Drug Allergy in Women.

Across all settings, women self-report more drug allergies than do men. Although there is epidemiologic evidence of increased drug allergy labeling in postpubertal females, the evidence base for female sex as a risk factor for true immune-mediated drug hypersensitivity reactions (DHRs), particularly in fatal drug-induced anaphylaxis, is low. A focus on the known immunologic mechanisms described in immediate and delayed DHR, layered on known hormonal and genetic sex differences that drive other immune-mediated diseases, could be the key to understanding biological sex variations in DHR. Particular conditions that highlight the impact of drug allergy in women include (1) pregnancy, in which a drug allergy label is associated with increased maternal and fetal complications; (2) multiple drug intolerance syndrome, associated with anxiety and depression; and (3) female-predominant autoimmune medical conditions in the context of mislabeling of the drug allergy or increased underlying risk. In this review, we describe the importance of drug allergy in the female population, mainly focusing on the epidemiology and risk, the mechanisms, and the associated conditions and psychosocial factors. By performing a detailed analysis of the current literature, we provide focused conclusions and identify existing knowledge gaps that should be prioritized for future research.

Safety and immunogenicity of the live-attenuated varicella vaccine in pediatric solid organ transplant recipients: A systematic review and meta-analysis.

This study aimed to synthesize the available evidence on the immunogenicity, safety, and effectiveness of live-attenuated varicella vaccine in solid organ transplant recipients. Medline and EMBASE were searched using predefined search terms to identify relevant studies. The included articles reported varicella vaccine administration in the posttransplant period in children and adults. A pooled proportion of transplant recipients who seroconverted and who developed vaccine-strain varicella and varicella disease was generated. Eighteen articles (14 observational studies and 4 case reports) were included, reporting on 711 transplant recipients who received the varicella vaccine. The pooled proportion was 88.2% (95% confidence interval 78.0%-96.0%, 13 studies) for vaccinees who seroconverted, 0% (0%-1.2%, 13 studies) for vaccine-strain varicella, and 0.8% (0%-4.9%, 9 studies) for varicella disease. Most studies followed clinical guidelines for administering live-attenuated vaccines, with criteria that could include being at least 1 year posttransplant, 2 months postrejection episode, and on low-dose immunosuppressive medications. Varicella vaccination in transplant recipients was overall safe in the included studies, with few cases of vaccine-strain-induced varicella or vaccine failure, and although it was immunogenic, the proportion of recipients who seroconverted was lower than that seen in the general population. Our data support varicella vaccination in select pediatric solid organ transplant recipients.

Rewiring of the 3D genome during acquisition of carboplatin resistance in a triple-negative breast cancer patient-derived xenograft.

Changes in the three-dimensional (3D) structure of the genome are an emerging hallmark of cancer. Cancer-associated copy number variants and single nucleotide polymorphisms promote rewiring of chromatin loops, disruption of topologically associating domains (TADs), active/inactive chromatin state switching, leading to oncogene expression and silencing of tumor suppressors. However, little is known about 3D changes during cancer progression to a chemotherapy-resistant state. We integrated chromatin conformation capture (Hi-C), RNA-seq, and whole-genome sequencing obtained from triple-negative breast cancer patient-derived xenograft primary tumors (UCD52) and carboplatin-resistant samples and found increased short-range (< 2 Mb) interactions, chromatin looping, formation of TAD, chromatin state switching into a more active state, and amplification of ATP-binding cassette transporters. Transcriptome changes suggested the role of long-noncoding RNAs in carboplatin resistance. Rewiring of the 3D genome was associated with TP53, TP63, BATF, FOS-JUN family of transcription factors and led to activation of aggressiveness-, metastasis- and other cancer-related pathways. Integrative analysis highlighted increased ribosome biogenesis and oxidative phosphorylation, suggesting the role of mitochondrial energy metabolism. Our results suggest that 3D genome remodeling may be a key mechanism underlying carboplatin resistance.

Comorbidity associated with worse outcomes in a population of limited cochlear implant performers.

Introduction: Most patients significantly benefit from cochlear implantation (CI). However, speech understanding varies widely, with a small proportion of patients demonstrating limited audiometric outcomes. While there are well-documented determinants of poor performance, there remains a cohort of patients that do not meet expected outcomes. Preoperative prognostication is desirable to manage expectations, ensure value of the intervention, and reduce risk. The objective of the study is to evaluate variables found within a single CI center's most limited functioning cohort following implantation. Methods: A retrospective review of a single CI program's cohort of (344 ears) patients implanted between 2011 and 2018 whose 1-year postimplantation AzBio scores fall 2 SDs below the mean was performed. Exclusion criteria includes skullbase pathology, pre/peri-lingual deafness, cochlear anatomic abnormalities, English as an additional language, and limited electrode insertion depth. Overall, 26 patients were identified. Results: The study population's postimplantation net benefit AzBio score is 18% compared to the entire program's 47% (p < 0.05). This group is older (71.8 vs. 59.0 years, p < 0.05) with a longer duration of hearing loss (26.4 vs. 18.0 years, p < 0.05) and with a lower preoperative AzBio score [14% lower (p < 0.05)]. A host of medical conditions were identified in the subpopulation, with a trend towards significance in those suffering from either malignancy or cardiac condition. Escalating comorbid status was associated with worse performance (p < 0.05). Conclusion: Within a cohort of limited-performing CI users, benefit tended to decrease with escalating number of comorbid conditions. This information may serve to inform preoperative patient counseling. Level of evidence: Level IV (evidence from a case control study).

Worldwide Prevalence of Antibiotic-Associated Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: A Systematic Review and Meta-analysis.

Importance: Antibiotics are an important risk for Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN), which are the most severe types of drug hypersensitivity reaction with a mortality rate up to 50%. To our knowledge, no global systematic review has described antibiotic-associated SJS/TEN. Objective: To evaluate the prevalence of antibiotics associated with SJS/TEN worldwide. Data Sources: The MEDLINE and Embase databases were searched for experimental and observational studies that described SJS/TEN risks since database inception to February 22, 2022. Study Selection: Included studies adequately described SJS/TEN origins and specified the antibiotics associated with SJS/TEN. Data Extraction and Synthesis: Two reviewers (E.Y.L. and C.K.) independently selected the studies, extracted the data, and assessed the risk of bias. A meta-analysis using a random-effects model was performed in the studies that described patient-level associations. Subgroup analyses were performed to explore the heterogeneity. The risk of bias was assessed using the Joanna Briggs Institute checklist, and the certainty of evidence was rated using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Main Outcomes and Measures: Prevalence of antibiotic-associated SJS/TEN was presented as pooled proportions with 95% CIs. Results: Among the 64 studies included in the systematic review, there were 38 studies that described patient-level associations; the meta-analysis included these 38 studies with 2917 patients to determine the prevalence of single antibiotics associated with SJS/TEN. The pooled proportion of antibiotics associated with SJS/TEN was 28% (95% CI, 24%-33%), with moderate certainty of evidence. Among antibiotic-associated SJS/TEN, the sulfonamide class was associated with 32% (95% CI, 22%-44%) of cases, followed by penicillins (22%; 95% CI, 17%-28%), cephalosporins (11%; 95% CI, 6%-17%), fluoroquinolones (4%; 95% CI, 1%-7%), and macrolides (2%; 95% CI, 1%-5%). There was a statistically significant heterogeneity in the meta-analysis, which could be partially explained in the subgroup analysis by continents. The overall risk of bias was low using the Joanna Briggs Institute checklist for case series. Conclusion and Relevance: In this systematic review and meta-analysis of all case series, antibiotics were associated with more than one-quarter of SJS/TEN cases described worldwide, and sulfonamide antibiotics remained the most important association. These findings highlight the importance of antibiotic stewardship, clinician education and awareness, and weighing the risk-benefit assessment of antibiotic choice and duration.

Barriers to Successful Discharge After Cardiac Surgery: A Focus Group Study and Cross-Sectional Survey.

At present, there is a lack of information on patient and caregiver values, and perceived priorities and barriers, to guide successful post-discharge recovery. This was a single center, multiple methods study that investigated patient, caregiver, and health care provider perceptions of the discharge process after cardiac surgery. Themes emerging from focus group discussions with patients and caregivers were used to develop surveys relating to values, barriers, and challenges relating to the discharge process. Thirty-two patients (n = 16) and caregivers (n = 16) participated in four separate focus groups. Four themes emerged from these discussions: (1) a lack of understanding about what the discharge process entails and when discharge is appropriate, (2) issues relating to the information provided to patients at the time of discharge, (3) participant experiences with the health care system, and (4) the experiences of caregivers. Seventy-eight patients, 34 caregivers, 53 nurses and/or other allied health professionals, and 8 surgeons completed the cross-sectional surveys. The most important component of the discharge process for patients and caregivers was "knowing what to do in an emergency." Health care providers less accurately identified what caregivers perceived as the most important aspects of the discharge process.Statements relating to informational barriers to discharge were the most discordant among patient and caregiver respondents. After discharge, patients and caregivers identified the need for longer-term follow up with the surgeon and more support in the community. Incorporation of patient and caregiver values to guide the post-cardiac surgery discharge process is essential to promote successful recovery.

Interleukin-6 and cytokine release syndrome: A new understanding in drug hypersensitivity reactions.

Immediate drug hypersensitivity reactions (DHRs) are historically thought to be because of immunoglobulin E (IgE) cross-linking, causing mast cell degranulation and release of mediators like tryptase and histamine. With the increasing use of monoclonal antibodies, it has become apparent that some patients present atypical features during immediate DHRs, including occurrence in initial exposure, a lack of urticaria and angioedema, and the presence of fever, chills, rigors and musculoskeletal pain as the predominant symptoms. This observation led to the recognition of a novel phenotype of immediate DHRs called cytokine release syndrome (CRS). Other types of immediate DHRs include infusion-related reactions (which present similarly to CRS), and mixed reactions (which share overlapping features of both type 1 reactions and CRS). Desensitization to culprit drugs can be a lifesaving option in patients who develop immediate DHRs to first-line treatment. Whereas robust data are supporting the safety and efficacy of drug desensitization, breakthrough reactions can still occur and CRS seems to be a more common cause than type 1 reactions. Tryptase has been the only available biomarker for immediate DHRs and is associated with type 1 reactions. Emerging evidence consistently found the association between increased serum interleukin 6 level and DHR-related CRS, suggesting that interleukin 6 can be a novel biomarker, in addition to tryptase, to distinguish various types of DHRs. In the era of precision medicine, phenotyping and endotyping hypersensitivity reactions to chemotherapy and monoclonal antibodies using validated biomarkers should be part of routine drug allergy care.

Successful mRNA COVID-19 vaccination in a patient with a history of severe polyethylene glycol anaphylaxis.

BACKGROUND: The mechanism of action behind anaphylactic reactions to the mRNA COVID-19 vaccines remains unknown, but the excipient polyethylene glycol, PEG-2000, has been implicated. Initial recommendations were made for excipient testing with PEG-3350 to help risk stratify individuals and identify an etiology. Here we present a case of a patient with a history of polyethylene glycol anaphylaxis and positive skin testing to PEG-3350, who successfully received both doses of the Pfizer-BioNTech COVID-19 mRNA vaccine in a single step with only premedication. CASE PRESENTATION: A 56-year-old man was referred to our clinic for assessment of his eligibility in receiving the COVID-19 vaccine given a history of anaphylaxis to PEG. He had two anaphylactic episodes: one in 2018 to methylprednisolone acetate intra-articular injection and one to oral PEG-3350 in 2020. Confirmatory skin prick testing was done in our clinic to PEG-3350 that was positive at 35 mm with appropriate positive and negative controls. Despite this he wanted to receive the PEG-containing mRNA COVID-19 vaccines and was counselled on the risks and benefits. He successfully received both doses of the Pfizer-BioNTech COVID-19 mRNA vaccine in a single step with only pre-treatment with Cetirizine 20 mg daily and Montelukast 10 mg daily for 5 days. CONCLUSIONS: In conclusion, our case demonstrates that a patient with a confirmed polyethylene glycol anaphylaxis could safely receive both doses of the COVID-19 mRNA vaccines in a single step with pre-treatment. We hope that our case will further support the limited role in skin testing to PEG in the assessment of COVID-19 mRNA vaccine allergy and highlight the need for further research to elucidate the mechanism of action behind these allergic reactions.

Returning childbirth to inuit communities in the Canadian Arctic.

While Inuit living in Nunavut have been advocating for decades for the return of birthing to their own communities, over two-third of births continue to occur outside of the territory. We conducted a literature review to answer the question, why has birthplace choice not been given back to Inuit yet. Based on our review we identified a number of factors impacting birthplace choice, including the organisation of the Nunavut medical system that is focused on primary health care and that cannot easily accommodate the potential clinical risks Western health care associates with birthing, often in isolation from socio-cultural risks; staffing vacancies and turn over in Nunavut, which creates challenges in continuity of care and in maintaining trust; and trends in Canada towards the medicalisation of birthing, which resulted in the displacement of traditional midwifery, and lately in the professionalisation of midwifery with training centres mostly located outside of Nunavut. We recognise that providing more options to birth in the north is complex. While birthing in the north as an option is a given objective, operationalising this objective in a consistent manner is likely going to be a challenge for years to come.

Monitoring patients with uncomplicated common variable immunodeficiency: a systematic review.

BACKGROUND: Non-infectious complications have become a major cause of morbidity and mortality in patients with Common Variable Immunodeficiency (CVID). The monitoring of patients with CVID prior to the development of non-infectious complications is not well defined. OBJECTIVE: Our objectives were to systematically review the current literature on the monitoring of CVID patients without non-infectious complications and to develop recommendations for such monitoring. METHODS: MEDLINE and EMBASE were searched from January 1st, 2000 to March 25th, 2021. Studies on any aspects of CVID monitoring were included. Studies that included only children, on monitoring CVID patients with existing non-infectious complications, or in the format of case reports were excluded. RESULTS: Nine studies on CVID monitoring, including 3 cohort studies, 3 experts' opinions, 2 consensus statements and a single guideline report were identified. These studies revealed that clinical assessment and bloodwork were preformed every 6 to 12 months in asymptomatic patients. Some centers performed computerized tomography scan of the chest every 2-5 years to identify chronic lung disease, although the majority did chest imaging in accordance with clinical indications. Pulmonary function tests were done annually at most centers. Most studies did not address the role of abdominal imaging to screen for liver diseases or endoscopy to screen for gastric cancer in asymptomatic patients with uncomplicated CVID. CONCLUSIONS: There is paucity of evidence-based information to guide the routine monitoring of CVID patients without non-infectious complications. Prospective studies are needed to determine the best monitoring practices in this group of patients.

Demographic and clinical characteristics of patients with hereditary angioedema in Canada.

BACKGROUND: Data on the clinical and demographic features of Canadian patients with hereditary angioedema (HAE) are lacking. OBJECTIVE: To describe the clinical and demographic features in a large Canadian HAE cohort and compare them with patients with HAE in other countries. METHODS: An online questionnaire was distributed to the members of 2 Canadian HAE patient groups to collect information on demographics and HAE clinical characteristics. All participants 18 years of age or older with HAE type I or II were eligible. Frequency, location, prodromes, and triggers of HAE attacks, including types of HAE treatment, were characterized. RESULTS: Among the 90 participants who completed the online survey, 57% self-identified as having HAE type 1 and 26% HAE type II. The average diagnostic delay was 11 years. In the preceding 6 months, 24% of the participants had no attacks and 35% experienced greater than 5 attacks. The most frequently affected regions of the body were the abdomen (83%), arms orlegs (63%), face (41%), and larynx or throat (41%). Approximately 87% of the participants reported having access to C1 inhibitor at home, and 69% reported using it for long-term prophylaxis. CONCLUSION: Canadian patients with HAE share common clinical characteristics with patients with HAE in other countries. They had a delay in HAE diagnosis and a high burden of disease, as indicated by the high frequency of attacks in the preceding 6 months. This study provides a better understanding of the demographic and clinical characteristics of Canadian patients with HAE.

Somali migration to the United States: Understanding adaptation through digital stories.

OBJECTIVES: The purpose of this study was to further understand the psychological process of migration through an interdisciplinary (psychology, history, and digital humanities) collaboration that examines the experiences of Somali refugees in the United States. METHOD: The sample consisted of 26 Somali American emerging adult and older adult refugees who created digital stories as part of the Immigrant Stories Project (https://immigrantstories.umn.edu/). Stories were analyzed through an examination of narrative structure and content. RESULTS: The structure of the authors' stories was primarily progressive or stable, with very few regressive stories. Although the distribution of these story structures did not differ for emerging adults and older adults, there were important variations in content. Emerging adults' stories reflected a struggle to find self-continuity across time and place, whereas older adults' stories indicated attempts to find meaning and optimally adapt to their current situations. Moreover, none of the stories took on a redemptive structure, a type of story that has been identified as culturally prevalent in U.S. culture but seldom examined across diverse populations. CONCLUSIONS: The findings highlight the varieties of paths toward successful immigration and the importance of taking a collaborative, participatory approach to understanding migration experiences. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Characterizing Physician-Staffing Models in the Care of Postoperative Cardiac Surgical Patients in Canada.

BACKGROUND: Current intensive care unit physician-staffing (IPS) models for postoperative cardiac surgery have not been previously investigated in Canada. The purpose of this study was to determine current IPS models at 2 time points and describe the evolution of Canadian cardiac surgery IPS models. METHODS: A survey of 32 Canadian cardiovascular intensive care units (CVICUs) was undertaken in 2012 and 2017 to determine IPS models of care during "daytime" and "after-hours" in each unit. Data were collected regarding surgical volume, base specialties, and style of IPS management ("open"; "semi-open"; "closed"). In addition, we collected the overnight experience level of the bedside healthcare provider for in-house intensive care units. RESULTS: Survey responses were received from 27 of 32 CVICUs (87%). As of 2017, the style of 1 (4%) was open, 7 (26%) were semi-open, and 19 (70%) were closed in their unit IPS strategy. Base specialties of CVICU physicians varied. A medical doctor provided after-hours coverage in 81% of CVICUs. Senior residents (37%) or critical care certified attending staff (25%) typically provided after-hours coverage for in-house CVICUs. Linked Canadian Institute for Health Information data did not indicate a difference among CVICU models in mortality or rehospitalization for coronary artery bypass graft or valve procedures. CONCLUSIONS: Considerable heterogeneity is demonstrated in CVICU staffing patterns. No consensus was identified regarding the appropriate level of training for "after-hours" coverage. In-house overnight physician staffing in CVICUs varies widely. Finally, semi-open and closed style models did not demonstrate differences compared to Canadian Institute for Health Information data. Variability among CVICUs does exist; however, benefits of one model over another have not been identified.

INTRODUCTION: Les modèles actuels de dotation en médecins aux soins intensifs (DMSI) postopératoires de chirurgie cardiaque n'ont pas fait l'objet d'études antérieures au Canada. L'objectif de la présente étude était de déterminer les modèles actuels de DMSI à deux points temporels et de décrire l'évolution des modèles de DMSI de chirurgie cardiaque au Canada. MÉTHODES: Nous avons entrepris une enquête auprès de 32 unités de soins intensifs cardiovasculaires du Canada (USICC) en 2012 et en 2017 pour déterminer les modèles de soins DMSI « pendant la journée ¼ et « après les heures normales ¼ dans chaque unité. Nous avons collecté les données relatives au volume d'interventions chi- rurgicales, aux spécialités de base et au style de gestion de la DMSI (« ouvert ¼, « semi-ouvert ¼, « fermé ¼). De plus, nous avons collecté les données sur le niveau d'expérience de nuit des prestataires de soins au chevet des patients des unités intégrées de soins intensifs. RÉSULTATS: Nous avons reçu les réponses à l'enquête de 27 des 32 USICC (87 %). Depuis 2017, le style de 1 (4 %) USICC était ouvert, de 7 (26 %) était semi-ouvert et de 19 (70 %) était fermé dans leur stra- tégie de DMSI à l'unité. Les spécialités de base des médecins de l'USICC variaient. Un docteur en médecine offrait ses services après les heures normales dans 81 % des USICC. Les résidents chevronnés (37 %) ou les médecins titulaires agréés en soins aux patients en phase critique (25 %) offraient habituellement leurs services après les heures normales aux USICC intégrées. Les données liées de l'Institut canadien d'information sur la santé n'indiquaient pas de différence entre les modèles des USICC en ce qui a trait à la mortalité ou à la réhospitalisation en raison de pontages aortocoronariens ou d'interventions valvulaires. CONCLUSIONS: Les modèles de dotation en personnel aux USICC démontrent une importante hétérogénéité. Aucun consensus n'a été établi quant au niveau approprié de formation pour les services offerts « après les heures normales ¼. Le personnel médical de nuit à l'interne des USICC varie grandement. Finalement, les modèles de styles semi-ouverts et fermés ne démontraient pas de différence par rapport aux données de l'Institut canadien d'information sur la santé. Une variabilité existe entre les USICC. Toutefois, les avantages d'un modèle par rapport à un autre n'ont pas été définis.

Characterizing telemedicine use in clinical immunology and allergy in Canada before the COVID-19 pandemic.

RATIONALE: There exists a geographic barrier to access CIA care for patients who live in rural communities; telemedicine may bridge this gap in care. Herein we characterized the use of telemedicine in CIA at a population-based level and single centre. METHODS: Before the COVID-19 pandemic, telemedicine care was provided via the Ontario Telemedicine Network (OTN) in Ontario, Canada. Descriptive data were collected from the OTN administrative database and from electronic medical records at a single academic centre during 2014 to 2019. The potential distance travelled and time saved by telemedicine visits were calculated using postal codes. RESULTS: A total of 1298 telemedicine visits was conducted over OTN, with an average of 216 visits per year. Only 11% of the allergists/immunologists used telemedicine to provide care before the COVID-19 pandemic. In the single centre that provided the majority of the telemedicine care, 66% patients were female and the overall mean age was 46. The most common diagnosis was immunodeficiency (40%), followed by asthma (13%) and urticaria (11%). Most patients required at least one follow-up via telemedicine. The average potential two-way distance travelled per visit was 718 km and the average potential time travelled in total was 6.6 h. CONCLUSION: Telemedicine was not widely used by allergists/immunologists in Ontario, Canada before the COVID-19 pandemic. It could offer a unique opportunity to connect patients who live in remote communities and allergists/immunologists who practice in urban centres in Canada. Independent of the current pandemic, our study further highlights the need for more physicians to adopt and continue telemedicine use as well as for healthcare agencies to support its use as a strategic priority once the pandemic is over.

Immediate hypersensitivity reaction followed by successful oral desensitization to ursodiol.

BACKGROUND: Immediate hypersensitivity reaction to ursodiol is rare and there is no previously published protocol on ursodiol desensitization. CASE PRESENTATION: A 59-year-old woman with primary biliary cholangitis (PBC) developed an immediate hypersensitivity reaction to ursodiol-the first-line treatment for PBC. When she switched to a second-line treatment, her PBC continued to progress. As such, she completed a novel 12-step desensitization protocol to oral ursodiol. She experienced recurrent pruritus after each dose following desensitization, which subsided after a month of being on daily ursodiol. CONCLUSION: Immediate hypersensitivity reaction to ursodiol is uncommon. Our case demonstrated that this novel desensitization protocol to ursodiol could be safely implemented when alternative options are not available or have proven inferior in efficacy.

Quality of life in patients with hereditary angioedema in Canada.

BACKGROUND: Hereditary angioedema (HAE) is associated with decreased quality of life (QoL), which has typically been measured using a generic non-disease-specific questionnaire. OBJECTIVE: We aimed to assess the QoL in patients with HAE type I and II in Canada using a previously validated HAE-specific questionnaire. METHODS: An online questionnaire was sent to the members of two Canadian HAE patient groups to collect data on demographics, HAE clinical course, and QoL scores. All patients 18 years of age or older with HAE type I or II were eligible. The impact of the available clinical factors on the QoL scores was evaluated. Multiple linear regression was performed using clinically relevant factors to predict HAE QoL outcome. RESULTS: Among the 72 patients in the study, the mean total HAE QoL score was 102 (±23) (SD) on a scale of 25 to 135, with higher scores indicating better QoL. Although the total QoL scores correlated positively with patients' level of satisfaction and perceived control (P < .001 for both), it correlated negatively with the number of acute attacks (P = .03). Yet, the types of treatment did not have an impact on the QoL. Predictors, including sex, comorbidities, and the number of attacks, only explained 12% of the variance in the total QoL scores. CONCLUSION: HAE continues to impair QoL in Canadian patients despite receiving recommended treatment. Although the frequency of attacks affects QoL, patients' experience with their HAE care also affects QoL substantially. The study highlights the importance of considering patients' experience with their HAE care as physicians develop an appropriate management plan.