Monitoring mepolizumab treatment in chronic rhinosinusitis with nasal polyps (CRSwNP): Discontinue, change, continue therapy?

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial inflammatory disease of the mucous membranes of the nose and sinuses. Eosinophilic inflammation is described as a common endotype. The anti-IL-5 antibody mepolizumab was approved in November 2021 as an add-on therapy to intranasal glucocorticosteroids for the treatment of adults with severe chronic rhinosinusitis with nasal polyps when systemic glucocorticosteroids or surgery do not provide adequate disease control. While national and international recommendations exist for the use of mepolizumab in CRSwNP, it has not yet been adequately specified how this therapy should be monitored, what follow-up documentation is necessary, and when it should be discontinued if necessary. MATERIALS AND METHODS: A literature search was performed to analyze previous data on the treatment of CRSwNP with mepolizumab and to determine the available evidence by searching Medline, Pubmed, the national and international trial and guideline registries, and the Cochrane Library. Human studies published in the period up to and including 10/2022 were considered. RESULTS: Based on the international literature and previous experience by an expert panel, recommendations for follow-up, adherence to therapy intervals, and possible therapy breaks as well as discontinuation of therapy when using mepolizumab for the indication CRSwNP in the German healthcare system are given on the basis of a documentation sheet. CONCLUSION: Understanding the immunological basis of CRSwNP opens up new non-surgical therapeutic approaches with biologics for patients with severe, uncontrolled courses. Here, we provide recommendations for follow-up, adherence to therapy intervals, possible therapy pauses, or discontinuation of therapy when mepolizumab is used as add-on therapy with intranasal glucocorticosteroids to treat adult patients with severe CRSwNP that cannot be adequately controlled with systemic glucocorticosteroids and/or surgical intervention.

[High interaction potential of online-only courses with breakout sessions-results of a pilot study]. / Hohes Interaktionspotenzial volldigitaler Lehrveranstaltungen mit Breakout-Sessions ­ Ergebnisse einer Pilotstudie.

BACKGROUND: The flipped classroom (FC) is nowadays a popular principle of blended student-centered learning. Students first prepare basic knowledge at home and subsequently meet for consolidation and a more in-depth look at a certain topic. During the COVID-19 pandemic, several groups developed approaches to also transform the characteristic FC second session into an online-only format. OBJECTIVE: Herein, we present a pilot study on establishing an online-only FC format with elements of collaborative learning and its evaluation by medical students. MATERIALS AND METHODS: The FC design related to diseases of the salivary glands was transformed into an online-only event. After studying the basic information online, supported by self-made interactive videos and/or lecture recordings, students met in a video conference enriched by breakout sessions, interactive demonstration of the related clinical examination including ultrasound, and a formative assessment. A questionnaire with 27 items was answered by participants to evaluate the concept and the event. RESULTS: Use of common hard- and software systems led to a technically stable video conference. A total of 55 students completed the questionnaire and were included into data analysis. During the breakout sessions, lively interaction between participants was observed. The evaluation of both the event itself and the related learning progress showed good results despite the lack of preparation beforehand in 27% of participants. CONCLUSION: Online-only FC designs can result in high satisfaction. High quality of online preparation, a solid technical platform, accurate time management, and a reasonable selection of topics are the main parameters contributing to successful course design. Nowadays, embedding medical imaging can be realized in appropriate quality for educational purposes. The implementation of breakout sessions and voting tools enables collaborative online learning with high levels of interaction and satisfaction for both teachers and students.

Inconsistent Skin Prick Tests for Allergy to Birch Homologous Trees May Result from Cross-Reacting Allergens or Technical Errors.

INTRODUCTION: Skin prick tests (SPTs) are the gold standard for diagnosis of allergic rhinitis (AR). A decrease in the number of allergens included in standard SPT panels has recently been debated - particularly regarding the cross-reacting homologous pollen from birch, alder, and hazel trees - but has not yet been implemented in clinical guidelines. METHODS: A subgroup of patients with AR (n = 69) who showed inconsistent SPT results among birch, alder, and hazel was investigated in detail. Beyond SPT, patient workup included assessment of clinical relevance and various serological parameters (total IgE, and specific IgE to birch, alder, and hazel and to Bet v 1, Bet v 2, and Bet v 4). RESULTS: More than half the study group had negative SPT results for birch but positive results for alder and/or hazel, and 87% of the study group was polysensitized, showing at least one more positive SPT result for other plants. Whereas 30.4% of patients showed serological sensitization to birch pollen extract, only 18.8% displayed positive specific IgE to Bet v 1. Clinical assessment revealed that most patients with AR were polysensitized and had perennial symptoms or symptoms also occurring during times other than tree flowering times. If the SPT panel is limited to testing birch only, 52.2% of patients in this subgroup would have been overlooked. CONCLUSION: Inconsistent SPT results in the birch homologous group may result from cross-reacting allergens or technical errors. If patients report convincing clinical symptoms despite negative results from a reduced SPT panel or inconsistent results for homologous allergens, SPT should be repeated, and molecular markers should be added to achieve a correct diagnosis.

Adherence and persistence in allergen immunotherapy (APAIT): A reporting checklist for retrospective studies.

BACKGROUND: Adherence is essential for the long-term efficacy of allergen immunotherapy (AIT) and has been evaluated in numerous retrospective studies. However, there are no published guidelines for best practice in measuring and reporting adherence or persistence to AIT, which has resulted in substantial heterogeneity among existing studies. The 'adherence and persistence in AIT (APAIT)' checklist has been developed to guide the reporting, design and interpretation of retrospective studies that evaluate adherence or persistence to AIT in clinical practice. METHODS: Five existing checklists, focussing on study protocol design, the use of retrospective databases/patient registries, and the appraisal and reporting of observational studies, were identified and merged. Relevant items were selected and tailored to be specific to AIT. The content of the checklist was discussed by 11 experts from Europe, the United States and Canada, representing allergy, healthcare and life sciences, and health technology appraisal. RESULTS: The APAIT checklist presents a set of items that should either be included or at least considered, when reporting retrospective studies that assess adherence or persistence to AIT. Items are organized into four categories comprising study objective, design and methods, data analysis, and results and discussion. The checklist highlights the need for clarity and transparency in reporting and emphasizes the importance of considering potential sources of bias in retrospective studies evaluating adherence or persistence to AIT. CONCLUSIONS: The APAIT checklist provides a pragmatic guide for reporting retrospective adherence and persistence studies in AIT. Importantly, it identifies potential sources of bias and discusses how these influence outcomes.

Lack of Harmonized Adherence Criteria in Allergen Immunotherapy Prevents Comparison of Dosing and Application Strategies: A Scoping Review.

Allergen immunotherapy (AIT) involves the application of increasing doses of allergen extract (as oral, sublingual, or subcutaneous immunotherapy) until immunologic tolerance is reached. Successful AIT relies on the consistent administration of allergen extract; therefore, adherence to these treatments is vital for compelling long-term results. Our review discusses the current terminology from adherence research in general, summarizes 25 current studies on adherence research in AIT in a scoping literature review, and delineates recommendations for tools and parameters for adherence research, aiming to improve outcomes in AIT. Almost every adherence study in AIT published to date used different tools, parameters, and data sources for measuring adherence and persistence rates. Unfortunately, an easily accessible, objective parameter or biomarker for monitoring treatment adherence and success has not yet been established for AIT. This situation calls for the development of an international core outcomes set for AIT that defines what is exactly meant by AIT adherence and how AIT adherence should be consistently measured. Therefore, we exemplarily present results and conclusions from adherence research in chronic diseases other than allergology. We aim to facilitate the development of advanced methods, considering the challenging disease specificities of these parameters in a routine care setting of AIT.

[New interdisciplinary teaching concept for the cross-sectional subject of allergology in human medicine studies]. / Interdisziplinäre Neukonzeption der Lehre im Querschnittsfach "Allergologie" im Studiengang Humanmedizin.

BACKGROUND: Although allergic diseases are among the most important health disorders, allergology is not anchored as an independent subject in the clinical part of medical studies in Germany. OBJECTIVE: As all universities and institutes face the same challenge, the aim of our project was to establish exemplary coordination and networking of education in allergology at one location in agreement with all involved departments and institutes. Particularly, Comprehensive Allergy Centers (CAC) offer an established infrastructure via which the revised allergology education program can be transferred to other universities. MATERIALS AND METHODS: After an extensive inventory of the current allergological curriculum at the University Medical Center Göttingen, a new teaching concept was developed in interdisciplinary consensus, supplemented by first-time provision of additional digital contents ("blended learning"), and finally evaluated. RESULTS: Initially, we observed a high level of fragmentation in the teaching of allergology in the clinical study sections of human medicine, with no coordination between the 12 clinical departments/institutes involved and no coherent framework for the specific learning content. Within the established structure of the interdisciplinary CAC, we revised, coordinated, and defined key areas for improved student education in clinical allergology. The allocation of new interactive learning elements as well as supplementary materials for self-studies was welcomed by the students and positively evaluated. A survey among students after completing the former vs. current curricula showed significant improvements in achieving the desired educational objectives.

The Impact of COVID-19 Pandemic on Medical Doctors' Work-Family Balance at German University Clinics.

The measures taken to cope with the COVID-19 pandemic by governments worldwide have vast consequences on all areas of life. To assess the impact of the COVID-19 pandemic on long-term career development, we evaluated the work-family balance of medical doctors at nine German university clinics. The results indicate a severely disturbed work-family balance, which was mostly due to insufficient childcare, based on restrictions in school operations and childcare. Despite the newly created emergency childcare options, aiming to ensure the functioning of the "systematically important" professional groups, medical doctors feel that they are not sufficiently supported by the measures taken by local governments. Women, in particular, see their professional development at risk. Our results underline that proper and flexible childcare is essential for the career advancement of female medical doctors and is particularly important in times of crises such as the current COVID-19 pandemic. At university medicine clinics, increased work time flexibility and optimized schooling and childcare are needed to promote the career development of female as well as male medical doctors in the early stage of their careers.

Sensitization against Fungi in Patients with Airway Allergies over 20 Years in Germany.

BACKGROUND: Fungal spores are ubiquitous allergens. Severe forms of asthma are particularly highly associated with fungal sensitization. National and international asthma guidelines recommend the implementation of allergen immunotherapy if indicated. Thus, detection and treatment of relevant allergies are key components of primary care of these patients. OBJECTIVES: The aims of the study were (i) to investigate trends in the prevalence of sensitization to twelve fungi in central Germany over the last 20 years and (ii) to dissect specific sensitization patterns among the 3 most important fungi: Aspergillus, Alternaria, and Cladosporium. METHODS: This single-center study evaluated skin prick test (SPT) results of 3,358 patients with suspected airway allergies over a period of 20 years (1998-2017). RESULTS: While 19.2% of all study patients had positive test results to at least 1 of the 3 fungi (Alternaria, Aspergillus, or Cladosporium) in the first study decade, this rate increased to 22.5% in the second decade. Slight increases in sensitization rates to almost all fungi were observed over the 20-year period. In the last decade, polysensitization to Alternaria, Aspergillus, and Cladosporium increased significantly. Sensitization to fungi is age-dependent and peaks in the age-group of 21-40 years during the second decade. CONCLUSION: Fungi are relevant allergens for perennial and seasonal allergy symptoms. We currently recommend including Aspergillus, Alternaria, and Cladosporium in the standard series of SPTs for airway allergies.

Sensitization rates to common inhaled allergens in Germany - increase and change patterns over the last 20 years.

BACKGROUND: Sensitization rates to aeroallergens are rising worldwide. The prevalence is increasing, especially in Western countries. We aimed to investigate (1) sensitization rates and (2) cross-sensitization patterns in skin prick tests (SPTs) for the most relevant inhaled allergens in central Germany over 20 years, adjusted for regional pollen counts. PATIENTS AND METHODS: This monocentric study evaluated SPTs for tree pollen, grass pollen and house dust mites (HDMs) in 4,315 patients (including children) with suspected airway allergies, from 1998-2017. RESULTS: Sensitization rates to almost all aeroallergens have increased significantly over time, without relevant changes in regional pollen counts. Current sensitization rates in all our symptomatic patients were highest for grass (55.3 %) and rye pollen (59.6 %), with most pronounced increases in HDM sensitization over time (from 37.8 % to the current figure of 50.1 %). However, a low but consistent proportion of tree-sensitized patients (3.6-7.8 %) showed isolated positive SPTs to alder and/or hazel pollen without sensitization to birch pollen. CONCLUSIONS: We demonstrate a significant rise in the total number of sensitized patients as well as increases in cross-sensitization between closely related allergens. Individuals with unusual mono-sensitization profiles to common inhaled allergens should be studied in more detail, since these patients are currently excluded from clinical trials for allergen immunotherapy.

Improving povidone-iodine and iodine preparations for patch testing.

BACKGROUND: Allergy evaluation by patch testing with povidone-iodine (PVP-I) or iodine remains challenging, because current patch test preparations frequently lead to false-positive or irritant skin reactions. OBJECTIVES: To investigate different preparations for iodine patch tests and to assess their clinical relevance with repeated open application tests (ROATs). METHODS: We monocentrically analyzed 95 patients with suspected allergy to disinfectants in retrospect who underwent parallel iodine patch testing with four preparations: PVP-I 2% aq., 5% aq., 10% aq., and iodine 0.5% pet. RESULTS: In 27 of 95 patients (28.4%), we found positive reactions to one of the four test preparations. After ROATs in 22 of these 27 positively tested individuals, only one patient was diagnosed with iodine allergy. In contrast, 31 of 95 patients (32.6%) showed irritant or questionable patch test reactions on day 2 (D2) and/or D3 and/or D7 to one or more test preparations. Testing with PVP-I 2% aq. resulted in the lowest number of doubtful skin reactions while detecting the single allergic patient. CONCLUSION: PVP-I 2% aq. was found to be the optimal patch test preparation. In general, iodine allergy appears to be substantially overestimated, and positive patch test responses to iodine should prompt an urgent ROAT for confirmation before diagnosing iodine allergy.

Sex- and Age-Dependent Changes in Polysensitization to Common Aeroallergens Over 20 Years.

INTRODUCTION: The prevalence of airway allergies in Europe has increased from 23% to 31% in recent years. Polysensitization is associated with the development and severity of relevant allergies, particularly allergic asthma. OBJECTIVE: We investigated age- and sex-dependent monosensitization and polysensitization profiles as well as patterns of sensitization using skin prick test (SPT) reactivity to the most common aeroallergens. PATIENTS AND METHODS: From 1998 to 2017, SPTs were retrospectively analyzed in 2886 symptomatic patients, referred to the University Medical Center Göttingen, located in central Germany. The major aeroallergen groups early flowering tree pollen, grass pollen, and house dust mites were evaluated in this study. Wheal diameters ≥2 mm were considered positive during the entire study period. RESULTS: Polysensitization to the most common aeroallergen groups increased significantly over 20 years. Boys and young men displayed the most remarkable rise in total sensitization rates in our study group over time. DISCUSSION: Our patient-based study demonstrates a continuing increase in polysensitization rates over the last 20 years, with boys and young men being most frequently affected. Our data-without being a population-based study-suggest a scenario with climbing rates of allergic rhinitis and asthma.

Allergic Rhinitis to Weed Pollen in Germany: Dominance by Plantain, Rising Prevalence, and Polysensitization Rates over 20 Years.

BACKGROUND: In contrast to the 3 major aeroallergens tree pollen, grass pollen, and house dust mites, allergic rhinitis caused by herbal pollen has received comparatively little attention in recent clinical studies. Since various weeds flower during summer until fall, allergic rhinitis to weeds may be underdiagnosed and/or mistakenly diagnosed as grass pollen allergy. OBJECTIVE: To investigate (i) the currently most frequent weed allergy between mugwort, ragweed, plantain, chamomile, nettle, and oilseed rape and (ii) time trends in prevalence of sensitization to weed pollen in the middle of Germany over the last 20 years. METHODS: This study, the largest of its kind to date, monocentrically evaluated the prick test results of a total of 6,220 patients with suspected RCA over a period of 20 years (1998-2017). RESULTS: In the study cohort, sensitization rates to plantain almost doubled from 26.6% in the decade 1998-2007 to 50.5% in 2008-2017. Identical increases were observed for ragweed, while sensitization rates for mugwort stayed largely unchanged. The most prominent increase in positive skin prick tests to plantain and ragweed pollen was mainly observed in younger patients. Further, we identified a trend toward polysensitization, currently dominated by plantain and ragweed. Sensitization to weed pollen was found to be highly associated with additional sensitizations to grass and/or birch pollen. CONCLUSION: Plantain is currently the best choice to screen rhinitis patients for weed allergy which identifies 86% of all weed-sensitized individuals, at least in Germany. Over the last 20 years, we demonstrate a significant rise in the total number of weed pollen sensitization as well as increases in polysensitization, predominantly in younger patients.

Cochlear obliteration after translabyrinthine vestibular schwannoma surgery.

The objective of the study was to determine the temporal occurrence of cochlear obliteration following translabyrinthine vestibular schwannoma resection. A retrospective chart review, cross-sectional study, and sequential analysis of the time series were performed. The retrospective study included patients undergoing translabyrinthine resection for stage T1-T2 vestibular schwannoma from 2007 to 2010 without prior therapy and postoperative follow-up including MRI of the brain and the cerebellopontine angle. Already 3 months after surgery a radiographic labyrinthine change was observed in 66.7 %, a partial obstruction in 50 %, and an obstruction limited to the saccule in 16.7 %. Only 33.3 % of the patients showed an unchanged inner ear. In consideration of early cochlear obstruction after translabyrinthine vestibular schwannoma resection, temporary follow-up is necessary. Since the indications for cochlear implantation (CI) have been extended, especially concerning patients with single-side deafness, a simultaneous or early second-stage CI after tumour removal should be discussed.