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 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.

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.

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.

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.

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.

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.

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.

Myelotomy promotes locomotor recovery in rats subjected to spinal cord injury： a meta-analysis of six randomized controlled trials

OBJECTIVE： To investigate the effects of myelotomy on locomotor recovery in rats subjected to spinal cord injury. DATA SOURCES： Electronic databases including Pub Med, Science Citation Index, Cochrane Library, China National Knowledge Infrastructure, Chinese Journals Full-text Database, China Biology Medicine disc, and Wanfang Database were searched to retrieve related studies published before September 2017. The Me SH terms（the Medical Subject Headings） such as ＂myelotomy＂, ＂spinal cord injuries＂, ＂rats＂, ＂randomized controlled trial＂ and all related entry terms were searched. DATA SELECTION： Randomized controlled trials using myelotomy for the treatment of acute spinal cord injury in rats were included. Basso, Beattie, and Bresnahan scores were adopted as the evaluation method. Rev Man Software（version 5.3） was used for data processing. The χ^2 and I^2 tests were used to assess heterogeneity. Using a random-effects model, a subgroup analysis was conducted to analyze the source of the heterogeneity. OUTCOME MEASURES： Basso, Beattie, and Bresnahan scores were observed 1–6 weeks after spinal cord injury.RESULTS： Six animal trials were included, using a total of 143 lab rats. The included trials were divided into two subgroups by injury degrees（moderate or severe）. The pooled results showed that, 1–6 weeks after spinal cord injury, the overall Basso, Beattie, and Bresnahan score was significantly higher in the myelotomy group than in the contusion group（weighted mean difference（WMD） = 0.60; 95% confidence interval（CI）： 0.23–0.97; P = 0.001; WMD = 2.10; 95% CI： 1.56–2.64; P 〈 0.001; WMD = 2.65; 95% CI： 1.73–3.57; P 〈 0.001; WMD = 1.66; 95% CI： 0.80–2.52; P 〈 0.001; WMD = 2.09; 95% CI： 0.92–3.26, P 〈 0.001; WMD = 2.25; 95% CI： 1.06–3.44, P 〈 0.001）. The overall heterogeneity was high（I^2 = 85%; I^2 = 95%; I^2 = 94%; I^2 = 88%; I^2 = 91%; I^2 = 89%）. The results in the moderate injury subgroup showed that Basso, Beattie, and Bresnahan scores were significantly higher in the myelotomy group than in the contusion group（WMD = 0.91, 95% CI： 0.52–1.3, P 〈 0.001; WMD = 2.10; 95% CI： 1.56–2.64, P 〈 0.001; WMD = 2.65; 95% CI： 1.73–3.57, P 〈 0.001; WMD = 2.50, 95% CI： 1.72–3.28, P 〈 0.001; WMD = 3.29, 95% CI： 2.21–4.38, P 〈 0.001; WMD = 3.27; 95% CI： 2.31–4.23, P 〈 0.001）. The relevant heterogeneity was low. However, there were no significant differences in Basso, Beattie, and Bresnahan scores between the myelotomy and contusion groups in the severe injury subgroup at 2 and 3 weeks after the injury（P = 0.75; P = 0.92）. CONCLUSION： To date, this is the first attempt to summarize the potential effect of myelotomy on locomotor recovery in rats with spinal cord injury. Our findings conclude that myelotomy promotes locomotor recovery in rats with spinal cord injury, especially in those with moderate injury.

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.

Aflibercept for diabetic macular oedema： a Meta-analysis of randomized controlled trials

AIM： To evaluate the relative efficacy and safety of aflibercept for treatment of diabetic macular oedema （DMO）. METHODS： A comprehensive search in MEDLINE, CENTRAL and EMBASE was undertaken for randomized controlled trials （RCTs） comparing intravitreal anti-vascular endothelial growth factor （anti-VEGF） versus another treatment. Primary outcome measures were proportion of patients with at least 15 letters of gain or loss on a logMAR visual acuity chart, and change in best corrected visual acuity （BCVA） and central macular thickness （CMT） from baseline. Safety outcomes were rates of death, thromboembolic events and any systemic or ocular serious adverse events. The final search was performed on November 2017. RESULTS： Four RCTs were included. Only one trial compared efficacy and safety of aflibercept with bevacizumab and ranibizumab over 1 or 2y. Three trials were included for Meta-analysis comprising 661 patients （331 in the aflibercept, and 330 in the photocoagulation group）. Aflibercept was more efficacious compared to photocoagulation in the proportion of patients with at least 15 letters of improvement and worsening, and in improvement of BCVA and reduction in CMT at 1 or 2y. The safety estimates at 1 or 2y did not differ statistically. CONCLUSION： Aflibercept offers superior benefits over photocoagulation in improving and preserving vision, with no differences in safety. Further comparative effectiveness trials between aflibercept and other anti-VEGF agents will aid ophthalmologists in treatment decisions.

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.

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.

Bibliometric analysis of randomized controlled trials of colorectal cancer over the last decade

BACKGROUND Colorectal cancer is one of the most common cancers globally.In China,its prevalence ranks fourth and fifth among females and males,respectively.Presently,treatment of rectal cancer follows a multidisciplinary comprehensive treatment approach involving surgery,radiotherapy,chemotherapy,and targeted therapy.With deepening theoretical and molecular research on colorectal cancer,randomized controlled trials(RCTs)on colorectal cancer have made significant progress.However,many RCTs have shortfalls.AIM To investigate the RCTs of global colorectal cancer spanning from 2008 to 2018.To provide suggestions for conducting Chinese RCTs of colorectal cancer.METHODS PubMed and Web of Science databases were searched to obtain RCTs of colorectal cancer carried out between January 1,2008,and January 1,2018.The bibliometric method was used for statistical analysis of the publication years,countries/regions,authors,institutions,source journals,quoted times,key words,and authors.RESULTS Colorectal cancer RCTs showed an upward trend between 2008 to 2018;the top 10 research institutions in the included literature were from the United States,the United Kingdom,and other countries with a high incidence of colorectal cancer.Most of the related research journals are sponsored by European and American countries.The 15 most cited studies involved international multicenter clinical research,having few participants from Chinese research institutions.Network visualization using key words showed that RCTs on colorectal cancer focus on screening,disease-free survival,drug treatment,surgical methods,clinical trials,quality of life,and prognosis.The result of the coauthorship network analysis showed that Chinese researchers are less involved in international exchanges compared to those from leading publication countries.CONCLUSION High-quality RCTs are increasingly favored by leading international journals.However,there is still a large gap in clinical research between China and leading countries.Researchers should implement standardized and accurate clinical trials,strengthen international multicenter cooperation,and emphasize quality control.

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.

Current situation on the reporting quality of randomized controlled trials in 5 leading Chinese medical journals

Objective:The Consolidated Standards for Reporting of Trials(CONSORT) statement has already proved to be an efficient standard for reporting quality of randomized controlled trials(RCTs).However,most of the Chinese medical journals have not endorsed the CONSORT statement.The current situation about the reporting quality of RCTs in Chinese medical journals is still unclear.The purpose of the study was to evaluate the reporting quality of RCTs on papers published in 5 leading Chinese medical journals.Methods:We evaluated 232 original RCT papers using a reporting quality scale based on CONSORT statement from 2001 to 2006 in 5 Chinese medical journals(Journal type 1) without adoption of CONSORT and Chinese Journal of Evidence-based Medicine(Journal type 2) which adopted CONSORT in 2004.We measured the inclusion of 26 items for the reporting quality scale and 6 core items of each RCT report,gave score to each item and calculated the total score obtained in each report and the proportion of reports including individual items.The reporting quality of RCT trials from 2001 to 2003(pre-adoption period) was compared with that from 2004 to 2006(post-adoption period).Results:The average reporting quality of RCTs was moderate(mean score,15.18),and the mean score of the 6 core items was low(mean score,1.09) in 5 leading journals.The difference in the total score and the score of the 6 core items between pre-adoption period(2001-2003) and post-adoption period(2004-2006) was statistically significant(P=0.003;P=0.000).Interaction between journal type and period was not significant(F=0.76;P=0.383).We concluded that the change tendency of reporting quality between Journal type 1 and 2 was not different.But as to the core items of sequence concealment and intention-to-treat analysis,the increases were greater for Journal type 2 when evaluated against Journal type 1(P=0.038;P=0.016).Conclusion:The reporting quality of RCT trials in 5 leading Chinese medical journals is improving.However,the lack of important items in RCT trials remains a serious problem.We recommend the endorsement of the Consolidated Standards for Reporting of Trials statement in Chinese medical journals and the continuing education on evidence-based medicine in China.

Neoadjuvant chemoradiotherapy for resectable esophageal cancer:an in-depth study of randomized controlled trials and literature review

Surgery following neoadjuvant chemoradiotherapy(NCRT) is a common multidisciplinary treatment for resectable esophageal cancer(EC). After analyzing 12 randomized controlled trials(RCTs), we discuss the key issues of surgery in the management of resectable EC. Along with chemoradiotherapy, NCRT is recommended for patients with squamous cell carcinoma(SCC) and adenocarcinoma(AC), and most chemotherapy regimens are based on cisplatin, fluorouracil(FU), or both(CF). However, taxane-based schedules or additional studies, together with newer chemotherapies, are warranted. In nine clinical trials, post-operative complications were similar without significant differences between two treatment groups. In-hospital mortality was significantly different in only 1 out of 10 trials. Half of the randomized trials that compare NCRT with surgery in EC demonstrate an increase in overall survival or disease-free survival. NCRT offers a great opportunity for margin negative resection, decreased disease stage, and improved loco-regional control. However, NCRT does not affect the quality of life when combined with esophagectomy. Future trials should focus on the identification of optimum regimens and selection of patients who are most likely to benefit from specific treatment options.

Pain reduction and adverse effects of intravenous metoclopramide for acute migraine attack: A systematic review and meta-analysis of randomized-controlled trials

BACKGROUND Metoclopramide may be used to treat people suffering from acute migraine.However,no comprehensive investigation on this issue has been recorded.This review will provide more solid evidence for the use of metoclopramide in treating acute migraine.AIM To compare the efficacy of intravenous metoclopramide with other therapies in migraine attack treatment in an emergency department(ED).METHODS We included randomized controlled trials of participants older than 18 years with acute migraine headaches,which included at least one arm that received intravenous(IV)metoclopramide at the ED.A literature search of PubMed,Web of Science,Cochrane Collaboration,and Reference Citation Analysis on December 31,2021 retrieved other drugs or placebo-controlled studies without language limitation.The risk of bias was assessed using the Cochrane risk of bias tool.The primary endpoint was pain reduction at 60 min or closest to 1 h after treatment,as measured by the pain scale.Secondary endpoints included adverse effects or reactions resulting from metoclopramide or comparisons.RESULTS Fourteen trials with a total of 1661 individuals were eligible for review.The risk of bias ranged from low to intermediate.IV metoclopramide administration was not associated with higher pain reduction at 1 h(Standard mean difference[SMD]=-0.03,95%confidence interval[CI]:-0.33-0.28,P=0.87).However,metoclopramide was associated with better pain reduction than placebo(SMD=1.04,95%CI:0.50-1.58,P=0.0002).In addition,side effects were not significantly different between IV metoclopramide and other drugs or placebo(odds ratio[OR]=0.76,95%CI:0.48-1.19,P=0.09 and OR=0.92,95%CI:0.31-2.74,P=0.54,respectively).CONCLUSION Metoclopramide is more effective than placebo in treating migraine in the ED.Despite the observed tendency of decreased side effects,its effectiveness compared to other regimens is poorly understood.More research on this area is needed to treat migraine in acute care settings effectively.

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.

Randomized controlled trials on Roy adaptation model nursing in patients with acute myocardial infarction in china: a systematic review

Objective:This study was to evaluate the quality of the randomized controlled trials on Roy adaptation model nursing in individuals suffering from acute myocardial infarction in China.Methods:We systematically searched the Cnki,Wanfang and Vipdatabases,to get randomized controlled trials on Roy adaptation model nursing in individuals suffering from acute myocardial infarction.The search period was from inception to October 2020.According to the Cochrane risk bias assessment tool,the quality of the studies included was appraised.Results:A total of 55 studies were retrieved,and 11 were eventually included in the study.Among the studies included,the first study was published in 2008.The overall quality of the 11 studies included was relatively low.Conclusions:The overall quality of the randomized controlled trials on Roy adaptation model nursing in individuals suffering from acute myocardial infarction was not high,which would hinder the evidence transformation as well as clinical practice.