How completely are randomized controlled trials of non-pharmacological interventions following concussion reported? A systematic review

Purpose:The study aimed to examine the reporting completeness of randomized controlled trials(RCTs)of non-pharmacological interventions following concussion.Methods:We searched MEDLINE,Embase,PsycInfo,CINAHL,and Web of Science up to May 2022.Two reviewers independently screened studies and assessed reporting completeness using the Template for Intervention Description and Replication(TIDieR),Consensus on Exercise Reporting Template(CERT),and international Consensus on Therapeutic Exercise aNd Training(i-CONTENT)checklists.Additional information was sought my study authors where reporting was incomplete.Risk of bias(ROB)was assessed with the Cochrane ROB-2 Tool.RCTs examining non-pharmacological interventions following concussion.Results:We included 89 RCTs(n=53 high ROB)examining 11 different interventions for concussion:sub-symptom threshold aerobic exercise,cervicovestibular therapy,physical/cognitive rest,vision therapy,education,psychotherapy,hyperbaric oxygen therapy,transcranial magnetic stimulation,blue light therapy,osteopathic manipulation,and head/neck cooling.Median scores were:TIDieR 9/12(75%;interquartile range(IQR)=5;range:5-12),CERT 17/19(89%;IQR=2;range:10-19),and i-CONTENT 6/7(86%;IQR=1;range:5-7).Percentage of studies completely reporting all items was TIDieR 35%(31/89),CERT 24%(5/21),and i-CONTENT 10%(2/21).Studies were more completely reported after publication of TIDieR(t_(87)=2.08;p=0.04)and CERT(t_(19)=2.72;p=0.01).Reporting completeness was not strongly associated with journal impact factor(TIDieR:rs=0.27;p=0.01;CERT:r_(s)=-0.44;p=0.06;i-CONTENT:r_(s)=-0.17;p=0.48)or ROB(TIDieR:rs=0.11;p=0.31;CERT:rs=0.04;p=0.86;i-CONTENT:rs=0.12;p=0.60).Conclusion:RCTs of non-pharmacological interventions following concussion demonstrate moderate to good reporting completeness,but are often missing key components,particularly modifications,motivational strategies,and qualified supervisor.Reporting completeness improved after TIDieR and CERT publication,but publication in highly cited journals and low ROB do not guarantee reporting completeness.

Can Tibetan medicine Honghua Ruyi pills relieve endometriosisassociated dysmenorrhea?Protocol for a randomized placebocontrolled trial

Objective:To provide high-quality clinical evidence of the efficacy of Tibetan medicine Honghua Ruyi(HHRY)pills for endometriosis-associated dysmenorrhea.Methods:This study constitutes a multicenter,randomized,double-blind,placebo-controlled trial encompassing a three-menstrual cycle intervention followed by a three-menstrual cycle follow-up period.A total of 164 eligible females with endometriosis-associated dysmenorrhea were randomly divided into HHRY pills and placebo groups in a 1:1 ratio.The primary outcome included dysmenorrhea symptoms assessed using Visual Analog Scale(VAS)scores and quality of life,whereas the secondary outcome measures included the maximum VAS for non-menstrual pelvic pain,duration of pain episodes(in days),frequency and quantity of the consumption of ibuprofen sustained-release capsules(or other non-steroidal anti-inflammatory drugs),and days off work/study for staff/student due to dysmenorrhea,ovarian cyst,and/or pelvic nodule size.The safety was monitored throughout the treatment period.All the analyses were based on the intention-to-treat principle.For continuous outcomes,simple or multiple linear regressions were used to estimate the differences between the HHRY pills and placebo groups,with categorical data expressed as the number and percentage of occurrences.Differences were compared using the chi-square test or Fisher's exact test.The predefined analysis was adjusted for concomitant treatment,a variable considered to be associated with outcomes but unaffected by treatment allocation.Estimates of treatment effects were reported with 95%confidence intervals.Two-tailed P values≤.05 were considered statistically significant.Conclusion:Positive results from this trial,upon completion would provide robust evidence for the efficacy and safety of HHRY pills in treating dysmenorrhea in patients with endometriosis.

Can propensity score matching replace randomized controlled trials?

Randomized controlled trials(RCTs)have long been recognized as the gold standard for establishing causal relationships in clinical research.Despite that,various limitations of RCTs prevent its widespread implementation,ranging from the ethicality of withholding potentially-lifesaving treatment from a group to relatively poor external validity due to stringent inclusion criteria,amongst others.However,with the introduction of propensity score matching(PSM)as a retrospective statistical tool,new frontiers in establishing causation in clinical research were opened up.PSM predicts treatment effects using observational data from existing sources such as registries or electronic health records,to create a matched sample of participants who received or did not receive the intervention based on their propensity scores,which takes into account characteristics such as age,gender and comorbidities.Given its retrospective nature and its use of observational data from existing sources,PSM circumvents the aforementioned ethical issues faced by RCTs.Majority of RCTs exclude elderly,pregnant women and young children;thus,evidence of therapy efficacy is rarely proven by robust clinical research for this population.On the other hand,by matching study patient characteristics to that of the population of interest,including the elderly,pregnant women and young children,PSM allows for generalization of results to the wider population and hence greatly increases the external validity.Instead of replacing RCTs with PSM,the synergistic integration of PSM into RCTs stands to provide better research outcomes with both methods complementing each other.For example,in an RCT investigating the impact of mannitol on outcomes among participants of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial,the baseline characteristics of comorbidities and current medications between treatment and control arms were significantly different despite the randomization protocol.Therefore,PSM was incorporated in its analysis to create samples from the treatment and control arms that were matched in terms of these baseline characteristics,thus providing a fairer comparison for the impact of mannitol.This literature review reports the applications,advantages,and considerations of using PSM with RCTs,illustrating its utility in refining randomization,improving external validity,and accounting for non-compliance to protocol.Future research should consider integrating the use of PSM in RCTs to better generalize outcomes to target populations for clinical practice and thereby benefit a wider range of patients,while maintaining the robustness of randomization offered by RCTs.

Safety and effectiveness of electromyography-induced rehabilitation treatment after epidural electrical stimulation for spinal cord injury:study protocol for a prospective,randomized,controlled trial

Epidural electrical stimulation is a new treatment method for spinal cord injury(SCI).Its efficacy and safety have previously been reported.Rehabilitation treatment after epidural electrical stimulation is important to ensure and improve the postoperative efficacy of epidural electrical stimulation in patients with SCI.Considering that electromyography(EMG)-induced rehabilitation treatment can accurately match the muscle contraction of patients with SCI,we designed a study protocol for a prospective,randomized controlled trial.In this trial,on the premise of adjusting the spinal cord electrical stimulator to obtain the maximum EMG signal of the target muscle,patients with SCI receiving epidural electrical stimulation will undergo EMG-induced rehabilitation treatment.Recovery of muscle strength of key muscles,quality of life,safety and therapeutic effects will be monitored.Twenty patients with SCI who are scheduled to undergo epidural electrical stimulation in Shanghai Ruijin Rehabilitation Hospital will be randomly divided into two groups with 10 patients per group.The control group will receive conventional rehabilitation treatment.The EMG-induced rehabilitation group will receive EMG-induced rehabilitation treatment of the target muscles of the upper and lower limbs based on conventional rehabilitation treatment.After rehabilitation treatment,follow up for all patients will occur at 2 weeks and 1,3 and 6 months.The primary outcome measure of this trial will be evaluation of target muscle recovery using the Manual Muscle Testing grading scale.Secondary outcome measures will include modified Barthel Index scores,integrated EMG values,the visual analogue scale,Spinal Cord Independence Measure scores,and modified Ashworth scale scores.The safety indicator will be the incidence of adverse events.This trial will collect data regarding the therapeutic effects of EMG-induced rehabilitation in patients with SCI receiving epidural electrical stimulation for 6 months after rehabilitation treatment.Findings from this trial will help develop rehabilitation methods in patients with SCI after epidural electrical stimulation.This study protocol was approved by Ethics Committee of Shanghai Ruijin Rehabilitation Hospital(Approval No.RKIRB2022-12)on February 15,2022 and was registered with Chinese Clinical Trial Registry(registration number:ChiCTR2200061674;date:June 30,2022).Study protocol version:1.0.

Benefits of Mindfulness Training on the Mental Health of Women During Pregnancy and Early Motherhood:A Randomized Controlled Trial

Objective This study aimed to evaluate the effects of a mindfulness-based psychosomatic intervention on depression,anxiety,fear of childbirth(FOC),and life satisfaction of pregnant women in China.Methods Women experiencing first-time pregnancy(n=104)were randomly allocated to the intervention group or a parallel active control group.We collected data at baseline(T0),postintervention(T1),3 days after delivery(T2),and 42 days after delivery(T3).The participants completed questionnaires for the assessment of the levels of depression,anxiety,FOC,life satisfaction,and mindfulness.Differences between the two groups and changes within the same group were analyzed at four time points using repeated-measures analysis of variance.Results Compared with the active control group,the intervention group reported lower depression levels at T2(P=0.038)and T3(P=0.013);reduced anxiety at T1(P=0.001)and T2(P=0.003);reduced FOC at T1(P<0.001)and T2(P=0.04);increased life satisfaction at T1(P<0.001)and T3(P=0.015);and increased mindfulness at T1(P=0.01)and T2(P=0.006).Conclusion The mindfulness-based psychosomatic intervention effectively increased life satisfaction and reduced perinatal depression,anxiety,and FOC.

Characteristics of Xiao Chai Hu decoction based on randomized controlled trials: A bibliometric analysis

Objective:To explore the characteristics of Xiao Chai Hu(XCH)decoction in randomized controlled trials(RCTs)using a bibliometric method.Methods:Seven databases including PubMed,Web of Science,Embase,Cochrane library,China National Knowledge Infrastructure(CNKI),Chinese Scientific Journal Database(VIP)and Wanfang database were retrieved from inception to May 27,2022.In the study,XCH decoction(or modified)used alone or combined with conventional Western medicine as an intervention measure was included.The basic characteristics,funding support,relevant diseases,intervention methods,and adverse events(AEs)were analyzed.Data analysis was performed using SPSS 26.0 software.Results:A total of 813 RCTs were included,published from 1989 to 2022.There was only one Englishlanguage literature with the recent impact factor of 5.374.There were 147 studies were from Chineselanguage core journals,with the highest impact factor of 2.414.Only 6.15%of the literatures mentioned funding support.96.31%of the included literature reported the statistical significance of using XCH decoction.The diseases treated mainly included chronic hepatitis B(9.35%),cough variant asthma(5.66%),dizziness(5.54%),bile reflux gastritis(4.43%),and fever(4.18%).However,the overall research design of the included literature was poor,and large sample size,multicenter RCTs are needed.The incidence of AEs of XCH decoction alone was 8.86%,which was significantly lower than that of conventional Western medicine treatment.The combination of XCH decoction and conventional Western medicine treatment could reduce the incidence of AEs,and no serious adverse event was reported.Conclusion:Although the included studies show that XCH decoction is widely used,and has good efficacy and few AEs.Due to the low quality of the included RCTs,there may be some bias,and its rational use based on the specific conditions is recommended in clinical practice.

External use of mirabilite to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis in children:A multicenter randomized controlled trial

BACKGROUND Acute pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography(ERCP).Currently,there is no suitable treatment for post-ERCP pancreatitis(PEP)prophylaxis.Few studies have prospectively evaluated interventions to prevent PEP in children.AIM To assess the efficacy and safety of the external use of mirabilite to prevent PEP in children.METHODS This multicenter,randomized controlled clinical trial enrolled patients with chronic pancreatitis scheduled for ERCP according to eligibility criteria.Patients were randomly divided into the external use of mirabilite group(external use of mirabilite in a bag on the projected abdominal area within 30 min before ERCP)and blank group.The primary outcome was the incidence of PEP.The secondary outcomes included the severity of PEP,abdominal pain scores,levels of serum inflammatory markers[tumor necrosis factor-alpha(TNF-α)and serum interleukin-10(IL-10)],and intestinal barrier function markers[diamine oxidase(DAO),D-lactic acid,and endotoxin].Additionally,the side effects of topical mirabilite were investigated.RESULTSA total of 234 patients were enrolled,including 117 in the external use of mirabilite group and theother 117 in the blank group.The pre-procedure and procedure-related factors were notsignificantly different between the two groups.The incidence of PEP in the external use ofmirabilite group was significantly lower than that in the blank group(7.7%vs 26.5%,P<0.001).The severity of PEP decreased in the mirabilite group(P=0.023).At 24 h after the procedure,thevisual analog scale score in the external use of mirabilite group was lower than that in the blankgroup(P=0.001).Compared with those in the blank group,the TNF-αexpressions weresignificantly lower and the IL-10 expressions were significantly higher at 24 h after the procedurein the external use of mirabilite group(P=0.032 and P=0.011,respectively).There were nosignificant differences in serum DAO,D-lactic acid,and endotoxin levels before and after ERCPbetween the two groups.No adverse effects of mirabilite were observed.CONCLUSIONExternal use of mirabilite reduced the PEP occurrence.It significantly alleviated post-proceduralpain and reduced inflammatory response.Our results favor the external use of mirabilite toprevent PEP in children.

Ulinastatin in the treatment of severe acute pancreatitis:A singlecenter randomized controlled trial

BACKGROUND Severe acute pancreatitis(AP)is one of the most common diseases of the gastrointestinal tract and carries a significant financial burden with high disability and mortality.There are no effective drugs in the clinical management of severe AP,and there is an absence of evidence-based medicine concerning the treatment of severe AP.AIM To explore whether ulinastatin(UTI)can improve the outcome of severe AP.METHODS The present research included patients who were hospitalized in intensive critical care units(ICUs)after being diagnosed with severe AP.Patients received UTI(400000 IU)or placebos utilizing computer-based random sequencing(in a 1:1 ratio).The primary outcome measures were 7-d mortality,clinical efficacy,inflammatory response,coagulation function,infection,liver function,renal function,and drug-related adverse effects were evaluated.RESULTS A total of 181 individuals were classified into two groups,namely,the placebo group(n=90)and the UTI group(n=91).There were no statistically significant differences in baseline clinical data between the two groups.The 7-d mortality and clinical efficacy in the UTI group were remarkably improved compared with those in the placebo group.UTI can protect against hyperinflammation and improve coagulation dysfunction,infection,liver function,and renal function.UTI patients had markedly decreased hospital stays and hospitalization expenditures compared with the placebo group.CONCLUSION The findings from the present research indicated that UTI can improve the clinical outcomes of patients with severe AP and has fewer adverse reactions.

Efficacy and safety of ivermectin in patients with mild and moderate COVID-19:A randomized controlled trial

Objective:To evaluate the effectiveness and safety of ivermectin in patients with mild and moderate COVID-19.Methods:This study was a single-center,randomized,open-label,controlled trial with a 2-arm parallel-group design on 68 patients with COVID-19.According to the 1:1 ratio between the study groups(ivermectin group and standard treatment group),patients were randomly admitted to each intervention arm.Results:The mean age of the participants in the ivermectin group was(48.37±13.32)years.Eighteen of them were males(54.5%)and the participants in the control group had a mean age of(46.28±14.47)years,with nineteen of them being males(59.4%).As a primary outcome,after 5 days of randomization,there was no significant difference between the ivermectin group and the control group in the length of stay in the hospital(P=0.168).ICU admission(P=0.764),length of stay in ICU(P=0.622),in-hospital mortality(P=0.427),adverse drug reactions,and changes in the mean difference of laboratory data had not any significant difference between the two groups(except for urea change).In addition,the radiologic findings of the two groups of patients were not significantly different.Linear regression analysis showed that for every 10 years increase of age,0.6 day of hospitalization duration was increased.There was no statistically significant association between other variables and clinical outcomes.Conclusions:Among adult hospitalized patients with moderate to severe COVID-19,there was no significant relationship between the administration of ivermectin single dose in a five-day course and clinical improvement,and mortality of the participants.

Traditional Chinese medicine for acute mountain sickness prevention: A systematic review and meta-analysis of randomized controlled trials

Objective: To evaluate the efficacy of traditional Chinese medicine(TCM) for preventing acute mountain sickness(AMS).Methods: We included randomized controlled trials(RCTs) which evalueded the effect of TCM for preventing AMS, compared with a placebo, no treatment or acetazolamide. The literature was searched in 6major databases. RevMan 5.4 software was used for the meta-analysis. The relative risk for discrete variables and the mean difference for continuous variables with 95% confidence intervals(CIs) were applied to express the effect size. The risk of bias in the included studies was evaluated using the Cochrane risk assessment tool 2.0(RoB 2.0), and the evidence certainty was assessed using the Grading of Recommendations Assessment and the Development and Evaluation(GRADE) approach.Results: Twenty RCTs involving 3015 participants and 16 TCM patent drugs were included. The overall risk of bias in the majority of studies(15/20) was of some concerns. In terms of the AMS incidence,Rhodiola rosea(R. rosea, Hong Jing Tian) and Ginkgo biloba(G. biloba, Yin Xing Ye) were equivalent to the placebo/no treatment [RR(95% CI): 0.66(0.43-1.01), 0.82(0.63-1.06), respectively]. The AMS incidence in the G. biloba group was higher than that in the acetazolamide group [RR(95% CI): 2.92(1.69-5.06)]. In terms of improving the AMS symptom score on days 1 and 3 in the plateau, R. rosea and G. biloba were superior to the placebo or no treatment [MD(95% CI):-0.98(-1.71,-0.25),-2.05(-3.14,-0.95), respectively]. The other 14 Chinese patent medicines were evaluated in a single trial, and the majority of the results were negative. The subgroup analysis showed that the effect of R. rosea was related to the intervention time, way of ascending, and altitude.Conclusion: R. rosea and G. biloba were effective in improving AMS symptoms but had no effect in reducing the AMS incidence. There was insufficient evidence to support the use of other TCM patent drugs to prevent AMS. More randomized double-blind placebo-controlled trials are warranted to evaluate and screen effective Chinese patent medicines for AMS prevention.

Current status of outcome reporting in randomized controlled trials of traditional Chinese medicine for mammary gland hyperplasia: A systematic review

Objective:To assess outcome indicators in clinical trials and provide a reference for establishing a core outcome set to treat hyperplasia of mammary gland(HMG)with traditional Chinese medicine(TCM).Methods:Eight online databases were searched from their inception to December 31,2022,to assess outcomes reported in randomized controlled trials(RCTs)of HMG treated with TCM.The quality of the included studies was assessed according to the Cochrane Risk of Bias Assessment Tool.All outcomes were extracted,classified,and described.Results:A total of 8249 articles were initially retrieved.Of these,70 articles were eligible and involved 10618 participants with HMG.A total of 17 outcome indicators with a frequency of 271 times were involved and were collected according to six outcome domains.Conclusions:The core outcomes of RCTs of HMG treated with TCM are large and divergent.There are problems in evaluation standards,primary and secondary outcomes,TCM characteristic indicators,long-term prognosis,and standardization of reporting.It is recommended to strengthen the trial design and actively construct the core outcome sets with TCM characteristics for HMG.

A comparison of the effect of Vitamin D and Vitamin E supplementations,alone,and in combination,on reducing the intensity and duration of dysmenorrhea in women:A randomized controlled trial

Objective:The aim of this study is to compare the effect of Vitamin D and Vitamin E supplementations,alone,and in combination,on reducing the intensity and duration of dysmenorrhea in women who were referred to the Kowsar gynecological clinics of Shahid Motahari Hospital of Urmia University of Medical Sciences.Materials and Methods:A double-blinded clinical trial was conducted on 112 women with dysmenorrhea who were randomly allocated into the four study groups.Finally,100 women complete the study and received capsules containing a placebo(n=25),1000 IU of Vitamin D(n=25),400 mg of Vitamin E(n=25),and 1000 IU of Vitamin D+400 mg of Vitamin E(n=25)every 24 h for 2 consecutive months at the beginning of the menstrual period.The pain intensity and duration among groups were compared before and after the intervention.Results:The mean menstrual pain duration in all three experimental groups(Vitamin E,Vitamin D,and the combination of them)was lower than the placebo group(all P<0.05),and the mean pain intensity scores in all three experimental groups were significantly lower than the placebo group(all P<0.05).The results(means)for all of the drugs administered at the end of the 2nd month were better than the 1st month(all P<0.01).Conclusions:Vitamin E and Vitamin D,as well as their combination,are recommended as an effective and safe treatment for the management of the complications of dysmenorrhea.

Efficacy and safety of mild-warm moxibustion in treating diarrhea-predominant irritable bowel syndrome(spleen deficiency and dampness excess syndrome):a study protocol for a randomized controlled trial

1Background:Irritable bowel syndrome(IBS)is a disorder of bowel function,and diarrhea-predominant irritable bowel syndrome(IBS-D)is the most common.The current treatment for IBS-D is focused on improving patients’gastrointestinal-related symptoms,but there are limitations such as unstable effects and adverse drug reactions.Acupuncture and moxibustion exerts advantages in treating IBS-D.They include several forms,of which moxibustion is one of the most commonly used.And moxibustion is a common way used in treating IBS-D,but there is a lack of relevant evidence-based medical research data.This protocol aims to compare the efficacy of moxibustion(mild-warm moxibustion)in treating IBS-D(spleen deficiency and dampness excess syndrome)with the first-line treatment.Methods:In this prospective,parallel,randomized controlled trial(RCT)protocol,patients will be randomly allocated for 4-week treatment or control therapies and then 4-week follow-up in both groups.We will use Irritable Bowel Syndrome-Symptom Severity Scale(IBS-SSS)score,Irritable Bowel Syndrome-Quality of Life(IBS-QOL)score,serum brain-gut peptide levels,and traditional Chinese medicine(TCM)syndrome scale score to produce more evidence on IBS-D treatment with moxibustion.Finally,we will use SPSS 22.0 software to statistically analyze the data.Discussion:Mild-warm moxibustion is a complementary alternative therapy that fits with the pathogenesis of IBS-D.We hope to see more clinical evidence for mild-warm moxibustion against IBS-D that this RCT supported.

Effects of ulinastatin therapy in deep vein thrombosis prevention after brain tumor surgery:A single-center randomized controlled trial

BACKGROUND Venous thromboembolism(VTE)is a common neurosurgical complication after brain tumor resection,and its prophylaxis has been widely studied.There are no effective drugs in the clinical management of venous thromboembolism,and there is an absence of evidence-based medicine concerning the treatment of severe multiple traumas.AIM To explore whether ulinastatin(UTI)can prevent VTE after brain tumor resection.METHODS The present research included patients who underwent brain tumor resection.Patients received UTIs(400,000 IU)or placebos utilizing computer-based random sequencing(in a 1:1 ratio).The primary outcome measures were the incidence of VTE,coagulation function,pulmonary emboli,liver function,renal function,and drug-related adverse effects.RESULTS A total of 405 patients were evaluated between January 2019 and December 2021,and 361 of these were initially enrolled in the study to form intention-to-treat,which was given UTI(n=180)or placebo(n=181)treatment in a random manner.There were no statistically significant differences in baseline clinical data between the two groups.The incidence of VTE in the UTI group was remarkably improved compared with that in the placebo group.UTI can improve coagulation dysfunction,pulmonary emboli,liver function,and renal function.No significant difference was identified between the two groups in the side effects of UTI-induced diarrhea,vomiting,hospital stays,or hospitalization costs.The incidence of allergies was higher in the UTI group than in the placebo group.CONCLUSION The findings from the present research indicated that UTI can decrease the incidence of VTE and clinical outcomes of patients after brain tumor resection and has fewer adverse reactions.

Effect of Zangfu ointment and massage therapy on functional constipation:a protocol for a randomised controlled trial

Introduction:Functional Constipation(FC)is a type of functional bowel disease that is in Clinically characterized by dysportia,decreased frequency of bowel movements,or incomplete bowel movements in the absence of irritable bowel syndrome syndrome,at least 6 months before diagnosis,and symptoms within the last 3 months.At present,commonly used drugs include enema and suppositories,laxatives,microecological preparations,gastrointestinal motility drugs and other treatments.However,the effect is limited.Traditional Chinese medicine(TCM)treatment of FC has advantages.Methods:In this randomized controlled study,244 eligible patients were randomly assigned in a 1:1 ratio to a treatment group(Zangfu ointment and massage therapy+Lactulose Oral Liquid)and a control group(Lactulose Oral Liquid)for 14 days.Number of spontaneous defecation per week and First defecation time will be used as primary outcomes,and Traditional Chinese Medicine(TCM)syndrome scores and syndrome scores,PAC-QOL form will be used as secondary outcomes.Blood routine,liver function,and renal function will be used as safety outcomes.The primary and secondary outcomes will be performed at 0th,7th,and 14th day,and the safety outcomes will be performed at 0th and 14th day.Ethics and dissemination:Ethical approval has been obtained from the Committee on Health Research Ethics of the Fangshan Hospital,Beijing University of Chinese Medicine,Beijing,People's Republic of China(FZY LK-2020-010)on September 18,2020.All patients will be provided oral and written information about the trial before screening.The study results will be disseminated by peer-review publications and conference presentations.Trial registration number:ChiCTR2000038754(registered on April 14,2021).This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial license,which permits others to distribute,remix,adapt,build upon this work non-commercially,and license their derivative works on different terms,provided the original work is properly cited,appropriate credit is given,any changes made indicated,and the use is non-commercial.STRENGTHS AND LIMITATIONS OF THIS STUDY(1)The efficacy of the Zangfu ointment and massage therapy is evaluated in a randomised,double-blind 2-week clinical trial in FC patients.(2)Form a complete and generalizable regimen for the treatment of FC(Qi stagnation)with the Zangfu ointment and massage therapy.

Systematic review of randomised controlled trials:Probiotics for functional constipation

AIM:To systematically evaluate and update evidence on the efficacy and safety of probiotic supplementation for the treatment of constipation. METHODS:The MEDLINE,EMBASE,CINAHL,and Cochrane Library databases were searched in May 2009 for randomised controlled trials(RCTs)performed in paediatric or adult populations related to the study aim. RESULTS:We included five RCTs with a total of 377 subjects(194 in the experimental group and 183 in the control group).The participants were adults (three RCTs,n=266)and children(two RCTs,n= 111)with constipation.In adults,data suggests a favourable effect of treatment with Bifidobacterium lactis DN-173 010,Lactobacillus casei Shirota,and Escherichia coli Nissle 1917 on defecation frequency and stool consistency.In children,L.casei rhamnosusLcr35,but not L.rhamnosus GG,showed a beneficial effect. CONCLUSION:Until more data are available,we believe the use of probiotics for the treatment of constipation condition should be considered investigational.

Huangqi Guizhi Wuwu Decoction for treating diabetic peripheral neuropathy：a meta-analysis of 16 randomized controlled trials

OBJECTIVE：This meta-analysis was performed to systematically assess the efficacy and safety of the Chinese herbal medicine Huangqi Guizhi Wuwu Decoction（HGWWD） for treating diabetic peripheral neuropathy.DATA SOURCES：Six electronic databases,including the Cochrane Library,MEDLINE database,Chinese Biomedical Database,Chinese National Knowledge Infrastructure Database,Chinese Science and Technique Journals Database,and the Wanfang Database,were search ed on the internet for randomized controlled trials published up until 1 December 2015.The search terms included ＂Chinese herbal medicine＂,＂diabetic peripheral neuropathy＂ and ＂randomized controlled trials＂ in Chinese and in English.DATA SELECTION：We included randomized controlled trials using HGWWD/modified HGWWD for the treatment group,without restriction for the control group.We assessed literature quality in accordance with the Cochrane Review Handbook.A random or a fixed effects model was used to analyze outcomes using Rev Man 5.2 software.OUTCOME MEASURES：The primary outcomes were changes in symptoms and nerve conduction velocities.The secondary outcomeswere fasting blood glucose and hemorheological indexes.RESULTS：Sixteen randomized controlled trials,with a total of 1,173 patients,were included.Meta-analysis revealed that the efficacy of HGWWD for diabetic peripheral neuropathy was significantly superior compared with the control treatment（i.e.,control group）（risk ratio = 0.36,95% confidence interval（CI）：0.29–0.46,Z =8.33,P 〈 0.00001） Compared with the control group,there was an increase in median motor nerve conduction velocity（mean difference（MD） = 3.46,95%CI：1.88–5.04,Z = 4.30,P 〈 0.01） and median sensory nerve conduction velocity（MD = 3.30,95%CI：2.04–4.56,Z = 5.14,P 〈 0.01）.There was also an increase in peroneal motor nerve conduction velocity（MD = 3.22,95%CI：2.45–3.98,Z = 8.21,P 〈 0.01） and peroneal sensory nerve conduction velocity（MD = 3.05,95%CI：2.01–4.09,Z = 5.75,P 〈 0.01） in the treatment groups.No significant difference in fasting blood glucose was found between the treatment groups and the control groups（MD =-0.12,95%CI：-0.42–0.19,Z = 0.76,P = 0.45）.Plasma viscosity was significantly decreased after treatment（MD =-0.11,95%CI：-0.21 to-0.02,Z = 2.30,P = 0.02）.No significant difference in fibrinogen was detectable（MD =-0.53,95%CI：-1.28–0.22,Z = 1.38,P = 0.17）.Four trials reported that treatment groups experienced no adverse reactions.Adverse events were not mentioned in the other 12 trials.No trial reported the incidence of complications,quality of life outcomes,or health economics.CONCLUSION：HGWWD treatment improves diabetic neurologic symptoms and ameliorates nerve conduction velocities.Our study suggests that HGWWD may have significant therapeutic efficacy for the treatment of diabetic peripheral neuropathy.However,the methodological quality of the randomized controlled trials was generally low.Larger and better-designed randomized controlled trials are required to more reliably assess the clinical effectiveness of HGWWD.

Traditional herbal medicine in preventing recurrence after resection of small hepatocellular carcinoma: a multicenter randomized controlled trial

BACKGROUND： Disease recurrence is a main challenge in treatment of hepatocellular carcinoma （HCC）. There is no generally accepted method for preventing recurrence of HCC after resection. OBJECTIVE： To compare the efficacy of a traditional herbal medicine （THM） regimen and transarterial chemoembolization （TACE） in preventing recurrence in post-resection patients with small HCC. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS： This is a multicenter, open- label, randomized, controlled study, which was undertaken in five centers of China. A total of 379 patients who met the eligibility criteria and underwent randomization were enrolled in this trial. One hundred and eighty-eight patients were assigned to the THM group and received Cinobufacini injection and Jiedu Granule, and the other 191 patients were assigned to the TACE group and received one single course of TACE. MAIN OUTCOME MEASURES： Primary outcome measures were the annual recurrence rate and the time to recurrence. Incidence of adverse events was regarded as the secondary outcome measure. RESULTS： Among the 364 patients who were included in the intention-to-treat analysis, 67 patients of the THM group and 87 of the TACE group had recurrence, with a hazard ratio of 0.695 （P = 0.048）. Median recurrence-free survival of the patients in the THM and TACE groups was 46.89 and 34.49 months, respectively. Recurrence rates at 1, 2 and 3 years were 17.7%, 33.0% and 43.5% for the THM group, and 28.8%, 42.5% and 54.0% for the TACE group, respectively （P = 0.026）. Multivariate analysis indicated that the THM regimen had a big advantage for prolonging the recurrence-free survival. Adverse events were mild and abnormality of laboratory indices of the two groups were similar. CONCLUSION： In comparison with TACE therapy, the THM regimen was associated with diminished risk of recurrence of small-sized HCC after resection, with comparable adverse events. TRIAL REGISTRTION IDENTIFIER： This trial was registered in the Chinese Clinical Trial Registry with the identifier ChiCTR-TRC-07000033.

Acupuncture for cerebral palsy: a meta-analysis of randomized controlled trials

OBJECTIVE： To evaluate the efficacy and safety of acupuncture therapy for children with cerebral palsy. DATA SOURCES： We conducted electronic searches of PUBMED（1950/2017）, EMBASE（1974/2017）, Science Direct（1986/2017）, Academic Source Premier（1887/2017）, the Cochrane Library（Issue 4, April 2017）, Science Citation Index Expanded（1900/2017）, China National Knowledge Infrastructure（1915/2017）, China Biological Medicine（1990/2017-04）, Wan Fang（1980/2017）, VIP（1989/2017）, and Chinese Science Citation Database（1989/2017）. DATA SELECTION： We included randomized controlled trials that aimed to compare the effect of acupuncture plus rehabilitation training versus rehabilitation training alone. Data about functional motor abilities, daily activity/social participation, effective rate, intellectual development, and adverse effects were included. We used Revman 5.2 software for statistical analysis. OUTCOME MEASURES： The primary outcomes included functional motor abilities, daily activity, and effective rate. The secondary outcomes included intellectual development and adverse effects.RESULTS： Twenty-one studies with a total of 1718 participants met the inclusion criteria. The effect size of gross motor function（SMD = 0.64, 95% CI： 0.52 to 0.76, P 〈 0.00001; I^2 = 0%, P = 0.69; in 13 studies with 1144 patients） and the total effective rate（RR = 1.28, 95% CI： 1.20 to 1.37, P 〈 0.00001; I^2 = 18%, P = 0.27; in 12 studies with 1106 patients） suggested that acupuncture plus rehabilitation produced a significant improvement in gross motor function and a high total effective rate. The pooled fine motor function（SMD = 3.48, 95% CI： 2.62 to 4.34, P 〈 0.00001; I^2 = 64%, P = 0.10; in 2 studies with 193 patients）, modified Ashworth scale scores（SMD = –0.31, 95% CI： –0.52 to –0.11, P = 0.003; I^2 = 74%, P = 0.004; in 5 studies with 363 patients） and activities of daily living（SMD = 1.45, 95% CI： 1.20 to 1.71, P 〈 0.00001; I^2 = 78%, P = 0.004; in 4 studies with 313 patients） also indicated improvements in children with cerebral palsy. Publication bias was not observed. Only mild adverse events related to acupuncture were reported. CONCLUSION： Acupuncture plus rehabilitation training improved gross motor function, reduced muscle spasms, and enhanced daily life activities in children with cerebral palsy. However, this conclusion should be interpreted with caution due to the small number of randomized controlled trials available and the small sample sizes. More high-quality and large-scale studies are needed.

Epigastric pain syndrome: What can traditional Chinese medicine do? A randomized controlled trial of Biling Weitong Granules

BACKGROUND Recent research suggests that although prokinetic agents,acid suppressors,and radical treatment for Helicobacter pylori infection may be effective in patients with functional dyspepsia(FD),a large proportion of patients still fail to respond to these treatments or may suffer from severe adverse reactions.Many traditional Chinese medicinal herbs can regulate the status of the entire body and have special advantages in the treatment of functional diseases.The present study was designed to verify the efficacy of Biling Weitong Granules(BLWTG),a traditional Chinese medicinal herbal compound formula,in alleviating epigastric pain syndrome(EPS)in FD patients,in an attempt to provide an effective prescription for the clinical treatment of this disease.AIM To evaluate the clinical efficacy and safety of BLWTG in treating EPS in patients with FD.METHODS In this multicenter,stratified,randomized,double-blind,placebo-controlled,parallel group clinical trial,eligible patients were randomized into the BLWTG and placebo groups who were treated for 6 wk.Efficacy indicators including the severity and frequency of EPS and the time to pain resolution and safety indicators including adverse events were observed and compared.RESULTS The baseline demographic data and clinical characteristics,such as epigastric pain symptoms,pain intensity,and frequency of attacks,were matched between the two groups before randomization.After 6 wk of treatment and after the center effect was eliminated,the epigastric pain was significantly improved in 28.33%and 85.59%of the patients in the placebo and BLWTG groups,respectively(P<0.05).At 6 wk,the resolution rate of epigastric pain was 15%and 69.49%in the placebo and BLWTG groups,respectively(P<0.05).The differences of total FD clinical score between these two groups were significant(P<0.05)at 2,4,and 6 wk(P<0.05).The scores of each item and the total score in the Functional Digestive Disorders Quality of Life Questionnaire showed significant differences between the two groups at 6 wk after both the center and interaction effects were eliminated(P<0.05).There was no significant difference in the incidence of adverse events between the two groups,and no serious adverse event was noted during the observation.CONCLUSION Compared with placebo,BLWTG markedly improved EPS in FD patients without causing serious adverse reactions.