Ditte Georgina Zhang

Summary: Our study confirms an association between basophil histamine content and features of type IIb CSU. However, this biomarker is not suitable for predicting omalizumab treatment response or treatment course.

Background: Omalizumab is an effective treatment for chronic spontaneous urticaria (CSU), but strategies and predictors for guiding long‐term management and discontinuation remain limited.Objectives: To examine real‐world treatment patterns, including dosing modifications and discontinuation, and identify potential predictive factors for these outcomes.Methods: This was a retrospective, observational, real‐life study of adult patients with CSU treated with omalizumab at a Urticaria Center of Reference and Excellence (UCARE) in Copenhagen, Denmark, between May 20, 2015, and April 4, 2024. The Kaplan‐Meier estimator was used to visualize time to discontinuation and dose escalation/reduction (using standard label dosing as reference), and Cox‐regressions with hazard ratios (HR) were used to investigate potential predictive variables.Results: Of 430 patients initiated on omalizumab, 139 (32.4%) escalated treatment, 161 (37.5%) reduced treatment, and 90 (21.0%) discontinued treatment directly from the standard dose. The median survival time for dose escalation was 2 years (95% CI: 1.17–3.55), and the strongest predictor was a positive basophil histamine release assay (BHRA) (HR: 2.79, 95% CI: 1.69–4.61). Fast treatment response (HR: 0.50, 95% CI: 0.33–0.75) and higher baseline UCT scores (HR: 0.89, 95% CI: 0.82–0.97) decreased the risk of dose escalation. The median survival time to dose reduction was 1.2 years (95% CI: 0.98–1.49) and was more likely in males (HR: 1.68, 95% CI: 1.13–2.50) and patients with fast treatment response (HR: 1.66, 95% CI: 1.12–2.48). Median survival time to discontinuation (all reasons) of omalizumab was 3 years (95% CI: 2.35–3.64).Conclusions: A considerable proportion of patients with CSU require modifications to the recommended omalizumab dosing regimen. A positive BHRA was the strongest predictor for dose escalation, while male sex and fast treatment response were the strongest predictors for dose reduction. Our study highlights the need for individualized strategies in managing CSU.

Introduction Omalizumab, an anti-IgE monoclonal antibody, is effective in treating antihistamine-refractory chronic spontaneous urticaria (CSU). However, tapering strategies for omalizumab are currently not well-studied, and patients may be treated longer than needed. Here, we present the rationale and design of the EXtending Omalizumab Treatment Intervals in patients with Chronic spontaneous urticaria trial, a multicentre, randomised, open-label, non-inferiority clinical trial. The objective of this trial is to investigate if patients with well-controlled CSU, achieved by standard treatment of 300 mg omalizumab administered subcutaneously every 4 weeks (Q4W) for 12 weeks, can maintain disease control with every 6 weeks (Q6W) dosing interval. Methods and analysis Participants who achieve an Urticaria Control Test (UCT) score ≥12 after 12 weeks on omalizumab will be randomised to 300 mg omalizumab treatment Q4W or Q6W. Treatment arms will be followed for a total of 36 weeks. The primary endpoint is the absolute difference in average UCT score between treatment arms at week 36. Blood samples, Weekly Urticaria Activity Score, Chronic Urticaria Quality of Life Questionnaire, Dermatology Life Quality Index and records of side effects and flares will be obtained throughout the study at weeks 0, 12, 24 and 36. Ethics and dissemination The study has been approved by the Scientific Ethical Committee of the Capital Region in Denmark, the local Data Protection Agency and the Danish Medicines Agency. All study participants must provide written informed consent. The study will be conducted according to the Helsinki Declaration and Good Clinical Practice. Findings will be disseminated through publication in peer-reviewed journals and presented at international conferences. Trial registration number EU CT no. 2023-506187-14-00, ClinicalTrials.gov: NCT05916937.

INTRODUCTION. Pre -graduate research is popular among medical students. Concerns about time constraints and lack of mentorship have been raised in international studies. The extent to which these issues affect Danish medical students remains unclear. We therefore aimed to assess the conditions and outcomes of pre -graduate research among medical students from the University of Copenhagen. METHODS. A descriptive, cross-sectional, questionnaire -based survey on experiences from pre -graduate research was distributed to medical students and recently graduated medical doctors from the University of Copenhagen who had engaged in full-time pre -graduate research. The survey covered 1) working hours and income, 2) publications and authorship and 3) work environment and well-being. RESULTS. A total of 437 pre -graduate researchers participated in the survey. Pre -graduate research often involved a period outside of medical school (88%) and typically lasted a year (56%), with clinical research being the most common focus (68%). Almost a third worked longer hours (29%) than agreed and additional hours were commonly provided after the research period. Scholarships of 10,000 DKK a month were the primary source of income (72%). Most participants achieved their publication goals (62%) and experiences on work environment and well-being were generally positive. CONCLUSION. Pre -graduate research provides a conducive environment for medical students to engage in scientific research. Hovewer, engaging in pre -graduate research entails long working hours, is inadequately remunerated and often requires students to take leave from medical school.

Introduction: The internet is a popular source of health information including images of disease manifestations. Online photographs of skin lesions may aid patients in identifying their disease, if these pictures are of good quality and of the disease they claim to show. If not, patients may be at risk of delayed diagnosis, misdiagnosis, and suboptimal treatment. For urticaria, the mismatch rate and quality of online pictures are unknown. The objective of this study was therefore to evaluate the content and quality of online images of urticaria. Methods: The search term “urticaria” was applied to Google Images and Shutterstock. The top 100 photographs from each search engine were retrieved on October 9th, 2022. Illustrations, drawings, and heavily edited photographs were excluded. Each image was evaluated for patient characteristics, characteristics of urticarial lesions, and image quality. Results: Across 194 unique images of urticaria (after removing duplicates), 35 (18.0%) did not depict urticarial lesions, and 38 (19.6%) were ambiguous. Less than two-thirds of images 121 (62.4%) showed bona fide urticarial lesions. Pictures of urticarial lesions under-represented children and did not reflect female preponderance of the disease. Images predominantly depicted urticaria lesions on Caucasian skin (59.8%) and were typical of spontaneous rather than inducible urticaria. Only 3 (1.5%) pictures showed angioedema, a common clinical sign in patients with urticaria. The overall quality of online urticaria pictures was mostly good or very good. Conclusion: Physicians and patients should be aware that one in five online pictures of urticaria does not show urticarial skin lesions, and children, females, non-Caucasian patients, inducible urticaria, and angioedema are under-represented. These findings should prompt efforts to improve the accuracy and representativeness of online urticaria pictures.

We report the design, fabrication, and characterization of a universal silicon p-n junction ring resonator for C band error-free communication links operated up to 50 Gb/s with co-designed optical modulation and detection performance. The universal p-n junction ring device shows co-designed detection responsivity up to 0.84 A/W, and in conjunction with a modulation efficiency of ~4 Vmm and >8 dB optical modulation extinction ratio (ER), enabling C band 50-Gb/s NRZ communication link with bit error rate (BER) ≤ 3×10^-12. Individually, the speed of modulation and detection is measured up to 112 Gb/s and 80 Gb/s, respectively. The principle of co-designing PN junction ring modulator and detector performance required for error-free communication links can significantly ease the fabrication yield challenges of ring structures by reducing the number of types of devices. The principle can also be applied to O band wavelengths. To the best of our knowledge, for the first time, a device of this type has achieved both error-free modulation and detection operation up to 50 Gb/s in the C band individually or in conjugation as an error free communication link, which paves the way to realize a >1.6 Tb/s all-silicon WDM based error free optical transceiver link in future and is essential for future programmable photonics circuits.