scholarly journals Striatal molecular alterations in HD gene carriers: a systematic review and meta-analysis of PET studies

2017 ◽  
Vol 89 (2) ◽  
pp. 185-196 ◽  
Author(s):  
Flavia Niccolini ◽  
Gennaro Pagano ◽  
Paolo Fusar-Poli ◽  
Andrew Wood ◽  
Ladislav Mrzljak ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Meta Analysis ◽  
Random Effect ◽  
Cochrane Library ◽  
Imaging Studies ◽  
Molecular Changes ◽  
Molecular Alterations ◽  
Positron Emission ◽  
Meta Analyses ◽  
Hd Gene

BackgroundOver the past years, positron emission tomography (PET) imaging studies have investigated striatal molecular changes in premanifest and manifest Huntington’s disease (HD) gene expansion carriers (HDGECs), but they have yielded inconsistent results.ObjectiveTo systematically examine the evidence of striatal molecular alterations in manifest and premanifest HDGECs as measured by PET imaging studies.MethodsMEDLINE, ISI Web of Science, Cochrane Library and Scopus databases were searched for articles published until 7 June 2017 that included PET studies in manifest and premanifest HDGECs. Meta-analyses were conducted with random effect models, and heterogeneity was addressed with I2 index, controlling for publication bias and quality of study. The primary outcome was the standardised mean difference (SMD) of PET uptakes in the whole striatum, caudate and putamen in manifest and premanifest HDGECs compared with healthy controls (HCs).ResultsTwenty-four out of 63 PET studies in premanifest (n=158) and manifest (n=191) HDGECs and HCs (n=333) were included in the meta-analysis. Premanifest and manifest HDGECs showed significant decreases in dopamine D2 receptors in caudate (SMD=−1.233, 95% CI −1.753 to −0.713, p<0.0001; SMD=−5.792, 95% CI −7.695 to −3.890, p<0.0001) and putamen (SMD=−1.479, 95% CI −1.965 to −0.992, p<0.0001; SMD=−5.053, 95% CI −6.558 to −3.549, p<0.0001), in glucose metabolism in caudate (SMD=−0.758, 95% CI −1.139 to −0.376, p<0.0001; SMD=−3.738, 95% CI −4.880 to −2.597, p<0.0001) and putamen (SMD=−2.462, 95% CI −4.208 to −0.717, p=0.006; SMD=−1.650, 95% CI −2.842 to −0.458, p<0.001) and in striatal PDE10A binding (SMD=−1.663, 95% CI −2.603 to −0.723, p=0.001; SMD=−2.445, 95% CI −3.371 to −1.519, p<0.001).ConclusionsPET imaging has the potential to detect striatal molecular changes even at the early premanifest stage of HD, which are relevant to the neuropathological mechanisms underlying the development of the disease.

scholarly journals TP6.1.7 Systematic review and meta-analyses of cholecystectomy as a treatment of biliary hyperkinesia

2021 ◽  
Vol 108 (Supplement_7) ◽  
Author(s):  
Hazim A. Eltyeb ◽  
Dhya Al-Leswas ◽  
Mutwakil O. Abdalla ◽  
John Wayman
Keyword(s):  
Ejection Fraction ◽  
Meta Analysis ◽  
Random Effect ◽  
Random Effect Model ◽  
Symptomatic Improvement ◽  
Cochrane Library ◽  
Biliary Colic ◽  
Cochrane Central Register ◽  
Mean Differences ◽  
Meta Analyses

Abstract Aims Biliary hyperkinesia is typically diagnosed in patients with biliary like pain and no evidence of gall stones on imaging modalities but who have had biliary scintigraphy scan (HIDA) that shows ejection fraction ≥80%. This study aims to identify whether the removal of the gall bladder can alleviate the symptoms associated with Biliary Hyperkinesia. Methods Systematic search following PRISMA guidelines was done from inception to January 2020 using PubMed/Medline, OVID, Embase, Cochrane database of systemic reviews, Cochrane central register of controlled trials, The Database of Abstracts of Reviews of Effects (DARE) and Cochrane library databases. Results were expressed as risk ratios (RR) for dichotomous outcomes together with 95% confidence intervals (CI) or mean differences (MD) or standardized MD (SMD) for continuous outcomes. A meta-analysis done using random-effect model in RevMan 5.4® software. Results Thirteen studies met the inclusion criteria and were included in the review. A total of 332 patients diagnosed with biliary hyperkinesia underwent cholecystectomy, of whom 303 (91.3%) reported symptomatic improvement RR 8.67 [95% CI 4.95, 15.16] P = 0.01. Six studies described abnormal histological features in 163/181 (90.05%) with high GB EF. RR 7.88 [95% CI 3.94, 15.75] P = 0.08. Chronic cholecystitis n = 155 (95%), cholesterolosis n = 7 (4.3%), and one showed features of acute cholecystitis. Conclusion Patients with typical biliary colic symptoms without gallstones and markedly high ejection fraction might benefit from having cholecystectomy to alleviate their symptoms.

scholarly journals Diagnostic Performance of PET Imaging Using Different Radiopharmaceuticals in Prostate Cancer According to Published Meta-Analyses

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2153 ◽  
Author(s):  
Salvatore Annunziata ◽  
Daniele Antonio Pizzuto ◽  
Giorgio Treglia
Keyword(s):  
Prostate Cancer ◽  
Positron Emission Tomography ◽  
Pet Imaging ◽  
Diagnostic Performance ◽  
Emission Tomography ◽  
Cochrane Library ◽  
Evidence Based ◽  
Positron Emission ◽  
Pet Ct ◽  
Meta Analyses

A significant number of meta-analyses reporting data on the diagnostic performance of positron emission tomography (PET) in prostate cancer (PCa) is currently available in the literature. In particular, different PET radiopharmaceuticals were used for this purpose. The aim of this review is to summarize information retrieved by published meta-analyses on this topic. The first step included a systematic search of the literature (last search date: June 2020), screening two databases (PubMed/MEDLINE and Cochrane Library). This combination of key words was used: (A) “PET” OR “positron emission tomography” AND (B) “prostate” OR “prostatic” AND (C) meta-analysis. Only meta-analyses on Positron Emission Tomography/Computed Tomography (PET/CT) or Positron Emission Tomography/Magnetic Resonance (PET/MR) in PCa were selected. We have summarized the diagnostic performance of PET imaging in PCa, taking into account 39 meta-analyses published in the literature. Evidence-based data showed the good diagnostic performance of PET/CT with several radiopharmaceuticals, including prostate-specific membrane antigen (PSMA)-targeted agents, radiolabeled choline, fluciclovine, and fluoride in restaging and staging settings. Less evidence-based data were available for PET/MR with different radiotracers. More prospective multicentric studies and cost-effectiveness analyses are warranted.

Laser Influence on Dental Sensitivity Compared to Other Light Sources Used During In-office Dental Bleaching: Systematic Review and Meta-analysis

2020 ◽  
Vol 45 (6) ◽  
pp. 589-597
Author(s):  
BGS Casado ◽  
EP Pellizzer ◽  
JR Souto Maior ◽  
CAA Lemos ◽  
BCE Vasconcelos ◽  
...  
Keyword(s):  
Randomized Clinical Trials ◽  
Color Change ◽  
Meta Analysis ◽  
Present Review ◽  
Cochrane Library ◽  
Light Sources ◽  
Eligibility Criteria ◽  
Tooth Color ◽  
Significant Difference ◽  
Meta Analyses

Clinical Relevance The use of laser light during bleaching will not reduce the incidence or severity of sensitivity and will not increase the degree of color change compared with nonlaser light sources. SUMMARY Objective: To evaluate whether the use of laser during in-office bleaching promotes a reduction in dental sensitivity after bleaching compared with other light sources. Methods: The present review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and is registered with PROSPERO (CDR42018096591). Searches were conducted in the PubMed/Medline, Web of Science, and Cochrane Library databases for relevant articles published up to August 2018. Only randomized clinical trials among adults that compared the use of laser during in-office whitening and other light sources were considered eligible. Results: After analysis of the texts retrieved during the database search, six articles met the eligibility criteria and were selected for the present review. For the outcome dental sensitivity, no significant difference was found favoring any type of light either for intensity (mean difference [MD]: −1.60; confidence interval [CI]: −3.42 to 0.22; p=0.09) or incidence (MD: 1.00; CI: 0.755 to 1.33; p=1.00). Regarding change in tooth color, no significant differences were found between the use of the laser and other light sources (MD: −2.22; CI: −6.36 to 1.93; p=0.29). Conclusions: Within the limitations of the present study, laser exerts no influence on tooth sensitivity compared with other light sources when used during in-office bleaching. The included studies demonstrated that laser use during in-office bleaching may have no influence on tooth color change.

scholarly journals A systematic review of pharmacist-led audit and feedback interventions to influence prescribing behaviour in general practice settings

2021 ◽  
Vol 29 (Supplement_1) ◽  
pp. i34-i35
Author(s):  
M Carter ◽  
N Abutheraa ◽  
N Ivers ◽  
J Grimshaw ◽  
S Chapman ◽  
...  
Keyword(s):  
General Practice ◽  
Systematic Reviews ◽  
Health Professionals ◽  
Meta Analysis ◽  
Cochrane Review ◽  
Audit And Feedback ◽  
Cochrane Library ◽  
Randomised Trials ◽  
Prescribing Behaviour ◽  
Meta Analyses

Abstract Introduction Audit and Feedback (A&F) involves measuring data about practice, comparing it with clinical guidelines, professional standards or peer performance, and then feeding back the data to individuals/groups of health professionals to encourage change in practice (if required). A 2012 Cochrane review (1) found A&F was effective in changing health professionals’ behaviour and suggested that the person who delivers the A&F intervention influences its effect. Increasingly, pharmacists work in general practice and often have responsibility for medication review and repeat prescriptions. The effectiveness of pharmacist-led A&F in influencing prescribing behaviour is uncertain. Aim This secondary analysis from an ongoing update of the original Cochrane review aims to identify and describe pharmacist-led A&F interventions and evaluate their impact on prescribing behaviour in general practice compared with no intervention. Methods This sub-review is registered with PROSPERO: CRD42020194355 and complies with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (2). For the updated Cochrane review, the Cochrane Effective Practice and Organization of Care Group searched MEDLINE (1946 to present), EMBASE, CINAHL and Cochrane Library (March 2019) to identify randomised trials featuring A&F interventions. For this sub-review, authors screened titles and abstracts (May 2020) to identify trials involving pharmacist-led A&F interventions in primary care, extracted data, and assessed risk of bias (RoB) in eligible studies. Review results are summarised descriptively. Heterogeneity will be assessed and a random-effects meta-analysis is planned. Publication bias for selected outcomes and the certainty of the body of evidence will be evaluated and presented. Sub-group analyses will be conducted. Results Titles and abstracts of 295 studies identified for inclusion in the Cochrane A&F review update were screened. Eleven studies (all cluster-randomised trials) conducted in 9 countries (Denmark, Italy, Netherlands, Norway, Republic of Ireland, UK, Australia, Malaysia, USA) were identified for inclusion (Figure 1). Six studies had low RoB, two had high risk due to dissimilarities between trial arms at baseline and/or insufficient detail about randomisation, and three studies had unclear RoB. Studies examined the effect of A&F on prescribing for specific conditions (e.g. hypertension), medications (e.g. antibiotics), populations (e.g. patients &gt;70), and prescribing errors (e.g. inappropriate dose). The pharmacist delivering A&F was a colleague of intervention participants in five studies. Pharmacists’ levels of skill and experience varied; seven studies reported details of pharmacist training undertaken for trial purposes. A&F interventions in nine studies demonstrated changes in prescribing, including reductions in errors or inappropriate prescribing according to the study aims and smaller increases in unwanted prescribing compared with the control group. Data analyses are ongoing (results will be available for the conference). Conclusion The preliminary results demonstrate the effectiveness of pharmacist-led A&F interventions in different countries and health systems with influencing prescribing practice to align more closely with guidance. Studies measured different prescribing behaviours; meta-analysis is unlikely to include all 11 studies. Further detailed analysis including feedback format/content/frequency and pharmacist skill level/experience, work-base (external/internal to recipients), will examine the impact of specific features on intervention effectiveness. References 1. Ivers N, Jamtvedt G, Flottorp S, Young JM, Odgaard-Jensen J, French SD, et al. Audit and feedback: effects on professional practice and healthcare outcomes. Cochrane Database Syst Rev. 2012(6):CD000259. 2. Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6(7):e1000097.

scholarly journals Resting Heart Rate as a Predictor of Cancer Mortality: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 10 (7) ◽  
pp. 1354
Author(s):  
Diana P. Pozuelo-Carrascosa ◽  
Iván Cavero-Redondo ◽  
I.M. Lee ◽  
Celia Álvarez-Bueno ◽  
Sara Reina-Gutierrez ◽  
...  
Keyword(s):  
Heart Rate ◽  
Cancer Mortality ◽  
Meta Analysis ◽  
Positive Association ◽  
Cochrane Library ◽  
Resting Heart Rate ◽  
Potential Marker ◽  
Meta Analyses ◽  
Risk Of Cancer ◽  
The Relationship

This work was aimed to synthetize the evidence available about the relationship between resting heart rate (RHR) and the risk of cancer mortality. A computerized search in the Medline, EMBASE, Web of Science, and Cochrane Library databases from their inception to 24 September 2020 was performed. We performed three meta-analyses: (1) cancer mortality comparing the “less than 60 bpm” and “more than 60 bpm” categories; (2) cancer mortality comparing “less than 60 bpm”, “60 to 80 bpm”, and “more than 80 bpm” categories; and (3) analysis for 10–12 and 20 bpm increase in RHR and risk of cancer mortality. Twenty-two studies were included in the qualitative review, and twelve of them met the inclusion criteria for the meta-analysis. Our results showed a positive association between RHR and the risk of cancer mortality. This association was shown in a meta-analysis comparing studies reporting mean RHR values below and above 60 bpm, when comparing three RHR categories using less than 60 bpm as the reference category and, finally, in dose response analyses estimating the effect of an increase of 10–12 bpm in RHR, both in men and in women. In conclusion, a low RHR is a potential marker of low risk of cancer mortality.

Mindfulness- and Acceptance-Based Interventions for Stroke Survivors: A Systematic Review and Meta-Analysis

2021 ◽  
pp. 003435522110432
Author(s):  
Areum Han
Keyword(s):  
Systematic Review ◽  
Depressive Symptoms ◽  
Meta Analysis ◽  
Random Effect ◽  
Random Effect Model ◽  
Mental Fatigue ◽  
Stroke Survivors ◽  
Positive Effects ◽  
Meta Analyses

Objective: Mindfulness- and acceptance-based intervention (MABI) is an emerging evidenced-based practice, but no systematic review incorporating meta-analyses for MABIs in stroke survivors has been conducted. The objective of this systematic review was to measure the effectiveness of MABIs on outcomes in people with stroke. Method: Three electronic databases, including PubMed, CINAHL, and PsycINFO, were searched to identify relevant studies published in peer-reviewed journals. The methodological quality of the included studies was assessed. Data were extracted and combined in a meta-analysis with a random-effect model to compute the size of the intervention effect. Results: A total of 11 studies met the eligibility criteria. Meta-analyses found a small-to-moderate effect of MABIs on depressive symptoms (standardized mean difference [SMD] = 0.39, 95% confidence interval [CI] = [0.12, 0.66]) and a large effect on mental fatigue (SMD = 1.22, 95% CI = [0.57, 1.87]). No statistically significant effect of MABIs on anxiety, quality of life, and mindfulness was found, but there was a trend in favor of MABIs overall. Conclusions: This meta-analysis found positive effects of MABIs on depressive symptoms and mental fatigue in stroke survivors, but future high-quality studies are needed to guarantee treatment effects of MABIs on varied outcomes in stroke survivors.

Novel oral anticoagulats for the treatment of left ventricle thrombosis: a systematic review and meta-analysis

EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
M Serenelli ◽  
F Vitali ◽  
R Pavasini ◽  
E Tonet ◽  
G Pompei ◽  
...  
Keyword(s):  
Primary Outcome ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Random Effect ◽  
Random Effect Model ◽  
Left Ventricular ◽  
Left Ventricular Thrombus ◽  
Cochrane Library ◽  
Secondary Outcome ◽  
Ventricular Thrombus

Abstract Funding Acknowledgements Type of funding sources: None. Background novel oral anticoagulants (NOACs) are not guideline-recommanded treatment for left ventricular thrombus.  Purpose: the aim of this meta-analysis is to compare NOACs versus vitamin-K atagonsits (VKAs) efficacy in treating left ventricular thrombus (LVT). Methods: we systematically searched MEDLINE, Cochrane Library, Biomed Central, and Web of Science for trials comparing NOACs versus VKAs in the setting of LVT. Five studies, out of the 74 initially selected after first screening, were included in the meta-analysis. For the development of this meta-analysis, the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines were followed. The shortlisted studies were retrieved as full articles and appraised independently by two unblinded reviewers. The Mantel-Haensel method with a random effect model was used for the pooled analysis. The primary outcome was the occurrence of stroke and systemic embolism. Secondary outcome was occurrence of left ventricular thrombosis resolution during treatment.  Results: 707 patients were included in the analysis for the primary outcome. Of these, 230 were treated with NOACs and 477 with VKAs. The pooled OR for the primary outcome was 0.71 (95% CI 0.18-2.86, I2 67%), thus showing similar effect in term of ischaemic protection. A total of 698 patients, 228 on NOACs and 470 on VKAs were included in the analysis of the secondary outcome. The pooled OR for the secondary outcome pooled OR 0.97, 95% CI 0.56-1.68, I2 46%. Conclusions and Relevance: NOACs seem to have a similar efficacy profile compare to VKAs and so they should be considered as an alternative treatment for left ventricular thrombosis. Large prospective randomized clinical trials are needed to confirm this exploratory finding. Abstract Figure 1

MO501INCREASED ALBUMINURIA RISK IN CHRONIC KIDNEY DISEASE PATIENTS WHOSE WHITE COAT-, MASKED-, AND SUSTAINED HYPERTENSION: SYSTEMATIC REVIEW AND META-ANALYSIS

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Boby Pratama Putra ◽  
Felix Nugraha Putra
Keyword(s):  
Meta Analysis ◽  
Blood Pressure Measurement ◽  
Target Organ Damage ◽  
Random Effect ◽  
White Coat ◽  
Cochrane Library ◽  
White Coat Hypertension ◽  
Masked Hypertension ◽  
Sustained Hypertension ◽  
Standard Mean Difference

Abstract Background and Aims Latest classification of hypertension based on ambulatory blood pressure measurement was normotension (NT), white coat hypertension (WCHT), masked hypertension (MHT), and sustained hypertension (SHT). Recent studies suggest that WCHT, MHT, and SHT increase risk of target organ damage, particularly albuminuria, although the results were still inconsistent. Albuminuria is not only the sign of early glomerular damage in CKD patients, but also the signs of hypertension progression and predictors for cardiovascular events mortality. This study aims to compare the albuminuria risk among NT and WCHT, MHT, also SHT in CKD patients. Method We searched the literature comprehensively in online databases of Pubmed, EMBASE, ScienceDirect, and Cochrane Library to include all relevant studies using predefined terms until December 2020. We included studies that analyzed the albuminuria risk and compared the log2 urinary albumin-to-creatinine ratio (ACR) among NT and WCHT, MHT, or SHT in CKD patients. We used the Newcastle-Ottawa Scale for Observational Study checklist for evaluating bias risks. Analysis of the studies was conducted to provide pooled Odds Ratio (OR) for albuminuria risk and standard mean difference (SMD) for log2 ACR comparison with 95% Confidence Interval (CI) with random-effect heterogeneity test. Results We included 7 observational studies met our inclusion criteria. WCHT increases albuminuria risk although not statistically significant (pooled OR = 1.72, 95%CI 0.97 to 3.07, p = 0.06, I2 = 75%), while MHT and SHT significantly increase albuminuria risk with pooled OR respectively 1.62 (95%CI 1.03 to 2.53, p = 0.04, I2 = 82%) and 3.17 (95%CI 1.66 to 6.05, p = 0.0005, I2 = 94%). Controlled hypertension significantly protects CKD patients against albuminuria risk based on log2 ACR comparison with WCHT (SMD = 0.52, 95%CI 0.38 to 0.67, p&lt;0.00001, I2 = 0%), MHT (SMD = 0.34, 95%CI 0.19 to 0.49, p&lt;0.0001, I2 = 39%), and SHT (SMD = 0.63, 95%CI 0.31 to 0.95, p=0.0001, I2 = 76%). Conclusion White coat hypertension, masked hypertension, and sustained hypertension increase albuminuria risks in CKD patients. However, further studies are needed to determine the causality.

Is first-line immune checkpoint inhibitors (ICI) beneficial to platinum-eligible patients (pts) with advanced urothelial carcinoma (aUC)? a meta-analysis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16506-e16506
Author(s):  
Ce Cheng ◽  
Iloabueke Gabriel Chineke ◽  
Ali McBride ◽  
Juan Chipollini ◽  
Edward Paul Gelmann ◽  
...  
Keyword(s):  
Publication Bias ◽  
Subgroup Analysis ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Random Effect ◽  
Fixed Effect Model ◽  
Cochrane Library ◽  
First Line ◽  
Significance Level ◽  
Line Setting

e16506 Background: ICI have proven to benefit patients diagnosed with aUC who are platinum-ineligible. The role of platinum-eligible patients, in the first-line setting is being further elucidated after single positive randomized clinical trial (RCT) with ICI. Hence, we performed a meta-analysis to interpret the association of Overall Survival (OS) and PD-1 or PD-L1 inhibitors as first-line therapies in platinum-eligible patients with aUC. Methods: Randomized controlled trials were retrieved from PubMed, Web of Science, and Cochrane Library according to established inclusion criteria. Each article was assessed by the Newcastle-Ottawa Scale. The Hazard Risk (HR) and 95% confidence intervals (CI) were calculated. Random effect or fixed-effect model was used to calculate the pooled HR, based on heterogeneity significance. Sensitivity analysis and publication bias detection were performed. All statistical analysis were performed using RevMan software (v5.4; Cochrane library) and R Core Team (2016, Vienna, Austria), and all p-values were two-tailed, and the significance level was 0.05. Results: Sixty-seven articles were obtained from the database search, and based on inclusion/exclusion criteria, five RCTs were selected involving 4063 patients. All studies were considered moderate to high quality. A statistically significant association was found between initiation of immunotherapy as first-line treatment to platinum-eligible patients and increased OS (HR 0.87; 95% CI: 0.81,0.94, p = 0.004, I2= 38%). The subgroup analysis included positive PD1 (HR 0.81; 95% CI: 0.70,0.94, p = 0.004, I2= 34%) vs. negative expression (HR 0.96; 95% CI: 0.83,1.11, p = 0.58, I2= 0%); cisplatin (HR 0.81; 95% CI: 0.69,0.96, p = 0.02, I2= 47%) vs. carboplatin administration (HR 0.87; 95% CI: 0.76,1.01, p = 0.06, I2= 21%); male (HR 0.87; 95% CI: 0.77,0.97, p = 0.01, I2= 44%) vs. female (HR 0.85; 95% CI: 0.70,1.04, p = 0.11, I2= 0%); ECOG score 0 (HR 0.77; 95% CI: 0.67,0.89, p = 0.0005, I2= 0%) vs. ≥ 1 (HR 0.90; 95% CI: 0.78,1.02, p = 0.11, I2= 6%); Caucasian (HR 0.81; 95% CI: 0.73, 0.91, p = 0.0003, I2= 39%) vs. other race (HR 0.92; 95% CI: 0.75, 1.13, p = 0.44, I2= 0%). Similar association regardless of visceral lesion or age. Funnel plot, Egger's test (p = 0.6944), and Begg's test (0.7726) found no publication bias of analysis. Conclusions: This meta-analysis showed improved OS in platinum-eligible patients receiving first-line ICI in aUC. Furthermore, a subgroup analysis yielded an increased OS and cisplatin, positive PD1 status, ECOG 0, male gender, and Caucasian race. In this rapidly evolving clinical practice changes, our meta-analysis provides support to currently recommended avelumab maintenance after platinum induction therapy in the first-line setting and further provide guidance on patient selection for aUC.

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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