A systematic review and meta-analysis of miRNAs for the detection of cervical cancer.

Aim: This study aimed to critically appraise the evidence of the diagnostic effectiveness of miRNAs for the detection of cervical cancer. Methods & materials: A systematic review and meta-analysis was performed, searching PubMed, EMBASE and Web of Science. An umbrella meta-analysis of meta-analyses of individual biomarkers was performed. A Grading of Recommendations, Assessment, Development and Evaluations (GRADE) assessment of evidence was also performed. Results: A total of 52 miRNAs were included. Umbrella meta-analysis revealed significant heterogeneity in terms of sensitivity, specificity, receiver operating characteristic (ROC), positive predictive value and/or negative predictive value. Umbrella effects were 0.76 (95% CI: 0.73-0.78), 0.78 (95% CI: 0.75-0.81), 0.77 (95% CI: 0.75-0.80), 0.75 (95% CI: 0.71-0.79) and 0.76 (95% CI: 0.74-0.79), respectively. Conclusion: Moderate quality evidence suggested miR199a-5p, miR21-5p and miR-141a had excellent diagnostic performance.

miRNAs are small chemical messengers that play a role in the regulation of protein produced inside the cytoplasm of cells, including cancer cells. In cervical cancer cells, miRNAs become dysregulated ­ that is, their levels become increased or decreased ­ and therefore detecting their relative abundance or absence in test samples may enable identification of cervical cancer. This study aimed to systematically collect and appraise the evidence for the diagnostic ability of miRNAs for detection of cervical cancer. A systematic appraisal of the evidence was conducted by searching three research databases (PubMed, EMBASE and Web of Science) to collect evidence published up to 13 November 2022. Results for diagnostic performance of 52 miRNAs were extracted from 20 relevant studies. An assessment of risk of bias for each study was performed using a standardized checklist, which identified one high-quality study, 18 moderate-quality studies and one low-quality study. Results for each individual biomarker were assessed by meta-analytic methods, which generated weighted averages for 38 of 52 miRNAs. All 52 miRNAs were then compared using an umbrella meta-analysis (a weighted average of all miRNA biomarkers), which identified significant differences in diagnostic ability between miRNAs. Sensitivity analyses suggested that these differences were partly explained by differences in grades of cervical cancer and differences in types of sample used for testing. A GRADE assessment of the overall evidence quality suggested that moderate-quality evidence supported further investigation of three miRNA biomarkers (miR-199a-5p, miR-21-5p and miR-141a), which performed excellently (i.e., better than the umbrella weighted average) across five performance parameters, including sensitivity, specificity, receiver operator characteristic, positive predictive value and negative predictive value. In summary, this study suggested miR-199a-5p, miR-21-5p and miR-141a had excellent diagnostic performance for detection of cervical cancer and recommends further investigation of these miRNAs in randomized controlled trials.

Infection and mortality of healthcare workers worldwide from COVID-19: a systematic review.

OBJECTIVES: To estimate COVID-19 infections and deaths in healthcare workers (HCWs) from a global perspective during the early phases of the pandemic. DESIGN: Systematic review. METHODS: Two parallel searches of academic bibliographic databases and grey literature were undertaken until 8 May 2020. Governments were also contacted for further information where possible. There were no restrictions on language, information sources used, publication status and types of sources of evidence. The AACODS checklist or the National Institutes of Health study quality assessment tools were used to appraise each source of evidence. OUTCOME MEASURES: Publication characteristics, country-specific data points, COVID-19-specific data, demographics of affected HCWs and public health measures employed. RESULTS: A total of 152 888 infections and 1413 deaths were reported. Infections were mainly in women (71.6%, n=14 058) and nurses (38.6%, n=10 706), but deaths were mainly in men (70.8%, n=550) and doctors (51.4%, n=525). Limited data suggested that general practitioners and mental health nurses were the highest risk specialities for deaths. There were 37.2 deaths reported per 100 infections for HCWs aged over 70 years. Europe had the highest absolute numbers of reported infections (119 628) and deaths (712), but the Eastern Mediterranean region had the highest number of reported deaths per 100 infections (5.7). CONCLUSIONS: COVID-19 infections and deaths among HCWs follow that of the general population around the world. The reasons for gender and specialty differences require further exploration, as do the low rates reported in Africa and India. Although physicians working in certain specialities may be considered high risk due to exposure to oronasal secretions, the risk to other specialities must not be underestimated. Elderly HCWs may require assigning to less risky settings such as telemedicine or administrative positions. Our pragmatic approach provides general trends, and highlights the need for universal guidelines for testing and reporting of infections in HCWs.