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.

Efficacy of a Nutritional Cream Intervention to Treat Depression in Rescuers:A Randomized Controlled Trial

Objective To explore the effectiveness of a nutritional intervention in rescuers who screened positive for depression.Methods A randomized controlled trial design was employed.From June to August,2022,4,460 rescuers were screened using the Self-Rating Depression Scale(SDS),and 1,615 positive cases were identified.Thirty-one volunteers were recruited and randomly divided into a nutritional intervention group and a control group.The intervention group received health education and nutritional intervention(a compound paste therapy primarily composed of red roses and Seville orange flowers),while the control group received psychological education.SDS scores were assessed before and after the intervention.Results There was a statistically significant decline in SDS scores in the nutritional intervention group after the intervention(P<0.05).Furthermore,the SDS scores of the intervention group were significantly lower than those of the control group,both before and after the intervention(P<0.05).No severe adverse reactions were observed during safety evaluation.Conclusion The nutritional intervention effectively reduced the depression scores in rescuers.Early nutritional intervention is recommended for rescuers who initially screen positive for depression.

Effect of Jianpi Shengxue Tablet on Iron Metabolism and Nutritional Status in Patients with Renal Anemia:A Prospective,Randomized,Open,Parallel Controlled and Multicenter Clinical Study

Objective This study aimed to analyze the clinical efficacy of the Jianpi Shengxue tablet for treating renal anemia.Methods A total of 200 patients with renal anemia from December 2020 to December 2022 were enrolled and randomly divided into two groups.Patients in the control group were treated with polysaccharide-iron complex,and those in the experimental group were administered Jianpi Shengxue tablet.After 8 weeks of continuous treatment,the therapeutic outcomes regarding anemia were compared between the two groups.Results After treatment,the red blood cell(RBC)count,hematocrit(HCT),reticulocyte percentage(RET),ferritin(SF),serum iron(SI),transferrin saturation(TSAT),and serum albumin(ALB)all increased(P<0.01),and the clinical symptom score and total iron binding capacity decreased(P<0.01)in the experimental group.Moreover,the improvements in RBC,HCT,RET,SF,SI,TAST,ALB,and clinical symptoms(fatigue,anorexia,dull skin complexion,numbness of hands and feet)in the experimental group were significantly greater than those in the control group(P<0.05).The total effective rate for treating renal anemia was significantly higher in the experimental group than in the control group(P<0.01).Conclusion The Jianpi Shengxue tablet demonstrates efficacy in treating renal anemia,leading to significant improvements in the laboratory examination results and clinical symptoms of patients with renal anemia.

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.

Multicenter Clinical Randomized Controlled Trial and Network Pharmacology Analysis of Zhenzhu Qingyuan Granules for the Treatment of Gastroesophageal Reflux Disease

Objective To evaluate the clinical efficacy and safety of Zhenzhu Qingyuan Granules through a clinical randomized controlled trial and to analyze the potential action targets and pathways of this formula using network pharmacology.Methods Patients with gastroesophageal reflux disease(GERD)of liver–stomach stagnant heat pattern who met the inclusion and exclusion criteria were randomly divided into the control group and the observation group.The control group received oral rabeprazole,whereas the observation group were given Zhenzhu Qingyuan Granules in addition to the rabeprazole.The treatment duration was 8 weeks.Clinical efficacy was observed in both groups after 8 weeks.Network pharmacology was used to analyze the action targets of ZhenzhuQingyuanGranules and the genes related to GERD,and core targets were inferred.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were conducted to explore the potential mechanisms of this formula.Results The clinical research results showed that the total effective rate in the treatment group was 92.68%,compared with 70.00%in the control group,with a statistically significant difference(p<0.05).After treatment,both Chinese medicine syndrome score and endoscopic score improved in both groups compared with before treatment(p<0.05),and the treatment group showed greater improvement than the control group(p<0.05).Network pharmacology identified effective components of Zhenzhu Qingyuan Granules for treating GERD,including quercetin,luteolin,andβ-sitosterol,with potential action targets such as tumor protein 53(TP53),protein kinase B(AKT1),and tumor necrosis factor.Conclusion Zhenzhu Qingyuan Granules can significantly improve clinical symptoms in patients with GERD of liver–stomach stagnated heat pattern,enhance clinical efficacy,and have high safety.This formula may exert therapeutic effects through multiple targets and pathways.

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.

Clinical study on the treatment of acute pancreatitis with external application of Yi-Dan Therapy based on the method of“stagnation requiring dispersion”:study protocol for a randomized controlled trial

Background:Acute pancreatitis is an unpredictable and potentially lethal disease,causing tremendous pain in patients.The initial treatment of acute pancreatitis in modern medicine is supportive,but it is generally ineffective in relieving abdominal pain and distension.Traditional Chinese medicine has been shown to be more effective in regulating the body’s homeostasis and reducing the clinical symptoms of pancreatitis.Yi-Dan ointment,derived from Dahuang-Mudan Decoction,is an effective external ointment for treating acute pancreatitis.The aim of this trial is to investigate the clinical efficacy of Yi-Dan ointment,providing a valuable complement to existing treatment options for pancreatitis.Methods:This is a randomized controlled clinical trial with two parallel groups.Patients in the control group were given basic treatment and nursing for 7 days;in the treatment group,Yi-Dan ointment was applied externally in addition to basic treatment and nursing.The main indicator is the overall efficacy,serum amylase,acute physiology and chronic health evaluationⅡscore,symptom score,inflammatory markers,and classification of computed tomography.Conclusion:The trial results will provide high-quality evidence for Yi-Dan ointment,and provide a complement to existing treatment options for pancreatitis.

Electroacupuncture with different waveforms for primary dysmenorrhea:A randomized controlled trial

Objective:To observe and compare the clinical effects of different electroacupuncture waveforms on primary dysmenorrhea.Methods: This was a prospective,randomized,three-group,parallel-controlled trial.Participants with primary dysmenorrhea were randomly divided into dense-sparse wave,continuous wave,and discontinuous wave groups in a 1:1:1 ratio.Two lateral Ciliao(BL 32)points were used.All three groups started treatment 3–5 days before menstruation,once a day for six sessions per course of treatment,one course of treatment per menstrual cycle,and three menstrual cycles.The primary outcome measure was the proportion with an average visual analog scale(VAS)score reduction of≥50%from baseline for dysmenorrhea in the third menstrual cycle during treatment.The secondary outcome measures included changes in dysmenorrhea VAS scores,Cox Menstrual Symptom Scale scores and the proportion of patients taking analgesic drugs.Results: The proportion of cases where the average VAS score for dysmenorrhea decreased by≥50%from baseline in the third menstrual cycle was not statistically significant(P>.05).Precisely 30 min after acupuncture and regarding immediate analgesia on the most severe day of dysmenorrhea,there was a statistically significant difference in the dense-sparse wave group compared with the other two groups during the third menstrual cycle(P<.05).Additionally,there was a statistically significant difference between the dense-sparse wave and discontinuous wave groups 24 h after acupuncture(P<.05).Conclusions: Waveform electroacupuncture can alleviate primary dysmenorrhea and its related symptoms in patients.The three groups showed similar results in terms of short-and long-term analgesic efficacy and a reduction in the number of patients taking analgesic drugs.Regarding achieving immediate analgesia,the dense-sparse wave group was slightly better than the other two groups.

A randomized controlled clinical trial on the treatment of Thymosin-a1 versus interferon-α in patients with hepatitis B

INTRODUCTIONChronic hepatitis B virus (HBV) infection is a serious problem because of its world wide distribution and possible adverse sequelae ,such as cirrhosis and hepatocellular carcinoma .The World Health Organization estimates that HBV has infected mord than 350 million people worldwide ,and up to 20% of them will become chromic carricrs and will be at significant risk for cirrhosis and HCC .The ultimate goal of the therapy for chronic hepatitis B is to prevent progression to cirrhosis and to prevent development of HCC.

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.

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.

Evaluating efficacy of screening for upper gastrointestinal cancer in China:a study protocol for a randomized controlled trial

Objective： To evaluate the efficacy and feasibility of screening procedure for upper gastrointestinal cancer in both high-risk and non-high-risk areas in China. Setting： Seven cities/counties, representing three economical-geographical regions （Eastern, Central and Western） in China, were selected as screening centers： three in high-risk areas and four in non-high-risk areas. Participants： Villages/communities in these seven centers regarded as clusters were randomly assigned to either intervention group （screening by endoscopic examination） or control group （with normal community care） in a 1：1 ratio stratified by each center. Eligible participants are local residents aged 40-69 years in the selected villages/communities with no history of cancer or endoscopic examination in the latest 3 years who are mentally and physically competent. Those who are not willing to take endoscopic examination or are unwilling to sign the consent form are excluded from the study. Totally 140,000 participants will be enrolled. Interventions： In high-risk areas of upper gastrointestinal cancer, all subjects in screening group will be screened by endoscopy. In non-high-risk areas, 30% of the subjects in screening group, identified through a survey, will be screened by endoscopy. Primary and secondary outcome measures： The primary outcome is the mortality caused by upper gastrointestinal cancer. The secondary outcomes include detection rate, incidence rate, survival rate, and clinical stage distribution. Additional data on quality of life and cost-effectiveness will also be collected to answer important questions regarding screening effects. Conclusions： Screening strategy evaluated in those areas with positive findings may be promoted nationally and applied to the majority of Chinese people. On the other hand, negative findings will provide scientific evidence for abandoning a test and shifting resources elsewhere. Trial registration： The study has been registered with the Protocol Registration System in Chinese Clinical Trial Registry （identifier： ChiCTR-EOR-16008577）.

Functional and psychosocial effects of pulmonary Daoyin on patients with COPD in China:study protocol of a multicenter randomized controlled trial

BACKGROUND： Chronic obstructive pulmonary disease （COPD） is a major public health problem worldwide. Pulmonary rehabilitation （PR） is an established intervention for the management of patients with COPD. Exercise training is an important part of PR, and its effectiveness in patients with COPD is well established. However, alternative methods of PR training such as Daoyin have not been appropriately studied. Hence, alternative forms of exercise training that require less exercise equipment and no specific training place should be evaluated. This paper describes the study protocol of a clinical trial that aims to determine if pulmonary Daoyin training will improve the exercise capacity and psychosocial function of patients with COPD in China. METHODS AND DESIGN： A multicenter, randomized, controlled trial will be conducted. A total of 464 patients meeting the inclusion criteria will be enrolled into this study with 232 patients in each of the trial group and the control group. Based on patient education, patients in the trial group will receive pulmonary Daoyin and continue with their usual therapy for three months. In the control group, patients will continue with their usual therapy. The primary outcome measures are exercise capacity assessed by the six-minute walking distance test and lung function. Secondary outcomes include dyspnea and quality of life. Measurements will be taken at baseline （month 0） and after the study period （month 3）. DISCUSSION： It is hypothesized that pulmonary Daoyin will have beneficial effects in improving exercise capacity and psychosocial function of patients with stable COPD, and will provide an alternative form of exercise training that is accessible for the large number of people with COPD. TRIAL REGISTRATION： This trial has been registered in ClinicalTrials.gov. The identifier is NCT01482000.

Human umbilical cord mesenchymal stem cells to treat spinal cord injury in the early chronic phase: study protocol for a prospective, multicenter, randomized, placebo-controlled, single-blinded clinical trial

Human umbilical cord mesenchymal stem cells(hUC-MSCs)support revascularization,inhibition of inflammation,regulation of apoptosis,and promotion of the release of beneficial factors.Thus,they are regarded as a promising candidate for the treatment of intractable spinal cord injury(SCI).Clinical studies on patients with early chronic SCI(from 2 months to 1 year post-injury),which is clinically common,are rare;therefore,we will conduct a prospective,multicenter,randomized,placebo-controlled,single-blinded clinical trial at the Third Affiliated Hospital of Sun Yat-sen University,West China Hospital of Sichuan University,and Shanghai East Hospital,Tongji University School of Medicine,China.The trial plans to recruit 66 early chronic SCI patients.Eligible patients will undergo randomization at a 2:1 ratio to two arms:the observation group and the control group.Subjects in the observation group will receive four intrathecal transplantations of stem cells,with a dosage of 1×106/kg,at one calendar month intervals.Subjects in the control group will receive intrathecal administrations of 10 mL sterile normal saline in place of the stem cell transplantations.Clinical safety will be assessed by the analysis of adverse events and laboratory tests.The American Spinal Injury Association(ASIA)total score will be the primary efficacy endpoint,and the secondary efficacy outcomes will be the following:ASIA impairment scale,International Association of Neural Restoration-Spinal Cord Injury Functional Rating Scale,muscle tension,electromyogram,cortical motor and cortical sensory evoked potentials,residual urine volume,magnetic resonance imaging–diffusion tensor imaging,T cell subtypes in serum,neurotrophic factors and inflammatory factors in both serum and cerebrospinal fluid.All evaluations will be performed at 1,3,6,and 12 months following the final intrathecal administration.During the entire study procedure,all adverse events will be reported as soon as they are noted.This trial is designed to evaluate the clinical safety and efficacy of subarachnoid transplantation of hUC-MSCs to treat early chronic SCI.Moreover,it will establish whether cytotherapy can ameliorate local hostile microenvironments,promote tracking fiber regeneration,and strengthen spinal conduction ability,thus improving overall motor,sensory,and micturition/defecation function in patients with early chronic SCI.This study was approved by the Stem Cell Research Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University,China(approval No.[2018]-02)on March 30,2018,and was registered with ClinicalTrials.gov(registration No.NCT03521323)on April 12,2018.The revised trial protocol(protocol version 4.0)was approved by the Stem Cell Research Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University,China(approval No.[2019]-10)on February 25,2019,and released on ClinicalTrials.gov on April 29,2019.

Chinese herbal medicine Xinfeng Capsule in treatment of rheumatoid arthritis:study protocol of a multicenter randomized controlled trial

BACKGROUND： Rheumatoid arthritis （RA）, as a common systemic inflammatory autoimmune disease, affects approximately 1 in 100 individuals. Effective treatment for RA is not yet available because current research does not have a clear understanding of the etiology and pathogenesis of RA. Xinfeng Capsule, a patent Chinese herbal medicine, has been used in the treatment of RA in recent years. Despite its reported clinical efficacy, there are no large-sample, multicenter, randomized trials that support the use of Xinfeng Capsule for RA. Therefore, we designed a randomized, double-blind, multicenter, placebo-controlled trial to assess the efficacy and safety of Xinfeng Capsule in the treatment of RA. METHODS AND DESIGN： This is a 12-week, randomized, placebo-controlled, double-blind, multicenter trial on the treatment of RA. The participants will be randomly assigned to the experimental group and the control group at a ratio of 1：1. Participants in the experimental group will receive Xinfeng Capsule and a pharmaceutical placebo （imitation leflunomide）. The control group will receive leflunomide and an herbal placebo （imitation Xinfeng Capsule）. The American College of Rheumatology （ACR） Criteria for RA will be used to measure the efficacy of the Xinfeng Capsule. The primary outcome measure will be the percentage of study participants who achieve an ACR 20% response rate （ACR20）, which will be measured every 4 weeks after randomization. Secondary outcomes will include the ACR50 and ACR70 responses, the side effects of the medications, the Disease Activity Score 28, RA biomarkers, quality of life, and X-rays of the hands and wrists. The first four of the secondary outcomes will be measured every 4 weeks and the others will be measured at baseline and after 12 weeks of treatment. DISCUSSION： The result of this trial will help to evaluate whether Xinfeng Capsule is effective and safe in the treatment of RA. TRIAL REGISTRATION： This trial has been registered in ClinicalTrials.gov. The identifier is N CT01774877.

Effects of Chinese herbal medicine Yiqi Huaju Qingli Formula in metabolic syndrome patients with microalbuminuria:a randomized placebo-controlled trial

BACKGROUND： Microalbuminuria （MAU） is a key component of metabolic syndrome （MetS） and is an early sign of diabetic nephropathy as well. Although routine Western medicine treatments are given to MetS patients to control high blood pressure, hyperglycemia and dyslipidemia, some patients still experience progressive renal lesions and it is necessary to modify and improve the treatment strategy for MetS patients. OBJECTIVE： To investigate the efficacy of Yiqi Huaju Qingli Herb Formula, a compound traditional Chinese herbal medicine, in MetS patients with MAU when it is combined with routine Western medicine treatment. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS： Sixty patients with MetS were randomized into the Chinese herbal formula group （CHF, Yiqi Huaju Qingli formula treatment in combination with Western medicine） and control group （placebo in combination with Western medicine）. All treatments were administered for 12 weeks. MAIN OUTCOME MEASURES： Urinary microalbumin （MA）, urinary albumin-to-creatinine ratio （UACR）, 24-hour total urine protein （24-hTP）, body mass index （BMI）, waist circumference （WC）, waist-to-hip ratio （WHR）, fasting plasma glucose （FPG）, 2-hour postprandial plasma glucose （2-hPPG）, glycosylated hemoglobin （HbAlc）, homeostasis model assessment for insulin resistance （HOMA-IR）, blood lipid profile and blood pressure were observed. RESULTS： Compared with the control group, CHF treatment significantly decreased BMI （P〈0.05）, WC （P〈0.01） and WHR （P〈0.01）. Both groups had significant decreases in FPG, 2-hPPG, HbAlc, HOMA-IR, MA, and UACR, with CHF treatment showing better effects on these parameters compared with the control treatment （P〈0.05）. Both treatments significantly reduced the levels of total cholesterol, low-density lipoprotein cholesterol and triacylglycerol （TAG）, and a greater reduction in TAG was observed with CHF treatment （P〈0.05）. The level of high-density lipoprotein cholesterol did not change in the control group after treatment （P〉0.05）, whereas it significantly increased with CHF treatment （P〈0.01）. Compared with before the treatment, significant decreases in systolic blood pressure, diastolic blood pressure and mean arterial blood pressure were observed in both groups （P〈0.01）. However, there was no significant difference between the two groups （P〉0.05）. CONCLUSION： Combined treatment ofYiqi Huaju Qingli Formula and Western medicine significantly alleviated MAU, which may correlate with the improvement of insulin sensitivity and glucose and lipid metabolism. TRIAL REGISTRATION IDENTIFIER： This trial was registered in the Chinese Clinical Trial Registry with the identifier ChiCTR-TRC-11001633.

Restrictive vs liberal transfusion for upper gastrointestinal bleeding:A meta-analysis of randomized controlled trials

AIM:To compare the outcome of upper gastrointestinal bleeding(UGIB) between patients receiving restrictive and liberal transfusion.METHODS:PubMed,EMBASE,and Cochrane Library databases were employed to identify all relevant randomized controlled trials regarding the outcome of UGIB after restrictive or liberal transfusion. Primary outcomes were death and rebleeding. Secondary outcomes were length of hospitalization,amount of blood transfused,and hematocrit and hemoglobin at discharge or after expansion.RESULTS:Overall,4 papers were included in this meta-analysis. The incidence of death was significantly lower in patients receiving restrictive transfusion than those receiving liberal transfusion(OR:0.52,95%CI:0.31-0.87,P = 0.01). The incidence of rebleeding was lower in patients receiving restrictive transfusion than those receiving liberal transfusion,but this difference did not reach any statistical significance(OR:0.26,95%CI:0.03-2.10,P = 0.21). Compared with those receiving liberal transfusion,patients receiving restrictive transfusion had a significantly shorter length of hospitalization(standard mean difference:-0.17,95%CI:-0.30--0.04,P = 0.009) and a significantly smaller amount of blood transfused(standard mean difference:-0.74,95%CI:-1.15--0.32,P = 0.0005) with a lower hematocrit and hemoglobin level at discharge or after expansion.CONCLUSION:Restrictive transfusion should be employed in patients with UGIB.

Evaluation on the efficacy and safety of Chinese herbal medication Xifeng Dingchan Pill in treating Parkinson's disease: study protocol of a multicenter, open-label, randomized active-controlled trial

BACKGROUND： Parkinson＇s disease （PD） is a complicated disease, commonly diagnosed among the elderly, which leads to degeneration of the central nervous system. It presently lacks an effective therapy for its complex pathogenesis. Adverse effects from Western drug-based medical intervention prevent long-term adherence to these therapies in many patients. Traditional Chinese medicine （TCM） has long been used to improve the treatment of PD by alleviating the toxic and adverse effects of Western drug-based intervention. Therefore, the aim of this study is to evaluate the efficacy and safety of Xifeng Dingchan Pill （XFDCP）, a compound traditional Chinese herbal medicine, taken in conjunction with Western medicine in the treatment of PD patients at different stages in the progression of the disease. METHODS AND DESIGN： This is a multicenter, randomized controlled trial. In total, 320 patients with early- （n = 160） and middle-stage PD （n = 160） will be enrolled and divided evenly into control and trial groups. Of the 160 patients with early-stage PD, the trial group （n = 80） will be given XFDCP, and the control group （n = 80） will be given Madopar. Of the 160 patients with middle-stage PD, the trial group （n = 80） will be given XFDCP combined with Madopar and Piribedil, and the control group （n = 80） will be given Madopar and Piribedil. The Unified Parkinson＇s Disease Rating Scale scores, TCM symptoms scores, quality of life, change of Madopar＇s dosage and the toxic and adverse effects of Madopar will be observed during a 3-month treatment period and through a further 6-month follow-up period. DISCUSSION： It is hypothesized that XFDCP, combined with Madopar and Piribedil, will have beneficial effects on patients with PD. The results of this study will provide evidence for developing a comprehensive therapy regimen, which can delay the progress of the disease and improve the quality of life for PD patients in different stages. TRIAL REGISTRATION： This trial has been registered in the Chinese Clinical Trial Registry with the identifer ChiCTR-TRC-12002150.

Early filiform needle acupuncture for poststroke depression: a meta-analysis of 17 randomized controlled clinical trials

OBJECTIVE： To evaluate the effectiveness and safety of filiform needle acupuncture for poststroke depression, and to compare acupuncture with the therapeutic efficacy of antidepressant drugs. DATA RETRIEVAL： We retrieved data from the Chinese National Knowledge Infrastructure （1979-2012）, Wanfang （1980-2012）, VIP （1989-2012）, Chinese Biomedical Literature （1975- 2012）, PubMed （1966-2012）, Ovid Lww （-2012）, and Cochrane Library （-2012） Database using the internet. SELECTION CRITERIA： Randomized controlled trials on filiform needle acupuncture versus antidepressant drugs for treatment of poststroke depression were included. Moreover, the in- cluded articles scored at least 4 points on the Jadad scale. Exclusion criteria： other acupuncture therapies as treatment group, not stroke-induced depression patients, score 〈 4 points, non-ran- domized controlled trials, or animal trials. MAIN OUTCOME MEASURES： These were the Hamilton Depression Scale scores, clinical ef- fective rate, Self-Rating Depression Scale scores, Side Effect Rating Scale scores, and incidence of adverse reaction and events. RESULTS： A total of 17 randomized controlled clinical trials were included. Meta-analysis results displayed that after 4 weeks of treatment, clinical effective rate was better in patients treated with fill- form needle acupuncture than those treated with simple antidepressant drugs [relative risk = 1.11, 95% confidence interval （C/）： 1.03-1.21, P = 0.01]. At 6 weeks, clinical effective rate was similar between filiform needle acupuncture and antidepressant drug groups. At 2 weeks after filiform needle acupuncture, Hamilton Depression Scale （17 items） scores were lower than in the antide- pressant drug group （mean difference = -2.34, 95%CI： -3.46 to -1.22, P 〈 0.000,1）. At 4 weeks, Hamilton Depression Scale （24 items） scores were similar between filiform needle acupuncture and antidepressant drug groups. Self-Rating Depression Scale scores were lower in filiform needle acupuncture group than in the antidepressant drug group. Side Effect Rating Scale was used in only two articles, and no meta-analysis was conducted. Safety evaluation of the 17 arti- cles showed that gastrointestinal tract reactions such as nausea and vomiting were very common in the antidepressant drug group. Incidence of adverse reaction and events was very low in the filiform needle acupuncture group. CONCLUSION： Early filiform needle acupuncture for poststroke depression can perfectly con- trol depression. Filiform needle acupuncture is safe and reliable. Therapeutic effects of filiform needle acupuncture were better than those of antidepressant drugs.

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.