Acupuncture and related therapy for constipation predominant irritable bowel syndrome: A network meta-analysis of randomized controlled trials

doi:10.21203/rs.3.rs-4175017/v2

Background: The aim of this study was to compare the clinical effectiveness of acupuncture and related therapies in adults with constipation-predominant irritable bowel syndrome (IBS-C) and to provide guidance for clinical management.

Methods: PubMed, The Cochrane Library, Embase, Web of Science, CNKI, Wanfang and VIP databases were searched for clinical randomised controlled trials (RCTs) of acupuncture and related therapies for IBS-C published from the inception of the database to January 2023. The literature was assessed for quality using the Cochrane 5.3 risk of bias assessment tool, and StataSE 15.0 and GeMTC 0.14.3 software were used for network meta-analysis (NMA)..

Results: Twenty-seven trials were finally included in the NMA, including 7 acupuncture-related therapies. The results of the NMA showed that 7 acupuncture-related therapies were more effective than conventional medicine. The overall efficacy rate showed that acupuncture combined with medication was the most effective therapy (OR=6.33, 95% CI: 2.01, 41.74, P<0.05). The recovery rate showed that acupoint catgut embedding was the best treatment for IBS-C (OR=8.38, 95% CI: 2.65, 38.00, P<0.05). The overall efficacy rate at follow-up showed that acupuncture combined with medication had the best sustained effect.

Conclusion: Acupuncture-related therapies are more clinically effective than conventional medicine in the treatment of IBS-C. Acupoint injection combined with medication has the best effect in both the short and long term, and combination therapy may be more beneficial. However, the existing trials have limitations and more high-quality randomised controlled trials are needed to confirm our findings.

IBS-C

acupuncture-related therapies

Randomised controlled trial

Network Meta-analysis

Irritable bowel syndrome (IBS) is a clinical gastrointestinal disorder characterised by abdominal pain and changes in bowel movements or bowel habits [1,2]. IBS is mainly divided into four subtypes based on the type of stool according to the latest Rome IV classification. The global prevalence of IBS is approximately 3.8%, of which 32.4% are constipated [3]. Conventional medicine mostly uses prokinetics and laxatives to relieve symptoms, and there are no specific drugs that may have more adverse effects [4,5]. Irritable bowel syndrome with predominant constipation (IBS-C) is characterised by abdominal distension and defecation difficulties [6], which has a long-term impact on patients' quality of life and represents an excessive demand on social health care resources.

In recent years, acupuncture has made significant progress in the treatment of IBS-C and has been accepted by most patients due to its efficacy and low side effects. Clinical trials of acupuncture for IBS have focused primarily on IBS with predominant diarrhoea (IBS-D), with IBS-C being the second most common. There are many studies of acupuncture interventions for IBS-C, such as those focusing mainly on research progress and the pattern of acupuncture points. Due to the paucity of literature on direct comparisons between different acupuncture treatments, there is no conclusive evidence on which treatment is more effective for IBS-C. Therefore, this paper used network meta-analysis (NMA) to examine the effectiveness of common acupuncture-related interventions for IBS-C to find the best way to address the clinical problem.

1.1 Literature search strategy

The search databases included PubMed, Cochrane Library, EMbase, Web of Science, CNKI, Wanfang and VIP, and the search period was from database inception to January 2023.

Search terms included: acupuncture, electro-acupuncture, moxibustion, acupoint catgut embedding, acupoint application, auricular points, irritable bowel syndrome, IBS-C, randomised controlled trial, etc.

1.2 Inclusion and exclusion criteria

Inclusion criteria were as follows: (1) Study design: Randomised controlled trial (RCT) of acupuncture and related therapies for IBS-C. (2) Study population: patients meeting the diagnostic criteria for IBS-C in Rome III, Rome IV, Consensus Opinions on the Treatment of Irritable Bowel Syndrome in Chinese Medicine, Guidelines for Clinical Research on New Chinese Medicines, Internal Medicine in Chinese Medicine or Practical Internal Medicine. Patients were not restricted in terms of age, sex, disease course (duration) and TCM syndrome type. The experimental group and the control group were comparable with the consistent baseline. (3) Intervention measure: The control group was treated with conventional medicine or Chinese herbal medicine. The treatment group was various acupuncture-related therapies, such as acupuncture, moxibustion, acupoint catgut embedding and other single therapies or combined therapies (two combined therapies). (4) Outcome measures: the overall efficacy rate and the recovery rate of IBS-C efficacy and the overall efficacy rate at follow-up refer to the Guiding Principles for Clinical Research on New Chinese Medicines (for trial conduct) [7] and the Diagnostic Efficacy Criteria for Chinese Medicine Evidence [8].

Exclusion criteria were as follows: (1) duplicate publications: only the most recently published was retained; (2) conference papers; (3) combination of other conditions that may influence efficacy results; (4) unavailability of original data; (5) specific interventions that appeared only once or were unique to certain practitioners.

1.3 Literature screening and data extraction

The literature was searched, extracted and reviewed independently by two researchers using Endnote X9. Based on the inclusion and exclusion criteria, titles and abstracts were reviewed to exclude irrelevant literature, and literature that might meet the inclusion criteria was downloaded and read to determine final inclusion. In case of disagreement, a third party was consulted to make a decision.

1.4 Evaluation of the quality of the literature

The quality of the included literature was assessed using the risk of bias assessment tool recommended in the Cochrane Handbook 5.3. The assessment included: choice of randomisation method, whether allocation concealment was used, whether participants were blinded, whether outcome assessors were blinded, whether outcome data were complete, whether there was selective reporting of outcomes and other biases. Each item was rated as low risk of bias (low risk), high risk of bias (high risk), and unknown risk (unclear risk)..

1.5 Statistical analysis

RevMan 5.3 software was used to assess risk of bias. Network meta-analysis was performed using Stata SE 15.0 software and GeMTC 0.14.3. Odd ratio (OR) was used for dichotomous data with 95% confidence interval (CI). StataSE 15.0 was used (1) to plot the network relationship; (2) for the inconsistency test, and if there was a closed loop formation, the loop inconsistency test was required, which chose the node splitting method. If the confidence interval included 0, this indicated that the loop inconsistency was not significant; (3) for comparison-corrected funnel plots to assess whether there was publication bias or a small sample effect in the included literature. GeMTC 0.14.3 was used to analyse the network metadata and to plot the cumulative probability ranking. The area under the cumulative ranking curves (SUCRA) was used to rank the advantages and disadvantages of interventions. The larger the area under the curve, the more likely it was to be the best intervention.

2.1 Literature search results

The literature search initially identified 721 relevant studies for this study. After eliminating duplicate literature, 401 articles remained. After careful reading of the titles and abstracts of the literature for the initial screening, 301 articles were excluded. Then, 73 studies did not meet the inclusion criteria and 27 literatures were finally included in this study. The flow chart of the literature search is shown in Figure 1.

2.2 Basic characteristics of the literature

This review included 27 RCTs and 2154 patients with IBS-C with 9 interventions including acupuncture (ACU), acupoint catgut embedding (ACE), traditional Chinese medicine (TCM), conventional medicine (CM), acupuncture + medicine (ACU+M), moxibustion + medicine (MOX+M), acupoint application + medicine (AAP+M), acupoint application + auricular pressure (AAP+AP), and acupoint injection + medicine (AI+M). 1 article was a three-arm study and 26 articles were two-arm studies. The main characteristics of the included studies are shown in Table 1.

2.3 Evaluation of the quality of the included literature

(1) Randomisation method: 27 [9-35] of the included studies used random allocation, of which 17 [9,10,12,13,15-18,20-22,24,25,27,29,31,32] studies used a completely random method, including random number table method, computer-generated random sequence method and lottery method, which were classified as low risk; the remaining studies mentioned grouping by randomisation but did not specify the exact method, which was classified as unknown risk. (2) Allocation concealment: one study [35] mentioned allocation concealment by opaque envelopes and was classified as low risk; other studies did not mention whether allocation concealment was used and were classified as unknown risk. (3) None of the included studies mentioned blinding; [4] completeness of outcome data: 2 [9,10] studies had no blinding, 4 [18,24,29,31] studies had an insufficient proportion of missing data to significantly affect the value of the intervention effect compared to the observed events and were rated as low risk, the remainder were rated as unknown risk. (5) The risk of selective reporting and other unknown bias was assessed as unknown risk (Figure 2).

2.4 Results of NMA

In the network evidence graph, the nodes represent different intervention methods, the size of the nodes represents the sample size of each intervention method, the lines between the nodes represent the direct comparison between the two methods, and the thickness of the lines represents the number of relevant trials. The results showed that 27 trials reported the overall efficacy rate after interventions for IBS-C, including 1 three-arm trial, which formed a total of four closed loops. 25 trials reported recovery rates after treatment, and all of these were two-arm trials with no closed loop. 14 trials reported follow-up effectiveness. Of these, 6 trials reported overall follow-up effectiveness, including 1 three-arm trial (Figure 3).

2.5 Inconsistency analysis

The total effective rate formed 4 closed loops and the consistency of each closed loop was tested (P>0.05). The lower limit of the 95% CI of the closed loops was 0, indicating good consistency. The inconsistency of the cure rate was tested (P>0.05), and the total effective rate of follow-up included only 1 three-arm test, so the consistency model was selected (Figure 4).

2.6 The overall efficacy rate

Compared with CM, the overall efficacy rate after intervention was higher with ACU (OR=2.66, 95% CI: 1.47, 5.38, P < 0.05), ACE (OR=4.62, 95% CI: 1.91, 11.74, P < 0.05), ACU+M (OR=3.40, 95% CI: 1.76, 6.57, P < 0.05), MOX+M (OR=3. 27, 95% CI: 1.83, 5.81, P < 0.05), AAP+M (OR=4.09, 95% CI: 1.49, 9.99, P < 0.05), AAP+AP (OR=2.30, 95% CI: 1.10, 5.05, P < 0.05) and AI+M (OR=6.33, 95% CI: 2.01, 41.74, P < 0.05), the difference being statistically significant. Compared with TCM, the overall efficacy rate was higher with ACE (OR=3.33, 95% CI: 1.12, 11.78, P < 0.05), ACU+M (OR=2.52, 95% CI: 1.08, 6.15, P < 0.05), MOX+M (OR=2. 46, 95% CI: 1.06, 5.49, P < 0.05), AAP+M (OR=3.05, 95% CI: 1.43, 6.62, P < 0.05) and AI+M (OR=4.77, 95% CI: 1.22, 38.47, P < 0.05) with statistically significant differences. When comparing the two interventions, there was no statistically significant difference in the overall effective rate of follow-up (Table 2).

2.7 Recovery rate

Compared with CM, the recovery rate was higher with ACU (OR=1.81, 95% CI: 1.05, 3.45, P < 0.05), ACE (OR=8.38, 95% CI: 2.65, 38.00, P < 0.05), ACU+M (OR=1.99, 95% CI: 1.10, 3.96, P < 0.05) and MOX+M (OR=3.01, 95% CI: 1.72, 5.40, P < 0.05), the difference being statistically significant. Recovery rate was higher with ACE (OR=6.59, 95% CI: 1.42, 39.07, P < 0.05) compared to TCM, with a statistically significant difference. When comparing two interventions, the recovery rate of ACE was better than ACU+M (OR=4.32, 95% CI: 1.05, 22.63, P < 0.05) and AAP+AP (OR=5.25, 95% CI: 1.37, 27.42, P < 0.05), and the difference was statistically significant. See Table 3.

2.8 The overall efficacy rate at follow-up

Compared with CM, the overall efficacy rate at follow-up with AI+M was significantly superior (OR=15.04, 95% CI: 1.30, 242.28, P < 0.05). No significant results with other ARTs for the treatment of IBS-C. There was also no significance when comparing different interventions.

2.9 SUCRA value ranking

Using GeMTC 0.14.3 to plot the prediction of the efficacy ranking, the results showed that (1)The overall efficacy rate: AI+M > ACE > AAP+M > ACU+M > MOX+M > ACU > AAP+AP > TCM > CM. (2) Recovery rate: ACE > MOX+M > AAP+M > AI+M > ACU+M > ACU > AAP+AP > TCM > CM. (3) Total efficacy rate at follow-up: AI+M > ACE > MOX+M > TCM > ACU > CM. See Figure 5.

2.10 Analysis of publication bias and small sample effect assessment

We further tested whether there was any bias in the included literature, using the overall efficacy rate and recovery rate as outcome measures. The results of the funnel plots suggested that there might be a slight publication bias and small sample size. See Figure 6.

2.11 Adverse events

Seven of the 27 included trials reported adverse events. Four studies [16,18,26,30] with CM reported adverse events such as haemogram changes, diarrhoea, thirst and drowsiness, dizziness and headache. One study [16] of CM reported liver function abnormalities. Three studies [18,26,30] with MOX+M reported adverse events including abdominal pain, mild nausea, and mild dizziness. One study [19] of ACU+M reported syncope. One study [24] with ACU reported 2 cases of local soreness and discomfort and 5 cases of needle bleeding. One study [35] of AI+M reported 2 cases of bruising around Zusanli. Overall, studies of acupuncture-related therapies showed a lower probability of adverse events than CM, indicating the safety of acupuncture-related therapies (Table 5).

This study was conducted by NMA to compare the effectiveness of nine acupuncture-related therapies. The ranking results showed that AI+M was the most effective measure to improve the overall efficacy rate, followed by ACE, AAP+M and ACU+M. In terms of improving the recovery rate, ACE ranked first among the nine therapeutic interventions, followed by MOX+M, AAP+M and AI+M. Then, in terms of the overall efficacy rate at follow-up, AI+M showed the most effective therapy and the second was ACE. In general, AI+M and ACE showed the better effect among the three outcome measures.

AI therapy is a unique therapy based on the fundamental theory of Traditional Chinese Medicine to stimulate the therapeutic effects of meridians and acupuncture points. On the one hand, acupuncture and drugs directly stimulate the acupoints on the meridians to produce dual therapeutic effects; on the other hand, after acupuncture injection, the drugs remain at the acupoint for a longer period of time, which can improve and prolong the therapeutic effect, and circulate along the meridians to unblock the meridians and reach the corresponding focal points, giving full play to the joint therapeutic effect of acupuncture points and drugs [35]. The action of drugs on acupoints can also affect the body through the nervous system and neurohumoral system to enhance the body's ability to resist disease [36]. Scientific research suggests that ACE may promote intestinal motility by stimulating the parasympathetic nervous system and strengthening the smooth muscles of the gastrointestinal tract [37]. AI+M remains more effective after long-term follow-up, but fewer reports were found on the overall efficacy rate at follow-up, which may be subject to large bias.

According to the theory of Traditional Chinese Medicine (TCM), IBS-C belongs to the category of "constipation" and "abdominal pain" caused by various reasons of large intestine conduction disorder. The location of the disease is mainly in the large intestine, which is closely related to the liver, spleen and kidney. The acupoints selected for IBS-C are based on improving spleen deficiency and liver depression, mainly by stimulating Tianshu (ST25), Zusanli (ST36), Shangjuxu (ST37), Dachangshu (BL25) and Zhongwan (RN12) [38]. IBS is usually treated with a combination of therapies due to the variety of symptoms. A clinical trial for the treatment of IBS [39] found that acupoint catgut embedding could reduce symptoms such as constipation and abdominal distension, and had effects on relieving anxiety and depression compared with the drug and sham groups. Currently, the pathogenesis of IBS is still unclear and the mechanism of pathophysiology is complex [40], and drug treatment has numerous side effects and does not improve patients' overall symptoms [41]. In the absence of satisfaction with existing treatments, acupuncture and related therapies are becoming an increasingly popular choice for IBS patients due to their simplicity and low side effects.

Strengths of this study are: (1) IBS was classified into four subtypes of evidence according to the latest Rome IV criteria, and the analysis of different treatment techniques mostly focused on IBS with diarrhoea, and there was no study on the comparative efficacy of acupuncture-related interventions in the treatment of IBS-C. (2) The outcome indicators of acupuncture-related interventions were statistically processed in a Bayesian framework and multiple interventions were compared with each other. (2) The outcome indicators of acupuncture-related therapies were statistically processed in a Bayesian framework, and multiple interventions were compared with each other to provide the optimal solution for the clinic. (3) To analyse the sustained effect and extent of treatment of commonly used acupuncture-related therapies from multiple perspectives using short- and long-term overall efficacy rates and recovery rates.

However, this study had some limitations, in particular: (1) The outcome "overall efficacy rate" for the treatment of IBS-C is widely used, but still variable. 14 of the 27 studies [9,10,12,15,16,18,24,26-28,31-34] mentioned follow-up, and only 6 studies [10,12,16,18,27,34] reported "overall efficacy rate" and had a complete number of follow-ups. There are 19 references to "symptom score comparison" or "Chinese medicine symptom score", but the scoring criteria were variable for statistical analysis. The irritable bowel syndrome quality of life (IBS-QOL) and the irritable bowel syndrome severity scoring system (IBS-SSS) are less well documented. (2) The technical demands of acupuncture-related therapies are high and blinding is difficult to achieve. The included literature is all in Chinese and the overall quality of the literature is low. (3) There are few studies in the literature comparing different interventions, which may lead to chance in the results.

In conclusion, acupuncture-related therapies are more clinically effective than conventional medicine in the treatment of IBS-C. Acupoint injection combined with medication has the best effect on both short and long term efficacy, and combined therapies may be more beneficial. However, only a few trials observed relevant professional outcomes such as IBS-QOL and IBS-SSS, and there were no clear comparisons of the safety of the interventions. The number and quality of existing trials are limited, and more multicentre, large-sample, high-quality randomised controlled trials are needed to validate our findings.

IBS: Irritable Bowel Syndrome

IBS-C: IBS With Predominant Constipation

IBS-D: IBS With Predominant Diarrhea

RCT: Randomized Controlled Trial

NMA: Network Meta-Analysis

SUCRA: Surface Under the Cumulative Ranking Curves

IBS-QOL: Irritable Bowel Syndrome Quality of Life

IBS-SSS: Irritable Bowel Syndrome Severity Scoring System

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Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Availability of data and materials

The datasets used in this study are available from the corresponding author upon reasonable request.

Competing interests

Not applicable.

Funding

This research was supported by "New Teacher Initiation Fund Project of Beijing University of Chinese Medicine (NO.2020-JYB-XJSJJ-016)".

Authors' contributions

XLK, XYL, ZSH, KZ and LYY performed the statistical analysis of the data; YMC, HLZ and XLK wrote the manuscript. All authors have read and approved the manuscript.

Acknowledgments

Not applicable.

Table 1: Basic characteristics of the included studies

Author	Intervention				Control				Course	Type of outcomes
Author	n	Years (Mean ± sd)	Treatment	Frequency	n	Years (Mean ± sd)	Treatment	Frequency	Course	Type of outcomes
Han [9]	21	37.62±14.12	ACU	5/week	20	35.60±12.79	CM	3/day	4w	①②
Dou [10]	30	/	ACU	Every other day	30	/	CM	2/day	4w	①②③
Jin [11]	32	40.3	ACE	Every 2 weeks	32	39.6	CM	3/day	30d	①②
Li et al. [12]	60	62.1±2.79	ACU	5/week	60	50.9±3.45	CM	3/day	4w	①②③
Fan et al. [13]	51	36±6.41	AAP+AP	Every other day +3/day	51	35±9.07	CM	3/day	4w	①②
Mao [14]	49	32.1±4.3	AP + M	Every other day +1 dose/day	49	31.5±5.0	TCM	1 dose/day	4w	①②
Pei et al. [15]	30	44±12	ACU	5/week	30	44±14	CM	3/day	4w	①②
Shi [16]	63	53.83±10.95	MOX+M	2/day + 1 dose/day	57	54.34±9.88	CM	6/day	1m	①②③
Yu [17]	52	/	ACU	5/week	52	/	CM	3/day	4w	①②
Que [18]	34	42.26±10.40	MOX+M	1/week+2/day	33	43.12±12.40	CM	3/day	4w	①②③
Tan et al. [19]	38	43.6 ± 2. 4	ACU+M	1/day+3/day	38	42.2±2.1	TCM	3/day	28d	①②
Gu et al. [20]	50	47.4±10.9	ACU+M	5/week+1 dose/day	50	44.7±9.9	CM	3/day	4w	①②
Yan [21]	63	42.14±3.89	AP+AAP	Every other day +3/day	63	43.12±3.83	CM	3/day	4w	①②
He et al. [22]	30	45.69±8.45	ACU+M	1/day+3/day	30	45.76±9.84	CM	3/day	2w	①②
Sun [23]	33	44.45±10.54	ACU+M	6/week+2/day	33	44.58±10.63	CM	3/day	4w	①②
Mao [24]	30	37.60±13.25	ACU	5/week	30	38.83±12.19	CM	5/week	4w	①②
Han [25]	40	33.4±2.2	ACU+M	1/day+4/day	40	32.2±2.5	CM	4/day	4w	①②
Zhao and Chen [26]	26	42.26±10.34	MOX+M	1/day +1 dose/day	26	41.45±10.25	CM	3/day	14d	①②
Liu [27]	47	/	ACE	1/2 weeks	47	/	CM	3/day	4w	①②③
Zhang et al. [28]	33	49.69±7.31	MOX+M	2/week+1 dose/day	33	52.8±11.48	TCM	1/day	4w	①②
Hua [29]	27	44.40±11.36	AAP+M	1/day + 1 dose/day	30	39.90±7.68	TCM	1 dose/day	2w	①②
Dou et al. [30]	36	42.7±6.1	MOX+M	/ +3/day	34	43.5±6.4	CM	3/day	4w	①②
Chen [31]	22	32.91±13.14	ACE	1/week	20	32.70±12.16	CM	3/day	4w	①②
Zhang and Liu [32]	32	43.17±8.65	AP+M	1/day + 2/day	32	42.67±9.34	CM	3/day	4w	①②
Yu et al. [33]	63	/	MOX+M	Every other day + 3/day	63	/	CM	3/day	4w	①
Xia and Deng [34]	35	/	AI+M	Every other day + 1 dose/ day	30	/	TCM	1 dose/day	1m	①③
Xia and Deng [34]	35	/	AI+M	Every other day + 1 dose/ day	25	/	CM	3/day	1m	①③
Shi et al. [35]	45	46.40±4.68	AI+M	First week: 1/week，last three weeks: 2/week +1 dose/day	44	47.16±5.42	CM	3/day	4w	①②

ACU, acupuncture; ACE, acupoint catgut embedding; TCM, traditional Chinese medicine; CM, conventional medicine; ACU+M, acupuncture + medicine; MOX+M, moxibustion + medication; AAP+M, acupoint application + medicine; AAP+AP, acupoint application + auricular acupressure; AI+M, acupoint injection + medicine.

Table 2: Network meta-analysis of the total efficiency rate of different acupuncture and moxibustion therapies for IBS-C [OR (95% CI)].

	ACU	ACE	ACU+M	MOX+M	AAP+M	AAP+AP	AI+M	TCM	CM
ACU	/
ACE	0.58 (0.19, 1.73)	/
ACU+M	0.79 (0.34, 1.96)	1.37 (0.47, 4.13)	/
MOX+M	0.82 (0.34, 2.16)	1.45 (0.50, 4.11)	1.03 (0.44, 2.34)	/
AAP+M	0.63 (0.21, 2.29)	1.09 (0.31, 4.51)	0.82 (0.29, 2.54)	0.79 (0.28, 2.25)	/
AAP+AP	1.15 (0.43, 3.08)	2.03 (0.60, 6.41)	1.44 (0.52, 4.15)	1.44 (0.53, 3.57)	1.72 (0.48, 5.70)	/
AI+M	0.42 (0.09, 1.40)	0.73 (0.12, 3.26)	0.53 (0.10, 1.96)	0.52 (0.08, 1.78)	0.66 (0.08, 3.04)	0.37 (0.05, 1.42)	/
TCM	1.93 (0.77, 5.97)	3.33 (1.12, 11.78)*	2.52 (1.08, 6.15)*	2.46 (1.06, 5.49)*	3.05 (1.43, 6.62)*	1.75 (0.60, 5.17)	4.77 (1.22, 38.47)*	/
CM	2.66 (1.47, 5.38)*	4.62 (1.91, 11.74)*	3.40 (1.76, 6.57)*	3.27 (1.83, 5.81)*	4.09 (1.49, 9.99)*	2.30 (1.10, 5.05)*	6.33 (2.01, 41.74)*	1.37 (0.64, 2.80)	/

ACU, acupuncture; ACE, acupoint catgut embedding; TCM, traditional Chinese medicine; CM, conventional medicine; ACU+M, acupuncture + medicine; MOX+M, moxibustion + medication; AAP+M, acupoint application + medicine; AAP+AP, acupoint application + auricular acupressure; AI+M, acupoint injection + medicine.

Table 3: Network meta-analysis of the recovery rate of different acupuncture and moxibustion therapies for IBS-C [OR (95% CI)].

	ACU	ACE	ACU+M	MOX+M	AAP+M	AAP+AP	AI+M	TCM	CM
ACU	/
ACE	0.21 (0.05, 0.80)	/
ACU+M	0.92 (0.39, 2.13)	4.32 (1.05, 22.63)*	/
MOX+M	0.60 (0.28, 1.43)	2.81 (0.76, 13.25)	0.66 (0.30, 1.51)	/
AAP+M	0.69 (0.19, 2.51)	3.30 (0.53, 22.45)	0.74 (0.22, 2.44)	1.15 (0.31, 3.79)	/
AAP+AP	1.11 (0.45, 3.10)	5.25 (1.37, 27.42)*	1.23 (0.49, 3.46)	1.85 (0.74, 4.81)	1.59 (0.42, 6.95)	/
AI+M	0.88 (0.26, 3.53)	4.28 (0.84, 25.18)	0.99 (0.28, 3.92)	1.49 (0.42, 5.42)	1.34 (0.24, 7.67)	0.80 (0.20, 3.17)	/
TCM	1.38 (0.47, 4.71)	6.59 (1.42, 39.07)*	1.51 (0.62, 4.41)	2.30 (0.88, 6.19)	2.02 (0.87, 5.49)	1.23 (0.36, 4.23)	1.55 (0.33, 7.36)	/
CM	1.81 (1.05, 3.45)*	8.38 (2.65, 38.00)*	1.99 (1.10, 3.96)*	3.01 (1.72, 5.40)*	2.63 (0.83, 8.86)	1.62 (0.76, 3.33)	2.03 (0.64, 6.33)	1.30 (0.49, 3.35)	/

ACU, acupuncture; ACE, acupoint catgut embedding; TCM, traditional Chinese medicine; CM, conventional medicine; ACU+M, acupuncture + medicine; MOX+M, moxibustion + medication; AAP+M, acupoint application + medicine; AAP+AP, acupoint application + auricular acupressure; AI+M, acupoint injection + medicine.

Table 4: Network meta-analysis of the total effective rate of follow-up of different acupuncture and moxibustion therapies for IBS-C [OR (95% CI)].

	ACU	ACE	MOX+M	AI+M	TCM	CM
ACU	/
ACE	0.47 (0.03, 9.93)	/
MOX+M	0.55 (0.06, 6.98)	1.10 (0.06, 22.83)	/
AI+M	0.19 (0.01, 4.54)	0.40 (0.01, 12.07)	0.37 (0.01, 6.53)	/
TCM	0.86 (0.04, 17.47)	1.89 (0.06, 51.43)	1.73 (0.08, 28.49)	4.91 (0.37, 64.51)	/
CM	2.86 (0.57, 18.27)	6.04 (0.60, 67.33)	5.36 (0.97, 29.80)	15.04 (1.30, 242.28)*	3.35 (0.32, 37.75)	/

ACU, acupuncture; ACE, acupoint catgut embedding; TCM, traditional Chinese medicine; CM, conventional medicine; MOX+M, moxibustion + medication; AI+M, acupoint injection + medicine.

Table 5 Adverse events

References	Adverse events
Han 2011 [9]	NR
Dou 2013 [10]	NR
Jin 2014 [11]	NR
Li et al. 2015 [12]	NR
Fan et al. 2015 [13]	NR
Mao 2015 [14]	NR
Pei et al. 2015 [15]	NR
Shi 2016 [16]	CM: 2 cases of altered blood picture (2/57), 1 case of liver function damage (1/57)
Yu 2017 [17]	NR
Que 2017 [18]	MOX+M: 1 case of abdominal discomfort (1/34) CM: 1 case of diarrhea with loose stools 2-3 times a day (1/33).
Tan et al. 2017 [19]	ACU+M: 1 case of acupuncture fainting (1/38)
Gu et al. 2017 [20]	NR
Yan 2017 [21]	NR
He et al. 2018 [22]	NR
Sun 2018 [23]	NR
Mao 2018 [24]	ACU: 2 cases of local soreness and discomfort (2/30), 5 cases of bleeding from the needles (5/30)
Han 2018 [25]	NR
Zhao and Chen 2019 [26]	MOX+M: 2 cases of bitterness in the mouth and occasional mild nausea (2/26) CM: 3 cases of occasional thirst and drowsiness after taking medicine (3/26), 1 case of dizziness and mild headache (1/26)
Liu 2019 [27]	NR
Zhang et al. 2020 [28]	NR
Hua 2020 [29]	NR
Dou et al. 2020 [30]	MOX+M: 1 case of mild dizziness (1/36) CM: 1 case of mild dizziness (1/34)
Chen 2020 [31]	NR
Zhang and Liu 2020 [32]	NR
Yu et al. 2012 [33]	NR
Xia and Deng 2006 [34]	NR
Shi et al. 2012 [35]	AI+M: 2 cases of bruising around Zusanli (ST36) (2/45)

ACU, acupuncture; TCM, traditional Chinese medicine; CM, conventional medicine; ACU+M, acupuncture + medicine; MOX+M, moxibustion + medication; AI+M, acupoint injection + medicine; NR: not related.

The authors declare no competing interests.

Acupuncture and related therapy for constipation predominant irritable bowel syndrome: A network meta-analysis of randomized controlled trials

Status:

Version 2

Abstract

Figures

Introduction

1. Information and methods

2. Results

3. Discussion

4. Conclusions

Abbreviations

References

Declarations

Tables

Additional Declarations

Status:

Version 2