1 Introduction
Dysphagia is 1 of the most common consequences of stroke, which occurs in 27% to 64% of stroke patients,[1–3] [4] [5,6] [7,8] [9] [10]
However, until today, dysphagia after stroke is an underdiagnosed and undertreated condition around the world, and most patients do not receive comprehensive care.[11] [12] [11] [12]
Acupuncture, belongs to traditional Chinese medicine practice, which means acupuncurist will insert needles into a person's skin, with the aim of balancing their energy named “qi”. Acupuncture is used routinely in stroke rehabilitation in China and elsewhere in East Asia over the past 1,000 years, and has been recommended by the World Health Organization as an alternative and complementary strategy for stroke treatment and care.[13,14] [15]
(1) regulation of the release of neurotransmitters;
(2) regulation of cerebral microcirculation;
(3) antiapoptosis;
(4) stimulation of neurogenesis and cell proliferation;
(5) regulation of neuroplasticity.[16,17]
Many studies have indicated that acupuncture might be beneficial in the rehabilitation of patients with swallowing dysfunction in post-stroke.[18–20]
Several systematic reviews reported that acupuncture and related therapies might be effective for dysphagia after stroke.[12,19–22] network meta-analysis (NMA) of the differences between different acupuncture and related therapies for dysphagia after stroke. The objective of this study is to assess the efficacy and safety of different acupuncture and related therapies, to synthesize all this evidence and perform a comprehensive rank of available acupuncture and related therapies for dysphagia after stroke, and to provide decision-making reference for clinical practitioners, patients, and health policy makers.
2 Methods
2.1 Protocol and registration
The NMA protocol has been registered on the Open Science Framework (OSF) platform (https://osf.io/tahnd/ [23] [24]
2.2 Ethics
Since NMA does not involve the collection of private information, this research does not require ethical approval.
2.3 Eligibility criteria
The participant (P), intervention (I), comparator (C), outcome (O), and study design (S) are the 5 main factors determining the inclusion and exclusion criteria of this research.
2.3.1 Type of study design
This study is a systematic review with NMA of randomized controlled trials (RCTs) on acupuncture and related therapies for dysphagia after stroke. All relevant RCTs using acupuncture therapies for dysphagia after stroke will be included. Quasi-RCTs, duplications, animal trails, review documents, clinical experience, and case reports will be excluded. Additionally, only English and Chinese literature will be searched for this study.
2.3.2 Type of participant
All cases included in the trial will be patients with dysphagia after stroke, regardless of gender, age, educational background, nationality, or outpatient therapy or inpatient therapy. Specific diagnostic criteria include:
(1) ischemic or hemorrhagic stroke confirmed by CT or MRI scan;
(2) dysphagia confirmed by videofluoroscopic swallowing study (VFSS) and/or Mann Assessment of Swallowing Ability.[25]
Swallowing disorders caused by other underlying neurological disorders will be excluded.
2.3.3 Type of interventions and comparators
We will consider acupuncture and related therapies (acupoint-based therapy), regardless of needling techniques and stimulation method including TA, EA, MA, SA, moxibustion, catgut embedding, transcutaneous electrical acupoint stimulation, acupoint injection, medium-frequency electric stimulation, and so on. These interventions can be used in any combinations or in combination with conventional therapy (conventional treatment or rehabilitation training in neurology department). Non-acupuncture-related treatments will be excluded, such as medicine, and transcranial electric/magnetic stimulation, and so on.
In order to ensure the consistency and transmissibility of the studies, controlled interventions will be limited to different acupuncture and related therapies, placebo group, or conventional therapy group. Trials comparing 2 acupoint selections or acupuncture manipulations will be excluded.
2.3.4 Type of outcomes
(1) Primary outcomes
Clinical efficiency (Total effective rate), will be measured as the proportion of effective patients to the total sample size in the studies, after treatment and/or during follow-up. The total effective rate is the sum of the data contained in the original literature on “recovery”, “significant effect”, “effective” and related terms.
VFSS score, will be measured as the dynamic passage of food from the mouth to the throat and the occurrence of aspiration, leakage, cough and food retention by swallowing angiography before and after treatment.
Kubota drinking water test grade, will be measured as the time taken to drinking water and the occurrence of choking cough before and after treatment.
(2) Secondary outcomes
Swallowing disorder specific quality of life score.
standardized swallowing assessment.
Adverse effects reported in the original studies (eg, skin or tissue damage, pain or discomfort, vascular, visceral or nerve injury).
The definitions of the outcomes are described in Table 1 . Those outcome measures, including clinical efficiency, VFSS score, Kubota Drinking Water Test grade, Swallowing disorder specific quality of life score, and standardized assessment will be used to assess for effectiveness, and the safety assessment will be measured by adverse effects.
Table 1: Characteristics of the outcome measures.
2.4 Literature retrieval strategy
Computer retrieval of published RCTs of acupuncture and related therapies for dysphagia after stroke is conducted in PubMed, the Cochrane Library (issue 3, 2020), EMbase, China National Knowledge Infrastructure, China Biological Medicine, Chinese Scientific Journals Database (VIP), and wan-fang databases. The time limit of document retrieval is from the establishment of each database to March 31, 2020. The language is limited to English and Chinese. In addition, the World Health Organization International Clinical Trials Registration Platform and Clinical Trials.gov will also be searched for ongoing experiments and Chinese RCTs related to the disease. The used retrieval mode will be a combination of free words and medical subject headings terms, including: “dysphagia”, “stroke”, “acupuncture”, “moxibustion”, “electro-acupuncture”, “moxibustion acupuncture”, “acupoint”, “auricular therapy”, “scalp acupuncture”, etc. The following terms will be used in the Chinese database retrieval: “tunyanzhangai”, “cuzhong”, “zhongfeng”, “zhenjiu”, “aijiu”, “dianzhen”, “wenzhen”, “touzhen”, “xuewei”, “suijiduizhao”, etc. Taking PubMed as an example, the initial search strategy is shown in Table 2 and will be adjusted according to the specific database.
Table 2: Search strategy of the PubMed.
2.5 Literature selection and data extraction
As shown in Figure 1 , Two researchers (Fanjie Xiong and Kai Song) will independently screen literatures according to the inclusion and exclusion criteria:
(1) The retrieved literatures will be imported into Endnote X9 software for rechecking, and duplicate references are removed;
(2) By reading the title and preliminaryly screening the abstract, exclude the literature that obviously does not meet the inclusion criteria;
(3) Download and read the full text for re-screening;
(4) After the final inclusion, the pre-designed data extraction table is used for data extraction, and the results will be cross-checked;
(5) If there is any disagreement, the third researcher (Ailing Huang) will be asked to assist in the judgment.
Figure 1: PRISMA flow diagram of the study selection process.
The main content of data extraction includes: basic information of literature (title, journal, author, and publication date), basic situation of the research object (sample size, gender, mean age, intervention and comparator, and course of treatment), and outcome data (numbers of response events, non-response events, dropouts, time points, mean, SD, follow-up time and adverse events). If the required data is lost or incomplete, we will contact the corresponding author of the original document or the relevant email address of the first author. If there is no response, the record is excluded. At the same time, the key factors of bias risk assessment will be extracted.
2.6 Risk of bias assessment
The methodological quality of systematic review reflects the risk of bias or validity in its process and results. Methodological quality will be assessed based on the Cochrane Handbook 5.2.0.[26]
(1) random sequence generation;
(2) allocation concealment;
(3) blinding of the subjects and researchers;
(4) blinding of outcome assessment;
(5) incomplete outcome data;
(6) selective reporting;
(7) other bias.
2.7 Data synthesis and statistical methods
2.7.1 NMA
This study will use Aggregate Data Drug Information System 1.16.8 for NMA.[27]
2.7.2 Statistical model selection
Node-split model will be used to verify the consistency of the corresponding data. If there is no statistical difference (P > .05) between direct comparison and indirect comparison, the consistency model is used, whereas the inconsistency model will be used for analysis. If the consistency model is adopted, then the stability of the results is verified by the inconsistency model: when the inconsistency factors including 0, and at the same time inconsistency standard deviation including 1 says the result of consistency model is more stable and reliable. At the same time, various analysis models are iterated with preset parameters, and the convergence of iteration effect will be judged by potential scale reduced factor (PSRF). When the PSRF value is close to or equal to 1 (1≤PSRF≤1.05), it indicates that the convergence is complete, the model has good stability, and the conclusion of analysis is reliable. If the PSRF value is not in this range, the iteration continues manually until the PSRF value reaches the range standard.
2.7.3 Assessment of heterogeneity
Before the combination of effect size, the heterogeneity of the included literature is tested using Stata 13.0. When inter-study heterogeneity exists, the random effect model will be used. For comparison of each pair, heterogeneity is assessed by the statistic I 2 I 2 I 2
2.7.4 Sensitivity analysis and subgroup analysis
If necessary, the sensitivity analysis will be used to assess the effect of each study on the random effects model. The sensitivity of the general combined effect of all outcome indicators is analyzed by the exclusion method. That is, all studies are excluded 1 by 1, and the remaining studies will be re-analyzed to determine the stability of the results. If there is no qualitative change in the combined effect showed in the results, the results are stable.
Based on the overall situation of the included study, subgroup analysis will be conducted as far as possible:
(1) short-term and long-term efficacy will be discussed according to the treatment and follow-up period;
(2) Average Age of patients;
(3) Intervention time of treatment measures;
(4) Different acupuncture manipulations and acupoint selection.
2.7.5 publication bias
If 10 or more studies are included in the NMA, a comparison-adjusted funnel plot is developed using Stata to evaluate the presence of small sample effects or publication bias in the intervention network. Descriptive analysis will be carried out through the symmetry of funnel plot. If the plot is asymmetric and there is no inverted funnel shape, it indicates that there may be publication bias. This may be related to the difficulty in the publication of the literature with negative results and the low quality of the inclusion methods.
2.7.6 Evaluating the quality of the evidence
To grade evidence quality and understand the current situation of evidence rating thereby analyzing possible problems, the Grading of Recommendations Assessment, Development and Evaluation system will be used to assess the quality of evidence in the NMA [28]
2.7.7 Patient and public involvement
There was no patient or public involvement in the preparation of this protocol.
3 Discussions
There are a significant number of patients with dysphagia after stroke in China, and acupuncture and related therapies have been a common intervention for swallowing dysfunction in post-stroke.[29]
There are numerous acupuncture and related therapies for dysphagia after stroke and their efficacy has been evaluated by previous RCTs. However, the research quality is uneven, and the intervention mode is relatively simple compared with the clinical practice, without considering multiple factors together. NMA, recognized as a valuable tool, can integrate direct and indirect comparisons across a set of multiple interventions.[30,31]
However, there are some potential limitations that are predictable in this NMA. Acupuncture therapy is widely used for stroke patients in China and other oriental countries, such as South Korea and Japan.[32]
Nevertheless, the ranking of different acupuncture therapies provided by this study is valuable, which can guide clinical decision makers to select the best treatment strategies for dysphagia after stroke. The findings and results of this study will be published in a peer-reviewed journal.
Author contributions
Fanjie Xiong and Kai Song made the same contribution to the research and design, and wrote the original draft of the protocol. Fanjie Xiong has developed a search strategy. Fanjie Xiong, Kai Song and Ailing Huang will conduct literature retrieval and collation. Fanjie Xiong, Kai Song and Hong Zhang will evaluate the risk of bias in the literature. Data analysis and article writing will be done by Fanjie Xiong, Kai Song. Hong Zhang, as the corresponding author, will be responsible for overseeing every process of the audit review to control the quality of the study. All the authors have approved the publication of the protocol.
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