S3 Guideline Urticaria. Part 2: Treatment of urticaria - German-language adaptation of the international S3 guideline.

This publication is the second part of the German-language S3 guideline on urticaria. It covers the management of urticaria and should be used together with Part 1 of the guideline on classification and diagnosis. This publication was prepared according to the criteria of the AWMF on the basis of the international English-language S3 guideline with special consideration of health system conditions in German-speaking countries. Chronic urticaria has a high impact on the quality of life and daily activities of patients. Therefore, if causal factors cannot be eliminated, effective symptomatic treatment is necessary. The recommended first-line treatment is to administer new generation, non-sedating H1 antihistamines. If the standard dose is not sufficiently effective, the dose should be increased up to fourfold. For patients who do not respond to this treatment, the second-line treatment in addition to antihistamines in the treatment algorithm is omalizumab and, if this treatment fails, ciclosporin. Other low-evidence therapeutic agents should only be used if all treatments in the treatment algorithm agreed upon by the guideline group fail. Both the benefit-risk profile and cost should be considered. Corticosteroids are not recommended for long-term treatment due to their inevitable severe side effects.

S3 Guideline Urticaria. Part 1: Classification and diagnosis of urticaria - German-language adaptation of the international S3 Guideline.

The lifetime prevalence of urticaria, a severe allergic disease, is almost 20%. It not only limits the quality of life of those affected, but also their general performance at work and in their daily activities. This publication is the first section of the Urticaria Guideline. It covers the classification and diagnosis of urticaria, taking into account the major advances in research into its causes, triggering factors and pathomechanisms. It also addresses strategies for the efficient diagnosis of the different subtypes of urticaria. This is crucial for individual, patient-oriented treatment, which is covered in the second part of the guideline, published separately. This German-language guideline was developed according to the criteria of the AWMF on the basis of the international English-language S3 guideline with special consideration of health system characteristics in the German-speaking countries. This first part of the guideline describes the classification of urticaria, distinguishing spontaneously occurring wheals (hives) and angioedema from forms of urticaria with inducible symptoms. Urticaria is defined as sudden onset of wheals, angioedema, or both, but is to be distinguished from conditions in which wheals occur as a short-term symptom, such as anaphylaxis. The diagnosis is based on (a limited number of) laboratory tests, but especially on medical history. In addition, validated instruments are available to measure the severity, activity and course of the disease.

S2k Guideline for the diagnosis and treatment of mucous membrane pemphigoid.

Mucous membrane pemphigoid (MMP) is a pemphigoid disease with predominant mucous membrane involvement. It mainly affects the mucous membranes of the mouth, eyes, nose and pharynx, but also the larynx, trachea, esophagus, genital and perianal regions. The manifestation of the disease covers a wide spectrum from gingival erythema and single oral lesions to severe tracheal strictures that obstruct breathing and conjunctival scarring with marked visual impairment and, not infrequently, blindness. In addition to a clinical picture of predominant mucosal involvement, diagnosis is based on direct immunofluorescence of a peri-lesional biopsy and serology. The main target antigen is BP180 (collagen XVII), and reactivity with laminin 332 is associated with malignancy in approximately 25 % of MMP patients. The treatment of MMP is challenging. On the one hand, due to the involvement of different mucous membranes, good interdisciplinary cooperation is required; on the other hand, due to the rarity of the disease, no randomized controlled clinical trials are available. The aim of this guideline is to present the clinical picture, including severity and scoring systems, and to give guidance for diagnosing and treating this complex disease. In MMP, interdisciplinary cooperation plays an essential role as well as the prompt diagnosis and initiation of adequate therapy in order to avoid irreversible damage to the mucous membranes with serious complications.

Perioperatives Management von Antithrombotika in der Dermatochirurgie - Eine Umfrage unter Dermatologen in Deutschland.

Hintergrund und Zielsetzung: Wir haben in zwei Querschnittsumfragen in den Jahren 2012 und 2017 eine erhebliche Heterogenität im perioperativen Management von Antithrombotika unter Dermatologen in Deutschland festgestellt. Die erste deutsche Leitlinie zu diesem Thema wurde 2014 veröffentlicht und im Jahr 2021 aktualisiert. Wir wollten herausfinden, wie sich der Umgang mit Antithrombotika verändert hat. Methodik: Wir haben eine papierbasierte Umfrage an 1115 Dermatologen in ganz Deutschland versandt und sie zu ihrem perioperativen Management von Antithrombotika bei Operationen an der Haut sowie zu ihrer Vertrautheit mit der Leitlinie befragt. Ergebnisse: Wir erhielten Antworten von 65 stationär tätigen und 202 niedergelassenen Dermatologen. Die meisten Dermatologen gaben an, Antithrombotika bei kleineren Operationen fortzuführen. Ein nennenswerter Anteil der Dermatologen gab an, bei invasiveren Operationen die Behandlung mit Phenprocoumon perioperativ zu pausieren und mit Heparin zu überbrücken. Bei Kombinationstherapien war das Fortführen der Behandlung weniger verbreitet. Schlussfolgerungen: Der Anteil der Dermatologen in Deutschland, die angaben, Antithrombotika bei Operationen an der Haut leitlinienkonform zu managen, ist seit 2012 gestiegen. Das Fortführen von Antithrombotika bei großen Exzisionen und Wächterlymphknotenexstirpationen, der Verzicht auf die Überbrückung von Phenprocoumon mit Heparin und das perioperative Fortführen antithrombotischer Kombinationstherapien müssen jedoch weiterhin propagiert werden, insbesondere unter niedergelassenen Dermatologen.

Perioperative management of antithrombotic drugs in skin surgery - A survey of dermatologists in Germany.

BACKGROUND: We identified substantial heterogeneity in the perioperative management of antithrombotic drugs in skin surgery in Germany in 2012 and 2017 in two cross-sectional surveys. The first national guideline on this subject was published in 2014 and updated in 2021. We sought to identify whether the management of these drugs had changed. METHODS: We sent a paper-based survey to 1115 dermatologists throughout Germany asking them about their perioperative management of antithrombotic drugs in skin surgery, as well as their familiarity with the guideline. RESULTS: We received responses from 65 hospital- and 202 office-based dermatologists. Most dermatologists reported continuing antithrombotic drugs in their patients when performing minor surgeries. A notable proportion of dermatologists reported discontinuing phenprocoumon treatment perioperatively and bridging patients with heparin when performing more invasive surgeries. Continuation was less common during combination therapies. CONCLUSIONS: The proportion of physicians in Germany who reported managing antithrombotic drugs during skin surgery in ways that are in concordance with the national guideline has increased since 2012. However, continuing antithrombotic drugs during large excisions and sentinel lymph node biopsies, abstaining from bridging patients on phenprocoumon with heparin, and continuing antithrombotic combination therapies perioperatively need to be further encouraged, especially among office-based dermatologists.

The international EAACI/GA²LEN/EuroGuiDerm/APAAACI guideline for the definition, classification, diagnosis, and management of urticaria.

This update and revision of the international guideline for urticaria was developed following the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. It is a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the Global Allergy and Asthma European Network (GA²LEN) and its Urticaria and Angioedema Centers of Reference and Excellence (UCAREs and ACAREs), the European Dermatology Forum (EDF; EuroGuiDerm), and the Asia Pacific Association of Allergy, Asthma and Clinical Immunology with the participation of 64 delegates of 50 national and international societies and from 31 countries. The consensus conference was held on 3 December 2020. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast cell-driven disease that presents with wheals, angioedema, or both. The lifetime prevalence for acute urticaria is approximately 20%. Chronic spontaneous or inducible urticaria is disabling, impairs quality of life, and affects performance at work and school. This updated version of the international guideline for urticaria covers the definition and classification of urticaria and outlines expert-guided and evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria.

Factors that motivate men who have sex with men in Berlin, Germany, to use or consider using HIV pre-exposure prophylaxis-A multi-methods analysis of data from a multicentre survey.

BACKGROUND: While our knowledge of what motivates men who have sex with men (MSM) to use HIV pre-exposure prophylaxis (PrEP) has grown in recent years, quantitative survey-based studies have not asked MSM explicitly to name their motivations. We did so using a qualitative open-ended question and aimed to categorise the responses and explore whether these were related to where MSM were located along a conceptual continuum of PrEP care. METHODS: In a multicentre survey examining knowledge and use of PrEP among MSM in Berlin, Germany, we additionally asked an open-ended question about motivations for using or considering PrEP. Data were collected from 10/2017-04/2018. One researcher developed a thematic framework deductively from the literature and another did so inductively from the free-text data, and a merged framework was used to code responses independently. We used Fisher's exact test to assess whether the frequency of motivations differed significantly between respondents using or considering PrEP. RESULTS: Of 875 questionnaires, 473 were returned and 228 contained a free-text response. Motivations in the following categories were reported: (1) Safety/protection against HIV (80.2% of participants, including general safety; additional protection to condoms), (2) Mental well-being and quality of life (23.5%, including reduced anxiety; better quality of life), (3) Condom attitudes (18.9% intent not to use condoms), (4) Expectations about sexuality (14.4%, including worry-free sex or more pleasurable sex, with explicit mention of sex or sexuality), (5) Norms/social perspectives (0.8%). The difference in frequencies of motivations between those using or considering PrEP was not statistically significant. CONCLUSIONS: Safety and protection against HIV, particularly having additional protection if condoms fail, were the most common motivations for using or considering PrEP, followed by mental well-being and quality of life. Many respondents reported several motivations, and responses overall were heterogeneous. This suggests that approaches to increase PrEP uptake that focus exclusively on its effectiveness in preventing HIV are unlikely to be as successful as a holistic approach that emphasises multiple motivations and how these fit into the broader sexual and psychological health of MSM.

HIV Pre-exposure Prophylaxis (PrEP): Knowledge, attitudes and counseling practices among physicians in Germany - A cross-sectional survey.

BACKGROUND: German statutory health insurance began covering the costs associated with HIV PrEP in September 2019; however, to bill for PrEP services, physicians in Germany must either be certified as HIV-specialists according to a nationwide quality assurance agreement, or, if they are non-HIV-specialists, have completed substantial further training in HIV/PrEP care. Given the insufficient implementation of PrEP, the aim of our study was to explore the potential to increase the number of non-HIV-specialists providing PrEP-related services. METHODS: We conducted an anonymous survey among a random sample of internists, general practitioners, dermatologists and urologists throughout Germany using a self-developed questionnaire. We calculated a knowledge score and an attitudes score from individual items in these two domains. Both scores ranged from 0-20, with high values representing good knowledge or positive attitudes. We also asked participants about the proportion of PrEP advice they provided proactively to men who have sex with men (MSM) and trans-persons who met the criteria to be offered PrEP. RESULTS: 154 physicians completed the questionnaire. Self-assessed knowledge among HIV-specialists was greater than among non-HIV-specialists [Median knowledge score: 20.0 (IQR = 0.0) vs. 4.0 (IQR = 11.0), p<0.001]. Likewise, attitudes towards PrEP were more positive among HIV-specialists than non-HIV-specialists [Median attitudes score: 18.0 (IQR = 3.0) vs. 13.0 (IQR = 5.25), p<0.001]. The proportion of proactive advice on PrEP provided to at-risk MSM and trans-persons by HIV-specialists [Median: 30.0% (IQR = 63.5%)] was higher than that provided by non-HIV-specialists [Median: 0.0% (IQR = 11.3%), p<0.001]. However, the results of our multiple regression suggest the only independent predictor of proactive PrEP advice was the knowledge score, and not whether physicians were HIV-specialists or non-HIV-specialists. CONCLUSIONS: These findings point to opportunities to improve PrEP implementation in individuals at risk of acquiring HIV. Targeted training, particularly for non-HIV-specialists, and the provision of patient-centered information material could help improve care, especially in rural areas.

German evidence and consensus-based (S3) guideline: Vaccination recommendations for the prevention of HPV-associated lesions.

Anogenital and oropharyngeal infections with human papilloma viruses (HPV) are common. Clinically manifest disease may significantly impact quality of life; the treatment of HPV-associated lesions is associated with a high rate of recurrence and invasive neoplasms, such as cervical, anal, vulvar, penile, and oropharyngeal cancers, which are characterized by significant morbidity and mortality. Vaccination against HPV is an effective and safe measure for the primary prevention of HPV-associated lesions, but immunization rates are still low in Germany. The present publication is an abridged version of the German evidence and consensus-based guideline "Vaccination recommendations for the prevention of HPV-associated lesions", which is available on the website of the German Association of the Scientific Medical Societies (AWMF). On the basis of a systematic review with meta-analyses, a representative panel developed and agreed upon recommendations for the vaccination of different populations against HPV. In addition, consensus-based recommendations were developed for specific issues relevant to everyday practice. Based on current evidence and a representative expert consensus, these recommendations are intended to provide guidance in a field in which there is often uncertainty and in which both patients and health care providers are sometimes confronted with controversial and emotionally charged points of view.

Clinical Practice Guideline: Anal Cancer­Diagnosis, Treatment and Follow-up

BACKGROUND: The number of anal cancer diagnoses has been rising steadily, so that the incidence has doubled in the past 20 years. Almost all anal cancers are induced by persistent infection with human papillomaviruses. Hitherto the care of patients with anal cancer has been heterogeneous and little experience exists with the primary management of anal cancer. METHODS: The guideline was developed in accordance with the requirements of the German Guideline Program in Oncology. In line with the GRADE approach, the certainty of the evidence was assessed on the outcome level following a systematic literature search. Interdisciplinary working groups were set up to compile suggestions for recommendations, which were discussed and agreed upon in a formal consensus conference. RESULTS: Ninety-three recommendations and statements were developed. No high-quality evidence was available to support recommendations for or against the treatment of stage I anal cancer with local excision alone as an alternative to chemoradiotherapy. Chemoradiotherapy is the gold standard in the treatment of stages II­III. Among other aspects regarding the timing and extent of response evaluation after chemoradiotherapy, the guideline panel recommended against obtaining a biopsy in the event of complete clinical response. Owing to lack of confidence in the available evidence, only open recommendations were given for treatment of stage IV. CONCLUSION: This evidence-based clinical practice guideline provides a sound basis for optimizing the interdisciplinary, cross-sector care of anal cancer patients. Among other areas, gaps in research were identified with respect to the care of patients with early-stage or metastatic anal cancer. Approaches such as chemoradiotherapy combined with regional deep hyperthermia require further investigation. The role for immunotherapy in the management of metastasized anal cancer has also been insufficiently explored to date.

State of the art treatment for stage I to III anal squamous cell carcinoma: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: This systematic review summarised and critically appraised evidence on the efficacy and safety of interventions for anal cancer to support the panel of experts developing the national evidence-based anal cancer guideline in Germany. MATERIALS AND METHODS: We conducted a systematic review and meta-analyses of interventions for the treatment of stage I to III anal squamous cell carcinoma (SCCA). We systematically searched several databases and included any randomised controlled trial (RCT) assessing the pre-specified patient populations, regardless of the interventions studied. Non-randomised controlled studies of selected, pre-specified interventions were included if RCTs were not available or contained insufficient information. Where possible, we conducted meta-analyses and critically assessed confidence in the effect estimates using the GRADE approach. RESULTS: Our searches yielded 10,325 (25 October 2018) and 889 hits (update search on 18 July 2019). Among the 41 studies (47 publications) included, we identified 19 comparisons of interventions for SCCA, and confidence in the effect estimates ranged from very low to high. Most RCTs compared various chemoradiation regimes. For other treatment options, such as local excision in early stages or different radiotherapies, we mostly identified comparative cohort studies. CONCLUSION: Our findings indicate that, in most clinical situations, primary chemoradiation based on 5-FU and MMC is still the gold standard. However, treatment options for stage I anal cancer, particularly of the anal margin, as well as newer treatment approaches should be investigated in future RCTs. Overall, our findings may help health care professionals and patients make informed decisions about treatment choices.

Measuring importance of outcomes to patients: a cross-sectional survey for the German anal cancer guideline.

OBJECTIVE: We aimed to generate evidence on patients' values and preferences to inform the development of the German national Evidence-based Anal Cancer Guideline. STUDY DESIGN AND SETTING: We developed a list of health outcomes based on a systematic search. We then asked anal cancer patients and experts of the guideline development group in an online survey to (a) rate the relative importance of the outcomes in different clinical situations using a nine-point, three-category scale, and (b) select seven outcomes they considered most important for decision-making in each situation. RESULTS: Participants rated almost half of the outcomes (45%) as critical for decision-making, and more than half (53%) as important. Only two outcomes (2%) were rated as low in importance. Agreement between expert and patient ratings was low to fair, and we found important discrepancies in how the relative importance of the outcomes was perceived. However, the rankings of outcomes were highly correlated. CONCLUSION: Determining the relative importance placed by anal cancer patients on outcomes provided useful information for developing guideline recommendations. Our approach may be useful for guideline developers who aim to include the patient perspective. Moreover, our findings may help health professionals caring for anal cancer patients in joint decision-making.

HIV Pre-Exposure Prophylaxis (PrEP) Counseling in Germany: Knowledge, Attitudes and Practice in Non-governmental and in Public HIV and STI Testing and Counseling Centers.

Background: Providers of sexual health services play an important role in counseling persons at risk of acquiring HIV. The aim of the present study was to investigate the knowledge of and attitudes toward HIV pre-exposure prophylaxis (PrEP) among counselors in non-governmental counseling centers ("NG counseling centers") and in counseling centers of the local health authorities ("local health offices") in Germany and to determine the extent to which PrEP plays a role in their current counseling practice. Methods: An anonymous cross-sectional study using an online questionnaire was conducted among counselors from sexual health centers across Germany. All NG counseling centers in Germany offering HIV testing were asked to participate. For each NG counseling center, a local health office in the same city was also invited. A "knowledge score" and an "attitudes score" were calculated from single items on various relevant aspects. The association of these scores with the proportion of PrEP advice provided proactively in sessions with men who have sex with men (MSM) and trans persons who met the German and Austrian guideline criteria for being offered PrEP ('at-risk clients') was quantified. Results: From Oct. to Dec. 2018, 145 counselors completed the survey. Both self-assessed knowledge of PrEP and attitudes toward PrEP were greater or more positive among counselors from NG counseling centers compared with counselors from local health offices [Median knowledge score (range 0-20): 18.0 (IQR = 5.0) vs. 14.0 (IQR = 4.0), p < 0.001; median attitudes score (range 0-20): 18.0 (IQR = 4.0) vs. 14.0 (IQR = 6.8), p < 0.001]. The proportion of PrEP advice provided proactively in sessions with at-risk clients was larger in counseling centers than in local health offices [50.0% (IQR = 60.0) vs. 30.0% (IQR = 70.0); p = 0.003]. The results of the multiple linear regression model indicate that knowledge and attitudes of the individual counselors, but not the type of center in which they worked, were independent predictors of the proportion of proactive advice on PrEP. Conclusions: There is room for improvement in the current PrEP counseling practice of sexual health services in Germany. The findings of the present study suggest opportunities to improve the implementation of PrEP as part of a comprehensive HIV prevention strategy.

Impact of pharmaceutical industry involvement in the external review of clinical practice guidelines-A case study.

RATIONALE AND AIM: External review is important when developing clinical practice guidelines. Involving pharmaceutical companies may influence guideline recommendations in their favour and is therefore controversial. Our study aimed to measure stakeholder participation in the external review of the 2016 European acne guideline and assess the extent to which comments submitted by pharmaceutical companies suggested changes favouring their own products. METHODS: Retrospective, partially blinded case study using qualitative analysis of comments submitted during external review. RESULTS: Four stakeholder groups participated in the review: pharmaceutical company representatives (five out of five invited), professional association members (2/222), journal reviewers (n = 2), and visitors to the project website (n = 1). Of 78 comments submitted, 48 were from company representatives, 24 from journal reviewers, and six from others. Each comment suggested one change to the guideline. Of the comments submitted by companies, 41.7% related to "writing or formatting," 16.7% to "presentation of results," 12.5% to "background information for main recommendations," and 12.5% to the "strength of treatment recommendation". In 54.2% (26/48) of these comments, a change was suggested that put the companies' own products in a more positive light. Five of these changes were implemented by the guideline authors in the way suggested by the company representatives. CONCLUSION: Participation of professional societies, patients, and the general public in the external review of the 2016 European acne guideline was unacceptably low. This is in concordance with reports of low participation of these groups in other European dermatology guidelines. While involving the pharmaceutical industry in the review substantially increased the number of comments received, many of these sought changes that would have put companies' own products in a more favourable light. Our findings underscore the need to manage reviewer comments in a robust and transparent fashion. Solutions to encourage participation of all relevant stakeholders are needed.

Correction: Incidence of sexually transmitted infections in men who have sex with men and who are at substantial risk of HIV infection - A meta-analysis of data from trials and observational studies of HIV pre-exposure prophylaxis.

[This corrects the article DOI: 10.1371/journal.pone.0208107.].