Sublingual Tablet Immunotherapy Improves Quality of Life in Adults With Allergic Rhinoconjunctivitis.

BACKGROUND: Allergic rhinitis with or without conjunctivitis can negatively impact many aspects of quality of life (QoL). The efficacy and safety of standardized quality (SQ) sublingual immunotherapy (SLIT) tablets have been confirmed across large clinical trials in adults with grass, tree, ragweed, and house dust mite (HDM) allergic rhinitis with or without conjunctivitis. OBJECTIVE: This pooled analysis investigates whether the reduction in symptom burden found across the clinical trials is supported by improvements in QoL. METHODS: A total of 11 phase II/III randomized placebo-controlled trials across the SQ grass, tree, ragweed, and HDM SLIT tablets (grass: N = 3179; ragweed: N = 767; tree: N = 634; HDM: N = 2221) were included. QoL was assessed using the standardized Rhinitis Quality of Life Questionnaire (RQLQ), with the exception of 3 grass trials, which used the nonstandardized version. The overall RQLQ scores were expressed as a mean of 7 domains. In the pooled analysis, treatment was used as fixed effect; and the trial, and the interaction between region/country and trial as random effects. RESULTS: The pooled analysis showed consistent and statistically significant improvements in overall RQLQ scores across all 4 SQ SLIT tablets versus placebo (pooled estimate [95% CI], P value-grass: -0.20 [-0.28 to -0.12], P < .001; tree: -0.42 [-0.58 to -0.26], P < .001; ragweed: -0.36 [-0.55 to -0.17], P < .001; HDM: -0.28 [-0.39 to -0.17], P < .001). Furthermore, significant improvements versus placebo for all 4 SQ SLIT tablets were seen across the 7 individual domains. CONCLUSIONS: The proven efficacy of SQ SLIT tablets to reduce symptoms across 4 of the most common respiratory allergens is supported by concurrent significant improvements in RQLQ scores overall and for all 7 domains.

Allergen Release Profiles of Fast-Dissolving Freeze-Dried Orodispersible Sublingual Allergy Immunotherapy Tablets.

Background: Sublingual allergy immunotherapy tablets (SLIT-tablets) provide a well-tolerated and clinically efficacious treatment for allergic disease such as allergic rhinitis and allergic asthma. In SLIT, uptake of allergen by immune-competent cells in the oral mucosa activates the immune system and leads to tolerance toward the sensitizing allergen. The ability to deliver the full allergen content into solution within the recommended sublingual holding time is therefore an essential quality of SLIT-tablets that must be supported by the tablet formulation for all relevant allergen sources. SLIT-tablets based on a fast-dissolving orodispersible freeze-dried formulation (Zydis) are currently available for 5 of the most prevalent allergens: tree (birch and related species from the birch-homologous group), grass, ragweed, Japanese cedar, and house dust mite. Objectives: The purpose of this study was to examine the allergen release properties of three freeze-dried SLIT-tablets containing tree, ragweed, and Japanese cedar extracts, respectively. The correlation between SLIT-tablet allergen release and the level of allergen-specific T-cell activation was examined for the tree SLIT-tablet. Methods: Allergen release kinetics and tablet disintegration times for the 3 freeze-dried SLIT-tablets were examined. For all 3 tablets, the magnitude of solubilized major allergen relative to time in solution was compared to external controls to achieve a measure of the total allergen release. Additional assessments of allergen release occurring after the initial timepoint (15 or 30 seconds in solution) were done independently of external controls by linear regression analyses. For the tree SLIT-tablet, the immunological potency of the released major allergen was assessed at each experimental timepoint by a Bet v-specific T-cell activation assay. Results: All 3 SLIT-tablets disintegrated within 1 second after contact with assay buffer without any detectible residue. Complete release of major allergens (Bet v 1, Amb a 1, and Cry j 1, respectively) was seen at the earliest experimental time points (15 or 30 seconds). For the tree SLIT-tablet, full T-cell activation was achieved at 30 seconds (earliest experimental time point). Conclusions: The freeze-dried SLIT-tablet formulation consistently provides rapid and complete release of allergen from a wide range of species in a standardized in vitro assay. Full release of the SLIT-tablet allergen content within the sublingual holding time is a prerequisite for maximal exposure of allergens to the sublingual mucosa immune system. The freeze-dried SLIT-tablet formulation examined here supports short sublingual holding times and furthermore offers a convenient administration form of allergy immunotherapy.

Bottle-feeding and the Risk of Pyloric Stenosis.

OBJECTIVES: Bottle-feeding has been suggested to increase the risk of pyloric stenosis (PS). However, large population-based studies are needed. We examined the effect of bottle-feeding during the first 4 months after birth, by using detailed data about the timing of first exposure to bottle-feeding and extensive confounder information. METHODS: We performed a large population-based cohort study based on the Danish National Birth Cohort, which provided information on infants and feeding practice. Information about surgery for PS was obtained from the Danish National Patient Register. The association between bottle-feeding and the risk of PS was evaluated by hazard ratios (HRs) estimated in a Cox regression model, adjusting for possible confounders. RESULTS: Among 70148 singleton infants, 65 infants had surgery for PS, of which 29 were bottle-fed before PS diagnosis. The overall HR of PS for bottle-fed infants compared with not bottle-fed infants was 4.62 (95% confidence interval [CI]: 2.78-7.65). Among bottle-fed infants, risk increases were similar for infants both breast and bottle-fed (HR: 3.36 [95% CI: 1.60-7.03]), formerly breastfed (HR: 5.38 [95% CI: 2.88-10.06]), and never breastfed (HR: 6.32 [95% CI: 2.45-16.26]) (P = .76). The increased risk of PS among bottle-fed infants was observed even after 30 days since first exposure to bottle-feeding and did not vary with age at first exposure to bottle-feeding. CONCLUSIONS: Bottle-fed infants experienced a 4.6-fold higher risk of PS compared with infants who were not bottle-fed. The result adds to the evidence supporting the advantage of exclusive breastfeeding in the first months after birth.

Male circumcision and sexual function in men and women: a survey-based, cross-sectional study in Denmark.

BACKGROUND: One-third of the world's men are circumcised, but little is known about possible sexual consequences of male circumcision. In Denmark (~5% circumcised), we examined associations of male circumcision with a range of sexual measures in both sexes. METHODS: Participants in a national health survey (n = 5552) provided information about their own (men) or their spouse's (women) circumcision status and details about their sex lives. Logistic regression-derived odds ratios (ORs) measured associations of circumcision status with sexual experiences and current difficulties with sexual desire, sexual needs fulfilment and sexual functioning. RESULTS: Age at first intercourse, perceived importance of a good sex life and current sexual activity differed little between circumcised and uncircumcised men or between women with circumcised and uncircumcised spouses. However, circumcised men reported more partners and were more likely to report frequent orgasm difficulties after adjustment for potential confounding factors [11 vs 4%, OR(adj) = 3.26; 95% confidence interval (CI) 1.42-7.47], and women with circumcised spouses more often reported incomplete sexual needs fulfilment (38 vs 28%, OR(adj) = 2.09; 95% CI 1.05-4.16) and frequent sexual function difficulties overall (31 vs 22%, OR(adj) = 3.26; 95% CI 1.15-9.27), notably orgasm difficulties (19 vs 14%, OR(adj) = 2.66; 95% CI 1.07-6.66) and dyspareunia (12 vs 3%, OR(adj) = 8.45; 95% CI 3.01-23.74). Findings were stable in several robustness analyses, including one restricted to non-Jews and non-Moslems. CONCLUSIONS: Circumcision was associated with frequent orgasm difficulties in Danish men and with a range of frequent sexual difficulties in women, notably orgasm difficulties, dyspareunia and a sense of incomplete sexual needs fulfilment. Thorough examination of these matters in areas where male circumcision is more common is warranted.

Risk of birth abnormalities in the offspring of men with a history of cancer: a cohort study using Danish and Swedish national registries.

BACKGROUND: The potential mutagenic effects of cancer therapies and the growing number of young male cancer survivors have given rise to concern about the health of their offspring. METHODS: We identified all singleton children born alive in Denmark between 1994 and 2004 and in Sweden between 1994 and 2005 (n = 1,777,765). Of the 8670 children with a paternal history of cancer, 8162 were conceived naturally and 508 were conceived using assisted reproductive technologies (ARTs) (in vitro fertilization or intracytoplasmatic sperm injection). Of the 1,769,095 children without a paternal history of cancer, 25,926 were conceived using ARTs. Associations between paternal history of cancer and risk of adverse birth outcomes of children conceived naturally or by ARTs were investigated using log-linear binomial models, yielding risk ratios (RRs) with 95% confidence intervals (CIs). All statistical tests were two-sided. RESULTS: The offspring of male cancer survivors were more likely to have major congenital abnormalities than the offspring of fathers with no history of cancer (RR = 1.17, 95% CI = 1.05 to 1.31, P = .0043, 3.7% vs 3.2%). However, the mode of conception (natural conception or ARTs) did not modify the association between paternal history of cancer and risk of congenital abnormalities (natural conception, RR = 1.17, 95% CI = 1.04 to 1.31; ARTs, RR = 1.22, 95% CI = 0.80 to 1.87, P(interaction) = .84). CONCLUSION: We observed a statistically significant but modest increase in the risk of major congenital abnormalities among offspring of males with a history of cancer, independent of the mode of conception.