scholarly journals Rate of adjudication of radiological progression in rheumatoid arthritis randomized controlled trials depending on preset limits of agreement: a pooled analysis from 15 randomized trials

Rheumatology ◽  
2013 ◽  
Vol 52 (8) ◽  
pp. 1404-1407 ◽  
Author(s):  
V. Navarro-Compan ◽  
R. Landewe ◽  
H. A. Ahmad ◽  
C. G. Miller ◽  
D. Xu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Randomized Controlled Trials ◽  
Randomized Trials ◽  
Pooled Analysis ◽  
Controlled Trials ◽  
Limits Of Agreement ◽  
Radiological Progression ◽  
Randomized Controlled

Cartilage Restoration of the Knee

2015 ◽  
Vol 44 (7) ◽  
pp. 1888-1895 ◽  
Author(s):  
Raman Mundi ◽  
Asheesh Bedi ◽  
Linda Chow ◽  
Sarah Crouch ◽  
Nicole Simunovic ◽  
...  
Keyword(s):  
Randomized Controlled Trials ◽  
Randomized Trials ◽  
Meta Analysis ◽  
Pooled Analysis ◽  
Cartilage Defects ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
Significant Difference ◽  
Standardized Mean Difference

Background: Focal cartilage defects of the knee are a substantial cause of pain and disability in active patients. There has been an emergence of randomized controlled trials evaluating surgical techniques to manage such injuries, including marrow stimulation (MS), autologous chondrocyte implantation (ACI), and osteochondral autograft transfer (OAT). Purpose: A meta-analysis was conducted to determine if any single technique provides superior clinical results at intermediate follow-up. Study Design: Systematic review and meta-analysis of randomized controlled trials. Methods: The MEDLINE, EMBASE, and Cochrane Library databases were systematically searched and supplemented with manual searches of PubMed and reference lists. Eligible studies consisted exclusively of randomized controlled trials comparing MS, ACI, or OAT techniques in patients with focal cartilage defects of the knee. The primary outcome of interest was function (Lysholm score, International Knee Documentation Committee score, Knee Osteoarthritis Outcome Score) and pain at 24 months postoperatively. A meta-analysis using standardized mean differences was performed to provide a pooled estimate of effect comparing treatments. Results: A total of 12 eligible randomized trials with a cumulative sample size of 765 patients (62% males) and a mean (±SD) lesion size of 3.9 ± 1.3 cm2 were included in this review. There were 5 trials comparing ACI with MS, 3 comparing ACI with OAT, and 3 evaluating different generations of ACI. In a pooled analysis comparing ACI with MS, there was no difference in outcomes at 24-month follow-up for function (standardized mean difference, 0.47 [95% CI, –0.19 to 1.13]; P = .16) or pain (standardized mean difference, –0.13 [95% CI, –0.39 to 0.13]; P = .33). The comparisons of ACI to OAT or between different generations of ACI were not amenable to pooled analysis. Overall, 5 of the 6 trials concluded that there was no significant difference in functional outcomes between ACI and OAT or between generations of ACI. Conclusion: There is no significant difference between MS, ACI, and OAT in improving function and pain at intermediate-term follow-up. Further randomized trials with long-term outcomes are warranted.

scholarly journals Effect of janus kinase inhibitors and methotrexate combination on malignancy in patients with rheumatoid arthritis: a systematic review and meta-analysis of randomized controlled trials

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Vinod Solipuram ◽  
Akhila Mohan ◽  
Roshniben Patel ◽  
Ruoning Ni
Keyword(s):  
Rheumatoid Arthritis ◽  
Combination Therapy ◽  
Randomized Controlled Trials ◽  
Random Effect ◽  
Janus Kinase ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
Increased Risk ◽  
Significant Difference ◽  
Risk Of Malignancy

Abstract Background Rheumatoid arthritis (RA) is a systemic autoimmune disease. The combination therapy of methotrexate (MTX) and Janus kinase inhibitor (JAKi) is commonly used. Patients with RA are at increased risk of malignancy, however, it remains unclear whether the combination therapy is associated with a higher risk. Objective To assess the malignancy risk among patients with RA receiving combination therapy of JAKi and MTX compared to MTX alone. Methods PubMed, Cochrane and Embase were thoroughly searched for randomized controlled trials (RCTs) in patients with RA receiving JAKi and MTX, from inception to July 2020. Primary endpoints were malignancy events, Non melanomatous skin cancer (NMSC) and malignancy excluding NMSC and secondary endpoints were serious adverse events (SAE), deaths. Risk ratio (RR) and 95% CI were calculated using the Mantel–Haenszel random-effect method. Results 659 publications were screened and 13 RCTs with a total of 6911 patients were included in the analysis. There was no statistically significant difference in malignancy [RR = 1.42; 95% CI (0.59, 3.41)], neither NMSC [RR = 1.44 (0.36, 5.76)] nor malignancies excluding NMSC [RR = 1.12 (0.40, 3.13)]. No statistically significant difference between the two groups for SAE [RR = 1.15 (0.90, 1.47)] and deaths [RR = 1.99 (0.75, 5.27)] was found. Conclusion The adjunction of JAKi to MTX is not associated with an increased risk of malignancy when compared to MTX alone. There is no increased risk of SAE and deaths when compared to MTX alone in patients with RA.

scholarly journals PubMed is Slightly More Sensitive but More Time Intensive to Search than Ovid MEDLINE

2011 ◽  
Vol 6 (2) ◽  
pp. 51
Author(s):  
Cari Merkley
Keyword(s):  
Rheumatoid Arthritis ◽  
Systematic Review ◽  
Randomized Controlled Trials ◽  
Controlled Trials ◽  
Medline Search ◽  
Search Results ◽  
Randomized Controlled ◽  
Ovid Medline ◽  
Mesh Terms ◽  
The University

Objective — To compare the results of searching the MEDLINE database through Ovid and the free online version of PubMed administered by the National Library of Medicine for randomized controlled trials on the subject of the drug methotrexate (MTX) for patients suffering from rheumatoid arthritis. Design — Comparative analysis of search results. Setting — Searches conducted by researchers affiliated with Mahidol University in Bangkok, Thailand, and the University of Toronto and the University Health Network in Toronto, Ontario. Subjects — A total of 3966 search results obtained from Ovid MEDLINE and PubMed. Methods — This study employs an Ovid MEDLINE search strategy originally created for a published systematic review that identified randomized controlled trials on MTX and rheumatoid arthritis (Katchamart, Trudeau, Phumethum, & Bombardier, 2009). Two of the authors of the original systematic review (Katchamart and Bombardier) are among the authors of this current study. Appropriate medical subject heading (MeSH) terms and their synonyms were identified for the three main concepts (rheumatoid arthritis, MTX, and randomized controlled trials). The search was performed in Ovid MEDLINE, seeking articles in any language that met the search criteria, from the earliest date covered by MEDLINE to January 2009. Each MeSH or keyword term within a concept was searched separately, and then combined with other like terms using the Boolean operator OR. The searches for the three concepts were finally combined using AND. The Ovid MEDLINE search was then translated for use in PubMed by an information professional. The formatting and terminology used in some of the original Ovid MEDLINE search statements had to be changed so they would work in the new database environment, but the researchers tried to ensure that the two searches were as similar as possible. The translated search was then executed in PubMed. The final results, as well as the number of articles retrieved for each key search concept (rheumatoid arthritis, MTX, and randomized controlled trials), were then compared. The final results were further analyzed for measures of sensitivity, precision, and number needed to read. Sensitivity is calculated by the number of eligible studies found in a database divided by the “total number of eligible studies in the review” multiplied by 100 (Katchamart, Faulkner, Feldman, Tomlinson, & Bombardier, p. 806). Eligible studies were identified using the inclusion/exclusion criteria developed by Katchamart et al. The figure for “total number of eligible studies in the review” is taken from that same study, which forms the “gold standard” for this analysis (Katchamart et al., p. 806). Precision is calculated by dividing the total number of eligible citations from a database by the total number of citations returned by the database for the search multiplied by 100 (Katchamart et al., p. 806). The number needed to read (NNR) formula used by the authors is 1/precision, taken from a study by Bachman, Coray, Estermann, and Ter Riet (2002). Main Results — The PubMed search found more results than Ovid MEDLINE for each of the three key concepts – rheumatoid arthritis, MTX and randomized controlled trials. Once the three concepts were combined, PubMed found 106 more articles than Ovid MEDLINE (2036 vs. 1930). Once the review eligibility criteria were applied to the search results from PubMed, 18 eligible articles were identified, one more article than in Ovid MEDLINE. The authors indicated that the additional article located in PubMed was from a journal that was not yet indexed by MEDLINE at the time the relevant article was published. To determine database sensitivity, these numbers were then divided by 20, the total number of eligible studies located in the Katachamart et al. 2009 review, which employed tools like EMBASE and strategies like hand searching in addition to MEDLINE in order to identify relevant studies. Because of the additional study it located, the sensitivity of PubMed was determined to be slightly higher than Ovid MEDLINE (90% vs. 85%). There was little difference between the two databases in terms of precision and NNR. Precision for Ovid MEDLINE was calculated at 0.881% and at 0.884% for PubMed. The NNR was 114 for Ovid MEDLINE and 113 for PubMed. Conclusion — The authors state that while PubMed had a higher calculated sensitivity than Ovid MEDLINE in the context of this particular search because it contained content not indexed by Ovid MEDLINE that proved to be relevant for this topic, its precision and NNR were almost equal to MEDLINE’s. Some technical limitations of the PubMed interface were experienced by researchers during the study, such as periodic instability and the inability to save and modify searches and their results line by line. These same issues did not arise while using Ovid MEDLINE. The need for a skilled translation of Ovid MEDLINE searches for use in the PubMed interface was also emphasized by the authors, as differences in syntax and formatting that are not properly addressed could impact PubMed’s sensitivity and precision.

scholarly journals High-cited favorable studies for COVID-19 treatments ineffective in large trials

2022 ◽  
Author(s):  
John P.A. Ioannidis
Keyword(s):  
Clinical Trials ◽  
Randomized Controlled Trials ◽  
Clinical Studies ◽  
Observational Studies ◽  
Randomized Trials ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
Wide Dissemination ◽  
Highly Cited Articles ◽  
Highly Cited

Importance. COVID-19 has resulted in massive production, publication and wide dissemination of clinical studies trying to identify effective treatments. However, several widely touted treatments failed to show effectiveness in large well-done randomized controlled trials (RCTs). Objective. To evaluate for COVID-19 treatments that showed no benefits in subsequent large RCTs how many of their most-cited clinical studies had declared favorable results for these interventions. Methods. Scopus (last update December 23, 2021) identified articles on lopinavir-ritonavir, hydroxycholoroquine/azithromycin, remdesivir, convalescent plasma, colchicine or interferon (index interventions) that represented clinical trials and that had received >150 citations. Their conclusions were assessed and correlated with study design features. The ten most recent citations for the most-cited article on each index intervention were examined on whether they were critical to the highly-cited study. Altmetric scores were also obtained. Findings. 40 articles of clinical studies on these index interventions had received >150 citations (7 exceeded 1,000 citations). 20/40 (50%) had favorable conclusions and 4 were equivocal. Highly-cited articles with favorable conclusions were rarely RCTs while those without favorable conclusions were mostly RCTs (3/20 vs 15/20, p=0.0003). Only 1 RCT with favorable conclusions had sample size >160. Citation counts correlated strongly with Altmetric scores, in particular news items. Only 9 (15%) of 60 recent citations to the most highly-cited studies with favorable or equivocal conclusions were critical to the highly-cited study. Conclusion. Many clinical studies with favorable conclusions for largely ineffective COVID-19 treatments are uncritically heavily cited and disseminated. Early observational studies and small randomized trials may cause spurious claims of effectiveness that get perpetuated.

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