Dafang Chen

Conception, early pregnancy loss, and time to clinical pregnancy: a population-based prospective study

OBJECTIVE To examine rates of conception and pregnancy loss and their relations with time to clinical pregnancy and reproductive outcomes. DESIGN A prospective observational study. SETTING Population-based cohort in China. PATIENT(S) Five hundred eighteen healthy newly married women who intended to conceive. Upon stopping contraception, daily records of vaginal bleeding and daily first-morning urine specimens were obtained for < or =1 year or until a clinical pregnancy was achieved. Daily urinary hCG was assayed to detect early pregnancy loss (EPL). INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Conception, pregnancy loss, and time to clinical pregnancy. RESULT(S) The conception rate per cycle was 40% over the first 12 months. Of the 618 detectable conceptions, 49 (7.9%) ended in clinical spontaneous abortion, and 152 (24.6%) in EPL. Early pregnancy loss was detected in 14% of all the cycles without clinically recognized pregnancy, but the frequencies were lower among women with delayed time to clinical pregnancy. Early pregnancy loss in the preceding cycle was associated with increased odds of conception (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.8-3.9), clinical pregnancy (OR, 2.0; 95% CI, 1.3-3.0), and EPL (OR, 2.4; 95% CI, 1.4-4.2) but was not associated with spontaneous abortion, low birth weight, or preterm birth in the subsequent cycle. CONCLUSION(S) We demonstrated substantial EPL in the non-clinically pregnant cycles and a positive relation between EPL and subsequent fertility.

Efficacy of Folic Acid Therapy in Primary Prevention of Stroke Among Adults With Hypertension in China: The CSPPT Randomized Clinical Trial

IMPORTANCE Uncertainty remains about the efficacy of folic acid therapy for the primary prevention of stroke because of limited and inconsistent data. OBJECTIVE To test the primary hypothesis that therapy with enalapril and folic acid is more effective in reducing first stroke than enalapril alone among Chinese adults with hypertension. DESIGN, SETTING, AND PARTICIPANTS The China Stroke Primary Prevention Trial, a randomized, double-blind clinical trial conducted from May 19, 2008, to August 24, 2013, in 32 communities in Jiangsu and Anhui provinces in China. A total of 20,702 adults with hypertension without history of stroke or myocardial infarction (MI) participated in the study. INTERVENTIONS Eligible participants, stratified by MTHFR C677T genotypes (CC, CT, and TT), were randomly assigned to receive double-blind daily treatment with a single-pill combination containing enalapril, 10 mg, and folic acid, 0.8 mg (n = 10,348) or a tablet containing enalapril, 10 mg, alone (n = 10,354). MAIN OUTCOMES AND MEASURES The primary outcome was first stroke. Secondary outcomes included first ischemic stroke; first hemorrhagic stroke; MI; a composite of cardiovascular events consisting of cardiovascular death, MI, and stroke; and all-cause death. RESULTS During a median treatment duration of 4.5 years, compared with the enalapril alone group, the enalapril-folic acid group had a significant risk reduction in first stroke (2.7% of participants in the enalapril-folic acid group vs 3.4% in the enalapril alone group; hazard ratio [HR], 0.79; 95% CI, 0.68-0.93), first ischemic stroke (2.2% with enalapril-folic acid vs 2.8% with enalapril alone; HR, 0.76; 95% CI, 0.64-0.91), and composite cardiovascular events consisting of cardiovascular death, MI, and stroke (3.1% with enalapril-folic acid vs 3.9% with enalapril alone; HR, 0.80; 95% CI, 0.69-0.92). The risks of hemorrhagic stroke (HR, 0.93; 95% CI, 0.65-1.34), MI (HR, 1.04; 95% CI, 0.60-1.82), and all-cause deaths (HR, 0.94; 95% CI, 0.81-1.10) did not differ significantly between the 2 treatment groups. There were no significant differences between the 2 treatment groups in the frequencies of adverse events. CONCLUSIONS AND RELEVANCE Among adults with hypertension in China without a history of stroke or MI, the combined use of enalapril and folic acid, compared with enalapril alone, significantly reduced the risk of first stroke. These findings are consistent with benefits from folate use among adults with hypertension and low baseline folate levels. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00794885.

Waist circumference, body mass index and waist to hip ratio for prediction of the metabolic syndrome in Chinese

BACKGROUND AND AIMS To explore the ability of waist circumference (WC), body mass index (BMI) and waist to hip ratio (WHR) to predict two or more non-adipose components of the metabolic syndrome (MetS) among individuals aged 18-85 in North China. METHODS AND RESULTS This study is a cluster sample survey of 101,510 individuals, complete data are 75,788 subjects, 59,874 males and 15,914 females. Their ages were 51.9+/-12.7 years (males) and 48.7+/-11.5 years (females). Receiver operating characteristic (ROC) analysis was used to examine discrimination and find optimal cut off values of WC, BMI and WHR to predict two or more non-adipose components of MetS. The area under the ROC curve (AURC) for WC (0.694) and BMI (0.692) in females showed no difference. In males BMI (0.657) had a better discrimination than WC (0.634). WHR was weaker in both sexes. The optimal cut off value of WC in males (86.5 cm) was higher than in females (82.1cm); and that of BMI was about 24 kg/m(2) in both genders. The optimal cut off values of WC, BMI, and WHR, increased with age in both sexes. CONCLUSIONS BMI and WC are more useful than WHR for predicting two or more non-adipose components of MetS. Cut off values for WC in males, and those of BMI and WHR in both sexes are lower than that in present MetS criteria; WC in females is slightly higher. Cut off values of WC, BMI and WHR were increased with age in the Chinese.

Exposure to benzene, occupational stress, and reduced birth weight

OBJECTIVES The association between birth weight and exposure to benzene, work stress, and other occupational and environmental hazards was investigated. METHODS In a large petrochemical industry, 792 pregnant workers were enrolled and followed up through delivery between May 1996 and December 1998. Exposure to benzene and other solvents was assessed by an industrial hygienist based on each womans job title and workplace information. Other occupational and environmental exposures and personal information, including perceived work stress, exposure to noise, physical exertion at work, and passive smoking, were obtained by an interview questionnaire. Univariate and multivariate regression models were used to examine the individual and combined associations of occupational and environmental exposures with birth weight, with adjustment for major confounders including gestational age. RESULTS In the univariate model, birth weight was negatively associated with exposure to benzene (−58 g (95% confidence interval (95% CI), −115 to −2)) and with work stress (−84 g (95% CI, −158 to −10)). In the multivariate model, there was a significant interaction between exposure to benzene and work stress relative to reduced birth weight, after adjustment for other environmental and occupational exposures and personal variables. Adjusted mean birth weight was 3445 g (95% CI 3401 to 3489) among those with neither exposure, 3430 g for those with exposure to benzene only, 3426 g for those with work stress only, and 3262 g (95% CI 3156 to 3369) for those with both exposures. In other words, there was 183 g (95% CI 65 to 301) reduction in birth weight among those with both exposure to benzene and work stress compared with those with neither exposure. Other work or environmental factors could not explain these findings. CONCLUSIONS Low level exposure to benzene and work stress interact to reduce birth weight in this population.

Polymorphisms of the paraoxonase gene and risk of preterm delivery.

Background: Human paraoxonase (PON) is an enzyme involved in vasodilation and thrombosis. Disruption of blood blow through the placenta could be part of the pathophysiological mechanism leading to preterm delivery. The purpose of this study was to examine the association between polymorphisms in 2 paraoxonase genes (PON1 and PON2) and preterm delivery. Methods: We conducted a case-control study using infant-parents triads in Anqing, China. Between July 1999 and June 2001, we enrolled the families of 105 infants born at term and 80 infants born preterm. Genotyping was performed for the polymorphisms of PON1 Q192R, PON2 A148G, and PON2 S311C using standard techniques. We used log-linear modeling to analyze the association of PON1 and PON2 gene polymorphisms with the risk of preterm delivery. Results: In the analysis of children’s genotypes, the relative risk was 3.6 (95% confidence interval [CI] = 1.3–11) for PON1 RR compared with PON1 QQ. An association was also seen for PON2 CC compared with PON2 SS (relative risk = 4.6; CI = 1.5–14). There was no association between the mother’s PON1 and PON2 genotypes and preterm delivery, and we did not observe an interaction between mothers’ and children’s genotypes. Analysis of control triads suggests Mendelian transmissions of the variant alleles of PON1 192R, PON2 148G, and PON2 311C. Conclusion: Infant PON1 RR and PON2 CC genotypes were associated with preterm delivery in our study population, which suggests a possible role for human paraoxonase variability in the etiology of preterm delivery.

Association of Genetic Polymorphisms and Age-Related Macular Degeneration in Chinese Population

PURPOSE We explored associations between age-related macular degeneration (AMD) and genetic variants of 10 genes in a nationwide Chinese population. METHODS In this multicenter case-control study, 535 AMD patients and 469 controls were recruited from 16 centers that spread from the north to the south of China. All participants underwent comprehensive eye examinations, and 40 single nucleotide polymorphisms (SNPs) of 10 genes were selected. DNA samples were genotyped with the MassArray system. The effect of the genotypes and haplotypes on AMD was assessed with logistic regression analysis, adjusted for age, sex, long-term residence, and family origin. RESULTS In our study, 11 SNPs in complement H (CFH), 2 in age-related maculopathy susceptibility 2 (ARMS2), and 2 in high-temperature requirement factor A1 (HTRA1) were associated significantly with AMD. They were rs551397, rs800292, rs1329424, rs1061170, rs10801555, rs12124794, rs10733086, rs10737680, rs2274700, rs1410996, and rs380390 in CFH; rs10490924 and rs2736912 in ARMS2; and rs11200638 and rs3793917 in HTRA1. Three haplotypes in CFH, predisposed the patients significantly to AMD (P<0.001, P=0.001, and P<0.001, respectively). With the sample size of our study, no relationship was found for AMD and the SNPs tested in complement 3 (C3); serpin peptidase inhibitor, clade G, member 1 (SERPING1); vascular endothelial growth factor (VEGF); cholesterol ester transfer protein (CETP); lipoprotein lipase (LPL); hepatic lipase (LIPC); and metallopeptidase inhibitor 3 (TIMP3) genes. CONCLUSIONS Gene variants in CFH, ARMS2, and HTRA1 contribute to AMD in the Chinese population.

Effects of exposure to organic solvents on menstrual cycle length.

Toinvestigate the association between organic solvent exposure and menstrualdisturbance, we conducted a cross-sectional study among 1408 petrochemicalworkers in China. Based on an industrial hygiene evaluation, we classified theworkshops according to the presence or absence of organic solvents (benzene,styrene, toluene, or xylene). We used logistic regression to estimate oddsratios and 95% confidence intervals for prolonged menstrual cycle length(oligomenorrhea: average cycle length >35 days during the previous year)associated with the exposure. After adjustment for confounders, eachadditional year of work in an exposed workshop was associated with a 7%increase in oligomenorrhea (odds ratio, 1.07; 95% confidence interval, 1.00 to1.14). Compared with no exposure, 3 or more years of exposure was associatedwith a 53% increase in oligomenorrhea (odds ratio, 1.53; 95% confidenceinterval, 1.00 to 2.34). We concluded that exposure to organic solvents isassociated with a trend toward increased frequency ofoligomenorrhea.

Incidence, Clinical Features and Impact on Anti-Tuberculosis Treatment of Anti-Tuberculosis Drug Induced Liver Injury (ATLI) in China

Background Anti-tuberculosis drug induced liver injury (ATLI) is emerging as a significant threat to tuberculosis control in China, though limited data is available about the burden of ATLI at population level. This study aimed to estimate the incidence of ATLI, to better understand its clinical features, and to evaluate its impact on anti-tuberculosis (TB) treatment in China. Methodology/Principal Findings In a population-based prospective study, we monitored 4,304 TB patients receiving directly observed treatment strategy (DOTS) treatment, and found that 106 patients developed ATLI with a cumulative incidence of 2.55% (95% Confidence Interval [CI], 2.04%–3.06%). Nausea, vomiting and anorexia were the top three most frequently observed symptoms. There were 35 (33.02%) ATLI patients with no symptoms, including 8 with severe hepatotoxicity. Regarding the prognosis of ATLI, 84 cases (79.25%) recovered, 18 (16.98%) improved, 2 (1.89%) failed to respond to the treatment with continued elevation of serum alanine aminotransferase, and 2 (1.89%) died as result of ATLI. Of all the ATLI cases, 74 (69.81%) cases changed their anti-TB treatment, including 4 (3.77%) cases with medication administration change, 21 (19.81%) cases with drugs replacement, 54 (50.94%) cases with therapy interruption, and 12 (11.32%) cases who discontinued therapy. In terms of treatment outcomes, 53 (51.46%) cases had TB cured in time, 48 (46.60%) cases had therapy prolonged, and 2 (1.94%) cases died. Compared with non-ATLI patients, ATLI patients had a 9.25-fold (95%CI, 5.69–15.05) risk of unsuccessful anti-TB treatment outcomes and a 2.11-fold (95%CI,1.23–3.60) risk of prolonged intensive treatment phase. Conclusions/Significance ATLI could considerably impact the outcomes of anti-TB treatment. Given the incidence of ATLI and the size of TB population in China, the negative impact is substantial. Therefore, more research and efforts are warranted in order to enhance the diagnosis and the prevention of ATLI.

Association of genetic polymorphisms with response to bevacizumab for neovascular age-related macular degeneration in the Chinese population

AIMS To determine whether there is an association between CFH, ARMS2, HTRA1, VEGF, SERPING1 or C3 genotypes and patient response to treatment with intravitreal bevacizumab for neovascular age-related macular degeneration (AMD). MATERIALS & METHODS This was a multicenter prospective study. One hundred and forty four patients with neovascular AMD treated with bevacizumab were recruited from 13 centers. Twelve SNPs were genotyped using Sequenom. Visual acuity score (VAS), central retinal thickness and maximum thickness of lesion were measured at each visit. RESULTS For the CFH rs800292 polymorphism, mean VAS changes were 4.4, 8.7 and 15.5 letters in the CC, CT and TT genotype carriers (p = 0.009). For ARMS2 rs10490924, mean VAS changes were 3.6, 12.1 and 9.6 letters for the TT, TG and GG genotypes (p = 0.001). For HTRA1 rs11200638, mean VAS changes were 3.6, 12.3 and 9.6 letters for the AA, AG and GG genotypes (p < 0.001). CONCLUSION CFH, ARMS2 and HTRA1 genotypes may influence patient response to treatment with intravitreal bevacizumab for neovascular AMD.

Risperidone Maintenance Treatment in Schizophrenia: A Randomized, Controlled Trial

OBJECTIVE Prevention of relapse is the crucial task in the maintenance treatment of schizophrenia. The investigators in this study sought to determine the duration of maintenance treatment needed with the initial therapeutic dose, in contrast to a reduced dose. METHOD In a multicenter open-label, randomized, controlled study, patients with schizophrenia who were clinically stabilized following an acute episode were randomly assigned to a no-dose-reduction group (initial optimal therapeutic dose continued throughout the study), a 4-week group (initial optimal therapeutic dose continued for 4 weeks, followed by a 50% dose reduction that was maintained until the end of the study), or a 26-week group (initial optimal therapeutic dose continued for 26 weeks, followed by a 50% dose reduction until the end of the study). All patients continued until the last recruited patient completed the 1-year follow-up. RESULTS Of the 404 patients who met the entry criteria and were randomly assigned, 374 completed the study. The estimated mean time from entry to relapse was 571 days in the 4-week group, 615 days in the 26-week group, and 683 days in the no-dose-reduction group, with estimated relapse rates of 30.5%, 19.5%, and 9.4%, respectively. Patients in the no-dose-reduction group experienced greater reduction in the severity of psychotic symptoms. CONCLUSIONS Patients who continued to receive the full risperidone dose used for their acute episode had fewer relapses than those who had dose reductions after 4 weeks or 26 weeks during the maintenance period. There was negligible difference in side effects among the three groups.