Experiences with pre-graduate research among Danish medical students and doctors.

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. FUNDING: None. TRIAL REGISTRATION: Not relevant.

Online Depiction of Urticaria Is Often Flawed and Does Not Reflect the Spectrum of Clinical Manifestation.

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.

Smartphone photographs of chronic urticaria taken by patients are of good quality and useful in the clinic.

BACKGROUND: Chronic urticaria (CU) is characterized by transient wheals and angioedema, which are often not present when patients see their treating physician. AIM: To evaluate the diagnostic value of smartphone photographs captured by patients prior to their first visit at an urticaria outpatient clinic. METHODS: A survey regarding the quality and utility of smartphone photographs of urticarial skin lesions in patients with CU attending the outpatient clinic for the first time was conducted. Up to three random patient-selected photographs of skin lesions were evaluated by a physician. RESULTS: Of 148 patients, 118 (79.7%) had taken photographs of their skin lesions prior to the consultation, and 75% took photographs with the intention of presenting it to their physician. The photographs were of wheals in 90% of the cases, and angioedema in 8%. In total, 72% of the smartphone photographs had the skin lesion in focus, 64% had good resolution, 48% had good lighting. Only 9% of the smartphone photographs were blurred, 10% had bad lighting, 4% had bad resolution, and 8% did not have the lesion in focus. Moreover, 86% of the smartphone photographs were found to be useful for clinical evaluation. At least one photograph of good/very good quality was presented by 86% of the patients, and 97% had at least one photograph that was useful for clinical evaluation. CONCLUSION: Patients with CU often take smartphone photographs of their skin lesions on their own initiative prior to their first consultation to present the photographs to their physician. These smartphone photographs are very often of good quality and suitable for clinical evaluation.

Biomarkers for Monitoring Treatment Response of Omalizumab in Patients with Chronic Urticaria.

Chronic urticaria (CU) is a debilitating skin disease affecting around 1% of the population. CU can be subdivided into chronic spontaneous urticaria (CSU) and chronic inducible urticaria (CIndU). Different pathophysiological mechanisms have been proposed to play a role in the development of CU, and these are also being investigated as potential biomarkers in the diagnosis and management of the disease. As of now the only assessment tools available for treatment response are patient reported outcomes (PROs). Although these tools are both validated and widely used, they leave a desire for more objective measurements. A biomarker is a broad subcategory of observations that can be used as an accurate, reproducible, and objective indicator of clinically relevant outcomes. This could be normal biological or pathogenic processes, or a response to an intervention or exposure, e.g., treatment response. Herein we provide an overview of biomarkers for CU, with a focus on prognostic biomarkers for treatment response to omalizumab, thereby potentially aiding physicians in personalizing treatments.

Risk of Atopic Disorders in Patients with Chronic Urticaria: A Systematic Review and Meta-Analysis.

BACKGROUND: Chronic urticaria (CU) has been associated with several systemic and autoimmune disorders. The association with atopic disorders is however controversial. The objective of this study was to perform a systematic review and meta-analysis to assess the association between CU and the atopic disorders: atopic dermatitis (AD), asthma, and allergic rhinoconjunctivitis (ARC). METHODS: Search hits from PubMed, Embase, Cochrane Library, and Web of Science were systematically reviewed. English papers from 2000 to present, containing original data of the association (prevalence, incidence, or risk) between CU and any atopic disorder(s), were included. Pooled point prevalence and OR with 95% confidence intervals were calculated with a random effects model. RESULTS: A total of 8,108 search hits were screened and reviewed. Thirty-eight studies met all inclusion criteria. The estimated pooled point prevalence of AD, asthma, and ARC in CU was 7% (5-11%, I2 = 99%), 12% (9-15%, I2 = 100%), and 22% (16-29%, I2 = 100%), respectively. Pooled ORs were estimated to 2.75 (2.05-3.68, I2 = 94%) for AD, 1.87 (1.01-3.45, I2 = 100%) for asthma, and 2.94 (1.84-4.68, I2 = 100%) for ARC. CONCLUSION: Pooled point prevalences of atopic disorders in CU were comparable to the general population. However, studies that compared prevalences with controls from the same population all found a significantly increased risk of atopic disorders in CU. Results should however be interpreted with caution as high heterogeneity was found in all analyses.

Early treatment with sumatriptan prevents PACAP38-induced migraine: A randomised clinical trial.

OBJECTIVE: To determine whether early treatment with sumatriptan can prevent PACAP38-induced migraine attacks. METHODS: A total of 37 patients with migraine without aura were enrolled between July 2018 to December 2019. All patients received an intravenous infusion of 10 picomole/kg/min of PACAP38 over 20 min followed by an intravenous infusion of 4 mg sumatriptan or placebo over 10 min on two study days in a randomised, double-blind, placebo-controlled, crossover study. RESULTS: Of 37 patients enrolled, 26 (70.3%) completed the study and were included in analyses. Of the 26 patients, four (15%) developed a PACAP38-induced migraine attack on sumatriptan and 11 patients (42%) on placebo (p = 0.016). There were no differences in area under the curve for headache intensity between sumatriptan (mean AUC 532) and placebo (mean AUC 779) (p = 0.35). Sumatriptan significantly constricted the PACAP38-dilated superficial temporal artery immediately after infusion (T30) compared with infusion of placebo (p < 0.001).Conclusions and relevance: Early treatment with intravenously administered sumatriptan prevented PACAP38-induced migraine. Prevention of migraine attacks was associated with vasoconstriction by sumatriptan in the earliest phases of PACAP provocation. These results suggest that sumatriptan prevents PACAP38-induced migraine by modulation of nociceptive transmission within the trigeminovascular system.Trial Registration: ClinicalTrials.gov (NCT03881644).

Infusion of Pituitary Adenylate Cyclase-Activating Polypeptide-38 in Patients with Rosacea Induces Flushing and Facial Edema that Can Be Attenuated by Sumatriptan.

BACKGROUND: The pathogenesis of rosacea is incompletely understood. Signaling neuropeptides, including PACAP, a regulator of vasodilation and edema, are upregulated in rosacea skin. Here, we evaluated PACAP38-induced rosacea features and examined whether a 5-HT1B/1D receptor agonist could reduce these features. METHODS: A total of 35 patients with erythematotelangiectatic rosacea received an intravenous infusion of 10 pmol/kg/minute of PACAP38 followed by an intravenous infusion of 4 mg sumatriptan or placebo (saline) on two study days in a double-blind, randomized, placebo-controlled, and cross-over trial. RESULTS: PACAP38 increased facial skin blood flow by 90%, dilated the superficial temporal artery by 56%, and induced prolonged flushing and facial edema. Compared with placebo, sumatriptan reduced PACAP38-induced facial skin blood flow for 50 minutes (P = 0.023), constricted the superficial temporal artery for 80 minutes (P = 0.010), and reduced duration of flushing (P = 0.001) and facial edema (P < 0.001). CONCLUSIONS: We established a clinical experimental model of rosacea features and showed that sumatriptan was able to attenuate PACAP38-induced rosacea flushing and edema. Findings support a key role of PACAP38 in rosacea flushing pathogenesis. It remains unknown whether PACAP38 inhibition can improve rosacea. TRIAL REGISTER: The trial was registered at ClinicalTrials.govNCT03878784 in March 2019.

Cohort profile: COpenhagen ROsacea COhort (COROCO) and COpenhagen MIgraine COhort (COMICO).

PURPOSE: Migraine has consistently been connected with rosacea. Commonalities in epidemiology, trigger factors and associated neuropeptides support shared aetiology and pathophysiological pathways, though underlying mechanisms remain unclear. We established two cohorts of patients diagnosed with either migraine and/or rosacea. All patients were phenotyped in regard to migraine and rosacea. In this article, we describe the baseline parameters of the cohorts. In the future, we expect that these cohorts will help uncover potential disease overlaps and allow for prolonged follow-up through national Danish health registers. PARTICIPANTS: COpenhagen ROsacea COhort (COROCO) and COpenhagen MIgraine COhort (COMICO) are prospective cohorts based in the Capital region of Denmark. Participants for COROCO were recruited primarily through two tertiary dermatology clinics in Copenhagen, Denmark and patients for COMICO were recruited through a tertiary neurology clinic in Copenhagen, Denmark. FINDINGS TO DATE: COROCO: 67.7% women (median age 51 years (interquartile range (IQR) 43.0-61.0)). Family history of migraine: 44.3%. Family history of rosacea: 45%. There were 13% who currently smoked, and 36.6% were former smokers. Regular intake of alcohol was present in 79.3% (median 4 items/week (IQR 1.0-9.0)). Median body mass index (BMI): 25.7 (IQR 23.1-29.0). Median Dermatology Life Quality Index (DLQI): 2 (IQR 1-5). COMICO: 88.5% women (median age 41 years (IQR 29.5-51.0)). Family history of migraine: 73.4%. Family history of rosacea: 18.4%. There were 17.1% who currently smoked, and 26.0% former smokers. Regular intake of alcohol was present in 62.2% (median intake: 2 item/week (IQR 1.0-3.0)). Median BMI was 24.6 (IQR 21.5-28.2). Median DLQI was 1 (IQR 0-2). FUTURE PLANS: COROCO and COMICO serve as strong data sources that will be used for future studies on rosacea and migraine with focus on risk factors, occurrence, treatment, natural history, complications, comorbidities and prognosis. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT03872050).

Plasma Glucose Levels Increase During Spontaneous Attacks of Migraine With and Without Aura.

OBJECTIVE: To investigate plasma glucose changes during the ictal state of migraine compared to the interictal state. BACKGROUND: Previous studies suggest abnormal glucose metabolism in migraine patients during and outside of attacks. It is not known if plasma glucose levels change during spontaneous migraine attacks. METHODS: Plasma glucose levels were measured during and outside of spontaneous migraine attacks with and without aura. Plasma glucose values were corrected for diurnal variation of plasma glucose by subtracting the difference between the moving average (intervals of 2 hours) and overall mean from the plasma glucose values. RESULTS: This was a sub-study of a larger study conducted at Rigshospitalet Glostrup in the Capital Region of Denmark. Thirty-one patients (24 F, 7 M, 13 with aura, 18 without aura) were included in the study. Mean time from attack onset to blood sampling was 7.6 hours. Mean pain at the time of investigation was 6 on a 0-10 verbal rating scale. Plasma glucose was higher ictally compared to the interictal phase (interictal mean: 88.63 mg/dL, SD 11.70 mg/dL; ictal mean: 98.83 mg/dL, SD 13.16 mg/dL, difference 10.20 mg/dL, 95% CI = [4.30; 16.10]), P = .0014). The ictal increase was highest in patients investigated early during attacks and decreased linearly with time from onset of migraine (-1.57 mg/dL/hour from onset of attack, P = .020). The attack-related increase in blood glucose was not affected by pain intensity or presence of aura symptoms. CONCLUSIONS: We demonstrated higher plasma glucose values during spontaneous migraine attacks, independent of the presence of aura symptoms and not related to pain intensity, peaking in the early phase of attacks. Additional studies are necessary to confirm our findings and explore the possible underlying mechanisms.