随着我国创新药品器械研发能力的不断提高,开展医疗器械临床试验的项目数量也在不断增多.医疗器械临床试验是验证器械安全性的重要环节,其结果的可靠性直接关系到器械上市后的安全,而临床试验的质量是临床试验的关键.通过对医疗器械临床试验各环节的质量风险因素进行规划、识别与评估,并探讨了降低风险的应对措施,建立完善医疗器械风险管理质量体系,实现临床试验全过程质量管理.

通过了解某医院药物临床试验保险购买情况,分析药物临床试验损害赔偿的归责原则及赔付的主体,建议通过强化伦理审查、临床试验管理和研究者GCP培训,完善临床试验保险制度,降低临床试验的风险,保障受试者的安全和合法权益等措施,希望对规范医疗产品临床试验研究发挥作用.

[目的]探讨我院医护人员对临床试验的认知情况和对教育需求情况,为我院药物临床机构制定培训政策提供依据.[方法]随机抽取我院25个临床试验资质料室医护人员200名医护人员进行问卷调查,回收问卷180份,回收率为90％.问卷内容主要包括人口学信息、临床试验知识认知情况、参加临床试验培训情况.[结果]比较我院参加培训组与未培训组医护人员基本得分情况,培训组医护人员在临床试验基本知识、伦理学知识、质量控制得分高于未培训组,差异均有统计学意义(P＜0.05);对医护人员基本得分情况进行多因素分析发现,基本知识得分情况影响因素主要有职称、学历、是否接受过培训,其中参加过相关培训、学历较高、职称较高的医护人员临床试验基本得分较高.[结论]我院医护人员对临床试验的认知水平不高,加强对医护人员培训可以提高对临床试验的认知水平,加强师资队伍建设,探索临床试验资格管理和将临床试验纳入医护人员职称评审体系,是提高医护人员对临床试验认知程度的有效措施.

Guided by good clinical practice ( GCP) , M hospital cooperated with the Ethics Committee in quali-ty management of clinical trials and took the specific measures including perfecting the institution and standard op-erating procedures, implementing three level quality control institution, strengthening the training of GCP, and closely cooperating with drug and data management of clinical trials, quality control in the clinical trial, ethical re-view and supervision, quality control in the whole process (seamless connection). Seamless connection from the beginning of project acceptance and quality control in the whole process of clinical trials can effectively solve the ex-isting problems in clinical trials and improve the quality of clinical trials.

按照JCI标准,通过建立不良事件管理小组和健全不良事件的管理机制,从不良事件的记录、处理、上报分析、追踪随访管理等环节对不良事件进行规范的管理,促进持续的质量改进,最大限度的保障受试者的安全和权益.并结合作者工作经历,对本院在JCI评审中对临床试验中不良事件的管理具体做法进行探讨和总结.

目的 通过对超重孕妇实施低血糖生成指数(GI)膳食的干预,探讨胎盘组织和脐血中与体重增长有关基因的甲基化的改变.方法 采用随机化单盲对照干预试验设计,研究对象为初次产检孕周≤12周且体重超重的孕妇.以研究对象纳入的顺序号为随机序列号,采用简单随机化的方法随机分为干预组和对照组.干预组在中国孕妇保健规范的基础上结合国家对孕妇的膳食和体力活动规范实施低GI膳食指导干预,对照组仅按照国家规范给予指导,不给予低GI膳食的指导.两组分别在孕早期、中期和晚期干预3次.干预组和对照组各纳入25例.孕妇分娩时收集胎盘组织和脐血,提取DNA,采用Illumina甲基化芯片进行两步法全基因组甲基化测定.结果 孕妇孕期相关暴露因素在干预组与对照组差异无统计学意义;胎儿出生体重干预组高于对照组[(3.7 ±0.5) vs(3.5±0.4)kg],但差异无统计学意义(P =0.248).本研究结果结合生物信息数据库分析,筛选出19个基因位点,所属18个基因,其中5个基因位于1号染色体,2个基因位于7号染色体,其余基因分布分散.比较干预组与对照组甲基化的改变,发现脐血中2个差异的甲基化CpG位点,分别位于TEKT5和MIR378C基因上,胎盘组织中1个差异的甲基化CpG位点,所属PGBD5基因.结论 通过对超重孕妇采取低GI膳食干预,胎盘组织和脐血中基因的甲基化可以发生改变,为中国超重、肥胖孕妇疾病的预防提供新的方法,对子代的健康成长有重要的意义.

目的 探索性研究川崎病(KD)患儿恢复期外周血管内皮功能与急性期血清C-反应蛋白(CRP)水平及冠状动脉损害(CAL)的关系,探讨外周血管内皮功能测定作为KD患儿血管内膜功能康复指标的可能性.方法 纳入复旦大学附属儿科医院(我院)心内科住院、具备完整的急性期临床资料、病程＞2个月,并于我院心内科随访的KD患儿.采用EndoPat2000仪器测定外周血管内皮功能,记录反应性充血-外周动脉张力指数(RHI).将血清CRP值转化为有序多分类资料进行分析,划分切点为第20、40、60、80和100百分位,分为5组.观察KD患儿RHI分布的特征.调整患儿年龄和性别后,分析RHI与急性期血清CRP的关系;比较发生和未发生CAL的KD患儿血清CRP和RHI水平的差异.结果 26例KD患儿进入本研究,男21例.平均年龄(83±24)个月,平均病程(27±17)个月.急性期CRP平均水平为91.9 mg·L-1.平均RHI为1.3 mL·mm-1Hg×100.调整了年龄和BMI Z评分后,RHI与CRP呈负相关(R2=0.4119,Pmodel=0.025 3,b=-0.483,PcRP =0.019).发生CAL的KD患儿的RHI水平低于未发生CAL患儿,(1.04 ±1.10)vs(1.34±0.08) mL.mm-1Hg×100,P=0.054,急性期的CRP水平在发生和未发生CAL的KD患儿间差异无统计学意义.结论 急性期CRP水平与KD恢复期外周血管内皮功能存在负相关,即CRP水平越高,内皮功能受损越严重;发生CAL患儿内皮功能损伤更严重.

Objective In order to find out the relationship between birth weight and systolic and diastolic blood pressure in preschool children.Methods Date for 4 642 healthy preschool children aged 2 to 6 were collected.All these children were born in Shanghai Minhang Maternal and Child Health Hospital.After rest in the sitting position for 5-10 min,the blood pressure(BP) and heart rate(HR) were measured on the right arm at the level of the heart,using appropriate size of cuff,by automated BP recorder(Model 45NEO-E6,Welch Allyn,USA).Elevated blood pressure was defined as systolic blood pressure(SBP) and/or diastolic blood pressure(DBP) equal or greater than the 95th percentile for gender and age,according to the reference based on Japanese preschool children(1997).Low birth weight was defined as < 2 500 g and macrosomia as ≥4 000 g.Multiple regression models were used to analyze the association between birth weight and childhood hypertension.Results In total 4 642 children were analyzed in this study,with 2 458(52.9%) being boys.The proportions of low birth weight and macrosomia were 3.2%(148/4 642) and 5.4%(251/4 642),respectively.The prevalence rate of hypertension was more common in boys than girls(9.4% vs 6.9%,P<0.05).Trend of negative correlation between birth weight and childhood DBP was observed in children with birth weight over 4 000 g.With gender,age,heart rate,body height and body weight adjusted,the relationship between birth weight and childhood hypertension was not significant in either low birth weight or macrosomia group.Rapid heart rate may increase the risk of hypertension at childhood(OR=2.55,95% CI:1.96-3.33).Conclusion Blood pressure levels of preschool children were not significantly associated with birth weight.Rapid heart rate may increase the risk of hypertension.

目的：利用妇幼保健院常规体检数据，观察学龄前儿童高血压的患病情况，分析出生体重与收缩压（SBP）、舒张压（DBP）以及血压升高的关系。

Objective To investigate the prevalence of hypertension in representative sample of children and adolescents aged 7-17 years in Shanghai,by using the current national age-and gender-specific cutoffs(NBPR) and using a new cutoffs including height percentiles(BPCH).Methods The data were from the 2010 routine survey of Shanghai Municipal Center for Students 'Physical Fitness and Health Surveillance involving 3 300 boys and girls respectively.Hypertension was defined as average SBP /DBP equal to or above the 95th percentile.BPCH was constructed by using GAMLSS program,for gender,age and height percentiles,based on non-overweight study subjects from 1991-2009 Chinese Health and Nutrition Survey.Children and adolescents' with inconsist results dignosed by BPCH and NBPR were analyzed,heights of them were compared by Z-score.Results The prevalence rate of hypertension diagnosed by NBPR was 11.3% for males and 10% for females.The rate was 6.9% for males and 6% for females by using NBPR.The prevalence rate increased with age by NBPR whereas it kept approximately stable by BPCH.The Kappa index of hypertension was 0.583 in male and 0.695 in female using the two references,and the consistent rate was 93%,95% respectively.377 samples(5.7% in total) were diagnosed as hypertensive by both cutoffs.50(boys:42,girls:8) hypertensive children were in BPCH who were missed by NBPR,with mean height lower than mean height of total samples by 17cm in boys(Z=-0.78,P<0.000 1) and 11 cm in girls(Z=-1.29,P=0.015 9) respectively.There were 329 students(5% in total) diagnosed by NBPR but missed by BPCH,with mean height being higher than average levels,13.9 cm in boys(Z=0.31,P<0.000 1) and 10.2 cm in girls(Z=0.39,P<0.000 1).Conclusion It is suggested that height should be considered in diagnosis of hypertension and included in cutoffs for accurate estimation of blood pressure in children and adolescents.

Objective To develop a new statistical method for comparing effectiveness of two treatments for the same disease indication.A statistical method needs to be developed to compare effectiveness of different treatments by using existing clinical data when lacking of evidence from randomized controlled trials.Methods Datasets including an outcome variable and a confounder for two treatments were simulated.Subjects in each dataset were randomly divided into two arms for 100 times,and the means were compared by using student-t tests and Per-protocol analysis strategy was applied.Subjects with assigned treatment by randomization that was contradictory to the actual received treatment were considered drop-out of conventional RCTs,and were excluded from comparisons of means.The ratio of the frequency of hypothesis tests that rejected H0 to the frequency of hypothesis tests that did not reject H0,called odds,was used to predict the probability of significant tests for group difference.To document the consistency and reliability of the method,the distribution of odds and its 95% CI,and the confounding effect were described in simulated datasets with various between-group mean differences and statistical power(ranging from 0.5 to 0.85) with varied sample sizes(n=50,100,500,and 1 000).Stata 11.0 was used to program and perform the analysis.Results The odds and its 95%CI of simulated RCTs were perfectly and linearly correlated with the change of between-group mean differences and statistical power,by difference sample size.A conclusion could be made based on the hypothesis of the simulated randomized controlled trials(sRCT).The probability of loss of balance of confounding was over 95% for equal and unequal sample size of two arms after excluding misclassified subjects.Conclusions The proposed novel analytical method,simulated RCTs based on real clinical treatment data,can be used to compare effectiveness of two treatments when evidence from RCTs is unavailable.

Objective The aim ofthis study was to develop a reference percentile curves of BP measured by automated device from a representative sample of preschool children in shanghai.Methods 4 619 healthy preschool children from 2 to 6 years of age were consecutive enrolled from March 2006 to November 2010 and allthese children were born and received regular physical examination in Shanghai Minhang Maternal and Child Health Hospital.BP and heart rate were measured onthe right arm atthe level ofthe heart after each child had rested inthe sitting position for 5 min,using automated BP recorder ( Model 45NEO-E6, Welch Allyn,USA) .All measurements were performed inthe clinic room ofthe hospital withthe temperature between 20℃ and 25℃ .Children were kept natural posture when BP was measured by trained pediatricians.Centile curves for SBP and DBP were drawn by sex using LMS method,the 5th ,50th ,90th ,95th ,99th percentiles of SBP and DBP were compared withthose from Japanese preschool children withthe same age.Results BP increased linearly with age for both boys and girls.Generally,the means of SBP and DBP for girls showed slightly lowerthan the boys ( female: 5.55 mmHg vs 2.05 mmHg; male: 6.62 mmHg vs 4.62 mmHg) , respectively.The percentiles of BP fromthe current study were significantly different fromthe Japanese references.The SBP 95th percentile of current study was significantly lowerthan Japanese references for boys and girls by 6-11 mmHg.The DBP 95th percentiles of boys aged 2 were slightly lowerthan Japanese reference,however,they remainedthe same levels from 3-6 years old.The percentiles of girls at 2-3 years old were lowerthan the Japanese reference,and exceeded at 3-4 years old and kept slightly higher to age of 6 years.Compared withthe data fromthe Japanese,children in our study were found to have a lower height duringthe age range for both sexes( male: 1.16 cm,3.16 cm,,6.06 cm,7.54cm and 6.3cm; female: 1.15,2.27,6.68,8.23, and 7.33 cm,respectively) .Conclusions This study providesthe median,90th and 95th percentile reference values of SBP and DBP based on a single-center large sample of children aged 2-6 years.These reference percentiles may be useful to primary child care providers forthe early screening and prevention of hypertension in Chinese preschool.

Objective The prevalence of obesity and related cardiometabolic comorbidities increased dramatically in Chinese populations at all ages. This study aimed at investigating the prevalence of metabolic syndrome (MS) and components among pregnant women in early gestation and evaluating the associations with macrosomia.Methods A population-based routine data from Kunshan Maternal and Child Health Care Hospital from 2009 to 2010 were retrospectively analyzed. The prenatal informations were analyzed among pregnant women who received the first prenatal examination less than 20 gestation weeks, including maternal anthropometrics and blood pressure at the first prenatal visit, fasting plasma glucose and serum lipids examined in the first trimester. Birth weight and gestational age were obtained from neonates' medical records in the hospital. MS was defined according to the International Diabetes Federation (IDF) criteria 2005. Owing to waist circumferences during pregnancy was imprecise, body mass index (BMI) ≥24 kg·m-2 in first prenatal visit was used to define overweight.Results Statistical analyses were performed among 1 405 subjects with complete prenatal data. The mean of maternal age and BMI at the first prenatal visit was (26.5±3.2) years and (20.8±2.7) kg·m-2, respectively. The mean of triglyceride, HDL-C and fasting glucose was (2.4±1.0), (2.0±0.4) and (4.5±0.5) mmol·L-1, respectively. The mean of SBP and DBP was (107.7±10.0) and (69.3±7.0) mmHg. The overall prevalence of MS, overweight, elevated triglyceride, reduced HDL-C, raised blood pressure and raised glucose among pregnant women in early gestation was 1.8%, 12.0%, 76.2%, 2.8%, 2.6% and 2.3%, respectively. The mean of the birth weight and gestational age was (3 365.0±418.6) g and (39.0±1.4) weeks with the incidence of macrosomia being 7.0%. Stepwise multiple logistic regressions for 497 subjects with the first prenatal visit within 20 gestational weeks and complete prenatal and neonatal birth weight showed in early gestation maternal overweight/obesity (OR=2.4, 95%CI: 1.0~5.5) significantly increased the risk of macrosomia. There was no significant difference in the proportion of maternal overweight in early gestation between analyzed subjects and those missing birth weight data by using Person's chi-square tests.Conclusions About 1.8% of Chinese pregnant women met the criteria of MS in early gestation. The commonest components of MS including raised triglyceride (76.2%) and overweight (12.0%), were the most important risk factors for macrosomia. The findings call for the urgent need for early and throughout management of metabolic risks among pregnant women in order to control the adverse gestation outcomes.