Cytokine IL-5 and HGF: combined prediction of non-/low immune response to hepatitis B vaccination at birth in infants born to HBsAg-positive mothers.

Background: The immune response to hepatitis B vaccine may be influenced by numerous factors, and patients with non/low response re-exposed to hepatitis B virus remain susceptible. Thus, a better understanding of the underlying mechanisms of non/low immune response in infants born to Hepatitis B surface antigen (HBsAg)-positive mothers is essential. Methods: 100 infants born to HBsAg-positive mothers from 2015 to 2020 were enrolled in the study, further divided into the non/low response group (n=13) and the moderate strong response group (n=87) based on the quantification of hepatitis B surface antibody at 12 months of age. The differential expression of 48 immune-related cytokines in the two groups was compared and analyzed in detail. The key cytokines were further identified and clinically predictive models were developed. Results: We found that 13 cytokines were lowly expressed and one cytokine was highly expressed in the non/low response group, compared with the moderate strong response group at birth. In addition, 9 cytokines were lowly expressed and one cytokine was highly expressed in the non/low response group at 12 months of age. Furthermore, we found that IL-5 and HGF were promising predictors for predicting the immunization response to hepatitis B vaccine in infants, and the combination of the two cytokines showed the best predictive efficiency, with an area under the curve (AUC) value of 0.844. Conclusion: The present study provides a theoretical basis on cytokines for developing and implementing effective immunotherapies against non/low immune response in infants born to HBsAg-positive mothers.

Low responders may benefit from undergoing ovarian stimulation with a long GnRH agonist protocol with corifollitropin alfa followed by hMG.

OBJECTIVE: To evaluate the outcomes of a long GnRH agonist protocol with corifollitropin alfa followed by hMG in low responders. METHODS: Retrospective cohort study. Patients with a suboptimal previous ovarian response (<9 oocytes) and a normal ovarian reserve (Poseidon groups 1 and 2) were classified in 1) Group 1 (n=88), submitted to a second cycle with a GnRH antagonist protocol using rFSH/hMG; 2) Group 2 (n=66), submitted to a long GnRH agonist protocol with corifollitropin alfa followed by hMG (named as simplified long protocol). Clinical outcomes were compared between groups and between the first/second cycle of each group. RESULTS: Clinical outcomes were similar between groups. There were no differences in the number of oocytes [7(5-11.75) versus 7(5-10), p=0.802], clinical pregnancy (19.3% versus 18.2%, p=0.858) and live birth rates (18.2% versus 15.2%, p=0.619). However, baseline characteristics were different, decoding a poor prognosis among women in group 2. Both groups (1 and 2) had significantly higher number of oocytes, pregnancy, and live birth rates in the second cycle. In group 2, there was a higher rate of embryo transfer (56.1% versus 27.3%, p<0.001). In group 1, despite the similar rate of embryo transfer, there was a higher positive hCG (23.9% versus 8.0%, p=0.004). CONCLUSIONS: Both simplified long protocol and GnRH antagonist protocol are suitable for low responders. The best second cycle clinical outcomes experienced in a population with worse prognosis (group 2) suggests that the simplified long protocol may be a better option, although prospective well-conducted studies must explore this hypothesis.

Mechanism of Guilu Erxian ointment based on targeted metabolomics in intervening in vitro fertilization and embryo transfer outcome in older patients with poor ovarian response of kidney-qi deficiency type.

Objective: To study the effect of Guilu Erxian ointment on the outcome of IVF-ET in older patients with poor ovarian response infertility of kidney-qi deficiency type, and to verify and analyze the mechanism of action of traditional Chinese medicine on improving older patients with poor ovarian response infertility of kidney-qi deficiency type from the perspective of metabolomics using targeted metabolomics technology, identify the related metabolic pathways, and provide metabolic biomarker basis and clinical treatment ideas for improving older patients with poor ovarian response infertility. Methods: This study was a double-blind, randomized, placebo-controlled trial, and a total of 119 infertile patients who underwent IVF-ET at Shandong Center for Reproduction and Genetics of Integrated Traditional Chinese and Western Medicine were selected. Eighty older patients with infertility undergoing IVF were randomly divided into older treatment group and older placebo group, and another 39 young healthy women who underwent IVF-ET or ICSI due to male factors were selected as the normal control group. Flexible GnRH antagonist protocol was used for ovulation induction in all three groups, and Guilu Erxian ointment and placebo groups started taking Guilu Erxian ointment and placebo from the third day of menstruation until IVF surgery. And ultra-high performance liquid chromatography-triple quadrupole mass spectrometer (UHPLC-QTRAP MS) was used to detect metabolites in the three groups of samples. Results: Compared with the placebo group, the number of oocytes retrieved, 2PN fertilization, high-quality embryos, total number of available embryos and estrogen on HCG day were increased in the treatment group, and the differences were statistically significant (P > 0.05), but the clinical pregnancy rate of fresh embryos and frozen embryos were not statistically significant (P > 0.05). The results of targeted metabolomics analysis showed that follicular fluid in the treatment group clustered with the normal young group and deviated from the placebo group. A total of 55 significant differential metabolites were found in the follicular fluid of older patients with poor ovarian response of kidney-qi deficiency type and patients in the normal young group, after Guilu Erxian ointment intervention, Metabolites such as L-Aspartic acid, Glycine, L-Serine, Palmitoleic Acid, Palmitelaidic acid, L-Alanine, Gamma-Linolenic acid, Alpha-Linolenic Acid, and N-acetyltryptophan were down-regulated, mainly involving amino acid metabolism and fatty acid metabolism. Conclusion: Guilu Erxian ointment can effectively improve the clinical symptoms and IVF outcomes of older patients with poor ovarian response of kidney-qi deficiency type. There were differences in follicular fluid metabolites between older patients with poor ovarian response of kidney-qi deficiency type and normal women. L-Aspartic acid, L-Alanine, Aminoadipic acid, L-Asparagine, L-Arginine, L-Serine, Gamma- Linolenic acid, Pentadecanoic acid and Alpha-Linolenic Acid are closely related to older patients with poor ovarian response due to deficiency of kidney-qi and may be inferred as biomarkers. The mechanism of Guilu Erxian ointment intervention may be mainly through amino acid metabolism and fatty acid metabolism regulation.

Quantitative analysis of immune responses to hepatitis B vaccination in children in Hangzhou and discussion on age of booster immunization / 中华实用儿科临床杂志

Objective:To investigate the appropriate age for booster doses of hepatitis B vaccine in children aged 0-14.Methods:Retrospective study.A total of 3 118 children aged 0-14 years who underwent quantitative serological marker testing for hepatitis B virus at the Affiliated Hospital of Hangzhou Normal University from January 2015 to October 2021 were recruited in this analysis.There were 1 702 males and 1 416 females, with a male to female ratio of 1.20∶1.00.Children were divided into 15 groups according to their age, and the classifying interval was 1 year.The hepatitis B virus surface antibody (Anti-HBs) titer was quantified by chemiluminescent microparticle immunoassay.The Anti-HBs positivity rates and hepatitis B immune response among groups of different sexes and age were compared by the chi- square test and rank- sum test, respectively. Results:A total of 3 118 children were investigated.The titer and effective response rate of Anti-HBs decreased gradually with age.The difference in the titer and effective response rate of Anti-HBs was statistically significant among groups of different age (all P<0.01), but not significant between males and females (all P>0.05). The median titer of Anti-HBs in children aged above 3 years was 58.49 IU/L(0-1 001.00 IU/L). About 59.1% (1 477/2 497 cases) of children aged 3 years and above had no immune response or low immune response (i.e., the titer of Anti-HBs was below 100 IU/L). Conclusions:The immune protective effect of the hepatitis B vaccine decreases year by year in children who have received the standardized vaccine, and the vaccine has poor protective effect on most children aged 3 years and above.Therefore, booster dose vaccination for preventing hepatitis B is necessary for children aged 3 and above.

[Evaluation of treatment adaptation for low response to ASA in vascular surgery]. / Evaluation einer Therapieanpassung bei ASS-Low-Response in der Gefäßchirurgie.

BACKGROUND: A decreased antiplatelet prophylaxis (low response, LR/high on-treatment platelet reactivity, HPR) with acetylsalicylic acid (ASA) is associated with an increased risk of thromboembolic events. The prevalence of a LR is frequent with about 20% and a therapeutic regimen is not yet established. The aim of this prospective study was to evaluate the effectiveness of a therapeutic regimen for treatment adaptation when LR/HPR is detected in vascular surgery patients. METHODS: Overall, 36 patients under long-term antiplatelet treatment with 100 mg/day ASA and a detected ASA low response (ALR) were included in the study. In this patient group a modification of the prophylactic medication was carried out according to the established treatment plan and a control aggregometry was performed. The therapeutic regimen followed the test and treat principle. To evaluate the effect of ASA impedance, aggregometry with multiple electrodes was used (multiplate). RESULTS: All 36 patients were successfully transferred to response status with the treatment scheme. In 32 (88.89%) patients an increased dose of 300 mg/day ASA was carried out and in 2 (5.56%) patients the medication was changed from ASA to clopidogrel. A further 2 (5.56%) patients were switched to oral anticoagulation with phenprocoumon, due to other indications. Bleeding complications or other side effects did not occur. CONCLUSION: The chosen treatment regime for a low response proved to be effective and safe in vascular surgery patients. A guideline-compliant increase of the ASA dose from 100 mg to 300 mg/day predominantly led to an effective inhibition of platelet aggregation in the aggregometry.

Serum uric acid level negatively correlated with the prevalence of clopidogrel low response in patients undergoing antiplatelet treatment with aspirin and clopidogrel.

BACKGROUND AND AIMS: It has been reported that elevated serum uric acid (SUA) is related to inflammation and potentially to platelet hyper-reactivity. However, the relationship between elevated SUA and residual platelet reactivity is uncertain in patients on dual antiplatelet treatment (DAPT) with aspirin and clopidogrel. METHODS AND RESULTS: A cross-sectional cohort study was conducted on 2569 patients undergoing DAPT with aspirin and clopidogrel. Patients' SUA levels, residual platelet aggregation, routine blood tests and clinical characteristics were recorded. The relationship between SUA level and residual platelet aggregation was assessed by correlation analysis, and the relationship between SUA level and the prevalence of clopidogrel low response (CLR) was assessed by multivariate logistic regression analysis. Adenosine diphosphate (ADP) induced platelet aggregation (PLADP) was higher in normal-SUA group than that in hyperuricemia group [30(21, 40) % vs. 27(19, 39) %, p = 0.032]. No significant difference was found for arachidonic acid (AA) induced platelet aggregation (PLAA) between the two groups [4(2, 5) % vs. 3(2, 5) %, p = 0.557]. The correlation between SUA and PLADP was statistically significant(r = -0.115, p < 0.001), while that between SUA and PLAA was non-significant (r = -0.012, p = 0.643). Using the multivariate logistic regression analysis, higher SUA concentration was associated with a decreased risk of clopidogrel low response (CLR) (OR [95%CI] = 0.997 [0.995-0.999], p = 0.001). CONCLUSION: This is the largest study to date showing that in patients receiving DAPT with aspirin and clopidogrel, SUA is independently and negatively associated with the prevalence of clopidogrel low response. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov Unique Identifier: NCT01955200.

Missing-data analysis: socio- demographic, clinical and lifestyle determinants of low response rate on self- reported psychological and nutrition related multi- item instruments in the context of the ATTICA epidemiological study.

BACKGROUND: Missing data is a common problem in epidemiological studies, while it becomes more critical, when the missing data concern a multi-item instrument, since lack of information in even one of its items, leads to the inability to calculate the total score of the instrument. The aim was to investigate the socio-demographic, lifestyle and clinical determinants of low response rate in two self- rating multi item scales, estimating the individuals' nutritional habits and psychological disorders, as well as, to compare different missing data handling techniques regarding the imputation of missing values in this context. METHODS: The sample from ATTICA epidemiological study was used, with complete baseline information (2001-2002) regarding their demographic characteristics [n = 2194 subjects (1364 men: 64 years old (SD = 12 years) and 830 women: 66 years old (SD = 12 years))]. Adherence to the Mediterranean diet and depressive symptomatology were assessed at baseline, with the MedDietScore scale and the Zung's Self- rating Depression Scale (SDS), respectively. Logistic and Poisson regression analysis were used, in order to explore the low response's determinants in each scale. Seven missing data handling techniques were compared in terms of the estimated regression coefficients and their standard errors, under different scenarios of missingness, in the context of a multivariable logistic regression model examining the association of each scale with the participants' likelihood of being hypertensive. RESULTS: Older age, lower educational level, poorer health status and unhealthy lifestyle habits, were found to be significant determinants of high nonresponse rates, both in the MedDietScore scale and the Zung's SDS. Female participants were more likely to have missing data in the items of the MedDietScore scale, while a significantly higher number of missing items in the depression scale was found for male participants. Concerning the analysis of such data, multiple imputation was found to be the most effective technique, even when the number of missing items was large. CONCLUSIONS: The present work augments prior evidence that higher non-response to health surveys is significantly affected by responders' background characteristics, while it gives rise to research towards unrevealed paths behind this claim, especially in the era of nutritional epidemiology.

Getting to the Heart of Low Sensitivity to Alcohol: Context Moderates Low Cardiovascular Response to Alcohol in Persons With a Family History of Alcohol Use Disorder.

BACKGROUND: Low sensitivity to alcohol in persons with a family history of alcoholism (FH+), compared to those without (FH-), contributes to risk for alcohol use disorder (AUD). However, sensitivity of FH+ cardiovascular response to alcohol is not well understood. This gap is significant because cardiovascular processes contribute to emotional regulation and stress response problems theorized to be central to the development and persistence of AUD. This study compared changes in heart rate (HR) and HR variability (HRV) between FH groups after consuming alcohol and control beverages and examined how these changes were moderated by emotional and alcohol-related contexts. METHODS: Young adults (N = 165) with FH+ (n = 110) or FH- (n = 55) each completed 2 sessions, separated by 1 week. They received one of 3 different beverages (alcohol, placebo, and told-no-alcohol) in each session. Electrocardiogram data were recorded during pre-beverage consumption and post-beverage consumption baselines, and then during 4 picture cue tasks (neutral, positive, negative, and alcohol-related). Generalized estimating equations were used to examine differences in cardiovascular reactivity (changes in HR and HRV power at ~ 0.1 Hz) across FH groups, beverage conditions, and picture cue tasks. RESULTS: A significant beverage condition × cue task × FH interaction effect on HRV was observed. The FH+ group, compared to the FH- group, showed (a) significantly less HRV suppression in specific cue contexts following alcohol, (b) a mixed pattern of more and less HRV suppression across cue contexts following placebo, and (c) a similar HRV reactivity pattern in the told-no-alcohol condition across cue tasks. For HR, there were no significant effects involving FH. CONCLUSIONS: Diminished cardiovascular sensitivity to oral alcohol in FH+ persons varied within a given drinking episode depending on emotional and alcohol-related features of the context, suggesting that environmental characteristics play a role in the expression of low sensitivity to alcohol among FH+ individuals.

Influence of Addition and Subtraction Therapy of Guyinjian to Ovarian Reserve Function for Patients with Poor Ovarian Response with Kidney Yin Deficiency Syndrome / 中国实验方剂学杂志

Objective:To observe the effect of addition and subtraction therapy of Guyinjian on oocyte quality, pregnancy outcome and ovarian reserve function in patients with poor ovarian response (POR) with kidney Yin deficiency syndrome. Method:Ninety patients were randomly divided into control group (45 cases) and observation group (45 cases) by random number table. The patients in both groups got antagonist. Based on such treatment, the patients in observation received additional addition and subtraction therapy of Guyinjian. The using time and amount of gonadotropin (Gn), ovum taking cycle, cycle canceling rate, fertilization rate, available embryo rate, quality embryo rate, ovulation cycle clinical pregnancy rate were recorded. Levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), serum estradiol (E2) and endometrial thickness, anti mullerian hormone (AMH), resistance index (RI), pulsation index (PI), end diastolic velocity (EDV) and peak systolic velocity (PSV) were detected. Ratio of PSV/EDV (S/D) was calculated, and scores of kidney yin deficiency syndrome were graded before and after treatment. Result:Total amount of Gn in observation group was less than that in control group (PP2 were higher than those in control group (PPPχ2=5.124, Pχ2=5.767, PPPPPConclusion:Addition and subtraction therapy of Guyinjian can increase ovarian blood supply, improve high ovarian reserve function, reduce Gn consumption, increase number of acquired eggs, alleviate symptoms of kidney yin deficiency, and can ameliorate ovarian responsiveness and pregnancy outcome.

Mitogen-activated protein kinase eight polymorphisms are associated with immune responsiveness to HBV vaccinations in infants of HBsAg(+)/HBeAg(-) mothers.

BACKGROUND: Infants born to hepatitis B surface antigen (HBsAg) positive mothers are at a higher risk for Hepatitis B virus (HBV) infection. Host genetic background plays an important role in determining the strength of immune response to vaccination. We conducted this study to investigate the association between Tumor necrosis factor (TNF) and Mitogen-activated protein kinase eight (MAPK8) polymorphisms and low response to hepatitis B vaccines. METHODS: A total of 753 infants of HBsAg positive and hepatitis Be antigen (HBeAg) negative mothers from the prevention of mother-to-infant transmission of HBV cohort were included. Five tag single nucleotide polymorphism (SNPs) (rs1799964, rs1800629, rs3093671, rs769177 and rs769178) in TNF and two tag SNPs (rs17780725 and rs3827680) in MAPK8 were genotyped using the MassARRAY platform. RESULTS: A higher percentage of breastfeeding (P = 0.013) and a higher level of Ab titers were observed in high responders (P < 0.001). The MAPK8 rs17780725 AA genotype increased the risk of low response to hepatitis B vaccines (OR = 3.176, 95% CI: 1.137-8.869). Additionally, subjects with the AA genotype may have a lower Ab titer than subjects with GA or GG genotypes (P = 0.051). Compared to infants who were breastfed, infants who were not breastfed had an increased risk of low response to hepatitis B vaccine (OR = 2.901, 95% CI:1.306-6.441). CONCLUSIONS: MAPK8 polymorphisms are associated with immune response to HBV vaccinations in infants of HBsAg(+)/HBeAg(-) mothers.

Impact of hepatitis B virus (HBV) infection on platelet response to clopidogrel in patients undergoing coronary stent implantation.

BACKGROUND: Hepatitis B virus (HBV) infection has been reported to down-regulate the expression of CYP2C19 gene, which may decrease the bioactivation of clopidogrel into active metabolites. We aimed to evaluate the impact of HBV infection on platelet response to clopidogrel in patients undergoing coronary stent implantation. METHODS: A total of 1805 patients who had received coronary stent implantation and taken aspirin 100 mg in combination with clopidogrel 75 mg daily ≥5 days were consecutively recruited. The serologic identifications for HBV, platelet aggregations in response to arachidonic acid (PLAA) and adenosine diphosphate (PLADP), as well as ABCB1, CYP2C19, CYP3A5, PON1 and P2RY12 genotypes were determined. Clopidogrel low response (CLR) was defined as PLADP > 40%. RESULTS: Among the recruited subjects, 102 patients showed hepatitis B surface antigen (HBsAg) positive and 1703 patients negative. PLADP was significantly higher in HBsAg positive group than that in HBsAg negative group [38 (24-48) % vs. 29 (20-39) %, p < 0.001] while the difference of PLAA was not statistically significant (p = 0.329). The incidence of CLR was significantly higher in HBsAg positive group compared with that in HBsAg negative group (43.1% vs. 23.4%, p < 0.001). After adjusted for CYP2C19 genotype and known risk factors, HBsAg positive patients exhibited a significantly higher risk of CLR (adjusted odds ratio: 2.81, 95% confidence interval: 1.73 to 4.58, p < 0.001). CONCLUSIONS: HBV infection is an independent risk factor of CLR, in addition to CYP2C19 gene mutations. (Pharmacogenetic and Pharmacokinetic Study of Clopidogrel; NCT01968499).

[Influencing factors for non/low-response to hepatitis-B vaccine in infants of HBsAg positive mothers].

Objective: To investigate the influencing factors for non/low-response to hepatitis B vaccine in infants of HBsAg-positive mothers. Methods: A total of 286 HBsAg-positive pregnant women and their infants were recruited from the Third People's Hospital of Taiyuan during July 2011 to January 2013. The infants were immunized with hepatitis B vaccine according to the 0-1-6 month vaccination schedule and followed up for 12 months. The serum HBV DNA level of mothers, neonates and infants were detected by electro chemilum inescence immunoassay kits and fluorescene quantiative polymerase chain rection. Results: Among 286 infants, the rate of non/low-response to hepatitis B vaccine was 18.53% (53/286). Non-conditional logistic regression analysis indicated that the mother's HBV DNA level ≥1×10(7) copies/ml (OR=2.592, 95%CI: 1.121-5.996) and natural birth (OR=1.932, 95%CI: 1.021-3.654) were the risk factors for non/low-response to hepatitis B vaccine, the risks were 2.592 times and 1.932 times higher compared with the infants whose mothers were HBV DNA negative and the infants whose mothers had cesarean delivery. There was no multiplicative or additive interaction between high HBV DNA load and natural birth (OR=1.055, 95%CI: 0.209-5.321), (RERI=1.617, 95%CI: -4.038-7.272; AP=0.364, 95%CI: -0.527-1.225; SI=1.195, 95%CI: 0.270-13.135). After stratified analysis of mother's HBV DNA level, delivery mode of mothers was not associated with non/low-response of their infants. Conclusion: The mother's load of HBV DNA≥1×10(7) copies/ml might be the factor for non/low-response to hepatitis B vaccine in infants of HBsAg positive mothers.

Pantoprazole Does Not Reduce the Antiplatelet Effect of Clopidogrel: A Randomized Controlled Trial in Korea.

BACKGROUND/AIMS: Concerns that proton pump inhibitors (PPIs) diminish the efficacy of clopidogrel could hamper the appropriate prescription of PPIs. We evaluated the influence of pantoprazole on the antiplatelet effect of clopidogrel compared with ranitidine, which is regarded as safe, after stratification of the population according to the presence of a cytochrome (CYP) 2C19 polymorphism in Korea. METHODS: Forty patients who underwent dual antiplatelet therapy were randomized to receive pantoprazole (n=20) or ranitidine (n=20). Platelet aggregation was evaluated by impedance aggregometry at baseline (D0) and 8 days after acid-lowering treatments (D9). CYP2C19 was genotyped by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: After co-treatment, the percentage of clopidogrel low-response was 11.1% (2/18) in the pantoprazole group and 10.5% (2/19) in the ranitidine group (p=0.954). The impedance values with adenosine diphosphate stimulus after acid-lowering treatments did not significantly differ between the two groups. In a multiple regression analysis, only ST-elevation myocardial infarction was marginally associated with a reduced antiplatelet effect (odds ratio, 12.07; 95% confidence interval, 0.84 to 173.78). However, pantoprazole use did not affect the antiplatelet effect after correction for the CYP2C19 polymorphism. CONCLUSIONS: This study showed that pantoprazole does not increase platelet aggregation in patients receiving dual antiplatelet therapy (ClinicalTrials.gov number: NCT02733640).

Hypersensitivity to ticagrelor and low response to clopidogrel: a case report.

Ticagrelor is widely used to treat acute coronary syndrome. Hypersensitivity reaction of ticagrelor is rarely recognized. A low response to clopidogrel, which occurs in up to 23% of patients, is an independent risk factor for stent thrombosis. Management of patients with a low response to clopidogrel and ticagrelor hypersensitivity who are undergoing antithrombotic therapy remains to be a challenge. Herein, we report a patient with low response to clopidogrel and ticagrelor hypersensitivity, who was successfully managed using aspirin and warfarin.

Hypersensitivity to ticagrelor and low response to clopidogrel: a case report

Ticagrelor is widely used to treat acute coronary syndrome. Hypersensitivity reaction of ticagrelor is rarely recognized. A low response to clopidogrel, which occurs in up to 23% of patients, is an independent risk factor for stent thrombosis. Management of patients with a low response to clopidogrel and ticagrelor hypersensitivity who are undergoing antithrombotic therapy remains to be a challenge. Herein, we report a patient with low response to clopidogrel and ticagrelor hypersensitivity, who was successfully managed using aspirin and warfarin.

Influencing factors for non/low-response to hepatitis-B vaccine in infants of HBsAg positive mothers / 中华流行病学杂志

Objective To investigate the influencing factors for non/low-response to hepatitis B vaccine in infants of HBsAg-positive mothers.Methods A total of 286 HBsAg-positive pregnant women and their infants were recruited from the Third People's Hospital of Taiyuan during July 2011 to January 2013.The infants were immunized with hepatitis B vaccine according to the 0-1-6 month vaccination schedule and followed up for 12 months.The serum HBV DNA level of mothers,neonates and infants were detected by electro chemilum inescence immunoassay kits and fluorescene quantiative polymerase chain rection.Results Among 286 infants,the rate of non/low-response to hepatitis B vaccine was 18.53％ (53/286).Non-conditional logistic regression analysis indicated that the mother's HBV DNA level ≥ 1 × 107 copies/ml (0R=2.592,95％CI:1.121-5.996) and natural birth (OR=1.932,95％CI:1.021-3.654) were the risk factors for non/low-response to hepatitis B vaccine,the risks were 2.592 times and 1.932 times higher compared with the infants whose mothers were HBV DNA negative and the infants whose mothers had cesarean delivery.There was no multiplicative or additive interaction between high HBV DNA load and natural birth (OR=1.055,95％CI:0.209-5.321),(RERI=1.617,95％CI:-4.038-7.272;AP=0.364,95％CI:-).527-1.225;SI=1.195,95％CI:0.270-13.135).After stratified analysis of mother's HBV DNA level,delivery mode of mothers was not associated with non/low-response of their infants.Conclusion The mother's load of HBV DNA ≥ 1 × 107 copies/ml might be the factor for non/low-response to hepatitis B vaccine in infants of HBsAg positive mothers.

Influencing factors for non/low-response to hepatitis-B vaccine in infants of HBsAg positive mothers / 中华流行病学杂志

Objective To investigate the influencing factors for non/low-response to hepatitis B vaccine in infants of HBsAg-positive mothers.Methods A total of 286 HBsAg-positive pregnant women and their infants were recruited from the Third People's Hospital of Taiyuan during July 2011 to January 2013.The infants were immunized with hepatitis B vaccine according to the 0-1-6 month vaccination schedule and followed up for 12 months.The serum HBV DNA level of mothers,neonates and infants were detected by electro chemilum inescence immunoassay kits and fluorescene quantiative polymerase chain rection.Results Among 286 infants,the rate of non/low-response to hepatitis B vaccine was 18.53％ (53/286).Non-conditional logistic regression analysis indicated that the mother's HBV DNA level ≥ 1 × 107 copies/ml (0R=2.592,95％CI:1.121-5.996) and natural birth (OR=1.932,95％CI:1.021-3.654) were the risk factors for non/low-response to hepatitis B vaccine,the risks were 2.592 times and 1.932 times higher compared with the infants whose mothers were HBV DNA negative and the infants whose mothers had cesarean delivery.There was no multiplicative or additive interaction between high HBV DNA load and natural birth (OR=1.055,95％CI:0.209-5.321),(RERI=1.617,95％CI:-4.038-7.272;AP=0.364,95％CI:-).527-1.225;SI=1.195,95％CI:0.270-13.135).After stratified analysis of mother's HBV DNA level,delivery mode of mothers was not associated with non/low-response of their infants.Conclusion The mother's load of HBV DNA ≥ 1 × 107 copies/ml might be the factor for non/low-response to hepatitis B vaccine in infants of HBsAg positive mothers.

Pantoprazole Does Not Reduce the Antiplatelet Effect of Clopidogrel: A Randomized Controlled Trial in Korea

BACKGROUND/AIMS: Concerns that proton pump inhibitors (PPIs) diminish the efficacy of clopidogrel could hamper the appropriate prescription of PPIs. We evaluated the influence of pantoprazole on the antiplatelet effect of clopidogrel compared with ranitidine, which is regarded as safe, after stratification of the population according to the presence of a cytochrome (CYP) 2C19 polymorphism in Korea. METHODS: Forty patients who underwent dual antiplatelet therapy were randomized to receive pantoprazole (n=20) or ranitidine (n=20). Platelet aggregation was evaluated by impedance aggregometry at baseline (D0) and 8 days after acid-lowering treatments (D9). CYP2C19 was genotyped by polymerase chain reaction restriction fragment length polymorphism. RESULTS: After co-treatment, the percentage of clopidogrel low-response was 11.1% (2/18) in the pantoprazole group and 10.5% (2/19) in the ranitidine group (p=0.954). The impedance values with adenosine diphosphate stimulus after acid-lowering treatments did not significantly differ between the two groups. In a multiple regression analysis, only ST-elevation myocardial infarction was marginally associated with a reduced antiplatelet effect (odds ratio, 12.07; 95% confidence interval, 0.84 to 173.78). However, pantoprazole use did not affect the antiplatelet effect after correction for the CYP2C19 polymorphism. CONCLUSIONS: This study showed that pantoprazole does not increase platelet aggregation in patients receiving dual antiplatelet therapy (ClinicalTrials.gov number: NCT02733640).

[Prevalence of acetylsalicylic acid (ASA) - low response in vascular surgery]. / Prävalenz der ASS-Low-Response in der Gefäßchirurgie.

BACKGROUND: Research has revealed that a decreased antiplatelet effect (low response [LR]/high on-treatment platelet reactivity [HPR]) of acetylsalicylic acid (ASA) and clopidogrel is associated with an increased risk of thromboembolic events. There are extensive ASA low response (ALR) and clopidogrel low response (CLR) prevalence data in the literature, but there are only a few studies concerning vascular surgical patients. The aim of this study was to examine the prevalence and risk factors of ALR and CLR in vascular surgical patients. MATERIALS AND METHODS: We examined n = 154 patients with an antiplatelet long-term therapy, who were treated due to peripheral artery occlusive disease (PAD) and/or arteria carotis interna stenosis (CVD). To detect an ALR or CLR, we examined full blood probes with impedance aggregometry (ChronoLog® Aggregometer model 590). Risk factors were examined by acquisition of concomitant disease, severity of vascular disease, laboratory test results and medication. RESULTS: We found a prevalence of 19.3 % in the ALR group and of 21.1 % in the CLR group. Risk factors for ALR were an increased platelet and leucocyte count and co-medication with pantoprazole. We found no significant risk factors for a decreased antiplatelet effect of clopidogrel treatment. CONCLUSION: The investigated prevalence for ALR and CLR are in the range of other studies, particularly based on cardiological patients. More investigations are needed to gain a better evaluation of the risk factors for HPR and to develop an effective antiplatelet therapy regime to prevent cardiovascular complications.

Trends in 'poor responder' research: lessons learned from RCTs in assisted conception.

BACKGROUND: A substantial minority of women undergoing IVF will under-respond to controlled ovarian hyperstimulation. These women-so-called 'poor responders'-suffer persistently reduced success rates after IVF. Currently, no single intervention is unanimously accepted as beneficial in overcoming poor ovarian response (POR). This has been supported by the available research on POR, which consists mainly of randomized controlled trials (RCTs ) with an inherent high-risk of bias. The aim of this review was to critically appraise the available experimental trials on POR and provide guidance towards more useful-less wasteful-future research. METHODS: A comprehensive review was undertaken of RCTs on 'poor responders' published in the last 15 years. Data on various methodological traits as well as important clinical characteristics were extracted from the included studies and summarized, with a view to identifying deficiencies from which lessons can be learned. Based on this analysis, recommendations were provided for further research in this field of assisted conception. RESULTS: We selected and analysed 75 RCTs. A valid, 'low-risk' randomization method was reported in three out of four RCTs. An improving trend in reporting concealment of patient allocation was also evident over the 15-year period. In contrast, <1 in 10 RCTs 'blinded' patients and <1 in 5 RCTs 'blinded' staff to the proposed intervention. Only 1 in 10 RCTs 'blinded' ultrasound practitioners to patient allocation, when assessing the outcome of early pregnancy. The majority of trials reported an intention-to-treat analysis for at least one of their outcomes, with an improving trend in the recent years. Substantial variation was noted in the definitions used for 'poor responders', the most popular being 'low ovarian response at previous stimulation'. The preferred cut-off value for defining previous low response has been 'less or equal to three retrieved oocytes'. The most popular tests used for diagnosing diminished ovarian reserve have been antral follicle count and FSH. Although the Bologna criteria for POR were only recently introduced, they are expected to become a popular definition in future 'poor responder' trials. Numerous interventions have been studied on 'poor responders'. Most of these have been applied before/during controlled ovarian hyperstimulation. The antagonist protocol, the microdose flare protocol and the long down-regulation protocol have been among the most popular interventions. The analysis of outcomes revealed a clear improving trend in reporting live birth. In contrast, only 10% of RCTs reported significant improvement in reproductive outcomes among tested interventions. Twelve 'significant' interventions were reported, each supported by a single 'positive' RCT. Finally, trials of higher methodological quality were more likely to have been published in a high-impact journal. CONCLUSIONS: Overall, the majority of published trials on POR suffer from methodological flaws and are, thus, regarded as being high-risk for bias. The same trials have used a variety of definitions for their poor responders and a variety of interventions for their head-to-head comparisons. Not surprisingly, discrepancies are also evident in the findings of trials comparing similar interventions. Based on the identified deficiencies, this novel type of 'methodology and clinical' review has introduced custom recommendations on how to improve future experimental research in the 'poor responder' population.