Patient Preference for Catheter-Based Hypertension Therapy and Subgroup Analysis: A Pilot Study Based on Taiwan Consensus on Renal Denervation.

Ojective: To understand hypertensive patients' preference for catheter-based therapy to manage hypertension. Methods: Survey data regarding catheter-based therapies performed at MacKay Memorial Hospital in Taipei, Taiwan, between 2019-2020 were analyzed. The questionnaire was circulated either in the clinics or during admission. A total of 46 patients completed the questionnaire. Results: A total of 46 patients (mean age 53.4 ± 13.5 years, 78.3% male) completed the questionnaire. In subgroup analysis according to Taiwan renal denervation (RDN) consensus, patients with drug intolerance (61.8% vs. 31.3%, p = 0.02) were more likely to choose RDN. Moreover, although lacking statistical significance, it is noteworthy that numerically more of the resistant hypertension group (55.6% vs. 28.0%, p = 0.09) and non-adherence group (38.5% vs. 30.0%, p = 0.20) were willing to undergo RDN. Conversely, numerically fewer patients with hypertension-mediated organ damage accepted RDN compared to those who did not have hypertension-mediated organ damage (26.1% vs. 43.5%, p = 0.21), although this disparity did not reach statistical significance. Conclusions: Approximately one-third of the patients expressed interest in considering RDN in this study. The most influential factor in patients' preference for RDN was drug intolerance due to medication-related side effects.

Case Series: Hyperbilirubinemia under elexacaftor/tezacaftor/ivacaftor in the presence of Gilbert's syndrome.

Liver-related side effects are a known complication of treatment with elexacaftor/tezacaftor/ivacaftor (ETI) for cystic fibrosis (CF). Gilbert's syndrome is caused by a genetic mutation that reduces activity of the enzyme UDP glucuronosyltransferase 1 polypeptide A1 (UGT1A1), causing elevated levels of unconjugated bilirubin in the blood and duodenal bile. The presence of Gilbert's syndrome and CF might represent additive risk factors for liver-related adverse events during ETI treatment. This case series describes six people with CF (pwCF) in whom previously unknown Gilbert's syndrome was unmasked after initiation of treatment with ETI. Although all patients had some level of hepatic dysfunction and/or elevated levels of bilirubin after initiation of ETI, the clinical course varied. Only one patient had to stop ETI therapy altogether, while the others were able to continue treatment (some at a reduced dosage and others at the full recommended daily dosage). All patients, even those using a lower dosage, experienced clinical benefit during ETI therapy. Gilbert's syndrome is not a contraindication for ETI therapy but may be mistaken for a risk factor for liver-related adverse events in pwCF. This is something that physicians need to be aware of in pwCF who show liver adverse events during ETI therapy.

A case of multiple ART intolerance responds to Albuvirtide and Dolutegravir: Case report and literature review.

Upon confirming an HIV diagnosis, patients need to start life-long antiretroviral therapy (ART) as soon as possible. During HIV treatment, ART drugs can cause intolerable adverse reactions, leading to poor medication compliance, treatment failure, and advancement of the HIV stage. Herein, we report a case of AIDS intolerant to multiple antiviral drugs due to side effects that we finally stabilized with the Albuvirtide (ABT) and Dolutegravir (DTG) combination. A 48 -year-old woman developed intractable nausea, vomiting and abdominal discomfort within one month of starting ART. Over the course of four years, she was switched to four different ART regimens due to her intolerance of severe adverse effects, mainly gastrointestinal symptoms, rash, and lethargy. Over four years, she failed to attain viral suppression due to poor drug compliance. After several ART changes, we started her on the Long-acting antiretroviral therapy (LA ART), Albuvirtide, combined with Dolutegravir, which she tolerated well. The patient's general condition improved significantly and attained marked virologic suppression. The patient's condition has been well controlled for nearly two years with good adherence. This case emphasizes the influence of ART treatment options on medication compliance and the outcome of HIV infection.

Severe Multiple Drug Intolerance Syndrome in Fibromyalgia and Irritable Bowel Syndrome.

BACKGROUND: Multiple drug intolerance syndrome (MDIS) describes patients with multiple nonimmunologically mediated adverse reactions to medications. Patients with more than 10 medication intolerance labels are considered to have severe MDIS. There is overlap in the characteristics of patients with MDIS and fibromyalgia and irritable bowel syndrome (IBS). Severe MDIS can limit treatment options in this already complex patient group. OBJECTIVE: This study assessed the prevalence of severe MDIS in patients with fibromyalgia and IBS and its associated risk factors. METHODS: A retrospective chart review identified patients diagnosed with fibromyalgia or IBS who had been seen at a large academic center from August 2019 to July 2020. Exact birthdate- and sex-matched controls who had been seen within the same time frame were selected at random. Listed drug intolerance data and patient characteristics were then analyzed with logistic regression and χ2 testing. RESULTS: Patients with fibromyalgia and IBS were 12 and 3 times more likely to have severe MDIS compared with controls, respectively. Severe MDIS was associated with polypharmacy in both groups. Opiates were the most frequently reported drug intolerance across all participants. Although patients with IBS more often reported gastrointestinal symptoms as adverse reactions, individuals with fibromyalgia did not more frequently report pain or behavioral changes as adverse reactions. CONCLUSIONS: There was an increased rate of severe MDIS in patients diagnosed with fibromyalgia and IBS. Additional studies are needed to better understand the morbidity of MDIS and how it can best be managed in patients with fibromyalgia and IBS.

Atherogenic Dyslipidemias: Unmet Needs and the Therapeutic Potential of Emerging and Novel Approaches and Drugs.

Innovative lipid-modifying agents are valuable resources to improve the control of atherogenic dyslipidemias and reduce the lipid-related residual cardiovascular risk of patients with intolerance or who are not fully responsive to a consolidated standard of care (statins plus ezetimibe). Moreover, some of the upcoming compounds potently affect lipid targets that are thus far considered "unmodifiable". The present paper is a viewpoint aimed at presenting the incremental metabolic and cardiovascular benefits of the emerging lipid-modulating agents and real-life barriers, hindering their prescription by physicians and their assumption by patients, which need to be worked out for a more diffuse and appropriate drug utilization.

Reacciones adversas a múltiples antibióticos / Adverse drug reactions to multiple antibiotics

Resumen La información sobre reacciones adversas es fundamental para conocer la seguridad real de los medicamentos comercializados. Existen casos de pacientes con síndrome de intolerancia a múl tiples drogas, una entidad poco reportada, la que puede presentarse cuando en un mismo paciente ocurren reacciones adversas a más de dos medicamentos no relacionados farmacológicamente. Se describe el caso de una mujer con diagnóstico de endocarditis por Staphylococcus aureus multisensible, que cursó con reacciones adversas a cinco antibióticos estructuralmente no relacionados y con mecanismos de acción diferentes, en dos internaciones consecutivas. Las reacciones fueron secundarias a cefazolina (tricitopenia), vancomicina (injuria renal), daptomicina (elevación de creatina fosfoquinasa) y linezolid (hepatotoxicidad) en la primera internación, y a cotrimoxazol (plaquetopenia) en la segunda. En todos los casos se observó daño transitorio en diferentes sistemas de órganos. Finalmente, se otorgó alta hospitalaria con clindamicina sin nuevas intercurrencias hasta finalizar tratamiento. Este caso podría corresponder al síndrome antes mencionado o a una entidad aún no caracterizada.

Abstract Adverse reaction reporting is essential to understand the actual safety of marketed medicines. There are cases of patients with multidrug intolerance syndrome, an under-reported entity, which can occur when adverse reactions to more than two pharmacologically unrelated drugs occur in the same patient. We describe the case of a woman diagnosed with multisensitive Staphylococcus aureus endocarditis who experienced adverse reactions to five structurally unrelated antibiotics with different mechanisms of action in two consecutive hospitalisations. The reactions were secondary to cefazolin (tricytopenia), vancomycin (renal injury), daptomycin (elevated creatine phosphokinase) and linezolid (hepatotoxicity) in the first hospitalization, and to cotrimoxazole (thrombocytopenia) in the second. Transient damage to different organ systems was observed in all cases. Finally, hospital discharge was granted with clindamycin without further intercurrences until treatment was completed. This case could cor respond to the aforementioned syndrome or to an as yet uncharacterized entity.

Toxicity of Asciminib in Real Clinical Practice: Analysis of Side Effects and Cross-Toxicity with Tyrosine Kinase Inhibitors.

(1) Background: Despite the prognostic improvements achieved with tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML), a minority of patients still fail TKIs. The recent introduction of asciminib may be a promising option in intolerant patients, as it is a first-in-class inhibitor with a more selective mechanism of action different from the ATP-competitive inhibition that occurs with TKIs. Therefore, our goal was to analyze toxicities shown with asciminib as well as to study cross-toxicity with previous TKIs. (2) Methods: An observational, multicenter, retrospective study was performed with data from 77 patients with CML with therapeutic failure to second-generation TKIs who received asciminib through a managed-access program (MAP) (3) Results: With a median follow-up of 13.7 months, 22 patients (28.5%) discontinued treatment: 32% (7/22) due to intolerance and 45% (10/22) due to resistance. Fifty-five percent of the patients reported adverse effects (AEs) with asciminib and eighteen percent grade 3-4. Most frequent AEs were: fatigue (18%), thrombocytopenia (17%), anemia (12%), and arthralgias (12%). None of the patients experienced cardiovascular events or occlusive arterial disease. Further, 26%, 25%, and 9% of patients required dose adjustment, temporary suspension, or definitive discontinuation of treatment, respectively. Toxicities under asciminib seemed lower than with prior TKIs for anemia, cardiovascular events, pleural/pericardial effusion, diarrhea, and edema. Cross-toxicity risk was statistically significant for thrombocytopenia, anemia, neutropenia, fatigue, vomiting, and pancreatitis. (4) Conclusion: Asciminib is a molecule with a good safety profile and with a low rate of AEs. However, despite its new mechanism of action, asciminib presents a risk of cross-toxicity with classical TKIs for some AEs.

[Adverse drug reactions to multiple antibiotics]. / Reacciones adversas a múltiples antibióticos.

Adverse reaction reporting is essential to understand the actual safety of marketed medicines. There are cases of patients with multidrug intolerance syndrome, an under-reported entity, which can occur when adverse reactions to more than two pharmacologically unrelated drugs occur in the same patient. We describe the case of a woman diagnosed with multisensitive Staphylococcus aureus endocarditis who experienced adverse reactions to five structurally unrelated antibiotics with different mechanisms of action in two consecutive hospitalisations. The reactions were secondary to cefazolin (tricytopenia), vancomycin (renal injury), daptomycin (elevated creatine phosphokinase) and linezolid (hepatotoxicity) in the first hospitalization, and to cotrimoxazole (thrombocytopenia) in the second. Transient damage to different organ systems was observed in all cases. Finally, hospital discharge was granted with clindamycin without further intercurrences until treatment was completed. This case could correspond to the aforementioned syndrome or to an as yet uncharacterized entity.

La información sobre reacciones adversas es fundamental para conocer la seguridad real de los medicamentos comercializados. Existen casos de pacientes con síndrome de intolerancia a múltiples drogas, una entidad poco reportada, la que puede presentarse cuando en un mismo paciente ocurren reacciones adversas a más de dos medicamentos no relacionados farmacológicamente. Se describe el caso de una mujer con diagnóstico de endocarditis por Staphylococcus aureus multisensible, que cursó con reacciones adversas a cinco antibióticos estructuralmente no relacionados y con mecanismos de acción diferentes, en dos internaciones consecutivas. Las reacciones fueron secundarias a cefazolina (tricitopenia), vancomicina (injuria renal), daptomicina (elevación de creatina fosfoquinasa) y linezolid (hepatotoxicidad) en la primera internación, y a cotrimoxazol (plaquetopenia) en la segunda. En todos los casos se observó daño transitorio en diferentes sistemas de órganos. Finalmente, se otorgó alta hospitalaria con clindamicina sin nuevas intercurrencias hasta finalizar tratamiento. Este caso podría corresponder al síndrome antes mencionado o a una entidad aún no caracterizada.

Characterization, epidemiology and risk factors of multiple drug allergy syndrome and multiple drug intolerance syndrome: A systematic review.

Background: Multiple drug allergy and multiple drug intolerance syndrome (MDAS/MDIS) labels are an impediment to clinical care and knowledge regarding these conditions is limited. This systematic review investigated the characterization, epidemiology, risk factors, clinical impact and pharmaco-economics of MDAS and MDIS. Methods: Systematic literature search across 11 databases (01 January 2000-06 November 2020) for MDIS, MDAS and related terminology. Studies were reviewed for quality of evidence and risk of bias by employing Critical Appraisal Skills Programme cohort study checklist. A narrative synthesis approach facilitated by systematic textual descriptions, tabulation and thematic analysis was adopted. Results: There was heterogeneity in terminology and methodology. Few studies applied standard drug allergy diagnostic methods. There is some evidence to suggest that multiple drug hypersensitivity syndrome (MDHS; i.e., confirmed allergies in MDAS) is a distinct clinical entity. Prevalence of MDIS and MDAS labels in unselected & selected populations varied between 2.1%-6.4% & 4.9%-90% and 1.2% & 0%-36% respectively. Reported risk factors included female gender, increasing age, body mass index, anxiety, depression, co-morbidities, concurrent allergies and increased healthcare utilization. Drugs commonly implicated were antibiotics and non-steroidal anti-inflammatory drugs. No studies relating to clinical impact and pharmaco-economics were found. Conclusion: There is considerable burden of MDAS and MDIS labels. Data needs cautious interpretation as majority of studies described involved unverified labels. Despite this limitation and heterogeneity of studies, there is some evidence to suggest that MDHS is a distinct clinical entity. Well-designed multi-centre studies applying standardized terminology and diagnostic methodology are needed to gain further insight into these conditions.

Population-Based Incidence, Severity, and Risk Factors Associated with Treated Acute-Onset COVID-19 mRNA Vaccination-Associated Hypersensitivity Reactions.

BACKGROUND: COVID-19 mRNA vaccination-associated acute-onset hypersensitivity reactions have caused anxiety and may be contributing to vaccine hesitancy. OBJECTIVE: To determine the incidence, severity, and risk factors for treated acute-onset COVID-19 mRNA vaccination-associated hypersensitivity reactions in a well-characterized population. METHODS: All Kaiser Permanente Southern California (KPSC) members who received COVID-19 mRNA vaccinations between December 15, 2020, and March 11, 2021, at a KPSC facility were identified and characterized, along with all treated acute-onset vaccination-associated hypersensitivity events. RESULTS: We identified 391,123 unique vaccine recipients (59.18% female, age 64.19 ± 17.86 years); 215,156 received 2 doses (53.54% Moderna), 157,615 only a first dose (50.13% Moderna) (1961 [1.46%] >2 weeks late getting a second dose), and 18,352 (74.43% Moderna) only a second dose. Only 104 (0.028%) (85.58% female, age 53.18 ± 15.96 years) had treated first dose events, 68 (0.030%) Moderna. Only 32 (0.014%) (93.75% female, age 57.28 ± 17.09 years) had treated second dose events, 21 (0.016%) Moderna. Only 2 (0.00033%) vaccinations resulted in anaphylaxis. Only 27 (20.77%) of those with treated first dose reactions failed to get a second dose. Only 6 of 77 (7.8%) with first dose reactions also had second dose reactions. Individuals with treated events were more likely to be female (P < .0001), younger (P < .0001), and had more pre-existing drug "allergies" (2.11 ± 2.12 vs 1.02 ± 1.41 [P < .0001] for average recipients). CONCLUSIONS: Treated acute-onset hypersensitivity events were mostly benign, more common with first COVID-19 mRNA vaccine doses, more likely to occur in younger females with typical risk factors associated with multiple drug intolerance syndrome, and very unlikely to be primarily immunologically mediated.

Why Do I Get Side Effects? Personalized (N-of-1) Trials for Statin Intolerance and the Nocebo Effect.

The ability of statins to reduce the morbidity and mortality of cardiovascular disease has ensured that they are among the most prescribed drugs in modern medicine. Unfortunately, most patients who start taking statins will end up stopping them, most commonly due to side effects. Confusingly, however, in blinded placebo-controlled trials, side effects appear no more common in those taking statins than those taking placebo. One possible explanation is that ever-present background symptoms are being falsely attributed to statins. However, another explanation is the nocebo effect, where the act of just taking a tablet (even a placebo) causes genuine side effects in patients. Two recent randomized placebo-controlled personalized (N-of-1) trials have been reported: StatinWise and SAMSON. In these trials, each participant was randomized to multiple periods of statin and placebo, with regular symptom burden assessments. Together, these trials support the existence of a significant nocebo effect from taking statins. Possibly even more importantly, they demonstrate the ability of personalized trials to inform and empower patients: up to half of the patients in these trials were able to successfully restart statins after taking part, despite previously having been statin intolerant. StatinWise and SAMSON have raised public awareness of the nocebo effect in statin intolerance. However, they also demonstrate a potential role for the personalized design outside of clinical trials. If taking part in these personalized experiments allows half of our patients to successfully restart life-saving medications, maybe we should be able to prescribe personalized experiments to our patients in the clinical setting?

Side Effect Patterns in a Crossover Trial of Statin, Placebo, and No Treatment.

BACKGROUND: Most people who begin statins abandon them, most commonly because of side effects. OBJECTIVES: The purpose of this study was to assess daily symptom scores on statin, placebo, and no treatment in participants who had abandoned statins. METHODS: Participants received 12 1-month medication bottles, 4 containing atorvastatin 20 mg, 4 placebo, and 4 empty. We measured daily symptom intensity for each using an app (scale 1-100). We also measured the "nocebo" ratio: the ratio of symptoms induced by taking statin that was also induced by taking placebo. RESULTS: A total of 60 participants were randomized and 49 completed the 12-month protocol. Mean symptom score was 8.0 (95% CI: 4.7-11.3) in no-tablet months. It was higher in statin months (16.3; 95% CI: 13.0-19.6; P < 0.001), but also in placebo months (15.4; 95% CI: 12.1-18.7; P < 0.001), with no difference between the 2 (P = 0.388). The corresponding nocebo ratio was 0.90. In the individual-patient daily data, neither symptom intensity on starting (OR: 1.02; 95% CI: 0.98-1.06; P = 0.28) nor extent of symptom relief on stopping (OR: 1.01; 95% CI: 0.98-1.05; P = 0.48) distinguished between statin and placebo. Stopping was no more frequent for statin than placebo (P = 0.173), and subsequent symptom relief was similar between statin and placebo. At 6 months after the trial, 30 of 60 (50%) participants were back taking statins. CONCLUSIONS: The majority of symptoms caused by statin tablets were nocebo. Clinicians should not interpret symptom intensity or timing of symptom onset or offset (on starting or stopping statin tablets) as indicating pharmacological causation, because the pattern is identical for placebo. (Self-Assessment Method for Statin Side-effects Or Nocebo [SAMSON]; NCT02668016).

Validation of a Brief Screening Instrument for Chemical Intolerance in a Large U.S. National Sample.

BACKGROUND: Chemical intolerance (CI) is characterized by multisystem symptoms triggered by low levels of exposure to xenobiotics including chemicals, foods/food additives, and drugs/medications. Prior prevalence estimates vary from 8-33% worldwide. Clinicians and researchers need a brief, practical screening tool for identifying possible chemical intolerance. This large, population-based study describes the validation of a three-item screening questionnaire, the Brief Environmental Exposure and Sensitivity Inventory (BREESI), against the international reference standard used for assessing chemical intolerance, the Quick Environmental Exposure and Sensitivity Inventory (QEESI). METHODS: More than 10,000 people in the U.S. responded to the BREESI and the QEESI in a population-based survey. We calculated the overall prevalence of CI in this sample, as well as by gender, age, and income. Common statistical metrics were used to evaluate the BREESI as a screener for CI against the QEESI. RESULTS: The prevalence estimate for QEESI-defined chemical intolerance in the U.S. was 20.39% (95% CI 19.63-21.15%). The BREESI had 91.26% sensitivity (95% CI: 89.20-93.04%) and 92.89% specificity (95% CI: 91.77-93.90%). The positive likelihood ratio was 12.83 (95% CI: 11.07-14.88), and the negative likelihood ratio was 0.09 (95% CI: 0.08-0.12). Logistic regression demonstrates that the predicted probability of CI increased sharply with each increase in the number of BREESI items endorsed (Odds Ratio: 5.3, 95% CI: 4.90-5.75). CONCLUSIONS: Chemical intolerance may affect one in five people in the U.S. The BREESI is a new, practical instrument for researchers, clinicians, and epidemiologists. As a screening tool, the BREESI offers a high degree of confidence in case ascertainment. We recommend: screen with the BREESI, confirm with the QEESI.

Intolerance to Multiple P2Y12 Inhibitors Following Percutaneous Coronary Intervention.

Dual antiplatelet therapy (DAPT), defined as administration of a P2Y12 receptor inhibitor (clopidogrel, prasugrel, or ticagrelor) and aspirin, is recommended after percutaneous coronary intervention. We describe a case of a 50-year-old gentleman with intolerance to the three previously mentioned P2Y12 inhibitors following the placement of a drug-eluting stent to the left anterior descending artery. To our knowledge, based on a thorough review of the literature, this is the second case reporting a similar medical dilemma. We have discussed the multidisciplinary approach implemented to overcome this clinical challenge, which involved the use of clopidogrel with simultaneous administration of a six-day course of oral steroids.

Drug Allergy Labels Lost in Translation: From Patient to Charts and Backwards.

The current method of defining, reporting, assessment, labeling, delabeling, and reconciliation of adverse drug reactions (ADRs), and specifically immunologically mediated drug hypersensitivity reactions (HSRs), in electronic health records (EHRs) is inadequate and compromises care quality and safety. It is critical to accurately and succinctly report the signs and symptoms associated with ADRs and suspected HSRs to enable clinicians to determine the plausible reaction type and help guide appropriate future management plans. Despite the current limitations of the EHR allergy module, we must encourage improved clinical documentation and demand technological improvements. Telehealth methods have been shown to be valuable in the assessment of ADRs and HSRs, particularly in the case of penicillin allergy evaluation and delabeling. The implementation, assessment, and refinement of advanced technologies, including clinical informatics and artificial intelligence, along with continued education of health care providers have potential to improve EHR documentation and communication, thereby advancing patient safety efforts.

Latent Tuberculosis Therapy Outcomes in Dialysis Patients: A Retrospective Cohort.

RATIONALE & OBJECTIVES: Maintenance dialysis patients are at an increased risk for active tuberculosis (TB). In 2012, British Columbia, Canada, began systematically screening maintenance dialysis patients for latent TB infection (LTBI) and treating people with evidence of LTBI when appropriate. We examined LTBI treatment outcomes and compared treatment outcomes before and after rollout of the systematic screening program. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: The study comprised 365 people in British Columbia, Canada, initiating at least 90 days of dialysis from January 1, 2001, to May 31, 2017, and starting LTBI therapy: 290 (79.5%) people in the recent cohort and 75 (20.5%) in the historical cohort. People starting LTBI therapy from January 1, 2012, onward were classified as the recent cohort, whereas people starting LTBI therapy before January 1, 2012, were classified as the historical cohort. EXPOSURE: Systematic LTBI screening and therapy. OUTCOMES: Proportion of people who experience grade 3 to 5 adverse events (AEs) or any grade rash and end-of-treatment outcomes. ANALYTICAL APPROACH: Outcomes were reported using descriptive statistics. 2-sample test of proportions using χ2 distribution was used to test for statistical significance between the recent and historical cohorts. RESULTS: 298 (81.6%) people successfully completed LTBI therapy. The proportion of people experiencing a grade 3 to 4 AE or any grade rash was 21.1%. Most AEs were related to gastrointestinal events, general malaise, or pruritus that resulted in regimen changes. 2 (0.5%) people were hospitalized for AEs related to LTBI therapy. No significant difference was found between the recent and historical cohorts in all outcomes of interest. No grade 5 AEs (deaths) were attributed to LTBI therapy. LIMITATIONS: Retrospective data and generalizability outside low-TB-burden settings. CONCLUSIONS: Our findings suggest that a high proportion of people receiving maintenance dialysis can complete LTBI therapy. The rate of grade 3 to 4 AEs was high and associated with frequent medication changes during therapy. LTBI therapy in maintenance dialysis may be safe but requires close monitoring.

Tackling the Patient with Multiple Drug "Allergies": Multiple Drug Intolerance Syndrome.

As populations age, the prevalence of reported drug "allergy" increases, often leading to suboptimal care and increased morbidity because of unnecessary avoidance of safe and effective medications. Evaluation by a drug allergy specialist is often warranted when a patient has more than 2 unrelated drug "allergies" listed in the medical record. In this commentary, we clarify and propose standard terminology to use when evaluating patients with multiple drug allergy labels including and more specifically when diagnosing multiple drug intolerance syndrome and the much rarer multiple drug hypersensitivity syndrome. We review epidemiology and key features of multiple drug intolerance syndrome and multiple drug hypersensitivity syndrome. We summarize the methodologic and practical diagnostic workup and management of individuals with MDIS to assist with the accurate delabeling of drug "allergies" in the electronic health record.

Patient Characteristics and Concerns about Drug Allergy: A Report from the United States Drug Allergy Registry.

BACKGROUND: Drug allergy is frequently reported, but uncommonly confirmed with diagnostic testing. Although drug allergy assessments can improve clinical care, patient concerns may impact the optimal diagnostic approach and/or the clinical effectiveness of diagnostic testing. OBJECTIVE: To assess drug allergy patient concerns. METHODS: Using data from a multisite, prospective longitudinal cohort study, the United States Drug Allergy Registry (January 16, 2019, to January 24, 2020), we determined patient self-reported characteristics and qualitatively coded free-text patient concerns about their drug allergy/allergies. We assessed associations between patient characteristics and drug allergy concerns using multinomial logistic regression models. RESULTS: Of 592 patients (mean age, 49 [standard deviation, 17] years, 74% female, 88% white), the most commonly reported drug allergies were penicillins (78%), cephalosporins (12%), and sulfonamides (12%) with common reactions of rash (62%), hives (54%), itching (48%), flushing or facial redness (28%), and swelling or angioedema (24%). Patient concerns, coded from free text, were optimal medication use (41%), no concern (17%), allergic reaction (14%), diagnosis (12%), and severe allergic reaction (12%). Using multinomial regression, the presence of drug allergy concerns increased with greater age, higher number of reported drug reactions, more antibiotic use, and certain reaction symptoms, most notably mouth or palate itching. Female sex was associated with increased severe allergic reaction concern. Poorer general and mental health was associated with increased allergic reaction concern. CONCLUSION: Patients with drug allergy were concerned about their options for medical treatment, having an allergic reaction, and receiving clarity about their diagnosis. Capturing and addressing patient concerns may improve the approach to patients with drug allergy and/or the effectiveness of drug allergy testing.

Adverse Drug Reactions After Administration of Emodepside/Praziquantel (Profender®) in an MDR1-Mutant Australian Shepherd Dog: Case Report.

A 3-year-old male Australian Shepherd was presented with signs of neurological toxicity following the administration of Profender® at the recommended dosage. Unfortunately, the owner had received the product from a veterinarian without any further instructions on fasting as recommended by the manufacturer, so the dog was fed prior to Profender® administration. Neurological toxicity included generalized tremor, agitation and panting, and required hospitalization of the dog. All neurological signs resolved after symptomatic treatment within 24 h and the dog was discharged without the need for further medication. MDR1 genotyping revealed a homozygous mutation of the MDR1 gene, which is normally important to prevent brain penetration of emodepside by an efflux-based transport mechanism at the blood brain barrier. This case indicates that Profender® can lead to serious, but transient neurological toxicity in dogs with homozygous MDR1 mutation even at therapeutic dosage, in particular when fasting recommendations are disregarded. Therefore, the case report highlights both the importance of MDR1 genotyping in predisposed dog breeds as well as strict compliance with fasting recommendations around the time of Profender® administration.

Polyallergy (Multiple Chemical Sensitivity) is Associated with Excessive Healthcare Utilization, Greater Psychotropic Use, and Greater Mental Health/Functional Somatic Syndrome Disorder Diagnoses: A Large Cohort Retrospective Study.

BACKGROUND: Associations between the crude capture of polyallergy-also known as multiple chemical sensitivity or multiple drug intolerance syndrome-and mental health/functional somatic syndrome disorders, healthcare utilization, or other clinical phenomenon have not been examined extensively. METHODS: An IRB-approved retrospective chart review of all patients between age 18 and 70 who had a clinical encounter at a large medical center between 2009 and 2014. Patients were stratified into 4 categories based on the absolute number of chart-documented allergies: (1) no allergies; (2) normal allergy (1-4 allergies); (3) polyallergy (5-9 allergies); and (4) "ultrapolyallergy," (≥10 allergies), which were corroborated through a sensitivity analysis. Demographics, comorbidities, and medications were clustered per allergy grouping. Analysis of variance, chi-square, and multivariable logistic regression analyses were employed to test for associations. RESULTS: 2,007,434 patients were examined ("no allergy" group, n = 1,423,631, 70.9%; "normal allergy" group: n = 549,927, 27.4%; "polyallergy" group n = 29,453, 1.5%; "ultrapolyallergy" group, n = 4,423, 0.22%). Proportion of females increased from 51% in the "no allergy" group to 89.6% in the "ultrapolyallergy" group (p < 0.001). Rates of mental health and functional somatic syndrome disorder diagnoses increased significantly across allergy groups (p < 0.001). All psychotropic medication classes were increased significantly across allergy groups (p < 0.001). Healthcare utilization was also significantly elevated across allergy cohorts (p <0.001). CONCLUSIONS: This study demonstrates that polyallergy/multiple chemical sensitivity may serve as a crude yet meaningful indicator of comorbid psychopathology. Drug intolerance mechanisms are reviewed, and both clinical and investigational implications are examined.