was suspected, it was initiated with patch tests. RESULTS: The median age of the patients was 59.7 years (range 28-95) and 80 (44%) were women. A total of 196 sets of diagnostic workups were performed, with 189 (96.4%) of them being tolerated. Only two patients had a positive meropenem IV DCT, both presenting a non-severe cutaneous reaction that completely resolved after treatment. CONCLUSIONS: This study evidenced that a bedside meropenem allergy assessment of hospitalized patients labelled with a 'penicillin allergy' who require a broad-spectrum antibiotic for empiric coverage is a safe and effective procedure, avoiding the use of second-line antimicrobial agents.

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.

Drug Challenge Tests With General Anesthetics: Predictive Value of Skin Tests.

BACKGROUND: The study of perioperative drug reactions remains a major challenge for both diagnosis and therapy. The lack of a standard assessment of allergy to general anesthetics and of data establishing the true value of skin tests for most drugs used in induction and maintenance of anesthesia, as well as the lack of commercially available reagents for in vitro tests, renders the study of these reactions problematic. The aims of this study were to provide a diagnostic protocol for drug challenge testing with general anesthetics, to establish an etiological diagnosis that is as specific as possible, and to determine the predictive value of skin tests. METHODS: Twenty-nine patients with perioperative drug reactions were included in the study from November 2008 to December 2018. RESULTS: We confirmed the high negative predictive value of the tests (96%-100%) in the case of propofol, rocuronium, and fentanyl. To our knowledge, this is the first study to describe drug challenge testing with general anesthetics and, therefore, to establish the true negative predictive value of skin tests, which leads to a definitive diagnosis and safer surgery. CONCLUSIONS: After assessing risks and benefits and considering the importance of this group of drugs, we conclude that drug challenge testing with general anesthetics is necessary. We propose a protocol for perioperative drug reactions that enables us to make a highly accurate etiological diagnosis with minimum risk for the patient.

Skin tests and challenge-based drug allergy diagnosis: a retrospective study of patients with confirmed drug allergy.

Summary: Objectives. To describe clinical manifestations and performed diagnostic workup, focusing drug challenge tests (DCT), in patients with drug allergy. Methods. Retrospective study including all patients with skin tests (STs) or DCT-based drug allergy diagnosis, between 01/2014 - 06/2018 in a Portuguese allergy unit. Data were collected from electronic and paper-based clinical records. Results. We had 75 drug allergy diagnoses. Most index reactions were mild and major or equal 1 hour after drug intake. 59 (78%) diagnoses were based on DCTs, all based on multistep protocols with major or equal 3 predicted steps. Only 10% of the DCT were positive during up-dosing; timing and severity of the index reaction predicted DCT interruption during up-dosing. Conclusions. Most drug allergy diagnoses were based on multistep DCT. The identified predictors of DCT interruption during up-dosing can support the development of more personalized DCTs protocols.

Impact of electrocardiogram screening during drug challenge test for the prediction of T-wave oversensing by a subcutaneous implantable cardioverter defibrillator in patients with Brugada syndrome.

Screening tests conducted at rest may be inadequate for the prediction of the T-wave oversensing (TWOS) in subcutaneous implantable cardioverter defibrillator (S-ICD) candidates with Brugada syndrome (BrS) because of the dynamic nature of electrocardiogram (ECG) morphology. We evaluated the utility of ECG screening during drug challenge (DC) for prediction of TWOS in BrS patients implanted with an S-ICD. The study enrolled 6 consecutive BrS patients implanted with an S-ICD. In addition to baseline ECG screening, pre-implant screening during DC using a sodium channel blocker was performed in all patients. All patients underwent appropriate morphological analysis on baseline ECG screening; however, 2 BrS patients (33%) showed inappropriate sensing during DC. During 243 days of follow-up after S-ICD implantation, no patient experienced an appropriate shock. TWOS was confirmed during exercise testing in one of 2 patients who showed inappropriate sensing during DC. However, one patient with appropriate sensing during DC experienced recurrent episodes of inappropriate shocks due to TWOS during exercise. The present initial experience indicates that further studies are needed to detect the risk for TWOS from an S-ICD in BrS patients.

[Diagnostics of drug hypersensitivity reactions]. / Diagnostik von Arzneimittelüberempfindlichkeiten.

Drug hypersensitivity reactions comprise approximately 25% of all adverse drug reactions and can be classified into allergic and pseudoallergic drug reactions. Immediate type anaphylactic and delayed type rash reactions of various clinical patterns can be distinguished, depending on the pathogenesis and clinical symptoms. The diagnostic work-up encompasses a thorough but also focused evaluation of the medical history, skin tests and when indicated challenge tests. Furthermore, in vitro tests, such as basophil activation tests and T cell assays not only add valuable additional information but can also yield decisive results for the diagnosis, especially in cases of severe drug reactions or reactions which cannot be further clarified by provocation tests. The aim of these measurements is not only the proof of drug intolerance and the detection of the causal drug but also the disclosure of the type of adverse reaction and the identification of potential, tolerated alternative drugs. This information is very important for the counseling of the patient and for prevention of new drug hypersensitivity reactions in the future.

Efficacy and safety of dextrose-insulin in unmasking non-diagnostic Brugada ECG patterns.

BACKGROUND: Typical diagnostic, coved-type 1, Brugada ECG patterns fluctuate spontaneously over time with a high proportion of non-diagnostic ECG patterns. Insulin modulates ion transport mechanisms and causes hyperpolarization of the resting potential. We report our experience with unmasking J-ST changes in response to a dextrose-insulin test. METHODS: Nine patients, mean age 40.5±19.4years (range: 15-65years), presented initially with a non-diagnostic ECG pattern, which was suggestive of Brugada syndrome (group I). They were compared with 10 patients with normal ECG patterns (group II). Participants received an infusion of 50g of 50% dextrose, followed by 10IU of intravenous regular insulin. Positive changes were defined by conversion to a diagnostic ECG pattern. RESULTS: The dextrose-insulin test was positive in six of seven (85.7%) patients (kappa 0.79, p=0.02) that was confirmed with a pharmacologic test (kappa 1, p=0.003). One had an inconclusive test, and two with a negative test had an early repolarization ECG pattern. All subjects in group II had a negative test (p<0.01). The maximum changes of the J-ST segment were observed 41.3±31.4minutes (range 3-90minutes) after dextrose-insulin infusion. One patient had monomorphic ventricular bigeminy without spontaneous or induced ventricular fibrillation. CONCLUSION: Changes in J-ST segment in the Brugada syndrome are influenced by glucose-insulin, and this report reproduces and supports the efficacy and safety of this metabolic test in the differential diagnosis of patients with non-diagnostic ECG patterns.

Typing safe antibiotics in amoxicillin hypersensitive patients--development of a stepwise protocol.

INTRODUCTION: A history of an adverse reaction to amoxicillin, irrespective of the mechanism involved, significantly elevates patients' anxiety and affects therapeutic decisions in the future, leading to unnecessary avoidance of antibiotics. As a consequence, it would be useful to find a safe and reliable protocol for typing safe alternative antibiotics. The aim of the study was to determine negative predictive value of typing safe antibiotic in patients with a history of hypersensitivity reaction to amoxicillin. MATERIAL AND METHODS: 71 patients, aged 20-83, with a history of an adverse reaction to amoxicillin were retrospectively analysed. On the basis of the reaction type they were divided into three groups: A - symptoms not typical for hypersensitivity reactions, B - allergy manifested by urticaria and/or angioedema, C - anaphylaxis. In group A amoxicillin was tested, in group B - cefuroxime, and in group C - macrolide: azithromycin or clarithromycin. Telephone follow-up visits were performed twice: 6-12 months and 3-5 years after the clinical assessment to evaluate tolerance of antibiotics. On the basis of the follow-up results, the negative predictive value (NPV) of the protocol was calculated. RESULTS: The full diagnostic protocol was applied in 62 participants. Amoxicillin was found safe in 22, cefuroxime - in 21 and macrolide - in 19 patients. No anaphylactic reactions were observed during the tests. On the basis of the telephone follow-up, the NPV of the protocol was 96% in the first follow-up and 97% in the second one. CONCLUSION: A stepwise approach including SPTs, ICTs and provocations with amoxicillin / cefuroxime/macrolide - depending on a patient's history - is safe and allows typing an antibiotic in the vast majority of patients.

[Utility of challenge test in immediate hypersensitivity to hydrocortisone sodium succinate]. / Utilidad de la prueba de reto en hipersensibilidad inmediata a succinato sódico de hidrocortisona.

Corticosteroid hypersensitivity is a complex phenomenon in which many factors interact, such as idiosyncrasy, intolerance or allergic reactions. The prevalence of immediate hypersensitivity reactions to corticosteroids is 0.2%-0.5%. Corticosteroids have major therapeutic implications; thus, when hypersensitivity is suspected, in-vitro and/or in-vivo testing can be performed to confirm diagnosis, being the drug challenge the gold standard. After definitive diagnosis, cross-reactivity among the different corticosteroid groups should be considered, to choose wisely if corticosteroid therapy is still required. In Coopman classification, steroids belonging to groups A, B and D2 have high cross-reactivity, however, more studies are needed to determine the degree of cross-reaction among these drugs. This paper presents the case of a woman, in who hypersensitivity to hydrocortisone succinate was confirmed by drug challenge test.

La hipersensibilidad a corticoesteroides es un fenómeno complejo en el que interactúan múltiples factores como idiosincrasia, intolerancia o alergia. La prevalencia de las reacciones de hipersensibilidad inmediata a corticoesteroides es de 0.2 a 0.5%. Debido a la relevancia terapéutica de los esteroides, es importante confirmar el diagnóstico de hipersensibilidad con pruebas in vivo, in vitro, o ambas, el patrón de referencia es la prueba de reto con el fármaco implicado. Una vez realizado el diagnóstico y en caso de que se requiera continuar con el tratamiento con esteroides, deberá considerarse la reactividad cruzada entre los diferentes grupos propuestos en la clasificación de Coopman, en la que los corticoesteroides pertenecientes a los grupos A, B y D2 tienen una elevada reactividad cruzada entre sí; sin embargo, hacen falta más estudios para determinar el grado de reactividad cruzada entre estos fármacos. Comunicamos el caso de una paciente en la que se confirmó el diagnóstico de hipersensibilidad a succinato de hidrocortisona con la prueba de reto.

Efficacy of Pharmacological Classification of Complex Regional Pain Syndrome caused by Brachial Plexus Injury : A Case Report / The Japanese Journal of Rehabilitation Medicine

Pharmacological classification, based on a so-called drug challenge test (DCT), is one method to evaluate intractable pain following experimental administration of medicines. In this scenario, the appropriate medicine is prescribed for a patient with intractable pain based on the result of the DCT. A 61-year-old man was healthy until 2003, when he sustained a brachial plexus injury caused by a gas explosion. He had experienced fulgurant pain in his left upper limb since 2006, and had undergone stellate ganglion blocks, and treatment with amitriptyline. He was admitted for further treatment in 2010 because these treatments did not alleviate his fulgurant pain. He could not move his shoulder, elbow, wrist and fingers because of severe paralysis and arthrodesis of his left shoulder joint, and complained of fulgurant pain and persistent dullness in his left upper limb. He was diagnosed to have complex regional pain syndrome (CRPS) due to the brachial plexus injury, and electromyographic examinations showed evidence of a partial regrowth after sural nerve transplantation. Gabapentin was prescribed for the patient's CRPS based on the remarkable effect of thiamilal on this fulgurant pain. The frequency of the fulgurant pain decreased following the initiation of gabapentin therapy, and the persistent dullness disappeared. DCT is recommended for patients with intractable pain such as CRPS, in addition to neurological and electromyographic examinations, in order to elucidate the details of the pain and select the appropriate medication.

Assessment and Treatment of Chronic Pain / 全日本鍼灸学会雑誌

The definition of Pain, “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage” (International Association for the Study of Pain : IASP, 1994), which is often used to explain its subjectivity. It is necessary to evaluate the pain objectively for diagnosis and effectiveness of therapy.<BR>As an evaluation method of chronic pain, Visual Analog Scale (VAS) and Numerical Rating Scale (NRS) are used. Recent years, face visual analog scale and Current Perception Threshold (CPT) testing are also used commonly. Drug challenge test draws attention as it combines an evaluation method and an effective therapy. Meanwhile as a therapy of chronic pain, the reports of epiduroscopy and phototherapy are increasing. The epiduroscopy is an endoscopic operation for patients with the chronic low back pain. In Japan the therapy is performed increasingly for patients with the low back pain of spinal canal stenosis, failed back syndrome and lumbar disc herniation. Regarding the phototherapy, the reports which show the effectiveness of linear polarized infrared raytherapy and xenon phototherapy are mainly observed. Though the nerve block is still the dominant therapy in pain clinics, acupuncture therapy and phototherapy are prospected to increase their demands in future.