scholarly journals Tocilizumab may slow radiographic progression in patients with systemic or polyarticular-course juvenile idiopathic arthritis: post hoc radiographic analysis from two randomized controlled trials

2020 ◽  
Vol 22 (1) ◽  
Author(s):  
Clara Malattia ◽  
◽  
Nicolino Ruperto ◽  
Silvia Pederzoli ◽  
Elena Palmisani ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Randomized Controlled Trials ◽  
Bone Growth ◽  
Radiographic Progression ◽  
Systemic Juvenile Idiopathic Arthritis ◽  
Joint Damage ◽  
Trial Registration ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
Link Type

Abstract Background Few clinical trials have investigated the prevention of radiographic progression in children with juvenile idiopathic arthritis treated with antirheumatic drugs. This study aimed to investigate radiographic progression in patients with systemic juvenile idiopathic arthritis (sJIA) and patients with polyarticular-course juvenile idiopathic arthritis (pcJIA) treated with the anti–interleukin-6 receptor antibody tocilizumab for 2 years in the TENDER and CHERISH randomized controlled trials, respectively. Methods Standard radiographs of both wrists and both hands in the posteroanterior view were obtained within 4 weeks of baseline and were repeated at weeks 52 ± 4 and 104 ± 4 in both trials. All films were scored by two independent readers using the adapted Sharp–van der Heijde (aSH) and Poznanski scoring methods. Although the Poznanski score indicates bone growth limitation or cartilage growth decrease, which are not the same as joint space narrowing in rheumatoid arthritis, its change reflects damage to cartilage. Therefore, impairment in the Poznanski score as well as the aSH score was considered as a measure of structural joint damage. Radiographic progression was defined as worsening of radiographic scores beyond the smallest detectable difference. Results Poznanski and aSH scores were available at baseline and at one or more postbaseline time points for 33 and 47 of 112 sJIA patients and 61 and 87 of 188 pcJIA patients, respectively, providing a representative subset of the study populations. The inter-reader and intra-reader agreement intra-class correlation coefficient was > 0.8. Median baseline Poznanski and aSH scores, respectively, were − 2.4 and 24.6 for sJIA patients and − 1.5 and 8.0 for pcJIA patients. Compared with baseline, aSH scores remained stable for all sJIA patients at week 52, whereas 9.4% of sJIA patients had radiographic progression according to Poznanski scores at week 52; at 104 weeks, radiographic progression according to aSH and Poznanski scores was observed in 5.4% and 11.5%, respectively. In pcJIA patients, radiographic progression from baseline at 52 weeks and at 104 weeks was 12.5% and 2.9%, respectively, using aSH scoring and 6.5% and 4%, respectively, using Poznanski scoring. Conclusion Tocilizumab may delay radiographic progression in children with sJIA and children with pcJIA. Trial registration Trial registration numbers and dates: TENDER, NCT00642460 (March 19, 2008); CHERISH, NCT00988221 (October 1, 2009)

scholarly journals Randomized, double-blinded, controlled non-inferiority trials evaluating the immunogenicity and safety of fractional doses of Yellow Fever vaccines in Kenya and Uganda

2019 ◽  
Vol 4 ◽  
pp. 182 ◽  
Author(s):  
Derick Kimathi ◽  
Aitana Juan ◽  
Philip Bejon ◽  
Rebecca F. Grais ◽  
George M. Warimwe ◽  
...  
Keyword(s):  
Immune Response ◽  
Randomized Controlled Trials ◽  
Yellow Fever ◽  
Vaccine Dose ◽  
World Health ◽  
Yellow Fever Vaccine ◽  
Controlled Trials ◽  
Post Vaccination ◽  
Randomized Controlled ◽  
Link Type

Introduction: Yellow fever is endemic in specific regions of sub-Saharan Africa and the Americas, with recent epidemics occurring on both continents. The yellow fever vaccine is effective, affordable and safe, providing life-long immunity following a single dose vaccination. However, the vaccine production process is slow and cannot be readily scaled up during epidemics. This has led the World Health Organization (WHO) to recommend the use of fractional doses as a dose-sparing strategy during epidemics, but there are no randomized controlled trials of fractional yellow fever vaccine doses in Africa. Methods and analysis: We will recruit healthy adult volunteers, adults living with HIV, and children to a series of randomized controlled trials aiming to determine the immunogenicity and safety of fractional vaccine doses in comparison to the standard vaccine dose. The trials will be conducted across two sites; Kilifi, Kenya and Mbarara, Uganda. Recruited participants will be randomized to receive fractional or standard doses of yellow fever vaccine. Scheduled visits will include blood collection for serum and peripheral blood mononuclear cells (PBMCs) before vaccination and on various days – up to 2 years – post-vaccination. The primary outcome is the rate of seroconversion as measured by the plaque reduction neutralization test (PRNT50) at 28 days post-vaccination. Secondary outcomes include antibody titre changes, longevity of the immune response, safety assessment using clinical data, the nature and magnitude of the cellular immune response and post-vaccination control of viremia by vaccine dose. Ethics and dissemination: The clinical trial protocols have received approval from the relevant institutional ethics and regulatory review committees in Kenya and Uganda, and the WHO Ethics Review Committee. The research findings will be disseminated through open-access publications and presented at relevant conferences and workshops. Registration: ClinicalTrials.gov NCT02991495 (registered on 13 December 2016) and NCT04059471 (registered on 15 August 2019).

A Meta-Analysis to Estimate the Placebo Effect in Randomized Controlled Trials in Juvenile Idiopathic Arthritis

2016 ◽  
Vol 68 (6) ◽  
pp. 1540-1550 ◽  
Author(s):  
Erkan Demirkaya ◽  
Stefano Lanni ◽  
Francesca Bovis ◽  
Roberta Galasso ◽  
Angelo Ravelli ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Randomized Controlled Trials ◽  
Placebo Effect ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Randomized Controlled

scholarly journals Efficacy and Safety of Fuzi Formulae on the Treatment of Heart Failure as Complementary Therapy: A Systematic Review and Meta-Analysis of High-Quality Randomized Controlled Trials

2019 ◽  
Vol 2019 ◽  
pp. 1-21
Author(s):  
Meng-Qi Yang ◽  
Yong-Mei Song ◽  
Huan-Yu Gao ◽  
Yi-Tao Xue
Keyword(s):  
Heart Failure ◽  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Controlled Trials ◽  
Efficacy And Safety ◽  
High Quality ◽  
Randomized Controlled ◽  
Link Type

Objective. Heart failure is a major public health problem worldwide nowadays. However, the morbidity, mortality, and awareness of heart failure are not satisfied as well as the status of current treatments. According to the standard treatment for chronic heart failure (CHFST), Fuzi (the seminal root of Aconitum carmichaelii Debx.) formulae are widely used as a complementary treatment for heart failure in clinical practice for a long time. We are aiming to assess the efficacy and safety of Fuzi formulae (FZF) on the treatment of heart failure according to high-quality randomized controlled trials (RCTs). Methods. RCTs in PubMed, Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP), and Wanfang Database were searched from their inception until June 2019. In addition, the U.S. National Library of Medicine (clinicaltrials.gov) and the Chinese Clinical Trial Registry (http://www.chictr.org.cn) were also searched. We included RCTs that test the efficacy and safety of FZF for the treatment of heart failure, compared with placebo, CHFST, or placebo plus CHFST. The methodological quality of included studies were evaluated by the Cochrane Collaboration’s tool for assessing risk of bias. RCTs with Cochrane risk of bias (RoB) score ≥4 were included in the analysis. The meta-analysis was conducted through RevMan 5.2 software. The GRADE approach was used to assess the quality of the evidence. Results. Twelve RCTs with 1490 participants were identified. The studies investigated the efficacy and safety of FZF, such as FZF plus the CHFST vs placebo plus CHFST (n = 4), FZF plus CHFST vs CHFST (n = 6), FZF plus digoxin tablets (DT) plus CHFST vs placebo plus DT plus CHFST (n = 1), and FZF plus placebo plus CHFST vs placebo plus DT plus CHFST (n = 1). Meta-analysis indicated that FZF have additional benefits based on the CHFST in reducing plasma NT-proBNP level, MLHFQ scores, Lee’s heart failure scores (LHFs), and composite cardiac events (CCEs). Meanwhile, it also improved the efficacy on TCM symptoms (TCMs), NYHA functional classification (NYHAfc), 6MWD, and LVEF. Adverse events were reported in 6 out of 12 studies without significant statistical difference. However, after assessing the strength of evidence, it was found that only the quality of evidence for CCEs was high, and the others were either moderate or low or very low. So we could not draw confirmative conclusions on its additional benefits except CCEs. Further clinical trials should be well designed to avoid the issues that were identified in this study. Conclusion. The efficacy and additional benefits of FZF for CCEs were certain according to the high-quality evidence assessed through GRADE. However, the efficacy and additional benefits for the other outcomes were uncertain judging from current studies. In addition, the safety assessment has a great room for improvement. Thus, further research studies are needed to find more convincing proofs.

scholarly journals Pharmacist and patient perspectives on recruitment strategies for randomized controlled trials: a qualitative analysis

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Jane M. Fletcher ◽  
Terry Saunders-Smith ◽  
Braden J. Manns ◽  
Ross Tsuyuki ◽  
Brenda R. Hemmelgarn ◽  
...  
Keyword(s):  
Focus Groups ◽  
Randomized Controlled Trials ◽  
Low Income ◽  
Intrinsic Value ◽  
Trial Registration ◽  
Controlled Trials ◽  
Patient Recruitment ◽  
Large Trial ◽  
Recruitment Strategies ◽  
Randomized Controlled

Abstract Background Although recruitment is a major challenge for most randomized controlled trials, few report on the difficulties of recruitment, or how it might be enhanced. The objective of our study was to qualitatively explore the experiences of both patients and pharmacists related to recruitment for ACCESS, a large trial involving low-income seniors, given that two of our most successful recruitment strategies were direct patient recruitment materials and use of community pharmacists. Methods Using qualitative descriptive methods, we collected data from pharmacists and study participants. Pharmacists were asked about their impressions of the study, as well as challenges they faced and methods they used to recruit potential participants. Focus groups with trial participants centered on the patient recruitment materials. Interviews and focus groups were recorded, transcribed and analyzed using thematic analysis. Results Pharmacists noted that their first impressions of the study were positive as they described being enticed to help the study team by the potential benefit of copayment elimination for their patients and the low time commitment. Pharmacists noted they were more likely to recruit if they were well informed on the study, as they could answer their patients’ questions. Participants noted that their primary motivations for participating were the tangible benefits of free medications and the intrinsic value of participating in research. Conclusions We noted that recruitment through pharmacies was an effective method as most patients have trusting relationships with their pharmacist. To optimize recruitment through pharmacies, study procedures should be straightforward, and pharmacists need to be equipped with good knowledge of the study. When promoting a study to potential participants, messaging should ensure the individuals are aware of the tangible benefits of participation while still presenting a full overview of the trial. Trial registration Trial Registration Number: NCT02579655 – initially registered Oct 19, 2015.

scholarly journals Randomized controlled trials in neurosurgery: an observational analysis of trial discontinuation and publication outcome

2017 ◽  
Vol 127 (4) ◽  
pp. 857-866 ◽  
Author(s):  
Aimun A. B. Jamjoom ◽  
Angus B. Gane ◽  
Andreas K. Demetriades
Keyword(s):  
Randomized Controlled Trials ◽  
Outcome Measures ◽  
Publication Rate ◽  
Secondary Outcome ◽  
Controlled Trials ◽  
Start Date ◽  
Randomized Controlled ◽  
Link Type ◽  
Unknown Status ◽  
Trial Discontinuation

OBJECTIVEThis study aimed to determine the trial discontinuation and publication rate of randomized controlled trials (RCTs) in neurosurgery.METHODSTrials registered from 2000 to 2012 were identified on the website clinicaltrials.gov using a range of key words related to neurosurgery. Any trials that were actively recruiting or had unknown status were excluded. Included trials were assessed for whether they were discontinued early on the clinicaltrials.gov database; this included trials identified as withdrawn, suspended, or terminated in the database. For included trials, a range of parameters was identified including the subspecialty, primary country, study start date, type of intervention, number of centers, and funding status. Subsequently, a systematic search for published peer-reviewed articles was undertaken. For trials that were discontinued early or were found to be unpublished, principal investigators were sent a querying email.RESULTSSixty-four neurosurgical trials fulfilled our inclusion criteria. Of these 64, 26.6% were discontinued early, with slow or insufficient recruitment cited as the major reason (57%). Of the 47 completed trials, 14 (30%) remained unpublished. Discontinued trials showed a statistically significant higher chance of remaining unpublished (88%) compared with completed trials (p = 0.0002). Industry-funded trials had a higher discontinuation rate (31%) compared with non–industry-funded trials (23%), but this result did not reach significance (p = 0.57). Reporting of primary outcome measures was complete in 20 (61%) of 33 trials. For secondary outcome measures, complete reporting occurred in only 11 (33.3%) of 33.CONCLUSIONSMore than a fifth (26.6%) of neurosurgical RCTs are discontinued early and almost a third of those that are completed remain unpublished. This result highlights significant waste of financial resources and clinical data.

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