Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized byclinical symptoms of diarrhea and mucopurulent bloody stools, and its incidenceis increasing globally. The etiology and pathogenesis of U...Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized byclinical symptoms of diarrhea and mucopurulent bloody stools, and its incidenceis increasing globally. The etiology and pathogenesis of UC remain elusive. Currenttherapeutic approaches, including anti-inflammatory, immunosuppressiveand immunomodulating agents, are often limited in efficacy and frequently associatedwith adverse drug reactions. Therefore, there is an urgent need to developsafer and more effective treatment strategies to address the limitations of existingtherapies. Scutellaria baicalensis Georgi (HQ), a traditional Chinese medicinal herb,has been employed in the treatment of UC for over 2000 years. Recent studieshave demonstrated that HQ contains multiple active components capable oftreating UC through anti-inflammation, immune modulation, intestinal barrierprotection, antioxidant activity, and regulation of the gut microbiota. This paperreviews recent studies on the mechanism of action and clinical trials of HQ intreating UC based on relevant literature, with the aim of providing valuable insightsinto future treatment approaches.展开更多
OBJECTIVE To evaluate the safety and effectiveness of robot-assisted percutaneous coronary intervention(R-PCI)compared to traditional manual percutaneous coronary intervention(M-PCI).METHODS This prospective,multicent...OBJECTIVE To evaluate the safety and effectiveness of robot-assisted percutaneous coronary intervention(R-PCI)compared to traditional manual percutaneous coronary intervention(M-PCI).METHODS This prospective,multicenter,randomized controlled,non-inferior clinical trial enrolled patients with coronary heart disease who met the inclusion criteria and had indications for elective percutaneous coronary intervention.Participants were randomly assigned to either the R-PCI group or the M-PCI group.Primary endpoints were clinical and technical success rates.Clinical success was defined as visually estimated residual post-percutaneous coronary intervention stenosis<30% with no 30-day major adverse cardiac events.Technical success in the R-PCI group was defined as successful completion of percutaneous coronary intervention using the ETcath200 robot-assisted system,without conversion to M-PCI in the event of a guidewire or balloon/stent catheter that was unable to cross the vessel or was poorly supported by the catheter.Secondary endpoints included total procedure time,percutaneous coronary intervention procedure time,fluoroscopy time,contrast volume,operator radiation exposure,air kerma,and dose-area product.RESULTS The trial enrolled 152 patients(R-PCI:73 patients,M-PCI:79 patients).Lesions were predominantly B2/C type(73.6%).Both groups achieved 100% clinical success rate.No major adverse cardiac events occurred during the 30-day follow-up.The R-PCI group had a technical success rate of 100%.The R-PCI group had longer total procedure and fluoroscopy times,but lower operator radiation exposure.The percutaneous coronary intervention procedure time,contrast volume,air kerma,and dose-area product were similar between the two groups.CONCLUSIONS For certain complex lesions,performing percutaneous coronary intervention using the ETcath200 robot-assisted system is safe and effective and does not result in conversion to M-PCI.展开更多
Objective： To evaluate the effectiveness and safety of lyophilized Salvia salt of lithospermic acid powder for injection （SSLA） in treating coronary heart diseases angina pectoris （CHD-AP） of Xin-blood stasis syn...Objective： To evaluate the effectiveness and safety of lyophilized Salvia salt of lithospermic acid powder for injection （SSLA） in treating coronary heart diseases angina pectoris （CHD-AP） of Xin-blood stasis syndrome type, and to conduct the non-inferiority trial with Danshen injection （丹参注射液, DSI） as positive control. Methods： An non-inferiority clinical layered, segmented, randomized, and blinded trial on three parallel and multiple centered groups was conducted in 480 patients with stable effort angina grade Ⅰ , Ⅱand Ⅲ, who had two or more times of attack every week. The 240 patients in test group A were treated with SSLA 200 mg added in 250 ml of 5% glucose solution for intravenous dripping every day; the 120 patients in test group B were treated with SSLA but the dosage doubled; and the 120 patients in the control group were treated with DSI 20 ml daily in the same method as SSLA was given. The clinical effectiveness and safety were evaluated after the patients were treated for 14 days. Results： The results showed that the markedly effective rate in test groups A, B and control group was 37.45 %, 36.75 % and 30.09 % respectively, while the total effective rate in them was 88.09%, 89.74% and 67.26% respectively. Statistical significance was shown in comparisons of the therapeutic effect between control group with test group A and test group B, with that in the two test groups superior to that in the control group, and non-inferiority trial showed eligibility （P〈0.01）. Adverse reaction appeared in 8 patients in the test groups and 2 in the control group. Conclusion： SSLA has definite therapeutic effect in treating patients with CHD-AP, with its effect not inferior to that of DSI, and no evident toxic-adverse reaction.展开更多
Background: Capecitabine and irinotecan combination therapy(XELIRI) has been examined at various dose levels to treat metastatic colorectal cancer(m CRC). Recently, in the Association of Medical Oncology of the German...Background: Capecitabine and irinotecan combination therapy(XELIRI) has been examined at various dose levels to treat metastatic colorectal cancer(m CRC). Recently, in the Association of Medical Oncology of the German Cancer Society(AIO) 0604 trial, tri?weekly XELIRI plus bevacizumab, with reduced doses of irinotecan(200 mg/m^2 on day 1) and capecitabine(1600 mg/m^2 on days 1–14), repeated every 3 weeks, has shown favorable tolerability and eicacy which were comparable to those of capecitabine and oxaliplatin(XELOX) plus bevacizumab. The doses of capecit?abine and irinotecan in the AIO trial are considered optimal. In a phase I/II study, XELIRI plus bevacizumab(BIX) as second?line chemotherapy was well tolerated and had promising eicacy in Japanese patients.Methods: The Asian XELIRI Projec T(AXEPT) is an East Asian collaborative, open?labelled, randomized, phase Ⅲ clinical trial which was designed to demonstrate the non?inferiority of XELIRI with or without bevacizumab versus standard FOLFIRI(5?fluorouracil, leucovorin, and irinotecan combination) with or without bevacizumab as second?line chemo?therapy for patients with m CRC. Patients with 20 years of age or older, histologically conirmed m CRC, Eastern Coop?erative Oncology Group performance status 0–2, adequate organ function, and disease progression or intolerance of the irst?line regimen will be eligible. Patients will be randomized(1:1) to receive standard FOLFIRI with or with?out bevacizumab(5 mg/kg on day 1), repeated every 2 weeks(FOLIRI arm) or XELIRI with or without bevacizumab(7.5 mg/kg on day 1), repeated every 3 weeks(XELIRI arm). A total of 464 events were estimated as necessary to show non?inferiority with a power of 80% at a one?sided α of 0.025, requiring a target sample size of 600 patients. The 95% conidence interval(CI) upper limit of the hazard ratio was pre?speciied as less than 1.3.Conclusion: The Asian XELIRI Projec T is a multinational phase III trial being conducted to provide evidence for XELIRI with or without bevacizumab as a second?line treatment option of mCRC.展开更多
Acupuncture is an ancient treatment method used in traditional Chinese medicine and has been popularized worldwide.Over the past decade,there has been an increase in the amount of acupuncture research,mostly comprised...Acupuncture is an ancient treatment method used in traditional Chinese medicine and has been popularized worldwide.Over the past decade,there has been an increase in the amount of acupuncture research,mostly comprised of randomized controlled trials(RCTs)that aimed to answer the question on the efficacy of acupuncture.However,poor methodology and low replicability in these acupuncture RCTs have resulted in uncertainty about the efficacy of acupuncture.In this review,current advancements and challenges in acupuncture RCTs,regarding the methodological aspects of randomization,blinding,sham acupuncture and quality of reporting,were discussed.While there have been advancements in various aspects,current acupuncture RCTs still face pressing issues such as inadequate randomization and blinding,unviable sham acupuncture controls,and poor reporting quality.Given these limitations,this review seeks to identify the methodological problems that are responsible for these problems and to suggest solutions that could help to overcome them so as to improve the quality of future studies evaluating the efficacy of acupuncture.展开更多
Objective Helicobacter pylori(HP)infection is associated with non-alcoholic fatty liver disease(NAFLD)and insulin resistance;however,the correlation between HP eradication and NAFLD remains controversial.This systemat...Objective Helicobacter pylori(HP)infection is associated with non-alcoholic fatty liver disease(NAFLD)and insulin resistance;however,the correlation between HP eradication and NAFLD remains controversial.This systematic review and meta-analysis examined the effect of HP treatment on clinical and laboratory parameters in NAFLD patients.Methods We conducted a literature search of the PubMed,Embase,Scopus,and Web of Science databases through Septem-ber 2023 for randomized controlled trials(RCTs)examining the effect of HP treatment on NAFLD patients versus lifestyle changes alone.The primary outcome was the change in steatosis parameters.The secondary endpoints were changes in anthropometric parameters,inflammatory markers(TNF-α),and metabolic parameters(fasting blood glucose,homeostasis model assessment of insulin resistance,AST/ALT,and lipid profile).The random effects model was used to calculate the standardized mean difference(SMD)with associated 95%confidence intervals(CIs)for our desired outcome.Results Four RCTs met our inclusion criteria.A total of 453 patients were included(mean age 42.8 years,58.5%males),228(50.3%)of whom were in the HP eradication group and 225(49.7%)of whom were in the lifestyle modification group.Compared with lifestyle modification alone,HP eradication had a significant effect on reducing liver steatosis and TNF-αlevels(SMD:-0.9;95%CI-14.67,-3.82,I^(2)=0%and SMD:-6.3;95%CI-9.04,-3.56,I^(2)=0%,respectively).No sig-nificant effect on other metabolic parameters was found.Conclusions HP eradication significantly reduced liver steatosis and TNF-αlevels in NAFLD patients.However,HP eradi-cation did not significantly affect other metabolic indices compared to lifestyle changes alone.展开更多
OBJECTIVE:To investigate the effectiveness and safety of Guilingji capsule(龟龄集胶囊,GLJC)in treatment of Alzheimer's disease(AD)patients with kidney-marrow deficiency pattern(KMDP)compared with gingko extract ta...OBJECTIVE:To investigate the effectiveness and safety of Guilingji capsule(龟龄集胶囊,GLJC)in treatment of Alzheimer's disease(AD)patients with kidney-marrow deficiency pattern(KMDP)compared with gingko extract tablets.METHODS:This is a secondary analysis of a large-scale multicenter randomized non-inferiority clinical trial.A total of 120 AD patients with KMDP were enrolled in this study.The participants were randomly categorized into two groups:(a)GLJC group(n=60)and(b)gingko group(n=60).The GLJC group was treated with GLJC and gingko extract mimetic tablets,whereas the gingko group received gingko extract tablets and mimetic GLJC.The data on the Mini-Mental State Examination(MMSE),Alzheimer's Disease Assessment Scale-Cognitive Subscale(ADAS-Cog),Activities of Daily Living(ADL),and Chinese Medicine Symptom Scale(CM-SS)was evaluated at 0,12,and 24 weeks of treatment.The serum levels of acetylcholine(Ach),acetylcholinesterase(AchE),B-cell lymphoma-2(Bcl-2),and Bcl-2-associated X protein(Bax)in the participants were measured before and after 24 weeks of treatment.The safety was based on the incidence of adverse events.RESULTS:Both interventions significantly increased the MMSE scores of the participants and decreased their ADAS-Cog,ADL,and CM-SS scores(P<0.01).Compared with the gingko group,the GLJC group had a higher effective rate of improvement in the symptoms of“amnesia”and“dull expression and slow thinking”at the 12th week and 24th week(P<0.05,P<0.01).In the GLJC group,serum Bcl-2 levels were significantly increased at the 24th week(P<0.05).Serum Bax and AchE levels of the two groups were significantly decreased at the 24th week(P<0.01).No treatmentrelated adverse events were reported in the two groups.CONCLUSIONS:GLJC is equivalent to the gingko extract tablets in terms of improving cognitive function and the quality of life in AD patients with KMDP and has good clinical efficacy and safety.When it comes to improving TCM symptoms and anti-aging,GLJC is even more advantageous.展开更多
OBJECTIVE:In recent years,the number of clinical research reports on acupuncture and manipulation for the treatment of greater occipital neuralgia has gradually increased,but the quality is uneven.There is currently n...OBJECTIVE:In recent years,the number of clinical research reports on acupuncture and manipulation for the treatment of greater occipital neuralgia has gradually increased,but the quality is uneven.There is currently no literature evaluating the quality of published reports,which is not conducive to the promotion of clinical use of these therapies.Therefore,this article assessed the reporting quality of randomized controlled trials on acupuncture and manipulation for greater occipital neuralgia.METHODS:Cochrane Library,PubMed,Web of Science,Embase,China National Knowledge Infrastructure(CNKI),VIP,WanFang Data,and Chinese BioMedical Literature Database(CBM)from inception to May 20,2024 were searched.The reporting quality of included randomized controlled trials was independently evaluated by two investigators using the CONSORT statement,STRICTA checklist,and Cochrane bias of risk assessment tool.A third investigator resolved any disagreement.RESULTS:A total of 62 articles were included.Based on the CONSORT statement,59.46%(22/37)of all entries had a reporting rate of less than 50%,mainly including“Identification as a randomized trial in the title(1/62,1.61%),”“How sample size was determined(7/62,11.29%),”“Implementation(1/62,1.61%),”“Blinding(1/62,1.61%),”and“Reports of Funding(4/62,6.45%).”According to the STRICTA checklist,29.41%(5/17)of all entries had a reporting rate of less than 50%,mainly including“Details of other interventions(7/58,12.07%),”“Setting and context of treatment(0/58,0%),”and“Description of participating acupuncturists(0/58,0%).”CONCLUSION:The reporting quality of randomized controlled trials on acupuncture and manipulation therapy for greater occipital neuralgia remains low.Future researchers need to make greater efforts to strictly adhere to the CONSORT statement and STRICTA checklist during trial design,implementation,and reporting.This will facilitate the standardization of research in this field and enhance the reliability and reproducibility of the research results.展开更多
Since 2016,the number of clinical trials registered in the World Health Organization-International Clinical Trials Registry Platform has been steadily increasing.The number of clinical trials registered between 2018 a...Since 2016,the number of clinical trials registered in the World Health Organization-International Clinical Trials Registry Platform has been steadily increasing.The number of clinical trials registered between 2018 and 2022 is 39765 for BRICS countries.Though India’s contribution increased from 33%to 40%in the interim,the number of infectious disease trials registered in India is low(325)compared to the number of oncology clinical trials(1936)[1].The number of phase 3 registrational antibacterial clinical trials conducted in India is also low(Table 1).This poses a serious public health challenge given the infectious disease burden in India[2].展开更多
The NI （non-inferiority） trial design based on the likelihood ratio test eliminates the dependency on the conventional NI margin, and it explicitly uses the MCID （minimum clinical important difference） that links ...The NI （non-inferiority） trial design based on the likelihood ratio test eliminates the dependency on the conventional NI margin, and it explicitly uses the MCID （minimum clinical important difference） that links the statistical analysis to the clinical sense. Different from the conventional trial design, the new methodology is self-adaptive to the change in the sample size and overall cure rate, and it has an asymptotic property. It is shown that MCID is de-composite into constant MCID and statistical MCID. Along with this concept, the concept of the allowed inferiority does not exist, the interpretation of the trial result is more accurate and consistent to the statistical theory as well as the clinical interpretations.展开更多
Objectives:This study aims to evaluate the current state of acupuncture randomized controlled trials(RCTs),their impact on guidelines,and future development trends,providing a reference for future re-search directions...Objectives:This study aims to evaluate the current state of acupuncture randomized controlled trials(RCTs),their impact on guidelines,and future development trends,providing a reference for future re-search directions.Methods:Search for acupuncture-related RCT articles in the Web of Science Core Collection and con-firm their guideline inclusion on Google Scholar.Analyze study characteristics to predict future research directions.Results:The analysis covered 1422 articles,reflecting a substantial rise in publications from 77 articles between 1993 and 2002 to 960 articles between 2013 and 2022.The Western Pacific region led in pub-lication numbers with 622 articles(43.7%),followed by Europe(466 articles;32.8%),Americas(250 articles;17.6%),Eastern Mediterranean(62 articles;4.4%),and Southeast Asia(22 articles;1.5%),with Africa showing a research void.Regrettably,only 29.6%(421 articles)were incorporated into guidelines.The low rate of inclusion of research results in guidelines and the uneven distribution of research fields are particularly prominent.From 1993 to 2002,there were 77 articles,among which 51(66.2%)were included in the guidelines;from 2003 to 2012,there were 385 articles,with 202(52.5%)included;from 2013 to 2022,there were 960 articles,and only 168(17.5%)were included,showing a decreasing trend in the inclusion rate year by year.Regarding geographical distribution,1167 articles were from the East-ern Hemisphere,with 326(27.9%)included;255 were from the Western Hemisphere,and 95(37.3%)were included.Regionally,179 articles(42.5%)from Europe were included,140(33.3%)from the West-ern Pacific,95(22.6%)from the Americas,6(1.4%)from the Eastern Mediterranean,and 1(0.2%)from Southeast Asia.China,the United States,and Germany were the top publishing countries,with consis-tent growth in countries like China,South Korea,Spain,Brazil,Turkey,and Iran.Noteworthy researchers such as Cesar Fernandez-de-las-Penas,Zhi-shun LIU,Jing-wen YANG,Cun-zhi LIU,Li-xing LAO,Stefan N Willich,and Benno Brinkhaus have collaborated on research in areas such as pain management,cognitive impairments,insomnia,digestive system diseases,and urinary system diseases.There has been a partic-ular increase in research focus on neck pain and myofascial trigger points.展开更多
Objective This study aimed to analyze the adverse effects(AEs)of sacituzumab govitecan(SG)through multiple sources of data to provide a reference for clinical safety management.Methods Clinical trials of SG with avail...Objective This study aimed to analyze the adverse effects(AEs)of sacituzumab govitecan(SG)through multiple sources of data to provide a reference for clinical safety management.Methods Clinical trials of SG with available safety data were retrieved and included in the pooled analysis.The adverse drug reaction(ADR)signals of SG were collected from the FDA Adverse Event Reporting System(FAERS)database.Drug interactions with SG in the DDInter database were summarized.Results A total of 6 clinical trials involving 1737 patients were included in the pooled analysis,and the most common AEs of≥grade 3 were neutropenia(46%),leukopenia(13%),and anemia(8%).In the pharmacovigilance study,1024 AE reports were extracted,and the most common toxicities of SG were hematologic and gastrointestinal.AEs not included in the drug instructions also presented high signals,such as meningitis,colitis and lymphedema.A total of 40 drugs identified could induce drug–drug interactions when they were concomitantly administered with SG.Conclusions This study provides the most comprehensive profile of SG toxicity on the basis of data from clinical trials and the FRAES and DDInter databases.Attention should be given not only to common ADRs but also to ADRs not reported in drug instructions,and potential drugs that can induce drug–drug interactions.展开更多
In the present study,a comprehensive systematic review and meta-analysis were conducted to assess the short-term efficacy and safety of blonanserin compared with control interventions,including placebo,risperidone,and...In the present study,a comprehensive systematic review and meta-analysis were conducted to assess the short-term efficacy and safety of blonanserin compared with control interventions,including placebo,risperidone,and haloperidol,in the treatment of schizophrenia.The goal was to provide a robust pharmacological foundation to inform clinical decision-making regarding the therapeutic use of blonanserin.We systematically searched five major databases-PubMed,Web of Science,Scopus,CNKI,and the WanFang Database-for randomized controlled trials(RCTs)evaluating blonanserin against standard comparators in patients with schizophrenia.Key data extracted included study authorship,publication year,geographic location,diagnostic criteria,sample size,treatment duration,dosing regimen,and clinical outcomes.Meta-analytic synthesis was performed using RevMan 5.3 software.Out of an initial pool of 718 articles,11 trials met the inclusion criteria and were incorporated into the final analysis.In terms of clinical efficacy,short-term administration of blonanserin demonstrated non-inferiority to risperidone,with no indication of inferior performance across Positive and Negative Syndrome Scale(PANSS)subscales.Moreover,blonanserin significantly outperformed the placebo in terms of PANSS response rates,underscoring its therapeutic potential in managing acute symptoms.Regarding safety,the incidence of overall and serious adverse events did not differ significantly between blonanserin and the comparator agents.However,noteworthy distinctions were observed in the adverse event profiles(≥5%incidence in either group),underscoring differences in tolerability among the antipsychotics examined.These findings collectively supported the short-term use of blonanserin as a viable and well-tolerated alternative in the pharmacological management of schizophrenia.展开更多
Central nervous system(CNS)tumors are the most common solid tumors in pediatric patients and the leading cause of childhood cancer-relatedmortality.Their rarity compared to adult cancers hasmade enrolling sufficient c...Central nervous system(CNS)tumors are the most common solid tumors in pediatric patients and the leading cause of childhood cancer-relatedmortality.Their rarity compared to adult cancers hasmade enrolling sufficient cases for clinical trials challenging.Consequently,pediatric CNS tumors were long treated with adult protocols despite distinct biological and clinical characteristics.This review examines key aspects of phase I pediatric oncology trials,including study design,primary outcomes,and pharmacological approaches,along with secondary considerations like clinical responses and ethical aspects.Firstly,we evaluated all phase I trial protocols focusing on pediatric CNS tumors with accessible results published in scientific databases(Pubmed,Scopus,Embase,Web of Science,and Google Scholar)from 1990 toNovember 2024.Secondly,we searched EudraCT and ClinicalTrials.gov on 30November 2024 for ongoing trials.Our search yielded 60 completed phase I studies and 15 trials in progress.Dividing them by chronological order revealed that study designs and the response assessments evolved as the understanding of CNS tumor biology increased.Despite advancements improving diagnosis,management,and prognostication,mortality remains high,and morbidity persists.Notably,pediatric pharmacokinetics and pharmacodynamics differ from adults,complicating trial comparisons and dosage optimization.Future efforts should focus on large-scale clinical data collection to enhance trial efficiency.展开更多
BACKGROUND Regulatory agencies are increasingly recognizing that minority trial repres-entation is inadequate,contributing to healthcare disparities.The scope of min-ority population disparities in clinical trial part...BACKGROUND Regulatory agencies are increasingly recognizing that minority trial repres-entation is inadequate,contributing to healthcare disparities.The scope of min-ority population disparities in clinical trial participation remains unclear,as previous studies have compiled enrollment data from published trials,which AIM To evaluate sex,racial and ethnic inequities in liver transplantation(LT)trials participation in the United States.METHODS We used data from completed United States liver transplant clinical trials registered and reported on the National Institute of Health(NIH)website(clincaltrials.gov).Demographic data,including race,ethnicity,sex,and age were collected.To make inferences to a larger population,95%CIs were computed for estimates in each demographic group using the Wilson method for binomial proportions.We also computed the simultaneous 95%CIs by applying a Bonferroni correction to reflect the multinomial distribution of race proportions.The numbers and percentages of racial/ethnic minority and female individuals compared with United States census data from 2010 and 2018.Secondary outcome measures were inclusion by trial funding source and year of completion.RESULTS A total of 69 United States based clinical trials involving 6990 participants were included in the analysis.Of these,35 trials(51%)were randomized,and 26(38%)were conducted across multiple United States regions.All trials reported sex,while 42(61%)reported race and 27(39%)reported ethnicity.Compared to United States census data,Asian individuals were overrepresented(9.3%;95%CI:8.1%-10.5%),whereas African American(7.8%;95%CI:6.7%-8.9%)and American Indian or Alaska Native individuals(0.4%;95%CI:0.1%-0.6%)were underrepresented.The proportion of White participants(75.9%;95%CI:74.1%-77.7%)was consistent with census estimates.Hispanic participants were underrepresented(13.3%;95%CI:12.2%-14.5%)regardless of the census year referenced.In industry-sponsored trials,Asian representation was three times higher than in the general population(15%).NIH funded trials showed overrepresentation of White participants(83.8%)and underrepresentation of Black participants(4.1%)relative to census data.Women comprised 31.1%of all participants(95%CI:30.0%-32.2%),in-dicating underrepresentation.Among trials that reported racial data,62(90%)did not include participants of American Indian or Alaska Native,Native Hawaiian,or Pacific Islander descent.CONCLUSION Our analysis indicates that women,African Americans,and Hispanic individuals are underrepresented in LT clinical trials compared to the general United States population.These results highlight the need for regulatory initiatives aimed at enhancing the inclusion of historically marginalized racial and ethnic groups in clinical re-search.展开更多
Background:The use of inserted sham acupuncture as a placebo in randomized controlled trials(RCTs)is controversial,because it may produce specific effects that cause an underestimation of the effect of acupuncture tre...Background:The use of inserted sham acupuncture as a placebo in randomized controlled trials(RCTs)is controversial,because it may produce specific effects that cause an underestimation of the effect of acupuncture treatment.Objective:This systematic survey investigates the magnitude of insert-specific effects of sham acupuncture and whether they affect the estimation of acupuncture treatment effects.Search strategy:PubMed,Embase and Cochrane Central Register of Controlled Trials were searched to identify acupuncture RCTs from their inception until December 2022.Inclusion criteria:RCTs that evaluated the effects of acupuncture compared to sham acupuncture and no treatment.Data extraction and analysis:The total effect measured for an acupuncture treatment group in RCTs were divided into three components,including the natural history and/or regression to the mean effect(controlled for no-treatment group),the placebo effect,and the specific effect of acupuncture.The first two constituted the contextual effect of acupuncture,which is mimicked by a sham acupuncture treatment group.The proportion of acupuncture total effect size was considered to be 1.The proportion of natural history and/or regression to the mean effect(PNE)and proportional contextual effect(PCE)of included RCTs were pooled using meta-analyses with a random-effect model.The proportion of acupuncture placebo effect was the difference between PCE and PNE in RCTs with non-inserted sham acupuncture.The proportion of insert-specific effect of sham acupuncture(PIES)was obtained by subtracting the proportion of acupuncture placebo effect and PNE from PCE in RCTs with inserted sham acupuncture.The impact of PIES on the estimation of acupuncture's treatment effect was evaluated by quantifying the percentage of RCTs that the effect of outcome changed from no statistical difference to statistical difference after removing PIES in the included studies,and the impact of PIES was externally validated in other acupuncture RCTs with an inserted sham acupuncture group that were not used to calculate PIES.Results:This analysis included 32 studies with 5492 patients.The overall PNE was 0.335(95%confidence interval[CI],0.255-0.415)and the PCE of acupuncture was 0.639(95%CI,0.567-0.710)of acupuncture's total effect.The proportional contribution of the placebo effect to acupuncture's total effect was 0.191,and the PIES was 0.189.When we modeled the exclusion of the insert-specific effect of sham acupuncture,the acupuncture treatment effect changed from no difference to a significant difference in 45.45%of the included RCTs,and in 40.91%of the external validated RCTs.Conclusion:The insert-specific effect of sham acupuncture in RCTs represents 18.90%of acupuncture's total effect and significantly affects the evaluation of the acupuncture treatment effect.More than 40%of RCTs that used inserted sham acupuncture would draw different conclusions if the PIES had been controlled for.Considering the impact of the insert-specific effect of sham acupuncture,caution should be taken when using inserted sham acupuncture placebos in RCTs.展开更多
BACKGROUND Systematic reviews(SRs)synthesize and evaluate data,mainly from randomized trials,which then guides the development of clinical recommendations in evidence-based medicine.However,the data and methodological...BACKGROUND Systematic reviews(SRs)synthesize and evaluate data,mainly from randomized trials,which then guides the development of clinical recommendations in evidence-based medicine.However,the data and methodological information in the included papers can often be lacking or unclear,and reviewers usually need to contact the authors of included studies for clarifications.Contacting authors is recommended,but it is unclear how often SR teams do it,or what the level of response is.AIM To investigate how often reviewers undertake contact with the authors of included randomized controlled trials(RCTs)for clarification on data and risk of bias concerns,to explore the factors that influence whether SR authors contact or do not contact the authors,and the content and level of responses.METHODS We conducted a systematic electronic database search in MEDLINE using the search string“(systematic review)”AND“(RCT OR randomized OR trial)”for articles published between 1 January 2024 and 19 February 2024,without language restrictions.Screening and data extraction was done independently by two reviewers,and conflicts resolved by a senior author.Contact authors of included SRs were contacted for clarifications.RESULTS Of the 329 included SRs,38%(n=125)explicitly mentioned contact with the authors of included studies.The remaining 62%(n=204)did not.We attempted contact with all SR teams for clarifications and received 90 responses(19.4%).Of the 50 respondents who did not explicitly mention contact in their SRs,25(50%)replied that they did make contact.We received a total of 64 responses on the level and content of information sought.The mean±SD contacts SR teams made were 10(10),replies received 5(6.7),and response waiting time 10.1(28.3)weeks.Resources,time,poor previous experience,perceived likelihood of poor response and bias concerns were reported as barriers to attempting contact.CONCLUSION The majority of SRs published in 2024 did not confirm seeking clarifying or missing information from primary study authors.However,SR teams reported that 50%of contacted primary authors respond.Additional research can clarify this rate of response and establish methods to increase the integration of this core methodological element in SRs.展开更多
基金Supported by National Natural Science Foundation of China,No.82374200Construction of Traditional Chinese Medicine Inheritance and Innovation Development Demonstration Pilot Projects in Pudong New Area-High-Level Research-Oriented Traditional Chinese Medicine Hospital Construction,No.YC-2023-0901.
文摘Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized byclinical symptoms of diarrhea and mucopurulent bloody stools, and its incidenceis increasing globally. The etiology and pathogenesis of UC remain elusive. Currenttherapeutic approaches, including anti-inflammatory, immunosuppressiveand immunomodulating agents, are often limited in efficacy and frequently associatedwith adverse drug reactions. Therefore, there is an urgent need to developsafer and more effective treatment strategies to address the limitations of existingtherapies. Scutellaria baicalensis Georgi (HQ), a traditional Chinese medicinal herb,has been employed in the treatment of UC for over 2000 years. Recent studieshave demonstrated that HQ contains multiple active components capable oftreating UC through anti-inflammation, immune modulation, intestinal barrierprotection, antioxidant activity, and regulation of the gut microbiota. This paperreviews recent studies on the mechanism of action and clinical trials of HQ intreating UC based on relevant literature, with the aim of providing valuable insightsinto future treatment approaches.
基金supported by the National Key Research and Development Program of China(No.2022YFC3602500)Beijing High-level Public Health Technical Talents Construction Project(Discipline Leader-03-24)Beijing Hospitals Authority’s Ascent Plan(DFL20240601).
文摘OBJECTIVE To evaluate the safety and effectiveness of robot-assisted percutaneous coronary intervention(R-PCI)compared to traditional manual percutaneous coronary intervention(M-PCI).METHODS This prospective,multicenter,randomized controlled,non-inferior clinical trial enrolled patients with coronary heart disease who met the inclusion criteria and had indications for elective percutaneous coronary intervention.Participants were randomly assigned to either the R-PCI group or the M-PCI group.Primary endpoints were clinical and technical success rates.Clinical success was defined as visually estimated residual post-percutaneous coronary intervention stenosis<30% with no 30-day major adverse cardiac events.Technical success in the R-PCI group was defined as successful completion of percutaneous coronary intervention using the ETcath200 robot-assisted system,without conversion to M-PCI in the event of a guidewire or balloon/stent catheter that was unable to cross the vessel or was poorly supported by the catheter.Secondary endpoints included total procedure time,percutaneous coronary intervention procedure time,fluoroscopy time,contrast volume,operator radiation exposure,air kerma,and dose-area product.RESULTS The trial enrolled 152 patients(R-PCI:73 patients,M-PCI:79 patients).Lesions were predominantly B2/C type(73.6%).Both groups achieved 100% clinical success rate.No major adverse cardiac events occurred during the 30-day follow-up.The R-PCI group had a technical success rate of 100%.The R-PCI group had longer total procedure and fluoroscopy times,but lower operator radiation exposure.The percutaneous coronary intervention procedure time,contrast volume,air kerma,and dose-area product were similar between the two groups.CONCLUSIONS For certain complex lesions,performing percutaneous coronary intervention using the ETcath200 robot-assisted system is safe and effective and does not result in conversion to M-PCI.
基金Supported by the Fund of National Project of High.technicResearch and Development,(No.2003AA223269)
文摘Objective： To evaluate the effectiveness and safety of lyophilized Salvia salt of lithospermic acid powder for injection （SSLA） in treating coronary heart diseases angina pectoris （CHD-AP） of Xin-blood stasis syndrome type, and to conduct the non-inferiority trial with Danshen injection （丹参注射液, DSI） as positive control. Methods： An non-inferiority clinical layered, segmented, randomized, and blinded trial on three parallel and multiple centered groups was conducted in 480 patients with stable effort angina grade Ⅰ , Ⅱand Ⅲ, who had two or more times of attack every week. The 240 patients in test group A were treated with SSLA 200 mg added in 250 ml of 5% glucose solution for intravenous dripping every day; the 120 patients in test group B were treated with SSLA but the dosage doubled; and the 120 patients in the control group were treated with DSI 20 ml daily in the same method as SSLA was given. The clinical effectiveness and safety were evaluated after the patients were treated for 14 days. Results： The results showed that the markedly effective rate in test groups A, B and control group was 37.45 %, 36.75 % and 30.09 % respectively, while the total effective rate in them was 88.09%, 89.74% and 67.26% respectively. Statistical significance was shown in comparisons of the therapeutic effect between control group with test group A and test group B, with that in the two test groups superior to that in the control group, and non-inferiority trial showed eligibility （P〈0.01）. Adverse reaction appeared in 8 patients in the test groups and 2 in the control group. Conclusion： SSLA has definite therapeutic effect in treating patients with CHD-AP, with its effect not inferior to that of DSI, and no evident toxic-adverse reaction.
基金funding from Chugai Pharmaceutical Co.Ltd.Roche Korea Co.Ltd.Roche Shanghai.Co.Ltd
文摘Background: Capecitabine and irinotecan combination therapy(XELIRI) has been examined at various dose levels to treat metastatic colorectal cancer(m CRC). Recently, in the Association of Medical Oncology of the German Cancer Society(AIO) 0604 trial, tri?weekly XELIRI plus bevacizumab, with reduced doses of irinotecan(200 mg/m^2 on day 1) and capecitabine(1600 mg/m^2 on days 1–14), repeated every 3 weeks, has shown favorable tolerability and eicacy which were comparable to those of capecitabine and oxaliplatin(XELOX) plus bevacizumab. The doses of capecit?abine and irinotecan in the AIO trial are considered optimal. In a phase I/II study, XELIRI plus bevacizumab(BIX) as second?line chemotherapy was well tolerated and had promising eicacy in Japanese patients.Methods: The Asian XELIRI Projec T(AXEPT) is an East Asian collaborative, open?labelled, randomized, phase Ⅲ clinical trial which was designed to demonstrate the non?inferiority of XELIRI with or without bevacizumab versus standard FOLFIRI(5?fluorouracil, leucovorin, and irinotecan combination) with or without bevacizumab as second?line chemo?therapy for patients with m CRC. Patients with 20 years of age or older, histologically conirmed m CRC, Eastern Coop?erative Oncology Group performance status 0–2, adequate organ function, and disease progression or intolerance of the irst?line regimen will be eligible. Patients will be randomized(1:1) to receive standard FOLFIRI with or with?out bevacizumab(5 mg/kg on day 1), repeated every 2 weeks(FOLIRI arm) or XELIRI with or without bevacizumab(7.5 mg/kg on day 1), repeated every 3 weeks(XELIRI arm). A total of 464 events were estimated as necessary to show non?inferiority with a power of 80% at a one?sided α of 0.025, requiring a target sample size of 600 patients. The 95% conidence interval(CI) upper limit of the hazard ratio was pre?speciied as less than 1.3.Conclusion: The Asian XELIRI Projec T is a multinational phase III trial being conducted to provide evidence for XELIRI with or without bevacizumab as a second?line treatment option of mCRC.
基金supported by the National High-Level Chinese Medicine Hospital Clinical Research Funding(No.DFGZRB-2024GJRC015)。
文摘Acupuncture is an ancient treatment method used in traditional Chinese medicine and has been popularized worldwide.Over the past decade,there has been an increase in the amount of acupuncture research,mostly comprised of randomized controlled trials(RCTs)that aimed to answer the question on the efficacy of acupuncture.However,poor methodology and low replicability in these acupuncture RCTs have resulted in uncertainty about the efficacy of acupuncture.In this review,current advancements and challenges in acupuncture RCTs,regarding the methodological aspects of randomization,blinding,sham acupuncture and quality of reporting,were discussed.While there have been advancements in various aspects,current acupuncture RCTs still face pressing issues such as inadequate randomization and blinding,unviable sham acupuncture controls,and poor reporting quality.Given these limitations,this review seeks to identify the methodological problems that are responsible for these problems and to suggest solutions that could help to overcome them so as to improve the quality of future studies evaluating the efficacy of acupuncture.
文摘Objective Helicobacter pylori(HP)infection is associated with non-alcoholic fatty liver disease(NAFLD)and insulin resistance;however,the correlation between HP eradication and NAFLD remains controversial.This systematic review and meta-analysis examined the effect of HP treatment on clinical and laboratory parameters in NAFLD patients.Methods We conducted a literature search of the PubMed,Embase,Scopus,and Web of Science databases through Septem-ber 2023 for randomized controlled trials(RCTs)examining the effect of HP treatment on NAFLD patients versus lifestyle changes alone.The primary outcome was the change in steatosis parameters.The secondary endpoints were changes in anthropometric parameters,inflammatory markers(TNF-α),and metabolic parameters(fasting blood glucose,homeostasis model assessment of insulin resistance,AST/ALT,and lipid profile).The random effects model was used to calculate the standardized mean difference(SMD)with associated 95%confidence intervals(CIs)for our desired outcome.Results Four RCTs met our inclusion criteria.A total of 453 patients were included(mean age 42.8 years,58.5%males),228(50.3%)of whom were in the HP eradication group and 225(49.7%)of whom were in the lifestyle modification group.Compared with lifestyle modification alone,HP eradication had a significant effect on reducing liver steatosis and TNF-αlevels(SMD:-0.9;95%CI-14.67,-3.82,I^(2)=0%and SMD:-6.3;95%CI-9.04,-3.56,I^(2)=0%,respectively).No sig-nificant effect on other metabolic parameters was found.Conclusions HP eradication significantly reduced liver steatosis and TNF-αlevels in NAFLD patients.However,HP eradi-cation did not significantly affect other metabolic indices compared to lifestyle changes alone.
基金the“Hundreds and Tens of Thousands”Talent Project(Qihuang Project)Qihuang Scholars Project of Traditional Chinese Medicine Inheritance and Innovation(No.020450003)。
文摘OBJECTIVE:To investigate the effectiveness and safety of Guilingji capsule(龟龄集胶囊,GLJC)in treatment of Alzheimer's disease(AD)patients with kidney-marrow deficiency pattern(KMDP)compared with gingko extract tablets.METHODS:This is a secondary analysis of a large-scale multicenter randomized non-inferiority clinical trial.A total of 120 AD patients with KMDP were enrolled in this study.The participants were randomly categorized into two groups:(a)GLJC group(n=60)and(b)gingko group(n=60).The GLJC group was treated with GLJC and gingko extract mimetic tablets,whereas the gingko group received gingko extract tablets and mimetic GLJC.The data on the Mini-Mental State Examination(MMSE),Alzheimer's Disease Assessment Scale-Cognitive Subscale(ADAS-Cog),Activities of Daily Living(ADL),and Chinese Medicine Symptom Scale(CM-SS)was evaluated at 0,12,and 24 weeks of treatment.The serum levels of acetylcholine(Ach),acetylcholinesterase(AchE),B-cell lymphoma-2(Bcl-2),and Bcl-2-associated X protein(Bax)in the participants were measured before and after 24 weeks of treatment.The safety was based on the incidence of adverse events.RESULTS:Both interventions significantly increased the MMSE scores of the participants and decreased their ADAS-Cog,ADL,and CM-SS scores(P<0.01).Compared with the gingko group,the GLJC group had a higher effective rate of improvement in the symptoms of“amnesia”and“dull expression and slow thinking”at the 12th week and 24th week(P<0.05,P<0.01).In the GLJC group,serum Bcl-2 levels were significantly increased at the 24th week(P<0.05).Serum Bax and AchE levels of the two groups were significantly decreased at the 24th week(P<0.01).No treatmentrelated adverse events were reported in the two groups.CONCLUSIONS:GLJC is equivalent to the gingko extract tablets in terms of improving cognitive function and the quality of life in AD patients with KMDP and has good clinical efficacy and safety.When it comes to improving TCM symptoms and anti-aging,GLJC is even more advantageous.
文摘OBJECTIVE:In recent years,the number of clinical research reports on acupuncture and manipulation for the treatment of greater occipital neuralgia has gradually increased,but the quality is uneven.There is currently no literature evaluating the quality of published reports,which is not conducive to the promotion of clinical use of these therapies.Therefore,this article assessed the reporting quality of randomized controlled trials on acupuncture and manipulation for greater occipital neuralgia.METHODS:Cochrane Library,PubMed,Web of Science,Embase,China National Knowledge Infrastructure(CNKI),VIP,WanFang Data,and Chinese BioMedical Literature Database(CBM)from inception to May 20,2024 were searched.The reporting quality of included randomized controlled trials was independently evaluated by two investigators using the CONSORT statement,STRICTA checklist,and Cochrane bias of risk assessment tool.A third investigator resolved any disagreement.RESULTS:A total of 62 articles were included.Based on the CONSORT statement,59.46%(22/37)of all entries had a reporting rate of less than 50%,mainly including“Identification as a randomized trial in the title(1/62,1.61%),”“How sample size was determined(7/62,11.29%),”“Implementation(1/62,1.61%),”“Blinding(1/62,1.61%),”and“Reports of Funding(4/62,6.45%).”According to the STRICTA checklist,29.41%(5/17)of all entries had a reporting rate of less than 50%,mainly including“Details of other interventions(7/58,12.07%),”“Setting and context of treatment(0/58,0%),”and“Description of participating acupuncturists(0/58,0%).”CONCLUSION:The reporting quality of randomized controlled trials on acupuncture and manipulation therapy for greater occipital neuralgia remains low.Future researchers need to make greater efforts to strictly adhere to the CONSORT statement and STRICTA checklist during trial design,implementation,and reporting.This will facilitate the standardization of research in this field and enhance the reliability and reproducibility of the research results.
文摘Since 2016,the number of clinical trials registered in the World Health Organization-International Clinical Trials Registry Platform has been steadily increasing.The number of clinical trials registered between 2018 and 2022 is 39765 for BRICS countries.Though India’s contribution increased from 33%to 40%in the interim,the number of infectious disease trials registered in India is low(325)compared to the number of oncology clinical trials(1936)[1].The number of phase 3 registrational antibacterial clinical trials conducted in India is also low(Table 1).This poses a serious public health challenge given the infectious disease burden in India[2].
文摘The NI （non-inferiority） trial design based on the likelihood ratio test eliminates the dependency on the conventional NI margin, and it explicitly uses the MCID （minimum clinical important difference） that links the statistical analysis to the clinical sense. Different from the conventional trial design, the new methodology is self-adaptive to the change in the sample size and overall cure rate, and it has an asymptotic property. It is shown that MCID is de-composite into constant MCID and statistical MCID. Along with this concept, the concept of the allowed inferiority does not exist, the interpretation of the trial result is more accurate and consistent to the statistical theory as well as the clinical interpretations.
基金Supported by the National Natural Science Foundation of China:82074529Guangdong Province Famous Traditional Chinese Medicine Inheritance Studio Construction Project:Guangdong Traditional Chinese Medicine Office Letter 2023_108+1 种基金Sanming Project of Medicine in Shenzhen:SZZYSM202108013Hainan General Hospital Science and Technology Start-up Fund for Braught-in Talents:YJRC2022001。
文摘Objectives:This study aims to evaluate the current state of acupuncture randomized controlled trials(RCTs),their impact on guidelines,and future development trends,providing a reference for future re-search directions.Methods:Search for acupuncture-related RCT articles in the Web of Science Core Collection and con-firm their guideline inclusion on Google Scholar.Analyze study characteristics to predict future research directions.Results:The analysis covered 1422 articles,reflecting a substantial rise in publications from 77 articles between 1993 and 2002 to 960 articles between 2013 and 2022.The Western Pacific region led in pub-lication numbers with 622 articles(43.7%),followed by Europe(466 articles;32.8%),Americas(250 articles;17.6%),Eastern Mediterranean(62 articles;4.4%),and Southeast Asia(22 articles;1.5%),with Africa showing a research void.Regrettably,only 29.6%(421 articles)were incorporated into guidelines.The low rate of inclusion of research results in guidelines and the uneven distribution of research fields are particularly prominent.From 1993 to 2002,there were 77 articles,among which 51(66.2%)were included in the guidelines;from 2003 to 2012,there were 385 articles,with 202(52.5%)included;from 2013 to 2022,there were 960 articles,and only 168(17.5%)were included,showing a decreasing trend in the inclusion rate year by year.Regarding geographical distribution,1167 articles were from the East-ern Hemisphere,with 326(27.9%)included;255 were from the Western Hemisphere,and 95(37.3%)were included.Regionally,179 articles(42.5%)from Europe were included,140(33.3%)from the West-ern Pacific,95(22.6%)from the Americas,6(1.4%)from the Eastern Mediterranean,and 1(0.2%)from Southeast Asia.China,the United States,and Germany were the top publishing countries,with consis-tent growth in countries like China,South Korea,Spain,Brazil,Turkey,and Iran.Noteworthy researchers such as Cesar Fernandez-de-las-Penas,Zhi-shun LIU,Jing-wen YANG,Cun-zhi LIU,Li-xing LAO,Stefan N Willich,and Benno Brinkhaus have collaborated on research in areas such as pain management,cognitive impairments,insomnia,digestive system diseases,and urinary system diseases.There has been a partic-ular increase in research focus on neck pain and myofascial trigger points.
基金supported by grants from the National Natural Science Foundation of China(82200212)and(81902934).
文摘Objective This study aimed to analyze the adverse effects(AEs)of sacituzumab govitecan(SG)through multiple sources of data to provide a reference for clinical safety management.Methods Clinical trials of SG with available safety data were retrieved and included in the pooled analysis.The adverse drug reaction(ADR)signals of SG were collected from the FDA Adverse Event Reporting System(FAERS)database.Drug interactions with SG in the DDInter database were summarized.Results A total of 6 clinical trials involving 1737 patients were included in the pooled analysis,and the most common AEs of≥grade 3 were neutropenia(46%),leukopenia(13%),and anemia(8%).In the pharmacovigilance study,1024 AE reports were extracted,and the most common toxicities of SG were hematologic and gastrointestinal.AEs not included in the drug instructions also presented high signals,such as meningitis,colitis and lymphedema.A total of 40 drugs identified could induce drug–drug interactions when they were concomitantly administered with SG.Conclusions This study provides the most comprehensive profile of SG toxicity on the basis of data from clinical trials and the FRAES and DDInter databases.Attention should be given not only to common ADRs but also to ADRs not reported in drug instructions,and potential drugs that can induce drug–drug interactions.
基金The Guangdong Provincial Hospital Pharmacy Research Fund(Grant No.2024A34)the Guangdong Provincial Medical Research Fund(Grant Nos.A2024493,A2024771)+2 种基金the International Medical Exchange Foundation of China(Grant No.Z-2014-08-2309-5)the Science and Technology Program of Guangzhou(Grant Nos.20251A011047,20252A011018)the Guangzhou Municipal Key Discipline in Medicine(Suiwei Letter[2024]No.2184)。
文摘In the present study,a comprehensive systematic review and meta-analysis were conducted to assess the short-term efficacy and safety of blonanserin compared with control interventions,including placebo,risperidone,and haloperidol,in the treatment of schizophrenia.The goal was to provide a robust pharmacological foundation to inform clinical decision-making regarding the therapeutic use of blonanserin.We systematically searched five major databases-PubMed,Web of Science,Scopus,CNKI,and the WanFang Database-for randomized controlled trials(RCTs)evaluating blonanserin against standard comparators in patients with schizophrenia.Key data extracted included study authorship,publication year,geographic location,diagnostic criteria,sample size,treatment duration,dosing regimen,and clinical outcomes.Meta-analytic synthesis was performed using RevMan 5.3 software.Out of an initial pool of 718 articles,11 trials met the inclusion criteria and were incorporated into the final analysis.In terms of clinical efficacy,short-term administration of blonanserin demonstrated non-inferiority to risperidone,with no indication of inferior performance across Positive and Negative Syndrome Scale(PANSS)subscales.Moreover,blonanserin significantly outperformed the placebo in terms of PANSS response rates,underscoring its therapeutic potential in managing acute symptoms.Regarding safety,the incidence of overall and serious adverse events did not differ significantly between blonanserin and the comparator agents.However,noteworthy distinctions were observed in the adverse event profiles(≥5%incidence in either group),underscoring differences in tolerability among the antipsychotics examined.These findings collectively supported the short-term use of blonanserin as a viable and well-tolerated alternative in the pharmacological management of schizophrenia.
文摘Central nervous system(CNS)tumors are the most common solid tumors in pediatric patients and the leading cause of childhood cancer-relatedmortality.Their rarity compared to adult cancers hasmade enrolling sufficient cases for clinical trials challenging.Consequently,pediatric CNS tumors were long treated with adult protocols despite distinct biological and clinical characteristics.This review examines key aspects of phase I pediatric oncology trials,including study design,primary outcomes,and pharmacological approaches,along with secondary considerations like clinical responses and ethical aspects.Firstly,we evaluated all phase I trial protocols focusing on pediatric CNS tumors with accessible results published in scientific databases(Pubmed,Scopus,Embase,Web of Science,and Google Scholar)from 1990 toNovember 2024.Secondly,we searched EudraCT and ClinicalTrials.gov on 30November 2024 for ongoing trials.Our search yielded 60 completed phase I studies and 15 trials in progress.Dividing them by chronological order revealed that study designs and the response assessments evolved as the understanding of CNS tumor biology increased.Despite advancements improving diagnosis,management,and prognostication,mortality remains high,and morbidity persists.Notably,pediatric pharmacokinetics and pharmacodynamics differ from adults,complicating trial comparisons and dosage optimization.Future efforts should focus on large-scale clinical data collection to enhance trial efficiency.
文摘BACKGROUND Regulatory agencies are increasingly recognizing that minority trial repres-entation is inadequate,contributing to healthcare disparities.The scope of min-ority population disparities in clinical trial participation remains unclear,as previous studies have compiled enrollment data from published trials,which AIM To evaluate sex,racial and ethnic inequities in liver transplantation(LT)trials participation in the United States.METHODS We used data from completed United States liver transplant clinical trials registered and reported on the National Institute of Health(NIH)website(clincaltrials.gov).Demographic data,including race,ethnicity,sex,and age were collected.To make inferences to a larger population,95%CIs were computed for estimates in each demographic group using the Wilson method for binomial proportions.We also computed the simultaneous 95%CIs by applying a Bonferroni correction to reflect the multinomial distribution of race proportions.The numbers and percentages of racial/ethnic minority and female individuals compared with United States census data from 2010 and 2018.Secondary outcome measures were inclusion by trial funding source and year of completion.RESULTS A total of 69 United States based clinical trials involving 6990 participants were included in the analysis.Of these,35 trials(51%)were randomized,and 26(38%)were conducted across multiple United States regions.All trials reported sex,while 42(61%)reported race and 27(39%)reported ethnicity.Compared to United States census data,Asian individuals were overrepresented(9.3%;95%CI:8.1%-10.5%),whereas African American(7.8%;95%CI:6.7%-8.9%)and American Indian or Alaska Native individuals(0.4%;95%CI:0.1%-0.6%)were underrepresented.The proportion of White participants(75.9%;95%CI:74.1%-77.7%)was consistent with census estimates.Hispanic participants were underrepresented(13.3%;95%CI:12.2%-14.5%)regardless of the census year referenced.In industry-sponsored trials,Asian representation was three times higher than in the general population(15%).NIH funded trials showed overrepresentation of White participants(83.8%)and underrepresentation of Black participants(4.1%)relative to census data.Women comprised 31.1%of all participants(95%CI:30.0%-32.2%),in-dicating underrepresentation.Among trials that reported racial data,62(90%)did not include participants of American Indian or Alaska Native,Native Hawaiian,or Pacific Islander descent.CONCLUSION Our analysis indicates that women,African Americans,and Hispanic individuals are underrepresented in LT clinical trials compared to the general United States population.These results highlight the need for regulatory initiatives aimed at enhancing the inclusion of historically marginalized racial and ethnic groups in clinical re-search.
基金the National Key R&D Program of China(No.2023YFC3503300 and No.2023YFC3503304)National Natural Science Foundation of China for Distinguished Young Scholars(No.82225049)and Youths(No.82305045)Fundamental Research Funds for the Central Public Welfare Research Institutes(No.2020YJSZX-3)。
文摘Background:The use of inserted sham acupuncture as a placebo in randomized controlled trials(RCTs)is controversial,because it may produce specific effects that cause an underestimation of the effect of acupuncture treatment.Objective:This systematic survey investigates the magnitude of insert-specific effects of sham acupuncture and whether they affect the estimation of acupuncture treatment effects.Search strategy:PubMed,Embase and Cochrane Central Register of Controlled Trials were searched to identify acupuncture RCTs from their inception until December 2022.Inclusion criteria:RCTs that evaluated the effects of acupuncture compared to sham acupuncture and no treatment.Data extraction and analysis:The total effect measured for an acupuncture treatment group in RCTs were divided into three components,including the natural history and/or regression to the mean effect(controlled for no-treatment group),the placebo effect,and the specific effect of acupuncture.The first two constituted the contextual effect of acupuncture,which is mimicked by a sham acupuncture treatment group.The proportion of acupuncture total effect size was considered to be 1.The proportion of natural history and/or regression to the mean effect(PNE)and proportional contextual effect(PCE)of included RCTs were pooled using meta-analyses with a random-effect model.The proportion of acupuncture placebo effect was the difference between PCE and PNE in RCTs with non-inserted sham acupuncture.The proportion of insert-specific effect of sham acupuncture(PIES)was obtained by subtracting the proportion of acupuncture placebo effect and PNE from PCE in RCTs with inserted sham acupuncture.The impact of PIES on the estimation of acupuncture's treatment effect was evaluated by quantifying the percentage of RCTs that the effect of outcome changed from no statistical difference to statistical difference after removing PIES in the included studies,and the impact of PIES was externally validated in other acupuncture RCTs with an inserted sham acupuncture group that were not used to calculate PIES.Results:This analysis included 32 studies with 5492 patients.The overall PNE was 0.335(95%confidence interval[CI],0.255-0.415)and the PCE of acupuncture was 0.639(95%CI,0.567-0.710)of acupuncture's total effect.The proportional contribution of the placebo effect to acupuncture's total effect was 0.191,and the PIES was 0.189.When we modeled the exclusion of the insert-specific effect of sham acupuncture,the acupuncture treatment effect changed from no difference to a significant difference in 45.45%of the included RCTs,and in 40.91%of the external validated RCTs.Conclusion:The insert-specific effect of sham acupuncture in RCTs represents 18.90%of acupuncture's total effect and significantly affects the evaluation of the acupuncture treatment effect.More than 40%of RCTs that used inserted sham acupuncture would draw different conclusions if the PIES had been controlled for.Considering the impact of the insert-specific effect of sham acupuncture,caution should be taken when using inserted sham acupuncture placebos in RCTs.
文摘BACKGROUND Systematic reviews(SRs)synthesize and evaluate data,mainly from randomized trials,which then guides the development of clinical recommendations in evidence-based medicine.However,the data and methodological information in the included papers can often be lacking or unclear,and reviewers usually need to contact the authors of included studies for clarifications.Contacting authors is recommended,but it is unclear how often SR teams do it,or what the level of response is.AIM To investigate how often reviewers undertake contact with the authors of included randomized controlled trials(RCTs)for clarification on data and risk of bias concerns,to explore the factors that influence whether SR authors contact or do not contact the authors,and the content and level of responses.METHODS We conducted a systematic electronic database search in MEDLINE using the search string“(systematic review)”AND“(RCT OR randomized OR trial)”for articles published between 1 January 2024 and 19 February 2024,without language restrictions.Screening and data extraction was done independently by two reviewers,and conflicts resolved by a senior author.Contact authors of included SRs were contacted for clarifications.RESULTS Of the 329 included SRs,38%(n=125)explicitly mentioned contact with the authors of included studies.The remaining 62%(n=204)did not.We attempted contact with all SR teams for clarifications and received 90 responses(19.4%).Of the 50 respondents who did not explicitly mention contact in their SRs,25(50%)replied that they did make contact.We received a total of 64 responses on the level and content of information sought.The mean±SD contacts SR teams made were 10(10),replies received 5(6.7),and response waiting time 10.1(28.3)weeks.Resources,time,poor previous experience,perceived likelihood of poor response and bias concerns were reported as barriers to attempting contact.CONCLUSION The majority of SRs published in 2024 did not confirm seeking clarifying or missing information from primary study authors.However,SR teams reported that 50%of contacted primary authors respond.Additional research can clarify this rate of response and establish methods to increase the integration of this core methodological element in SRs.
