Guideline for the management of pediatric off-label use of drugs in China (2021).

BACKGROUND: The "Law on Doctors of the People's Republic of China," which was officially implemented on March 1, 2022, emphasizes the requirements for rational drug use and the necessity for appropriate management of off-label drug use. The safety and ethical considerations related to off-label drug use are different in children than in adults. There is so far no management guideline for pediatric off-label use of drugs in China, and the applicability of foreign guidelines is limited. Establishing a localized evidence-based management guideline for pediatric off-label use of drugs to support the national legislation and clinical practice is of critical importance. METHODS: We established a guideline working group, including experts from a broad range of disciplines and developed recommendations following the guidance of the World Health Organization Handbook and the Chinese Medical Association. The following themes were identified by questionnaires and expert interviews to be of great concern in the management of off-label drug use in children: general principles and characteristics of management of pediatric off-label drug use; establishment of expert committees; evidence evaluation; risk-benefit assessment; informed consent; monitoring and assessment of the risk; and monitoring and patient education. Two rounds of Delphi surveys were organized to determine the final recommendations of this guideline. We graded the recommendations based on the body of evidence, referring to the evaluation tool of the Evidence-based management (EBMgt) and the Oxford Center for Evidence-Based Medicine: Level of Evidence (March 2009). RESULTS: We developed the first guideline for the management of pediatric off-label use of drugs in China. CONCLUSIONS: The guideline is to offer guidance for pediatricians, pharmacists, medical managers, policymakers, and primary care physicians on how to manage off-label drug use in pediatrics and to provide recommendations for Chinese healthcare policy in the future.

Various application roles for Campbell systematic reviews: a citation analysis.

OBJECTIVES: Systematic reviews (SRs) are becoming essential evidence in the decision-making process within the field of social sciences. This study aimed to investigate how Campbell SRs were cited and explore their specific application roles. STUDY DESIGN AND SETTING: We included Campbell SRs published between 2016 and 2020 by searching the Wiley online library, and retrieved the articles and documents citing Campbell SRs from the Web of Science and Google Scholar by December 31, 2021. We described the characteristics of the SRs and citations, and formulated a set of application roles by analyzing the sentences or paragraphs where the SRs were cited. RESULTS: Sixty nine Campbell SRs were published between 2016 and 2020; they were cited in 641 articles or documents a total of 1,289 times. The primary types of articles that cited Campbell SRs were cross-sectional studies (n = 226, 35.3%), SRs (n = 112, 17.5%), randomized controlled trials (n = 77, 12.0%), and policy reports (n = 57, 8.8%). Articles utilizing Campbell SRs were predominantly led by authors from the United States (n = 184, 28.7%), the United Kingdom (n = 98, 15.3%), and Australia (n = 51, 8.0%). We formulated a set of 10 application roles for the Campbell SRs, of which the most frequent were: describing the current status in the field of interest (n = 691, 53.6%), corroboration of the results (n = 140, 10.9%), identifying research gaps (n = 130, 10.1%), and providing methodological references (n = 126, 9.8%); the role of supporting policy recommendations or decisions accounted for 6.0% (n = 77) of the citations. Approximately 12% of Campbell SRs were used to support policy recommendations or decisions. CONCLUSION: Campbell SRs are widely applied, particularly in scientific research, to describe the current status in the field of interest. Although the current application of Campbell SRs in supporting policy recommendations and decisions may not be predominant, there is a growing recognition of their value in using Campbell SRs to inform decision-making.

Exploring the diverse definitions of 'evidence': a scoping review.

OBJECTIVES: To systematically collect and analyse diverse definitions of 'evidence' in both health and social sciences, and help users to correctly use the term 'evidence' and rethink what is the definition of 'evidence' in scientific research. DESIGN: Scoping review. METHODS: Definitions of evidence in the health sciences and social sciences were included. We have excluded the definition of evidence applied in the legal field, abstracts without full text, documents not published in either Chinese or English and so on. We established a multidisciplinary working group and systematically searched five electronic databases including Medline, Web of Science, EBSCO, the Chinese Social Sciences Citation Index and the Chinese Science Citation Database from their inception to 26 February 2022. We also searched websites and reviewed the reference lists of the identified studies. Six reviewers working in pairs, independently, selected studies according to the inclusion and exclusion criteria, and extracted information. Any differences were discussed in pairs, and if there was disagreement, it was resolved via discussion or with the help of a third reviewer. Reviewers extracted document characteristics, the original content for the definitions of 'evidence', assessed definitions as either intensional or extensional, and any citations for the given definition. RESULTS: Forty-nine documents were finally included after screening, and 68 definitions were obtained. After excluding duplicates, a total of 54 different definitions of 'evidence' were identified. There were 42 intensional definitions and 12 extensional definitions. The top three definiens were 'information', 'fact' and 'research/study'. The definition of 'evidence' differed between health and social sciences. The term 'research' appeared most frequently in the definitions. CONCLUSIONS: The definition of 'evidence' has gradually attracted the attention of many scholars and decision-makers in health and social sciences. Nevertheless, there is no widely recognised and accepted definition in scientific research. Given the wide use of the term, we need to think about whether, or under what circumstances, a standardised, clear, meaningful and widely applicable definition of 'evidence' might be helpful.

Characteristics of the sources, evaluation, and grading of the certainty of evidence in systematic reviews in public health: A methodological study.

Objectives: To systematically explore how the sources of evidence, types of primary studies, and tools used to assess the quality of the primary studies vary across systematic reviews (SRs) in public health. Methods: We conducted a methodological survey of SRs in public health by searching the of literature in selected journals from electronic bibliographic databases. We selected a 10% random sample of the SRs that met the explicit inclusion criteria. Two researchers independently extracted data for analysis. Results: We selected 301 SRs for analysis: 94 (31.2%) of these were pre-registered, and 211 (70.1%) declared to have followed published reporting standard. All SRs searched for evidence in electronic bibliographic databases, and more than half (n = 180, 60.0%) searched also the references of the included studies. The common types of primary studies included in the SRs were primarily cross-sectional studies (n = 132, 43.8%), cohort studies (n = 126, 41.9%), randomized controlled trials (RCTs, n = 89, 29.6%), quasi-experimental studies (n = 83, 27.6%), case-control studies (n = 58, 19.3%) qualitative studies (n = 38, 12.6%) and mixed-methods studies (n = 32, 10.6%). The most frequently used quality assessment tools were the Newcastle-Ottawa Scale (used for 50.0% of cohort studies and 55.6% of case-control studies), Cochrane Collaboration's Risk of Bias tool (50.7% of RCTs) and Critical Appraisal Skills Program (38.5% of qualitative studies). Only 20 (6.6%) of the SRs assessed the certainty of the body of evidence, of which 19 (95.0%) used the GRADE approach. More than 65% of the evidence in the SRs using GRADE was of low or very low certainty. Conclusions: SRs should always assess the quality both at the individual study level and the body of evidence for outcomes, which will benefit patients, health care practitioners, and policymakers.

Prevalence of human immunodeficiency virus, syphilis, and hepatitis B and C virus infections in pregnant women: a systematic review and meta-analysis.

BACKGROUND: At the 74th World Health Assembly, the WHO issued a strategy for the prevention and control of several major infectious diseases. To achieve the WHO-initiated targets for these infectious diseases, the elimination of mother-to-child transmission is essential. To date, a systematic review of the global and regional prevalence of infections with relevant mother-to-child transmission and outside the spectrum of congenital infections is lacking. OBJECTIVES: We aimed to systematically review the prevalence of HIV, hepatitis B virus (HBV), hepatitis C virus (HCV), and syphilis in pregnant women. DATA SOURCES: MEDLINE, Embase, The Cochrane Library, Web of Science, China National Knowledge Infrastructure, WanFang database and China Biology Medicine disc database, and five WHO Regional Index Medicus databases. STUDY ELIGIBILITY CRITERIA: Original studies reporting the prevalence of infection or coinfection of HIV, HBV, HCV, and syphilis in pregnant women. METHODS: This systematic review followed the preferred reporting items for systematic reviews and meta-analyses 2020 checklist. We used random-effects models to generate pooled prevalence estimates for each infection. RESULTS: The global pooled prevalence in pregnant women of HIV, HBV, HCV, and syphilis was 2.9% (95% CI, 2.4-3.4%), 4.8% (3.8-5.8%), 1.0% (0.8-1.3%), and 0.8% (0.7-0.9%). The pooled prevalence of HIV, HBV, HCV, and syphilis in low-income countries was higher than the global level (HIV: 5.2% [1.6-10.5%); HBV: 6.6% (5.4-7.9%); HCV: 2.7% (1.6-4.1%); syphilis: 3.3% (2.2-4.6%]). The pooled prevalence of HIV, HBV, HCV, and syphilis in lower-middle-income countries was higher than the global level (HIV: 2.9% [0.8-6.1%]; HBV: 4.9% [3.8-6.1%]; HCV: 2.3% [1.2-3.6%]; syphilis: 1.5% [1.0-2.2%]). CONCLUSIONS: The prevalence of these infections among pregnant women was particularly high in resource-poor settings. The relevance and feasibility of current global practice guidelines for the prevention of mother-to-child transmission of these infections in lower-middle-income countries must be evaluated, including timely access to screening and therapeutics.

How about the evidence assessment tools used in education and management systematic reviews?

Objectives: To systematically analyze the use of evidence assessment tools in systematic reviews of management and education. Study design and setting: We systematically searched selected literature databases and websites to identify systematic reviews on management and education. We extracted general information of the included studies and information about the evidence assessment tool they applied, including whether it was used for methodological quality assessment, reporting quality assessment or evidence grading, as well as the name, reference, publication year, version and original intended use of the tool, the role of the tool in the systematic review, and whether the quality determination criteria were given. Results: A total of 299 systematic reviews were included, of which only 34.8% used evidence assessment tools. A total of 66 different evidence assessment tools were used, of which Risk of Bias (ROB) and its updated version (n = 16, 15.4%) were the most frequent. The specific roles of the evidence assessment tools were reported clearly in 57 reviews, and 27 reviews used two tools. Conclusion: Evidence assessment tools were seldom used in systematic reviews in social sciences. The understanding and reporting of evidence assessment tools among the researchers and users still needs improvement.

Three new triterpenoid saponins from Aralia echinocaulis.

Objective: To study the active ingredients in the root bark of Aralia echinocaulis. Methods: Three triterpenoid saponins were separated from the 70% ethanol extracts and purified by column chromatography and their structures were determined by spectroscopic analysis. Compound 1 and 3 were evaluated for antioxidant activity by the in vitro DPPH free radical scavenging ability and the protective effect of OH- induced DNA oxidative damage. Results: Compound 1 was a new type of triterpenoid saponin, named as echinocaulisaglycone 3-O-ß-D-glucopyranoside (echinocaulisaponin A), and it had good antioxidant activity. Compound 2 was similar to compound 1, named as 1-hydroxyl-echinocaulisaglycone 3-O-ß-D-glucopyranoside (echinocaulisaponin B). Compound 3 was also a new type of triterpenoid saponin, named as echinocaulisaglycone II 3-O-α-L-arabinopyranosyl-(1″→4')-ß-D-glucopyranosiduronic acid (echinocaulisaponin C), and its antioxidant activity was weaker than compound 1. Conclusion: In this study, three new compounds were discovered and two of them were carried out in vitro anti-oxidation studies, laying the foundation for further research on the treatment of related diseases (cardiovascular disease, arthritis, age-related macular degeneration, etc.) through anti-oxidation or quenching free radical function.

Applications of artificial intelligence in the field of air pollution: A bibliometric analysis.

Background: Artificial intelligence (AI) has become widely used in a variety of fields, including disease prediction, environmental monitoring, and pollutant prediction. In recent years, there has also been an increase in the volume of research into the application of AI to air pollution. This study aims to explore the latest trends in the application of AI in the field of air pollution. Methods: All literature on the application of AI to air pollution was searched from the Web of Science database. CiteSpace 5.8.R1 was used to analyze countries/regions, institutions, authors, keywords and references cited, and to reveal hot spots and frontiers of AI in atmospheric pollution. Results: Beginning in 1994, publications on AI in air pollution have increased in number, with a surge in research since 2017. The leading country and institution were China (N = 524) and the Chinese Academy of Sciences (N = 58), followed by the United States (N = 455) and Tsinghua University (N = 33), respectively. In addition, the United States (0.24) and the England (0.27) showed a high degree of centrality. Most of the identified articles were published in journals related to environmental science; the most cited journal was Atmospheric Environment, which reached nearly 1,000 citations. There were few collaborations among authors, institutions and countries. The hot topics were machine learning, air pollution and deep learning. The majority of the researchers concentrated on air pollutant concentration prediction, particularly the combined use of AI and environmental science methods, low-cost air quality sensors, indoor air quality, and thermal comfort. Conclusion: Researches in the field of AI and air pollution are expanding rapidly in recent years. The majority of scholars are from China and the United States, and the Chinese Academy of Sciences is the dominant research institution. The United States and the England contribute greatly to the development of the cooperation network. Cooperation among research institutions appears to be suboptimal, and strengthening cooperation could greatly benefit this field of research. The prediction of air pollutant concentrations, particularly PM2.5, low-cost air quality sensors, and thermal comfort are the current research hotspot.

Recommendations on Off-Label Drug Use in Pediatric Guidelines.

Objective: To systematically analyze the supporting evidence, drug information, and the type of off-label drug use in recommendations on off-label drug use in pediatric guidelines. Methods: A cross-sectional study was performed by systematic search through MEDLINE (via PubMed) and Embase databases to identify literature published from 1 January 2018, to 31 December 2020. Only pediatric clinical practice guidelines that included recommendations on off-label use of drugs were included. We present descriptive information on the sources of the included guidelines, country, publication year, evidence grading system used, details on the types of off-label drug use, and the types of studies used as references to support the recommendations. Results: A total of 66 pediatric guidelines with 605 recommendations were included. Eighty-seven (14.4%) recommendations did not cite any references; and the remaining 518 recommendations were supported by 2,240 references (mean 4.3 references/recommendation). The most common types of studies cited were pediatric RCTs (n = 314, 14.0%), pediatric case series studies (n = 260, 11.6%), and reviews (n = 255, 11.4%). Twenty-one percent (n = 470) of the references were studies on adults. One hundred and forty (23.1%) recommendations were graded using the Grading of Recommendations, Assessments, Development, and Evaluations (GRADE) system, of which 37 (26.4%) were graded as strong but supported with only C or D level of evidence. The most commonly reported type of information in the recommendations was indication (n = 499, 82.5%). The most commonly addressed type of off-label drug use in the 523 positive recommendations was unapproved population (n = 255, 48.8%). Sixty-nine (11.4%) recommendations explicitly reported the drug use as off-label. Conclusion: Children may be exposed to medical risks due to gaps in reporting and evidence of off-label drug use recommendations in pediatric guidelines.

Management guideline for the off-label use of medicine in China (2021).

BACKGROUND: Off-label drug use embodies a thorough clinical diagnosis and evaluation of treatment needs and should not be confused with unreasonable drug use, but it also faces potential risks with drug safety and legal issues. RESEARCH DESIGN AND METHODS: We first established a guideline working group. Following the guideline development process recommended by the World Health Organization Handbook and the Chinese Medical Association, the key questions were determined through literature searches of PubMed, CNKI (Chinese National Knowledge Infrastructure) and other databases. Both the evidence and the clinicians' diagnosis and treatment workload were considered to formulate the initial recommendations. Finally, two rounds of Delphi surveys and one expert seminar were organized to determine the final recommendations of this guideline. Meanwhile, we graded the recommendations based on the body of evidence. RESULTS: We determined nine questions and proposed a total of 23 recommendations regarding the definition of off-label use of drugs, applicable circumstances, classification of evidence, informed consent, legal basis, adverse drug reaction monitoring and evaluation, management procedure, responsibilities and obligations of different stakeholders, medical insurance reimbursement, and the national approval system. CONCLUSIONS: This guideline standardized clinical off-label drug use and provided suggestions and references for the management of off-label drug use.

Analysis of COVID-19 Guideline Quality and Change of Recommendations: A Systematic Review.

Background: Hundreds of coronavirus disease 2019 (COVID-19) clinical practice guidelines (CPGs) and expert consensus statements have been developed and published since the outbreak of the epidemic. However, these CPGs are of widely variable quality. So, this review is aimed at systematically evaluating the methodological and reporting qualities of COVID-19 CPGs, exploring factors that may influence their quality, and analyzing the change of recommendations in CPGs with evidence published. Methods: We searched five electronic databases and five websites from 1 January to 31 December 2020 to retrieve all COVID-19 CPGs. The assessment of the methodological and reporting qualities of CPGs was performed using the AGREE II instrument and RIGHT checklist. Recommendations and evidence used to make recommendations in the CPGs regarding some treatments for COVID-19 (remdesivir, glucocorticoids, hydroxychloroquine/chloroquine, interferon, and lopinavir-ritonavir) were also systematically assessed. And the statistical inference was performed to identify factors associated with the quality of CPGs. Results: We included a total of 92 COVID-19 CPGs developed by 19 countries. Overall, the RIGHT checklist reporting rate of COVID-19 CPGs was 33.0%, and the AGREE II domain score was 30.4%. The overall methodological and reporting qualities of COVID-19 CPGs gradually improved during the year 2020. Factors associated with high methodological and reporting qualities included the evidence-based development process, management of conflicts of interest, and use of established rating systems to assess the quality of evidence and strength of recommendations. The recommendations of only seven (7.6%) CPGs were informed by a systematic review of evidence, and these seven CPGs have relatively high methodological and reporting qualities, in which six of them fully meet the Institute of Medicine (IOM) criteria of guidelines. Besides, a rapid advice CPG developed by the World Health Organization (WHO) of the seven CPGs got the highest overall scores in methodological (72.8%) and reporting qualities (83.8%). Many CPGs covered the same clinical questions (it refers to the clinical questions on the effectiveness of treatments of remdesivir, glucocorticoids, hydroxychloroquine/chloroquine, interferon, and lopinavir-ritonavir in COVID-19 patients) and were published by different countries or organizations. Although randomized controlled trials and systematic reviews on the effectiveness of treatments of remdesivir, glucocorticoids, hydroxychloroquine/chloroquine, interferon, and lopinavir-ritonavir for patients with COVID-19 have been published, the recommendations on those treatments still varied greatly across COVID-19 CPGs published in different countries or regions, which may suggest that the CPGs do not make sufficient use of the latest evidence. Conclusions: Both the methodological and reporting qualities of COVID-19 CPGs increased over time, but there is still room for further improvement. The lack of effective use of available evidence and management of conflicts of interest were the main reasons for the low quality of the CPGs. The use of formal rating systems for the quality of evidence and strength of recommendations may help to improve the quality of CPGs in the context of the COVID-19 pandemic. During the pandemic, we suggest developing a living guideline of which recommendations are supported by a systematic review for it can facilitate the timely translation of the latest research findings to clinical practice. We also suggest that CPG developers should register the guidelines in a registration platform at the beginning for it can reduce duplication development of guidelines on the same clinical question, increase the transparency of the development process, and promote cooperation among guideline developers all over the world. Since the International Practice Guideline Registry Platform has been created, developers could register guidelines prospectively and internationally on this platform.