219 Long-term clinical outcomes associated with sequential treatment of BRAF mutant advanced melanoma patients

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A238-A238
Author(s):  
Ahmad Tarhini ◽  
David McDermott ◽  
Apoorva Ambavane ◽  
Agnes Benedict ◽  
Cho-Han Lee ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Clinical Outcomes ◽  
Randomized Clinical Trials ◽  
Advanced Melanoma ◽  
Lifetime Horizon ◽  
Mek Inhibitors ◽  
Life Years ◽  
Braf Mutant ◽  
Treatment Sequences

BackgroundPatients with BRAF mutant advanced melanoma can be treated sequentially with immunotherapies (IO) and BRAF+MEK inhibitors. We evaluated the clinical outcomes associated with various treatment sequences for BRAF mutant advanced melanoma based on the 5-year follow-up data from clinical trials.MethodsIn the absence of head-to-head trial data, a matching-adjusted indirect comparison (MAIC) was conducted for IO vs. BRAF+MEK inhibitors, using the longest follow-up available in the published literature. Multivariate risk equations were developed to predict time-to-event outcomes based on patient-level data from pooled CheckMate-067 &-069 trials. Risk equations were inserted into a discrete event simulation to estimate the average life-years (LYs) and quality-adjusted life-years (QALYs) that can be gained with various treatment sequences over a lifetime horizon. Treatment sequences and corresponding efficacy data sources are presented below (table 1). Utility weights for quality-adjustment of LYs were obtained from published literature.ResultsTreatment sequences starting with IO followed by BRAF+MEK were associated with 2.9–4.3 years of additional survival and 2.2–3.3 years of quality-adjusted survival versus sequences starting with BRAF+MEK followed by anti-PD-1. After 1L IO, the time spent in the treatment-free interval (TFI) is 3.3–5.0 years. LYs, QALYs, and time spent in TFI were higher with sequences starting with anti-PD-1+anti-CTLA-4 vs. anti-PD-1 alone.ConclusionsIn this sequencing model with 5-year data from randomized clinical trials, initiating 1L treatment with IO provided prolonged survival compared to initiating 1L treatment with BRAF+MEK. Time spent in TFI represents a significant proportion of survival time for patients on IO initiating sequences. Limitations of the study are the reliance on published information for BRAF+MEK, which could lead to biases due to unmeasured differences in the patient populations or trial conduct and the absence of data on 2L combination IO. Anti-PD-1+anti-CTLA-4 as second line option has not been included because of a lack of clinical evidence. Findings from this analysis will require validation in ongoing prospective randomized clinical trials.Abstract 219 Table 1Clinical outcomes on treatment sequences for BRAF MT melanoma

scholarly journals Vitamin E highly cross-linked polyethylene reduces mid-term wear in primary total hip replacement: a meta-analysis and systematic review of randomized clinical trials using radiostereometric analysis

2021 ◽  
Vol 6 (9) ◽  
pp. 759-770
Author(s):  
Zeng Li ◽  
Shuai Xiang ◽  
Cuijiao Wu ◽  
Yingzhen Wang ◽  
Xisheng Weng
Keyword(s):  
Clinical Trials ◽  
Vitamin E ◽  
Total Hip Arthroplasty ◽  
Clinical Outcomes ◽  
Hip Arthroplasty ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Wear Properties ◽  
Total Hip

Vitamin E incorporation into highly cross-linked polyethylene (HXLPE) has been introduced to improve wear resistance, and vitamin E incorporated HXLPE (VEPE) has been used in total hip arthroplasty. The aim of this meta-analysis was to investigate the wear properties of VEPE in clinical practice by synthesizing the data provided in randomized clinical trials. The effects on implant stability, functional outcomes and revision rate of VEPE were also compared with those of HXPLE or ultra-high molecular weight polyethylene (UHMWPE). Literature searches were conducted on 1 January 2020 using MEDLINE, EMBASE, Cochrane and ClinicalTrials.gov databases. Randomized controlled trials (RCTs) comparing the aforementioned parameters between VEPE and standard HXPLE/UHMWPE liners were included. Methodological quality and the bias of the included studies were analysed. Meta-analyses were performed using the Review Manager software. Nine RCTs met the eligibility criteria and were included. At early and mid-term follow-up, the vertical penetration and the total penetration of the femoral head were both significantly reduced in the VEPE group. The steady state wear rate of the VEPE group was also remarkably lower. However, at two-year follow-up, significantly increased cup migration was observed in the VEPE group. Moreover, the mid-term clinical outcomes of the VEPE group were worse, while the total revision rates between the two groups were not significantly different. The limited number of included studies may compromise our conclusion regarding clinical outcomes of the VEPE bearing surface. More RCTs with longer follow-up periods are needed to further investigate the effects of VEPE in total hip arthroplasty. Cite this article: EFORT Open Rev 2021;6:759-770. DOI: 10.1302/2058-5241.6.200072

scholarly journals What can we learn from randomized clinical trials about the construct validity of self-report measures of mindfulness? A meta-analysis

2019 ◽  
Author(s):  
Simon Goldberg ◽  
Raymond P. Tucker ◽  
Preston A. Greene ◽  
Tracy L. Simpson ◽  
William T. Hoyt ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Construct Validity ◽  
Clinical Outcomes ◽  
Randomized Clinical Trials ◽  
Experimental Manipulation ◽  
Post Treatment ◽  
Self Report ◽  
Treatment Comparison ◽  
Bona Fide

Because they provide data on responsiveness to experimental manipulation, clinical trials involving mindfulness-based inter- ventions are a source of evidence for the construct validity of self-report measures of mindfulness. Within-group and between- group changes in mindfulness were examined from randomized clinical trials comparing mindfulness interventions to other bona fide treatment comparison conditions or waitlist control conditions. We also examined changes in clinical outcomes and the magnitude of these changes relative to changes in mindfulness. We included 69 published studies representing 55 unique samples (n = 4743). Self-report mindfulness measures showed relatively larger gains in mindfulness intervention conditions vis-à-vis waitlist comparison conditions at both post-treatment (effect size [ES] = 0.52, 95% CI [0.40, 0.64]) and follow-up (ES = 0.52 [0.20, 0.84]), although the effect at follow-up diminished to non-significance in a trim-and-fill analysis intended to account for publication bias (ES = 0.35 [− 0.03, 0.72]). Measures of mindfulness also showed relatively larger gains in mindfulness inter- vention conditions vis-à-vis bona fide comparison conditions, but only at post-treatment (ES = 0.25 [0.11, 0.38], 0.10 [− 0.08, 0.28], at post-treatment and follow-up, respectively). All three conditions (mindfulness, bona fide, waitlist) showed relatively larger improvements on measures of clinical outcomes than measures of mindfulness, with the exception of waitlist conditions for which this effect was no longer significant at follow-up. Taken together, findings provide partial support for the unique respon- siveness of mindfulness self-report measures to interventions that include promotion of mindfulness meditation practice.

scholarly journals Preparation Methods and Clinical Outcomes of Platelet-Rich Plasma for Intra-articular Hip Disorders: A Systematic Review and Meta-analysis of Randomized Clinical Trials

2020 ◽  
Vol 8 (10) ◽  
pp. 232596712096041
Author(s):  
Flávio Luís Garcia ◽  
Brady T. Williams ◽  
Evan M. Polce ◽  
Daniel B. Heller ◽  
Zachary S. Aman ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Clinical Outcomes ◽  
Randomized Clinical Trials ◽  
Platelet Rich Plasma ◽  
Meta Analysis ◽  
Preparation Methods ◽  
Significant Difference ◽  
Patient Reported

Background: Despite its increasing use in the management of musculoskeletal conditions, questions remain regarding the preparation methods of platelet-rich plasma (PRP) and its clinical applications for intra-articular hip disorders, including femoroacetabular impingement syndrome (FAIS), labral pathology, and osteoarthritis (OA). Purpose: To systematically review and assess the preparation methods and clinical outcomes from randomized clinical trials (RCTs) on the use of PRP for intra-articular hip disorders. Study Design: Systematic review; Level of evidence, 2. Methods: A systematic review in accordance with the 2009 PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines was performed in September 2019. The Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, PubMed, Ovid Medline, and Embase were queried for studies regarding the use of PRP to treat intra-articular hip disorders. Qualifying articles were English-language RCTs describing the use of PRP for intra-articular hip disorders, either as standalone treatment or surgical augmentation. Two authors independently assessed article eligibility. Data pertaining to patient characteristics, indication for treatment, PRP preparation method, follow-up period, and clinical outcomes were extracted. Study results were qualitatively reported and quantitatively compared using meta-analysis when appropriate. Results: Seven RCTs met inclusion criteria. Four studies described the use of PRP for hip OA and 3 utilized PRP at arthroscopy for FAIS and labral tears. Outcomes after PRP for OA demonstrated improvement in validated patient-reported outcome measures for up to 1 year; however, pooled effect sizes found no statistically significant difference between PRP and hyaluronic acid (HA) regarding pain visual analog scale scores at short-term (≤2 months; P = .27), midterm (4-6 months; P = .85), or long-term (1 year; P = .42) follow-up. When injected at arthroscopy, 1 study reported improved outcomes, 1 reported no difference in outcomes, and 1 reported worse outcomes compared with controls. The meta-analysis demonstrated no statistically significant difference on the modified Harris Hip Score (mHHS) between PRP and control cohorts at a minimum 1-year follow-up. There were considerable deficiencies and heterogeneity in the reporting of PRP preparation methods for both indications. Conclusion: Treatment of OA with PRP demonstrated reductions in pain and improved patient-reported outcomes for up to 1 year. However, there was no statistically significant difference between PRP and HA in pain reduction. Likewise, for FAIS and labral surgery there was no statistically significant difference in mHHS outcomes between patients treated with PRP and controls. Given the limited number of studies and variability in PRP preparations, additional high-quality randomized trials are warranted.

Abstract P476: Safety and Efficacy of Balloon Mounted Drug-Eluting Stent in the Treatment of Symptomatic Intracranial Atherosclerotic Disease Multicenter International Experience

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Mahmoud Mohammaden ◽  
Raul G Nogueira ◽  
WONDWOSSEN TEKLE ◽  
farhan siddiq ◽  
Diogo C Haussen ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Endovascular Treatment ◽  
Medical Management ◽  
Randomized Clinical Trials ◽  
Atherosclerotic Disease ◽  
Drug Eluting Stent ◽  
Safety And Efficacy ◽  
Intracranial Atherosclerotic Disease ◽  
Drug Eluting

Introduction: Intracranial atherosclerotic disease (ICAD) is a common cause of refractory stroke. Randomized clinical trials failed to prove the safety and efficacy of the endovascular treatment options of symptomatic ICAD (sICAD). However, there are many concerns regarding inclusion criteria in these trials which made them less effective than standard medical management. Herein, we aim to study the safety and efficacy of drug-eluting balloon mounted stents (DES) in the treatment of sICAD. Methods: A retrospective review of endovascular database from 10 comprehensive stroke centers inside and outside the USA from January 2017 to January 2020 was reviewed. Patients were included if they had symptomatic intracranial stenosis ≥70% in the target vessel, failed best medical management, and underwent intracranial stenting with DES. The primary outcome was the occurrence of ischemic stroke, hemorrhage, or mortality within 72 hours of the procedure. Secondary outcomes included rates of symptomatic and angiographic recurrence within 6 months of the procedure. Results: There was a total of 129 patients, the median age was 65 [58-72] years, 40 (31%) were females. The intracranial stenotic lesions were located in anterior circulation in 74 (57.4%) of cases [24 (18.6%) supraclinoid ICA, 5 (3.9%) cavernous ICA, 17 (13.2%) petrous ICA, 5 (19.4%) MCA-M1, and 3 (2.3%) M2] and in posterior circulation in 55 (42.6%) of cases [36 (27.9) vertebral artery V4 segment, 18 (14%) basilar and 1 (0.7%) PCA]. Recurrent stroke was the qualifying event in 101 (78.3%) while transient ischemic attacks (TIA) were identified in 28 (21.7%) of cases. The median time from the qualifying event to stenting was 6 [2-24] days. Strokes were reported within 72 hours of the procedure; 2 (1.6%) ischemic, 2 (1.6%) hemorrhagic strokes and 2 (1.6%) patients suffered inpatient mortality. The median follow-up time was 6 [3-6.75] months. Among 99 patients who had clinical follow up 2 (2%) had TIA and 6 (6.1%) had strokes. Fifty-one patients had follow-up imaging of whom symptomatic ISR was reported in 8 (15.7%). Conclusion: Our study has shown that in appropriately selected patients with sICAD, endovascular treatment using DES is safe and effective. Prospective randomized clinical trials are warranted.

scholarly journals Clinical and Molecular Characteristics Associated with Survival in Advanced Melanoma Treated with Checkpoint Inhibitors

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Sunil Badami ◽  
Sunil Upadhaya ◽  
Ravi Kanth Velagapudi ◽  
Pushyami Mikkilineni ◽  
Ranju Kunwor ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Random Effect ◽  
Eastern Cooperative Oncology Group ◽  
Advanced Melanoma ◽  
Cochrane Library ◽  
Molecular Characteristics ◽  
Significant Heterogeneity

Background. We performed meta-analysis to gather more evidence regarding clinical-molecular subgroups associated with better overall survival (OS) in advanced melanoma treated with checkpoint inhibitors. Materials and Methods. We performed a systematic search of PubMed, Scopus, Cochrane Library, and clinical trial.gov. Randomized clinical trials that compared a checkpoint inhibitor (nivolumab or pembrolizumab) with investigator choice chemotherapy or ipilimumab were included in our study. Hazard ratios (HR) and confidence interval (CI) were calculated for progression-free survival (PFS) and OS for each subgroup using generic inverse model along with the random effect method. Results. A total of 6 clinical trials were eligible for the meta-analysis. OS was prolonged in wild BRAF subgroup (HR 0.65, 95% CI 0.49-0.85, p 0.002), Programmed cell death subgroup (PD-1+) (HR 0.57, 95% CI 0.41-0.80, p 0.001), and high lactate dehydrogenase (LDH) level subgroup (HR 0.60, 95% CI 0.38-0.95, p 0.03). Similarly, we found increased OS in eastern cooperative oncology group (ECOG) 1, males and age >65 years subgroups. Conclusions. Checkpoint inhibitors significantly increased OS in patients with wild BRAF, positive PD-1, and high LDH. However, results should be interpreted keeping in mind associated significant heterogeneity. The results of this study should help in designing future clinical trials.

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