This evidence‐ and consensus‐based guideline was developed following the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working ...group. The conference was held on 1 December 2016. It is a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the EU‐founded network of excellence, the Global Allergy and Asthma European Network (GA²LEN), the European Dermatology Forum (EDF) and the World Allergy Organization (WAO) with the participation of 48 delegates of 42 national and international societies. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast cell‐driven disease, presenting with wheals, angioedema, or both. The lifetime prevalence for acute urticaria is approximately 20%. Chronic spontaneous urticaria and other chronic forms of urticaria are disabling, impair quality of life and affect performance at work and school. This guideline covers the definition and classification of urticaria, taking into account the recent progress in identifying its causes, eliciting factors and pathomechanisms. In addition, it outlines evidence‐based diagnostic and therapeutic approaches for the different subtypes of urticaria.
Allergic rhinoconjunctivitis (AR) is an allergic disorder of the nose and eyes affecting about a fifth of the general population. Symptoms of AR can be controlled with allergen avoidance measures and ...pharmacotherapy. However, many patients continue to have ongoing symptoms and an impaired quality of life; pharmacotherapy may also induce some side‐effects. Allergen immunotherapy (AIT) represents the only currently available treatment that targets the underlying pathophysiology, and it may have a disease‐modifying effect. Either the subcutaneous (SCIT) or sublingual (SLIT) routes may be used. This Guideline has been prepared by the European Academy of Allergy and Clinical Immunology's (EAACI) Taskforce on AIT for AR and is part of the EAACI presidential project “EAACI Guidelines on Allergen Immunotherapy.” It aims to provide evidence‐based clinical recommendations and has been informed by a formal systematic review and meta‐analysis. Its generation has followed the Appraisal of Guidelines for Research and Evaluation (AGREE II) approach. The process included involvement of the full range of stakeholders. In general, broad evidence for the clinical efficacy of AIT for AR exists but a product‐specific evaluation of evidence is recommended. In general, SCIT and SLIT are recommended for both seasonal and perennial AR for its short‐term benefit. The strongest evidence for long‐term benefit is documented for grass AIT (especially for the grass tablets) where long‐term benefit is seen. To achieve long‐term efficacy, it is recommended that a minimum of 3 years of therapy is used. Many gaps in the evidence base exist, particularly around long‐term benefit and use in children.
Background
Since 1988, numerous allergen immunotherapy guidelines (AIT‐GLs) have been developed by national and international organizations to guide physicians in AIT. Even so, AIT is still severely ...underused.
Objective
To evaluate AIT‐GLs with AGREE‐II, developed in 2010 by McMaster University methodologists to comprehensively evaluate GL quality.
Methods
Allergist, from different continents, knowledgeable in AIT and AGREE‐II trained were selected into the project team. The project received methodologists’ guidance. AIT‐GLs in any language were sought from 1980 to 2016; AIT‐GLs were AGREE II‐evaluated by at least 2 team members, independently; discrepancies were resolved in a second round, by team discussion or methodologists’ consulting.
Results
We found 31 AIT‐GLs (15 post‐2010), ranging from local consensus reports to international position papers (EAACI, AAAAI‐ACAAI, WAO). Pre‐2010 GLs scored 1.6‐4.6 (23%‐67%) and post‐2010 GLs scored 2.1‐6 (30%‐86%), on a 7‐point Likert scale. The highest scores went to: German‐Austrian‐Swiss (6.0), Mexican (5.1), and the AAAAI/ACAAI AIT‐GL (4.7). These were also the only 3 GLs that received “yes” of both evaluators to the item: “I would recommend this GL for use.” The domains of “Stakeholder involvement” and “Rigor of Development” only scored 3/7, and “Applicability” scored the lowest. Strikingly, newer GLs only scored clearly better in “Editorial independence” and “Global evaluation.”
Conclusions
In AIT‐GLs, there is still a lot of room for improvement, especially in domains crucial for the dissemination. For some GLs, the “Scientific rigor” domain flawed. When resources are limited, transculturizing a high‐quality GL might be preferable over developing a GL from zero. Our study and AGREE‐II could help to select the best candidate.
Clinical Implications
We here evaluate allergen immunotherapy guideline (AIT‐GL) quality. Only high‐quality AIT‐GLs should be consulted for AIT management decisions. In low‐resource settings, transculturization of these is preferred over developing low‐quality guidelines.
Background
The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing Guidelines on Allergen Immunotherapy (AIT) for Allergic Rhinoconjunctivitis. To inform the ...development of clinical recommendations, we undertook a systematic review to assess the effectiveness, cost‐effectiveness, and safety of AIT in the management of allergic rhinoconjunctivitis.
Methods
We searched nine international biomedical databases for published, in‐progress, and unpublished evidence. Studies were independently screened by two reviewers against predefined eligibility criteria and critically appraised using established instruments. Our primary outcomes of interest were symptom, medication, and combined symptom and medication scores. Secondary outcomes of interest included cost‐effectiveness and safety. Data were descriptively summarized and then quantitatively synthesized using random‐effects meta‐analyses.
Results
We identified 5960 studies of which 160 studies satisfied our eligibility criteria. There was a substantial body of evidence demonstrating significant reductions in standardized mean differences (SMD) of symptom (SMD −0.53, 95% CI −0.63, −0.42), medication (SMD −0.37, 95% CI −0.49, −0.26), and combined symptom and medication (SMD −0.49, 95% CI −0.69, −0.30) scores while on treatment that were robust to prespecified sensitivity analyses. There was in comparison a more modest body of evidence on effectiveness post‐discontinuation of AIT, suggesting a benefit in relation to symptom scores.
Conclusions
AIT is effective in improving symptom, medication, and combined symptom and medication scores in patients with allergic rhinoconjunctivitis while on treatment, and there is some evidence suggesting that these benefits are maintained in relation to symptom scores after discontinuation of therapy.
Background
Large observational implementation studies are needed to triangulate the findings from randomized control trials as they reflect “real‐world” everyday practice. In a pilot study, we ...attempted to provide additional and complementary insights on the real‐life treatment of allergic rhinitis (AR) using mobile technology.
Methods
A mobile phone app (Allergy Diary, freely available in Google Play and Apple App stores) collects the data of daily visual analog scales (VAS) for (i) overall allergic symptoms, (ii) nasal, ocular, and asthma symptoms, (iii) work, as well as (iv) medication use using a treatment scroll list including all medications (prescribed and over the counter (OTC)) for rhinitis customized for 15 countries.
Results
A total of 2871 users filled in 17 091 days of VAS in 2015 and 2016. Medications were reported for 9634 days. The assessment of days appeared to be more informative than the course of the treatment as, in real life, patients do not necessarily use treatment on a daily basis; rather, they appear to increase treatment use with the loss of symptom control. The Allergy Diary allowed differentiation between treatments within or between classes (intranasal corticosteroid use containing medications and oral H1‐antihistamines). The control of days differed between no best control, single, or multiple treatments (worst control).
Conclusions
This study confirms the usefulness of the Allergy Diary in accessing and assessing everyday use and practice in AR. This pilot observational study uses a very simple assessment (VAS) on a mobile phone, shows novel findings, and generates new hypotheses.
A major challenge in quantum metrology is the generation of entangled states with a macroscopic atom number. Here, we demonstrate experimentally that atomic squeezing generated via nonlinear dynamics ...in Bose-Einstein condensates, combined with suitable trap geometries, allows scaling to large ensemble sizes. We achieve a suppression of fluctuations by 5.3(5) dB for 12,300 particles, from which we infer that similar squeezing can be obtained for more than 10(7) atoms. With this resource, we demonstrate quantum-enhanced magnetometry by swapping the squeezed state to magnetically sensitive hyperfine levels that have negligible nonlinearity. We find a quantum-enhanced single-shot sensitivity of 310(47) pT for static magnetic fields in a probe volume as small as 90 μm3.
Background
Allergen exposure chambers (AECs) are clinical facilities allowing for controlled exposure of subjects to allergens in an enclosed environment. AECs have contributed towards characterizing ...the pathophysiology of respiratory allergic diseases and the pharmacological properties of new therapies. In addition, they are complementary to and offer some advantages over traditional multicentre field trials for evaluation of novel therapeutics. To date, AEC studies conducted have been monocentric and have followed protocols unique to each centre. Because there are technical differences among AECs, it may be necessary to define parameters to standardize the AECs so that studies may be extrapolated for driving basic immunological research and for marketing authorization purposes by regulatory authorities.
Methods
For this task force initiative of the European Academy of Allergy and Clinical Immunology (EAACI), experts from academia and regulatory agencies met with chamber operators to list technical, clinical and regulatory unmet needs as well as the prerequisites for clinical validation.
Results
The latter covered the validation process, standardization of challenges and outcomes, intra‐ and interchamber variability and reproducibility, in addition to comparability with field trials and specifics of paediatric trials and regulatory issues.
Conclusion
This EAACI Position Paper aims to harmonize current concepts in AECs and to project unmet needs with the intent to enhance progress towards use of these facilities in determining safety and efficacy of new therapeutics in the future.
We experimentally demonstrate a nonlinear detection scheme exploiting time-reversal dynamics that disentangles continuous variable entangled states for feasible readout. Spin-exchange dynamics of ...Bose-Einstein condensates is used as the nonlinear mechanism which not only generates entangled states but can also be time reversed by controlled phase imprinting. For demonstration of a quantum-enhanced measurement we construct an active atom SU(1,1) interferometer, where entangled state preparation and nonlinear readout both consist of parametric amplification. This scheme is capable of exhausting the quantum resource by detecting solely mean atom numbers. Controlled nonlinear transformations widen the spectrum of useful entangled states for applied quantum technologies.
Allergic rhinitis often impairs social life and performance. The aim of this cross‐sectional study was to use cell phone data to assess the impact on work productivity of uncontrolled rhinitis ...assessed by visual analogue scale (VAS). A mobile phone app (Allergy Diary, Google Play Store and Apple App Store) collects data from daily visual analogue scales (VAS) for overall allergic symptoms (VAS‐global measured), nasal (VAS‐nasal), ocular (VAS‐ocular) and asthma symptoms (VAS‐asthma) as well as work (VAS‐work). A combined nasal‐ocular score is calculated. The Allergy Diary is available in 21 countries. The app includes the Work Productivity and Activity Impairment Allergic Specific Questionnaire (WPAI:AS) in six EU countries. All consecutive users who completed the VAS‐work from 1 June to 31 October 2016 were included in the study. A total of 1136 users filled in 5818 days of VAS‐work. Symptoms of allergic rhinitis were controlled (VAS‐global <20) in approximately 60% of the days. In users with uncontrolled rhinitis, approximately 90% had some work impairment and over 50% had severe work impairment (VAS‐work >50). There was a significant correlation between VAS‐global calculated and VAS‐work (Rho=0.83, P<0.00001, Spearman's rank test). In 144 users, there was a significant correlation between VAS‐work and WPAI:AS (Rho=0.53, P<0.0001). This pilot study provides not only proof‐of‐concept data on the work impairment collected with the app but also data on the app itself, especially the distribution of responses for the VAS. This supports the interpretation that persons with rhinitis report both the presence and the absence of symptoms.
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