Systemic Treatments for Atopic Dermatitis: Systematic Review and Network Meta-Analysis of Randomized Trials

Objective:To provide procedure-specific estimates of symptomatic venous thromboembolism (VTE) and major bleeding after abdominal surgery.Background:The use of pharmacological thromboprophylaxis represents a trade-off that depends on VTE and bleeding risks that vary between procedures; their magnitude remains uncertain.Methods:We identified observational studies reporting procedure-specific risks of symptomatic VTE or major bleeding after abdominal surgery, adjusted the reported estimates for thromboprophylaxis and length of follow-up, and estimated cumulative incidence at 4 weeks postsurgery, stratified by VTE risk groups, and rated evidence certainty.Results:

We report the short-and long-term results of the SOLIDARITY Finland on mortality and other patient-important outcomes in patients hospitalised for COVID-19. Between 08/2021 and 03/2023, we randomised 156 patients in 15 hospitals. In the imatinib group, 7.2% of patients had died at 30 days and 13.3% at 1 year and in the standard of care group 4.1% and 8.3%(adjusted HR at 30 days 1.09, 95% CI 0.23-5.07). In a meta-analysis of randomised trials of imatinib versus standard of care (n= 732), allocation to imatinib was associated with a mortality risk ratio of 0.73 (95% CI 0.32-1.63). At 1-year, self-reported recovery occurred in 79.0% in imatinib and in 88.3% in standard of care (RR 0.91, 95% CI 0.78-1.06). Of the 21 potential long COVID symptoms, patients often reported moderate or major bother from fatigue (24%), sleeping problems (19%) and memory difficulties (17%). We found no convincing difference between imatinib and standard of care groups in quality of life or symptom outcomes. The evidence raises serious doubts regarding the benefit of imatinib in reducing mortality, improving recovery and preventing potential long COVID symptoms when given to patients hospitalised for COVID-19.

Annals of Allergy, Asthma & Immunology

BackgroundGuidance addressing atopic dermatitis (AD) management, last issued in 2012 by the American Academy of Allergy, Asthma and Immunology/American College of Allergy, Asthma and Immunology Joint Task Force, requires updating as a result of new treatments and improved guideline and evidence synthesis methodology.ObjectiveTo produce evidence-based guidelines that support patients, clinicians, and other decision-makers in the optimal treatment of AD.MethodsA multidisciplinary guideline panel consisting of patients and caregivers, AD experts (dermatology and allergy/immunology), primary care practitioners (family medicine, pediatrics, internal medicine), and allied health professionals (psychology, pharmacy, nursing) convened, prioritized equity, diversity, and inclusiveness, and implemented management strategies to minimize influence of conflicts of interest. The Evidence in Allergy Group …

JAMA

To the Editor Although sometimes considered the pinnacle of scientific evidence, meta-analyses can be problematic. Combining outcomes from heterogeneous trials performed in different settings or populations may give results directly applicable to few. Conclusions are also beholden to methodological design, often discordant from those of subsequent randomized clinical trials. 1 Such may be the case with the recently published dose-response meta-analysis of studies examining efficacy and tolerability of gefapixant for refractory or unexplained chronic cough. 2 Because gefapixant is the first novel efficacious therapy for refractory and unexplained chronic cough, its development involved changes in study design and participant inclusion criteria as well as drug formulation. 3 Four drug formulations were ultimately tested, with maximum bioavailability achieved for the formulation used in the phase 3 trials, such that …

New England Journal of Medicine

Background Food allergies are common and are associated with substantial morbidity; the only approved treatment is oral immunotherapy for peanut allergy. Methods In this trial, we assessed whether omalizumab, a monoclonal anti-IgE antibody, would be effective and safe as monotherapy in patients with multiple food allergies. Persons 1 to 55 years of age who were allergic to peanuts and at least two other trial-specified foods (cashew, milk, egg, walnut, wheat, and hazelnut) were screened. Inclusion required a reaction to a food challenge of 100 mg or less of peanut protein and 300 mg or less of the two other foods. Participants were randomly assigned, in a 2:1 ratio, to receive omalizumab or placebo administered subcutaneously (with the dose based on weight and IgE levels) every 2 to 4 weeks for 16 to 20 weeks, after which the challenges were repeated. The primary end point was ingestion of peanut …

The Lancet

Their stated aim is to summarise the “benefits and harms of weight-lowering drugs”, but the main findings and discussion focus on weight loss, without due consideration to the scarcity of evidence for benefits to health and wellbeing. For instance, quality of life and depression data are reported as low quality or insufficient, and there is no mention of the absence of long-term cardiovascular outcomes. A review on long-term effects of weight-reducing pharmacotherapy included only one trial with cardiovascular outcomes; it found no benefit.

Journal of Critical Care

IntroductionThe objective of this study was to create a definition of patient-important upper gastrointestinal bleeding during critical illness as an outcome for a randomized trial.DesignThis was a sequential mixed-methods qualitative-dominant multi-center study with an instrument-building aim. In semi-structured individual interviews or focus groups we elicited views from survivors of critical illness and family members of patients in the intensive care unit (ICU) regarding which features indicate important gastrointestinal bleeding. Quantitative demographic characteristics were collected. We analyzed qualitative data using inductive content analysis to develop a definition for patient-important upper gastrointestinal bleeding.SettingCanada and the United States.Participants51 ICU survivors and family members of ICU patients.ResultsParticipants considered gastrointestinal bleeding to be important if it resulted in death …

Annals of Allergy, Asthma & Immunology

Food allergies affect an estimated 8% of the US population and have risen significantly in the past 20 years. 1 IgE− mediated reactions to food can range from simple urticaria to life-threatening anaphylaxis. The only treatment was the avoidance of the allergen and treatment of allergic reactions with epinephrine until 2020 when an oral immunotherapy (OIT) product (Palforzia [Stallergenes Greer, Boston, Massachusetts]) was approved for the treatment of peanut allergy. 2 There was no approved treatment by the US Food and Drug Administration for other foods or multiple foods until the recent approval of omalizumab for any food allergy for patients aged 1 year or older with the appropriate total IgE and weight. In the pivotal trial, Wood et al 3 reported in a randomized, placebo-controlled study that 67% of patients on omalizumab tolerated a single dose of 600 mg (1044 mg cumulative dose) or greater of peanut …

Journal of Allergy and Clinical Immunology

MethodsSixty-seven adult subjects enrolled at URMC as part of Atopic Dermatitis Research Network Registry (ADRN02) were classified as mild (n= 33; EASI≤ 7) or severe (n= 34; EASI≥ 20). Serum proteomic analysis was performed using Olink Explore 3072. Differentially expressed proteins (DEPs, mild vs severe) were identified using independent t-tests and False Discovery Rate correction (FDR). HPAStainR and StringDB were used for enrichment pathway analysis. Pearson Correlation analyses determine associations of biomarkers with relevant clinical parameters (FDR≤ 0.05 and r≥ 0.6).Results469 DEPs (FDR≤ 0.05) were identified between mild and severe AD, with 46 downregulated and 423 upregulated in severe cases. HPAStainR matched 233 of DEPs in the “Skin Epidermal” category. StringDB of the DEPs revealed significant (FDR≤ 0.01) association with terms related to cornification, protease …

Food allergy in atopic dermatitis is mediated by complex immune interactions between genetics, diet, environment, and the microbiome. When contact between inflamed skin and food antigens occurs, contact hypersensitivity can develop. Consequently, systemic contact dermatitis (SCD) can occur after ingestion of allergenic foods or food additives in the setting of a Th2 response with CLA-positive T cells, triggering dermatitis where skin resident memory lymphocytes reside. This phenomenon explains food-triggered dermatitis. Atopy patch tests (APTs) detect sensitization to food proteins responsible for SCD, which in turn can be confirmed by oral food challenge with delayed interpretation. We summarize the literature on using APTs to identify foods for oral challenge with dermatitis as an outcome. In dermatitis patients at risk for Th2 skewing based on a history of childhood-onset flexural dermatitis, shared decision …

Most current algorithms for multivariate time series classification tend to overlook the correlations between time series of different variables. In this research, we propose a framework that leverages Eigen-entropy along with a cumulative moving window to derive time series signatures to support the classification task. These signatures are enumerations of correlations among different time series considering the temporal nature of the dataset. To manage dataset's dynamic nature, we employ preprocessing with dense multi scale entropy. Consequently, the proposed framework, Eigen-entropy-based Time Series Signatures, captures correlations among multivariate time series without losing its temporal and dynamic aspects. The efficacy of our algorithm is assessed using six binary datasets sourced from the University of East Anglia (UEA), in addition to a publicly available sepsis dataset and an institutional sepsis dataset from the Mayo Clinic. We employ recall as a metric for evaluation against the baseline algorithm, Dependent Dynamic Time Warping with 1 Nearest Neighbor. Our algorithm outperforms the baseline algorithm for UEA datasets in terms of recall with an average value of 10% across all datasets, and by 38% for an institutional sepsis dataset. For the public sepsis dataset, the performance of our algorithm is comparable to the baseline algorithm.

Topical corticosteroids (TCSs) are the most widely used treatment for atopic dermatitis (AD), but they can have adverse effects such as skin atrophy, telangiectasias, and hypopigmentation, especially with prolonged use of higher potency steroids. Many patients also have a fear of using TCSs, known as “corticophobia.” With the development of biologics and Janus kinase inhibitors, a nonsteroidal approach to the treatment of AD may be possible and may be preferred by certain patients. Given what is known about these nonsteroidal therapies, we propose a structured treatment ladder and action plan that can guide clinicians and patients on the use of these therapies for the treatment of AD. The ladder divides nonsteroidal medication classes into treatments for exacerbation versus maintenance therapies in an escalating order of increasing potential for adverse effects, both real and perceived. This treatment …

MethodsWe systematically identified randomized controlled trials addressing topical treatments for AD from MEDLINE, EMBASE, CENTRAL, CINAHL, LILACS, ICTRP, and GREAT to July 8, 2023. We excluded split-body trials. We performed Bayesian random-effects network meta-analyses on AD severity, itch severity, sleep disturbance, AD-related quality of life, AD exacerbations, and harms. We used GRADE to rate certainty of evidence. A multidisciplinary panel including patient partners determined thresholds for patient-important benefits and harms.ResultsWe analyzed 235 trials enrolling 46,315 patients (pediatrics and adults) and evaluated 69 unique interventions over a median 4 weeks for induction and 16 weeks for maintenance (overall range 1–156). To gain AD control, pimecrolimus improved the most outcomes, while tacrolimus, moderatepotency corticosteroids, delgocitinib, and ruxolitinib had …

Atopic dermatitis (AD) has a complex pathogenesis that leads to the characteristic itchy, eczematous skin findings. Treatment of AD is aimed at alleviating symptoms, preventing exacerbations and infections, and minimizing long-term risks. Treatment depends on the extent and severity of the AD but almost always includes topical therapies as a first line and often in addition to other treatments. These topicals include a variety of moisturizers and non-pharmacologic preparations, steroids, crisaborole, and calcineurin inhibitors, as well as a topical Janus kinase (JAK) inhibitor. Each has strengths and weaknesses in terms of efficacy, accessibility, and safety/tolerability. Given the heterogeneity of AD, it is important to be able to call upon a variety of topical therapies to meet individual needs.

Journal of Allergy and Clinical Immunology

MethodsWe conducted a retrospective review of patients aged 4-8 years, treated with dupilumab and the age of measles, mumps, rubella (MMR) and varicella dose 2 vaccine administration (IRB 19-016617). Data extracted from electronic medical records included demographics, immunization administration, and dupilumab history.Results162 children were identified to be on dupilumab, of which 114 were included in final analyses. The average age of our population was 5.7 years and the average age of initiation of dupilumab was 4.7 years. Dupilumab was initiated for atopic dermatitis (AD)(n= 107), asthma (n= 5), eosinophilic esophagitis (EoE)(n= 1), and EoE+ asthma (n= 1).

Clinics in Dermatology

ConclusionsAI-powered language models perform adequately on dermatology CME questions but do not consistently achieve the passing score required to receive credit. AI developers may wish to target procedural questions to push AI's performance into the passing range. AI is still a valuable resource for CME. Limitations of this study include a relatively small number of questions (N= 100) and categories of questions (N= 10). The external validity of ChatGPT and Claude's performance may vary considering the number of questions asked.

JAAD International

BackgroundEmpirical decisions to select therapies for psoriasis (PSO) and atopic dermatitis (AD) can lead to delays in disease control and increased healthcare costs. However, routine molecular testing for AD and PSO are lacking.ObjectiveTo examine 1) how clinicians choose systemic therapies for patients with PSO and AD without molecular testing and 2) to determine how often the current approach leads to patients switching medications.MethodsA 20-question survey designed to assess clinician strategies for systemic treatment of AD and PSO was made available to attendees of a national dermatology conference in 2022.ResultsClinicians participating in the survey (265/414, 64% response rate) ranked “reported efficacy” as the most important factor governing treatment choice (P<.001). However, 62% (165/265) of clinicians estimated that two or more systemic medications were typically required to achieve …

MethodsWe systematically identified randomized controlled trials addressing topical treatments for AD from MEDLINE, EMBASE, CENTRAL, CINAHL, LILACS, ICTRP, and GREAT to July 8, 2023. We excluded split-body trials. We performed Bayesian random-effects network meta-analyses on AD severity, itch severity, sleep disturbance, AD-related quality of life, AD exacerbations, and harms. We used GRADE to rate certainty of evidence. A multidisciplinary panel including patient partners determined thresholds for patient-important benefits and harms.ResultsWe analyzed 235 trials enrolling 46,315 patients (pediatrics and adults) and evaluated 69 unique interventions over a median 4 weeks for induction and 16 weeks for maintenance (overall range 1–156). To gain AD control, pimecrolimus improved the most outcomes, while tacrolimus, moderatepotency corticosteroids, delgocitinib, and ruxolitinib had …

JACC: Heart Failure

BackgroundA recent study showed that the accuracy of heart failure (HF) cardiologists and family doctors to predict mortality in outpatients with HF proved suboptimal, performing less well than models.ObjectivesThe authors sought to evaluate patient and physician factors associated with physician accuracy.MethodsThe authors included outpatients with HF from 11 HF clinics. Family doctors and HF cardiologists estimated patient 1-year mortality. They calculated predicted mortality using the Seattle HF Model and followed patients for 1 year to record mortality (or urgent heart transplant or ventricular assist device implant as mortality-equivalent events). Using multivariable logistic regression, the authors evaluated associations among physician experience and confidence in estimates, duration of patient-physician relationship, patient-physician sex concordance, patient race, and predicted risk, with concordant results …