Strategies used for measuring long-term control in atopic dermatitis trials: A systematic review.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease. There are no standardized methods for capturing long-term control of AD. OBJECTIVE: We sought to identify how long-term control has been captured in published randomized controlled trials (RCTs). Results will initiate consensus discussions on how best to measure long-term control in the core outcome set for AD. METHODS: We conducted a systematic review of RCTs of AD treatments published between 2000 and 2013, with a follow-up period of 3 months or longer, at least 1 outcome measure recorded at 3 or more time points, full article available, and published in English. RESULTS: In all, 101 of 353 RCTs were eligible. Methods to capture long-term control included: repeated measurement of AD outcomes (92 RCTs; 91%), use of AD medication (29 RCTs; 28.7%), and AD flares/remissions (26 RCTs; 25.7%). Repeated measurements of AD outcomes were typically collected 3 to 5 times during a trial, but analysis methods often failed to make best use of the data. Time to first flare was most commonly used for trials including flare data (21/52). Medication use was recorded based on quantity, potency, and frequency of application. LIMITATIONS: We included RCT data only. CONCLUSION: This review illustrates the difficulties in measuring long-term control, and points to the need for improved harmonization of outcomes.

GLP-1 receptor agonists have a sustained stimulatory effect on corticosterone release after chronic treatment.

OBJECTIVE: Glucagon-like peptide 1 (GLP-1) receptor agonists are a new group of antidiabetic medications quickly gaining popularity. We aimed to examine behavioural and neuroendocrine changes following chronic treatment with GLP-1 receptor agonists in animal models. METHODS: The effects of chronic treatment with GLP-1 receptor agonists were determined on behavioural parameters [anxiety level in the light-dark compartment test, the motor activity in automated activity cages, immobility in the forced swimming test (FST)] and on corticosterone release in mice. The possible antidepressant effect of chronic liraglutide treatment was also studied in Flinders Sensitive Line (FSL) rats, a genetic model of depression. RESULTS: Two weeks of treatment with exenatide (10 µg/kg twice daily) or liraglutide (1200 µg/kg once daily) did not affect the anxiety level in a light-dark compartment test nor induce an antidepressant-like effect in the FST in mice. Moreover, chronic treatment with liraglutide had no effect on depression-related behaviour in FSL rats. Interestingly, hypolocomotion induced by the drugs in mice disappeared after chronic dosing. Both of the GLP-1 receptor agonists induced robust increases in corticosterone levels in mice under basal conditions as well as in the case of combination with swimming stress. Remarkably, exenatide was as potent a stimulator of corticosterone release after 2 weeks as after acute administration. CONCLUSIONS: The increases in corticosterone release seen after acute exenatide or liraglutide treatment do not abate after 2 weeks of treatment demonstrating that tolerance does not develop towards this particular effect of GLP-1 agonists.

12-month prevalence of atopic dermatitis in resource-rich countries: a systematic review and meta-analysis.

There is a lack of robust prevalence estimates of atopic dermatitis (AD) globally and trends over time due to wide variation of populations and age groups studied, different study methodologies and case definitions used. We sought to characterize 12-month AD prevalence across the life span and change over time in resource-rich countries focusing on population-based studies and using a standardized AD case definition. This systematic review was conducted according to PRISMA guidelines. Medline (Ovid), Embase, WOS core collection, Cinahl, and Popline were searched for studies published since inception through August 15, 2016. Studies were synthesized using random effects meta-analysis. Sources of heterogeneity were investigated using subgroup analyses and meta-regression. From 12,530 records identified, 45 studies met the inclusion criteria. Meta-analysis with random effects revealed the 12-month period prevalence of 9.2% (95% confidence interval 8.4-10.1%). The prevalence was significantly higher among 0-5-year-old children (16.2%; 95% confidence interval 14.2-18.7%) than in older age groups. Studies using a random sampling strategy yielded lower prevalence estimates than studies relying on other sampling methods. There was no clear time trend in AD prevalence over the period of 1992-2013.

Dual effect of nickel on L-arginine/nitric oxide system in RAW 264.7 macrophages.

The immunogenic mechanisms of the potent contact allergen nickel are not completely clear. Nitric oxide (NO) serves as a fundamental signalling and effector molecule in the immune system, but little is known about its possible role in immune reactions elicited by nickel. We investigated the effects of nickel on the L-arginine/inducible NO synthase (iNOS) system in a murine macrophage cell line, RAW 264.7. Both LPS-stimulated and non-stimulated RAW 264.7 cells were incubated in the presence of 0-100 µM nickel sulphate for 24 h. Subsequently, NO production, iNOS protein expression, L-arginine uptake and gene expression of iNOS and cationic amino acid transporter systems (CAT) were measured. We found that 100 µM NiSO4 increased LPS-induced nitrite production as well as the formation of [(3)H]-L-citrulline from [(3)H]-L-arginine in the RAW 264.7 cells. Correspondingly, the expression of iNOS gene and protein was also remarkably enhanced. Nevertheless, nickel had an inhibitory effect on L-arginine transport which disappeared gradually upon LPS-stimulation in parallel with an increase in NO output. LPS was found to significantly amplify CAT-3 as well as CAT-2 mRNA expression, mirroring the increase in L-arginine transport. In the range of 1-10 µM, NiSO4 did not have any additional effect on CAT mRNA expression, but at 100 µM it was able to enhance CAT-1 and CAT-3 mRNA expression upon LPS stimulation. Our data indicate that nickel interferes with macrophages' L-arginine/NOS system on multiple levels. Considering the potent biological effects of NO, these influences may contribute to nickel toxicity.