House dust mite sublingual immunotherapy tablet safety in adolescents with allergic rhinoconjunctivitis: Worldwide clinical trial results.

BACKGROUND: The house dust mite (HDM) sublingual immunotherapy (SLIT)-tablet is a treatment option for allergic rhinitis with/without conjunctivitis (AR/C) approved in adults worldwide and in adolescents in some countries. OBJECTIVE: To supplement existing adolescent HDM SLIT-tablet safety data by conducting the MT-18 trial in adolescents. METHODS: MT-18 (EudraCT:2020-000446-34) was a phase 3, open-label, single-arm, 28-day safety trial of daily HDM SLIT-tablet (12 SQ-HDM dose) in European adolescents (12-17 years) with HDM AR/C, with or without asthma. The primary end point was at least 1 treatment-emergent adverse event (TEAE). MT-18 results were compared with 12 SQ-HDM adolescent subpopulation data from previously described 1-year phase 3 trials conducted in North America (P001; clinicaltrials.gov:NCT01700192) or Japan (TO-203-3-2; JapicCTI:121848). RESULTS: No treatment-related anaphylaxis, epinephrine administrations, severe local swellings, severe mouth or throat edema, or eosinophilic esophagitis occurred in the trials. For MT-18 (N = 253), P001 (N adolescents = 189), and TO-203-3-2 (N adolescents = 206), the percentage of adolescents treated with 12 SQ-HDM reporting any TEAE was 88%, 95%, and 93%, respectively, and the percentage reporting any treatment-related AE (TRAE) was 86%, 93%, and 66%, respectively. The most common TRAEs were local application site reactions. Most TRAEs were mild in intensity and were typically experienced the first 1 to 2 days of treatment. There were no asthma-related TEAEs with the HDM SLIT-tablet. The safety profile appears similar between adolescents with or without asthma at baseline. CONCLUSION: The HDM SLIT-tablet was well tolerated in European, North American, and Japanese adolescents with HDM AR/C, indicating safety of the HDM SLIT-tablet is insensitive to age or geographic region. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: (P001: NCT01700192); EudraCT: (MT-18; 2020-000446-34); JapicCTI: (TO-203-3-2; 121848).

The impact of a meat- versus a vegetable-based diet on iron status in women of childbearing age with small iron stores.

BACKGROUND: Single-meal and short-term studies have shown an enhancing effect of meat on iron absorption, but there are few interventions of longer duration comprising measurements of biomarkers of iron status. AIMS OF THE STUDY: To assess the impact of a meat-based and a vegetable-based diet on iron status of women of childbearing age. METHODS: For 20 weeks, 57 women aged 19-39 years with low iron stores (serum ferritin < or =30 microg/l and haemoglobin > or =120 g/l) consumed either a meat-based or a vegetable-based diet. Haemoglobin and serum ferritin concentrations were measured at baseline, after 10 and 20 weeks. Information about dietary intake before and during intervention, meat/fish intake, menstruation and contraceptive methods were recorded. RESULTS: The women who consumed the meat-based diet had a significantly (P < 0.001) higher intake of meat/fish, 152 (147-168) g/day (median (Q1-Q3)) compared to the women consuming the vegetable-based diet 31 (24-36) g/day, while the total iron intake was similar in the two groups (mean +/- SE) 11.0 +/- 0.5 and 12.3 +/- 0.3/day mg/day, respectively. Serum ferritin remained unchanged in women on the meat-based diet (n = 29)(before intervention (median (Q1-Q3)): 16.3 (12.7-25.3) microg/l and after intervention: 16.5 (10.3-25.3) microg/l, but declined from 17.3 (10.9-23.7) to 11.2 (8.8-14.6) mug/l (P < 0.001) in women on the vegetable-based diet (n = 28). CONCLUSION: Our results emphasize the importance of the delicate balance between dietary iron content and iron bioavailability for the maintenance of blood indicators of iron stores in women with initially low iron status.

The importance of dietary composition for efficacy of iron absorption measured in a whole diet that includes rye bread fortified with ferrous fumerate: a radioisotope study in young women.

Fe absorption is affected by many dietary factors. The objective of the present study was to measure the effects of high v. low content of vitamin C, meat and phytic acid in whole diets with Fe-fortified bread on the efficacy of Fe absorption. Thirty-two healthy women with low Fe stores were randomised to three groups, each of which was given two of six test diets containing either low/high amounts of vitamin C, meat or phytic acid, respectively, in a cross-over design. Each diet was served throughout a 5 d period. Fe-fortified rye bread, extrinsically labelled with (59)Fe, was given with all main meals. Fe absorption was determined from whole-body counter measurements of (59)Fe retention. The fractional non-haem Fe absorption (corrected to a 40 % standard absorption by measurements from the reference dose) was 1.9 % v. 3.4 % (P=0.04) for the low/high vitamin C diets, 3.0 % v. 3.5 % (P=0.58) on the low/high meat diets and 4.9 % v. 3.8 % (P=0.24) on the low/high phytic acid diet, respectively. The total Fe absorbed (geometric mean with standard error) varied from 0.43 (se 0.11) mg from the diet with lowest bioavailability to 1.09 (se 0.18) mg from the diet with highest bioavailability (P<0.001). The present whole-diet study indicates that diet composition is a strong predictor of Fe absorption. In the diet with a low content of enhancers and a high content of inhibitors, vitamin C improved non-haem Fe absorption. The total Fe absorption varied 2.5-fold after small alterations of the content of enhancers and inhibitors in the diet.

Day-to-day variation in iron-status measures in young iron-deplete women.

In intervention and observational studies, it is necessary to determine the number of blood samples required to estimate the true value of Fe-status measures. The aim of the present study was to determine the number of days for blood sampling required in order to measure the 'true value' of five Fe-status parameters in young Fe-depleted women and to investigate the effect of menstrual cycle on these measures. Twelve women (aged 23-30 years), non-anaemic but with low Fe stores, participated in the study. Venous blood samples were collected under standardised conditions on fifteen non-consecutive days during a 5-week period. All blood samples were analysed for Hb, serum ferritin (SF), serum transferrin receptors (sTfR), red blood cell volume distribution width (RDW) and reticulocytes (RET), and body Fe stores were calculated as the ratio between sTfR and SF. No systematic changes were found in the investigated parameters during the study. When analytical variations were accounted for, the day-to-day variations (CV%) were as follows: Hb 2.9 %, SF 8.2 %, RET 26.0 %, RDW 2.4 % and sTfR 8.1 %. Calculating the 'true value' with a 5 % significance level and 80 % power showed that one blood sample was sufficient for Hb, SF, sTfR and RDW, whereas seven blood-sampling days were needed for RET. In this study, no significant differences in Fe status were found across the menstrual cycle. The conclusions from this study are valid for studies conducted under similar strict conditions.

Short-term effects on bone turnover of replacing milk with cola beverages: a 10-day interventional study in young men.

In the Western world, increased consumption of carbonated soft drinks combined with a decreasing intake of milk may increase the risk of osteoporosis. This study was designed to reflect the trend of replacing milk with carbonated beverages in a group of young men on a low-calcium diet and studies the effects of this replacement on calcium homeostasis and bone turnover. This controlled crossover intervention study included 11 healthy men (22-29 years) who were given a low-calcium basic diet in two 10-day intervention periods with an intervening 10-day washout. During one period, they drank 2.5 l of Coca Cola per day and during the other period 2.5 l of semi-skimmed milk. Serum concentrations of calcium, phosphate, 25-hydroxycholecalciferol, 1,25-dihydroxycholecalciferol (1,25(OH)2D), osteocalcin, bone-specific alkaline phosphatase (B-ALP) and cross-linked C-telopeptides (CTX), plasma intact parathyroid hormone (PTH) and urinary cross-linked N-telopeptides (NTX) were determined at baseline and endpoint of each intervention period. An increase in serum phosphate (P<0.001), 1,25(OH)2D (P<0.001), PTH (P=0.046) and osteocalcin (P<0.001) was observed in the cola period compared to the milk period. Also, bone resorption was significantly increased following the cola period, seen as increased serum CTX (P<0.001) and urinary NTX (P<0.001) compared to the milk period. No changes were observed in serum concentrations of calcium or B-ALP. This study demonstrates that over a 10-day period high intake of cola with a low-calcium diet induces increased bone turnover compared to a high intake of milk with a low-calcium diet. Thus, the trend towards a replacement of milk with cola and other soft drinks, which results in a low calcium intake, may negatively affect bone health as indicated by this short-term study.