Prevalence of and association between atopic dermatitis and food sensitivity, food allergy and challenge-proven food allergy: A systematic review and meta-analysis.

Atopic dermatitis (AD) and food allergy (FA) share similar type 2 inflammation and commonly co-occur, but the precise proportion of AD patients with FA and vice versa, as well as the effect of AD disease severity on the strength of this association remains uncertain. The aim of this comprehensive systematic review and meta-analysis was to determine the prevalence and bidirectional associations of AD with food sensitivity (FS), FA and challenge-proven food allergy (CPFA). We searched PubMed and EMBASE and three independent reviewers performed title/abstract and full-text review and data extraction. Overall, 557 articles (n = 225,568 individuals with AD, n = 1,128,322 reference individuals; n = 1,357,793 individuals with FS, FA or CPFA, n = 1,244,596 reference individuals) were included in quantitative analyses. The overall pooled prevalence of FS, FA and CPFA in individuals with AD were 48.4% (95% confidence interval: 43.7-53.2), 32.7% (28.8-36.6) and 40.7% (34.1-47.5) respectively. AD prevalence among individuals with FS, FA and CPFA were 51.2% (46.3-56.2), 45.3% (41.4-49.3) and 54.9% (47.0-62.8) respectively. Children with AD had higher pooled FS (49.8% (44.4-55.1)) and FA (31.4% (26.9-36.1)) prevalences than adults with AD (28.6% (13.4-46.8) and 24.1% (12.1-38.7) respectively). Prevalences of FS and FA numerically increased with AD severity. FS, FA and CPFA are common comorbidities of AD and are closely related. Physicians should be attentive to this relationship to optimize management and treatment strategies in patients.

Prevalence and characterization of treatment-refractory psoriasis and super-responders to biologic treatment: a nationwide study.

INTRODUCTION: Treatment with biologics often leads to clearance of psoriasis. However, some patients do repeatedly fail to respond and/or lose an achieved response (treatment refractory) to the biologic, whereas other patients achieve excellent response to one biologic and remain clear of psoriasis for several years (super-responders). OBJECTIVE: To identify and characterize patients with treatment refractory psoriasis and patients who are super-responders to biologic treatment. MATERIAL AND METHODS: Patients registered in DERMBIO between January 2007 and November 2019 were included. Patients were categorized as being treatment refractory if they had had treatment failure to ≥3 biologics targeting ≥2 different pathways. Super-responders were patients treated with their first biologic for minimum 5 years without an absolute psoriasis area and severity index (PASI) > 3 between 6 months and 5 years of treatment. All remaining patients from DERMBIO served as comparators. RESULTS: In total, 3280 patients were included with a mean age of 45.0 years. 1221 (37%) of the patients were females. Of the included patients, 214 (6.5%) were categorized as treatment refractory and 207 (6.3%) were categorized as super-responders. Treatment refractory patients had higher mean body weight (100.6 kg vs. 90.6 kg, P < 0.0001) and higher mean BMI (32.2 vs. 29.4, P < 0.0001) compared with the rest of patients in DERMBIO. Super-responders had higher socioeconomic status and fewer comorbidities compared with the comparator group (P < 0.0001). CONCLUSION: A small proportion of patients with psoriasis treated with biologics are either super-responders or treatment refractory. Treatment refractory patients have higher body weight, whereas super-responders have fewer comorbidities and higher socioeconomic status.

Atopic dermatitis among children and adolescents in the Arctic region - a systematic review and meta-analysis.

The prevalence of atopic dermatitis (AD) varies across the globe, and the clinical phenotype with racial background and ethnicity. AD in the Arctic region has only been scarcely studied. We performed a systematic review and meta-analysis to examine the prevalence, clinical manifestations and risk factors for AD among children and adolescents in the Arctic. Three medical databases PubMed, Embase and Web of Science were screened. All studies published between 1990 to 2020 with epidemiologic data on AD in children and adolescents in the Arctic region, were included. Data were extracted and a meta-analysis was performed to obtain pooled proportions and incidences with 95% confidence intervals (CI). We identified 21 studies from 8 different Arctic regions with 31 403 participants. The cumulative incidence of AD was 23% (95% CI 20-26) and 1-year prevalence was 19% (95% CI 15-25). The incidence of AD was higher in the Arctic parts of Scandinavia and lower in Greenland and Russia. Children of indigenous descent had a slightly lower incidence of AD (19%, 95% CI 13-26) compared to the overall population. The dominant phenotype of AD was mild to moderate flexural dermatitis with facial involvement. Asthma and allergic rhinitis were common and observed in 20-30% of children with AD. In conclusion, AD is highly prevalent in the Arctic, but varies between regions and races. Indigenous children living in less urbanized countries appear to have a slightly lower risk of AD. Future studies should confirm this and examine whether this correlation relates to behavioural differences or genetic signature.

Adverse events with IL-17 and IL-23 inhibitors for psoriasis and psoriatic arthritis: a systematic review and meta-analysis of phase III studies.

Biologics targeting interleukin (IL)-17 and IL-23 are generally well-tolerated and considered safe, though adverse events are seen more often compared with placebo. The objectives of this systematic review and meta-analysis were to assess the prevalence of adverse events in patients with psoriasis or psoriatic arthritis with any adverse events after 12, 16, 24 and 52 weeks of treatment with IL-17 or IL-23 inhibitors. Two independent authors searched the databases PubMed and EMBASE for studies reporting on adverse events in phase 3 trials of IL-17 and IL-23 inhibitors for patients with psoriasis and psoriatic arthritis. The study was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data synthesis was performed using a random-effects model. In total, 44 publications (43 studies) were included in the analyses. The proportion of patients with any adverse events for all treatments pooled were 0.57 [95% confidence interval (CI): 0.55-0.59] after 12 weeks, 0.52 (95% CI: 0.49-0.55) after 16 weeks, 0.72 (95% CI: 0.66-0.78) after 24 weeks and 0.81 (95% CI: 0.76-0.86) after 52 weeks. Across therapies, the most prevalent AEs were infections, nasopharyngitis and headache. For ixekizumab one of the most prevalent AEs was injection site reactions, reported in 15.7% of the patients after 52 weeks. Overall, IL-17 and IL-23 inhibitors appear to be well-tolerated with good safety profiles. Our findings may aid the clinical decision making when choosing the most appropriate therapy for patients with moderate-to-severe psoriasis.

Associations between functional polymorphisms and response to biological treatment in Danish patients with psoriasis.

Biological agents including anti-tumor necrosis factor (anti-TNF; adalimumab, infliximab, etanercept) and anti-interleukin-12/13 (IL12/23; ustekinumab) are essential for treatment of patients with severe psoriasis. However, a significant proportion of the patients do not respond to a specific treatment. Pharmacogenetics might be a way to predict treatment response. Using a candidate gene approach, 62 mainly functional single-nucleotide polymorphisms (SNPs) in 44 different genes were evaluated in 478 Danish patients with psoriasis undergoing 376 series of anti-TNF treatment and 230 series of ustekinumab treatment. Associations between genetic variants and treatment outcomes (drug survival and Psoriasis Area Severity Index reduction) were assessed using logistic regression analyses (crude and adjusted for gender, age, psoriatic arthritis and previous treatment). After correction for multiple testing controlling the false discovery rate, six SNPs (IL1B (rs1143623, rs1143627), LY96 (rs11465996), TLR2 (rs11938228, rs4696480) and TLR9 (rs352139)) were associated with response to anti-TNF treatment and 4 SNPs (IL1B (rs1143623, rs1143627), TIRAP (rs8177374) and TLR5 (rs5744174)) were associated with response to ustekinumab treatment (q<0.20). The results suggest that genetic variants related to increased IL-1ß levels may be unfavorable when treating psoriasis with either anti-TNF or ustekinumab, whereas genetic variants related to high interferon-γ levels may be favorable when treating psoriasis with ustekinumab.

Realization of efficient quantum gates with a superconducting qubit-qutrit circuit.

Building a quantum computer is a daunting challenge since it requires good control but also good isolation from the environment to minimize decoherence. It is therefore important to realize quantum gates efficiently, using as few operations as possible, to reduce the amount of required control and operation time and thus improve the quantum state coherence. Here we propose a superconducting circuit for implementing a tunable system consisting of a qutrit coupled to two qubits. This system can efficiently accomplish various quantum information tasks, including generation of entanglement of the two qubits and conditional three-qubit quantum gates, such as the Toffoli and Fredkin gates. Furthermore, the system realizes a conditional geometric gate which may be used for holonomic (non-adiabatic) quantum computing. The efficiency, robustness and universality of the presented circuit makes it a promising candidate to serve as a building block for larger networks capable of performing involved quantum computational tasks.