Characterization of patients with atopic dermatitis based on flare patterns and severity of disease: A Danish population-based study.

BACKGROUND: Flare patterns are not routinely considered in the severity classification or in clinical decision-making of atopic dermatitis (AD), but frequent or severe flares may contribute considerably to the disease burden. OBJECTIVES: To characterize patients with AD in relation to their flare pattern and compare flare patterns to disease severity, life quality and treatment satisfaction. METHODS: Patients with AD from the Danish Skin Cohort were included if they had active AD with and available data on number of flare-ups within the last 12 months. Categorical variables were presented as frequencies and percentages, whereas numerical variables were presented as median and interquartile ranges (IQR). Between-group differences were tested with chi-squared tests. RESULTS: A total of 1557 patients were included, with 57 reporting 0 flares, 698 (1-5 flares), 324 (6-10 flares) and 478 reporting >10 flares during the past 12 months. Both the severity measured by PO-SCORAD and the impairment of life quality measured by DLQI were higher among patients with more flares (median [IQR] PO-SCORAD: 13.0 [5.6-22.3], 29.7 [20.8-40.6], 36.3 [26.7-47.6]and 42.9 [30.7-55.6], respectively for the four flares strata, and median [IQR] DLQI: 1.0 [0.0-2.0], 3.0 [1.0-7.0], 4.0 [1.8-9.0] and 7.0 [3.0-11.0]). Satisfaction with the current treatment was generally higher among patients with no flares. However, 36.8%, 24.6% and 23.7% of patients with 1-5, 6-10 and >10 flares reported being extremely or very satisfied with their current treatment. CONCLUSIONS: Patients with many flares often report a higher severity and impairment of life quality compared to patients with fewer flares. Information on flaring could benefit treatment decisions, thereby decreasing undertreatment of patients with mild AD but severe flaring.

S-Ketamine Mediates Its Acute and Sustained Antidepressant-Like Activity through a 5-HT1B Receptor Dependent Mechanism in a Genetic Rat Model of Depression.

Rationale: The mechanisms responsible for the unique antidepressant properties of ketamine have only been partly resolved. Recent preclinical reports implicate the neurotransmitter serotonin [5-hydroxytryptamine (5-HT)] in the antidepressant-like response of ketamine, and modulation of 5-HT1B receptors has been hypothesized to attain an important role. Objectives: To evaluate the role of endogenous stimulation of 5-HT1B heteroreceptors in the antidepressant-like activity of S-ketamine. Method: Flinders sensitive line (FSL) rats, a genetic model of depression, were depleted of endogenous 5-HT by 4-chloro-DL-phenylalanine methyl ester HCl administration (pCPA; 86 mg/kg/day for 3 days). In pCPA-pretreated and control FSL rats, the acute and sustained effects of a single dose of S-ketamine (15 mg/kg) and the selective 5-HT1B receptor agonist CP94253 (1-6 mg/kg) alone and in combination with S-ketamine were studied in the forced swim test (FST), a commonly used assay that detects antidepressant activity. Results: pCPA pretreatment decreased cortical 5-HT levels to ∼6% but did not affect the baseline behavioral phenotype of FSL rats. S-ketamine demonstrated acute and sustained antidepressant-like activity, both of which were abolished by 5-HT depletion. Combining S-ketamine with a sub-effective dose of CP94253 (1 mg/kg) rescued S-ketamine's acute and sustained antidepressant-like effects, when CP94253 was administered 2 h prior to the FST. Co-administration of S-ketamine and CP94253 did not affect the plasma level of either compound, suggesting that the observed behavioral interaction could not be ascribed to a kinetic drug-drug interaction. Conclusion: 5-HT1B receptor activation during testing appears to be critical for S-ketamine's antidepressant-like potentials in this model.