Faculty Opinions recommendation of Network meta-analysis on the log-hazard scale, combining count and hazard ratio statistics accounting for multi-arm trials: a tutorial.

2010 ◽  
Author(s):  
Oliver Keene
Keyword(s):  
Meta Analysis ◽  
Hazard Ratio

scholarly journals Mortality due to cancer treatment delay: systematic review and meta-analysis

BMJ ◽  
2020 ◽  
pp. m4087 ◽  
Author(s):  
Timothy P Hanna ◽  
Will D King ◽  
Stephane Thibodeau ◽  
Matthew Jalink ◽  
Gregory A Paulin ◽  
...  
Keyword(s):  
Systematic Review ◽  
Overall Survival ◽  
Confidence Interval ◽  
Cancer Treatment ◽  
Head And Neck ◽  
Adjuvant Radiotherapy ◽  
Systemic Treatment ◽  
Meta Analysis ◽  
Treatment Delay ◽  
Hazard Ratio

Abstract Objective To quantify the association of cancer treatment delay and mortality for each four week increase in delay to inform cancer treatment pathways. Design Systematic review and meta-analysis. Data sources Published studies in Medline from 1 January 2000 to 10 April 2020. Eligibility criteria for selecting studies Curative, neoadjuvant, and adjuvant indications for surgery, systemic treatment, or radiotherapy for cancers of the bladder, breast, colon, rectum, lung, cervix, and head and neck were included. The main outcome measure was the hazard ratio for overall survival for each four week delay for each indication. Delay was measured from diagnosis to first treatment, or from the completion of one treatment to the start of the next. The primary analysis only included high validity studies controlling for major prognostic factors. Hazard ratios were assumed to be log linear in relation to overall survival and were converted to an effect for each four week delay. Pooled effects were estimated using DerSimonian and Laird random effect models. Results The review included 34 studies for 17 indications (n=1 272 681 patients). No high validity data were found for five of the radiotherapy indications or for cervical cancer surgery. The association between delay and increased mortality was significant (P<0.05) for 13 of 17 indications. Surgery findings were consistent, with a mortality risk for each four week delay of 1.06-1.08 (eg, colectomy 1.06, 95% confidence interval 1.01 to 1.12; breast surgery 1.08, 1.03 to 1.13). Estimates for systemic treatment varied (hazard ratio range 1.01-1.28). Radiotherapy estimates were for radical radiotherapy for head and neck cancer (hazard ratio 1.09, 95% confidence interval 1.05 to 1.14), adjuvant radiotherapy after breast conserving surgery (0.98, 0.88 to 1.09), and cervix cancer adjuvant radiotherapy (1.23, 1.00 to 1.50). A sensitivity analysis of studies that had been excluded because of lack of information on comorbidities or functional status did not change the findings. Conclusions Cancer treatment delay is a problem in health systems worldwide. The impact of delay on mortality can now be quantified for prioritisation and modelling. Even a four week delay of cancer treatment is associated with increased mortality across surgical, systemic treatment, and radiotherapy indications for seven cancers. Policies focused on minimising system level delays to cancer treatment initiation could improve population level survival outcomes.

Long-Term Blood Pressure Variability Increases Risks of Dementia and Cognitive Decline: A Meta-Analysis of Longitudinal Studies

Hypertension ◽  
2021 ◽  
Author(s):  
Pingping Jia ◽  
Helen W.Y. Lee ◽  
Joyce Y.C. Chan ◽  
Karen K.L. Yiu ◽  
Kelvin K.F. Tsoi
Keyword(s):  
Blood Pressure ◽  
Risk Factor ◽  
Cognitive Impairment ◽  
Cognitive Decline ◽  
Longitudinal Studies ◽  
Meta Analysis ◽  
Hazard Ratio ◽  
Literature Searches ◽  
Meta Regression

High blood pressure (BP) is considered as an important risk factor for cognitive impairment and dementia. BP variability (BPV) may contribute to cognitive function decline or even dementia regardless of BP level. This study aims to investigate whether BPV is an independent predictor for cognitive impairment or dementia. Literature searches were performed in MEDLINE, Embase, PsycINFO, CINAHL, and Web of Science to May 2021. Longitudinal studies that assessed the risk of dementia or cognitive impairment with BPV as the predictor was included. Meta-analysis and meta-regression were performed to evaluate the effect of BPV on the risk of dementia or cognitive impairment. A total of 5919 papers were identified, and 16 longitudinal studies were included, which had >7 million participants and a median age from 50.9 to 79.9 years and a median follow-up of around 4 years. Thirteen studies reported visit-to-visit BPV and concluded that systolic BPV increases the risk of dementia with a pooled hazard ratio of 1.11 (95% CI, 1.05–1.17), and increases the risk of cognitive impairment with a pooled hazard ratio of 1.10 (95% CI, 1.06–1.15). Visit-to-visit diastolic BPV also increased the risk of dementia and cognitive decline. A meta-regression revealed a linear relationship between higher BPV and risks of dementia and cognitive impairment. Similar findings were observed in the studies with day-to-day BPV. This study suggests that long-term BPV is an independent risk factor for cognitive impairment or dementia, so an intervention plan for reducing BPV can be a target for early prevention of dementia.

scholarly journals Better survival of patients with oligo- compared with polymetastatic cancers:  a systematic review and meta-analysis of 173 studies

F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 423
Author(s):  
Fausto Petrelli ◽  
Antonio Ghidini ◽  
Michele Ghidini ◽  
Roberta Bukovec ◽  
Francesca Trevisan ◽  
...  
Keyword(s):  
Meta Analysis ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Hazard Ratio ◽  
Modern Concept ◽  
Cochrane Library ◽  
Published Data ◽  
Risk Of Death ◽  
Personalized Approach ◽  
The Cochrane Library

Background: The modern concept of oligometastatic (OM) state has been initially developed to describe patients with a low burden of disease and with a potential for cure with local ablative treatments. We systematically assessed the risk of death and relapse of oligometastatic (OM) cancers compared to cancers with more diffuse metastatic spread, through a meta-analysis of published data.  Methods: PubMed, the Cochrane Library, and EMBASE were searched for studies reporting prognosis of patients with OM solid tumors. Risk of death and relapse were extracted and pooled to provide an adjusted hazard ratio with a 95% confidence interval (HR 95%CI).  The primary outcome of the study refers to overall mortality in OM vs. polymetastatic (PM) patients.  Results. Mortality and relapse associated with OM state in patients with cancer were evaluated among 104,234 participants (n=173 studies). Progression-free survival was better in patients with OM disease (hazard ratio [HR] = 0.62, 95% CI 0.57–0.68; P <.001; n=69 studies). Also, OM cancers were associated with a better overall survival (OS) (HR = 0.65, 95% CI 0.62-0.68; P<.01; n=161 studies). In colorectal (CRC), breast, non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC) the reduction in the risk of death for OM patients were 35, 38, 30 and 42%, respectively. Biliary tract and cervical cancer do not significantly better in OM stage likely for paucity of data. Conclusions. Patients with OM cancers have a significantly better prognosis than those with more widespread stage IV tumors. In OM cancer patients a personalized approach should be pursued.

scholarly journals Genome-Wide Meta-Analysis Validates a Role for S1PR1 in Microtubule Targeting Agent-Induced Sensory Peripheral Neuropathy

2020 ◽  
Author(s):  
Katherina C. Chua ◽  
Chenling Xiong ◽  
Carol Ho ◽  
Taisei Mushiroda ◽  
Chen Jiang ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Association Studies ◽  
Meta Analysis ◽  
Regulatory Elements ◽  
Hazard Ratio ◽  
European Ancestry ◽  
Genome Wide Association Studies ◽  
Sensory Peripheral Neuropathy ◽  
Genome Wide ◽  
Microtubule Targeting Agents

AbstractMicrotubule targeting agents (MTAs) are anticancer therapies commonly prescribed for breast cancer and other solid tumors. Sensory peripheral neuropathy (PN) is the major dose-limiting toxicity for MTAs and can limit clinical efficacy. The current pharmacogenomic study aimed to identify genetic variations that explain patient susceptibility and drive mechanisms underlying development of MTA-induced PN. A meta-analysis of genome-wide association studies (GWAS) from two clinical cohorts treated with MTAs (CALGB 40502 and CALGB 40101) was conducted using a Cox regression model with cumulative dose to first instance of grade 2 or higher PN. Summary statistics from a GWAS of European subjects (n = 469) in CALGB 40502 that estimated cause-specific risk of PN were meta-analyzed with those from a previously published GWAS of European ancestry (n = 855) from CALGB 40101 that estimated the risk of PN. Novel single nucleotide polymorphisms in an enhancer region downstream of sphingosine-1-phosphate receptor 1 (S1PR1 encoding S1PR1; e.g., rs74497159, βCALGB40101 per allele log hazard ratio (95% CI) = 0.591 (0.254 - 0.928), βCALGB40502 per allele log hazard ratio (95% CI) = 0.693 (0.334 - 1.053); PMETA = 3.62×10−7) were the most highly ranked associations based on P-values with risk of developing grade 2 and higher PN. In silico functional analysis identified multiple regulatory elements and potential enhancer activity for S1PR1 within this genomic region. Inhibition of S1PR1 function in iPSC-derived human sensory neurons shows partial protection against paclitaxel-induced neurite damage. These pharmacogenetic findings further support ongoing clinical evaluations to target S1PR1 as a therapeutic strategy for prevention and/or treatment of MTA-induced neuropathy.

MRD assessment using NGS in patients with acute myeloid leukemia undergoing hematopoietic stem cell transplantation: Meta-analysis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e19002-e19002
Author(s):  
Osama Mosalem ◽  
Mahmoud Abdelsamia ◽  
Haitham Abdelhakim
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Meta Analysis ◽  
Hazard Ratio ◽  
P Value ◽  
Hematopoietic Stem

e19002 Background: The presence of measurable residual disease (MRD) preceding hematopoietic stem cell transplantation (HSCT) in acute myeloid leukemia (AML) is increasingly recognized as a risk factor for leukemic relapse and decreased survival. Over many years, attempts have been looking at developing tools to detect MRD; this includes multiparametric flow cytometry, quantitative polymerase chain reaction, and most recently, next-generation sequencing (NGS). NGS offers higher sensitivity and detection rate of disease-related gene mutations, thereby potentially improving disease outcomes. Our study sought to review the scientific literature that included NGS‐detected molecular MRD in patients with AML who underwent bone marrow transplantation. Methods: We performed a systematic search using PubMed, Google Scholar, EMBASE, and SCOPUS up until October 2020. Inclusion criteria included articles that reported the association between pre-HSCT MRD detected by NGS and post HSCT outcome in patients with AML. We extracted hazard ratios for the cumulative incidence of relapse (CIR), overall survival (OS) and leukemia free survival (LFS). A random-effect model was utilized to calculate the hazard ratio (HR) with a 95% confidence interval (CI). Results: Six studies met our inclusion criteria. Our meta-analysis showed that the detection of pre-transplant MRD by NGS was associated with increased risk of cumulative incidence of relapse (hazard ratio=2.5, CI= 1.6-3.9, with p-value <0.001) and decreased overall survival (hazard ratio=1.6, CI= 1.6-2.3, p-value 0.005). LFS was significantly higher in those who had negative MRD detection by NGS before transplantation (HR=1.9, CI= 1.3-2.8 with p-value 0.001). These results were independent of the cytogenetic risk of conditioning intensity. There was heterogeneity between our studies (I2 = 53%, 52%, and 59% for CIR, OS, and LFS, respectively). Conclusions: The application of NGS to detect MRD is a strong predictor of outcome in patients with AML who are undergoing hematopoietic stem cell transplantation. NGS-detected MRD positive status prior to HSCT is indicative of a higher risk of relapse and decreased overall survival in this meta-analysis. Despite the limitations in our study, it demonstrates the value of MRD detection by NGS in HSCT recipients.

scholarly journals Antiplatelet Therapy After Spontaneous Intracerebral Hemorrhage and Functional Outcomes

Stroke ◽  
2019 ◽  
Vol 50 (11) ◽  
pp. 3057-3063
Author(s):  
Santosh B. Murthy ◽  
Alessandro Biffi ◽  
Guido J. Falcone ◽  
Lauren H. Sansing ◽  
Victor Torres Lopez ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Functional Outcome ◽  
Antiplatelet Therapy ◽  
Functional Outcomes ◽  
Randomized Clinical Trials ◽  
Massachusetts General Hospital ◽  
Meta Analysis ◽  
Hazard Ratio ◽  
Stroke Registry ◽  
All Cause Mortality

Background and Purpose— Observational data suggest that antiplatelet therapy after intracerebral hemorrhage (ICH) alleviates thromboembolic risk without increasing the risk of recurrent ICH. Given the paucity of data on the relationship between antiplatelet therapy after ICH and functional outcomes, we aimed to study this association in a multicenter cohort. Methods— We meta-analyzed data from (1) the Massachusetts General Hospital ICH registry (n=1854), (2) the Virtual International Stroke Trials Archive database (n=762), and (3) the Yale stroke registry (n=185). Our exposure was antiplatelet therapy after ICH, which was modeled as a time-varying covariate. Our primary outcomes were all-cause mortality and a composite of major disability or death (modified Rankin Scale score 4–6). We used Cox proportional regression analyses to estimate the hazard ratio of death or poor functional outcome as a function of antiplatelet therapy and random-effects meta-analysis to pool the estimated HRs across studies. Additional analyses stratified by hematoma location (lobar and deep ICH) were performed. Results— We included a total of 2801 ICH patients, of whom 288 (10.3%) were started on antiplatelet medications after ICH. Median times to antiplatelet therapy ranged from 7 to 39 days. Antiplatelet therapy after ICH was not associated with mortality (hazard ratio, 0.85; 95% CI, 0.66–1.09), or death or major disability (hazard ratio, 0.83; 95% CI, 0.59–1.16) compared with patients not started on antiplatelet therapy. Similar results were obtained in additional analyses stratified by hematoma location. Conclusions— Antiplatelet therapy after ICH appeared safe and was not associated with all-cause mortality or functional outcome, regardless of hematoma location. Randomized clinical trials are needed to determine the effects and harms of antiplatelet therapy after ICH.

Impact of Smoking on Survival Outcomes in HPV-Related Oropharyngeal Carcinoma: A Meta-analysis

2020 ◽  
Vol 163 (6) ◽  
pp. 1114-1122
Author(s):  
Ryan Ference ◽  
David Liao ◽  
Qi Gao ◽  
Vikas Mehta
Keyword(s):  
Overall Survival ◽  
Meta Analysis ◽  
Hazard Ratio ◽  
Cochrane Library ◽  
Survival Outcomes ◽  
Oropharyngeal Carcinoma ◽  
Disease Specific Survival ◽  
Free Survival ◽  
Current Smoking ◽  
Disease Specific

Objective Characterize the survival impact of smoking on HPV-related (human papillomavirus) oropharyngeal squamous cell carcinoma. Data Sources Articles from 2000 to 2019 in the PubMed, Embase, and Cochrane Library databases were systematically reviewed for content and inclusion/exclusion criteria. Review Methods Two reviewers independently analyzed the databases for eligibility and quality of the articles. Demographic data, smoking history, and survival outcomes were recorded. Hazard ratios and 95% CIs were collectively analyzed through a random effects meta-analysis model. Results Fifteen articles were included in the meta-analysis for overall survival, disease-specific survival, disease-free survival, progression-free survival, and locoregional recurrence outcomes. The overall survival hazard ratio was 2.4 for ever having smoked (95% CI, 1.4-4.0; P = .0006, I2 = .384) and 3.2 for current smoking (95% CI, 2.2-4.6; P < .0001, I2 = 0). The hazard ratio for disease-specific survival in current smokers was 6.3 (95% CI, 1.3-29.3; P = .0194, I2 = 0). Ever smoking had a larger impact on overall survival and disease-specific survival than the 10–pack year smoking threshold. Conclusion Smoking negatively affects survival in patients with HPV-related oropharyngeal carcinoma across all outcomes. Current smoking during treatment is associated with the greatest reduction in survival, possibly secondary to diminished radiation therapy efficacy.

scholarly journals The Prognostic Significance of NEK2 in Hepatocellular Carcinoma: Evidence from a Meta-Analysis and Retrospective Cohort Study

2018 ◽  
Vol 51 (6) ◽  
pp. 2746-2759 ◽  
Author(s):  
YuSheng Cheng ◽  
XiaoLong Chen ◽  
LinSen Ye ◽  
YinCai Zhang ◽  
Jing Liang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Multivariate Analysis ◽  
Risk Factor ◽  
Cohort Study ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Meta Analysis ◽  
Normal Liver ◽  
Hazard Ratio ◽  
Free Survival

Background/Aims: Numerous studies have shown that NIMA-related kinase 2 (NEK2) expression in hepatocellular carcinoma (HCC) tissue is associated with survival and clinicopathological features; however, the evidence remains inconclusive. Thus, we aimed to further explore the prognostic and clinicopathological significance of NEK2 expression in HCC using a two-part study consisting of a retrospective cohort study and a meta-analysis. Methods: In the cohort study, NEK2 expression in 206 HCC samples and adjacent normal liver tissues was detected by immunohistochemistry (IHC). Patients were divided into a high NEK2 expression group and a low NEK2 expression group by the median value of the immunohistochemical scores. The Kaplan–Meier method with the log-rank test was used to analyze survival outcomes in the two groups, and multivariate analysis based on Cox proportional hazard regression models was applied to identify independent prognostic factors. In the meta-analysis, eligible studies were searched in PubMed, EMBASE, Web of Science, and CNKI databases. STATA version 12.0 (Stata Corporation, College Station, TX) was used for statistical analyses. Results: The IHC results of our cohort study showed higher NEK2 expression in HCC tissues compared with adjacent normal liver tissues. Multivariate analysis revealed that high NEK2 expression was an independent risk factor for poor overall survival (OS) [hazard ratio (HR) = 1.763; 95% CI, 1.060–2.935; P = 0.029] and disease-free survival (DFS) [hazard ratio (HR) = 1.687; 95% CI, 1.102–2.584; P = 0.016] in HCC patients. A total of 11 studies with 1,698 patients were enrolled in the meta-analysis, consisting of 10 studies from the database search and our cohort study. The pooled results revealed that high NEK2 expression correlated closely with poor OS among HCC patients (HR = 1.47; 95% CI, 1.21–1.80; P < 0.01), and DFS/recurrence-free survival (RFS) (HR = 1.92; 95% CI, 1.41–2.63; P < 0.01). Additionally, our meta-analysis also showed that the proportion of HCC patients with high NEK2 expression was greater in the group with larger tumors (> 5 cm) than in the group with smaller tumors (≤ 5 cm) [odds ratio (OR) = 2.02; 95% CI, 1.13–3.64; P < 0.01). Conclusion: Our study demonstrated that high NEK2 expression is a risk factor for poor survival in HCC patients. More prospective, homogeneous, and multiethnic studies are required to validate our findings.

Prognostic efficacy of circulating asymmetric dimethylarginine in patients with peripheral arterial disease: A meta-analysis of prospective cohort studies

Vascular ◽  
2017 ◽  
Vol 26 (3) ◽  
pp. 322-330
Author(s):  
Renzhu Chu ◽  
Dawei Yu ◽  
Junyi Chu ◽  
Mingqiang Lin ◽  
Hongbo Yu
Keyword(s):  
Confidence Interval ◽  
Peripheral Arterial Disease ◽  
Asymmetric Dimethylarginine ◽  
Meta Analysis ◽  
Arterial Disease ◽  
Hazard Ratio ◽  
Adjusted Hazard Ratio ◽  
Sensitivity Analyses ◽  
Increased Risk ◽  
Peripheral Arterial

Background Asymmetric dimethylarginine is suggested to be a marker of poor prognosis in patients with atherosclerosis. However, the predictive role of circulating asymmetric dimethylarginine for clinical outcome in patients with peripheral arterial disease has not been determined. Aims To quantitatively assess the predictive value of circulating asymmetric dimethylarginine for clinical outcome in patients with peripheral arterial disease in a meta-analysis of prospective cohort studies. Methods Relevant studies were identified by systematically searching of PubMed and Embase databases. A random-effect model was used to synthesize the results. Sensitivity analyses by omitting one study at a time were performed to evaluate the robustness of the results. Results Six studies with 2535 peripheral arterial disease patients were included. Patients with higher circulating asymmetric dimethylarginine at baseline were associated with higher risk of all-cause mortality (adjusted hazard ratio: 1.63, 95% confidence interval: 1.28–2.06, I2 = 16%), and major adverse cardiovascular events (adjusted hazard ratio: 2.01, 95% confidence interval: 1.08–3.73, I2 = 78%) as compared with those with lower circulating asymmetric dimethylarginine at baseline. Specifically, every increment of 0.1 µmol/l of asymmetric dimethylarginine was associated with 18% (adjusted hazard ratio: 1.18, 95% confidence interval: 1.06–1.31) increased risk for all-cause mortality and 14% (adjusted hazard ratio: 1.14, 95% confidence interval: 1.04–1.25) increased risk for major adverse cardiovascular disease. Sensitivity analyses by omitting one study at a time did not significantly change the results. Conclusion Higher circulating asymmetric dimethylarginine at baseline may be associated with higher incidence of cardiovascular events and mortality in patients with peripheral arterial disease.

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