Immunogenicity and Safety of AS03-adjuvanted H5N1 Influenza Vaccine in Children 6-35 Months of Age: Results From a Phase 2, Randomized, Observer-blind, Multicenter, Dose-ranging Study.

BACKGROUND: This phase 2 observer-blind, randomized, multicenter, dose-ranging study evaluated immunogenicity and safety of different formulations of an AS03-adjuvanted H5N1 influenza vaccine in children 6-35 months of age. METHODS: One hundred eighty-five children randomized into 5 groups [1.9 µg hemagglutinin (HA)/AS03B, 0.9 µg HA/AS03C, 1.9 µg HA/AS03C, 3.75 µg HA/AS03C or 3.75 µg HA/AS03D] were to receive 2 doses administered 21 days apart (primary vaccination). AS03 was classified by amount of DL-α-tocopherol, with AS03B the highest amount. One year later, all subjects were to receive unadjuvanted 3.75 µg HA as antigen challenge. Immunogenicity was assessed 21 days after primary vaccination (day 42) and 7 days after antigen challenge (day 392). Immunogenicity-fever index, based on hemagglutination inhibition and microneutralization antibody titers at day 42 and fever 7 days after each vaccination, was used to guide the selection of an acceptable formulation. RESULTS: After primary vaccination, formulations elicited strong homologous immune responses with all subjects' hemagglutination inhibition titers ≥1:40 post-vaccination. Immunogenicity-fever index based on hemagglutination inhibition and microneutralization assays showed that 1.9 µg HA/AS03B ranked the highest. Antibody levels persisted >4 times above baseline 12 months after primary vaccination with all formulations (day 385). Antibodies increased >4-fold after antigen challenge (day 392/day 385) with 1.9 µg HA/AS03B, 0.9 µg HA/AS03C and 1.9 µg HA/AS03C formulations. Overall per subject, the incidence of fever ranged from 28.6% (3.75 µg HA/AS03D) to 60.5% (1.9 µg HA/AS03B). CONCLUSIONS: All formulations were highly immunogenic and demonstrated acceptable safety profiles, with the 1.9 µg HA/AS03B providing the most favorable balance of immunogenicity versus reactogenicity for use in children 6-35 months of age.

Efficacy and safety of Huaiqihuang granule as adjuvant treatment for primary nephrotic syndrome in children: a meta-analysis and systematic review.

BACKGROUND: Huaiqihuang (HQH) granule is a traditional Chinese herbal complex that has been used as an adjuvant treatment in clinics for the primary nephrotic syndrome (PNS) for many years. However, the effectiveness and safety of HQH have not been systematically discussed. This review aimed to evaluate the effectiveness and safety of HQH in paediatric patients with PNS. METHODS: The following databases were searched from inception to Mar 2019: MEDLINE, Cochrane Library, EMBASE, CNKI, Wanfang Database, the Chinese Scientific Journal Database and the Chinese biomedical literature service system. All the randomized controlled trials (RCTs) eligible for inclusion were included. The primary outcomes were relapse, infection, remission and adverse events. The secondary outcomes included serum immunoglobulin levels (IgA, IgG or IgM), T-lymphocyte subtype (CD3+ , CD4+ , CD8+ , CD4+ /CD8+), IL-10, TNF-α, TNF-γ, total cholesterol and time of proteinuria turning negative. RESULTS: Fourteen RCTs (885 patients) were identified. Treatment with HQH reduced the chance of relapse [relative risk (RR): 0.47; 95% CI: 0.34, 0.66; P < 0.001] and infections (RR: 0.47; 95% CI: 0.35, 0.62; P < 0.001). No significant difference was found in adverse events. HQH also increased the serum levels of IgA [weighted mean difference (WMD): 0.40; 95% CI: 0.20, 0.60; P < 0.001] and IgG (WMD: 1.58; 95% CI: 1.38-1.78; P < 0.001), as well as CD4+ [standard mean difference (SMD): 0.90; 95% CI: 0.12-1.68; P = 0.02], CD3+ (WMD: 4.04; 95% CI: 3.27-4.82; P < 0.001), and the CD4+/CD8+ratio (WMD: 0.31; 95% CI: 0.21-0.41; P < 0.001), but decreased the level of CD8+ cells (WMD: -3.39; 95% CI: -5.73-1.05; P = 0.004). No statistically significant difference was found in IgM (WMD: 0.05; 95% CI: -0.13, 0.24; P = 0.57). CONCLUSIONS: HQH could reduce the rate of relapse and the frequency of infection in children with PNS. No apparent adverse effects were found. Moreover, the beneficial influence of HQH may act through immunomodulation. Additional multi-center, large-sample, high-quality studies are needed to confirm the effectiveness and safety of HQH.

Effects of influenza vaccine and sun exposure time against laboratory-confirmed influenza hospitalizations among young children during the 2012-13 to 2015-16 influenza seasons.

BACKGROUND: Influenza is a major cause of acute respiratory infection burden worldwide, leading to many hospitalizations. An annual influenza vaccine is believed to be the best way to prevent influenza-related illnesses. We focused on the efficacies of other possible preventive measures such as increasing sun exposure time and dietary supplements to prevent these illnesses. METHODS: We conducted a matched-pair case-control study along with the Taiwan Pediatric Infectious Disease Alliance. We included influenza-related hospitalized patients with age ranging from 6 months to 5 years during the 2012-2013, 2013-2014, 2014-2015, and 2015-2016 influenza seasons. The controls were comparable to cases in age, sex, and residential area and had no influenza-related hospitalization records in the same season. We extracted data from vaccination histories and got the patients' guardians to complete questionnaires. Data were analyzed using conditional logistic regression. RESULTS: We enrolled 1514 children (421 influenza-infected cases and 1093 controls) in the study. We found seasonal influenza vaccination to be an independent protective factor against hospitalizations owing to influenza [p < 0.01; odds ratio (OR), 0.427; 95% confidence interval (CI), 0.306-0.594]. Children with mean sun exposure time of >7 h/week had a significantly lower risk of influenza-related hospitalizations than those with the mean sun exposure time of ≤7 h/week (p < 0.05; OR, 0.667; 95% CI, 0.491-0.906). CONCLUSIONS: Seasonal influenza vaccination effectively prevents influenza-related hospitalizations in children aged ≤5 years. Besides, >7 h of sun exposure/week may also be associated with lower risk of influenza-related hospitalizations in children.

[Effects of slope direction on soil nutrient and its ecological stoichiometry in bamboo forest]. / å¡å‘å¯¹æ¯›ç«¹æž—åœŸå£¤å »åˆ†åŠå ¶ç”Ÿæ€åŒ–å­¦è®¡é‡ç‰¹å¾çš„å½±å“.

We analyzed the effects of slope direction on soil nutrients and ecological stoichiometry by collecting soil samples from different slope directions (shady slope and sunny slope) of the bamboo forest in Longyou County, Zhejiang Province. The results showed that soil nutrients were affected by slope direction and soil depth. The nutrients level of soils in the sampling area showed the trends of shady slope > sunny slope, and surface soil > bottom soil. Compared to sunny slope, the cation exchange capacity (CEC), the contents of total organic carbon, total nitrogen, alkaline hydrolyzed nitrogen, available phosphorus, total potassium and available potassium of shady soils significantly increased by 43.7%, 103.8%, 92.0%, 75.5%, 22.4%, 89.4% and 240.7%, respectively. There was no significant difference in total phosphorus contents between shady slope and sunny slope. At all soil layers, there was no significant difference of C/N ratio between shady and sunny slopes. The average C/P ratio of shady slope was 180.8%, 42.0% and 54.3% higher than that of sunny slope at 0-20 cm, 20-40 cm and 40-60 cm, respectively. At each soil layer, the average C/K and N/K ratios between shady and sunny slopes had no significant difference. The average C/K and N/K ratios of shady slope and sunny slope were all significantly different among the three soil layers. In the shady slope, the contents of soil organic carbon showed significantly positive correlation with total nitrogen, total phosphorus, total potassium, and soil available nutrients. Overall, soil nutrients and ecological stoichiometry characteristics of shady slope of bamboo forest were superior to those of sunny slope.

National database study of survival of pediatric congenital heart disease patients in Taiwan.

BACKGROUND/PURPOSE: The incidence of congenital heart disease (CHD) and severe CHD is 13.08 and 1.51/1000 live births, respectively, in Taiwan, which has had national health insurance since 1995 and child health indices similar to those in the US. This study sought to further elucidate the fatality of CHD patients and their survival from a national database. METHODS: From the national health insurance database 2000-2010, we retrieved data from CHD patients who were diagnosed at age <6 years. The survival status at discharge was ascertained for estimation of survival. RESULTS: In total, 18,843 pediatric CHD patients were identified. The overall prevalence of CHD was 1288 per 100 000 live-births. Severe CHD (tetralogy of Fallot (4.4%), transposition of the great arteries (1.6%) and double outlet right ventricle (1.1%)) accounted for 11.5% of all cases. The 1-month/5-year survival in simple and severe CHD was 99.1%/97.5% and 90.2%/76.4%, respectively (p < 0.0001). The Kaplan-Meier survival at 5 years of age was lowest for hypoplastic left heart syndrome (19.7%), followed by transposition of the great arteries (66.7%), double outlet right ventricle (69.0%), and common ventricle (66.0%). The 5-year survival of the birth cohort in the same study period was 99.3%. CONCLUSION: This national database study revealed that the survival of children with simple CHD was still slightly lower than that of the general population and the survival of severe CHD patients, though only accounting for one-tenth of CHD cases, remained unsatisfactory. Such survival profiles are similar to those from Western reports and warrant a refined and dedicated medical care program for children with CHD.

Drug susceptibility and treatment response of common urinary tract infection pathogens in children.

BACKGROUND/PURPOSE: To document the trends of sensitivity and to find whether it is necessary to change antibiotics in selected patients according to the sensitivity test results in our clinical practice. METHODS: We collected urine culture results from 0-18-year-old patients in the National Taiwan University Hospital from January 1, 2003 to October 31, 2012. Their medical chart was reviewed to identify true pathogens responsible for their urinary tract infection (UTI). We checked the percentage of susceptibility of these pathogens to ampicillin, amoxicillin-clavulanate (AMC), cefazolin, cefmetazole, ceftriaxone, gentamicin, and trimethoprim-sulfamethoxazole (TMP-SMX) according to the Clinical and Laboratory Standards Institute (CLSI) guideline. The extended-spectrum-beta-lactamases (ESBLs) rate was also checked. In addition, we reviewed the treatment response of different antibiotics. Defervescence within 48 hours after initial antibiotics use was considered responsive. RESULTS: A total of 7758 urine cultures positive for Escherichia coli infection were collected during the 10-year period. The E. coli cefazolin susceptibility rate was 62-73% during 2003-2010, but it dropped to 23% in 2011 and 28% in 2012 after the new CLSI guideline (M100-S21) was released. However, other antibiotics did not show a significant difference. In UTI caused by E. coli, on average, the sensitivity rates for various antibiotics were as follows: cefmetazole, 90%; ceftriaxone, 85%; gentamicin, 77%; AMC, 61%; TMP-SMX, 47%; and ampicillin, 20%. The ESBL rate was also found to increase (2-11%; p < 0.01). The overall response rate of UTI caused by E. coli to first-line antibiotics such as first-generation cephalosporin and/or gentamicin was 78%. CONCLUSION: The susceptibility of common urinary tract pathogens to cefazolin has decreased dramatically since 2010. This trend may be due to the change in the CLSI guideline. Although the susceptibility rate to first-line empirical antibiotics shows a decreasing trend, we found that the clinical response was acceptable for our first-line empirical antibiotics.