Defining disease severity in atopic dermatitis and psoriasis for the application to biomarker research- an inter-disciplinary perspective.

More severe atopic dermatitis (AD) and psoriasis are associated with a higher cumulative impact on quality of life, multimorbidity and healthcare costs. Proactive, early intervention in those most at risk of severe disease may reduce this cumulative burden and modify the disease trajectory to limit progression. The lack of reliable biomarkers for this at-risk group represents a barrier to such a paradigm shift in practice. To expedite discovery and validation, the BIOMAP consortium (Biomarkers in AD and Psoriasis, a large-scale European, inter-disciplinary research initiative) has curated clinical and molecular data across diverse study designs and sources including cross-sectional and cohort studies (small scale through to large multi-centre registries), clinical trials, electronic health records and large-scale population-based biobanks. We map all dataset disease severity instruments and measures to three key domains (symptoms, inflammatory activity and disease course), and describe important co-dependencies and relationships across variables and domains. We prioritise definitions for more severe disease with reference to international consensus, reference standards and/or expert opinion. Key factors to consider when analysing datasets across these diverse study types include explicit early consideration of biomarker purpose and clinical context, candidate biomarkers associated with disease severity at a point in time and over time and how they are related, taking the stage of biomarker development into account when selecting disease severity measures for analyses and, validating biomarker associations with disease severity outcomes using both physician- and patient-reported measures and across domains. The outputs from this exercise will ensure coherence and focus across the BIOMAP consortium so that mechanistic insights and biomarkers are clinically relevant, patient-centric and more generalisable to current and future research efforts.

Topical steroid withdrawal: a survey of UK dermatologists' attitudes.

The term topical steroid withdrawal (TSW) refers to a condition widely discussed on social media, but rarely mentioned in the medical literature. It typically involves a patient with chronic eczema who abruptly discontinues topical corticosteroids (TCS) believing they are ineffective and damaging. Symptoms include an acute eruption, worse than the previous eczema, of painful erythema followed by oozing, crusting, desquamation and sometimes prolonged systemic weakness. Patients self-diagnose and often avoid healthcare professionals who dismiss the diagnosis and persist in offering TCS, leaving them unsupported. We analysed 121 responses to a survey of UK dermatologists' attitudes to TSW. Views on aetiology included relapsed eczema, erythroderma and a social construct. A total of 88.4% (107/121) agreed that TSW needs better understanding and more research. Respondents earlier in their careers are more cautious than senior respondents about prescribing TCS long term because of TSW, suggesting a trend that might lead to better understanding, communication and management.

Do people with eczema and their carers understand topical steroid potency? Results of two surveys.

Topical corticosteroids (TCSs) are classified into four potencies: mild, moderate, potent and very potent. Confusion arises from the wide range of products available, none of which have the potency level printed on the tubes or packaging. An online survey of patients and carers of people with eczema showed that only 17% of 984 respondents knew how many potencies there are. In a second survey, 315 respondents provided 1520 assignments of the potency of commonly used TCSs: 55.5% were correct, 21% were underestimates and 23.5% overestimates. Some errors were extreme: 12 (8%) of those using a very potent TCS considered it mild while 9 (27%) using a mild TCS considered it potent or very potent. Other themes expressed in free-text comments included inadequate and conflicting advice about using TCSs and lack of warnings about long-term adverse effects, particularly topical steroid withdrawal. Ninety-five per cent of respondents wanted TCSs to be clearly labelled with potency.

British Society for Paediatric and Adolescent Dermatology assessment and support of mental health in children and young people with skin conditions: a multidisciplinary expert consensus statement and recommendations.

BACKGROUND: Psychological and mental health difficulties are common in children and young people (CYP) living with skin conditions and can have a profound impact on wellbeing. There is limited guidance on how best to assess and support the mental health of this population, who are at risk of poor health outcomes. OBJECTIVES: To provide consensus-based recommendations on the assessment and monitoring of and support for mental health difficulties in CYP with skin conditions (affecting the skin, hair and nails); to address practical clinical implementation questions relating to consensus guidance; and to provide audit and research recommendations. METHODS: This set of recommendations was developed with reference to the AGREE II instrument. A systematic review and literature appraisal was carried out. A multidisciplinary consensus group was convened, with two virtual panel meetings held: an initial meeting to discuss the scope of the study, to review the current evidence and to identify areas for development; and a second meeting to agree on the content and wording of the recommendations. Recommendations were then circulated to stakeholders, following which amendments were made and agreed by email. RESULTS: The expert panel achieved consensus on 11 recommendations for healthcare workers managing CYP with skin conditions. A new patient-completed history-taking aid ('You and Your Skin') was developed and is being piloted. CONCLUSIONS: The recommendations focus on improved mental health assessments for CYP presenting with a skin condition, with clinical guidance and suggested screening measures included. Information on accessing psychological support for CYP, when required, is given, and recommendations for staff training in mental health and neurodiversity provided. Embedding a psychosocial approach within services treating CYP with skin disease should ensure that CYP with psychological needs are able to be identified, listened to, supported and treated. This is likely to improve health outcomes.

Patients' and Caregivers' Experiences With Atopic Dermatitis-Related Burden, Medical Care, and Treatments in 8 Countries.

BACKGROUND: Previous studies have documented the high patient and caregiver burden associated with atopic dermatitis (AD). Less is known about the factors-especially those related to treatment options and the delivery of medical care-that may relate to burden and unmet needs among patients and their caregivers. OBJECTIVE: Our primary aim was to characterize and compare health-related quality of life, long-term control of symptoms, satisfaction with treatments, the financial burden, and the prevalence of patient-centered care among adult and pediatric patients with AD in 8 developed nations. METHODS: We developed a 53-item anonymous online survey for adult patients and caregivers of children with AD (N = 3171; self-reported disease severity: 8.2% clear, 33.2% mild, 41.1% moderate, 17.6% severe). The survey included questions across 7 domains selected by a steering committee of 11 patient organizations that advocate for patients with AD in the 8 countries. We used validated instruments when available including the 5-level EuroQol five-dimensional questionnaire and the Atopic Dermatitis Control Tool. The survey was offered in 5 languages and promoted through social media and other communication channels of the patient organizations. RESULTS: The health-related quality-of-life scores for adult patients with AD (driven by 2 domains: pain/discomfort and anxiety/depression) were worse than those reported for asthma and type 2 diabetes in previous studies (0.72; 95% CI, 0.65-0.78). Patients and caregivers reported substantial financial impacts even in countries with government-funded health care systems, though the greatest impact was in the United States. In all countries, adults reported better control of symptoms than children, but neither group nor any nationality reported adequate control on average (rescaled mean, 57.5; 95% CI, 56.1-58.9), and control correlated negatively with disease severity. Similarly, satisfaction with treatments, which was moderate across countries on average, was much lower for respondents with more severe disease symptoms (F(3,3165) = 5.5; P < .001). Patients who saw a specialist (a dermatologist or an allergist) instead of a general practitioner for AD care indicated better long-term control of symptoms (by 4 points on average on the 100-point scale; 95% CI, 2.6-5.4; P < .001). Finally, self-management training and shared decision making were uncommonly reported by patients in all countries except by respondents from the United States, but both were associated with better long-term control of symptoms and higher satisfaction. CONCLUSIONS: The burden of AD, evaluated as health-related quality-of-life detriments, financial impacts, and uncontrolled symptoms, is significant and highest for patients with more severe atopic dermatitis who report greater challenges in achieving symptom resolution with existing treatments and approaches to care. The better outcomes associated with respondents who saw specialists suggest that patients, especially those with more severe AD, might benefit from medical care that is guided by providers with more in-depth knowledge of this complex condition. Finally, wider use of patient-centered care practices (specifically, self-management training and shared decision making) could improve outcomes and boost satisfaction with treatments for AD, though more research on this topic is warranted.

Palbociclib in combination with aromatase inhibitors in patients ≥ 75 years with oestrogen receptor-positive, human epidermal growth factor receptor 2 negative advanced breast cancer: A real-world multicentre UK study.

BACKGROUND: Breast cancer incidence increases with age and real-world data is essential to guide prescribing practices in the older population. The aim of this study was to collect large scale real-world data on tolerability and efficacy of palbociclib + AI in the first line treatment of ER+/HER2-advanced breast cancer in those aged ≥75 years. METHODS: 14 cancer centres participated in this national UK retrospective study. Patients aged ≥75 years treated with palbociclib + AI in the first line setting were identified. Data included baseline demographics, disease characteristics, toxicities, dose reductions and delays, treatment response and survival data. Multivariable Cox regression was used to assess independent predictors of PFS, OS and toxicities. RESULTS: 276 patients met the eligibility criteria. The incidence of febrile neutropenia was low (2.2%). The clinical benefit rate was 87%. 50.7% of patients had dose reductions and 59.3% had dose delays. The 12- and 24- month PFS rates were 75.9% and 64.9%, respectively. The 12- and 24- month OS rates were 85.1% and 74.0%, respectively. Multivariable analysis identified PS, Age-adjusted Charlson Comorbidity Index (ACCI) and number of metastatic sites to be independent predictors of PFS. Dose reductions and delays were not associated with adverse survival outcomes. Baseline ACCI was an independent predictor of development and severity of neutropenia. CONCLUSION: Palbociclib is an effective therapy in the real-world older population and is well-tolerated with low levels of clinically significant toxicities. The use of geriatric and frailty assessments can help guide decision making in these patients.

Personalized predictions of patient outcomes during and after hospitalization using artificial intelligence.

Hospital systems, payers, and regulators have focused on reducing length of stay (LOS) and early readmission, with uncertain benefit. Interpretable machine learning (ML) may assist in transparently identifying the risk of important outcomes. We conducted a retrospective cohort study of hospitalizations at a tertiary academic medical center and its branches from January 2011 to May 2018. A consecutive sample of all hospitalizations in the study period were included. Algorithms were trained on medical, sociodemographic, and institutional variables to predict readmission, length of stay (LOS), and death within 48-72 h. Prediction performance was measured by area under the receiver operator characteristic curve (AUC), Brier score loss (BSL), which measures how well predicted probability matches observed probability, and other metrics. Interpretations were generated using multiple feature extraction algorithms. The study cohort included 1,485,880 hospitalizations for 708,089 unique patients (median age of 59 years, first and third quartiles (QI) [39, 73]; 55.6% female; 71% white). There were 211,022 30-day readmissions for an overall readmission rate of 14% (for patients ≥65 years: 16%). Median LOS, including observation and labor and delivery patients, was 2.94 days (QI [1.67, 5.34]), or, if these patients are excluded, 3.71 days (QI [2.15, 6.51]). Predictive performance was as follows: 30-day readmission (AUC 0.76/BSL 0.11); LOS > 5 days (AUC 0.84/BSL 0.15); death within 48-72 h (AUC 0.91/BSL 0.001). Explanatory diagrams showed factors that impacted each prediction.

Crowdsourcing hypothesis tests: Making transparent how design choices shape research results.

To what extent are research results influenced by subjective decisions that scientists make as they design studies? Fifteen research teams independently designed studies to answer five original research questions related to moral judgments, negotiations, and implicit cognition. Participants from 2 separate large samples (total N > 15,000) were then randomly assigned to complete 1 version of each study. Effect sizes varied dramatically across different sets of materials designed to test the same hypothesis: Materials from different teams rendered statistically significant effects in opposite directions for 4 of 5 hypotheses, with the narrowest range in estimates being d = -0.37 to + 0.26. Meta-analysis and a Bayesian perspective on the results revealed overall support for 2 hypotheses and a lack of support for 3 hypotheses. Overall, practically none of the variability in effect sizes was attributable to the skill of the research team in designing materials, whereas considerable variability was attributable to the hypothesis being tested. In a forecasting survey, predictions of other scientists were significantly correlated with study results, both across and within hypotheses. Crowdsourced testing of research hypotheses helps reveal the true consistency of empirical support for a scientific claim. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Strategies for Producing and Incorporating Conjugated Linoleic Acid-Rich Oils in Foods.

Conjugated linoleic acid (CLA) is in ruminant-derived foods and is known to combat obesity-related diseases. However, CLA levels in a healthy diet are too low to produce a clinical effect. Therefore, CLA has been produced by linoleic isomerization through fermentation and chemical catalysis. Many of these techniques are not practical for food production, but a recent development has enabled production of CLA-rich triglyceride vegetable oils from high linoleic acid oils by a minor modification of conventional food-oil processing techniques. These oils were used to produce common lipid-based food, such as margarine, shortenings, and salad dressings, whose quality was enhanced by the presence of CLA-rich oil and provided a significant CLA source. Meat and egg CLA content and subsequent food quality can also be increased by addition of dietary CLA. However, consumer awareness of CLA benefits needs to increase prior to commercial-scale production of CLA-rich oil.

Isolation and Characterization of Chicken Yolk Vitelline Membrane Lipids Using Eggs Enriched With Conjugated Linoleic Acid.

The vitelline membrane (VM) encloses the chicken egg yolk, separating it from albumen. The VM weakens during storage, and dietary lipid modification significantly affects its strength. However, no studies have characterize the fatty acyl residue (FA) composition of the VM, and reports of VM isolation and quantified lipid content are inconsistent. Therefore, the objectives of this study were: (1) to develop a washing and isolation method that removes residual yolk from VM without damage; (2) to determine the FA and lipid composition of CLA-rich egg yolk VM, relative to controls; (3) to determine the effect of 20 days of refrigeration on VM FA and lipid composition. To determine VM FA and lipid composition, 36 hens received either a corn-soybean meal-based control diet ("Control"), or the Control supplemented with either 10 % soy oil ("Soy control"), or 10 % CLA-rich soy oil ("CLA") for 30 days. VM were analyzed the day of collection ("fresh"), or after 20 days of refrigeration ("refrigerated"). There were no differences in FA compositions of fresh and refrigerated membranes within a treatment. CLA-rich yolk VM contains CLA, greater SFA, and significantly greater DHA relative to controls. Direct MALDI-TOF-MS identified 15 phosphatidylcholines, three phosphatidylethanolamines, one sphingomyelin, and 15 triacylglycerols in VM. Lipid species that showed significant differences among egg types included nine phosphatidylcholines and six triacylglycerols. MALDI analysis indicated significant differences in nine lipid classes on the VM inner layer. After refrigeration, five lipid classes on the inner layer and seven lipid classes on the outer layer had statistically significant differences among VM types.

Effect of feeding CLA on plasma and granules fatty acid composition of eggs and prepared mayonnaise quality.

Eggs rich in trans, trans conjugated linoleic acid (CLA) are significantly more viscous, have more phospholipids containing linoleic acid (LA), and more saturated triacylglycerol species than control eggs. However, the fatty acid (FA) composition of yolk plasma and granule fractions are unreported. Furthermore, there are no reports of mayonnaise rheological properties or emulsion stability by using CLA-rich eggs. Therefore, the objectives were (1) compare the FA composition of CLA-rich yolk granules and plasma, relative to standard control and LA-rich control yolks, (2) compare the rheological properties of mayonnaise prepared with CLA-rich eggs to control eggs and (3) compare the emulsion stability of CLA-yolk mayonnaise. CLA-rich eggs and soy control eggs were produced by adding 10% CLA-rich soy oil or 10% of control unmodified soy oil to the hen's diet. The eggs were used in subsequent mayonnaise preparation. CLA-yolk mayonnaise was more viscous, had greater storage modulus, resisted thinning, and was a more stable emulsion, relative to mayonnaise prepared with control yolks or soy control yolks.

Three hen strains fed photoisomerized trans,trans CLA-rich soy oil exhibit different yolk accumulation rates and source-specific isomer deposition.

Most CLA chicken feeding trials used cis,trans (c,t) and trans,cis (t,c) CLA isomers to produce CLA-rich eggs, while reports of trans,trans (t,t) CLA enrichment in egg yolks are limited. The CLA yolk fatty acid profile changes and the 10-12 days of feeding needed for maximum CLA are well documented, but there is no information describing CLA accumulation during initial feed administration. In addition, no information on CLA accumulation rates in different hen strains is available. The aim of this study was to determine a mathematical model that described yolk CLA accumulation and depletion in three hen strains by using t,t CLA-rich soybean oil produced by photoisomerization. Diets of 30-week Leghorns, broilers, and jungle fowl were supplemented with 15% CLA-rich soy oil for 16 days, and eggs were collected for 32 days. Yolk fatty acid profiles were measured by GC-FID. CLA accumulation and depletion was modeled by both quadratic and piecewise regression analysis. A strong quadratic model was proposed, but it was not as effective as piecewise regression in describing CLA accumulation and depletion. Broiler hen eggs contained the greatest concentration of CLA at 3.2 mol/100 g egg yolk, then jungle fowl at 2.9 mol CLA, and Leghorns at 2.3 mol CLA. The t,t CLA isomer levels remained at 55% of total yolk CLA during CLA feeding. However, t-10,c-12 (t,c) CLA concentration increased slightly during CLA accumulation and was significantly greater than c-9,t-11 CLA. Jungle fowl had the smallest increase in yolk saturated fat with CLA yolk accumulation.

Effect of trans, trans CLA egg enrichment from CLA-rich soy oil on yolk fatty acid composition, viscosity and physical properties.

CLA egg accumulation studies using cis, trans (c,t) isomers have been effective, but they reported adverse egg quality. trans, trans (t,t) CLA isomers have shown superior nutritional effects in rodent studies, but reports of t,t CLA-rich yolks are limited. The objectives were to determine the effect of t,t CLA-rich soy oil in feed on egg yolk viscosity, and yolk quality during refrigerated storage. Yolk fatty acids, viscosity, weight, index, moisture, pH, and vitelline membrane strength (VMS) were determined at 0, 20, and 30 storage days. CLA had minimal effect on fatty acid profiles, relative to c,t reports. CLA-rich yolk viscosity was greater than controls, and CLA yolks maintained higher viscosities during storage. Yolk weight and index were not affected by t,t CLA-rich soy oil. Yolks with the greatest CLA concentrations had the greatest VMS after 20 days of storage, and yolks containing lower CLA levels maintained greater VMS throughout 30 days of storage, relative to controls.