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.

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.

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.

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.

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.

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.

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.

Randomized control trial of a culturally adapted behavioral activation therapy for Muslim patients with depression in Pakistan

BACKGROUND Behavioral activation therapy(BA)is as effective as cognitive behavior therapy(CBT)in treating depression and can be delivered by practitioners with much less psychological training,making it particularly suitable for low resource settings.BA that is culturally adapted for Muslims(BA-M)is a culturally adapted form of BA that has been found acceptable and feasible for Muslims with depression in the United Kingdom and Turkey;however,this is the first time that its efficacy has been determined through a definitive randomized controlled trial.AIM To compare the effectiveness of BA-M with CBT for Muslim patients with depression in Pakistan.METHODS One hundred and eight patients were randomized 1:1 to treatment arms in a parallel-group randomized controlled trial in hospital or community sites in Lahore,Pakistan.Recruitment followed self-referral or referrals from clinicians,consultants or relevant professionals at each site.Four measures were recorded by blinded assessors:The patient health questionnaire-9(PHQ-9);the BA for depression scale short form(BADS-SF);symptom checklist-revised and the World Health Organization Quality-of-Life Brief Scale.All measures were recorded at baseline and post treatment;PHQ-9 and BADS-SF were also recorded at each session and at three month follow up.The primary analysis was to regress the PHQ-9 score after therapy upon the PHQ-9 score before therapy(baseline)and the type of therapy given,that is,analysis of covariance.In addition,analysis using PHQ-9 scores collected at each therapy session was employed in a 2-level regression model.RESULTS Patients in the BA-M arm experienced greater improvement in PHQ-9 score of 1.95 units compared to the CBT arm after adjusting for baseline values(P=0.006)The key reason behind this improvement was that patients were retained in therapy longer under BA-M,in which patients were retained for an average 0.75 sessions more than CBT patients(P=0.013).Patients also showed significant differences on physical(P<0.001),psychological(P=0.004)and social(P=0.047)domains of Quality of Life(QoL)at post treatment level,indicating an increased QoL in the BA-M group as compared to the treatment as usual group.Some baseline differences were noted in both groups for BA scores and two domains of QoL scale:Physical and environment,which might have influenced the results,though the BA-M group showed more improvement at completion of therapy.CONCLUSION Results proved the efficacy of BA-M in reducing symptoms for depressed patients in Pakistan,indicating BA-M is a promising treatment modality for depression in future,particularly in low resource settings.

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.