BACKGROUND: Any benefit of adjuvant interferon alfa-2b for melanoma could depend on dose and duration of treatment. Our aim was to determine whether pegylated interferon alfa-2b can facilitate prolonged exposure while maintaining tolerability. METHODS: 1256 patients with resected stage III melanoma were randomly assigned to observation (n=629) or pegylated interferon alfa-2b (n=627) 6 mug/kg per week for 8 weeks (induction) then 3 mug/kg per week (maintenance) for an intended duration of 5 years. Randomisation was stratified for microscopic (N1) versus macroscopic (N2) nodal involvement, number of positive nodes, ulceration and tumour thickness, sex, and centre. Randomisation was done with a minimisation technique. The primary endpoint was recurrence-free survival. Analyses were done by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00006249. FINDINGS: All randomised patients were included in the primary efficacy analysis. 608 patients in the interferon group and 613 patients in the observation group were included in safety analyses. The median length of treatment with pegylated interferon alfa-2b was 12 (IQR 3.8-33.4) months. At 3.8 (3.2-4.2) years median follow-up, 328 recurrence events had occurred in the interferon group compared with 368 in the observation group (hazard ratio 0.82, 95% CI 0.71-0.96; p=0.01); the 4-year rate of recurrence-free survival was 45.6% (SE 2.2) in the interferon group and 38.9% (2.2) in the observation group. There was no difference in overall survival between the groups. Grade 3 adverse events occurred in 246 (40%) patients in the interferon group and 60 (10%) in the observation group; grade 4 adverse events occurred in 32 (5%) patients in the interferon group and 14 (2%) in the observation group. In the interferon group, the most common grade 3 or 4 adverse events were fatigue (97 patients, 16%), hepatotoxicity (66, 11%), and depression (39, 6%). Treatment with pegylated interferon alfa-2b was discontinued because of toxicity in 191 (31%) patients. INTERPRETATION: Adjuvant pegylated interferon alfa-2b for stage III melanoma has a significant, sustained effect on recurrence-free survival.

In school-aged children, 1) Tg is a sensitive indicator of both low and excess iodine intake; 2) a median Tg of <13 μg/L and/or <3% of Tg values >40 μg/L indicates iodine sufficiency in the population; 3) the acceptable range of median UIC in monitoring iodized salt programs could be widened to a single category of sufficient iodine intake from 100 to 299 μg/L.

Iodine status in populations is usually assessed by the median urinary iodine concentration (UIC). However, iodine is also excreted in breast milk during lactation; thus, breast milk iodine concentration (BMIC) may be a promising biomarker of iodine nutrition in lactating women. Whether the mammary gland can vary fractional uptake of circulating iodine in response to changes in dietary intake is unclear. We evaluated UIC and BMIC as biomarkers for iodine status in lactating women with a wide range of iodine intakes. We recruited 866 pairs of lactating mothers and exclusively breastfed infants from 3 iodine-sufficient study sites: Linfen, China ( = 386); Tuguegarao, Philippines ( = 371); and Zagreb, Croatia ( = 109). We also recruited iodine-deficient lactating women from Amizmiz, Morocco ( = 117). We collected urine and breast milk samples and measured UIC and BMIC. In the 3 iodine-sufficient sites, a pooled regression analysis of the estimated iodine excretion revealed higher fractional iodine excretion in breast milk than in urine at borderline low iodine intakes. In contrast, in the iodine-deficient site in Morocco, a constant proportion (∼33%) of total iodine was excreted into breast milk. In iodine-sufficient populations, when iodine intake in lactating women is low, there is increased partitioning of iodine into breast milk. For this reason, maternal UIC alone may not reflect iodine status, and BMIC should also be measured to assess iodine status in lactating women. Our data suggest a BMIC reference range (2.5th and 97.5th percentiles) of 60-465 μg/kg in exclusively breastfeeding women. This trial was registered at clinicaltrials.gov as NCT02196337.

Salivary immunoglobulin subclasses vary in different oral mucosal conditions and may play a role in oral mucosal inflammatory diseases and/or reflect clinical changes in these conditions.

A commercial optically stimulated luminescence (OSL) dosimetry system was investigated for invivo dosimetry in radiation therapy. Dosimetric characteristics of InLight dot dosimeters and a microStar reader (Landauer Inc.) were tested in 60 Co beams. Reading uncertainty of a single dosimeter was 0.6%. The reproducibility of a set of dosimeters after a single irradiation was 1.6%, while in repeated irradiations of the same dosimeters it was found to be 3.5%. When OSL dosimeters were optically bleached between exposures, the reproducibility of repeated measurements improved to 1.0%. Dosimeters were calibrated for the entrance dose measurements and a full set of correction factors was determined. A pilot patient study that followed the phantom validation testing included more than 100 measured fields with a mean relative difference of the measured entrance dose from the expected dose of 0.8% and the standard deviation of 2.5%. In conclusion, these results demonstrate that OSL dot dosimeters represent a valid alternative to already established in-vivo dosimetry systems.

PEG-IFN-alpha-2b leads to a significant and sustained improvement in RFS. There is an expected negative effect on global HRQOL and selected symptoms when patients undergo PEG-IFN-alpha-2b treatment.

Salt iodization at ∼25 mg/kg that covers a high proportion of the total amount of salt consumed supplies sufficient dietary iodine to ensure adequate iodine nutrition in all population groups, although intakes may be borderline low during pregnancy. Large variations in salt iodine concentrations increase the risk for both low and high iodine intakes. Strict monitoring of the national salt iodization program is therefore essential for optimal iodine nutrition. This trial was registered at clinicaltrials.gov as NCT02196337.

Context: Thyroglobulin (Tg) could be a sensitive biomarker of iodine nutrition in pregnant women (PW). A dried blood spot (DBS) assay would simplify collection and transport in field studies. Objectives: Our aims were to (1) establish and test a reference range for DBS-Tg in PW; (2) determine whether co-measurement of Tg antibodies (Abs) is necessary to define population iodine status. Design, Setting, and Participants: Standardized cross-sectional studies of 3870 PW from 11 countries. For the DBS-Tg reference range, we included TgAb-negative PW (n = 599) from 3 countries with sufficient iodine intake. Main Outcome Measures: We measured the urinary iodine concentration and DBS thyroidstimulating hormone, total thyroxin, Tg, and TgAb. Results: In the reference population, the median DBS-Tg was 9.2 g/L (95% confidence interval, 8.7 to 9.8 g/L) and was not significantly different among trimesters. The reference range was 0.3 to 43.5 g/L. Over a range of iodine intake, the Tg concentrations were U-shaped. Within countries, the median DBS-Tg and the presence of elevated DBS-Tg did not differ significantly between all PW and PW who were TgAb-negative. Conclusions: A median DBS-Tg of 10 g/L with <3% of values 44 g/L indicated population iodine sufficiency. Concurrent measurement of TgAb did not appear necessary to assess the population iodine status.