Fen Zhou,Yun-Peng Lv,Xian Wang

1School of Nursing, Beijing University of Chinese Medicine, Beijing, China; 2Joanna Briggs Institute Centre of Excellence, Beijing University of Chinese Medicine, Beijing, China; 3Department of General Surgery, First Medical Center, Chinese PLA General Hospital,Medical School of Chinese PLA,Beijing,China.

Abstract Objective: Lactation mastitis is a kind of disease with high incidence during puerperium.In the early stage,breast massage can effectively eliminate the symptoms.However, the value of breast massage is not fully known to the public,which restricts its promotion and popularization.One important reason is the absence of a multi-dimensional and overall evaluation of outcome.COS is strongly advocated internationally as the outcome in clinical research to promote the transformation of clinical evidence into practice.At present,there is no systematic review of the existing outcome.This protocol aims to provide a set of outcomes and outcome evaluation schemes for developing COS of breast massage in lactation mastitis early stage.Methods:We will search PubMed,Embase,Web of Science,CNKI,Wan-fang,VIP,SinoMed,Grey literature databases (master and doctoral thesis databases and conference literature databases of CNKI, Wan-fang and SinoMed), Clinical Trials Registry Platform portal, the Clinical Trials Registry, Australian, New Zealand Clinical Trials Registry, the Center Watch Registry, before March 1, 2021.We will include randomized controlled trials and non-randomized trials, cohort studies,case series,case reports.We will assess the quality of outcome reporting according to the MOMENT, classify all outcomes using the OMERACT Filter 2.0 conceptual framework.Descriptive analysis will be performed for all categorical variables using frequency and mean.Result:This protocol aims to help guide the design of systematic review to summarize the existing outcomes, and comprehensively evaluate existing outcomes, classify outcomes and provide schemes of outcome evaluation for developing COS of breast massage in the early stage of lactation mastitis.Percentage and mean will be used to describe the extracted data.Conclusion:This is the first systematic review protocol to summarize outcomes, measurement instruments, assessment times, measurement frequencies, measurers about breast massage in the early stage of lactational mastitis.

Keywords:Lactation mastitis,Breast massage,Protocol,Systematic review,Outcome

Introduction

Lactational mastitis (LM) is defined as inflammation of the breast tissue and is commonly experienced by breastfeeding women [1].A systematic review shows,the percentage of participants who experience mastitis ranged from 2.5%to 20%,and it is possible to develop mastitis even more than once,women could experience LM many times [2].Patients have endured heavy postpartum physiological and psychological pressure during puerperal period, the LM undoubtedly aggravates the pain, which more likely to lead to anxiety, or even depression, and seriously affects their body recovery,psychological health status, and quality of life [3,4].For infants, LM mothers are forced to wean due to severe mammary duct blockage, which directly affects the growth and development of their infants[5].If LM mothers suddenly stop breastfeeding,it will lead to a risk of abscess and increase the economic burden on their family [6,7].Besides, it is reported that LM may increase the risk of mother-to-child transmission of HIV[8].

LM can be divided into three stages:Milk stasis(early stage),abscess stage,and ulcer stage[9].Timely treatment in the early stage is very important.If not,it will lead to severe chronic prolonged inflammation even abscess, which patients may necessitate hospitalization and surgery, the treatment becomes more complex [10].A Cochrane systematic review published in 2013 also confirmed that antibiotics could be helpful to eliminate infection, but they couldn’t effectively solve the problem of blocked ducts[11].At the same time, patients choose to suspend breastfeeding due to the concern of the potential adverse effect of drugs on their infants,which leads to the women can’t express the milk from the breast by herself, even aggravating the symptom and occurs repeatedly.

Breast massage is a nursing technology that can fully express the milk through hands to dredge the patient's mammary gland with different skills to relieve symptoms of LM [12,13].Both Traditional Chinese Medicine (TCM) dominated hospital and Western Medicine dominated hospital nurses use breast massage in China.Still, there are significant differences in mechanism, operation skills and operators(Table 1).Breast massage is known as“green therapy” in China because it is believed safe enough without any medicine,it is especially significant in the early stage of LM.Studies have shown relatively high cure rates(71.8～84.4%)for patients in the early stage of LM with appropriate breast massage[14-15].

However, breast massage has not been promoted in clinical practice.After visited some hospitals in China, we found that patients with solid demands for breast massage, even supply fell short of demand.Almost all western medicine dominated hospitals in China ignored to provide technical support of breast massage; while in TCM dominated hospitals, this technique is limited to carry out in TCM breast clinic.Based on the literature review, we found that outcome evaluation is not comprehensive in existing studies.Hence, the effectiveness of breast massage can’t be evaluated from multi-angles and comprehensively.As a result, the stakeholders (policymakers, clinical managers, health professionals, etc.) cannot fully recognize the significance of breast massage, which could be one of the reasons for restricting its development and promotion.

Core outcome set (COS) is the minimum,recognized, standardized set of outcomes that must be measured and reported for all clinical trials of a specific condition [16].It is strongly advocated internationally that choosing COS as the outcome in clinical research can improve the reliability and practicability of clinical research, to promote the transformation of clinical evidence into clinical practice [17].Besides, the use of COS can reduce inconsistency in outcome reports and allow outcomes in different studies to be compared and combined[18].In Core Outcome Measures in Effectiveness Trials(COMET)database,there is a total 337 published COS,relating to 410 studies of COS, and increasing year by year [19].More and more researchers are paying attention to the role of COS [20-22].At present, there is no study on COS of breast massage in LM early stage.And we also found there is indeed a significant heterogeneity in outcomes used to evaluate the effectiveness of breast massage in current clinical studies in LM early stage, which directly hinders the production of evidence synthesis, such as systematic reviews, clinical practice guidelines, and evidence summaries, etc [23].In 2014, the Outcome Measures in Rheumatology initiative (OMERACT) Filter 2.0 conceptual framework was developed to collect outcomes in a more comprehensively way and guide the classification of outcomes [24].This conceptual framework includes two concepts:Impact of health conditions and pathophysiological manifestations.It covers five areas:death, life impact, resource use/economical impact, pathophysiological manifestations, and adverse events.“Adverse events”belongs to neither impact of health conditions nor pathophysiological manifestations.At present, it has been applied to develop COS of psoriasis,gastrointestinal diseases,nervous system diseases,et al[25-27].

Therefore, our first purpose is to review what outcomes have been reported in the early stage of LM,and to categorize these outcomes scientifically so that appropriate measurement instruments can be selected.The second purpose is to determine measurement instruments,assessment times,measurement frequencies, and measurers; The third objective is to evaluate the quality of outcome reporting in studies about breast massage in LM early stage.The purpose of this study is to provide a set of outcomes to evaluate outcomes comprehensively, and provide a scheme of outcome evaluation for developing COS of breast massage in LM early stage.

Methods

Protocol registration

Our protocol is registered in Open Software Foundation(OSF),registration doi:10.17605/OSF.IO/2BZU7, and reported according to Preferred Reporting Items for Systematic reviews and Meta-Analysis Protocol guidelines (PRISMA-P) [28].In the future, PRISMA will be used for reporting our systematic review [29].We make a flow chart (Figure 1) in advance to guide the specific conduct of the research.

Eligibility criteria

Inclusion criteria:

(1) Types of studies:Publish types are not limited.We will include randomized controlled trials (RCTs) and non-randomized trials(non-RCTs),cohort studies,case series and case reports, without limitation of publication type.(2) Participants:Studies focused on puerperal/postpartum patients,who are diagnosed with LM early stage.(3) Interventions:Different types of breast massage alone, include massage, acupoint massage, meridian massage, knead and squeeze on breast, et al.(4) Controls:Standard care, drug therapy(such as antibiotics, Chinese herbs, external application with Chinese medicine, et al.), non-drug therapy(such as hot compress,cold compress,physical therapy, et al.).(5) Outcome:We will extract primary and secondary outcomes for patients,newborns/infants,and caregivers, as well as information about the measurement instruments, assessment times,measurement frequencies,and measurers.(6) Settings:In hospital, community,and other medical institutions.(7)Language:Published in Chinese or English.

Exclusion criteria:

(1) Full texts are unavailable.(2) Contradictions existed in the study,such as the contradiction between the result and the conclusion.

Information sources

We will systematically search for all literatures published before March 1, 2021.Databases will include three sources as follows:(1) Electronic databases:PubMed, Embase, Web of Science, CNKI,Wan-fang,VIP,SinoMed.(2)Grey literature databases:Master and doctoral thesis databases and conference literature databases of CNKI, Wan-fang and SinoMed.(3)Clinical trials registration platforms:Clinical Trials Registry Platform portal (http://www.who.int/ictrp/en),the Clinical Trials Registry(http://www.clinicaltrials.gov/),Australian,New Zealand Clinical Trials Registry(http://www.anzctr.org.au/), the Center Watch Registry(http://www.centerwatch.com/).

Search strategy

We will apply the medical subject headings (MeSH),as well as Title/Abstract (such as “l(fā)actation mastitis”,“puerperal mastitis”, “breast massage”, “acupoint massage” and “acupoint tuina”).The example of the search strategy of PubMed shows in Figure 2.

Figure 2.Search strategy of PubMed

Selection and data extraction

Selection process:Firstly, search results will be imported to NoteExpress3.2 software to remove duplicates.The titles and abstracts will be screened to remove irrelevant studies.Then full texts will be downloaded and screened to exclude studies against the inclusion criteria and eligible studies will be obtained.

Data extraction:Two reviewers will independently extract study information include study characteristics such as title, author, publication year, setting, study design, sample size (each group), intervention,comparison, and outcome related information include outcomes,measurement instruments,assessment times,measurement frequencies and measurers.Any disagreements will be resolved by discussion or consultation with the third reviewer.

Outcome reported quality

All included studies will be scored according to the standard of the Management of Otitis Media with Effusion in Children with Cleft Palate (MOMENT)[30].This standard is the most common used quality appraisal tool of outcomes upon COS development and in good feasibility.The score range is from 0 ～ 6.A score above 4 will be considered as“high quality”,2～4 “moderate quality”, and less than 2 “l(fā)ow quality”.There are six evaluation items, include:(1) Clearly stated primary outcome; (2) Clearly defined primary outcome;(3)Clearly reported secondary outcomes;(4)Clearly defined secondary outcomes; (5) Reasons for selection of outcomes; (6) Quality of outcome measurement.Each item will be scored “1” for “Yes”or“0”for“No”[31].

Two reviewers will be professionally trained prior to assess the quality of outcome reported.We will resolve disagreements by discussion or consultation with the third reviewer.

Outcome classification

Two reviewers will independently classify outcomes according to OMERACT Filter 2.0 conceptual framework.As illustrated in Table 2, this framework includes 2 concepts and 5 separate areas,each of these areas can include one or more domains, each included domain may include one or more outcomes.Reviewers will find the right concept, whether it is the impact of health conditions or pathophysiological manifestations,and select the appropriate areas according to the specific outcome (Table 2).Outcomes with different expressions but the same meaning in included studies will be grouped into the same domain by two reviewers.For example, the outcome in the included studies is described as “induration”, “l(fā)ump” or“agglomeration”.In fact,they all were used to describe the “l(fā)ump” in early stage of LM, it will be grouped into “l(fā)ocal symptom” domain.All outcomes,measurement instruments, assessment times,measurement frequencies, and measurers in each domain will be reported.

Statistical analysis

We will list the details of each included studies, such as title, publication year, study design, sample size,intervention, primary and secondary outcomes,measurement instruments, assessment times,measurement frequencies, and measurers, and the result of each outcome.Percentage and mean will be used to describe the extracted data.

In our study, the breast massage in early stage of LM might include different types as mentioned before.According to mechanism and techniques, the intervention will be divided into two subgroups:TCM breast massage and non-TCM breast massage.We will analyze and compare differences in outcomes between the two groups.Subgroup analyses could also be performed according to different people involved in outcomes (maternal herself, infants, and caregivers);Other subgroups will be determined according to the specific studies.

Discussion

This protocol aims to help guide the design of systematic review to summarize the existing outcomes,and comprehensively evaluate outcomes, provide scheme of outcomes evaluation for the development of COS about breast massage in LM early stage.As far as we know,this systematic review will provide outcome evaluation scheme of clinical studies on breast massage in the early stage of LM for the first time.It will reveal the outcomes, measurement instruments,assessment times, measurement frequencies, and measurers in the clinical studies of breast massage in LM early stage, and explore the heterogeneity in content and the quality of outcome report.In terms of methodology, we will use MOMENT to assess the quality of outcome report, MOMENT is the most widely used standard and it is applied for the first time to develop a COS of breast massage in LM early stage.In addition, the OMERACT Filter 2.0 conceptual framework we will use is also the commonly used framework for outcome classification in the world,which can better guide our study to classify outcomes and select appropriate measurement instruments.Some results may not be paid enough attention in literature,so we expect this study will help find new research points for researchers in this field in the future to fill the knowledge gap.We also believe that our systematic review will provide an essential basis for developing COS of breast massage in LM early stage, and to achieve the purpose of enabling potential users to understand the clinical effect of breast massage better.

This systematic review protocol will be reported according to the reporting guidelines provided in PRISMA-P.Any revisions or modifications to this program will be described and reported in the final systematic review.

Funding

This work is supported by Education Science Research Project of Beijing University of Chinese Medicine(XJYB2029),and Fundamental Research Funds for the Central Universities(2020-JYB-ZDGG-082).

Acknowledgements

Thank Associate Hui Liu, who is from the Zhejiang Sci-Tech University for her invaluable help in the English modification of this manuscript.