Optimising the introduction of multiple childhood vaccines in Japan: A model proposing the introduction sequence achieving the highest health gains.

BACKGROUND: Many countries struggle with the prioritisation of introducing new vaccines because of budget limitations and lack of focus on public health goals. A model has been developed that defines how specific health goals can be optimised through immunisation within vaccination budget constraints. METHODS: Japan, as a country example, could introduce 4 new pediatric vaccines targeting influenza, rotavirus, pneumococcal disease and mumps with known burden of disease, vaccine efficacies and maximum achievable coverages. Operating under budget constraints, the Portfolio-model for the Management of Vaccines (PMV) identifies the optimal vaccine ranking and combination for achieving the maximum QALY gain over a period of 10 calendar years in children <5 years old. This vaccine strategy, of interest and helpful for a healthcare decision maker, is compared with an unranked vaccine selection process. RESULTS: Results indicate that the maximum QALY gain with a fixed annual vaccination budget of 500 billion Japanese Yen over a 10-year period is 72,288 QALYs using the optimal sequence of vaccine introduction (mumps [1st], followed by influenza [2nd], rotavirus [3rd], and pneumococcal [4th]). With exactly the same budget but without vaccine ranking, the total QALY gain can be 20% lower. CONCLUSION: The PMV model could be a helpful tool for decision makers in those environments with limited budget where vaccines have to be selected for trying to optimise specific health goals.

Successful every-other-day liothyronine therapy for severe resistance to thyroid hormone beta with a novel THRB mutation; case report.

BACKGROUND: Resistance to thyroid hormone beta (RTHß) is a rare and usually dominantly inherited syndrome caused by mutations of the thyroid hormone receptor ß gene (THRB). In severe cases, it is rarely challenging to control manifestations using daily therapeutic replacement of thyroid hormone. CASE PRESENTATION: The present case study concerns an 8-year-old Japanese girl with a severe phenotype of RTH (TSH, fT3, and fT4 were 34.0 mU/L, >25.0 pg/mL and, >8.0 ng/dL, respectively), caused by a novel heterozygous frameshift mutation in exon 10 of the thyroid hormone receptor beta gene (THRB), c.1347-1357 del actcttccccc : p.E449DfsX11. RTH was detected at the neonatal screening program. At 4 years of age, the patient continued to suffer from mental retardation, hyperactivity, insomnia, and reduced resting energy expenditure (REE), despite daily thyroxine (L-T4) therapy. Every-other-day high-dose liothyronine (L-T3) therapy improved her symptoms and increased her REE, without thyrotoxicosis. CONCLUSION: In a case of severe RTH, every-other-day L-T3 administration enhanced REE and psychomotor development, without promoting symptoms of thyrotoxicosis. Every-other-day L-T3 administration may be an effective strategy for the treatment of severe RTH.

Bilirubin uridine diphosphate-glucuronosyltransferase variation is a genetic basis of breast milk jaundice.

OBJECTIVE: To evaluate the role of bilirubin UDP-glucuronosyltransferase family 1, polypeptide A1 (UGT1A1) gene variations on prolonged unconjugated hyperbilirubinemia associated with breast milk feeding (breast milk jaundice [BMJ]). STUDY DESIGN: UGT1A1 gene allelic variation was analyzed in 170 Japanese infants with BMJ with polymerase chain reaction-direct sequencing, and their genotypes compared with serum bilirubin concentrations. In 62 of 170 infants, serum bilirubin concentration was followed after 4 months of life. Genotypes were examined in 55 infants without BMJ. RESULTS: Of 170 infants with BMJ, 88 (51.8%) were homozygous UGT1A1*6. Serum bilirubin concentrations (21.8 ± 3.65 mg/dL) were significantly greater than in infants with other genotypes (P < .0001). The Gilbert UGT1A1*28 allele was not detected in infants with BMJ, except in an infant who was compound heterozygous with UGT1A1*6. At 4 months of age, serum bilirubin concentration improved to >1 mg/dL, except in 2 infants who were homozygous UGT1A1*7. Homozygous UGT1A1*6 was not detected in the control group. CONCLUSION: One-half of the infants with BMJ were homozygous UGT1A1*6 and exhibited a serum bilirubin concentration significantly greater than other genotypes. This finding indicates that UGT1A1*6 is a major cause of BMJ in infants in East Asia. Previous finding have demonstrated that 5ß-pregnane-3α,20ß-diol present in breast milk inhibits p.G71R-UGT1A1 bilirubin glucuronidation activity. Thus, prolonged unconjugated hyperbilirubinemia may develop in infants with UGT1A1*6 who are fed breast milk.