Objective To evaluate the methodological quality and level of publications in Chinese Journal of Evidence-Based Pediatrics and to improve the methodological quality of Chinese journals in the field of pediatrics further. Methods All articles published from May 2006 to December 2009 were manually reviewed. Articles relevant to human health care were evaluated on the quality of research and report according to clinical epidemiology/DME methodology. To evaluate the methodological quality of the articles, Hedges Project criteria were adopted and all studies were classified into original study, review article, case report and general or miscellaneous article. Each article was evaluated according to the methodological rigor for its corresponding category and rated dichotomously as pass or fail. In addition to using the Hedges Project criteria, each article was classified according to the Oxford Centre for Evidence-based Medicine levels of evidence. Using the classification system the validity of the evidence was ranked into a hierarchy, with level Ⅰ being the highest level and level Ⅴ the lowest. Articles were also assessed by Hedges Project criteria and Oxford Centre for Evidence-based Medicine levels of evidence stratifiedly by the purpose of the article. All the results above were compared with the related data of the articles published in 4 clinical ophthalmic journals abroad. Results ①According to clinical epidemiology/DME methodology, 187/310 articles were relevant to human health care. Among them, there were 7 RCTs, 19(10.2%) Meta-analyses, 1(0.5%) systematic review, 3(1.6%) self controlled studies, 4(2.1%) prospective cohort studies, 7(3.7%) retrospective cohort studies, 35(18.7%) case-control studies, 30(16.0%) cross-section surveys and 81(43.3%) descriptive studies; ②According to Hedges Project criteria to classify the purpose of the articles, there were 9/231(3.9%) articles were on etiology, 29(126%) on diagnosis, 47(20.3%) on treatment, 1(0.4%) on clinical prediction guide, 3(1.3%) on qualitative analysis and 142(615%) on others; ③According to the Oxford criteria, 14.7% of the articles were defined as level Ⅰ, 5.5% level Ⅱ, 25.7% level Ⅲ, 17.4% level Ⅳ, 36.7% level Ⅴ; ④Overall, 41(47.7%) of the 86 articles relevant to human health care for assessment met Hedges Project criteria, of which 32 articles were defined as level Ⅰ and 9 level Ⅱ. Conclusions The methodological quality of the articles published in Chinese Journal of Evidence-Based Pediatrics from 2006 to 2009 was almost equal to that in 4 clinical ophthalmic journals in 2004, but some aspects like estimation of sample size, bias and confounding factors needed to be improved.
Objective To establish the baseline data on awareness about evidence-based medicine of Chinese pediatricians in order to compare with future related studies. Methods Twenty one cities were selected as the implementation sites of the cross-section survey. The survey began at April 28th 2009 and ended at July 18th 2009. The questionnaire of the cross-section study was designed by editorial department of Chinese Journal of Evidence-Based Pediatrics, consisting of 20 items, of which basic data (education, work experience, position and hospital levels) and awareness about evidence-based medicine (listening to evidence-based medical lectures, applying evidences to medical works, the main basis for making clinical decisions and sequence of reading articles apart from abstract) were analyzed. Results We received 2 102 replies(963%) of the 2 182 questionnaires we sent out, of which 57 questionnaires were invalid. The data of 2 045 valid questionnaires were analyzed.The number of college education was 191/2 032, undergraduate 1 283, master 502 and doctor 56; residents 678/1 983, doctors 556, deputy chief physicians 471 and chief physicians 278; hospital grade Ⅰ 150/2 020, grade Ⅱ 641 and grade Ⅲ 1 229; work experiences <2 years 399/2 035, -5 years 362,-10 years 259 and more than 10 years 1 015. ① 401/2 023（19.8％） respondents never listened to any lectures on evidence-based medicine, 965(47.7%) listened 1-2 times and 657(325%) listened more than 3 times. Stratified analysis revealed that the proportion of listening to evidence-based medicine significantly increased with the elevation of education, work experience, position and hospital levels (P<0.05). ② 205/1 988（10.3%） respondents never applied evidences to clinical works, 1 021（51.4％）occasionally and 762（38.3％） often. Stratified analysis showed that the proportion of applying evidences to clinical works significantly increased with the elevation of education, work experience, position and hospital levels (P<0.000 1）. ③ The percentages of using clinical guidelines, textbooks, experiences and original papers to make clinical decisions were 71.2%, 59.6%, 41.7% and 15.3%, respectively. Stratified analysis revealed that using textbooks to make clinical decisions had no relations to education, work experience, position and hospital levels; the proportion of using clinical guidelines and original papers to make clinical decisions increased with the elevation of work experience, position and hospital levels, not related to education ④ The respondents firstly reading foreword were 1 202/1 970（61.0％）, firstly reading methods were 98/1 941（5.0％）, firstly reading results were 560/1 986（28.2％）, firstly reading discussion were 126/1 964（6.4％）. The reading sequence of 1 202 firstly reading foreword was analyzed again. It showed 723/1 941（37.2％） respondents firstly read methods, the ratio of which significantly increased with the elevation of education. 890/1 986（44.8％）respondents firstly read results, the ratio of which significantly increased with the elevation of education and hospital levels. Conclusions Chinese pediatricians are certainly aware of evidence-based medicine, but the percentage of applying clinical guidelines, textbooks, experiences to make clinical decisions is higher than that of applying original literatures. Chinese pediatricians put emphasis on the results when reading literatures.
Objective To design the hour-specific bilirubin nomogram of healthy term and near-term newborns and assess its predictive ability to screen risks of sequent hyperbilirubinemia. Methods ranscutaneous bilirubin(TCB) was measured for healthy infants (gestational age≥35 weeks and birth weight≥2 000 g) from birth to 7 days. Infants whose TCB≥250 μmol·L-1 were detected for bilirubin with microdetermination. We designed the hour-specific bilirubin nomogram with these data. Newborns were divided into 4 groups based on the predischarge bilirubin "risk zone" (≤40th, -75th, -95th, and ＞95th percentile defined as low, low-intermediate, high-intermediate and high risk zones on the hour-specific bilirubin nomogram) to predict subsequent hyperbilirubinemia. Results Four thousand and four hundred sixty-two infants with 27 271 hour-specific bilirubin data were enrolled into the study. Before discharge, total serum bilirubin(TSB) values of 5.2%(233/4 462) infants were in the high-risk zone; of them, 48.9% (114/233) remained in that zone ［likelihood ratio(LR) 9.5, sensitivity 26.7%; specificity 97.1%, probability 48.9%］ post discharge. Before discharge, TSB values of 23.2%(1 034/4 462) infants were in the high-risk and intermediate-risk zone（sensitivity 78.9%, specificity 82.5%）.The predischarge TSB values in 41.3% (1 845/4 462) infants were in the low-risk zone and there was no measurable risk for hyperbilirubinemia (LR 0, sensitivity 100%, specificity 45.5%, probability 0). The receiver operating characteristic(ROC) curves were drawn to assess the predictive abilities of the predischarge bilirubin level and prediction model that was combined with gestational age. The areas under the ROC curves were 0.870 and 0.908, respectively. Conclusions The study showed good predictivity of hour-specific TSB to the risk of hyperbilirubinemia of newborns. Gestational age improved prediction of subsequent hyperbilirubinemia compared with early TSB levels alone.
Objective To analyze the long-term prognosis of Kawasaki disease (KD) with GCAA. Methods From May 2001 to May 2006, inpatients diagnosed as KD with coronary arterial lesion(CAL) in Guangzhou Women and Children's Medical Centre were enrolled into the study, who were divided into coronary arterial dilation(CAD) group, small or medium coronary artery aneurysm (CAA) group and GCAA group.The follow-up started from discharge after acute stage and ended in May,2009.They were followed up at the end of the 6th month, the 1st year, the 2nd year, and the 3rd year after discharge by echocardiography (Echo); The patients whose CA didn′t return to normal by Echo or whose EKG presented suspectable myocardial ischemia in 3 months after acute stage were underwent ATP stress Echo and coronary angiography. The patients died were taken autopsy and pathological examinations. Results Fifteen patients with GCAA were enrolled into GCAA group. The average age was (2.7±2.6) years(3 months-10 years). One hundred sixty patients with CAD and 59 patients with small or medium CAA were enrolled into control group. ①At the 3 years follow-up time point, in GCAA group 2/15 cases(13.3%) showed normal coronary artery by Echo,which was significantly different from CAD group and small or medium CAA group (P<0.001);1/15 case(6.7%) showed dilation,10/15 cases(66.7%) prestened CAA, including 3 cases with GCAA and 3 cases with stenosis or oclussion in CA. ②The rate of abnormalities of wall motion in GCAA group by ATP stress Echo was significantly different from that in CAD group(χ2＝12.3，P<0.001), but no difference was found from that in small or medium CAA group (χ2＝0.4，P>0.05). Parametric test showed that the rate of abnormalities of wall motion in GCAA group was higher(Z=-4.2，P<0.001). ③In GCAA group, 6/15 cases were underwent coronary angiography. Four out of 6 cases (66.7%) still presented CAA，1/6 case was regressed to CAD.Five out of 6 cases were found stenosis and(or) occlusions , including 1 case with coronary recanalization after occlusion and 1 case with branch vessels. ④2 cases died in GCAA group. Autopsy findings: LCA and RCA were markedly and continuously beaded dilated; The aneurysms contained dark red thrombus, which almost occluded the entire lumen, and mural thickening was also noted. Pathological findings:inflammatory cell infiltration was shown and intimal was thickening. Conclusions The long-term prognosis of children with GCAA caused by KD is poor.The CAL will last for a long time or even causing death.The GCAA will develop to stenosis and occlusions which may lead to ischemic heart disease in late stage. It is useful to apply the Echo combined with ATP stress Echo and coronary angiography in the long-term follow-up of KD with GCAA.
Objective Cytochrome P450 (CYP450) is a family of the body′s more powerful detoxic enzymes that involve in the biotransformation of various endogenous and exogenous compounds including clinical drugs. Genetic and phenotypic polymorphism of CYP results in the individual differences of xenobiotic metabolisms. The aim of this study was to understand the genetic polymorphism and the metabolic phenotype of CYP450 subtypes in normal Chinese Han population, and to obtain the genetic data of these loci in Chinese Han population. Methods We identified 300 children who were randomly sampled from the outpatient and inpatient departments from March, 2005 to December, 2008. Members of these children were of Chinese Han nationality. The mean age of them was 5.0 years (SD: 4.3; range: 0.17-16.0 years), and the proportion of female children was 39.3%. Information on these children were obtained from the patients′ files, and all the participants and their parents provided written informed consent. Genomic DNA was extracted from peripheral blood by EDTA anticoagulation, using a standard salting-out procedure. The concentration and purity of DNA were estimated spectrophotometrically. Eight important SNPs in 6 important CYP450 subtypes (CYP2C9 1075A>C, CYP2C19 636G>A, CYP2C19 681G>A/C, CYP2D6 100C>T, CYP2E1 -1053C>T, CYP2E1 7632T>A, CYP3A4 878T>C and CYP3A5 6986A>G) were chosen for this study. The genotypes of these SNPs in 300 random Chinese Han children were typed by real-time PCR, and then by sequencing to examine the reliability of the results. The frequencies of genotypes and alleles were calculated by SHEsis on-line software. And the Hardy-Weinberg equilibrium (HWE), which indicates the absence of a discrepancy between the genotypic and allelic frequencies, was carried out using SPSS software, version 13.0. Results The frequencies of wild heterozygote on the loci of CYP2C19 681G>A/C,CYP2D6 100C>T and CYP3A5 6986A>G (46.3％, 47.0％ and 43.7％) were high in Chinese Han population, and the frequencies of mutant homozygote on the loci of CYP2D6 and CYP3A5 were higher than those of wild homozygote (35.3％ vs 17.7％, 41.7％ vs 14.7％), so the frequencies of the corresponding alleles were also higher (34.5％, 58.8％ and 63.5％). The frequencies of wild homozygote on the loci of CYP2C19 636G>A, CYP2E1 -1053C>T, CYP2E1 7632T>A and CYP3A4 878T>C(100％,89.3%, 61.3%, 58.3% and 98.0%) were high in Chinese Han population, the genetic variability on the loci of CYP2C9 1075A>C and CYP3A4 878T>C (0, 2.0％) were especially rare in Chinese Han population. The metabolic phenotypes of CYP2C19,CYP2D6 and CYP3A5 in Chinese Han population were mostly intermediate and/or poor metablizer(11.4%, 35.3% and 41.7％). The metabolic phenotypes of CYP2C9, CYP2E1 and CYP3A4 in Chinese Han population were mostly extensive and/or ultrarapid metablizer (100%, 95.0% and 100%). Conclusions The mutation frequencies of these three SNPs (CYP2D6 100C>T, CYP2C19 681G>A/C and CYP3A5 6986A>G) are high in random Chinese Han population, and the frequencies of these three subtypes with intermediate and poor metablizer were also high, so they could be the candidate loci for subsequent optimization grouping SNPs research and guiding the individualized medication.
Objective To evaluate the results of PPD test influenced by different standards, and to compare PPD test and the whole-blood interferon-γ(IFN-γ) assay for the diagnosis of tuberculosis(TB) infection in children. Methods All the participants were grouped into 5 groups according to the risk of infection: Group 1, children with pulmonary disease, without identifiable risk of M.tuberculosis infection (n=40); Group 2, children with pulmonary disease ,with identifiable risk of M.tuberculosis infection(n=11); Group 3, children with TB diagnosed on the basis of clinical findings ,without identifiable risk of M.tuberculosis infection(n=29); Group 4, children with TB diagnosed on the basis of clinical findings, with identifiable risk of M.tuberculosis infection(n=27); Group 5, children with TB confirmed by pathogeny or pathology(n=18). The indexes of PPD test and IFN -γ assay, including sensitivity, specificity, likelihood ratio et al, was evaluated in all the subjects. The correlation of the two tests with the risk of tuberculosis infection was measured by estimating the coefficient of correlation. Results The sensitivity decreased significantly with positive standard increasing gradually. Especially when a 15-mm induration cutoff was used, we found a false-negative tuberculin skin test result. Of 74 TB patients, 15（15/74，20.3%）children had positive IFN-γ assay results and negative PPD test results, 16（16/74，21.6%）children had the PPD induration ranged from 10-14 mm. When a 10-mm induration cutoff was used in active TB patients which suggested that 10-mm was the best critical value of PPD test in patients. When the 10-mm induration cutoff was used in detection of latent tuberculosis infection, the specificity of PPD test decreased significantly. The sensitivity and specificity of PPD test(10-mm cutoff value) were 77.0% and 70.6%, respectively.We considered that the false-positive result was caused by BCG vaccination or nontuberculosis mycobacterial(NTM) infection. The result indicated that BCG vaccination was the influencing factor of PPD test. When the cutoff point was increased to 15mm, 12.5%(5/40) and 9.1%（1/11）children were diagnosed as tuberculosis infection in group A and B by PPD test, which was in accordance with the predicted prevalence of TB infection(9%). The sensitivity and specificity of IFN -γ assay were 85.1% and 94.1% respectively, which were significantly higher than PPD tests. The result suggested that IFN-γ assay was an important tool in the diagnosis of active TB and TB infection. Although both of the two tests were related to the exposure factors of tuberculosis infection, IFN -γ assay was better than PPD test. Conclusions When detection of latent tuberculosis infection, the 15-mm cutoff point could help to avoid the effect of BCG vaccination or NTM infection. In the diagnosis of active TB patients, the 10-mm cutoff point could help to increase the sensitivity of PPD test. The whole-blood IFN-γ assay could be used as a important assistant tool of the tuberculin test in the clinical diagnosis of pediatric tuberculosis infection.
Objective The reliable measurement of glomerular filtration rate(GFR) is of great importance in clinical practice and research. The usage of radionuclides has offered an alternative method of estimating GFR that avoids some of the practical disadvantages of inulin clearance. But radioisotopic method has the disadvantage of precautions being required in handling and disposing of radioactive materials and is also expensive. To circumvent the practical difficulties of formal measurement of clearance, several prediction formulas have been published. The most common usage in children and adolescents is the Schwartz formula based on the serum creatinine level. The aim of this study was to identify an adequate measurement of GFR in pediatric clinical practice. Methods Children with chronic kidney disease from Children′s Hospital of Fudan University from April 2002 to December 2006 were collected. 99Tcm-DTPA clearance (mGFR) was measured as GFR marker in patients with different kidney disease. At the same time estimated GFR (eGFR) was calculated via the equation developed from Schwartz formula according to serum creatinine level. eGFRs were compared with measured GFRs. The agreements between them were evaluated by B kappa statistics. The precision was evaluated by R2 from linear regression. The accuracy was measured by the percentage of GFR estimate within ±30％of the measured GFR (P30). Results 170 patients with CKD(100 boys and 70 girls) were enrolled into the study. The mGFR was (73.3±26.8) mL·min-1·173 m-2. The eGFR from Schwartz formula was (74.2 ±27.9) mL·min-1·173 m-2. Pearson correlation analysis showed good correlation between mGFR and eGFR（r＝0.871,P< 0.05). The concordance study using the Bland-Altman method showed that there was better consistency between eGFR and mGFR in CKD stage 1 to stage 2 than that in CKD stage 3 to stage 5. The over estimate of the Schwartz formula increased with GFR decreasing. Conclusions Compared with the reference standard, the Schwartz formula shows a certain degree of accuracy．In non-examination condition situation, the Schwartz formula is suitable for estimating GFR of children and adolescents. The formula remains useful for following changes of renal function in patients.
Objective To evaluate the fetal cardiac function in the mothers with hypertensive disorders complicating pregnancy. Methods From two obstetric clinical centers, hypertensive and uncomplicated pregnant women were included. According to the severity the hypertensive women were divided into Group A (gestational hypertension or mild pre-eclampsia) and Group B (severe pre-eclampsia). Parameters of fetal cardiac systolic, diastolic and global function were evaluated by fetal echocardiography. Results Thirty one hypertensive pregnant women were selected into Group A(n=16) and Group B(n=15), and 36 uncompliacted pregnant women were enrolled into the control group.The comparisons showed Group B>A>Control in maternal ages, Group BA>Control however the differences were not significant (P=0.071 and 0.092, respectively). Comparisons in left ventricular shortening fraction and ejection fraction showed Group BA>Control however the differences were not significant. Right ventricular Tei index in Group B was obviously larger than in control group (P=0.023). Conclusions In hypertensive disorders complicating pregnancy fetal left ventricular blood volumes increase, systolic function and ventricular compliance are impaired. In fetuses of severe pre-eclampsia right ventricular global function decrease. The results may contribute to evaluate the states and outcomes of fetuses and better prenatal monitoring in hypertensive pregnancy.
Objective To establish Hirschsprung′s disease(HD) neonatal rat model similar to human being and evaluate the model． Methods Ninety neonatal SD rats，6-7 days old，were randomly divided into normal group，experimental group and control group．All rats were operated under ether anesthesia．In experimental group，0．1% benzalkonium chloride (BAC) solution was applied to the descending colon for 15 minutes to set up the model，0．9% normal saline was applied in control group．There was no treatmetnt in normal group．At an interval of 1 week，3 weeks，5 weeks，6 weeks and 7 weeks after BAC treatment，general observation was performed．The expression of S-100 protein and neuron-specific enolase（NSE） were detected with immunohistochemistry．The distribution and expression of c-Kit in each group interstitial cells of Cajal (ICC) were detected with immunofluorescence． Results〓 ① 7 weeks after BAC treatment，the rats had abdominal distention，defecation decrease，spirit flagging，emaciation，fecal pellets were significantly larger and drier than the control group and the normal group．Autopsy revealed a narrowed segment at the site of BAC treatment，spasm and no peristalsis，accompanied by distended proximal colon filled with massive feces．② 1 week，3 weeks，5 weeks and 6 weeks after BAC treatment，the results of HE staining showed gradually ganglion cells in the myenteric and submucous plexuses decreased．Seven weeks after BAC treatment，ganglion cells in the myenteric and submucous plexuses completely disappeared without scar formation and inflammatory cell infiltration．The control group and the normal group showed normal ganglion cells in myenteric and submucoous plexuses．③ 1 week，3 weeks，5 weeks and 6 weeks after BAC treatment，the expression of S-100 protein and NSE decreased in ganglion cells of myenteric and submucous plexuses. 7 weeks after BAC treatment，ganglion cells of myenteric and submucous plexuses completely disappeared．S-100 protein expressed in cytoplasm and nuclei of ganglion cells and appeared as brown particles， NSE expressed in cytoplasm and nuclei of ganglion cells and appeared as brown particles．There were no significant differences in changes of expression of between control group and the normal group．④ 1 week，3 weeks，5 weeks，6 weeks and 7 weeks after BAC treatment，the expression of c-Kit decreased，and the distribution of ICC was decreased obviously，compared with the control group and the normal group．The network was disappeared，and the configuration of the residual ICC was abnormal．The ICC got blunted and short processes．In the control group and the normal group there were no significant changes in expression． Conclusions HD model can be established successfully in neonatal rats by applying BAC to ablate enteric plexus，which provides an experimental basis for ICC as the target of the treatment of HD．
