1 Introduction
Chronic pelvic inflammatory disease (CPID)[1] [2]
At present, the global incidence of PID is about 2% ∼ 12%,[3] [4] [5,6] [7] [8] [9] [10] [11]
The etiological factors are complex, which include polymicrobial infection, pelvic musculoskeletal disorders, and psychoneurological causes.[12] [13] [14]
Western medicine in the treatment of CPID is given priority to antibiotic treatment against infection, and surgical treatment when necessary. However, as the course deferment, illness becomes increasingly complex, of which often by a variety of pathogenic bacteria mixed infection of the disease. Combination of broad-spectrum antibiotics is not targeted therapy, so the effect is not very ideal. What's more, using antibiotics in large doses over long periods leads to a double infection, as well as the resistance easily.[15] [16]
Pelvic inflammation is unrecorded in ancient Books of Traditional Chinese medicine, and its clinical characteristics lump it as “heat discharge into the blood chamber”, “abdominal pain”, “carrying the disease”, “postpartum fever”, “infertility”.[17] [18] [19] [20] [21]
Nowadays, a large number of clinical studies in moxibustion regulating CPID have been carried out. Nevertheless, no systematic reviews has reported the effectiveness of moxibustion on CPID. Thus, we conducted this protocol of moxibustion as an intervention for CPID patients in order to achieve a better therapeutic effect.
2 Objectives
This study is aimed at summarizing the clinical evidence about the effectiveness and safety of moxibustion for CPID and provide doctors, patients, policy decision-makers with reliable recommendations.
3 Methods and analysis
3.1 Study registration
This protocol report is structured according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis Protocols in the Cochrane Handbook.[22] Systematic Reviews (PROSPERO no. CRD42020158744; in PROSPERO 2020; Available at: http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42020158744
Ethics approval is not required for this review as we will analyze published literature only.
3.2 Inclusion certain for study selection
3.2.1 Types of studies
Without restrictions on language and publication status, all the randomized controlled trials (RCTs), which is stated the “randomization” phrase and without blinding restriction, will be included. The animal mechanism studies, case reports, or non-RCTs are excluded.
3.2.2 Types of participants
Patients diagnosed as CPID regardless of race, age, status or education, marital status, and economic status. Trials will be included which applying validated diagnosed criteria, for instance, WHO/NIH/OSHK guideline, Chinese guidelines for diagnosis, and treatment of CPID.
3.2.3 Types of interventions
RTCs that involved any form of moxibustion (eg, direct moxibustion, indirect moxibustion, heat-sensitive moxibustion, moxa burner moxibustion, warm-needling, crude drug moxibustion, or natural moxibustion) as the sole treatment or as a part of combination therapy with another intervention (eg, conventional drugs) will be included. While combined with any complementary therapy will be excluded, for example, Chinese herb decoction, acupuncture, and other complementary therapy.
3.2.4 Type of comparator(s)/control
There is no limit to the treatment of the control group, including no treatment, or placebo, or
The following treatment comparisons will be included in the analysis:
(1) Moxibustion compared with no treatment;
(2) moxibustion compared with placebo or sham moxibustion therapy;
(3) moxibustion compared with other active therapy;
(4) moxibustion plus other active therapy compared with the same active therapy.
3.2.5 Types of outcome measures
3.2.5.1 Primary outcomes
The effective rate, pelvic inflammatory mass diameter and Pelvic fluid depth.
3.2.5.2 Secondary outcomes
Secondary outcome measures will include:
(1) Patient reported outcome scale
(2) Visual analog scale.
(3) C-reactive protein.
(4) transforming growth factor β1 = transforming growth factor β1.
(5) incidence of any adverse events
3.3 Exclusion certain for study selection
The exclusion certain contain the following items:
(1) Patients with acute medical conditions or pregnancy
(2) The literature related to the same study, and duplicated publications
(3) Unable to get literature for available data or full text through various means
3.4 Search methods for identification of studies
Seven databases as following: PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, WangFang Database, Chinese Scientific Journal Database, Chinese Biomedical Literatures Database will be searched from their inception to May 2020. To describe moxibustion for CPID, the initial search strategy (Table 1 ) was conducted for the PubMed database using MeSH items and free words. Search strategies for the other databases will be adapted as necessary. The following search terms will be used: CPID, chronic pelvic inflammation, chronic pelvic infection, chronic endometritis, sequelae of pelvic inflammatory disease, chronic salpingitis, chronic parametritis, moxibustion, thunder fire miraculous moxa roll, thunder fire moxibustion, taiyi miraculous moxa roll, suspended moxibustion, mild moxibustion, needle warming moxibustion, randomized controlled trial, controlled clinical trial, randomized etc.
Table 1: The search strategy for Pubmed.
Also, we will search for eligible trials, which are ongoing or unpublished, in the WHO International Clinical Trial Registration Platform and the China Clinical Trial Registration Platform to make a comprehensive literature search.
3.5 Data collection and analysis
3.5.1 Pilot search
To better understand the inclusion and exclusion criteria of each systematic review, we will conduct a pre-test, which is to randomly select some literature for screening. As for the differences of literature screening results, we will exchange and discuss to make the future literature selection more uniform.
3.5.2 Selection of studies
Each literature of title and abstract is scanned by 2 reviewers (QSH and JX) respectively to eliminate some ineligible articles. Then all relevant articles of full text are investigated. When the 2 reviewers cannot agree on the selection process through consultations, the third reviewer (XHZ) will ultimately make the decision. If there is an article with unclear information or missing data, HFH will attempt to contact the original author for the full text and data. The primary selection process is shown in a Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow chart (Fig. 1 ).
Figure 1: Flowchart of literature selection.
3.5.3 Data extraction
Two independent reviewers (QSH and HFH) shall design a standardized data extraction form, which will be performed by Microsoft Excel, independently extract data and cross-check. The extracted information includes descriptions of studies, characteristics of participants, interventions of both the observation group and control group, quality, randomization, allocation concealment and blinding methods, outcome measures, primary outcomes, adverse effects, duration of follow-up, type and source of financial support, and the Standards for Reporting Interventions in Controlled Trials of Moxibustion (STRICTM) checklist. In case of any discrepancies, we will resolve by discussion and reach a consensus, and if necessary, seek arbitration from a third reviewer (JX). For RCTs lacking important information or data, the reviewers will track back to the primary studies of them.
3.6 Assessment of risk of bias and reporting of study quality
The assessment will be conducted by 2 reviewers (QSH and JX) with the risk-of-bias assessment method from Cochrane Reviewer's Handbook 5.0.24,[23] [24] [25]
3.7 Measures of treatment effect
We will be conduct statistical analyses by RevMan 5.4 software. Weight Mean difference (WMD) with 95% CIs will be used to analyze continuous data. Other forms of data will be changed into WMD values. As for the results of dichotomous data, risk ratio (RR) and its 95% CI will be used.
3.8 Data analysis
Data from parallel-group studies will be collected for analysis. If multiple nonmoxibustion control groups are included, pooled analyses of the control groups against the intervention group will be used. We will gather individual data of each result index for evaluation.
3.9 Management of missing data
If there are missing or incomplete data for the primary results, we will contact the corresponding authors for the missing data to get specific information by telephone or email. If we can’t obtain that missing information, we will exclude from the analysis.
3.10 Assessment of heterogeneity
The difference among studies in the systematic review,[26] I 2 . The magnitude of heterogeneity was categorized by the I 2 statistic with I 2 of 0% to 24% = no heterogeneity, I 2 of 25% to 49% = moderate heterogeneity, I 2 of 50% to 74% = substantial heterogeneity, and I 2 of 75% to 100% = considerable heterogeneity. When the results are substantial heterogeneity or considerable heterogeneity, sensitivity analysis or subgroup analysis will be made to look for the possible causes.
3.11 Assessment of reporting biases
If more than 10 trials are included, the funnel plots will be used to assess reporting biases. If funnel plot asymmetry is detected, the reasons will be analyzed.
3.12 Synthesis of data
We will use RevMan for all statistical analyses. There are 2 modes to choose from: the random-effects model (I 2 ≥50%) or fixed-effects model (I 2 < 50%). If the substantial heterogeneity cannot be identified or there are not enough RCTs, we will perform a narrative, the qualitative summary or subgroup analysis.
3.13 Subgroup analysis
If the necessary data are available, subgroup analysis will be carried out according to different factors as follows: the type of CPID, type of moxibustion, the duration or dosage of moxibustion, period of treatment, and the type of intervention in the control group or the study group.
3.14 Sensitivity analysis
A sensitivity analysis will be performed when there is significant heterogeneity according to the following aspects: sample size, heterogeneity qualities, methodological elements, and characteristic of research. If heterogeneity is reduced after low-quality or small sample studies are excluded, and we must be more cautious in concluding.
3.15 Grading the quality of evidence
The grading of evidence quality will be conducted by 2 independent reviewers using the grading of recommendations, assessment, development and evaluation system instrument.[27] [28]
4 Discussion
CPID is a major gynecological health problem affecting more than 1 million women yearly. It begins with cervicitis and progress leading to serious clinical consequences, which including endometritis, salpingitis, pelvic peritonitis, tubal infertility, ectopic pregnancy, pelvic adhesions, pelvic abscess and chronic pelvic pain.[29] [30]
This review, which will be the first summary of existing RTCs of moxibustion treatment of CPID, can help medical workers choose effective and safe interventions. The full discussion section of the report is planned to include the following: main findings, advantages and limitations, comparison with other studies and opinions, interpretation of results and conclusion.
Author contributions
All authors have read and approved the publication of the protocol.
Conceptualization: Fanghui Hua, Jun Xiong.
Data curation: Jie Xiang, XiaoHong Zhou, Shouqiang Huang.
Formal analysis: Shouqiang Huang, Jie Xiang.
Investigation: Jun Xiong, Honglian Li, XiaoHong Zhou.
Methodology: Fanghui Hua, Shouqiang Huang, Jie Xiang.
Software: XiaoHong Zhou, Honglian Li.
Supervision: Jun Xiong, Honglian Li.
Writing – original draft: Jun Xiong, Fanghui Hua, Shouqiang Huang, Jie Xiang.
Writing – review & editing: XiaoHong Zhou, Honglian Li.
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