Altered stress responses in children exposed to early adversity: A systematic review of salivary cortisol studies.

Pathological stress responses are implicated in numerous disorders. Hypothalamic-pituitary-adrenal axis function is influenced by gene-environment interaction, with early-life environmental adversity having long-lasting effects. We examine the evidence that, in humans, these effects are apparent from infancy. We systematically reviewed published findings on cortisol response to a stressor, in 0-5-year-olds already exposed to adversity. Adversity was defined as a negative environmental influence present post-conception. We searched Ovid MEDLINE (1950-May 2010), EMBASE (1980-May 2010) and PsychINFO (1806-May 2010). We included peer-reviewed, English language studies that analysed salivary cortisol before and after a standardised stressor. We identified 30 studies, of which 27 reported a significant effect of adversity on the cortisol response to stress. Six of these demonstrated an effect of prenatal substance exposure. Thirteen studies found that psychosocial adversity increased cortisol reactivity. Three studies reported that cortisol reactivity could be normalised by intervention programmes. The studies were heterogeneous, both in nature of adversity studied and in stressor used, precluding meta-analysis and assessment of publication bias. Our review presents evidence that adversity disrupts the stress response from an early age. Longitudinal studies are required to determine whether effects persist, alter with time, or are reversible with intervention

International eDelphi Study to Reach Consensus on the Methotrexate Dosing Regimen in Patients With Psoriasis.

A clear dosing regimen for methotrexate in psoriasis is lacking, and this might lead to a suboptimal treatment. Because methotrexate is affordable and globally available, a uniform dosing regimen could potentially optimize the treatment of patients with psoriasis worldwide. To reach international consensus among psoriasis experts on a uniform dosing regimen for treatment with methotrexate in adult and pediatric patients with psoriasis and identify potential future research topics. Between September 2020 and March 2021, a survey study with a modified eDelphi procedure that was developed and distributed by the Amsterdam University Medical Center and completed by 180 participants worldwide (55 [30.6%] resided in non-Western countries) was conducted in 3 rounds. The proposals on which no consensus was reached were discussed in a conference meeting (June 2021). Participants voted on 21 proposals with a 9-point scale (1-3 disagree, 4-6 neither agree nor disagree, 7-9 agree) and were recruited through the Skin Inflammation and Psoriasis International Network and European Academy of Dermatology and Venereology in June 2020. Apart from being a dermatologist/dermatology resident, there were no specific criteria for participation in the survey. The participants worked mainly at a university hospital (97 [53.9%]) and were experienced in treating patients with psoriasis with methotrexate (163 [91.6%] had more than 10 years of experience). In a survey with eDelphi procedure, we tried to reach consensus on 21 proposals. Consensus was defined as less than 15% voting disagree (1-3). For the consensus meeting, consensus was defined as less than 30% voting disagree. Of 251 participants, 180 (71.7%) completed all 3 survey rounds, and 58 participants (23.1%) joined the conference meeting. Consensus was achieved on 11 proposals in round 1, 3 proposals in round 2, and 2 proposals in round 3. In the consensus meeting, consensus was achieved on 4 proposals. More research is needed, especially for the proposals on folic acid and the dosing of methotrexate for treating subpopulations such as children and vulnerable patients. In this eDelphi consensus study, consensus was reached on 20 of 21 proposals involving methotrexate dosing in patients with psoriasis. This consensus may potentially be used to harmonize the treatment with methotrexate in patients with psoriasis