Effects of vitamin D supplements on influenza A illness during the 2009 H1N1 pandemic: a randomized controlled trial.

In a prior randomized trial, we found that the incidence of influenza A was less in the vitamin D3 group than among those on placebo, but the total incidence of either influenza A or B did not differ between groups. In this trial, the incidence of influenza A or B was less in the vitamin D3 group than in the placebo group only during the first half of the study. To elucidate whether vitamin D3 has preventive actions against influenza A, we conducted another trial during the 2009 pandemic of the H1N1 subtype of influenza A. Students (n = 247) of a Japanese high school were randomly assigned to receive vitamin D3 supplements (n = 148; 2000 IU per day) or a placebo (n = 99) in a double-blind study for 2 months. The primary outcome was incidence of influenza A diagnosed by a rapid influenza diagnostic test by medical doctors. Influenza A was equally likely in the vitamin D3 group (20/148: 13.5%) compared with the placebo group (12/99: 12.1%). By post hoc analysis, influenza A occurred significantly less in the vitamin D3 group (2/148: 1.4%) compared with the placebo group (8/99: 8.1%) (risk ratio, 0.17; 95% confidence interval, 0.04 to 0.77; P = 0.009) in the first month. However, during the second month, the vitamin D3 group experienced more events and effectively caught up with the placebo group. Vitamin D3 supplementation did not lower the overall incidence of influenza A during the 2009 H1N1 pandemic. A post hoc analysis suggests that the initial benefit during the first month of treatment was lost during the second month.

Distinct effects of alcohol consumption and smoking on genetic alterations in head and neck carcinoma.

BACKGROUND: Tobacco and alcohol consumption are risk factors for head and neck squamous cell carcinoma (HNSCC). Recently, whole-exome sequencing clarified that smoking increased TP53 and other mutations in HNSCC; however, the effects of alcohol consumption on these genetic alterations remain unknown. We explored the association between alcohol consumption and somatic copy-number alterations (SCNAs) across the whole genome in human papillomavirus (HPV)-negative HNSCCs, and compared with the effects of smoking on genetic alterations. METHODS: SCNA and TP53 mutations in tumor samples were examined by high-resolution comparative genomic hybridization microarray 180K and by direct sequencing, respectively, and statistically analyzed for associations with alcohol consumption and smoking during the 20 years preceding diagnosis of HNSCC. Probes with a corrected p-value (=q-value) less than 0.05 and fold change greater than 1.2 or less than -1.2 were considered statistically significant. RESULTS: A total of 248 patients with HNSCC were enrolled. In the HPV-negative patients (n=221), heavy alcohol consumption was significantly associated with SCNAs of oncogenes/oncosuppressors that were previously reported to occur frequently in HNSCCs: CDKN2A (q=0.005), FHIT (q=0.005), 11q13 region including CCND1, FADD and CTTN (q=0.005), ERBB2 (HER2) (q=0.009), 3q25-qter including CCNL1, TP63, DCUN1D1 and PIK3CA (q=0.014), and CSMD1 (q=0.019). But, TP53 mutations were not affected. In contrast, smoking was associated with increased risk of TP53 mutations, but did not induce any significant SCNAs of oncogenes/oncosuppressors. CONCLUSION: These results suggest that both alcohol consumption and smoking had distinct effects on genetic alterations in HNSCCs. Heavy alcohol consumption may trigger previously known and unknown SCNAs, but may not induce TP53 mutation. In contrast, smoking may induce TP53 mutation, but may not trigger any SCNAs.

Randomized, double-blind, placebo-controlled trial of vitamin D supplementation in Parkinson disease.

BACKGROUND: In our previous study, higher serum 25-hydroxyvitamin D [25(OH)D] concentrations and the vitamin D receptor (VDR) FokI CC genotype were associated with milder Parkinson disease (PD). OBJECTIVE: We evaluated whether vitamin D3 supplementation inhibits the progression of PD on the basis of patient VDR subgroups. DESIGN: Patients with PD (n = 114) were randomly assigned to receive vitamin D3 supplements (n = 56; 1200 IU/d) or a placebo (n = 58) for 12 mo in a double-blind setting. Outcomes were clinical changes from baseline and the percentage of patients who showed no worsening of the modified Hoehn and Yahr (HY) stage and Unified Parkinson's Disease Rating Scale (UPDRS). RESULTS: Compared with the placebo, vitamin D3 significantly prevented the deterioration of the HY stage in patients [difference between groups: P = 0.005; mean ± SD change within vitamin D3 group: +0.02 ± 0.62 (P = 0.79); change within placebo group: +0.33 ± 0.70 (P = 0.0006)]. Interaction analyses showed that VDR FokI genotypes modified the effect of vitamin D3 on changes in the HY stage (P-interaction = 0.045), UPDRS total (P-interaction = 0.039), and UPDRS part II (P-interaction = 0.021). Compared with the placebo, vitamin D3 significantly prevented deterioration of the HY stage in patients with FokI TT [difference between groups: P = 0.009; change within vitamin D3 group: -0.38 ± 0.48 (P = 0.91); change within placebo group, +0.63 ± 0.77 (P = 0.009)] and FokI CT [difference between groups: P = 0.020; change within vitamin D3 group: ±0.00 ± 0.60 (P = 0.78); change within placebo group: +0.37 ± 0.74 (P = 0.014)] but not FokI CC. Similar trends were observed in UPDRS total and part II. CONCLUSION: Vitamin D3 supplementation may stabilize PD for a short period in patients with FokI TT or CT genotypes without triggering hypercalcemia, although this effect may be nonspecific for PD. This trial was registered at UMIN Clinical Trials Registry as UMIN000001841.

25-hydroxyvitamin D, vitamin D receptor gene polymorphisms, and severity of Parkinson's disease.

We aimed to examine associations among serum 25-hydroxyvitamin D levels, 1,25-dihyroxyvitamin D levels, vitamin D receptor polymorphisms, vitamin D binding protein gene polymorphisms, and the severity of Parkinson's disease. In 137 patients, the severity of Parkinson's disease was evaluated using Hoehn & Yahr stage and Unified Parkinson's Disease Rating Stage by neurologists and compared with 25-hydroxyvitamin D, 1,25-hydroxyvitamin D, vitamin D receptor polymorphisms, ie, FokI (rs10735810), BsmI (rs1544410), Cdx2 (rs11568820), ApaI (rs7976091), and TaqI (rs731236), and vitamin D binding protein gene polymorphisms GC1 (rs7041)/GC2 (rs4588) in a cross-sectional study. Mean ± standard deviation levels of 25-hydroxyvitamin D were 21.1 ± 9.0 ng/mL. Levels were deficient (<20 ng/mL) in 49% of patients. In contrast, 1,25-hydroxyvitamin D levels were considered normal in all patients. Higher circulating 25-hydroxyvitamin D levels were significantly associated with milder Parkinson's disease evaluated by Hoehn & Yahr stage (P = .002) and total Unified Parkinson's Disease Rating Stage (P = .004) even after multivariate adjustment for 8 covariates, including disease duration. However, significant associations were not observed in 1,25-hydroxyvitamin D levels. Under multivariate analysis with 25-hydroxyvitamin D as well as other 8 covariates including disease duration, carriers of vitamin D receptor FokICC genotype had a milder form of Parkinson's disease: odds ratio, 0.32; 95% confidence interval, 0.16 to 0.66, P = 0.002. These results suggest that higher 25-hydroxyvitamin D levels and the vitamin D receptor FokICC genotype may be independently associated with milder forms of Parkinson's disease. However, significant associations were not observed in 1,25-hydroxyvitamin D levels.

Bimodal effects of obesity ratio on disease duration of respiratory syncytial virus infection in children.

BACKGROUND: Morbid obesity may be associated with hospitalization and possibly death from the 2009 pandemic H1N1 infection, suggesting a yet unknown association between obesity and the severity of viral infections. Thus, we examined association between obesity ratios and duration of disease in children with Respiratory Syncytial Virus (RSV) infection. METHODS: A retrospective survey of 243 children admitted for bronchitis, bronchiolitis, pneumonia, and those who tested positive for a RSV test, were observed from a single institute in Japan. Primary outcome was set as the total days of wheezing in both the outpatient clinic and during hospitalization. Secondary outcomes were as follows: 1) total days of fever (37.5°C≤) during hospitalization, and 2) days of drip infusion during hospitalization. RESULTS: When the obesity ratio was 6 and less, days of wheezing showed significant negative association with obesity ratios. In contrast, when the obesity ratio was more than 6, days of wheezing, days of fever during admission and days of drip infusion showed significant positive association with obesity ratios. CONCLUSIONS: These results suggest that disease duration of RSV infection may be prolonged not only in lean but also in obese children.

An association of gastroschisis and fatal respiratory distress: does prenatal bile aspiration cause early-onset respiratory failure in neonates?

We present a neonate with gastroschisis and evidence of bile aspiration in utero, who developed severe respiratory distress that did not respond to postnatal intensive respiratory care. Although rare, a newborn with gastroschisis may develop severe respiratory distress due to bile aspiration in utero. Given the poor outcome in this case, we suggest a possible role for prenatal diagnosis and therapy.