Shiyan Yan

Acupuncture for Chronic Severe Functional Constipation: A Randomized Trial

Chronic constipation affects approximately 16% of the worlds population (1), 17.1% of persons in Europe (2), 12% to 19% of those in North America (3), and 10.8% of those in Asia (1). Patients with severe chronic constipation have complete spontaneous bowel movements (CSBMs) no more than twice per week, with hard stools, frequent straining, and the sensation of incomplete evacuation (4). Most chronic constipation is functional and is associated with decreased quality of life (5). Laxatives produce only temporary relief, and constipation tends to reoccur after discontinuing medication (6, 7). Nearly half of patients are dissatisfied with their traditional therapies, such as laxatives (8). Other treatment options may include prokinetic agents. In a trial, 1 to 2 mg of prucalopride (an agonist for 5-hydroxytryptamine receptor 4) per day was reported to normalize BMs in 37.9% of patients with severe chronic constipation (9). However, the adverse cardiac effects induced by some prokinetic agents cannot be ignored (10), and their long-term effects remain unknown. A systematic review supports the use of acupuncture for chronic constipation (11), and our previous study indicates that electroacupuncture (EA) might have some sustained effects (12). However, the evidence for the therapeutic effects of acupuncture is limited because many randomized, controlled trials have had small sample sizes or other methodological limitations (11). Our goal was to determine the efficacy of EA for the treatment of chronic severe functional constipation (CSFC) over an 8-week treatment period and evaluate the maintenance of effects throughout the 12-week follow-up. We hypothesized that EA would be superior to sham EA (SA) at both end points. Methods Design Overview We conducted a multicenter, randomized, parallel, sham-controlled trial at 15 sites in China. The study duration per patient was 22 weeks: 2 weeks before randomization (baseline assessment); 8 weeks of treatment; and 12 weeks of follow-up without treatment. Researchers screened candidates for study participation, and experienced physicians at digestive or anorectal departments made diagnoses. Participants Participants were included if they met the diagnosis of functional constipation based on the Rome III diagnostic criteria for functional gastrointestinal disorders (13), had CSFC with 2 or fewer mean weekly CSBMs for more than 3 months, were aged between 18 and 75 years, had not taken constipation medication for a minimum of 2 weeks before enrollment except for rescue medicine (glycerol or sorbitol anal enema), had not received acupuncture for constipation, and had not participated in any other trial in the previous 3 months. The exclusion criteria were constipation caused by irritable bowel syndrome or drugs or that was secondary to endocrine, metabolic, neurologic, or postoperative diseases; severe cardiovascular, hepatic, or renal diseases; cognitive dysfunction, aphasia, mental disorders, or illness that could affect patient cooperation; pregnant or lactating women; abdominal aortic aneurysm or hepatosplenomegaly; blood coagulation disorders or regular anticoagulant use, including warfarin or heparin (an exception was antiplatelet treatment using aspirin or clopidogrel); and cardiac pacemaker implantation. Candidates signed informed consent. After the 2-week baseline assessment, eligible participants were randomly assigned and received their first treatment on the same day. The study was performed according to common guidelines for clinical trials (Declaration of Helsinki and International Conference on Harmonisation Good Clinical Practice E6 guidance). The study protocol (14) adhered to the Standards for Reporting Interventions in Clinical Trials of Acupuncture guidelines and was approved by the ethics committees of each responsible site. Randomization and Blinding Participants were allocated to the EA or SA group using stratified block randomization. The randomization sequences were generated by using PROC PLAN in SAS, version 9.4 (SAS Institute), with the study site as the stratification factor and the block length as 4. Acupuncturists obtained each patients random number and assignment through the central randomization system (Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences). All participants were treated separately to prevent communication. Except for acupuncturists, all relevant parties were blinded to the intervention (EA vs. SA) groups. Participants were informed that they had an equal chance of allocation to the EA or SA group before study participation. To test the success of blinding, we randomly selected 140 participants (70 from each group, with 9 to 10 participants at each site) for the blinding assessment; the acupuncturists asked them to guess whether they received EA or SA after treatments in weeks 4 and 8. Intervention Study interventions were developed by the consensus of acupuncture experts and per the results of our pilot study (Cai Y, Wu J, Liu Z. Electroacupuncture versus sham electroacupuncture for chronic severe functional constipation: a randomized controlled pilot study. 2012. Unpublished data.). Fifteen acupuncturists with 2 to 3 years of experience at the 15 sites administered the EA and SA treatments. All acupuncturists had at least a 5-year undergraduate education and were registered practitioners of traditional Chinese medicine. All research assistants and acupuncturists received a 2-day training session before study initiation. Both treatments consisted of 28 sessions, each for 30 minutes, and were administered over 8 weeks (5 sessions in each of the first 2 weeks, and 3 sessions in each of the remaining 6 weeks). Disposable needles (Huatuo) and the SDZ-V EA apparatus (Suzhou Medical Appliance) were used. Participants in the EA group received EA at the bilateral acupoints of Tianshu (ST25), Fujie (SP14), and Shangjuxu (ST37) (15). When participants were supine, 0.3050mm or 0.3575mm needles were inserted approximately 30 to 70 mm into ST25 and SP14 slowly and vertically, without manipulation, until they pierced the muscle layer of the abdominal wall. Paired alligator clips from the EA apparatus were attached transversely to the needle holders at bilateral ST25 and SP14. The EA stimulation lasted for 30 minutes with a dilatational wave of 10/50 Hz and a current intensity of 0.1 to 1 mA depending on the participants comfort level (preferably with skin around the acupoints shivering mildly without pain). In addition, 0.3040mm needles were inserted vertically about 30 mm into ST37 and 3 small, equal manipulations of twirling, lifting, and thrusting (once every 10 minutes) were performed to reach acupuncture de qia soreness, heaviness, and distension sensation when needling (16). Participants in the SA group received shallow needling at bilateral sham ST25, sham SP14, and sham ST37 (nonacupoints that were located at different physical locations than ST25, SP14, and ST37 for EA) (Supplement). Specifically, 0.3025mm needles were inserted vertically about 3 to 5 mm into nonacupoints without manipulation. Similar to EA, paired alligator clips from the specially constructed EA apparatus were attached to the needle holders of sham ST25 and sham SP14. When switched on, the EA apparatus in the SA group had the same working power indicator and sound without actual current output. Supplement. Data Supplement In both groups, participants without BMs for 3 or more consecutive days were allowed to use 110-mL glycerol or 40- to 60-mL sorbitol anal enema as rescue medicine with documentation in the stool diary. Outcomes and Follow-up Participants completed a stool diary during the 22-week study period and the Patient Assessment of Constipation Quality of Life questionnaire (PAC-QOL) (17) at baseline and weeks 4 and 8. The main components of the stool diary included BMs, SBMs, CSBMs, stool consistency, straining, and medication use. Participants documented their stool consistency according to the Bristol Stool Form Scale (18) (scored from 1 to 7 for stool types 1 to 7, respectively). Straining was rated with scores of 0, 1, 2, and 3 indicating not difficult; a little difficult, need some straining to defecate; difficult, need straining to defecate; and very difficult, need hard straining to defecate, respectively. An SBM was defined as a BM that occurred without use of any medication or other methods to assist defecation in the previous 24 hours (4). A BM was not considered as an SBM when it occurred within 24 hours after the use of any assisted method for defecation. The PAC-QOL allowed participants to score the effects of constipation on physical discomfort, psychosocial discomfort, worriedness and concerns, and satisfaction in their daily lives. Higher scores indicate greater impairment or dissatisfaction. The primary outcome was the change from baseline in mean CSBMs per week, calculated as the total number of CSBMs divided by the number of weeks in the assessment period, during weeks 1 to 8. Secondary outcomes included the changes from baseline in mean CSBMs per week during weeks 9 to 20, mean SBMs per week during weeks 1 to 8, mean scores for stool consistency and straining of SBMs during weeks 1 to 8, and health-related quality of life via PAC-QOL score at weeks 4 and 8; the proportion of participants with 3 or more mean CSBMs per week (4); the proportion of participants using rescue medicine and other defecation measures; and the mean weekly frequency of using rescue medicine and other defecation aids during weeks 1 to 4, 1 to 8, and 9 to 20. We also assessed the CSBMs per week and their change from baseline during treatment and follow-up (not prespecified). Adverse events (AEs) were appropriately assessed, managed, and categorized by the acupuncturists and related clinical specialists within 24 hours. Severe AEs had to be reported to the principal investigator and the independent data and safety monitoring

Effect of Electroacupuncture on Urinary Leakage Among Women With Stress Urinary Incontinence: A Randomized Clinical Trial

Importance Electroacupuncture involving the lumbosacral region may be effective for women with stress urinary incontinence (SUI), but evidence is limited. Objective To assess the effect of electroacupuncture vs sham electroacupuncture for women with SUI. Design, Setting, and Participants Multicenter, randomized clinical trial conducted at 12 hospitals in China and enrolling 504 women with SUI between October 2013 and May 2015, with data collection completed in December 2015. Interventions Participants were randomly assigned (1:1) to receive 18 sessions (over 6 weeks) of electroacupuncture involving the lumbosacral region (n = 252) or sham electroacupuncture (n = 252) with no skin penetration on sham acupoints. Main Outcomes and Measures The primary outcome was change from baseline to week 6 in the amount of urine leakage, measured by the 1-hour pad test. Secondary outcomes included mean 72-hour urinary incontinence episodes measured by a 72-hour bladder diary (72-hour incontinence episodes). Results Among the 504 randomized participants (mean [SD] age, 55.3 [8.4] years), 482 completed the study. Mean urine leakage at baseline was 18.4 g for the electroacupuncture group and 19.1 g for the sham electroacupuncture group. Mean 72-hour incontinence episodes were 7.9 for the electroacupuncture group and 7.7 for the sham electroacupuncture group. At week 6, the electroacupuncture group had greater decrease in mean urine leakage (−9.9 g) than the sham electroacupuncture group (−2.6 g) with a mean difference of 7.4 g (95% CI, 4.8 to 10.0; P < .001). During some time periods, the change in the mean 72-hour incontinence episodes from baseline was greater with electroacupuncture than sham electroacupuncture with between-group differences of 1.0 episode in weeks 1 to 6 (95% CI, 0.2-1.7; P = .01), 2.0 episodes in weeks 15 to 18 (95% CI, 1.3-2.7; P < .001), and 2.1 episodes in weeks 27 to 30 (95% CI, 1.3-2.8; P < .001). The incidence of treatment-related adverse events was 1.6% in the electroacupuncture group and 2.0% in the sham electroacupuncture group, and all events were classified as mild. Conclusions and Relevance Among women with stress urinary incontinence, treatment with electroacupuncture involving the lumbosacral region, compared with sham electroacupuncture, resulted in less urine leakage after 6 weeks. Further research is needed to understand long-term efficacy and the mechanism of action of this intervention. Trial Registration clinicaltrials.gov Identifier: NCT01784172.

The efficacy and safety study of electro-acupuncture for severe chronic functional constipation: study protocol for a multicenter, randomized, controlled trial

BackgroundPrevious research has shown that electro-acupuncture (EA) may be effective for functional constipation. We report a protocol for a randomized controlled trial using EA to confirm the efficacy and safety for severe chronic functional constipation.Methods/designThis is a randomized, controlled trial. A total of 1,034 patients will be randomly allocated into the EA group (n=517) and the sham EA group (n=517). The EA group receives needling at ST25, SP14 and ST37 and the sham EA group receives needling at sham ST25, SP14 and ST37. The primary outcome measure is the changed number of weekly average complete spontaneous bowel movements(CSBMs) during 8 weeks of treatment, compared with baseline. The secondary outcome measures are: 1) the proportion of participants having three or more CSBMs on average per week; 2) the changed number of weekly average CSBMs during weeks 9 to 20; 3) the changed number of weekly average spontaneous bowel movements during 8 weeks of treatment; 4) stool consistency; 5) degree of difficulty in defecation; 6) patient assessment of constipation quality of life questionnaire (PAC-QOL); 7) incidence of adverse events; and 8) usage of medicine for constipation.DiscussionThis trial will evaluate the efficacy and safety of EA for severe chronic functional constipation.Trial registrationProtocol Registration System of ClinicalTrial.gov, NCT01726504

Effect of blinding with a new pragmatic placebo needle: a randomized controlled crossover study.

AbstractPlacebo control is a useful method for determining the efficacy of a therapy. In acupuncture researches, the preferred method for placebo control is acupuncture using a placebo needle that has a blunt tip and achieves no skin penetration.We performed a crossover study to validate the blinding effect of a new type of placebo needle. Sixty volunteers were randomized to receive acupuncture using 2 types of needles with different sequences: sequence AB, involving first the pragmatic placebo needle and then the real needle, and sequence BA, in a reverse order. Placebo acupuncture was performed by administering the placebo needle through an adhesive pad without skin penetration on the acupoints LI4, RN12, BL25, and BL36. Real acupuncture was performed by needling through the pad and penetrating the skin to 15 mm using a real needle on the same acupoints. The acupuncture was administered every other day with 3 sessions for 1 type of needle. The primary outcome was the perception of needle penetration. Besides degree of acupuncture pain, type, and degree of needle sensation, needle acceptability and factors influencing the subject blinding effect were assessed.Needle penetration was felt by 100%, 90% (54/60), 88.3% (53/60), and 95% (57/60) of volunteers receiving placebo acupuncture and 98.3% (59/60), 96.7% (58/60), 95% (57/60), and 95% (57/60) of volunteers receiving real acupuncture on LI4, RN12, BL25, and BL36, respectively. Differences of the volunteers’ perception of needle penetration between the placebo needle and real needle were not significant for the 4 acupoints (all P > 0.05). Volunteers experienced fewer distension sensations (P = 0.01), a lower degree of needle sensation (P = 0.007), and less pain (P = 0.006) during placebo acupuncture than during real acupuncture. The placebo needle was more easily accepted than the real needle (OR = 1.63, 95% CI, 1.01–2.64). The influences of age, sex, educational level, acupuncture experience, needle sensation, acupuncture pain, and needle acceptability on volunteers’ perception of needle penetration were not significant.The pragmatic placebo needle is a valid control for acupuncture research. It produces a good subject blinding effect with a similar appearance to conventional acupuncture needles and no skin penetration when applied.

Exploring effective core drug patterns in primary insomnia treatment with Chinese herbal medicine: study protocol for a randomized controlled trial

BackgroundChinese herbal medicine is one of the most popular Chinese medicine (CM) therapies for primary insomnia. One of the important characteristics of CM is that different Chinese clinicians give different prescriptions even for the same patient. However, there must be some fixed drug patterns in every clinician’s prescriptions. This study aims to screen the effective core drug patterns in primary insomnia treatment of three prestigious Chinese clinicians.Methods/designA triple-blind, randomized, placebo-controlled, parallel-group clinical trial will be performed. Three clinicians will diagnose and treat every eligible patient individually and independently, producing three prescriptions from three clinicians for every patient. Patients will equally be randomized to one of four groups – medical group A, medical group B, medical group C, or placebo group – and observed for efficacy of treatment. The sample will include primary insomnia patients meeting DSM IV-TR criteria, Spiegel scale score >18, and age 18 to 65 years. A sequential design is employed. Interim analysis will be conducted when between 80 and 160 patients complete the study. The interim study could be stopped and treated as final if a statistically significant difference between treatment and placebo groups can be obtained and core effective drug patterns can be determined. Otherwise, the study continues until the maximum sample size reaches 300. Treatment of the CM group is one of three Chinese clinicians’ prescriptions, who provide independently prescriptions based on their own CM theory and the patient’s disease condition. Assessment will be by sleep diary and Pittsburgh sleep quality index, and CM symptoms and signs will be measured. Primary outcome is total sleep time. Assessment will be carried out at the washout period, weeks 1, 2, 3, and 4 and 4th week after the end of treatment. Effectiveness analysis will be per intent to treat. A multi-dimension association rule and scale-free networks method will be used to explore the effective core drug patterns.DiscussionThe effective core drug patterns will be found through analyzing several prestigious CM clinicians’ treatment information. Screening the effective core drug patterns from prestigious clinicians can accelerate the development of new CM drugs.Trial registrationNCT01613183

Clinical phenotype network: the underlying mechanism for personalized diagnosis and treatment of traditional Chinese medicine

Traditional Chinese medicine (TCM) investigates the clinical diagnosis and treatment regularities in a typical schema of personalized medicine, which means that individualized patients with same diseases would obtain distinct diagnosis and optimal treatment from different TCM physicians. This principle has been recognized and adhered by TCM clinical practitioners for thousands of years. However, the underlying mechanisms of TCM personalized medicine are not fully investigated so far and remained unknown. This paper discusses framework of TCM personalized medicine in classic literatures and in real-world clinical settings, and investigates the underlying mechanisms of TCM personalized medicine from the perspectives of network medicine. Based on 246 well-designed outpatient records on insomnia, by evaluating the personal biases of manifestation observation and preferences of herb prescriptions, we noted significant similarities between each herb prescriptions and symptom similarities between each encounters. To investigate the underlying mechanisms of TCM personalized medicine, we constructed a clinical phenotype network (CPN), in which the clinical phenotype entities like symptoms and diagnoses are presented as nodes and the correlation between these entities as links. This CPN is used to investigate the promiscuous boundary of syndromes and the co-occurrence of symptoms. The small-world topological characteristics are noted in the CPN with high clustering structures, which provide insight on the rationality of TCM personalized diagnosis and treatment. The investigation on this network would help us to gain understanding on the underlying mechanism of TCM personalized medicine and would propose a new perspective for the refinement of the TCM individualized clinical skills.

Investigation into the Influence of Physician for Treatment Based on Syndrome Differentiation

Background. The characteristics of treatment based on syndrome differentiation (TBSD) cause great challenges to evaluate the effectiveness of the clinical methods. Objectives. This paper aims to evaluate the influence of physician to personalized medicine in the process of TBSD. Methods. We performed a randomized, triple-blind trial involving patients of primary insomnia treated by 3 physicians individually and independently. The patients (n = 30) were randomly assigned to receive treatments by the 3 physicians for every visit. However, they always received the treatment, respectively, prescribed by the physician at the first visit. The primary outcome was evaluated, respectively, by the Pittsburgh Sleep Quality Index (PSQI) and the TCM symptoms measuring scale. The clinical practices of the physicians were recorded at every visit including diagnostic information, syndrome differentiation, treating principles, and prescriptions. Results. All patients in the 3 groups (30 patients) showed significant improvements (>66%) according to the PSQI and TCM symptoms measuring scale. Conclusion. The results indicate that although with comparable effectiveness, there exist significant differences in syndrome differentiation, the treating principles, and the prescriptions of the approaches used by the 3 physicians. This means that the physician should be considered as an important factor for individualized medicine and the related TCM clinical research.

Acupuncture for Chronic Severe Functional Constipation: A Randomized, Controlled Trial.

Chronic constipation affects approximately 16% of the worlds population (1), 17.1% of persons in Europe (2), 12% to 19% of those in North America (3), and 10.8% of those in Asia (1). Patients with severe chronic constipation have complete spontaneous bowel movements (CSBMs) no more than twice per week, with hard stools, frequent straining, and the sensation of incomplete evacuation (4). Most chronic constipation is functional and is associated with decreased quality of life (5). Laxatives produce only temporary relief, and constipation tends to reoccur after discontinuing medication (6, 7). Nearly half of patients are dissatisfied with their traditional therapies, such as laxatives (8). Other treatment options may include prokinetic agents. In a trial, 1 to 2 mg of prucalopride (an agonist for 5-hydroxytryptamine receptor 4) per day was reported to normalize BMs in 37.9% of patients with severe chronic constipation (9). However, the adverse cardiac effects induced by some prokinetic agents cannot be ignored (10), and their long-term effects remain unknown. A systematic review supports the use of acupuncture for chronic constipation (11), and our previous study indicates that electroacupuncture (EA) might have some sustained effects (12). However, the evidence for the therapeutic effects of acupuncture is limited because many randomized, controlled trials have had small sample sizes or other methodological limitations (11). Our goal was to determine the efficacy of EA for the treatment of chronic severe functional constipation (CSFC) over an 8-week treatment period and evaluate the maintenance of effects throughout the 12-week follow-up. We hypothesized that EA would be superior to sham EA (SA) at both end points. Methods Design Overview We conducted a multicenter, randomized, parallel, sham-controlled trial at 15 sites in China. The study duration per patient was 22 weeks: 2 weeks before randomization (baseline assessment); 8 weeks of treatment; and 12 weeks of follow-up without treatment. Researchers screened candidates for study participation, and experienced physicians at digestive or anorectal departments made diagnoses. Participants Participants were included if they met the diagnosis of functional constipation based on the Rome III diagnostic criteria for functional gastrointestinal disorders (13), had CSFC with 2 or fewer mean weekly CSBMs for more than 3 months, were aged between 18 and 75 years, had not taken constipation medication for a minimum of 2 weeks before enrollment except for rescue medicine (glycerol or sorbitol anal enema), had not received acupuncture for constipation, and had not participated in any other trial in the previous 3 months. The exclusion criteria were constipation caused by irritable bowel syndrome or drugs or that was secondary to endocrine, metabolic, neurologic, or postoperative diseases; severe cardiovascular, hepatic, or renal diseases; cognitive dysfunction, aphasia, mental disorders, or illness that could affect patient cooperation; pregnant or lactating women; abdominal aortic aneurysm or hepatosplenomegaly; blood coagulation disorders or regular anticoagulant use, including warfarin or heparin (an exception was antiplatelet treatment using aspirin or clopidogrel); and cardiac pacemaker implantation. Candidates signed informed consent. After the 2-week baseline assessment, eligible participants were randomly assigned and received their first treatment on the same day. The study was performed according to common guidelines for clinical trials (Declaration of Helsinki and International Conference on Harmonisation Good Clinical Practice E6 guidance). The study protocol (14) adhered to the Standards for Reporting Interventions in Clinical Trials of Acupuncture guidelines and was approved by the ethics committees of each responsible site. Randomization and Blinding Participants were allocated to the EA or SA group using stratified block randomization. The randomization sequences were generated by using PROC PLAN in SAS, version 9.4 (SAS Institute), with the study site as the stratification factor and the block length as 4. Acupuncturists obtained each patients random number and assignment through the central randomization system (Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences). All participants were treated separately to prevent communication. Except for acupuncturists, all relevant parties were blinded to the intervention (EA vs. SA) groups. Participants were informed that they had an equal chance of allocation to the EA or SA group before study participation. To test the success of blinding, we randomly selected 140 participants (70 from each group, with 9 to 10 participants at each site) for the blinding assessment; the acupuncturists asked them to guess whether they received EA or SA after treatments in weeks 4 and 8. Intervention Study interventions were developed by the consensus of acupuncture experts and per the results of our pilot study (Cai Y, Wu J, Liu Z. Electroacupuncture versus sham electroacupuncture for chronic severe functional constipation: a randomized controlled pilot study. 2012. Unpublished data.). Fifteen acupuncturists with 2 to 3 years of experience at the 15 sites administered the EA and SA treatments. All acupuncturists had at least a 5-year undergraduate education and were registered practitioners of traditional Chinese medicine. All research assistants and acupuncturists received a 2-day training session before study initiation. Both treatments consisted of 28 sessions, each for 30 minutes, and were administered over 8 weeks (5 sessions in each of the first 2 weeks, and 3 sessions in each of the remaining 6 weeks). Disposable needles (Huatuo) and the SDZ-V EA apparatus (Suzhou Medical Appliance) were used. Participants in the EA group received EA at the bilateral acupoints of Tianshu (ST25), Fujie (SP14), and Shangjuxu (ST37) (15). When participants were supine, 0.3050mm or 0.3575mm needles were inserted approximately 30 to 70 mm into ST25 and SP14 slowly and vertically, without manipulation, until they pierced the muscle layer of the abdominal wall. Paired alligator clips from the EA apparatus were attached transversely to the needle holders at bilateral ST25 and SP14. The EA stimulation lasted for 30 minutes with a dilatational wave of 10/50 Hz and a current intensity of 0.1 to 1 mA depending on the participants comfort level (preferably with skin around the acupoints shivering mildly without pain). In addition, 0.3040mm needles were inserted vertically about 30 mm into ST37 and 3 small, equal manipulations of twirling, lifting, and thrusting (once every 10 minutes) were performed to reach acupuncture de qia soreness, heaviness, and distension sensation when needling (16). Participants in the SA group received shallow needling at bilateral sham ST25, sham SP14, and sham ST37 (nonacupoints that were located at different physical locations than ST25, SP14, and ST37 for EA) (Supplement). Specifically, 0.3025mm needles were inserted vertically about 3 to 5 mm into nonacupoints without manipulation. Similar to EA, paired alligator clips from the specially constructed EA apparatus were attached to the needle holders of sham ST25 and sham SP14. When switched on, the EA apparatus in the SA group had the same working power indicator and sound without actual current output. Supplement. Data Supplement In both groups, participants without BMs for 3 or more consecutive days were allowed to use 110-mL glycerol or 40- to 60-mL sorbitol anal enema as rescue medicine with documentation in the stool diary. Outcomes and Follow-up Participants completed a stool diary during the 22-week study period and the Patient Assessment of Constipation Quality of Life questionnaire (PAC-QOL) (17) at baseline and weeks 4 and 8. The main components of the stool diary included BMs, SBMs, CSBMs, stool consistency, straining, and medication use. Participants documented their stool consistency according to the Bristol Stool Form Scale (18) (scored from 1 to 7 for stool types 1 to 7, respectively). Straining was rated with scores of 0, 1, 2, and 3 indicating not difficult; a little difficult, need some straining to defecate; difficult, need straining to defecate; and very difficult, need hard straining to defecate, respectively. An SBM was defined as a BM that occurred without use of any medication or other methods to assist defecation in the previous 24 hours (4). A BM was not considered as an SBM when it occurred within 24 hours after the use of any assisted method for defecation. The PAC-QOL allowed participants to score the effects of constipation on physical discomfort, psychosocial discomfort, worriedness and concerns, and satisfaction in their daily lives. Higher scores indicate greater impairment or dissatisfaction. The primary outcome was the change from baseline in mean CSBMs per week, calculated as the total number of CSBMs divided by the number of weeks in the assessment period, during weeks 1 to 8. Secondary outcomes included the changes from baseline in mean CSBMs per week during weeks 9 to 20, mean SBMs per week during weeks 1 to 8, mean scores for stool consistency and straining of SBMs during weeks 1 to 8, and health-related quality of life via PAC-QOL score at weeks 4 and 8; the proportion of participants with 3 or more mean CSBMs per week (4); the proportion of participants using rescue medicine and other defecation measures; and the mean weekly frequency of using rescue medicine and other defecation aids during weeks 1 to 4, 1 to 8, and 9 to 20. We also assessed the CSBMs per week and their change from baseline during treatment and follow-up (not prespecified). Adverse events (AEs) were appropriately assessed, managed, and categorized by the acupuncturists and related clinical specialists within 24 hours. Severe AEs had to be reported to the principal investigator and the independent data and safety monitoring

Effect of electroacupuncture versus prucalopride for severe chronic constipation: protocol of a multi-centre, non-inferiority, randomised controlled trial

BackgroundAcupuncture is safe and may be effective for severe chronic constipation. The World Gastroenterology Organisation recommends prucalopride for patients for whom previous laxative use failed to provide satisfactory relief.Methods/designIn this prospective, multi-centre, randomised controlled trial, five hundred sixty patients with severe chronic constipation (two or less spontaneous complete bowel movements per week) from 14 centres will be randomised to receive either electroacupuncture or prucalopride. Participants in the electroacupuncture group will receive electroacupuncture for eight weeks, while participants in the control group will take prucalopride (2 mg once daily) for 32 weeks. The primary outcome measure is the proportion of patients having ≥3 spontaneous, complete bowel movements per week, averaged over week three to eight. The secondary outcome measures include eight items, including the proportion of patients having ≥3 spontaneous, complete bowel movements per week averaged over week 9–32, the proportion of patients with one or more increases in spontaneous, complete bowel movements per week from baseline, mean Bristol Stool Scale, etc. Statistical analysis will include the CMH test, nonparametric tests and t tests.DiscussionWe aimed to compare the effect of electroacupuncture versus prucalopride for severe chronic constipation. The limitation of this study is that participants and acupuncturists will not be blinded.Trial registrationClinicalTrials.gov Identifier: NCT02047045.

The efficacy and safety of electroacupuncture for women with pure stress urinary incontinence: study protocol for a multicenter randomized controlled trial

BackgroundAlthough available evidence relating to its effectiveness is weak, acupuncture is used as an alternative therapy for stress urinary incontinence. We report a protocol of a randomized controlled trial using electroacupuncture (the passing of a weak current between inserted acupuncture needles) to treat women with pure stress urinary incontinence.Methods/DesignThis is a large-scale multicenter subject-blinded randomized controlled trial. A total of 500 women with pure stress urinary incontinence will be randomly assigned to two groups: a treatment group and a control group. The treatment group will receive electroacupuncture with deep needling at acupuncture points BL33 and BL35. The control group will receive sham electroacupuncture with non-penetrating needling at sham locations for the acupuncture points of BL33 and BL35. Participants will be given three sessions a week for 6 weeks. A 24-week-long follow-up will be conducted. The primary outcome will be the change in amount of urine leakage at the sixth week from a baseline measured by a 1-h pad test. The secondary outcomes include: the 72-h incontinence episode frequency based on a 72-h bladder diary; the score of International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form; the degree of urinary incontinence based on a 72-h bladder diary; self-assessment of the therapeutic effect; weekly consumption of pads; application of other treatments for stress urinary incontinence; and subgroup analysis stratified by incontinence severity. The safety of electroacupuncture will also be assessed.DiscussionThis trial will help to identify whether electroacupuncture is effective for stress urinary incontinence, and, if so, whether it is a therapeutic effect rather than a placebo effect.Trial RegistrationClinical Trials.gov NCT01784172