Xiaoxia Peng

The critical gap for pediatric reference intervals of complete blood count in China

BACKGROUND We examined the critical gap for pediatric reference intervals in China byvalidating 3 existing pediatric reference intervals (RIs) of complete blood count(CBC) respectively. METHODS A total of 2255 healthy children attended physical examination in Beijing Childrens Hospital. Fasted blood was sampled and CBC, including red blood cell (RBC) count, hemoglobin (HGB), hematocrit (HCT), platelet count (PLT) and white blood cell (WBC) count were measured by automated hematological analyzer Sysmex Xs-800i. The observed proportions of out-of-range (OOR) values were calculated by three RIs in order to examine its applicability. RESULTS Compared with RIs of CBC recommended by Zhu Futang Practice of Pediatrics, the upper side OORs of RBC count, HGB, WBC count, and PLT deviated from upper reference limit, which ranged from 10% to 91.9%. On the contrary, the lower side OOR of WBC count was 64%. Compared with Chinese adult RIs, the upper side OORs of WBC count and PLT were >10%. While the lower sides OORs of RBC count, HGB and HCT were >10% among boys <14y. It appears that the RIs validated by Beijing Childrens Hospital were relatively accurate RIs for children. CONCLUSIONS There is a gap for pediatric RIs in China. It is imperative to initiate research on establishing and validating pediatric RIs in China.

Postrandomization Confounding Challenges the Applicability of Randomized Clinical Trials in Comparative Effectiveness Research

whAt Is the PRoBleM? Different from trials for regulatory approvals of new interventions aimed to test the efficacy, comparative effectiveness research (CER) is the direct comparison of existing health‐care interventions (compared with active controls) to examine which treatment works best, for whom, and under what settings.[1] Therefore, CER is indispensable to assist consumers, clinicians, purchasers, and policy makers to make evidence‐based decisions. Actually, an obvious uprising tendency of CER after 2004 was displayed and a majority of CER was performed by randomized clinical trials (RCTs) with active controlled interventions.

Prenatal and perinatal risk factors for solid childhood malignancies: A questionnaire-based study

Childhood solid tumors account for the highest proportion of childhood cancers and are one of the leading causes of death in childhood. However, their pathogenesis is unclear.

Validity of web-based self-assessment of pubertal development against pediatrician assessments

A web‐based instrument for self‐assessment of puberty could be convenient and feasible for large‐scale multicenter population‐based epidemiological studies for Tanner stages evaluation.

Method Development for Clinical Comprehensive Evaluation of Pediatric Drugs Based on Multi-Criteria Decision Analysis: Application to Inhaled Corticosteroids for Children with Asthma

BackgroundEstablishing a comprehensive clinical evaluation system is critical in enacting national drug policy and promoting rational drug use. In China, the ‘Clinical Comprehensive Evaluation System for Pediatric Drugs’ (CCES-P) project, which aims to compare drugs based on clinical efficacy and cost effectiveness to help decision makers, was recently proposed; therefore, a systematic and objective method is required to guide the process.MethodsAn evidence-based multi-criteria decision analysis model that involved an analytic hierarchy process (AHP) was developed, consisting of nine steps: (1) select the drugs to be reviewed; (2) establish the evaluation criterion system; (3) determine the criterion weight based on the AHP; (4) construct the evidence body for each drug under evaluation; (5) select comparative measures and calculate the original utility score; (6) place a common utility scale and calculate the standardized utility score; (7) calculate the comprehensive utility score; (8) rank the drugs; and (9) perform a sensitivity analysis. The model was applied to the evaluation of three different inhaled corticosteroids (ICSs) used for asthma management in children (a total of 16 drugs with different dosage forms and strengths or different manufacturers).ResultsBy applying the drug analysis model, the 16 ICSs under review were successfully scored and evaluated. Budesonide suspension for inhalation (drug ID number: 7) ranked the highest, with comprehensive utility score of 80.23, followed by fluticasone propionate inhaled aerosol (drug ID number: 16), with a score of 79.59, and budesonide inhalation powder (drug ID number: 6), with a score of 78.98. In the sensitivity analysis, the ranking of the top five and lowest five drugs remains unchanged, suggesting this model is generally robust.ConclusionsAn evidence-based drug evaluation model based on AHP was successfully developed. The model incorporates sufficient utility and flexibility for aiding the decision-making process, and can be a useful tool for the CCES-P.

Evaluation of reporting quality for observational studies using routinely collected health data in pharmacovigilance

ABSTRACT Objectives: To appraise the reporting quality of studies which concerned linezolid-related thrombocytopenia referring to REporting of studies Conducted using Observational Routinely collected health Data (RECORD) statement. Methods: Medline, Embase, Cochrane library and clinicaltrial.gov were searched for observational studies concerning linezolid-related thrombocytopenia using routinely collected health data from 2000 to 2017. Two reviewers screened potential eligible articles and extracted data independently. Finally, reporting quality assessment was performed by two senior researchers using RECORD statement. Results: Of 25 included studies, 11 (44.0%) mentioned the type of data in the title and/or abstract. In 38 items derived from RECORD statement, the median number of items reported in the included studies was 22 (inter-quartile range 18–27). Inadequate reporting issues were discovered in the following aspects: validation studies of the codes or algorithms, study size estimation, quantitative variables, subgroup statistical methods, missing data, follow-up/matching or sampling strategy, sensitivity analysis and cleaning methods, funding and role of funders and accessibility of protocol, raw data. Conclusion: This study provides the evidence that the reporting quality of post-marketing safety evaluation studies conducted using routinely collected health data was often insufficient. Future stakeholders are encouraged to endorse the RECORD guidelines in pharmacovigilance.

Algorithm on age partitioning for estimation of reference intervals using clinical laboratory database exemplified with plasma creatinine

Abstract Background: We describe an algorithm to determine age-partitioned reference intervals (RIs) exemplified for creatinine using data collection from the clinical laboratory database. Methods: The data were acquired from the test results of creatinine of 164,710 outpatients aged <18 years in Beijing Children’s Hospital laboratories’ databases between January 2016 and December 2016. The tendency of serum creatinine with age was examined visually using box plot by gender first. The age subgroup was divided automatically by the decision tree method. Subsequently, the statistical tests of the difference between subgroups were performed by Harris-Boyd and Lahti methods. Results: A total of 136,546 samples after data cleaning were analyzed to explore the partition of age group for serum creatinine from birth to 17 years old. The suggested age partitioning of RIs for creatinine by the decision tree method were for eight subgroups. The difference between age subgroups was demonstrated to be statistically significant by Harris-Boyd and Lahti methods. In addition, the results of age partitioning for RIs estimation were similar to the suggested age partitioning by the Canadian Laboratory Initiative in Pediatric Reference Intervals study. Lastly, a suggested algorithm was developed to provide potential methodological considerations on age partitioning for RIs estimation. Conclusions: Appropriate age partitioning is very important for establishing more accurate RIs. The procedure to explore the age partitioning using clinical laboratory data was developed and evaluated in this study, and will provide more opinions for designing research on establishment of RIs.

Better reporting quality for improved pediatric investigation: Application of health research reporting guidelines

Institute of Health and at the leading pediatric departments throughout the United States and England. At Boston Children’s Hospital, we’ve been the leaders in pediatric innovation since the hospital opened its doors nearly 150 years ago. Innovation is in our hearts and in our heads. It’s our history and our future. Whether we are delivering care at the bedside or supporting those who do, we are all focused on the same mission-providing the highest quality care to the children and families who put their trust in us. We innovate for the future-for the children and families we care for, the ones whose faces we know and for the many more whom we don’t yet know. With the establishment of the Innovation and Digital Health Accelerator (IDHA), Boston Children’s is taking the next step in shaping the future of health care and extending our pediatric leadership through new technologies, collaborations with industry, and the development of a comprehensive digital health platform. IDHA draws together a team from across Boston Children’s, including innovators and trailblazers in the fields of informatics, technology, clinical, digital, business development talent, and the TeleHealth team, and provides Boston Children’s with a mechanism for sourcing, vetting, resourcing, building, piloting and commercializing innovations in collaboration with others across the enterprise. Through the creation of the Innovation and Digital Health Accelerator, Boston Children’s reinforces a commitment to, and investment in pediatric innovation. We are combining our data, clinical expertise, and health care technology development experience, with leading worldwide industry partners— including start-ups—to transform health care. COMMUNICATION | 11

Can statistic adjustment of OR minimize the potential confounding bias for meta-analysis of case-control study? A secondary data analysis

BackgroundDifferent confounder adjustment strategies were used to estimate odds ratios (ORs) in case-control study, i.e. how many confounders original studies adjusted and what the variables are. This secondary data analysis is aimed to detect whether there are potential biases caused by difference of confounding factor adjustment strategies in case-control study, and whether such bias would impact the summary effect size of meta-analysis.MethodsWe included all meta-analyses that focused on the association between breast cancer and passive smoking among non-smoking women, as well as each original case-control studies included in these meta-analyses. The relative deviations (RDs) of each original study were calculated to detect how magnitude the adjustment would impact the estimation of ORs, compared with crude ORs. At the same time, a scatter diagram was sketched to describe the distribution of adjusted ORs with different number of adjusted confounders.ResultsSubstantial inconsistency existed in meta-analysis of case-control studies, which would influence the precision of the summary effect size. First, mixed unadjusted and adjusted ORs were used to combine individual OR in majority of meta-analysis. Second, original studies with different adjustment strategies of confounders were combined, i.e. the number of adjusted confounders and different factors being adjusted in each original study. Third, adjustment did not make the effect size of original studies trend to constringency, which suggested that model fitting might have failed to correct the systematic error caused by confounding.ConclusionsThe heterogeneity of confounder adjustment strategies in case-control studies may lead to further bias for summary effect size in meta-analyses, especially for weak or medium associations so that the direction of causal inference would be even reversed. Therefore, further methodological researches are needed, referring to the assessment of confounder adjustment strategies, as well as how to take this kind of bias into consideration when drawing conclusion based on summary estimation of meta-analyses.