Assessing the Effect of Clinical Trial Evidence and Anecdote on Caregivers' Willingness to Use Corticosteroids: A Randomized Controlled Trial [Formula: see text].

BACKGROUND: Treatment of childhood atopic dermatitis (AD) is hindered by nonadherence, but caregiver reassurance may help overcome this hurdle. OBJECTIVES: To assess caregivers' willingness to treat childhood AD with a corticosteroid when presented with clinical trial evidence, anecdote, or both. METHODS: A total of 476 caregivers were recruited through a dermatology clinic and online crowdsourcing platform. Subjects were randomized to receive clinical trial evidence, anecdote, or both, using either the term "medication" or "topical steroid." Additional caregivers were queried about their willingness to treat with the doctor's recommendation or without knowledge of its safety information. Responses were recorded on a 10-point Likert scale. RESULTS: Caregivers' willingness to treat was higher in all information assignment groups compared to those not provided with safety information: clinical trial evidence of a "medication" (P = .003; Cohen's d = 0.83) or "topical steroid" (P = .030; d = 0.55), anecdote of a "medication" (P < .0001; d = 1.37) or "topical steroid" (P < .0001; d = 0.85), both clinical trial evidence and anecdote of a "medication" (P < .0001; d = 1.00) or "topical steroid" (P = .000; d = 0.89), and simply the doctor's recommendation (P < .0001; d = 0.92). Significance was corrected for multiple comparisons to 0.0018. There were no differences between caregivers of children with and without AD (P = .36). CONCLUSIONS: Providing anecdotal reassurance, even in the setting of reported high willingness to treat with the doctor's recommendation, may be an effective strategy to improve caregivers' perceptions of starting new medications.

Endogenous, regulatory cysteine sulfenylation of ERK kinases in response to proliferative signals.

ERK-dependent signaling is key to many pathways through which extracellular signals are transduced into cell-fate decisions. One conundrum is the way in which disparate signals induce specific responses through a common, ERK-dependent kinase cascade. While studies have revealed intricate ways of controlling ERK signaling through spatiotemporal localization and phosphorylation dynamics, additional modes of ERK regulation undoubtedly remain to be discovered. We hypothesized that fine-tuning of ERK signaling could occur by cysteine oxidation. We report that ERK is actively and directly oxidized by signal-generated H2O2 during proliferative signaling, and that ERK oxidation occurs downstream of a variety of receptor classes tested in four cell lines. Furthermore, within the tested cell lines and proliferative signals, we observed that both activation loop-phosphorylated and non-phosphorylated ERK undergo sulfenylation in cells and that dynamics of ERK sulfenylation is dependent on the cell growth conditions prior to stimulation. We also tested the effect of endogenous ERK oxidation on kinase activity and report that phosphotransfer reactions are reversibly inhibited by oxidation by as much as 80-90%, underscoring the importance of considering this additional modification when assessing ERK activation in response to extracellular signals.

Relative versus absolute risk of comorbidities in patients with psoriasis.

BACKGROUND: Psoriasis is associated with numerous comorbidities, often reported in terms of relative risk. Both doctors and the general population tend to overestimate the effects of exposures when presented in relative terms, leading to anxiety and potentially poor treatment decisions. Absolute risks might provide a better basis for risk assessment. OBJECTIVE: To characterize and compare relative and absolute risks of comorbidities in patients with psoriasis. METHODS: A systematic review using Medline identified comorbidities associated with psoriasis, their relative risks, and information for calculating absolute risks. RESULTS: The comorbidities associated with psoriasis with the highest relative risk were nonmelanoma skin cancer, melanoma, and lymphoma, with relative risks of 7.5, 6.12, and 3.61, respectively; the attributable risk for these 3 conditions were 0.64, 0.05, and 0.17 per 1000 person-years, respectively. To attribute 1 event of these conditions to psoriasis would require seeing 1551; 20,135; and 5823 patients, respectively. LIMITATIONS: Database studies might not fully account for confounders, resulting in overestimates of the risk impact of comorbidities. CONCLUSIONS: Presenting attributable risk in the form of the number needed to harm provides a clearer picture of the magnitude of risk and a basis for wiser medical decision making and patient education.