Systematic Review on Acupuncture for Treatment of Dysphagia after Stroke

Objective To assess the therapeutic efficacy of acupuncture for dysphagia after stroke. Methods Seven electronic databases were searched from their inception until 31 September 2016. All randomized controlled trials (RCTs) incorporating acupuncture or acupuncture combined with other interventions for treatment of dysphagia after stroke were enrolled. Then they were extracted and assessed by two independent evaluators. Direct comparisons were conducted in RevMan 5.3.0 software. Results 6010 patients of 71 papers were included. The pooled analysis of efficacy rate of 58 studies indicated that acupuncture group was superior to the control group with moderate heterogeneity (RR = 1.17, 95% CI: 1.13 1.21, Z = 9.08, and P < 0.00001); meta-analysis of the studies using blind method showed that the efficacy rate of acupuncture group was 3.01 times that of control group with no heterogeneity (RR = 3.01, 95% CI: 1.95 4.65, Z = 4.97, and P < 0.00001). Only 13 studies mentioned the safety evaluation. Conclusion The result showed that the acupuncture group was better than control group in terms of efficacy rate of dysphagia after stroke. And the combining result of those researches using blind method was more strong in proof. Strict evaluation standard and high-quality RCT design are necessary for further exploration.


Introduction
Dysphagia was one of the most common sequelae after stroke. The incidence reached 81% [1]. There were many complications in dysphagia, such as cacotrophy [2], dehydration, aspiration, and pneumonia [3]. Those complications improve the morbidity, mortality, the rehabilitation, and the quality of life of the patients. So the medication and intervention time are very important for recovery. Acupuncture was an effective method and more and more welcomed and applied clinically [4]. There were many studies [5][6][7] about the acupuncture for treatment of dysphagia after stroke internationally, including the scalp acupuncture, nape needle, auricular needling, or combing with other methods.
Though, there were some systematic reviews focusing on the acupuncture for treatment of dysphagia in stroke. There was lack of higher quality research or the positive conclusion could not be obtained. Thus, the inclusion and exclusion criteria were formulated after integrating the previous relevant reports. And the studies using single blind method were pooled to be analysed alone.  (4) 1996 Chinese Medicine Internal Medicine Association "criterion for evaluating curative effect of apoplexy"; (5) the guidelines for diagnosis and treatment of acute ischemic stroke composed by cerebrovascular branch of Neurology of Chinese Medical Association; (6) the guidelines for diagnosis and treatment of acute ischemic stroke in China 2010 Edition; (7) National Institutes of Health Stroke Scale (NIHSS) [8,9]; (8) the therapeutic efficacy evaluation standard of TCM diagnosis for stroke; (9) confirmed by head CT or MRI and other imaging methods for stroke; (10) Summary of the Sixth National Conference on cerebrovascular diseases.

Interventions.
For the intervention in acupuncture group, acupuncture alone or combined with other interventions was all included, such as the rehabilitation training, swallowing therapeutic apparatus, swallowing training, and electrical stimulation. There was no distinction for the acupuncture manipulation, acupoint, stimulation intensity, and course of treatment. It is available for blank control group, drugs, or rehabilitation training in control group.
2.6. Data Extraction. Data were extracted independently by two authors (Qiuping Ye and Yu Xie) using a specifically designed data extracted form. The disagreements were solved by the third author's assistance (Junheng Shi) if necessary.
The following information was extracted: (1) the first author, year of publication and the journal; (2) the research design; (3) the basic situation of the patients; (4) the inclusion and exclusion criteria; (5) the indicators of evaluation; and so on. After recording the reasons for exclusion, we got the flow diagram (see Table 1 and Figure 1) including 71 studies .

Quality Assessment.
The methodological quality of each study was assessed from the following aspects: (1) random sequence generation; (2) allocation concealment; (3) blinding of participants and personnel; (4) blinding of outcome assessment; (5) incomplete outcome data; (6) selective reporting; (7) other bias and judging from "yes (low risk)," "no (high risk)," or "unclear (information is insufficient to evaluate)" and reporting the risk of bias graph (Figures 2 and 3).

Result
71 studies including 6010 patients were enrolled finally. There were 2991 participants in acupuncture group and 3019 participants in control group.
3.1. The Basic Characteristics. Two groups were compared statistically based on age, gender, duration, and degree of dysphagia. And the baseline was comparable. See Table 2; 12 studies used the complete random and allocation concealment; 10 studies used the single blind method in the outcome assessment and statistics analysis. For the incomplete outcome data, 12 studies reported the fall off and exit of patients without any effect on the result; 17 studies mentioned the funding support, and not the others.

Data
Analysis. RevMan 5.3.0 software was used for data analysis. And the different outcome assessment indicators were used to be classified and analysed. They were presented as risk ratio (RR) or mean difference (MD) with a 95% confidence interval.

Efficacy
Rate. 62 studies used the clinical efficacy rate as the evaluation indicator with the dichotomous data. So the risk ratio (RR) was used to show the result. We found the medium heterogeneity ( 2 = 68%) after combining data. We could observe from the funnel plot that 3 studies [19,31,82] had deviated from the center line. After sensitivity analysis, we found that one study [19] considered the significantly effective result as recovery and the other as invalidation, which led to difference in results. At the same time, the intervention group of the two studies [31,82] was treated with acupuncture combined with western medicine. And the curative effect was significantly higher than that of the control group. All the dots were equally distributed on both sides of the dashed line in the funnel plot with no publication bias after removing them ( Figure 4). The moderate heterogeneity was found after remerging ( 2 = 58%). So we chose the random effect model ( Figure 5). The pooled analysis showed that the total rectangle was on the right of the equivalent line, which indicated the curative effect of acupuncture group was  better than the control group (RR = 1.17, 95% CI: 1.13 1.21, = 9.08, and < 0.00001).

Standard Swallowing Assessment (SSA).
There were 11 studies that used the SSA as the effective evaluation standard with the continuous data. The meta-analysis of them was showed in mean difference with high heterogeneity ( 2 = 83%). So the random effect model was used ( Figure 6). The figure showed that acupuncture group could lower the SSA cores (MD = 3.7, 95% CI: −4.93 −2.48, = 5.94, and < 0.00001).

Watian Swallowing
Test. The Watian Swallowing Test was used in 24 studies; 9 of them used the dichotomous data. The risk ratio was selected to demonstrate the count data. The results ( Figure 7) showed high heterogeneity ( 2 = 87%).
Hence the random effect model was used. And the rectangle was on the right of the equivalent line, which indicated that acupuncture group could improve the efficacy of dysphagia after stroke (RR = 1.25, 95% CI: 1.03 1.50, = 2.31, and = 0.02 < 0.05).
15 studies used the continuous data. And the mean difference was applied. The results showed that the heterogeneity of the merger was large. So we did the subgroup analysis according to the course of disease. Then the heterogeneity decreased from 95% to 67.4% ( Figure 8). There was no publication bias in the funnel plot ( Figure 9). Meanwhile, the pooled analysis showed that the acupuncture could lower the Watian Swallowing Test score (MD = 0.97, 95% CI: −1.11 −0.47, = 4.82, and < 0.00001).  ?

Swallowing Disorder
Integral. 5 studies selected the swallowing disorder scoring as evaluated standard. The metaanalysis of the 5 dichotomous data sets showed that the heterogeneity decreased from 85% to 40% after removing one study [59]. The sensitivity analysis indicated that the heterogeneity might be the treatment course of this study which was longer than the others. We could see from the figure that the score of the control group was higher than the acupuncture group ( Figure 11). It illustrated that acupuncture group was able to lower the swallowing disorder integral (MD = −0.71, 95% CI: −1.08 −0.33, = 3.7, and = 0.0002).

Swallowing-Related
Quality of Life (SWAL-QOL). 5 studies used the SWAL-QOL to express the Swallowing-Related Quality of Life before and after treatment. They all used the continuous data and mean difference to exhibit the results.
The pooled analysis showed that rectangle was intersected with the equivalent line with high heterogeneity ( 2 = 100%), which means nothing ( Figure 12). [67,78] used ADL to express the curative effect, two [27,45] used the Barthel index, and the other one [54] used modified Barthel index. Among them, the activities of daily living before and after treatment were showed using the continuous data and mean difference. The meta-analysis indicted that acupuncture group obviously improved the activities of daily living of the patients with lower heterogeneity ( 2 = 22%) ( Figure 13). And it was 7.31 times as much as the control group (MD = 7.46, 95% CI: 5.49 9.47, = 7.31, and < 0.0001).
The pooled analysis ( Figure 15) of the 2 studies [44,56] using Ichiro Fujishima Rating Scale (IFRS) showed no meaning with medium heterogeneity ( 2 = 69%), neither the result of 2 studies [17,45] using mini-nutritional assessment (MNA). Only one study [54] used Hamilton Depression Scale (HAMD), which showed that the depression degree of acupuncture group was lighter than the control group.
3.11. Blind Method Analysis. We extracted 7 studies using blind method from the enrolled studies, among which 4 studies used the clinical therapeutic efficiency and 5 used Watian Swallowing Test efficacy rate. There was no heterogeneity ( 2 = 0%) after pooling them with dichotomous data and risk ratio (RR) ( Figure 16). So the fixed effect model was used. The rectangle was on the right of equivalent line and the therapeutic efficiency of acupuncture group was 3.01 times Evidence-Based Complementary and Alternative Medicine  Among the studies employing blind method, 4 of them used the SSA as the assessment indicator with continuous data and mean difference (MD). High heterogeneity was found after combined analysis. Sensitivity analysis revealed that heterogeneity might be due to the use of the test method and the gender imbalance in the clinical cases from one study [17]. The heterogeneity was lower ( 2 = 21%) after removing it. We could see from the figure (Figure 17) that the rectangle was on the left of equivalent line, with a trend that acupuncture group could lower the SSA scores (MD = −4.47, 95% CI: −6.59 −3.36, = 7.85, and < 0.00001).

Adverse Reactions Report.
Only 13 studies mentioned the security index, including how to prevent the subcutaneous hemorrhage, needle sickness, curved needle, broken needle, and the handing method during acupuncture process.
Meanwhile, some studies reported the influence caused by the adverse reactions, not the others.

Discussion
The study indicated that the therapeutic efficacy of acupuncture or acupuncture combined with other intervention was better than the control group, though some pooled results had higher heterogeneity. The interventions such as the acupuncture, rehabilitation training, and swallowing training were related to the professional skill of the practitioners, the same as the efficacy evaluation. Meanwhile, the various source of cases might lead to difference statistic results.

Comparison with Other
Literatures. The acupuncture alone or combined with other interventions is widely used for dysphagia after stroke in China. There exists some evidence about the acupuncture for dysphagia after stoke. One report [88] stated although acupuncture had a tendency to improve dysphagia after stroke, it could not get the positive conclusion. There was report [89] which indicated that acupuncture combined with the swallowing rehabilitation training had certain advantage. Long and Wu [90] pointed out that acupuncture may be benefit for dysphagia, but highquality research was needed. The present study reworked out inclusion and exclusion criteria to evaluate the efficacy of acupuncture for treatment of dysphagia after stroke and showed stronger evidence in the result.
So it was employed in many researches clinically [18,21,23]. Therefore, the choice of evaluation criteria needs to be more rigorous and scientific in the clinical trial design. In order to increase the reliability, high level evaluators should be chosen to evaluate the efficacy for dysphagia simultaneously.
However, there were several limitations of this review. Some research used the acupuncture combined with other interventions on the basic of the control group. And it was easily mixed with the effect of the acupuncture. Therefore, for experiment group, acupuncture alone or combined with       Some studies [94,95] showed that acupuncture seemed to be safe in the subacute phase of ischemic stroke and cardiac arrhythmia. Others [96] indicated that the safety of acupuncture needs further evidence. And some researches [97,98] show that the occurrence of the adverse events during acupuncture was closely related to the competency of the practitioners and the safety system of acupuncture. However, in the process of literature retrieval, we found that most of the literatures included in this paper paid too much attention to the validity of acupuncture and ignored the influence of adverse event during acupuncture. Therefore, we should consider the security issues in the research design. The unfinished trials caused by the security issues should be reported perfectly according to international standard [99] to ensure the data's integrity.

Conclusion
In conclusion, acupuncture for dysphagia after stroke has therapeutic efficacy. And the acupuncture is safe and reliable within a certain range. More strict evaluation standard and high-quality RCT design are necessary for further exploration on the acupuncture for treatment of dysphagia after stroke.       Heterogeneity:  2 = 0.00, d＠ = 1 (P = 1.00); I 2 = 0%

Disclosure
Qiuping Ye is the first author. The funding agency was not involved in data collection, data analysis, data interpretation, or manuscript development.