Five-Flavor Sophora flavescens Enteric-Coated Capsules for Ulcerative Colitis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

Background. Ulcerative colitis (UC), a chronic inflammatory bowel disease, is characterized by abdominal pain, diarrhea, and mucopurulent bloody stool. In recent years, the incidence and prevalence of UC have been increasing consistently. Five-flavor Sophora falvescens enteric-coated capsule (FSEC), a licensed Chinese patent medicine, was specifically used to treat UC. This review was aimed to assess the effectiveness and safety of FSEC for the treatment of UC. Methods. Six electronic databases were searched from inception to March 2021. Randomized clinical trials (RCTs) comparing FSEC or FSEC plus conventional Western medicine with conventional Western medicine in participants with UC were included. Two authors screened all references, assessed the risk of bias, and extracted data independently. Binary data were presented as risk ratios (RRs) with 95% confidence intervals (CIs) and metric data as mean difference (MD) with 95% CI. The overall certainty of the evidence was assessed by GRADE. Results. We included 15 RCTs (1194 participants, 763 in the FSEC group and 431 in the control group). The treatment duration ranged from 42 to 64 days. Twelve trials compared FSEC with conventional Western medicine, and two trials compared FSEC plus conventional medicine with conventional medicine. Another trial compared FSEC plus mesalazine with compound glutamine enteric capsules plus mesalazine. FSEC showed a higher clinical effective rate (improved clinical symptoms, colonoscopy results, and stools) (RR 1.12, 95% CI 1.05 to 1.20; 729 participants; 8 trials; low-quality evidence) as well as the effective rate of traditional Chinese medicine (TCM) syndromes (RR 1.10, 95% CI 1.01 to 1.20; 452 participants; 5 trials; low-quality evidence) compared to mesalazine. There was no significant difference in the adverse events between FSEC and control groups. Conclusions. FSEC may show effectiveness in UC treatment compared to conventional medicine, and the use of FSEC may not increase the risk of adverse events. Due to the limited number of clinical trials and low methodological quality of the included trials, our findings must be interpreted with discretion.

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Acupuncture for ulcerative colitis: a systematic review and meta-analysis of randomized clinical trials

BMC Complementary Medicine and Therapies ◽

10.1186/s12906-020-03101-4 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Xiao Wang ◽

Nan-qi Zhao ◽

Yu-xin Sun ◽

Xue Bai ◽

Jiang-tao Si ◽

...

Keyword(s):

Ulcerative Colitis ◽

Clinical Trials ◽

Clinical Effect ◽

Conventional Medicine ◽

Risk Of Bias ◽

Cochrane Library ◽

Stool Examination ◽

Moderate Quality ◽

Significant Difference ◽

Quality Evidence

Abstract Background Ulcerative colitis, characterized by diarrhea, bloody stools and abdominal pain, is a chronic, idiopathic inflammatory disease of the colonic mucosa. In recent years, the incidence of ulcerative colitis presents an increasing trend year by year. Acupuncture, as a potential effective treatment for ulcerative colitis, is widely used in clinical practice. Methods We searched PubMed, the Cochrane Library, Chinese CBM Database, China National Knowledge Infrastructure, Chinese VIP Information, and Wanfang Database from the date of the establishment of each database up to March, 2019. We included randomized controlled clinical trials (RCT) comparing acupuncture versus conventional conventional medicine or comparing acupuncture combined with conventional medicine versus conventional medicine in participants with ulcerative colitis. Two authors screened all references, assessed the risk of bias and extracted data independently. We summarized data using risk ratios (RR) with 95% confidence intervals (CI) for binary outcomes. We performed meta-analyses using random effects model. We assessed overall quality of evidence using GRADE. Results We included 13 RCTs (1030 participants, 515 in the acupuncture group and 515 in the control group). Only one study tested head acupuncture, and the other 12 tested body acupuncture. The treatment duration ranged from 14 to 60 days. Seven trials compared acupuncture alone versus conventional medicine, and six compared acupuncture combined with conventional medicine versus conventional medicine. Acupuncture combined with mesalazine showed better clinical effect (improved clinical symptoms, colonoscopy results and stool examination results) (RR 1.25, 95% CI 1.19 to 1.41; 232 participants; 4 trials; low quality evidence) and better colonoscopy curative effect (RR 1.33, 95% CI 1.04 to 1.71; 108 participants; 2 trials; moderate quality evidence) compared to mesalazine. Acupuncture showed better clinical effect compared to the combination of metronidazole and sulfasalazine (RR 1.21, 95%CI 1.10, 1.34; 318 participants; 3 trials; moderate quality evidence). There was no significant difference in the incidence of adverse events between groups. Conclusions Both acupuncture alone and acupuncture combined with conventional medicine may be effective in treating ulcerative colitis compared to conventional medicine. Our findings must be interpreted with caution due to high or unclear risk of bias of the included trials.

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Efficacy and Safety of Modified Duhuo Jisheng Decoction in the Treatment of Lumbar Disc Herniation: A Systematic Review and Meta-Analysis

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/2381462 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11

Author(s):

Zhencheng Xiong ◽

Ping Yi ◽

Liubo Zhang ◽

Haoning Ma ◽

Wenhao Li ◽

...

Keyword(s):

Adverse Events ◽

Western Medicine ◽

Total Effective Rate ◽

Lumbar Disc ◽

Meta Analysis ◽

Diclofenac Sodium ◽

Effective Rate ◽

Efficacy And Safety ◽

Cure Rate ◽

Enteric Coated

Objective. Lumbar disc herniation (LDH) is based on the degenerative changes of the intervertebral disc. Many drugs are used to treat and prevent LDH, including Western medicine and Chinese medicine. Duhuo Jisheng Decoction (DHJSD) is one of the most classic Chinese medicine prescriptions. The purpose of our meta-analysis is to evaluate the efficacy and safety of modified DHJSD in the treatment of LDH. Methods. We searched multiple databases including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI) databases, Wanfang Database, and Chinese Scientific Journal Database (VIP) to identify studies that met the inclusion criteria. This meta-analysis was registered at INPLASY with reference number ID: INPLASY202060053. Results. Fourteen randomized controlled trials (RCTs) were identified, including 1560 patients. This meta-analysis showed that the total effective rate and cure rate of modified DHJSD are higher than those of diclofenac sodium enteric-coated tablets (total effective rate: RR = 1.18, 95% CI: 1.12 to 1.25, P<0.0001, I2 = 0%; cure rate: RR = 1.60, 95% CI: 1.30 to 1.97, P<0.00001, I2 = 2%), diclofenac sodium enteric-coated tablets plus ibuprofen and indomethacin (total effective rate: RR = 1.23, 95% CI: 1.11 to 1.37, P=0.0001, I2 = 0%; cure rate: RR = 1.58, 95% CI: 1.22 to 2.04, P=0.0005, I2 = 0%), and diclofenac sodium sustained-release capsule (total effective rate: RR = 1.49, 95% CI: 1.27 to 1.74, P<0.00001, I2 = 0%; cure rate: RR = 10.07, 95% CI: 3.29 to 30.88, P<0.00001, I2 = 5%). Modified DHJSD was also better than Western medicine (MD = −1.56, 95% CI: −2.42 to −0.70, P=0.0004, I2 = 74%) in terms of visual analogue scale (VAS) scores. Three RCTs showed no adverse events in the modified DHJSD group, but adverse events existed in the Western medicine group. Conclusion. This meta-analysis showed that modified DHJSD had a more favorable effect on the treatment of LDH than Western medicine, and there were no obvious adverse events. More high-quality RCTs are needed to complement existing conclusions.

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The Detection of Adverse Events in Randomized Clinical Trials: Can we Really Say New Medicines are Safe?

Current Drug Safety ◽

10.2174/15748863113089990030 ◽

2013 ◽

Vol 8 (2) ◽

pp. 104-113 ◽

Cited By ~ 6

Author(s):

Izyan Wahab ◽

Nicole Pratt ◽

Lisa Kalisch ◽

Elizabeth Roughead

Keyword(s):

Clinical Trials ◽

Adverse Events ◽

Randomized Clinical Trials

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Adverse events of special interest in clinical trials of rheumatoid arthritis, psoriatic arthritis, ulcerative colitis and psoriasis with 37 066 patient-years of tofacitinib exposure

RMD Open ◽

10.1136/rmdopen-2021-001595 ◽

2021 ◽

Vol 7 (2) ◽

pp. e001595

Author(s):

Gerd R Burmester ◽

Peter Nash ◽

Bruce E Sands ◽

Kim Papp ◽

Lori Stockert ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Ulcerative Colitis ◽

Clinical Trials ◽

Psoriatic Arthritis ◽

Adverse Events ◽

Special Interest ◽

Phase 1 ◽

Incidence Rates ◽

Study Data ◽

System Organ Class

ObjectivesTo analyse adverse events (AEs) of special interest across tofacitinib clinical programmes in rheumatoid arthritis (RA), psoriatic arthritis (PsA), ulcerative colitis (UC) and psoriasis (PsO), and to determine whether the incidence rates (IRs; unique patients with events per 100 patient-years) of these events are consistent across diseases.MethodsThe analysis included data from patients exposed to ≥1 dose of tofacitinib in phase 1, 2, 3 or 3b/4 clinical trials and long-term extension (LTE) studies (38 trials) in RA (23 trials), PsA (3 trials), UC (5 trials) and PsO (7 trials). All studies were completed by or before July 2019, except for one ongoing UC LTE study (data cut-off May 2019). IRs were obtained for AEs of special interest.Results13 567 patients were included in the analysis (RA: n=7964; PsA: n=783; UC: n=1157; PsO: n=3663), representing 37 066 patient-years of exposure. Maximum duration of exposure was 10.5 years (RA). AEs within the ‘infections and infestations’ System Organ Class were the most common in all diseases. Among AEs of special interest, IRs were highest for herpes zoster (non-serious and serious; 3.6, 1.8, 3.5 and 2.4 for RA, PsA, UC and PsO, respectively) and serious infections (2.5, 1.2, 1.7 and 1.3 for RA, PsA, UC and PsO, respectively). Age-adjusted and sex-adjusted mortality ratios (weighted for country) were ≤0.2 across cohorts.ConclusionsThe tofacitinib safety profile in this analysis was generally consistent across diseases and with longer term follow-up compared with previous analyses.

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Recombinant Human Adenovirus-p53 Therapy for the Treatment of Oral Leukoplakia and Oral Squamous Cell Carcinoma: A Systematic Review

Medicina ◽

10.3390/medicina57050438 ◽

2021 ◽

Vol 57 (5) ◽

pp. 438

Author(s):

Jagadish Hosmani ◽

Shazia Mushtaq ◽

Shahabe Saquib Abullais ◽

Hussain Mohammed Almubarak ◽

Khalil Assiri ◽

...

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Oral Cancer ◽

Adverse Events ◽

Randomized Clinical Trials ◽

Oral Leukoplakia ◽

Research Articles ◽

Original Research ◽

Therapeutic Effects ◽

The World

Background and Objectives: Oral cancer is the 6th most common cancer in the world and oral leukoplakia is an oral potentially malignant disorder that could develop into oral cancer. This systematic review focusses on randomized clinical trials for recombinant adenovirus p-53 (rAD-p53) therapy for the treatment of oral leukoplakia and cancer. Materials and Methods: We searched for research articles on various databases such as Pubmed/Medline, Embase, CNKI (China National Knowledge Infra-structure), Springerlink, cochrane and Web of sciences from 2003 to 2020. MeSH (Medical Subject Headings) terms were used for the search. Inclusion criteria included original research, randomized clinical trials and articles only in English language. Exclusion criteria were any articles that were not research articles, not randomized trials, non-human studies, etc. The articles were further graded on the Jadad scale. Results: 578 articles were assessed from various databases; only 3 articles were found to be appropriate for this review. Thus, meta-analysis was not performed because of heterogeneity and lack of data. In the three studies, whether rAD-p53 was used as a standalone therapy or with other therapies, there was a beneficial effect of the therapy. Furthermore, there were no serious adverse events and the only adverse events reported were fever, pain at the local injection site, flu-like symptoms and lowered WBC count. Conclusions: Thus, we can conclude that this therapy has a potential for beneficial therapeutic effects and further clinical trials with more patients need to be performed to get better understanding of the effect of rAD-p53 therapy, which probably will pave the way to its approval in other parts of the world.

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Impact of body mass index on survival and serious adverse events in advanced non-small cell lung cancer treated with bevacizumab: a meta-analysis of randomized clinical trials

Current Medical Research and Opinion ◽

10.1080/03007995.2021.1900091 ◽

2021 ◽

pp. 1-1

Author(s):

Soham Shukla ◽

Zachary Babcock ◽

Laura Pizzi ◽

Luigi Brunetti

Keyword(s):

Lung Cancer ◽

Body Mass Index ◽

Clinical Trials ◽

Adverse Events ◽

Small Cell Lung Cancer ◽

Randomized Clinical Trials ◽

Meta Analysis ◽

Small Cell ◽

Small Cell Lung ◽

Serious Adverse Events

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675 FUNDOPLICATION VERSUS ORAL PROTON PUMP INHIBITORS FOR GASTROESOPHAGEAL REFLUX DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED CLINICAL TRIALS

Diseases of the Esophagus ◽

10.1093/dote/doab052.675 ◽

2021 ◽

Vol 34 (Supplement_1) ◽

Author(s):

Luca Schiliró Tristão ◽

Francisco Tustumi ◽

Guilherme Tavares ◽

Letícia Nogueira Datrino ◽

Maria Carolina Andrade Serafim ◽

...

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Gastroesophageal Reflux Disease ◽

Gastroesophageal Reflux ◽

Adverse Events ◽

Proton Pump ◽

Reflux Disease ◽

Randomized Clinical Trials ◽

Meta Analysis ◽

Oral Intake

Abstract Gastroesophageal reflux disease (GERD) is a widely studied and highly prevalent condition. However, few is reported about the exact efficacy and safety of fundoplication (FPT) compared to oral intake proton-pump inhibitors (PPI). This systematic review and meta-analysis of randomized clinical trials (RCT) aims to compare PPI and FPT in relation to the efficacy, as well as the adverse events associated with these therapies. Methods This systematic review was guided by PRISMA statement. Search carried out in June 2020 was conducted on Medline, Cochrane, EMBASE and LILACS. The inclusion criteria were (I) patients with GERD; (II) Randomized clinical trials, comparing oral intake PPI with FPT; (III) relevant outcomes for this review. The exclusion criteria were (I) reviews, case reports, editorials and letters (II) transoral or endoscopic FPT (III) studies with no full text. No restrictions were set for language or period. Certainty of evidence and risk of bias were assessed with GRADE Pro and with Review Manager Version 5.4 bias assessment tool. Results Ten RCT were included. Meta-analysis showed that heartburn (RD = −0.19; 95% CI = −0.29, −0.09) was less frequently reported by patients that underwent FPT. Furthermore, patients undergoing surgery had greater pressure on the lower esophageal sphincter than those who used PPI (MD = 7.81; 95% CI 4.79, 10.83). There was no significant difference between groups in the percentage of time with pH less than 4 in 24 hours, sustained remission and Gastrointestinal Symptom Rating Scale. Finally, FPT did not increase significantly the risk for adverse events such as postoperative dysphagia and impaired belching. Conclusion FPT is a more effective therapy than PPI treatment for GERD, without significantly increasing the risk for adverse events. However, before indicating a possible surgical approach, it is extremely important to correctly assess and select the patients who would benefit from FPT, such as those with severe erosive esophagitis, severe respiratory symptoms, low adherence to continuous drug treatment and patients with non-acid reflux, to ensure better results.

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Opportunities for selective reporting of harms in randomized clinical trials: Selection criteria for nonsystematic adverse events

10.21203/rs.2.268/v1 ◽

2019 ◽

Author(s):

Evan Mayo-Wilson ◽

Nicole Fusco ◽

Hwanhee Hong ◽

Tianjing Li ◽

Joseph K. Canner ◽

...

Keyword(s):

Clinical Trials ◽

Adverse Events ◽

Selection Criteria ◽

Randomized Clinical Trials ◽

Bipolar Depression ◽

Selective Reporting ◽

Journal Articles ◽

Multiple Sources ◽

Study Results ◽

Meta Analyses

Abstract Background: Adverse events (AEs) in randomized clinical trials may be reported in multiple sources. Different methods for reporting adverse events across trials, or across sources for a single trial, may produce inconsistent and confusing information about the adverse events associated with interventions Methods: We sought to compare the methods authors use to decide which AEs to include in a particular source (i.e., “selection criteria”) and to determine how selection criteria could impact the AEs reported. We compared sources (e.g., journal articles, clinical study reports [CSRs]) of trials for two drug-indications: gabapentin for neuropathic pain and quetiapine for bipolar depression. We identified selection criteria and assessed how criteria affected AE reporting. Results: We identified 21 gabapentin trials and 7 quetiapine trials. All CSRs (6 gabapentin, 2 quetiapine) reported all AEs without applying selection criteria; by comparison, no other source reported all AEs, and 15/68 (22%) gabapentin sources and 19/48 (40%) quetiapine sources reported using selection criteria. Selection criteria greatly affected the number of AEs that would be reported. For example, 67/316 (21%) AEs in one quetiapine trial met the criterion “occurring in ≥2% of participants in any treatment group,” while only 5/316 (2%) AEs met the criterion, “occurring in ≥10% of quetiapine-treated patients and twice as frequent in the quetiapine group as the placebo group.” Conclusions: Selection criteria for reporting AEs vary across trials and across sources for individual trials. If investigators do not pre-specify selection criteria, they might “cherry-pick” AEs based on study results. Even if investigators pre-specify selection criteria, selective reporting of AEs will produce biased meta-analyses and clinical practice guidelines. Data about all AEs identified in clinical trials should be publicly available; however, sharing data will not solve all the problems we identified in this study. Keywords: Harms, adverse events, clinical trials, reporting bias, selective outcome reporting, data sharing, trial registration

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Safety and Efficacy of Four Drug Versus Three Drug Regimens Among Patients with Newly Diagnosed Multiple Myeloma: A Systematic Review and Meta-Analysis

Blood ◽

10.1182/blood-2020-143379 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 3-3

Author(s):

Saad Ullah Malik ◽

Nazma Hanif ◽

Priyanka Kumari ◽

Khadija Noor Sami ◽

Chase Warner ◽

...

Keyword(s):

Multiple Myeloma ◽

Clinical Trials ◽

Adverse Events ◽

Randomized Clinical Trials ◽

Standard Of Care ◽

Drug Regimen ◽

P Value ◽

Newly Diagnosed ◽

Drug Regimens ◽

Grade 3

Introduction: During recent years there has been a boom in the availability of treatments for multiple myeloma (MM). Based on the status of disease (newly diagnosed or relapsed/refractory), several regimens have successfully improved progression free survival (PFS) and overall survival (OS) in these two types of patients. Triple drug regimen is considered the current standard of care for newly diagnosed MM patients. However, with the advent of four drug regimens, some studies demonstrated a significant improvement in PFS and OS compared to standard of care where as others showed marginal to no difference. Also, it remains unclear whether the benefits of using four drug regimen outweigh the risks. Thus, the aim of our meta-analysis was to compare the efficacy and safety of four drug versus three drug regimens among newly diagnosed multiple myeloma patients. Methods: We built a PICO based search strategy using keywords like "multiple myeloma", "randomized clinical trials" and ran literature search on PubMed, Embase, Wiley Cochrane Library, Web of Science and ClinicalTrials.gov ranging from the date of inception till 16th July, 2020. A pre-validated data extraction sheet was used to extract data on PFS, OS and ≥Grade 3 hematologic adverse events at the longest follow-up. We included only randomized clinical trials (RCTs) comparing four versus three drug regimen in newly diagnosed MM patients. We excluded studies other than RCTs, studies conducted on relapsed refractory MM patients or other plasma cell dyscrasias. A generic variance weighted random effects model (DerSimonian and Laird) was used to derive hazard ratio estimates along with their 95% confidence intervals (CIs) for PFS and OS. Risk ratio along with its 95% CIs was estimated for Grade ≥3 hematologic adverse events. Heterogeneity was assessed with Cochrane Q -statistic and was quantified with I2 test (I2 >50% was consistent with a high degree of heterogeneity). A pre-specified sensitivity analysis was also performed for risk of adverse events. Cochrane Collaboration's tool was used to assess the quality of included RCTs and GRADE was used to rate the quality of evidence. Results: Initial search retrieved 7622 titles. After duplicate removal, 4880 articles were left. Following initial screening, 58 articles were considered for full text review. Of these only 3 studies (n=2277) met inclusion criteria. Four drug regimens included daratumumab, bortezomib, melphalan-prednisone (D-VMP), daratumumab, bortezomib, thalidomide-dexamethasone (D-VTd) and bortezomib and melphalan prednisone and thalidomide (VMPT-VT) respectively. Whereas, three drug regimens were bortezomib, melphalan-prednisone (VMP), bortezomib, thalidomide-dexamethasone (VTd) and bortezomib, melphalan and prednisone (VMP) respectively. There was a significant improvement in PFS when 4 vs 3 drug regimens were compared in patients with newly diagnosed MM (HR: 0.53, 95% CI: 0.46-0.62, p-value:<0.001, I2: 0%). Also, OS improved significantly in four drug regimen group (HR: 0.62, 95% CI: 0.51-0.76, p-value:<0.001, I2: 3.5%). There was no statistically significant difference in any grade ≥3 hematologic adverse events when 4 vs 3 drug regimens were compared (RR: 1.26, 95% CI: 0.93-1.73, p-value:0.14, I2: 93%). Sensitivity analysis after removing D-VTd regimen from any grade ≥3 hematologic adverse events revealed similar results (RR: 1.05, 95% CI: 0.97-1.13, p-value:0.23, I2: 23%) confirming the robustness of analysis. When each hematologic adverse event was looked at separately, there was no difference between 4 vs 3 drug regimen in rates of anemia (RR: 0.99, 95% CI: 0.76-1.28, p-value:0.92, I2: 0%), neutropenia (RR: 1.39, 95% CI: 1.00-1.94, p-value:0.05, I2: 85%) and thrombocytopenia (RR: 1.13, 95% CI: 0.92-1.39, p-value:0.24, I2: 33%). There was low risk of bias and strength of evidence was of moderate. Conclusion: Using four drug regimens, compared to three drug regimens, significantly improves PFS and OS among newly diagnosed multiple myeloma patients without any difference in the risk of ≥3 grade hematologic adverse events. Further randomized clinical trials are required to establish four drug regimen as standard of care for patients with newly diagnosed multiple myeloma. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

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