scholarly journals Safety, efficacy and immunogenicity of therapeutic vaccines in the treatment of patients with high-grade cervical intraepithelial neoplasia associated with human papillomavirus: a systematic review protocol

BMJ Open ◽  
2019 ◽  
Vol 9 (7) ◽  
pp. e026975 ◽  
Author(s):  
Caroline Amélia Gonçalves ◽  
Luís Carlos Lopes-Júnior ◽  
Fernando Kenji Nampo ◽  
Adriana Zilly ◽  
Paulo César Morales Mayer ◽  
...  

IntroductionEighty per cent of the sexually active population will get human papillomavirus (HPV) infection, which is the most prevalent sexually transmitted disease worldwide. Persistence of high-grade HPV infection may evolve to a cervical intraepithelial neoplasia (CIN), and these lesions may be precursors of cervical cancer. However, this progression can be prevented by the administration of therapeutic vaccines which use the main oncoproteins responsible for cancer development in an attempt to trigger a more specific and effective immunological response against this disorder. We aim to evaluate the safety, efficacy and immunogenicity of therapeutic vaccines in the treatment of patients with high-grade CIN 2/3 associated with HPV.Methods and analysisA systematic review of clinical trials will be undertaken. Medline, Excerpta Medica Database, Cochrane Central Register of Controlled Trials, Web of Science, Latin American and Caribbean Health Sciences Literature, Scientific Electronic Library Online and Scopus will be searched, with no restriction regarding publication date. Primary outcomes will include measures related to safety, efficacy and the immunogenicity of the therapeutic vaccines used in these patients. Study selection will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Methodological appraisal of the studies will be assessed by the Cochrane Risk-of-Bias Tool for randomised controlled trials, and the quality evidence of the risk of bias in single studies will be evaluated by Grading of Recommendations Assessment, Development and Evaluation. A narrative synthesis will be done for all included studies. Outcomes will be analysed according to the subgroups of HPV type, CIN grade, route of vaccine administration and vaccine type. Also, if sufficient data are available, a meta-analysis will be conducted. The effect sizes will be generated using Hedges’ g score for both fixed and random effect models. I2statistics will be used to assess heterogeneity and identify their potential sources.Ethics and disseminationEthical approval is not required as primary data will not be collected. Findings will be disseminated widely via peer-reviewed publication and in different media, for example, conferences, congresses or symposia.PROSPERO registration numberCRD42017077428.

2020 ◽  
Vol 54 ◽  
pp. 27 ◽  
Author(s):  
Yamilée Hurtado-Roca ◽  
Naysha Becerra-Chauca ◽  
Magaly Malca

OBJECTIVES: To determine the efficacy and safety of the use of cryotherapy, cold knife or thermocoagulation compared to Loop Electrosurgical Excision Procedure (LEEP) for the treatment of cervical intraepithelial neoplasia. METHODS: Systematic review with meta-analysis of randomized controlled trials in women with cervical intraepithelial neoplasia undergoing treatment with cryotherapy, cold knife, or thermo-coagulation compared with LEEP, to estimate its efficacy and safety. The search was conducted on MEDLINE/PUBMED, Cochrane Central Register of Controlled Trials (CENTRAL) and Scopus, until September 2018. RESULTS: The total of 72 studies were identified, of which only 8 studies met the inclusion criteria. The treatment of CIN with cold knife decreases the risk of residual disease compared with LEEP (RR, 0.54, 95%CI, 0.30–0.96, p = 0.04). The management of premalignant lesions with cryotherapy, compared with LEEP, increases the risk of disease recurrence by 86% (RR, 1.86, 95%CI, 1.16–2.97, p = 0.01), increases the risk of infections (RR, 1.17, 95%CI, 1.08–1.28, p < 0.001) and reduces the risk of minor bleeding by 51% (RR, 0.49, 95%CI) %, 0.40–0.59, p ≤ 0.001). CONCLUSIONS: The treatment of premalignant lesions of cervical cancer with cold knife reduces the risk of residual disease. Nevertheless, cryotherapy reduces the risk of minor bleeding in the 24 hours after treatment and increases the risk of recurrence of disease and infections.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Severien Van Keer ◽  
Annina P. van Splunter ◽  
Jade Pattyn ◽  
Annemie De Smet ◽  
Sereina A. Herzog ◽  
...  

AbstractHost cell DNA methylation analysis in urine provides promising triage markers for women diagnosed with a high-risk (HR) human papillomavirus (HPV) infection. In this study, we have investigated a panel of six host cell methylation markers (GHSR, SST, ZIC1, ASCL1, LHX8, ST6GALNAC5) in cervicovaginal secretions collected within the first part of the urine void (FVU) from a referral population. Cytology, histology, and HPV DNA genotyping results on paired FVU and cervical samples were available. Urinary median methylation levels from HR-HPV (n = 93) positive women were found to increase for all markers with severity of underlying disease. Significantly elevated levels were observed for GHSR and LHX8 in relation to high-grade cervical intraepithelial neoplasia (CIN2 +; n = 33), with area under de curve values of 0.80 (95% Confidence Interval (CI) 0.59–0.92) and 0.76 (95% CI 0.58–0.89), respectively. These findings are the first to support the assertion that methylation analysis of host cell genes is feasible in FVU and holds promise as molecular, triage strategy to discern low- from high-grade cervical disease in HR-HPV positive women. Molecular testing on FVU may serve to increase cervical cancer screening attendance in hard-to-reach populations whilst reducing loss to follow-up and await further optimization and validation studies.


BMJ Open ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. e042997
Author(s):  
Lili Chen ◽  
Xinhua Xu ◽  
Huizhen Cao ◽  
Hong Li

IntroductionAlzheimer’s disease (AD) is the most common neurodegenerative disease and is characterised by cognitive impairment. Non-pharmacological treatments such as diet therapy have been widely investigated in studies on AD. Given the synergistic effects of nutrients present in foods, considering overall dietary composition rather than focusing on a single nutrient may be more useful for evaluating the relationship between diet and AD cognition. The present study aimed to assess the efficacy of different dietary interventions (eg, ketogenic and Mediterranean diets) on cognitive function in patients with AD in a systematic review and pairwise and network meta-analyses of randomised controlled trials or clinical trials.Methods and analysisTwo reviewers will independently conduct searches of PubMed, Cochrane Central Register of Controlled Trials, Embase, CINAHL, PsycINFO and China National Knowledge Infrastructure databases. Data will be extracted from selected studies and risk of bias will be assessed using the revised Cochrane risk-of-bias tool, and evidence quality will be assessed according to the Grading of Recommendations, Assessment, Development and Evaluation framework. The primary outcome of interest is cognitive function in patients with AD; secondary outcomes include biochemical biomarkers of AD and oxidative stress and/or inflammatory biomarkers in cerebrospinal fluid or plasma. For each outcome, random-effects pairwise and network meta-analyses will be carried out to determine the pooled relative effect of each intervention relative to every other intervention.Ethics and disseminationAs this study is based solely on published literature, no ethics approval is required. The research will be published in a peer-reviewed journal.


2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Haonan Tian ◽  
Congman Xie ◽  
Min Lin ◽  
Hongmei Yang ◽  
Aishu Ren

Abstract Background Temporary anchorage devices have been used for decades in orthodontic practice for many applications. The aim of this systematic review was to assess the effectiveness of orthodontic temporary anchorage devices in canine retraction during the two-step technique. Methods A search was systematically performed for articles published prior to June 30, 2019 in five electronic databases (PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, Scopus). The risk of bias was assessed using the Cochrane risk of bias tool for randomized controlled trials (RCTs) and the risk of bias in nonrandomized studies of interventions (ROBINS-I) tool for controlled clinical trials (CCTs). The Grading of Recommendation, Assessment, Development and Evaluation (GRADE) approach was used for the quality assessment. Data concerning the mean difference in mesial molar movement and extent of canine retraction were extracted for statistical analysis. The mean differences and 95% confidence intervals were analyzed for continuous data. A meta-analysis with a random-effects model for comparable outcomes was carried out. Results Three RCTs and five CCTs were finally included. Meta-analysis showed a significant increase not only in anchorage preservation in the implant anchorage group in both the maxilla (1.56 mm, 95% CI: 1.14 to 1.98, P < 0.00001) and the mandible (1.62 mm, 95% CI: 1.24 to 2.01, P < 0.00001) but also in canine retraction in the implant anchorage group in both the maxilla (0.43 mm, 95% CI: 0.16 to 0.69, P = 0.001) and the mandible (0.26 mm, 95% CI: 0.02 to 0.49, P = 0.03). Conclusions There is very low-quality evidence showing that implant anchorage is more efficient than conventional anchorage during canine retraction. Additional high-quality studies are needed.


2021 ◽  
Author(s):  
Rabiu Ibrahim ◽  
Isa Usman Lawal ◽  
Conran Joseph

Abstract Background This study aimed to describe and present detailed protocol of a systematic review aimed at determining available research evidence regarding the intensity, and frequency of task-specific training ( TST ) that can best result in improved motor function and mobility outcomes in both upper and lower extremities in acute, sub-acute and chronic stroke survivors. Methods Literature search strategies were developed using Medical Subject Headings (MeSH) terms and text key words related to stroke rehabilitation and the use of TST to search for relevant randomized controlled trials (RCTs). The Cochrane Central Register of Controlled Trials, MEDLINE (PubMed search engine), Excerpta Medica dataBASE (EMBASE), Physiotherapy Evidence Database (PEDro), Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Google Scholar were searched for eligible articles published from inception to date. Two reviewers independently screened the titles, selected appropriate abstract/studies and extracted relevant data as yielded by the search based on the study inclusion criteria. Assessment of the study risk of bias and quality of included studies were appraised using the Cochrane’s tool for assessing risk of bias or other appropriate tools. Discussion This paper presented the description of the systematic review methods, and it is expected to guide researchers in conducting systematic review in similar fields of research. Sources of literature search terms and reviewers have been determined. Systematic review registration The study protocol has been registered with PROSPERO (130991)


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