scholarly journals META-ANALYSIS OF CONTINUOUS PHENOTYPES IDENTIFIES A GENE SIGNATURE THAT CORRELATES WITH COPD DISEASE STATUS

2016 ◽  
Author(s):  
MADELEINE SCOTT ◽  
FRANCESCO VALLANIA ◽  
PURVESH KHATRI
Keyword(s):  
Meta Analysis ◽  
Disease Status ◽  
Gene Signature

A perspective on role of calcium and vitamin D in cardiovascular outcomes and lipid profile

2015 ◽  
Vol 26 (5) ◽  
Author(s):  
Tarun Arora ◽  
Harmeet Singh Rehan
Keyword(s):  
Vitamin D ◽  
Calcium Supplementation ◽  
Meta Analysis ◽  
Disease Status ◽  
Controlled Trials ◽  
Lipid Levels ◽  
Randomized Controlled ◽  
The Past ◽  
Vitamin D Supplements

AbstractRecent concerns on increased incidence of myocardial infarction and stroke on administration of calcium and vitamin D supplements have alarmed the physicians about safety of these drugs. Although both calcium and vitamin D have been shown in the past to have beneficial effect on cardiovascular disease status through lowering of harmful lipids, these findings have been contradicted by some recent meta-analysis and randomized controlled trials that have shown no beneficial or in some cases a deteriorating effect of these supplements on lipid levels. In particular, calcium supplementation has been associated more with increased incidence of cardiovascular morbidity than vitamin D, but the convincing proof is still lacking. Here we have highlighted the results of some significant studies that might impact the prescription of these drugs.

scholarly journals Epigenetic analysis of Paget’s disease of bone identifies differentially methylated loci that predict disease status

2021 ◽  
Author(s):  
Ilhame Diboun ◽  
Sachin Wani ◽  
Stuart H Ralston ◽  
Omar M E Albagha
Keyword(s):  
Dna Methylation ◽  
Meta Analysis ◽  
Cpg Islands ◽  
Osteoclast Differentiation ◽  
Paget’S Disease ◽  
Disease Status ◽  
Paget's Disease ◽  
Paget’S Disease Of Bone ◽  
Paget's Disease Of Bone ◽  
Body Regions

AbstractPaget’s Disease of Bone (PDB) is characterized by focal increases in disorganized bone remodeling. This study aims to characterize PDB associated changes in DNA methylation profiles in patients’ blood. Meta-analysis of data from the discovery and replication set, comprising of 116 PDB cases and 130 controls, revealed significant differences in DNA methylation at 14 CpG sites, 4 CpG islands, and 6 gene-body regions. These loci, including two characterized as functional through eQTM analysis, were associated with functions related to osteoclast differentiation, mechanical loading, immune function, and viral infection. A multivariate classifier based on discovery samples was found to discriminate PDB cases and controls from the replication with a sensitivity of 0.84, specificity of 0.81, and an area under curve of 92.8%. In conclusion, this study has shown for the first time that epigenetic factors contribute to the pathogenesis of PDB and may offer diagnostic markers for prediction of the disease.

scholarly journals 119. Prospective Validation of a 3-Gene Signature for Tuberculosis Diagnosis, Predicting Progression and Evaluating Treatment Response

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S5-S5
Author(s):  
Hayley Warsinske ◽  
Aditya Rao ◽  
Flora Martinez Figueira Moreira ◽  
Paulo Cesar Pereira Dos Santos ◽  
Andrew Liu ◽  
...  
Keyword(s):  
Treatment Response ◽  
Disease Onset ◽  
Disease Status ◽  
Gene Signature ◽  
Case Control ◽  
World Health ◽  
Response To Treatment ◽  
Screening Study ◽  
Health Organization ◽  
Triage Test

Abstract Background The World Health Organization (WHO) has identified the need for a nonsputum-based triage test for tuberculosis (TB) that can be used to identify those who need further testing to identify active disease. We investigated whether our previously described 3-gene TB score could identify individuals with active tuberculosis (ATB) prior to seeking care (“active case detection”) and how the 3-gene TB score correlated with the timing of disease onset, disease severity, and response to treatment. Methods This study consisted of a prospective nested case–control trial, Brazil Active Screening Study (BASS; 2016), and re-analysis of data from 2 prospective cohort studies, the Adolescent Cohort Study (ACS; 2005–2007), and the Catalysis Treatment Response Cohort (CTRC; 2010–2013). The BASS case–control subcohort contained 81 adults (ages 20–72 years, 33 ATB, 48 controls). The ACS contained 153 adolescents (ages 12–18 years, 46 ATB, 107 LTBI). The CTRC-contained 138 adults (ages 17–67 years, 100 ATB, 17 other lung disease patients, 21 healthy controls). Results The 3-gene TB score diagnosed ATB patients with high accuracy: BASS cohort AUC = 0.87 (95% CI = 0.82–0.91, Figure 1A), ACS cohort AUC = 0.86 (95% CI = 0.76–0.97, Figure 1B), and CTRC AUC = 0.93 (95% CI = 0.88–0.97). In the ACS, the 3-gene TB score predicted progression from LTBI to ATB 6 months prior to positive sputum test (AUC = 0.86; 95% CI = 0.79–0.92, Figure 1B). In the CTRC, the 3-gene TB score correlated with glycolytic activity ratio of PET-CT at baseline (correlation = 0.54, P = 3.98 × 10−8, Figure 1C) and at the end of treatment (correlation = −0.408, P = 3.72 × 10−5). In the CTRC, the 3-gene TB score at baseline predicted the likelihood of prolonged sputum positivity following treatment initiation and treatment response at 6 months (P = 3.6 × 10−5). Collectively, across all cohorts, the 3-gene TB score identified ATB patients with 90% sensitivity and 70% specificity, and had 99% negative predictive value (NPV) at 5% prevalence. Conclusion Across 3 independent prospective cohorts, the 3-gene TB score closely approaches the WHO target product profile benchmarks for non-sputum–based triage test at high NPV. These performance characteristics make it a potential test for ruling out ATB and for monitoring disease status. Disclosures T. E. Sweeney, Inflammatix, Inc.: Employee and Shareholder, Salary. P. Khatri, Inflammatix Inc.: Board Member, Equity

Depressive symptoms prospectively predict cardiovascular disease among older adults: Findings from the Maine-Syracuse Longitudinal Study

2018 ◽  
Vol 25 (12) ◽  
pp. 2006-2016
Author(s):  
Emily AP Haigh ◽  
Olivia E Bogucki ◽  
Peter J Dearborn ◽  
Michael A Robbins ◽  
Merrill F Elias
Keyword(s):  
Cardiovascular Disease ◽  
Older Adults ◽  
Depressive Symptoms ◽  
Meta Analysis ◽  
Disease Status ◽  
Depression Status ◽  
Increased Risk ◽  
Long Term Follow Up ◽  
Prospective Association

A recent meta-analysis identified a prospective association between depression and cardiovascular disease; however, there was no association for studies with long-term follow-up periods. The literature has primarily focused on baseline depression status or symptoms, which may not capture the chronic nature of depression. This study examined the prospective relationship between depressive symptoms and cardiovascular disease up to 15 years later in 274 cardiovascular disease–free older adults. Depressive and anxiety symptoms, mean arterial pressure, and cardiovascular disease status were assessed. Baseline and chronic depressive symptoms predicted increased risk of cardiovascular disease, underscoring the importance of assessing and treating depression in older adults.

scholarly journals Validation of Gene Expression-Based Predictive Biomarkers for Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4642
Author(s):  
Tomoyuki Momma ◽  
Hirokazu Okayama ◽  
Yasuyuki Kanke ◽  
Satoshi Fukai ◽  
Hisashi Onozawa ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rectal Cancer ◽  
Meta Analysis ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Predictive Biomarkers ◽  
Advanced Rectal Cancer ◽  
Gene Signature ◽  
Locally Advanced Rectal Cancer ◽  
Predictive Values

Background: Neoadjuvant chemoradiotherapy (nCRT) followed by surgery is widely used for patients with locally advanced rectal cancer. However, response to nCRT varies substantially among patients, highlighting the need for predictive biomarkers that can distinguish non-responsive from responsive patients before nCRT. This study aimed to build novel multi-gene assays for predicting nCRT response, and to validate our signature and previously-reported signatures in multiple independent cohorts. Methods: Three microarray datasets of pre-therapeutic biopsies containing a total of 61 non-responders and 53 responders were used as the discovery cohorts to screen for genes that were consistently associated with nCRT response. The predictive values of signatures were tested in a meta-analysis using six independent datasets as the validation cohorts, consisted of a total of 176 non-responders and 99 responders. Results: We identified four genes, including BRCA1, GPR110, TNIK, and WDR4 in the discovery cohorts. Although our 4-gene signature and nine published signatures were evaluated, they were unable to predict nCRT response in the validation cohorts. Conclusions: Although this is one of the largest studies addressing the validity of gene expression-based classifiers using pre-treatment biopsies from patients with rectal cancer, our findings do not support their clinically meaningful values to be predictive of nCRT response.

P6268Cardiovascular outcomes of new anti-diabetic agents - A meta-analysis of randomized controlled trials

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
Y Lin ◽  
C Parco ◽  
M Brockmeyer ◽  
A Karathanos ◽  
V Schulze ◽  
...  
Keyword(s):  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Disease Status ◽  
Placebo Control ◽  
Diabetic Patients ◽  
Controlled Trials ◽  
Coronary Syndrome ◽  
Randomized Controlled ◽  
Major Cardiovascular Events ◽  
All Cause Mortality

Abstract Background and purpose The risk of major cardiovascular events (MACE) is increased in patients with diabetes mellitus. Recently published clinical trials of three different pharmacological classes (DPP4 inhibitors (DPP4i), SGLT2-inhibitors (SGLT2i), GLP-1-receptor-antagonists (GLP1RA)) of new anti-diabetic agents (ADA) showed potential benefits for cardiovascular (CV) outcomes. We thus aimed to perform a meta-analysis of randomized controlled trials (RCTs) of these ADA to elucidate benefits on CV outcomes in diabetic patients. Methods Following a systematic online database search, all RCTs reporting CV outcomes of DPP4i, SGLT2i or GLP1RA vs. Placebo in diabetic patients up until December 2018 were eligible for inclusion in the meta-analysis. Studies including patients with acute coronary syndrome (ACS) were excluded. Data were abstracted and analyzed with the inverse-variance method and a random-effects model, hazard ratios (HR) with 95% confidence intervals (CI) were used as summary statistics. CV outcomes of MACE, myocardial infarction (MI), stroke, heart failure (HF), CV death and all-cause mortality were analyzed. Results Eleven RCTs (DPP4i: SAVOR, TECOS, CARMELINA; GLP1RA: LEADER, SUSTAIN-6, EXSCEL, Harmony; SGLT2i: EMPA-REG OUTCOME, CANVAS Program, DECLARE) with 109,316 patients were selected for inclusion. ELIXA and EXAMINE were excluded due to their inclusion of patients with ACS, CAROLINA was excluded for lack of placebo-control. In the pooled meta-analysis of all trials, ADA significantly reduced the risk for MACE (Hazard ratio (HR) 0.91, CI 0.86–0.96, p=0.0004), MI (HR 0.91, CI 0.85–0.96, p=0.02), CV death (HR 0.9, CI 0.82–0.99, P=0.02) and all-cause mortality (HR 0.92, CI 0.85–0.99, p=0.03). There was no difference in the risk for stroke (HR 0.94, CI 0.87–1.02, p=0.16) and HF (HR 0.88, CI 0.76–1.02, p=0.08). In agent-specific subgroup analyses, GLP1RA and SGLT2i showed significant reductions in MACE (GLP1RA: HR 0.85, CI 0.78–0.92, p<0.0001; SGLT2i: HR 0.89, CI 0.83–0.96, p=0.001), MI (GLP1RA: HR 0.86, CI 0.76–0.98, p=0.02; SGLT2i: HR 0.88, CI 0.79–0.97, p=0.01) and all-cause mortality (GLP1RA: HR 0.88, CI 0.81–0.95; p=0.001; SGLT2i: HR 0.83, CI 0.70–0.99; p=0.03). GLP1RA significantly reduced risk for stroke (HR 0.85, CI 0.75–0.96, p=0.008) and CV death (HR 0.86, CI 0.78–0.95, p=0.002). SGLT2I were especially effective in the reduction of risk for HF (HR 0.69, CI 0.61–0.79; p<0.0001). DPP4i inhibitors however failed to show superiority in all analyzed outcomes. Conclusions This meta-analysis lends evidence to GLP1RA and SGLT2i benefits for MACE, MI and all-cause mortality, while DPP4i failed to show superiority in cardiovascular outcomes. Individualized medication for diabetic patients depending on CV disease status should be considered.

scholarly journals A Meta-Analysis of the Performance of a Blood-Based Exposure Response Gene Signature Across Clinical Studies on the Tobacco Heating System 2.2 (THS 2.2)

2019 ◽  
Vol 10 ◽  
Author(s):  
Florian Martin ◽  
Marja Talikka ◽  
Nikolai V. Ivanov ◽  
Christelle Haziza ◽  
Julia Hoeng ◽  
...  
Keyword(s):  
Clinical Studies ◽  
Meta Analysis ◽  
Heating System ◽  
Gene Signature ◽  
Response Gene ◽  
Exposure Response
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