DataSheet1_Detection of pediatric drug-induced kidney injury signals using a hospital electronic medical record database.docx

Background: Drug-induced kidney injury (DIKI) is one of the most common complications in clinical practice. Detection signals through post-marketing approaches are of great value in preventing DIKI in pediatric patients. This study aimed to propose a quantitative algorithm to detect DIKI signals in children using an electronic health record (EHR) database.Methods: In this study, 12 years of medical data collected from a constructed data warehouse were analyzed, which contained 575,965 records of inpatients from 1 January 2009 to 31 December 2020. Eligible participants included inpatients aged 28 days to 18 years old. A two-stage procedure was adopted to detect DIKI signals: 1) stage 1: the suspected drugs potentially associated with DIKI were screened by calculating the crude incidence of DIKI events; and 2) stage 2: the associations between suspected drugs and DIKI were identified in the propensity score-matched retrospective cohorts. Unconditional logistic regression was used to analyze the difference in the incidence of DIKI events and to estimate the odds ratio (OR) and 95% confidence interval (CI). Potentially new signals were distinguished from already known associations concerning DIKI by manually reviewing the published literature and drug instructions.Results: Nine suspected drugs were initially screened from a total of 652 drugs. Six drugs, including diazepam (OR = 1.61, 95%CI: 1.43–1.80), omeprazole (OR = 1.35, 95%CI: 1.17–1.54), ondansetron (OR = 1.49, 95%CI: 1.36–1.63), methotrexate (OR = 1.36, 95%CI: 1.25–1.47), creatine phosphate sodium (OR = 1.13, 95%CI: 1.05–1.22), and cytarabine (OR = 1.17, 95%CI: 1.06–1.28), were demonstrated to be associated with DIKI as positive signals. The remaining three drugs, including vitamin K1 (OR = 1.06, 95%CI: 0.89–1.27), cefamandole (OR = 1.07, 95%CI: 0.94–1.21), and ibuprofen (OR = 1.01, 95%CI: 0.94–1.09), were found not to be associated with DIKI. Of these, creatine phosphate sodium was considered to be a possible new DIKI signal as it had not been reported in both adults and children previously. Moreover, three other drugs, namely, diazepam, omeprazole, and ondansetron, were shown to be new potential signals in pediatrics.Conclusion: A two-step quantitative procedure to actively explore DIKI signals using real-world data (RWD) was developed. Our findings highlight the potential of EHRs to complement traditional spontaneous reporting systems (SRS) for drug safety signal detection in a pediatric setting.</p

Proportions of <i>Staphylococcus aureus</i> and Methicillin-Resistant <i>Staphylococcus aureus</i> in Patients with Surgical Site Infections in Mainland China: A Systematic Review and Meta-Analysis

<div><p>Background</p><p>Sufficient details have not been specified for the epidemiological characteristics of <i>Staphylococcus aureus</i> (<i>S. aureus</i>) and methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) among surgical site infections (SSIs) in mainland China. This systematic review aimed to estimate proportions of <i>S. aureus</i> and MRSA in SSIs through available published studies.</p><p>Methods</p><p>PubMed, Embase and four Chinese electronic databases were searched to identify relevant primary studies published between 2007 and 2012. Meta-analysis was conducted on the basis of logit-transformed metric for proportions of <i>S. aureus</i> and MRSA, followed by pre-defined subgroup meta-analysis. Random-effects meta-regression was also conducted to explore the impact of possible factors on <i>S. aureus</i> proportions.</p><p>Results</p><p>106 studies were included, of which 38 studies involved MRSA. <i>S. aureus</i> accounted for 19.1% (95%CI 17.2-21.0%; I² = 84.1%) of all isolates in SSIs, which was roughly parallel to 18.5% in the United States (US) (P-value = 0.57) but significantly exceeded those calculated through the surveillance system in China (P-value<0.001). In subgroup analysis, <i>S. aureus</i> in patients with thoracic surgery (41.1%, 95%CI 26.3-57.7%; I² = 74.4%) was more common than in those with gynecologic surgery (20.1%, 95%CI 15.6-25.6%; I² = 33.0%) or abdominal surgery (13.8%, 95%CI 10.3-18.4%; I² = 70.0%). Similar results were found in meta-regression. MRSA accounted for 41.3% (95%CI 36.5-46.3%; I² = 64.6%) of <i>S. aureus</i>, significantly lower than that in the US (P-value = 0.001). MRSA was sensitive to vancomycin (522/522) and linezolid (93/94), while 79.9% (95%CI 67.4-88.4%; I² = 0%) and 92.0% (95%CI 80.2-97.0%; I² = 0%) of MRSA was resistant to clindamycin and erythromycin respectively.</p><p>Conclusion</p><p>The overall proportion of <i>S. aureus</i> among SSIs in China was similar to that in the US but seemed higher than those reported through the Chinese national surveillance system. Proportions of <i>S. aureus</i> SSIs may vary with different surgery types. Commonly seen in SSIs, MRSA tended to be highly sensitive to vancomycin and linezolid but mostly resistant to clindamycin and erythromycin.</p></div

Additional file 3: of Can statistic adjustment of OR minimize the potential confounding bias for meta-analysis of case-control study? A secondary data analysis

Summary of included original study. (PDF 1 mb

General information of all the included studies.

<p>* In this column multiple surgeries refer to the different kinds of surgeries involved in the study which cannot be discriminated or classified into a specific type of surgery.</p><p>General information of all the included studies.</p

Additional file 1: of Can statistic adjustment of OR minimize the potential confounding bias for meta-analysis of case-control study? A secondary data analysis

Search strategy. (PDF 86 kb

Province distribution of proportions of <i>S. aureus</i> isolates in China.

<p>Province distribution of proportions of <i>S. aureus</i> isolates in China.</p

Overall proportion of <i>S. aureus</i> in patients with SSIs.

<p>Overall proportion of <i>S. aureus</i> in patients with SSIs.</p

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

<p><b>Objectives</b>: 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.</p> <p><b>Methods</b>: 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.</p> <p><b>Results</b>: 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.</p> <p><b>Conclusion</b>: 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.</p

Overall proportion of MRSA in patients with <i>S. aureus</i> SSIs.

<p>Overall proportion of MRSA in patients with <i>S. aureus</i> SSIs.</p

Summary of the pooled results of proportions of <i>S. aureus</i> and MRSA isolates.

<p>* Others refer to: 1) multiple surgeries involved in the study which cannot be classified into a specific type of surgery or 2) a specific type of surgery, rather than orthopedic, abdominal, gynecologic, or thoracic surgeries, which was reported in a small number of studies.</p><p>** Non-retrospective design comprises prospective, cross-sectional, ambispective study and surveillance.</p><p>*** Sample size in the proportions of <i>S. aureus</i> isolates refers to the number of all the detected bacteria isolates; in the proportions of MRSA it refers to the number of all <i>S. aureus</i> isolates.</p><p>Summary of the pooled results of proportions of <i>S. aureus</i> and MRSA isolates.</p