Background: The global pandemic coronavirus disease 2019 (COVID-19) has become a major public health problem and presents an unprecedented challenge. However, no specific drugs were currently proven. This study aimed to evaluate the comparative efficacy and safety of pharmacological interventions in patients with COVID-19. Methods: Medline, Embase, the Cochrane Library, and clinicaltrials.gov were searched for randomized controlled trials (RCTs) in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)/SARS-CoV. Random-effects network meta-analysis within the Bayesian framework was performed, followed by the Grading of Recommendations Assessment, Development, and Evaluation system assessing the quality of evidence. The primary outcome of interest includes mortality, cure, viral negative conversion, and overall adverse events (OAEs). Odds ratio (OR) with 95% confidence interval (CI) was calculated as the measure of effect size. Results: Sixty-six RCTs with 19,095 patients were included, involving standard of care (SOC), eight different antiviral agents, six different antibiotics, high and low dose chloroquine (CQ_HD, CQ_LD), traditional Chinese medicine (TCM), corticosteroids (COR), and other treatments. Compared with SOC, a significant reduction of mortality was observed for TCM (OR = 0.34, 95% CI: 0.20–0.56, moderate quality) and COR (OR = 0.84, 95% CI: 0.75–0.96, low quality) with improved cure rate (OR = 2.16, 95% CI: 1.60–2.91, low quality for TCM; OR = 1.17, 95% CI: 1.05–1.30, low quality for COR). However, an increased risk of mortality was found for CQ_HD vs . SOC (OR = 3.20, 95% CI: 1.18–8.73, low quality). TCM was associated with decreased risk of OAE (OR = 0.52, 95% CI: 0.38–0.70, very low quality) but CQ_HD (OR = 2.51, 95% CI: 1.20–5.24) and interferons (IFN) (OR = 2.69, 95% CI: 1.02–7.08) vs . SOC with very low quality were associated with an increased risk. Conclusions: COR and TCM may reduce mortality and increase cure rate with no increased risk of OAEs compared with standard care. CQ_HD might increase the risk of mortality. CQ, IFN, and other antiviral agents could increase the risk of OAEs. The current evidence is generally uncertain with low-quality and further high-quality trials are needed.

We conducted a systematic review and meta-analysis to compare the screening performance of synthesized mammography (SM) plus digital breast tomosynthesis (DBT) with digital mammography (DM) plus DBT or DM alone. Methods: Medline, Embase, Web of Science, and the Cochrane Library databases were searched from January 2010 to January 2021. Eligible population-based studies on breast cancer screening comparing SM/DBT with DM/DBT or DM in asymptomatic women were included. A random-effect model was used in this meta-analysis. Data were summarized as risk differences (RDs), with 95 % confidence intervals (CIs). Results: Thirteen studies involving 1,370,670 participants were included. Compared with DM/DBT, screening using SM/DBT had similar breast cancer detection rate (CDR) (RD ¼ À0.1/1000 screens, 95 % CI ¼ À0.4 to 0.2, p ¼ 0.557, I 2 ¼ 0 %), but lower recall rate (RD ¼ À0.56 %, 95 % CI ¼ À1.03 to À0.08, p ¼ 0.022, I 2 ¼ 90 %) and lower biopsy rate (RD ¼ À0.33 %, 95 % CI ¼ À0.56 to À0.10, p ¼ 0.005, I 2 ¼ 78 %). Compared with DM, SM/DBT improved CDR (RD ¼ 2.0/1000 screens, 95 % CI ¼ 1.4 to 2.6, p < 0.001, I 2 ¼ 63 %) and reduced recall rate (RD ¼ À0.95 %, 95 % CI ¼ À1.91 to À0.002, p ¼ 0.049, I 2 ¼ 99 %). However, SM/DBT and DM had similar interval cancer rate (ICR) (RD ¼ 0.1/1000 screens, 95 % CI ¼ À0.6 to 0.8, p ¼ 0.836, I 2 ¼ 71 %) and biopsy rate (RD ¼ À0.05 %, 95 % CI ¼ À0.35 to 0.24, p ¼ 0.727, I 2 ¼ 93 %). Conclusions: Screening using SM/DBT has similar breast cancer detection but reduces recall and biopsy when compared with DM/DBT. SM/DBT improves CDR when compared with DM, but they have little difference in ICR. SM/DBT could replace DM/DBT in breast cancer screening to reduce radiation dose.

ObjectiveThis study systematically evaluated the effectiveness and safety of therapeutic vaccines for precancerous cervical lesions, providing evidence for future research.MethodsWe systematically searched the literature in 10 databases from inception to February 18, 2021. Studies on the effectiveness and safety of therapeutic vaccines for precancerous cervical lesions were included. Then, we calculated the overall incidence rates of four outcomes, for which we used the risk ratio (RR) and 95% confidence interval (95% CI) to describe the effects of high-grade squamous intraepithelial lesions (HSILs) on recurrence.ResultsA total of 39 studies were included, all reported in English, published from 1989 to 2021 in 16 countries. The studies covered 22,865 women aged 15–65 years, with a total of 5,794 vaccinated, and 21 vaccines were divided into six types. Meta-analysis showed that the overall incidence rate of HSIL regression in vaccine therapies was 62.48% [95% CI (42.80, 80.41)], with the highest rate being 72.32% for viral vector vaccines [95% CI (29.33, 99.51)]. Similarly, the overall incidence rates of HPV and HPV16/18 clearance by vaccines were 48.59% [95% CI (32.68, 64.64)] and 47.37% [95% CI (38.00, 56.81)], respectively, with the highest rates being 68.18% [95% CI (45.13, 86.14)] for bacterial vector vaccines and 55.14% [95% CI (42.31, 67.66)] for DNA-based vaccines. In addition, a comprehensive analysis indicated that virus-like particle vaccines after conization reduced the risk of HSIL recurrence with statistical significance compared to conization alone [RR = 0.46; 95% CI (0.29, 0.74)]. Regarding safety, only four studies reported a few severe adverse events, indicating that vaccines for precancerous cervical lesions are generally safe.ConclusionVirus-like particle vaccines as an adjuvant immunotherapy for conization can significantly reduce the risk of HSIL recurrence. Most therapeutic vaccines have direct therapeutic effects on precancerous lesions, and the effectiveness in HSIL regression, clearance of HPV, and clearance of HPV16/18 is great with good safety. That is, therapeutic vaccines have good development potential and are worthy of further research.Systematic Review RegistrationPROSPERO https://www.crd.york.ac.uk/PROSPERO/, CRD42021275452.

Background: To evaluate comparative efficacy and safety of pharmacological interventions in patients with coronavirus disease 2019. Methods: Medline, Embase, the Cochrane Library and clinicaltrials.gov were searched for randomized controlled trials (RCTs) in patients infected with SARS-COV-2/SARS-COV. Random-effects network meta-analysis within Bayesian framework was performed, followed by Grading of Recommendations Assessment, Development and Evaluation (GRADE) system assessing quality of evidence. The primary outcome of interest includes mortality, cure, viral negative conversion (VNC) and overall adverse events (OAE). Odds ratio (OR) with 95% confidence interval (CI) was calculated as the measure of effect size.Results: 66 RCTs with 19,095 patients were included, involving standard care (SOC), 8 different antiviral agents, 6 different antibiotics, high and low dose chloroquine (CQ_HD, CQ_LD), traditional Chinese medicine (TCM), corticosteroids and other treatments. Compared with SOC, significant reduction of mortality was observed for TCM (OR=0.34, 95%CI: 0.20-0.56, moderate quality) and corticosteroids (OR=0.84, 0.75-0.96, low quality) with improved cure rate (OR=2.16, 1.60-2.91, low quality for TCM; OR=1.17, 1.05-1.30, low quality for corticosteroids). However, increased risk of mortality was found for CQ_HD versus SOC (OR=3.20, 1.18-8.73, low quality). TCM was associated with decreased risk of OAE (OR=0.52, 0.38-0.70, very low quality) but CQ_HD (OR=2.51, 1.20-5.24) and IFN (OR=2.69, 1.02-7.08) versus SOC with very low quality) were associated with an increased risk. Conclusions: Corticosteroids and TCM may reduce mortality and increase cure rate with no increased risk of OAEs compared with standard care. CQ_HD might increase the risk of mortality. CQ, IFN and other antiviral agents could increase the risk of OAEs. The current evidence is generally uncertain with low quality and further high-quality trials are needed.