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.

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.

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.

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.

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.

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.

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.

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.

Early Application of Citicoline in the Treatment of Acute Stroke:A Meta-analysis of Randomized Controlled Trials

This study was to evaluate the efficacy and safety of early application of citicoline in the treatment of patients with acute stroke by meta-analysis. Randomized controlled trials published until May 2015 were electronically searched in MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, WHO International Clinical Trial Registration Platform, Clinical Trial.gov, and China Biology Medicine disc. Two reviewers independently screened the articles and extracted the data based on the inclusion and exclusion criteria. The quality of included articles was evaluated by using Revman5.0, and meta-analysis was performed. The results showed that 1027 articles were obtained in initial retrieval, and finally 7 articles, involving a total of 4039 cases, were included for analysis. The meta-analysis showed that no significant differences were found in the long-term mortality（OR=0.91, 95% CI 0.07 to 1.09, P=0.30）, the rate of dependency（OR=1.02, 95% CI 0.87 to 1.24, P=0.85）, and the effective rate（OR=0.98, 95% CI 0.84 to 1.14, P=0.82） between citicoline group and control group. The overall rate of adverse events in citicoline group was not significantly different from that in control group（P=0.30）. The quality of included articles reached moderate-low level. In conclusion, citicolne cannot reduce long-term mortality and dependence rate in the treatment of acute stroke, and the effective rate of citivoline may be not better than that of controls but with reliable safety.

Incidence of adverse reactions to COVID-19 vaccination:A meta-analysis of randomized controlled trials

Objective:To systematically evaluate the incidence of adverse reactions to coronavirus disease 2019(COVID-19)vaccination.Methods:We systematically searched PubMed,Embase,The Cochrane Library,Web of Science,CNKI,WanFang Data,and VIP Database from the inception of each database to August 31,2021.Randomized controlled clinical trials(RCTs)on the safety of different types of COVID-19 vaccines were retrieved and analyzed.A random or fixed-effects model was used with an odds ratio as the effect size.The quality of each reference was evaluated.The incidence of the adverse reactions of the placebo group and the vaccination group was compared.Heterogeneity and publication bias were taken care of by meta-regression and sub-group analyses.Results:A total of 13 articles were included,with 81287 subjects.Compared with the placebo group,the vaccination group showed a higher combined risk ratio(RR)of total adverse reactions(RR=1.67,95%CI:1.46-1.91,P<0.01),local adverse reactions(RR=2.86,95%CI:2.11-3.87,P<0.01),systemic adverse reactions(RR=1.25,95%CI:0.92-1.72,P=0.16),pain(RR=2.55,95%CI:1.75-3.70,P<0.01),swelling(RR=4.16,95%CI:1.71-10.17,P=0.002),fever(RR=2.34,95%CI:1.84-2.97,P<0.01),fatigue(RR=1.36,95%CI:1.32-1.41,P<0.01)and headache(RR=1.22,95%CI:1.18-1.26,P<0.01).The subgroup analysis showed the incidence of adverse reactions of the vaccination group after injection of the three COVID-19 vaccines(inactivated viral vaccines,mRNA vaccines and adenovirus vector vaccines)was higher than that of the placebo group,and the difference between the placebo group and the vaccination group in the mRNA vaccine subgroup and the adenovirus vector vaccine subgroup was statistically significant(P<0.01).The incidence of adverse reactions after injection of COVID-19 vaccine in subgroups of different ages was significantly higher than that in the placebo group(P<0.01).Conclusions:COVID-19 vaccines have a good safety,among which adenovirus vector vaccine has the highest incidence of adverse reactions.Both adolescents and adults vaccinated with novel coronavirus vaccine have a certain proportion of adverse reactions,but the symptoms are mild and can be relieved by themselves.Our meta-analysis can help boost global awareness of vaccine safety,promote mass vaccination,help build regional and global immune barriers and effectively curb the recurrency of COVID-19.

Adding Chinese herbal medicine to probiotics for irritable bowel syndrome-diarrhea:A systematic review and meta-analysis of randomized controlled trials

Objective:This study assessed whether Chinese herbal medicine(CHM)combined with probiotics/synbiotics for irritable bowel syndrome-diarrhea(IBS-D)was more effective and safer than probiotics/synbiotics alone.Methods:Ten databases were searched for randomized control trials(RCTs)of IBS-D as diagnosed by Manning or Rome criteria.Trials comparing probiotics and probiotics with CHM were included.The Cochrane risk of bias(ROB)was evaluated for each trial.RevMan 5.3 was used to conduct a meta-analysis.Results:Twenty-six RCTs were included(25 Chinese,1 English),involving 2045 participants.Metaanalysis was conducted on two outcomes:overall symptom improvement and relapse.CHM combined with live Bifidobacterium and Lactobacillus preparations reduced relapse rate(RR 0.28,95%CI 0.15e0.52,3 trials,n?205)compared with probiotics alone.The subgroup analysis showed the benefit of CHM prescriptions based on soothing liver and invigorating spleen(1.28,1.14e1.44,3,244),invigorating spleen and resolving dampness(1.20,1.03e1.41,2,128),or warming and invigorating spleen and kidney formulae(1.27,1.09e1.46,2,210)combined with triple Bifidobacterium preparations than the same probiotics alone which improved overall symptoms for IBS-D.There was unclear bias in almost domains of ROB.Most studies had a high risk of bias due to lack of blinding of investigator and participants,and selective reporting.Conclusions:This study showed that CHM combined with probiotics may reduce relapse rate by 72%,and improve overall symptoms of IBS-D(as diagnosed by Rome II and III)compared to probiotics alone.From the limited subgroup analysis,only soothing liver and invigorating spleen formulae,represented by Tongxie Yaofang,added to triple Bifidobacterium preparations may be superior to the single preparations in terms of overall symptoms.However,due to the poor methodological quality and small sample size of the trials,these findings must be interpreted with caution.

Characteristics of 240 randomized controlled trials for adjusting constitution in preventive treatment of disease:A bibliometric analysis

Background:A growing number of randomized controlled trials(RCTs)have explored the significance of adjusting constitution for preventive treatment of disease in traditional Chinese medicine(TCM).In this study,we sought to comprehensively analyze the characteristics of these RCTs.Methods:All RCTs related to constitutional adjustment and preventive treatment of disease were included in the study.Literature was screened searching seven databases,including Pubmed,Web of Science,Embase,SinoMed,CNKI,Chongqing VIP,and Wangfang Database,from inception to December 2018.Data pertaining to bibliometrics,participants,and interventions were extracted and analyzed.Results:Two hundred and forty papers were published between 2007 and 2018,involving 240 RCTs with 55977 total participants.Sample size in these RCTs ranged from 30 to 7800.Among them,59 RCTs addressed disease prevention prior to onset involving 11 healthy states of participants,mainly for general health or sub-health population(40.68%)using health care and non-drug therapy.In control the development of existing disease(n Z 174),59 diseases were involved.Based on the number of RCTs and sample sizes,diseases including type 2 diabetes mellitus,primary hypertension,nonalcoholic fatty liver disease,and hyperlipoproteinemia accounted for 51.15%of the total patients studied.Drug therapy as an intervention was frequently used.In preventing recurrence after recovery(n Z 7),over 4 kinds of health status in participants were involved.Drug therapy combined with health care was mostly used.Most RCTs reported positive outcomes,with only one reporting negative findings(1/240).Conclusion:The number of RCTs of constitutional adjustment on preventive treatment of disease has gradually increased since 2012.Participants and intervention measures from the above-mentioned types of RCTs exhibit their own characteristics.Future systematic reviews or meta-analyses on constitutional adjustment for preventive treatment of disease are warranted.

Evolution of evidence in spinal surgery–past,present and future Scientometric analysis of randomized controlled trials in spinal surgery

BACKGROUND Spine surgery is evolving and in the due course of its evolution,it is useful to have a comprehensive summary of the process to have a greater understanding to refine our future directives.With the multiple domains of research in the spine,it has become difficult for a surgeon to find the potential hotspots in research or identify the emerging research frontiers.AIM To analyze RCTs(1990–2019)for potential research domains along with their research networks and identify the hot topics for future research.METHODS A comprehensive and systematic analysis of all the RCTs published on spinal surgery from 1990 to 2019 retrieved from the Web of Science Core Collection database.Scientometric and visual analysis of their characteristics,cooperation networks,keywords,and citations were made using CiteSpace software.Journal and article impact index were retrieved from Reference Citation Analysis(RCA)Database.RESULTS A total of 696 RCTs were published on spinal surgery from 1990 to 2019;of which,the United States(n=263)and China(n=71)made a significant contribution.Thomas Jefferson University(n=16)was the leading contributor to RCTs on spinal surgery.Weinstein JN was the most cited author in the field followed by Deyo RA.Spine(n=559)remained the top-cited journal for RCTs on spinal surgery.On literature co-citation analysis,spinal stenosis,anterior cervical discectomy and fusion,degenerative disc disease,and minimally invasive decompression were identified as the hotspots and potential research frontiers.CONCLUSION The identified hotspots that extending the frontiers in the management of degenerative disorders of the spine through further research holds the potential for advancement in spinal care.

Randomized Controlled Trials and Ph.D. Level Training in Educational Research

This invited paper reviews recent initiatives in teaching about randomized field trials at the graduate level in education research. Reports in a book on randomized trials by Mosteller and Boruch are used as a benchmark. The initiatives have been driven heavily by recent governmental emphasis on ＂evidence based policy＂ in education, criminology, welfare and other sectors. This policy has been backed, in the US at least, by substantial investments in mounting randomized controlled trials to evaluate curriculum packages and programs in grades K-12, crime prevention programs, welfare, and other work. Accelerated growth in randomized trials has entailed cross discipline pre-doctoral and post-doctoral institutes and graduate education programs aimed at enhancing the quality in trial design, execution, and analysis of results. Specific illustrations of graduate education in this area of statistics are taken mainly from experience at the University of Pennsylvania＇s Graduate School of Education and selected other institutions.

Evaluation of reporting quality of randomized controlled trials for cognitive interventions among Alzheimer’s Disease using the CONSORT

Background:The increasing number of Alzheimer’s Disease has become a global health issue.Whether randomized controlled trials are fully reported has an immediate effect on the translation as well as implementation of research conclusions.However,the overall reporting quality of randomized controlled trials for cognitive interventions among Alzheimer’s Disease is unclear.Methods:Randomized controlled trials of cognitive inter-ventions among Alzheimer’s Dementia were searched from Cnki,Embase,Pubmed,Web of Science,WanFang Data,Cochrane Library,and VIP from their inception to December9th 2019.Firstly,the average CONSORT(Consolidated Standards of Reporting Trials)compliance of randomized controlled trials for cognitive interventions among Alzheimer’s Disease was estab-lished.Secondly,the compliance of per CONSORT item was calculated.Furthermore,the possible factors that determine the reporting quality were explored using univariate analysis and binary logistic regression.Results:A total of 55 studies were included.Mean CONSORT compliance of randomized controlled trials was 57.16%and standard deviation was 0.11.Univariate analysis showed that journal impact factor(p<0.001),sample size(p=0.002)as well as number of authors(p<0.001)were statistically significant,but post-2010 publication(p=0.206)as well as reporting of funding(p=0.221)had no significance.However,none of the above factors had statistical significance in binary logistic regression.Conclusions:The overall reporting quality was low,which would not be conducive to the evidence transformation and implementation.Furthermore,the reporting quality was not probably affected by aforementioned factors.

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.

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.

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.

Essentials of Nursing Care in Randomized Controlled Trials of Nurse-Led Interventions in Somatic Care: A Systematic Review

Background: Nursing practice has to contribute to evidence pointing out why there is a need for more nurse-designed randomized control trials (RCTs) focusing on evidence-based practice (EBP). How far this EBP has progressed in different health aspects is usually established by systematic reviews of RCTs. Nurse-led RCTs exist but no study has addressed the essentials of nursing care. Aim: The aim was therefore to determine the essentials of nurses’ interventions by means of nurse-led RCTs in somatic care focusing on the stated context, goals, content, strategies as well as the nurse’s role related to effectiveness. Methods: A systematic review was realized according to Cochrane review assumptions to identify, appraise and synthesize all empirical evidence meeting pre-specified eligibility criteria. The PRISMA statement guided the data extraction process (n = 55) from PubMed and CINAHL. Results: Of the RCTs in somatic care, 71% showed a positive effectiveness of nurse-led interventions, of which the nurse had a significant role with regard to being the main responsible in 67% of the studies. Also, 47% of the RCTs presented a theoretical standpoint related to the nurse-led interventions and most prominent were international evidence-based guidelines. Goals were found to have either a patient-centered or a professional-centered ambition. Strategies were based on patient-directed initiatives, nurse-patient-directed initiatives or nurse-directed initiatives, while contents were built upon either a patient-nurse interaction or a nursing management plan. Conclusions: This review underlines the necessity of a holistic view of a person, as nurse-led RCTs comprising a patient-centered ambition, patient-directed initiative and patient-nurse interaction plan showed beneficial nursing care effectiveness, particularly if theory-based. In a nurse-led RCT, a basic theoretical perspective is advantageous as well as to elucidate the role of the nurse in relation to the estimated effects.