Epidemiologic Methods ; Humans ; Prevalence ; Rare Diseases ; epidemiology

[Objective]To evaluate the effects of sutureless technique in comparison to conventional techniques for repair of total anomalous pulmonary venous connection(TAPVC)with the method of propensity score analysis.[Methods]From October 2007 to December 2013,179 consecutive patients were enrolled in this study. Patients were operated with sutureless technique(n = 81)or Conventional technique(n=98),and followed up at an interval of 1 month,3 months,6 months and then once a year post-operation. During analysis,three type of propensity-score matching methods,including nearest neighbor caliper matching,Mahalanobis metric matching with propensity score ,optimal full matching were used to create balanced groups of patients receiving each treatment. Surgeons’performance difference was assessed with random frailty proportional hazards models with gamma. Composite endpoints was defined by postoperative death or late death or postoperative pulmonary venous obstruction(PVO),which was evaluated with Kaplan-Meier curve and multivariable Cox proportional hazard model,adjusted by Preoperative-PVO,age,gender,weight and TAPVC type.[Results]Nearest neighbor caliper matching method was the best choice during propensity score analysis. After matching ,sutureless group included 73 patients and Conventional group73 patients. In sutureless group,cardiopulmonary bypass(CPB)time(Z=2.18, P=0.030),cross-clamp time(Z=3.63,P<0.001),rate of composite endpoints(HR 95%CI=0.20(0.06~0.61),P=0.005),late death(HR 95%CI=0.03(0.01~0.55),P=0.017)were significantly better than that in Conventional group. In subgroup analysis ,for patients with pre-PVO,decreased composite endpoints was seen in sutureless group.[Conclusion]Comparison using thepropensity score analysis demonstrated that sutureless strategy for primary repair of TAPVC may associate with decreased mortality rate of post-PVO and CPB time and cross-clamp time.

Objective:To explore the environmental risk factors of different categories of congenital heart defects ( CHD) and provide evidence for further risk factors and prevention research of CHD pheno-types. Methods:Data of Guangdong CHD Register Study from 2004 to 2012 were used. In the study, 3 038 CHD cases and 3 038 paired controls from 34 hospitals distributed in 17 cities were registered and related information were collected using uniform, and structured questionnaires. All the CHD phenotypes were coded according to the International Classification of Diseases 10th Revision (ICD-10) and classified into 6 categories according to their pathological features. Univariate analyses were adopted to filter poten-tial risk factors for each category of CHD. Then multivariate conditional Logistic regression was used to calculate the odds ratios of the risk factors for each category of CHD. Results:The risk factors for left-to-right shunt CHD included low ( OR=2 . 63 , 95%CI:2 . 04 -3 . 39 ) or over birth weight ( OR =2 . 21 , 95%CI:1 . 47-3 . 32 ) , premature delivery ( OR=1 . 95 , 95%CI:1 . 53-2 . 49 ) , polyembryony ( OR=1. 99, 95%CI: 1. 22 -3. 26), maternal low education, mother as factory worker (OR =1. 62, 95%CI:1 . 32-1 . 98 ) , parity≥2 ( OR =1 . 38 , 95%CI: 1 . 13 -1 . 69 ) , maternal abnormal reproduction history ( OR=2 . 29 , 95%CI:1 . 75-3 . 01 ) , fever ( OR=2 . 38 , 95%CI:1 . 26-4 . 48 ) , virus infection ( OR=1 . 80 , 95%CI:1 . 29 -2 . 51 ) , medicine usage ( OR=1 . 73 , 95%CI:1 . 11 -2 . 69 ) , passive smoking ( OR=1 . 69 , 95%CI:1 . 26-2 . 29 ) , chemical agent contact ( OR=8 . 71 , 95%CI:2 . 33 -32 . 58 ) , living in newly decorated houses ( OR=2 . 56 , 95%CI:1 . 60-4 . 09 ) or room close to the main road ( OR=1 . 40 , 95%CI:1 . 14-1 . 72 ) in the first 3 months of pregnancy and father as factory worker ( OR=1 . 46 , 95%CI:1 . 23-1 . 73 ) . The risk factors for pulmonary outflow tract obstruction CHD in-cluded low ( OR =5 . 98 , 95% CI: 2 . 88 -12 . 44 ) or over birth weight ( OR = 6 . 56 , 95% CI:1. 19-36. 26), maternal low education, parity≥2 (OR=2. 08, 95%CI:1. 03-4. 22), virus infection in the first 3 months of pregnancy ( OR =4 . 30 , 95%CI: 1 . 27 -13 . 45 ) . The risk factors for left ventricular outflow tract obstruction CHD included father as factory worker ( OR=6 . 01 , 95%CI:1 . 05-34. 59). The risk factors for transposition of the great arteries included low birth weight (OR=12. 93, 95%CI:1. 14-146. 26), maternal low education, mother as factory worker (OR=3. 69, 95%CI:1. 53-8. 91). The risk factors for conditions with intra cardiac mixing of oxygenated and deoxygenated blood in-cluded parity=2 ( OR=3 . 45 , 95%CI:1 . 42-8 . 38 ) . The risk factors for other CHD included over birth weight (OR=4. 87, 95%CI:1. 19-19. 94), maternal abnormal reproduction history (OR=2. 96, 95%CI:1. 14 - 7. 68 ), virus infection ( OR = 4. 92, 95% CI: 1. 56 - 15. 47 ), medicine usage (OR=4. 90, 95%CI:1. 22-19. 77) or passive smoking (OR=10. 31, 95%CI:1. 25-85. 05) in the first 3 months of pregnancy. Conclusion:The environmental risk factors were discrepant among different categories of CHD. Further risk factors study of CHD phenotypes should be performed specially. To prevent CHD, attention should be paid to the risk factors which are related to multi or complex categories of CHD.

Objective This retrospective cohort study aims to evaluate and compare the prognosis of surgical repair for total anomalous pulmonary venous connection(TAPVC) with different drainage type.Methods From January 2006 to Decem-ber 2013, 328 consecutive patients were enrolled in this study .The distribution of the defects was 109 cases with cardiac, 161 with supracardiac, 32 with infracardiac, and 26 with mixed type of the drainage into the systemic circulation .The clinical re-cords of all the patients were reviewed.Studied variables were extracted from the clinical records.Followed-up was conducted at an interval of 1 month, 3 months, 6 months and then once a year post-operation.Prevalence of peri-operative conditions were compared among four different types.Studied endpoints was defined by postoperative total death or pulmonary venous obstruc-tion(PVO), which was evaluated with Kaplan-Meier curve and multivariable Cox proportional hazard model, adjusted by differ-ent surgical strategy, emergency operation, preoperative-PVO, neonates, weight, combing with other complex cardiac defects,NYHA cardiac function, severe pulmonary hypertension and severe tricuspid regurgitation.Results There were significant discrepancyof preoperative conditions among four types of TAPVC.Patients with infracardiac TAPVC presented the most criticalsymptoms and clinical indexes, which included having largest proportion of neonates, preoperative PVO, severe NYHA grading,pulmonary hypertension and tricuspid regurgitation, having lowest body weight at operation and youngest age.The cardiopulmonarybypass time, aortic crossclamp time and mechanical ventilation time were significantly longer in infracadiac and mixedTAPVC comparing to the other two types.For early mortality(death in hospital), infracadiac(9.4%) and mixed(11.5%)TAPVC demonstrated higher rates of death than cardiac(4.6%) and supracardiac(7.5%)TAPVC, although had no statisticalsignificance.For intermediate-term results, mortality in infracadiac(21.9%) and mixed(30.8%) TAPVC were significantlyhigher than cardiac ( 8.3%) and supracardiac (11.8%) TAPVC.Reoperation was more frequently required in mixed(19.2%), then infracadiac(15.6%)TAPVC.Mixed and infracadiac types are independent risk factors for TAPVC prognosis,after adjusting by the confounding factors.Conclusion Mixed and infracadiac types are independent risk factors for postoperativedeath and PVO among TAPVC patients.This study provided evidence for clinical assessment and management strategy fordifferent types of TAPVC.

Abnormal aggregation of amyloid-β protein (Aβ) in brain plays a vital role in the occurrence of Alzheimer's disease (AD). Hence, inhibiting Aβ aggregation is one major tactic for therapy of AD. Previous studies have found that tolcapone can inhibit Aβ42 aggregation and reduce the cytotoxicity induced by Aβ42 aggregates, but clinical studies have found that tolcapone has strong liver toxicity. To reduce the liver toxicity of tolcapone, its side chain structure was modified to obtain its derivative phenethyl (E)-2-cyano-3-(3,4 dihydroxy-5-nitrobenzene)-acrylate (PCDNA). Thioflavin T (ThT) and atomic force microscopy (AFM) assays were used to explore the inhibitory effect of PCDNA on Aβ42 fibrillogenesis. The cytotoxicity assays were used to explore the inhibitory effect of PCDNA against the cytotoxicity induced by Aβ42 aggregates. In addition, the depolymerization effect of PCDNA on mature Aβ42 fibrils was also explored. Finally, molecular docking was used to explore the interaction between PCDNA and Aβ42 pentamer. These results lay the foundation for the study of the structural analogues of tolcapone as Aβ inhibitors.

Conditional logistic regression analysis and unconditional logistic regression analysis are commonly used in case control study,but Cox proportional hazard model is often used in survival data analysis.Most literature only refer to main effect model,however,generalized linear model differs from general linear model,and the interaction was composed of multiplicative interaction and additive interaction.The former is only statistical significant,but the latter has biological significance.In this paper,macros was written by using SAS 9.4 and the contrast ratio,attributable proportion due to interaction and synergy index were calculated while calculating the items of logistic and Cox regression interactions,and the confidence intervals of Wald,delta and profile likelihood were used to evaluate additive interaction for the reference in big data analysis in clinical epidemiology and in analysis of genetic multiplicative and additive interactions.

Competing risks occur frequently in the analysis of survival data that should be dealt with competing risk models.Competing risk is an event whose occurrence precludes the occurrence of the primary event of interest.Previous commonly used Kaplan-Meier method tends to overestimate the cumulative survival functions,while the traditional Cox proportional hazards model falsely evaluates the effects of covariates on the hazard related to the occurrence of the event.There are few domestic reports mentioning the concept,application and methodology of competing risk model as well as the implementation procedures or resolution of model conditions and parameters.The current work aims to explain the core concept and methodology of the competing risk model and to illustrate the process of analysis on cumulative incidence rate,using both the cause-specific hazard function model and the sub-distribution hazard function model.Software macro code in SAS 9.4 is also provided to assist clinical researchers to further understand the application of the model so to properly analyze the survival data.

China ; epidemiology ; Hemophilia A ; epidemiology ; Hemophilia B ; epidemiology ; Humans ; Prevalence

Objective To explore the effect of the surgical treatment in neonates with congenital heart disease(CHD) and the factors related to the perioperative mortality during cardiopulmonary bypass. Methods Totally,666 neonates undergo-ing CHD operation were reviewed in a single center from Jan 2006 to Dec 2014,of which,431 cases had complete cardiopul-monary bypass records. Analysis was performed to investigate the association between perioperative mortality and potential fac-tors,especially the cardiopulmonary bypass factors during different periods. In the multivariate Cox proportional hazard model, factors with statistical significance(P < 0. 1)in the univariate analysis were included in the model,such as,surgeon grouping, year of surgery,Aristotle score,preoperative weight,preoperative and intraoperative sodium bicarbonate volume and postopera-tive low cardiac output. Results The neonates enrolled ranged 8 - 22 days after birth,and 2. 7 - 3. 6 kg at weight. The mor-tality rate decreased from 23. 7％ in 2006 to 12. 4％ in 2014,showing a gradual decline(P = 0. 02). The mortalities of differ-ent CHDs were:pulmonary atresia(24. 4％),coarctation of the aorta( 16. 7％),transposition of the great arteries( 13. 1％), total anomalous pulmonary venous connection( 11. 0％),ventricular septal defect( 10. 6％),and so on. The volume of preop-erative and intraoperative 5％ sodium bicarbonate was 30(20 - 50)mL in death group,higher than that in survival group[23 ( 15 - 30)ml]. While the preoperative weight was 3. 1(2. 7 - 3. 5)kg,lower than that in survival group[3. 3(3. 0 - 3. 6) kg]. The total amount of Plasmalyte/ Ringer,erythrocytes,ultrafiltration volume and the cardiac assist ratio were higher in the death group than in the survival group. After controlling the confounding effect of surgeons,the multivariable Cox proportional hazard model showed that:the independent risk factors for perioperative mortality were pulmonary atresia[aHR = 3. 89( 1. 78 -8. 42)],5％ sodium bicarbonate volume ≥50 ml[aHR = 2. 62( 1. 14 - 6. 04)],erythrocytes volume > 200 ml[aHR = 2. 26 ( 1. 1 - 4. 06)]and postoperative low cardiac output[aHR = 6. 76(3. 30 - 13. 87)]. Conclusion During the study period, the preoperative mortality for neonates with CHD had a dramatical decrease,although the preoperative risk factors for the pa-tients increased. Pulmonary atresia repair surgery had the highest mortality in neonates. Factors associated with the periopera-tive mortality includedpreoperative acidosis and postoperative low cardiac output. There is a significant association between the improvement of perioperative mortality and the improvement of the technology of minimized cardiopulmonary bypass circuit dur-ing neonatal operation. It is suggested that the total erythrocytes volume maintains less than 200 ml.

Objective To explore the feasibility and option of different surgeries for neonates with pulmonary atresia and ventricular septal defect (PA/VSD) through assessing the effect of common surgeries. Methods Fourteen neonates who underwent their first surgery in our center from July 2004 to October 2014 were included. Their basic characteristics, operation and pre- and postoperative clinical information were extracted. Follow up was conducted and the last visit was on October 10, 2016. Short- and midterm survival and total correction rate were compared among different surgeries. Results Among the 14 patients, there were 4 (28.6%) patients, 6 (42.9%) and 4 (28.6%) who underwent one-stage repair, right ventricular outflow tract (RVOT) reconstruction, and systemic to PA shunt operation respectively. The overall in-hospital mortality after the first operation was 28.6% (4/14). At last visit, no death occurred resulting the 5-year survival rate of 71.4% (10/14). The overall total correction rate for all neonates was 64.3% (9/14). Although no statistical difference was found in the mortality among the one-stage repair , RVOT reconstruction and systemic to PA shunt group(50.0% vs. 33.3% vs. 0.0%, P=0.280), the survival and hazard analysis implied better outcomes of the systemic to PA shunt palliation operation. There was no statistical difference in the total correction rate and months from the first palliative operation to correction between those who underwent RVOT reconstruction and systemic to PA shunt (75.0% vs. 50.0%, P=0.470; 32.0 months vs. 18.0 months, P=0.400). Conclusion Performing surgeries for neonates with PA/VSD is still a great challenge. However, the midterm survival rate was optimistic for the early survivors. Systematic to PA shunt seemed to be a better choice with lower mortality for the neonates with PA/VSD who need the surgery to survive.