Add-On Effect of Selenium and Vitamin D Combined Supplementation in Early Control of Graves' Disease Hyperthyroidism During Methimazole Treatment.

Prompt and stable control of hyperthyroidism is fundamental to avoid the detrimental effects of thyroid hormone excess, and antithyroid drugs, mainly methimazole (MMI), represent the first-line treatment for Graves' disease (GD) hyperthyroidism. Decreased serum concentrations of selenium (Se) and calcifediol (25(OH)D, VitD) have been reported in newly diagnosed GD patients in observational studies. Low Se levels might exacerbate oxidative stress by compromising the antioxidant machinery's response to reactive oxygen species, and low VitD levels might hamper the anti-inflammatory immune response. We performed a randomized controlled clinical trial (EudraCT 2017-00505011) to investigate whether Se and cholecalciferol (VitD) addition to MMI is associated with a prompter control of hyperthyroidism. Forty-two consecutive patients with newly-onset GD and marginal/insufficient Se and VitD levels were randomly assigned to treatment with either MMI monotherapy or MMI combined with Se and VitD. Se treatment was withdrawn after 180 days, while the other treatments were continued. Combination therapy resulted in a significantly greater reduction in serum FT4 concentration at 45 days (-37.9 pg/ml, CI 95%, -43.7 to -32.2 pg/ml) and 180 days (-36.5 pg/ml, CI 95%, -42 to -30.9 pg/ml) compared to MMI monotherapy (respectively: -25.7 pg/ml, CI 95%, -31.6 to -19.7 pg/ml and -22.9 pg/ml, CI 95%, -28 to -17.3 pg/ml, p 0.002). Data at 270 days confirmed this trend (-37.8 pg/ml, CI 95%, -43.6 to -32.1 pg/ml vs -24.4 pg/ml, CI 95%, -30.3 to -18.4 pg/ml). The quality of life (QoL) score was investigated by the validated "Thyroid-related Patient-Reported Outcome" questionnaire (ThyPRO). ThyPRO composite score showed a greater improvement in the intervention group at 45 days (-14.6, CI 95%, -18.8 to -10.4), 180 (-9, CI 95%, -13.9 to -4.2) and 270 days (-14.3, CI 95%, -19.5 to -9.1) compared to MMI group (respectively, -5.2, CI 95%, -9.5 to -1; -5.4, CI 95%, -10.6 to -0.2 and -3.5, CI 95%, -9 to -2.1, p 0-6 months and 6-9 months <0.05). Our results suggest that reaching optimal Se and VitD levels increases the early efficacy of MMI treatment when Se and VitD levels are suboptimal.

Modeling population exposure to ultrafine particles in a major Italian urban area.

Average daily ultrafine particles (UFP) exposure of adult Milan subpopulations (defined on the basis of gender, and then for age, employment or educational status), in different exposure scenarios (typical working day in summer and winter) were simulated using a microenvironmental stochastic simulation model. The basic concept of this kind of model is that time-weighted average exposure is defined as the sum of partial microenvironmental exposures, which are determined by the product of UFP concentration and time spent in each microenvironment. In this work, environmental concentrations were derived from previous experimental studies that were based on microenvironmental measurements in the city of Milan by means of personal or individual monitoring, while time-activity patterns were derived from the EXPOLIS study. A significant difference was observed between the exposures experienced in winter (W: 28,415 pt/cm3) and summer (S: 19,558 pt/cm3). Furthermore, simulations showed a moderate difference between the total exposures experienced by women (S: 19,363 pt/cm3; W: 27,623 pt/cm3) and men (S: 18,806 pt/cm3; W: 27,897 pt/cm3). In addition, differences were found as a function of (I) age, (II) employment status and (III) educational level; accordingly, the highest total exposures resulted for (I) 55-59 years old people, (II) housewives and students and (III) people with higher educational level (more than 10 years of scholarity). Finally, significant differences were found between microenvironment-specific exposures.