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Background: In March 2018, the European pregnancy prevention programme for oral retinoids was updated as part of risk minimisation measures (RMM), emphasising their contraindication in pregnant women. Objective: To measure the impact of the 2018 revision of the RMMs in Europe by assessing the utilisation patterns of isotretinoin, alitretinoin and acitretin, contraceptive measures, pregnancy testing, discontinuation, and pregnancy occurrence concomitantly with a retinoid prescription. Methods: An interrupted time series (ITS) analysis to compare level and trend changes after the risk minimisation measures implementation was conducted on a cohort of females of childbearing age (12-55 years of age) from January 2010 to December 2020, derived from six electronic health data sources in four countries: Denmark, Netherlands, Spain, and Italy. Monthly utilisation figures (incidence rates [IR], prevalence rates [PR] and proportions) of oral retinoids were calculated, as well as discontinuation rates, contraception coverage, pregnancy testing, and rates of exposed pregnancies to oral retinoids, before and after the 2018 RMMs. Results: From 10,714,182 females of child-bearing age, 88,992 used an oral retinoid at any point during the study period (mean age 18.9-22.2 years old). We found non-significant level and trend changes in incidence or prevalence of retinoid use in females of child-bearing age after the 2018 RMMs. The reason of discontinuation was unknown in >95% of cases. Contraception use showed a significant increase trend in Spain; for other databases this information was limited. Pregnancy testing was hardly recorded thus was not possible to model ITS analyses. After the 2018 RMM, rates of pregnancy occurrence during retinoid use, and start of a retinoid during a pregnancy varied from 0.0 to 0.4, and from 0.2 to 0.8, respectively. Conclusion: This study shows a limited impact of the 2018 RMMs on oral retinoids utilisation patterns among females of child-bearing age in four European countries. Pregnancies still occur during retinoid use, and oral retinoids are still prescribed to pregnant women. Contraception and pregnancy testing information was limited in most databases. Regulators, policymakers, prescribers, and researchers must rethink implementation strategies to avoid any pregnancy becoming temporarily related to retinoid use. [ABSTRACT FROM AUTHOR]

Simple Summary: Recent studies have mostly focused on the treatment of advanced mycosis fungoides and Sézary syndrome and less on the treatment of relapsed or refractory (R/R) cases of cutaneous T-cell lymphoma (CTCL). There is also a paucity of data on the treatment and outcomes of primary cutaneous anaplastic large cell lymphoma and other rare CTCL subtypes. This European observational study provided real-world data on the current treatments used in the management of CTCL across three lines of therapy. As a result, there was a significant level of heterogeneity in treatment types than expected by European guidelines. These findings highlight the lack of consensus in relapsed CTCL, as well as the urgent unmet treatment needs. The treatment pattern of cutaneous T-cell lymphoma (CTCL) remains diverse and patient-tailored. The objective of this study was to describe the treatment patterns and outcomes in CTCL patients who were refractory or had relapsed (R/R) after a systemic therapy. A retrospective chart review study was conducted at 27 sites in France, Germany, Italy, Spain and the United Kingdom (UK) of patients who received a first course of systemic therapy and relapsed or were refractory. Data were collected longitudinally from diagnosis to first-, second- and third-line therapy. The study included 157 patients, with a median follow-up of 3.2 years. In total, 151 proceeded to second-line and 90 to third-line therapy. In the first line (n = 147), patients were treated with diverse therapies, including single- and multi-agent chemotherapy in 67 (46%), retinoids in 39 (27%), interferon in 31 (21%), ECP in 4 (3%), corticosteroids in 3 (2%) and new biological agents in 3 (2%). In the second line, the use of chemotherapy and retinoids remained similar to the first line, while the use of new biologics increased slightly. In sharp contrast to the first line, combination chemotherapy was extremely diverse. In the third line, the use of chemotherapy remained high and diverse as in the second line. From the time of first R/R, the median PFS was 1.2 years and the median OS was 11.5 years. The presented real-world data on the current treatments used in the management of R/R CTCL in Europe demonstrate the significant heterogeneity of systemic therapies and combination therapies, as expected from the European guidelines. [ABSTRACT FROM AUTHOR]

Intake of chromium was estimated using a duplicate diet sampling method of 108 meals (36 breakfasts, 36 lunches and 36 dinners) from the restaurant of the Hospital of Motril (S.E. Spain), corresponding to 36 consecutive days. Total and dialyzable Cr levels were measured by a validated electro-thermal atomic absorption spectrometry (ETAAS) method. A mean Cr fraction of 26±12 μg meal-1 was found. The Cr uptake from meals was directly and significantly (p< 0.001) correlated with their macronutrient (carbohydrates, fibre and protein) content. Cereals and cereal by-products, legumes, dry fruits, meat, potatoes, dairy products and seafood are the primary sources of Cr. The mean Cr fraction dialyzed through dialysis tubing was 1.2±1.1 μg meal-1 (4.6±3.8% as mean Cr dialysability). Cr intake for breakfasts was significantly lower (p < 0.001). A correlation between the logarithmic data of total and dialyzable fraction of Cr in meals (p=0.020) was found and dialysis ratio enhancement and, therefore, bioavailability increased with total Cr. The dialysed element content present in meals was significantly correlated with fibre, protein, Fe, Na, I, F, sodium, ascorbic acid and vitamin A levels (p <0.05). At Fe contents in meals higher than ≅7.5mg meal-1, the net absorption of Cr decreased significantly. The mean Cr daily dietary intake (DDI) was 77±17 μg day-1, which indicates that no adverse effects in relation to Cr nutrition (deficiency or toxicity) should occur in individuals from the area. [ABSTRACT FROM AUTHOR]

Abstract: The vitamin C and provitamin A carotenoids contents of 25 commercially available Spanish orange juices were studied. Large differences in the levels of these compounds were found. On average, ultrafrozen orange juices (UFOJ) and orange juices from the ecological agriculture (OJFEA) showed the highest ascorbic acid contents (518 and 412mg/l respectively) among the different kinds of orange juices studied. Some disagreement between the declared and the actual amounts of vitamin C were found. Provitamin A carotenoids were determined by means of the corresponding standards. The monohydroxycarotenoid accompanying β-cyptoxanthin in orange juices was identified as the non-provitamin A carotenoid, zeinoxanthin, on the basis of the methylation test with acidified methanol. Unusually high contents of β-carotene (>0.5mg/l) were found in two samples, which could indicate that substantial amounts of the pigment were added to those juices. The mandarin juice analyzed showed the highest provitamin A activity (359.3 retinol activity equivalents/l) Among the orange juices surveyed, UFO proved to be the best source of provitamin A (78.5 retinol activity equivalents/l, on average). The lowest contents were found in orange juices from concentrate (OJFC) (22.4 retinol activity equivalents/l, on average, without considering the orange juices with unusual β-carotene contents). [Copyright &y& Elsevier]

Abstract: The effect of age, sex, nutritive condition and organochlorine concentration on blubber retinoid concentrations was examined in 74 common dolphins incidentally caught off northwestern Spain. Age and blubber lipid content were strong determinants of the retinoid concentrations in males, while these variables did not account for the variation found in females. Retinoids were positively correlated with organochlorines in males and negatively in females. However, pollution levels were moderate and likely to be below threshold levels above that a toxicological response is to be expected. Thus, a cause–effect relationship between organochlorine and retinoid concentrations could not be properly established, and the observed correlation may be the result of an independent association of the two variables with age. Further research on the influence of the best predictor variables on retinoid dynamics is required to implement the use of retinoids as biomarkers of pollutant exposure in cetaceans. [Copyright &y& Elsevier]