The diagnostic accuracy of serum and plasma microRNAs in detection of cervical intraepithelial neoplasia and cervical cancer: A systematic review and meta-analysis.

Studies suggest a need for new diagnostic approaches for cervical cancer including microRNA technology. In this review, we assessed the diagnostic accuracy of microRNAs in detecting cervical cancer and Cervical Intraepithelial Neoplasia (CIN). We performed a systematic review following the Preferred Reporting Items for Systematic Review and Meta-Analysis guideline for protocols (PRISMA-P). We searched for all articles in online databases and grey literature from 01st January 2012 to 16th August 2022. We used the quality assessment of diagnostic accuracy studies tool (QUADAS-2) to assess the risk of bias of included studies and then conducted a Random Effects Meta-analysis. We identified 297 articles and eventually extracted data from 24 studies. Serum/plasma concentration miR-205, miR-21, miR-192, and miR-9 showed highest diagnostic accuracy (AUC of 0.750, 0.689, 0.980, and 0.900, respectively) for detecting CIN from healthy controls. MicroRNA panels (miR-21, miR-125b and miR-370) and (miR-9, miR-10a, miR-20a and miR-196a and miR-16-2) had AUC values of 0.897 and 0.886 respectively for detecting CIN from healthy controls. For detection of cervical cancer from healthy controls, the most promising microRNAs were miR-21, miR-205, miR-192 and miR-9 (AUC values of 0.723, 0.960, 1.00, and 0.99 respectively). We report higher diagnostic accuracy of upregulated microRNAs, especially miR-205, miR-9, miR-192, and miR-21. This highlights their potential as stand-alone screening or diagnostic tests, either with others, in a new algorithm, or together with other biomarkers for purposes of detecting cervical lesions. Future studies could standardize quantification methods, and also study microRNAs in higher prevalence populations like in sub-Saharan Africa and South Asia. Our review protocol was registered in PROSPERO (CRD42022313275).

Efficacy of antimalarial herbal medicines used by communities in malaria affected regions globally: a protocol for systematic review and evidence and gap map.

INTRODUCTION: With the rising resistance to artemisinin-based combination treatments, there is a need to hasten the discovery and development of newer antimalarial agents. Herbal medicines are key for the development of novel drugs. Currently, herbal medicine usage in communities for treatment of malaria symptoms is common as an alternative to conventional (modern) antimalarial agents. However, the efficacy and safety of most of the herbal medicines has not yet been established. Therefore, this systematic review and evidence gap map (EGM) is intended to collate and map the available evidence, identify the gaps and synthesise the efficacy of herbal antimalarial medicines used in malaria affected regions globally. METHODS AND ANALYSIS: The systematic review and EGM will be done following PRISMA and Campbell Collaboration guidelines respectively. This protocol has been registered in PROSPERO. Data sources will include PubMed, MEDLINE Ovid, EMBASE, Web of Science, Google Scholar and grey literature search. Data extraction will be done in duplicate using a data extraction tool tailored in Microsoft Office excel for herbal antimalarials discovery research questions following the PICOST framework. The Risk of Bias and overall quality of evidence will be assessed using Cochrane risk of bias tool (clinical trials), QUIN tool (in vitro studies), Newcastle-Ottawa tool (observational studies) and SYRCLE's risk of bias tool for animal studies (in vivo studies). Data analysis will be done using both structured narrative and quantitative synthesis. The primary review outcomes will be clinically important efficacy and adverse drug reactions. Laboratory parameters will include Inhibitory Concentration killing 50% of parasites, IC50; Ring Stage Assay, RSA0-3 hou; Trophozoite Survival Assay, TSA50. ETHICS AND DISSEMINATION: The review protocol was approved by the School of Biomedical Science Research Ethics Committee, Makerere University College of Health Sciences (SBS-2022-213). PROSPERO REGISTRATION NUMBER: CRD42022367073.

The diagnostic accuracy of serum microRNAs in detection of cervical cancer: a systematic review protocol.

BACKGROUND: Cervical cancer remains a public health problem worldwide, especially in sub-Saharan Africa. There are challenges in timely screening and diagnosis for early detection and intervention. Therefore, studies on cervical cancer and cervical intraepithelial neoplasia suggest the need for new diagnostic approaches including microRNA technology. Plasma/serum levels of microRNAs are elevated or reduced compared to the normal state and their diagnostic accuracy for detection of cervical neoplasms has not been rigorously assessed more so in low-resource settings such as Uganda. The aim of this systematic review was therefore to assess the diagnostic accuracy of serum microRNAs in detecting cervical cancer. METHODS: We will perform a systematic review following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) statement. We will search for all articles in MEDLINE/PubMed, Web of Science, Embase, and CINAHL, as well as grey literature from 2012 to 2022. Our outcomes will be sensitivity, specificity, negative predictive values, positive predictive values or area under the curve (Nagamitsu et al, Mol Clin Oncol 5:189-94, 2016) for each microRNA or microRNA panel. We will use the quality assessment of diagnostic accuracy studies (Whiting et al, Ann Intern Med 155:529-36, 2011) tool to assess the risk of bias of included studies. Our results will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis for Diagnostic Test Accuracy studies (PRISMA-DTA). We will summarise studies in a flow chart and then describe them using a structured narrative synthesis. If possible, we shall use the Lehmann model bivariate approach for the meta analysis USE OF THE REVIEW RESULTS: This systematic review will provide information on the relevance of microRNAs in cervical cancer. This information will help policy makers, planners and researchers in determining which particular microRNAs could be employed to screen or diagnose cancer of the cervix. SYSTEMATIC REVIEW REGISTRATION: This protocol has been registered in PROSPERO under registration number CRD42022313275.

Data sharing practices in collaborative human genomic research in low- and middle-income countries: A systematic review protocol.

INTRODUCTION: The practice of creating large databases has become increasingly common by combining research participants' data into larger repositories. Funders now require that data sharing be considered in newly funded research project, unless there are justifiable reasons not to do so. Access to genomic data brings along a host of ethical concerns as well as fairness and equity in the conduct of collaborative research between researchers from high- income and low-and middle-income countries. MATERIALS AND METHODS: This systematic review protocol will be developed in line with PRISMA -guidelines which refers to Open Science Framework, registered in PROSPERO (https://www.crd.york.ac.uk/prospero/) record CRD42022297984 and published in a peer reviewed journal. Data sources will include PubMed, google scholar, EMBASE, Web of science and MEDLINE. Both published and grey literature will be searched. Subject matter experts including bioethicists, principal investigators of genomic research projects and research administrators will be contacted. After de-duplication, titles and abstracts will be screened for eligibility. Data extraction will be undertaken using a piloted form designed in EPPI-Reviewer software before conducting risk of bias assessments by a pair of reviewers, acting independently. Any discrepancies will be resolved by consensus. Analysis will be done using a structured narrative synthesis and where feasible metanalysis. This review will attempt to highlight the context of data sharing practices in the global North-South and South-South collaborative human genomic research in low- and middle-income countries. This review will enhance the body of evidence on ethical, legal and social implications of data sharing in international collaborative genomic research setting criteria for data sharing. The full report will be shared with relevant stakeholders including universities, civil society, funders, and departments of genomic research to ensure an adequate reach in low-and middle-income countries (LMICs).

Interventions to increase youth employment: An evidence and gap map.

Background: Globally, 13% of the youth are not in education, employment or training (NEET). Moreover, this persistent problem has been exacerbated by the shock of Covid-19 pandemic. More youth from disadvantaged backgrounds are likely unemployed than those from better off backgrounds. Thus, the need for increased use of evidence in the design and implementation of youth employment interventions to increase effectiveness and sustainability of interventions and outcomes. Evidence and gap maps (EGMs) can promote evidence-based decision making by guiding policy makers, development partners and researchers to areas with good bodies of evidence and those with little or no evidence. The scope of the Youth Employment EGM is global. The map covers all youth aged 15-35 years. The three broad intervention categories included in the EGM are: strengthening training and education systems, enhancing labour market and, transforming financial sector markets. There are five outcome categories: education and skills; entrepreneurship; employment; welfare and economic outcomes. The EGM contains impact evaluations of interventions implemented to increase youth employment and systematic reviews of such single studies, published or made available between 2000 and 2019. Objectives: The primary objective was to catalogue impact evaluations and systematic reviews on youth employment interventions to improve discoverability of evidence by decision makers, development patterners and researchers, so as to promote evidence-based decision making in programming and implementation of youth employment initiatives. Search Methods: Twenty databases and websites were searched using a validated search strategy. Additional searches included searching within 21 systematic reviews, snowballing 20 most recent studies and citation tracking of 10 most recent studies included in the EGM. Selection Criteria: The study selection criteria followed the PICOS approach of population, intervention, relevant comparison groups, outcomes and study design. Additional criterion is; study publication or availability period of between 2000 and 2021. Only impact evaluations and systematic reviews that included impact evaluations were selected. Data Collection and Analysis: A total of 14,511 studies were uploaded in EPPI Reviewer 4 software, upon which 399 were selected using the criteria provided above. Coding of data took place in EPPI Reviewer basing on predefined codes. The unit of analysis for the report is individual studies where every entry represents a combination of interventions and outcomes. Main Results: Overall, 399 studies (21 systematic reviews and 378 impact evaluations) are included in the EGM. Impact evaluations (n = 378) are much more than the systematic reviews (n = 21). Most impact evaluations are experimental studies (n = 177), followed by non-experimental matching (n = 167) and other regression designs (n = 35). Experimental studies were mostly conducted in both Lower-income countries and Lower Middle Income countries while non-experimental study designs are the most common in both High Income and Upper Middle Income countries. Most evidence is from low quality impact evaluations (71.2%) while majority of systematic reviews (71.4% of 21) are of medium and high quality rating. The area saturated with most evidence is the intervention category of 'training', while the underrepresented are three main intervention sub-categories: information services; decent work policies and; entrepreneurship promotion and financing. Older youth, youth in fragility, conflict and violence contexts, or humanitarian settings, or ethnic minorities or those with criminal backgrounds are least studied. Conclusions: The Youth Employment EGM identifies trends in evidence notably the following: Most evidence is from high-income countries, an indication of the relationship between a country's income status and research productivity.The most common study designs are experimental.Most of the evidence is of low quality. This finding serves to alert researchers, practitioners and policy makers that more rigorous work is needed to inform youth employment interventions. Blending of interventions is practiced. While this could be an indication that blended intervention could be offering better outcomes, this remains an area with a research gap.

PROTOCOL: Interventions to increase youth employment: An evidence and gap map.

The research question guiding the production of the youth employment evidence and gap map (EGM) is stated as follows: What is the nature and extent of the evidence base of impact evaluations and systematic reviews on youth employment programmes in the world? The primary objective of is to catalogue impact evaluations and systematic reviews on youth employment interventions to enhance discoverability of evidence by decision makers, development patterners and researchers, so as to promote evidence-based decision making in programming and delivery of youth employment initiatives. This evidence gap map is also a primary input into the implementation of Mastercard Foundation's strategy titled "Africa Works: Mastercard Foundation Strategy 2018-2030", which points out sharing of evidence-based knowledge and innovation with stakeholders as a key strategy to be used (Mastercard Foundation). The time frame for the development of the youth EGM will run from the last quarter of 2019 to December 2020. The five secondary objectives are: (i) To construct a framework for the classification of youth employment effectiveness studies. The objective will be achieved through the development of an intervention and outcome framework using an engaged consultative process involving the review team, Mastercard Foundation and other stakeholders. (ii) To identify available evidence, and clusters of evidence, including its quality rating. This will involve activities such as identification of studies using a standardised study search strategy, screening and coding of studies in EPPI Reviewer 4, which is a web-based software program for production of reviews. (iii) To create a map of youth employment effectiveness studies equipped with an appealing user-friendly web-based search content visualisation using interactive mapping software. To achieve this object, data coded in EPPI Reviewer 4 will be exported to another software (EPPI mapper) which is designed for generating EGMs. (iv) To produce a narrative report of the youth employment EGM. This will be achieved through analysis of data in EPPI Reviewer 4 and report writing. To disseminate the EGM to users to increase awareness to support evidence-informed decision-making across countries. We will achieve this objective by organising dissemination workshops, participating in conferences and hosting the evidence and gap on our websites.

Role and utility of COVID-19 laboratory testing in low-income and middle-income countries: protocol for rapid evidence synthesis.

INTRODUCTION: Accurate and affordable laboratory testing is key to timely diagnosis and appropriate management of patients with COVID-19. New laboratory test protocols are released into the market under emergency use authorisation with limited evidence on diagnostic test accuracy. As such, robust evidence on the diagnostic accuracy and the costs of available tests is urgently needed to inform policy and practice especially in resource-limited settings. We aim to determine the diagnostic test accuracy, cost-effectiveness and utility of laboratory test strategies for COVID-19 in low-income and middle-income countries. METHODS AND ANALYSIS: This will be a multistaged, protocol-driven systematic review conducted in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for diagnostic test accuracy studies. We will search for relevant literature in at least six public health databases, including PubMed, Google Scholar, MEDLINE, Scopus, Web of Science and the WHO Global Index Medicus. In addition, we will search Cochrane Library, COVID-END and grey literature databases to identify additional relevant articles before double-screening and abstraction of data. We will conduct a structured narrative and quantitative synthesis of the results guided by the Fryback and Thornbury framework for assessing a diagnostic test. The primary outcome is COVID-19 diagnostic test accuracy. Using the GRADE approach specific to diagnostic accuracy tests, we will appraise the overall quality of evidence and report the results following the original PRISMA statement. The protocol is registered with the International Prospective Register of Systematic Reviews (PROSPERO; https://www.crd.york.ac.uk/prospero/). ETHICS AND DISSEMINATION: Ethical review was done by the School of Biomedical Sciences Research Ethics Committee and the Uganda National Council for Science and Technology. The published article will be accessible to policy and decision makers. The findings of this review will guide clinical practice and policy decisions and highlight areas for future research.PROSPERO registration number CRD42020209528.