Cost-effectiveness of nirmatrelvir/ritonavir for high-risk adult outpatients with COVID-19 in Japan.

INTRODUCTION: This study aimed to evaluate the cost-effectiveness of nirmatrelvir/ritonavir (Nir/Rit) for adult outpatients with COVID-19 from the perspective of a Japanese public healthcare payer. METHODS: A cost-effectiveness simulation was conducted comparing Nir/Rit for the outpatient treatment of high-risk COVID-19 patients to best supportive care (BSC) without antiviral or antibody drugs. The analytical model was divided into two phases: the treatment phase, lasting 35 days from the start of COVID-19 treatment, and the post-treatment phase. Patients who survived the treatment phase were assumed to follow a general population survival curve. Expected costs and expected quality-adjusted life years (QALYs) for both BSC and Nir/Rit were calculated for ages 40 to 80 to obtain the incremental cost-effectiveness ratio (ICER). The robustness of the results was evaluated through deterministic and probabilistic sensitivity analysis (PSA). RESULTS: The ICERs for patients aged 40, 50, 60, 70, and 80 were 18,854,276 Japanese Yen (JPY)/QALY, 8,482,034 JPY/QALY, 4,976,612 JPY/QALY, 2,636,096 JPY/QALY, and 1,597,783 JPY/QALY, respectively. In the deterministic sensitivity analysis, both the mortality risk during the treatment phase and the relative mortality risk with Nir/Rit had a high impact on ICER across all ages. In the PSA, when the willingness-to-pay (WTP) threshold was set at 5 million JPY/QALY, the probability of the ICER being below the WTP threshold was 0%, 0.2%, 45.4%, 99.9%, and 100% at ages 40, 50, 60, 70, and 80, respectively. CONCLUSION: Nir/Rit is cost-effective for older individuals aged 60 and over but not for younger age groups.

Food allergy is linked to season of birth, sun exposure, and vitamin D deficiency.

The season of birth and ultraviolet B exposure have been related to the occurrence of food allergy. The levels of vitamin D produced from skin by ultraviolet B exposure might reflect this relationship. Vitamin D is known to induce antimicrobial peptides, protect intestinal flora, enhance the gut epithelial barrier, suppress mast cell activation and IgE synthesis from B cells, and increase the number of tolerogenic dendritic cells and IL-10-producing regulatory T cells. Vitamin D deficiency has been shown to exacerbate sensitization and allergic symptoms in a murine model of food allergy. However, in clinical situations, contradictory observations have been reported regarding the relationship between food allergy and vitamin D deficiency/supplementation. In this review, we have explored the links between food allergy and vitamin D levels. One explanation for the discrepant findings is confounding factors such as race, age, residency, skin color, and epigenetic changes that contribute to vitamin D levels. In addition, the season of birth influences the development of atopic dermatitis, which could lead to food sensitization. Finally, ultraviolet radiation could lead to regulatory T cell expansion and immunosuppression, irrespective of vitamin D status. Based on our current understanding, we believe that correction of vitamin D deficiency by supplementation, appropriate skin care, and sufficient ultraviolet radiation exposure could alter the prognosis of food allergy. To identify potential treatment strategies for food allergy, it is essential to gain a better understanding of the appropriate levels of vitamin D and ultraviolet radiation exposure.

Immune suppression of food allergy by maternal IgG in murine models.

BACKGROUND: Most of the patients develop food allergy early in life. The factors related to parental immune condition might be one of the conceivable causes. METHODS: We reported murine models of food allergy and oral OVA tolerance. To investigate the influence of parental immune condition on infant food allergy, female and male mice with food allergy or oral tolerance were mated with each other. RESULTS: Food allergy was suppressed by decreased IgE production in the offspring of mice with food allergy. On the contrary, anaphylaxis for OVA was induced in the offspring of mice with oral tolerance. The suppression of food allergy being dependent on a maternal factor was revealed in the offspring after cross-mating mice with food allergy and oral tolerance. Because OVA-specific IgG, presumed to be from the allergic mother, was detected in the serum of naïve infants from mothers allergic to food, we assumed that the suppression was dependent on a specific IgG. The serum IgG purified by a G-protein column was administered before OVA sensitization in the food allergy model, and OVA-specific IgE production was found to be diminished in the administered mice. However, OVA-specific monoclonal IgG1 and IgG2a administration could not suppress food allergy. Because we detected OVA-IgG immune complex in the serum of mothers allergic to food, it might be a cause of maternal immune suppression. CONCLUSIONS: We demonstrated that maternal specific IgG conjugated food antigen is an important factor related to the development of food allergy and acquiring tolerance.