Search

Treating atopic dermatitis (AD) in pregnant or breastfeeding women, and in women and men with AD aspiring to be parents is difficult and characterized by uncertainty, as evidence to inform decision‐making on systemic anti‐inflammatory treatment is limited. This project mapped consensus across dermatologists, obstetricians and patients in Northwestern Europe to build practical advice for managing AD with systemic anti‐inflammatory treatment in men and women of reproductive age. Twenty‐one individuals (sixteen dermatologists, two obstetricians and three patients) participated in a two‐round Delphi process. Full consensus was reached on 32 statements, partial consensus on four statements and no consensus on four statements. Cyclosporine A was the first‐choice long‐term systemic AD treatment for women preconception, during pregnancy and when breastfeeding, with short‐course prednisolone for flare management. No consensus was reached on second‐choice systemics preconception or during pregnancy, although during breastfeeding dupilumab and azathioprine were deemed suitable. It may be appropriate to discuss continuing an existing systemic AD medication with a woman if it provides good disease control and its benefits in pregnancy outweigh its risks. Janus kinase (JAK) inhibitors, methotrexate and mycophenolate mofetil should be avoided by women during preconception, pregnancy and breastfeeding, with medication‐specific washout periods advised. For men preconception: cyclosporine A, azathioprine, dupilumab and corticosteroids are appropriate; a 3‐month washout prior to conception is desirable for methotrexate and mycophenolate mofetil; there was no consensus on JAK inhibitors. Patient and clinician education on appropriate (and inappropriate) AD treatments for use in pregnancy is vital. A shared‐care framework for interdisciplinary management of AD patients is advocated and outlined. This consensus provides interdisciplinary clinical guidance to clinicians who care for patients with AD before, during and after pregnancy. While systemic AD medications are used uncommonly in this patient group, considerations in this article may help patients with severe refractory AD. [ABSTRACT FROM AUTHOR]

Background: Abrocitinib improved signs and symptoms of moderate‐to‐severe atopic dermatitis (AD) at Weeks 12 and 16 in phase 3 studies, with a manageable safety profile. Patient‐reported outcomes with long‐term abrocitinib treatment were not reported. Objective: To evaluate patient‐reported outcomes with long‐term abrocitinib treatment in patients with moderate‐to‐severe AD. Methods: JADE EXTEND (NCT03422822) is an ongoing, phase 3, long‐term extension study that enrolled patients from previous abrocitinib AD trials. This analysis includes patients from the phase 3 trials JADE MONO‐1 (NCT03349060), JADE MONO‐2 (NCT03575871) and JADE COMPARE (NCT03720470) who completed the full treatment period of placebo or abrocitinib (200 or 100 mg once daily) and subsequently entered JADE EXTEND and were randomised to receive once‐daily abrocitinib 200 or 100 mg. Patient‐reported endpoints to Week 48 included the proportion of patients who achieved Dermatology Life Quality Index (DLQI) scores of 0/1 (no effect of AD on quality of life [QoL]) and a ≥4‐point improvement in Patient‐Oriented Eczema Measure (POEM) score (clinically meaningful improvement). Data cut‐off: April 22, 2020. Results: Baseline DLQI mean scores were 15.4 and 15.3 in the abrocitinib 200‐ and 100‐mg groups, respectively, which corresponded to a 'very large effect' on QoL; at Week 48, mean DLQI scores were lower with abrocitinib 200 mg (4.6; 'small effect' on QoL) and abrocitinib 100 mg (5.9; 'moderate effect' on QoL). Baseline POEM mean scores were 20.4 and 20.5 in the abrocitinib 200‐ and 100‐mg groups, respectively; at Week 48, mean POEM scores were 8.2 and 11.0. Week 48 patient‐reported responses with abrocitinib 200 mg and abrocitinib 100 mg were 44% and 34% for DLQI 0/1, and 90% and 77% for a ≥4‐point reduction in POEM score. Conclusion: In patients with moderate‐to‐severe AD, long‐term abrocitinib treatment resulted in clinically meaningful improvement in patient‐reported symptoms of AD, including QoL. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis (AD) is a heterogeneous inflammatory skin disease with different clinical phenotypes based on factors such as age, race, comorbidities, and clinical signs and symptoms. The effect of these factors on therapeutic responses in AD has only been scarcely studied and not for upadacitinib. Currently, there is no biomarker predicting response to upadacitinib. Objectives: Evaluate the efficacy of the oral Janus kinase inhibitor upadacitinib across patient subgroups (baseline demographics, disease characteristics and prior treatment) in patients with moderate‐to‐severe AD. Methods: Data from phase 3 studies (Measure Up 1, Measure Up 2 and AD Up) were utilized for this post hoc analysis. Adults and adolescents with moderate‐to‐severe AD were randomized to receive once daily oral upadacitinib 15 mg, upadacitinib 30 mg or placebo; patients enrolled in the AD Up study received concomitant topical corticosteroids. Data from the Measure Up 1 and Measure Up 2 studies were integrated. Results: A total of 2584 patients were randomized. A consistently greater proportion of patients achieved at least 75% improvement in the Eczema Area and Severity Index, a 0 or 1 on the validated Investigator Global Assessment for Atopic Dermatitis, and improvement in itch (including an achievement of a reduction of ≥4; and score of 0/1 in Worst Pruritus Numerical Rating Scale) with upadacitinib compared with placebo at Week 16, regardless of age, sex, race, body mass index, AD severity, body surface area involvement, history of atopic comorbidities or asthma, or previous exposure to systemic therapy or cyclosporin. Conclusions: Upadacitinib had consistently high skin clearance rates and itch efficacy across subgroups of patients with moderate‐to‐severe AD through Week 16. These results support upadacitinib as a suitable treatment option in a variety of patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT03569293 (Measure Up 1), NCT03607422 (Measure Up 2) and NCT03568318 (AD Up). [ABSTRACT FROM AUTHOR]

Background: It is not fully understood how different degrees of improvements in atopic dermatitis (AD) clinical outcome measures translate to improvements in patient‐reported outcome (PRO) measures, such as those assessing itch, symptoms, sleep, anxiety, depression, quality of life (QoL), and work productivity. Objectives: This post hoc analysis of three clinical studies assessed how more robust improvements in clinical responses are associated with improvements in PROs and QoL. Methods: Data from three randomized, double‐blind, placebo‐controlled, phase 3 trials in adults and adolescents with moderate to severe atopic dermatitis (Measure Up 1, Measure Up 2, and AD Up) were included. Patients were randomly assigned (1:1:1) to upadacitinib (15 or 30 mg) or placebo once daily (alone or in combination with topical corticosteroids). The mean percentage improvement from baseline to week 16 and percentage of patients achieving responses at week 16 were summarized by the Eczema Area and Severity Index (EASI) and validated Investigator Global Assessment of Atopic Dermatitis (vIGA‐AD) response level categories. Results: A total of 2392 patients from the three trials were included in the analysis. Increasingly greater mean percentage improvement and proportion of patients achieving response was observed at higher clinical response levels (i.e., stepwise pattern). Mean percentage improvement and proportion of patients achieving response exceeded 69% and 70% at EASI ≥ 90 and vIGA‐AD 0/1, respectively, for most PROs including Worst Pruritus Numeric Rating Scale, Patient Oriented Eczema Measure, and Dermatology Life Quality Index. Conclusions: Greater degrees of clinical responses are related to more robust improvements across multiple dimensions impacted by AD, including itch, skin pain, sleep, anxiety, depression, and QoL. [ABSTRACT FROM AUTHOR]

Objective: The My Baby's Movements (MBM) trial aimed to evaluate the impact on stillbirth rates of a multifaceted awareness package (the MBM intervention). Design: Stepped‐wedge cluster‐randomised controlled trial. Setting: Twenty‐seven maternity hospitals in Australia and New Zealand. Population: Women with a singleton pregnancy without major fetal anomaly at ≥28 weeks of gestation from August 2016 to May 2019. Methods: The MBM intervention was implemented at randomly assigned time points, with the sequential introduction of eight groups of between three and five hospitals at 4‐monthly intervals. Using generalised linear mixed models, the stillbirth rate was compared in the control and the intervention periods, adjusting for calendar time, study population characteristics and hospital effects. Main outcome measures: Stillbirth at ≥28 weeks of gestation. Results: There were 304 850 births with 290 105 births meeting the inclusion criteria: 150 053 in the control and 140 052 in the intervention periods. The stillbirth rate was lower (although not statistically significantly so) during the intervention compared with the control period (2.2/1000 versus 2.4/1000 births; aOR 1.18, 95% CI 0.93–1.50; P = 0.18). The decrease in stillbirth rate was greater across calendar time: 2.7/1000 in the first versus 2.0/1000 in the last 18 months. No increase in secondary outcomes, including obstetric intervention or adverse neonatal outcome, was evident. Conclusions: The MBM intervention did not reduce stillbirths beyond the downward trend over time. As a result of low uptake, the role of the intervention remains unclear, although the downward trend across time suggests some benefit in lowering the stillbirth rate. In this study setting, an awareness of the importance of fetal movements may have reached pregnant women and clinicians prior to the implementation of the intervention. The My Baby's Movements intervention to raise awareness of decreased fetal movement did not significantly reduce stillbirth rates. The My Baby's Movements intervention to raise awareness of decreased fetal movement did not significantly reduce stillbirth rates. Linked article This article is commented on by Alexander E. P. Heazell, p. 42 in this issue. To view this mini commentary visit https://doi.org/10.1111/1471-0528.16954. [ABSTRACT FROM AUTHOR]

Background: Janus kinase (JAK) inhibition is a new mode of action in atopic dermatitis (AD); clarity about drug class safety considerations in the context of AD is important. Baricitinib, an oral, reversible, selective inhibitor of JAK1/JAK2, is in late‐stage development for adult patients with moderate‐to‐severe AD. Objective: To report pooled safety data for baricitinib in patients with moderate‐to‐severe AD in the clinical development program including long‐term extension (LTE) studies. Methods: This analysis included patient‐level safety data from six double‐blinded, randomized, placebo‐controlled studies (one phase 2 and five phase 3), one double‐blinded, randomized, LTE study and one open‐label LTE study, reported in three data sets: placebo‐controlled, 2‐mg – 4‐mg extended and All‐bari AD. Safety outcomes include treatment‐emergent adverse events, adverse events of special interest and abnormal laboratory changes. Proportions of patients with events and incidence rates were calculated. Results: Data were collected for 2531 patients who were given baricitinib for 2247 patient‐years (median duration 310 days). The frequency of serious infections, opportunistic infections and conjunctival disorders was low and similar between treatment groups in the placebo‐controlled period. The most common serious infections were eczema herpeticum [n = 11, incidence rates (IR) = 0.5], cellulitis (n = 6, IR = 0.3) and pneumonia (n = 3, IR = 0.1). There were four opportunistic infections (IR = 0.2). No malignancies, gastrointestinal perforations, positively adjudicated cardiovascular events or tuberculosis were reported in the placebo‐controlled period in baricitinib‐treated patients. Frequency of herpes simplex was higher in the 4‐mg group (6.1%) vs. the 2‐mg (3.6%) and placebo group (2.7%); IRs in the extended data set (2‐mg IR = 9.6; 4‐mg IR = 14.5) were lower vs. the placebo‐controlled data set (2‐mg IR = 12.4; 4‐mg IR = 21.3). In the All‐bari AD data set, there were two positively adjudicated major adverse cardiovascular events (2‐mg group): two venous thrombosis events (4‐mg group) and one death. Conclusion: This integrated safety analysis in patients with moderate‐to‐severe AD confirms the established safety profile of baricitinib. [ABSTRACT FROM AUTHOR]

Mantle convection and, by association, plate tectonics is driven by the transport of heat from a planetary interior. This heat comes from the internal energy of the mantle and from heat flowing into the base of the mantle from the core. Past investigations of such mixed mode heating have revealed unusual behavior that confounds our intuition based on end‐member cases. In particular, increased internal heating leads to a decrease in convective velocity. We investigate this behavior using a suite of numerical experiments and develop a scaling for velocity in the mixed heating case. We identify a planform transition, as internal heating increases, from sheet‐like to plume‐like downwellings that impacts heat flux and convective velocities. More significantly, we demonstrate that increased internal heating leads not only to a decrease in internal velocities but also a decrease in the velocity of the upper thermal boundary layer (a model analog of the Earth's lithosphere). This behavior is connected to boundary layer interactions and is independent of any particular rheological assumptions. In cases with a temperature‐dependent viscosity and weak plate margin analogs, increased internal heating does not cause an absolute decrease in surface velocity but does cause a decrease relative to purely bottom or internally heated cases as well as a transition to rigid‐lid behavior at high heating rates. The differences between a mixed system and end‐member cases have implications for understanding the connection between plate tectonics and mantle convection and for planetary thermal history modeling. Key Points: In mixed heated thermal convection, velocities can decrease with increased internal heatingScaling theory and numerical models show that velocity trends reflect changing levels of boundary layer interactionThe energtics of mixed heating mantle convection differs from bottom and internally heated end‐members [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a highly pruritic, chronic inflammatory skin disease. The diagnosis is made using evaluated clinical criteria. Disease activity and burden are best measured with a composite score, assessing both objective and subjective symptoms, such as SCORing Atopic Dermatitis (SCORAD). AD management must take into account clinical and pathogenic variabilities, the patient's age and also target flare prevention. Basic therapy includes hydrating and barrier‐stabilizing topical treatment universally applied, as well as avoiding specific and unspecific provocation factors. Visible skin lesions are treated with anti‐inflammatory topical agents such as corticosteroids and calcineurin inhibitors (tacrolimus and pimecrolimus), which are preferred in sensitive locations. Topical tacrolimus and some mid‐potency corticosteroids are proven agents for proactive therapy, which is defined as the long‐term intermittent anti‐inflammatory therapy of frequently relapsing skin areas. Systemic anti‐inflammatory or immunosuppressive treatment is a rapidly changing field requiring monitoring. Oral corticosteroids have a largely unfavourable benefit–risk ratio. The IL‐4R‐blocker dupilumab is a safe, effective and licensed, but expensive, treatment option with potential ocular side‐effects. Other biologicals targeting key pathways in the atopic immune response, as well as different Janus kinase inhibitors, are among emerging treatment options. Dysbalanced microbial colonization and infection may induce disease exacerbation and can justify additional antimicrobial treatment. Systemic antihistamines (H1R‐blockers) only have limited effects on AD‐related itch and eczema lesions. Adjuvant therapy includes UV irradiation, preferably narrowband UVB or UVA1. Coal tar may be useful for atopic hand and foot eczema. Dietary recommendations should be patient‐specific, and elimination diets should only be advised in case of proven food allergy. Allergen‐specific immunotherapy to aeroallergens may be useful in selected cases. Psychosomatic counselling is recommended to address stress‐induced exacerbations. Efficacy‐proven 'Eczema school' educational programmes and therapeutic patient education are recommended for both children and adults. [ABSTRACT FROM AUTHOR]

Background and purpose: Stroke is a dreaded complication in patients with cancer. Besides paraneoplastic coagulopathy, chemotherapy, radiotherapy and tumor‐directed invasive procedures, circulating cancer cells may contribute to thrombus formation and embolic stroke. However, the incidence of tumor cells within the blood clots of cancer patients with stroke is unknown and the role of circulating tumor cells in the formation of cerebrovascular thrombi remains unclear. Methods: All patients who had undergone cerebrovascular thrombectomy at the University Hospital Zurich between 2014 and 2017 were screened for history of cancer. Clinical information was retrieved from the local stroke registry and the electronic charts and thrombi underwent a thorough histopathological re‐review. Results: Thirty‐two of 182 patients (18%) with thrombectomy had a history of cancer. The majority of patients had advanced stage cancer. However, even after extensive histopathological re‐review, only one specimen revealed tumor cells in the thrombus: a 75‐year‐old patient with acute occlusion of the middle cerebral artery who had been diagnosed with non‐small‐cell lung cancer 8.1 months prior to stroke. Conclusions: The presence of cancer cells in clots from cerebrovascular thrombectomy, indicative of a direct involvement of circulating tumor cells in the causation of stroke, is rare. [ABSTRACT FROM AUTHOR]

Background: Cross‐sectional data on patient burden in adults with atopic dermatitis (AD) from real‐world clinical practice are limited. Objective: This study compared patient‐reported burden associated with adult AD across severity levels from clinical practices in Canada and Europe. Methods: This study included adults (18–65 years) diagnosed with AD by dermatologists, general practitioners or allergists. Participants categorized as mild (n = 547; 37.3%), moderate (n = 520; 35.4%) or severe (n = 400; 27.3%) based on Investigator's Global Assessment completed a questionnaire that included pruritus and pain numerical rating scales, Patient‐Oriented‐Scoring of Atopic Dermatitis (PO‐SCORAD) itch and sleep visual analogue scales, Dermatology Life Quality Index (DLQI), and the Hospital Anxiety and Depression Scale (HADS). Participants were also stratified by inadequate efficacy/intolerance/contraindication to cyclosporine [Cyclo; n = 62 (4 mild, 18 moderate, 40 severe)] and any systemic immunomodulatory agent [IMM; n = 104 (13 mild, 31 moderate, 60 severe)] and compared with the severe group excluding participants identified as Cyclo/IMM. Results: Age was similar across severity groups; the proportion of women was higher in the mild group relative to severe (61.2% vs. 50.5%; P < 0.001). Compared with moderate and mild, participants with severe AD had more comorbidities, higher itch and pain severity, worse sleep and higher levels of anxiety and depression (all P < 0.001). Mean ± SD DLQI score among participants with severe AD (16.2 ± 6.9) showed a large effect on quality of life that was higher than those with moderate (10.2 ± 6.3) and mild (5.5 ± 4.9) (both P < 0.001). The burden among Cyclo and IMM subgroups was generally similar to that of participants with severe AD. Conclusions: Adults with AD reported a substantial burden across multiple domains that was significantly higher in those with severe disease. The burden among participants in the Cyclo/IMM subgroups was similar to those with severe AD. [ABSTRACT FROM AUTHOR]

Aims: Aberrant expression of microRNAs (miRNAs) is frequent in various cancers including gliomas. We aimed to characterize the role of miR‐16‐5p as a candidate tumour suppressor miRNA in gliomas. Methods: Real‐time PCR‐based approaches were used for miRNA and mRNA expression profiling of glioma and non‐neoplastic brain tissues as well as glioma cell lines. Protein levels were determined by Western blotting. In vitro analyses were performed following overexpression of miR‐16‐5p, trichostatin A (TSA) treatment, and siRNA‐mediated knock‐down of HDAC3 in glioma cells. Effects of miR‐16‐5p on glioma cell viability, apoptosis and response to irradiation and temozolomide (TMZ) were assessed. Results: Expression of miR‐16‐5p was reduced relative to control brain tissue in isocitrate dehydrogenase (IDH)‐mutant astrocytomas of World Health Organization (WHO) grades II, III and IV, and a subset of IDH‐wildtype glioblastomas WHO grade IV. MiR‐16‐5p expression was lower in IDH‐mutant than in IDH‐wildtype gliomas, and down‐regulated in IDH‐wildtype glioma lines. MiR‐16‐5p overexpression reduced expression of important cell cycle and apoptosis regulators in glioma cells, including CDK6, CDC25A, CCND3, CCNE1, WEE1, CHEK1, BCL2 and MCL1. In line, CDK6, WEE1, CHEK1, BCL2 and MCL1 transcript levels were increased in WHO grade III or IV gliomas. TSA treatment and HDAC3 knockdown in glioma cells induced miR‐16‐5p up‐regulation and reduced expression of its targets. Moreover, miR‐16‐5p overexpression inhibited proliferation and induced apoptosis in various glioma cell lines and increased sensitivity of A172 glioma cells to irradiation and TMZ. Conclusion: Reduced expression of miR‐16‐5p contributes to glioma cell proliferation, survival and resistance to cytotoxic therapy. [ABSTRACT FROM AUTHOR]

Background and purpose: Fampridine leads to significant improvements in walking in many people with multiple sclerosis (PwMS). However, a relevant proportion of PwMS does not respond to fampridine and predictors of initial drug responsiveness are unknown. Methods: Drug response to prolonged‐release (PR)‐fampridine was assessed in 55 PwMS using the timed 25‐foot walk (T25FW), 6‐min walk test (6MWT) and 12‐item multiple sclerosis walking scale as outcome parameters. Patients were treated with PR‐fampridine and placebo for 6 weeks each in a randomized, double‐blind, placebo‐controlled trial with crossover design (NCT01576354). Possible predictors of drug responsiveness were investigated by multiple correlation analysis and binary logistic regression models. An additional longitudinal analysis followed the drug responses of 32 patients treated with PR‐fampridine over 3 years to identify potential predictors of long‐term drug responsiveness. Results: Severity of walking disability was positively correlated with enhanced responses to PR‐fampridine. The strongest single predictor of drug responsiveness was poor 6MWT performance at baseline, which was positively correlated with enhanced drug response in the 6MWT (R = −0.541; P < 0.001). A multivariable logistic regression model including 6MWT and T25FW baseline performances predicted PR‐fampridine responder status with an accuracy of 85.5% (specificity, 90.0%; sensitivity, 73.3%), with a threshold of 211 m in the 6MWT best separating responders from non‐responders. Enhanced drug responsiveness after 3 years correlated with decline in walking endurance during this period (R = −0.634; P = 0.001). Conclusions: Initial walking impairment is a good predictor of therapeutic responsiveness to PR‐fampridine. Valid predictors of patients' responsiveness to PR‐fampridine are essential for patient stratification and optimization of multiple slcerosis treatment. [ABSTRACT FROM AUTHOR]

Summary: Progesterone signaling and uterine function are crucial in terms of pregnancy establishment. To investigate how the uterine tissue and its secretion changes in relation to puberty, we sampled tissue and uterine fluid from six pre‐ and six post‐pubertal Brahman heifers. Post‐pubertal heifers were sampled in the luteal phase. Gene expression of the uterine tissue was investigated with RNA‐sequencing, whereas the uterine fluid was used for protein profiling with mass spectrometry. A total of 4034 genes were differentially expressed (DE) at a nominal P‐value of 0.05, and 26 genes were significantly DE after Bonferroni correction (P < 3.1 × 10−6). We also identified 79 proteins (out of 230 proteins) that were DE (P < 1 × 10−5) in the uterine fluid. When we compared proteomics and transcriptome results, four DE proteins were identified as being encoded by DE genes: OVGP1, GRP, CAP1 and HBA. Except for CAP1, the other three had lower expression post‐puberty. The function of these four genes hypothetically related to preparation of the uterus for a potential pregnancy is discussed in the context of puberty. All DE genes and proteins were also used in pathway and ontology enrichment analyses to investigate overall function. The DE genes were enriched for terms related to ribosomal activity. Transcription factors that were deemed key regulators of DE genes are also reported. Transcription factors ZNF567,ZNF775,RELA,PIAS2,LHX4,SOX2,MEF2C,ZNF354C,HMG20A,TCF7L2,ZNF420,HIC1,GTF3A and two novel genes had the highest regulatory impact factor scores. These data can help to understand how puberty influences uterine function. [ABSTRACT FROM AUTHOR]

Background Although atopic dermatitis (AD) is a very common skin disease, data on the percentage of patients with really difficult-to-treat AD are scarce. From socio-economic perspective, it is important to have more insight into these numbers, as new very effective, but expensive, treatment options will be available in the near future for difficult-to-treat AD. Estimating the number of patients with AD using oral immunosuppressive drugs can give an impression of the percentage of difficult-to-treat patients in the total AD population. Objective To give an overview of the use of oral immunosuppressive drugs in patients with AD in the Netherlands. Methods Prescription data of oral immunosuppressive drugs in the Netherlands were extracted from a pharmaceutical database (NControl) containing data of 557 million prescriptions and 7.2 million patients. An algorithm, based on the WHO Anatomical Therapeutic Chemical (ATC) codes, was used to identify patients with AD. The prescription of oral immunosuppressive drugs in patients with AD between 1 January 2012 and 1 January 2017 was evaluated. Results Based on the algorithm, 65 943 patients with AD were selected. 943 patients with AD (1.4%) used cyclosporine A, methotrexate, azathioprine or mycophenolic acid. Methotrexate was most commonly used, followed by azathioprine and cyclosporine A. A switch in medication was rarely seen. In the evaluation period, a decrease in the prescription of cyclosporine A was seen, together with an increase in the prescription of methotrexate. In 31% of the patients who stopped treatment, the discontinuation took place within the first months of treatment. Conclusion In this study population, 1.4% of the patients with AD used oral immunosuppressive drugs for their eczema in a 5-year period. Methotrexate was the most commonly used systemic drug in the Netherlands for the treatment of AD. [ABSTRACT FROM AUTHOR]

Abstract: Background: There are gaps in our knowledge of the prevalence of adult atopic dermatitis (AD). Objective: To estimate the prevalence of AD in adults and by disease severity. Methods: This international, cross‐sectional, web‐based survey was performed in the United States, Canada, France, Germany, Italy, Spain, United Kingdom, and Japan. Adult members of online respondent panels were sent a questionnaire for AD identification and severity assessment; demographic quotas ensured population representativeness for each country. A diagnosis of AD required subjects to be positive on the modified UK Working Party/ISAAC criteria and self‐report of ever having an AD diagnosis by a physician. The proportion of subjects with AD who reported being treated for their condition was determined and also used to estimate prevalence. Severity scales were Patient‐Oriented SCORAD, Patient‐Orientated Eczema Measure, and Patient Global Assessment. Results: Among participants by region, the point prevalence of adult AD in the overall/treated populations was 4.9%/3.9% in the US, 3.5%/2.6% in Canada, 4.4%/3.5% in the EU, and 2.1%/1.5% in Japan. The prevalence was generally lower for males vs females, and decreased with age. Regional variability was observed within countries. Severity varied by scale and region; however, regardless of the scale or region, proportion of subjects reporting severe disease was lower than mild or moderate disease. Conclusions: Prevalence of adult AD ranged from 2.1% to 4.9% across countries. Severe AD represented a small proportion of the overall AD population regardless of measure or region. [ABSTRACT FROM AUTHOR]

Abstract: Genetic association studies in forest trees would greatly benefit from information on the response of trees to environmental stressors over time, which can be provided by dendroecological analysis. Here, we jointly analysed dendroecological and genetic data of surviving silver fir trees to explore the genetic basis of their response to the iconic stress episode of the 1970s and 1980s that led to large‐scale forest dieback in Central Europe and has been attributed to air pollution. Specifically, we derived dendrophenotypic measures from 190 trees in the Bavarian Forest that characterize the resistance, resilience and recovery during this growth depression, and in the drought year in 1976. By focusing on relative growth changes of trees and by standardizing the dendrophenotypes within stands, we accounted for variation introduced by micro‐ and macroscale environmental differences. We associated the dendrophenotypes with single nucleotide polymorphisms (SNPs) in candidate genes using general linear models (GLMs) and the machine learning algorithm random forest with subsequent feature selection. Most trees at our study sites experienced a severe growth decline from 1974 until the mid‐1980s with minimum values during the drought year. Fifteen genes were associated with the dendrophenotypes, including genes linked to photosynthesis and drought stress. With our study, we show that dendrophenotypes can be a powerful resource for genetic association studies that permit to account for micro‐ and macroenvironmental variation when data are derived from natural populations. We call for a wider collaboration of dendroecologists and forest geneticists to integrate individual tree‐level dendrophenotypes in genetic association studies. [ABSTRACT FROM AUTHOR]