Effectiveness of neuromuscular electrical stimulation for interstitial cystitis: a protocol of systematic review and meta-analysis

Background This study will examine the effectiveness and safety of neuromuscular electrical stimulation (NMES) for the treatment of patients with interstitial cystitis (IC). Methods We will retrieve the following electronic databases from their commencements to the March 1, 2020 to discover all related potential studies: MEDLINE, EMBASE, Cochrane Library, Web of Science, CINAHL, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, Chinese Scientic Journal Database, and WANFANG Database. Randomized controlled trials (RCTs) related to the NMES for the treatment of patients with IC will be included, regardless publication status and language. Literature selection, data collection, and study quality assessment will be independently performed by two authors. The extracted data will be expressed as risk ratio and 95% condence intervals (CIs) for dichotomous data, and mean difference or standard mean difference and 95% CIs for continuous data. RevMan V.5.3 software will be employed for statistical analysis.


Background
Interstitial cystitis (IC) is a chronic, progressive debilitating bladder disorder [1][2][3], which is characterized by intermittent ares of frequency, urgent voiding, and pelvic pain [4][5][6].It is estimated that the prevalence rate of IC ranges from 0.3% to 2% according to clinical diagnosis around the world [7][8].The etiology of IC remains poorly understood [9].Despite several therapies are reported to manage IC, none of them can effectively treat this condition [10][11].Thus, it is very urgent to nd potential candidates.
Fortunately, neuromuscular electrical stimulation (NMES) is recommended as a potential candidate and a variety of studies reported that NMES can be used to treat IC [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26], which offers us new data for conducting this systematic review.Accordingly, this present study is designed to critically synthesize the most recent published data to appraise the effectiveness and safety of NMES for the treatment of patients with IC.

Study registration
This protocol has been registered on PROSPERO (CRD42020170495), and it is reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISRMA) Protocol statement guidelines [27][28].

Study eligibility criteria
Types of studies Without limitations on language and publication status, this study will include randomized controlled trials (RCTs) that explore the effectiveness and safety of NMES for the treatment of patients with IC.

Types of participants
All patients who were diagnosed as IC will be included, regardless gender, race, age, economic status, duration and severity of IC.

Experimental interventions
All patients in the experimental group were treated with NMES only.Any treatments combined with NMES will be excluded.

Control interventions
All patients in the control group were treated with any interventions, such as oral medication, moxibustion, and physical therapy.However, any management combined with NMES will be excluded.

Type of outcome measurements
Primary outcomes are pain intensity (as measured by Visual Analog Scale or other pain scales), and improvement of overall symptoms (as assessed by patient-reported global response assessment or other tools).
Secondary outcomes are urinary frequency episodes, quality of life (as checked by 36-Item Short Form Survey or other questionnaires), and adverse events.

Search strategy
The electronic databases will be comprehensively retrieved from their commencements to the March 1, 2020 to identify all related potential studies: MEDLINE, EMBASE, Cochrane Library, Web of Science, CINAHL, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, Chinese Scienti c Journal Database, and WANFANG Database.There are no limitations to publication language and status.A search strategy for MEDLINE has been established (table 1).Identical search strategies will be applied to all other electronic databases.
We will also search relevant conference abstracts, clinical trial registries for ongoing trials, and reference lists of all related reviews.

Study selection
Two authors will independently import all citations into EndNote X9 to eliminate duplicated ones.
Titles/abstracts of all potential records will be screened to remove any irrelevant studies.If necessary, we will obtain and read full-text of remaining literatures according to the eligibility criteria.All excluded studies will be noted and summarized with reasons.Any differences will be worked out with the help of another author and a consensus will be made.The results of study selection will be summarized in a PRISRMA ow diagram.

Data extraction and management
Two authors will independently extract data by a standardized data form developed speci cally for this study.Any confusion will be cleared up with the help of another author and a nal conclusion will be made.The information includes study general information (e.g.title, rst author, year of publication), participant characteristics (age, gender), diagnostic criteria, inclusion and exclusion criteria, study design, sample size, interventions, outcomes, results, ndings, adverse events, and funding information.

Dealing with missing data
Any insu cient or missing data will be requested from primary authors.If they can not provide those data, we will perform data analysis based on the available data, and we will discuss its affects on the study ndings.

Study quality assessment
The Cochrane Collaboration's tool will be utilized to assess study quality of included trials by two independent authors.Each study will be identi ed at seven aspects, and each one is graded as 3 levels: low, unclear, and high risk of bias.Divergences will be arbitrated with the help of another author.

Statistical analysis
Data synthesis RevMan 5.3 software will be utilized for statistical analysis.Risk ratio with 95% con dence intervals (CIs) will be used to measure the treatment effect for dichotomous outcome data.Mean difference or standardized mean difference and 95% CIs will be suggested to measure the treatment effect for continuous outcome data.Statistical heterogeneity will be examined by I² test.I² ≤ 50% suggests homogeneity, and we will use a xed-effect model.If possible, we will conduct a meta-analysis when su cient trials are included.I² >50% indicates considerable heterogeneity, and we will place a randomeffect model.In addition, we will perform subgroup analysis to check sources of obvious heterogeneity.If there is still remarkable heterogeneity after subgroup analysis, a meta-analysis will not be carried out.However, we will report outcome results using a narrative synthesis.

Supplementary Files
This is a list of supplementary les associated with this preprint.Click to download. PRISMAPchecklist.doc