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The Cochrane Database of Systematic... May 2014Bronchiectasis is predominantly an acquired disease process that represents the end stage of a variety of unrelated pulmonary insults. It is defined as persistent... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Bronchiectasis is predominantly an acquired disease process that represents the end stage of a variety of unrelated pulmonary insults. It is defined as persistent irreversible dilatation and distortion of medium-sized bronchi. It has been suggested that with widespread use of high-resolution computed tomography, more bronchiectasis diagnoses are being made. Patients diagnosed with bronchiectasis frequently have difficulty expectorating sputum. Sputum therefore is retained in the lungs and may become infected, leading to further lung damage. Mucolytic agents target hypersecretion or changed physiochemical properties of sputum to make it easier to clear. One drug, recombinant human DNase, breaks down the DNA that is released at the site of infection by neutrophils.Mucus clearance along with antimicrobial therapy remains an integral part of bronchiectasis management. Chest physiotherapy along with mucolytic agents is commonly used in practice without clear supportive evidence.
OBJECTIVES
To determine whether ingested or inhaled mucolytics are effective in the treatment of patients with bronchiectasis.
SEARCH METHODS
We searched the Cochrane Airways Group Specialised Register and reference lists of relevant articles. We contacted experts in the field and drug companies. Searches were current as of June 2013.
SELECTION CRITERIA
Randomised trials of mucolytic treatment in people with bronchiectasis but not cystic fibrosis.
DATA COLLECTION AND ANALYSIS
Data extraction was performed independently by two review authors. Study authors were contacted for confirmation.
MAIN RESULTS
Four trials (with a combined total of 528 adult participants) were included, but almost none of the data from these studies could be aggregated in a meta-analysis.One trial (with 88 participants) compared bromhexine versus placebo. Compared with placebo, high doses of bromhexine with antibiotics eased difficulty in expectoration (mean difference (MD) -0.53, 95% confidence interval (CI) -0.81 to -0.25 at 16 days); the quality of the evidence was rated as low. A reduction in sputum production was noted with bromhexine (MD -21.5%, 95% CI -38.9 to -4.1 at day 16); again the quality of the evidence was rated as low. No significant differences between bromhexine and placebo were observed with respect to reported adverse events (odds ratio (OR) 2.93; 95% CI 0.12 to 73.97), and again the quality of the evidence was rated as low.In a single small, blinded but not placebo-controlled trial of older (> 55 years) participants with stable bronchiectasis and mucus hypersecretion, erdosteine combined with physiotherapy over a 15-day period improved spirometry and sputum purulence more effectively compared with physiotherapy alone. The spirometric improvement was small (MD 200 mL in forced expiratory volume in one second (FEV1) and 300 mL in forced vital capacity (FVC)) and was apparent only at day 15, not at earlier time points.The remaining two studies (with a combined total of 410 participants) compared recombinant human DNase (RhDNase) versus placebo. These two studies were very different (one was a two-week study of 61 participants, and the other ran for 24 weeks and included 349 participants), and the opportunity for combining data from the two studies was very limited. Compared with placebo, recombinant human DNase showed no difference in FEV1 or FVC in the smaller study but showed a significant negative effect on FEV1 in the larger and longer study. For reported adverse events, no significant differences between recombinant human DNase and placebo were noted. In all of the above comparisons of recombinant human DNase versus placebo, the quality of the evidence was judged to be low.
AUTHORS' CONCLUSIONS
Given the harmful effects of recombinant human DNase in one trial and no evidence of benefit, this drug should be avoided in non-cystic fibrosis bronchiectasis, except in the context of clinical trials. Evidence is insufficient to permit evaluation of the routine use of other mucolytics for bronchiectasis. High doses of bromhexine coupled with antibiotics may help with sputum production and clearance, but long-term data and robust clinical outcomes are lacking. Similarly, erdosteine may be a useful adjunct to physiotherapy in stable patients with mucus hypersecretion, but robust longer-term trials are required.Generally, clinical trials in children on the use of various mucolytic agents are lacking. As the number of agents available on the market, such as RhDNase, acetylcysteine and bromhexine, is increasing, improvement of the evidence base is needed.
Topics: Anti-Bacterial Agents; Bromhexine; Bronchiectasis; Deoxyribonucleases; Drug Therapy, Combination; Expectorants; Humans; Randomized Controlled Trials as Topic; Recombinant Proteins; Thioglycolates; Thiophenes
PubMed: 24789119
DOI: 10.1002/14651858.CD001289.pub2 -
Biomarkers : Biochemical Indicators of... Sep 2023Colorectal cancer (CRC) poses a substantial health burden, with early detection paramount for improved prognosis. This study aims to evaluate potential CRC biomarkers...
INTRODUCTION
Colorectal cancer (CRC) poses a substantial health burden, with early detection paramount for improved prognosis. This study aims to evaluate potential CRC biomarkers and detection techniques.
MATERIALS AND METHODS
This systematic review, reported in adherence to PRISMA Statement 2020 guidelines, collates the latest research on potential biomarkers and detection/prognosis methods for CRC, spanning the last decade.
RESULTS
Out of the 38 included studies, diverse biomarkers and detection methods emerged, with DNA methylation markers like SFRP2 and SDC2, microRNAs including miR-1290, miR-506, and miR-4316, and serum and plasma markers such as NTS levels and U2 snRNA fragments standing out. Methylated cfDNA and m5C methylation alteration in immune cells of the blood, along with circular RNA, showed promise as diagnostic markers. Meanwhile, techniques involving extracellular vesicles and lateral flow immunoassays exhibited potential for swift and effective CRC screening.
DISCUSSION
Our state-of-the-art review identifies potential biomarkers, including SFRP2, SDC2, miR-1290, miR-506, miR-4316, and U2 snRNA fragments, with significant potential in enhancing CRC detection. However, comprehensive validation studies and a rigorous evaluation of clinical utility and cost-effectiveness remain necessary before integration into routine clinical practice.
CONCLUSION
The findings emphasize the need for continued research into biomarkers and detection methods to improve patient outcomes.
Topics: Humans; DNA Methylation; Biomarkers, Tumor; MicroRNAs; Prognosis; Early Detection of Cancer; Colorectal Neoplasms
PubMed: 37585692
DOI: 10.1080/1354750X.2023.2247185 -
Frontiers in Genetics 2023In the last years, liquid biopsy gained increasing clinical relevance for detecting and monitoring several cancer types, being minimally invasive, highly informative and... (Review)
Review
In the last years, liquid biopsy gained increasing clinical relevance for detecting and monitoring several cancer types, being minimally invasive, highly informative and replicable over time. This revolutionary approach can be complementary and may, in the future, replace tissue biopsy, which is still considered the gold standard for cancer diagnosis. "Classical" tissue biopsy is invasive, often cannot provide sufficient bioptic material for advanced screening, and can provide isolated information about disease evolution and heterogeneity. Recent literature highlighted how liquid biopsy is informative of proteomic, genomic, epigenetic, and metabolic alterations. These biomarkers can be detected and investigated using single-omic and, recently, in combination through multi-omic approaches. This review will provide an overview of the most suitable techniques to thoroughly characterize tumor biomarkers and their potential clinical applications, highlighting the importance of an integrated multi-omic, multi-analyte approach. Personalized medical investigations will soon allow patients to receive predictable prognostic evaluations, early disease diagnosis, and subsequent treatments.
PubMed: 37077538
DOI: 10.3389/fgene.2023.1152470 -
Drugs in R&D Sep 2023At present, the therapies of dilated cardiomyopathy concentrated on the symptoms of heart failure and related complications. The study is to evaluate the clinical... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVE
At present, the therapies of dilated cardiomyopathy concentrated on the symptoms of heart failure and related complications. The study is to evaluate the clinical efficacy of a combination of various conventional and adjuvant drugs in treating dilated cardiomyopathy via network meta-analysis.
METHODS
The study was reported according to the PRISMA 2020 statement. From inception through 27 June 2022, the PubMed, Embase, Cochrane library, and Web of Science databases were searched for randomized controlled trials on medicines for treating dilated cardiomyopathy. The quality of the included studies was evaluated according to the Cochrane risk of bias assessment. R4.1.3 and Revman5.3 software were used for analysis.
RESULTS
There were 52 randomized controlled trials in this study, with a total of 25 medications and a sample size of 3048 cases. The network meta-analysis found that carvedilol, verapamil, and trimetazidine were the top three medicines for improving left ventricular ejection fraction (LVEF). Ivabradine, bucindolol, and verapamil were the top 3 drugs for improving left ventricular end-diastolic dimension (LVEDD). Ivabradine, L-thyroxine, and atorvastatin were the top 3 drugs for improving left ventricular end-systolic dimension (LVESD). Trimetazidine, pentoxifylline, and bucindolol were the top 3 drugs for improving the New York Heart Association classification (NYHA) cardiac function score. Ivabradine, carvedilol, and bucindolol were the top 3 drugs for reducing heart rate (HR).
CONCLUSION
A combination of different medications and conventional therapy may increase the clinical effectiveness of treating dilated cardiomyopathy. Beta-blockers, especially carvedilol, can improve ventricular remodeling, cardiac function, and clinical efficacy in patients with dilated cardiomyopathy (DCM). Hence, they can be used if patients tolerate them. If LVEF and HR do not meet the standard, ivabradine can also be used in combination with other treatments. However, since the quality and number of studies in our research were limited, large sample size, multi-center, and high-quality randomized controlled trials are required to corroborate our findings.
Topics: Humans; Cardiomyopathy, Dilated; Carvedilol; Ivabradine; Stroke Volume; Trimetazidine; Network Meta-Analysis; Ventricular Function, Left; Verapamil; Randomized Controlled Trials as Topic
PubMed: 37556093
DOI: 10.1007/s40268-023-00435-5 -
PloS One 2017Breastfeeding benefits both infants and mothers. Recent research shows long-term health and human capital benefits among individuals who were breastfed. Epigenetic... (Review)
Review
BACKGROUND
Breastfeeding benefits both infants and mothers. Recent research shows long-term health and human capital benefits among individuals who were breastfed. Epigenetic mechanisms have been suggested as potential mediators of the effects of early-life exposures on later health outcomes. We reviewed the literature on the potential effects of breastfeeding on DNA methylation.
METHODS
Studies reporting original results and evaluating DNA methylation differences according to breastfeeding/breast milk groups (e.g., ever vs. never comparisons, different categories of breastfeeding duration, etc) were eligible. Six databases were searched simultaneously using Ovid, and the resulting studies were evaluated independently by two reviewers.
RESULTS
Seven eligible studies were identified. Five were conducted in humans. Studies were heterogeneous regarding sample selection, age, target methylation regions, methylation measurement and breastfeeding categorisation. Collectively, the studies suggest that breastfeeding might be negatively associated with promoter methylation of LEP (which encodes an anorexigenic hormone), CDKN2A (involved in tumour suppression) and Slc2a4 genes (which encodes an insulin-related glucose transporter) and positively with promoter methylation of the Nyp (which encodes an orexigenic neuropeptide) gene, as well as influence global methylation patterns and modulate epigenetic effects of some genetic variants.
CONCLUSIONS
The findings from our systematic review are far from conclusive due to the small number of studies and their inherent limitations. Further studies are required to understand the actual potential role of epigenetics in the associations of breastfeeding with later health outcomes. Suggestions for future investigations, focusing on epigenome-wide association studies, are provided.
Topics: Breast Feeding; Cyclin-Dependent Kinase Inhibitor p16; Cyclin-Dependent Kinase Inhibitor p18; DNA Methylation; Epigenesis, Genetic; Female; Glucose Transporter Type 4; Humans; Infant; Longitudinal Studies; Male; Milk, Human
PubMed: 28257446
DOI: 10.1371/journal.pone.0173070 -
Translational Research : the Journal of... Aug 2014Type 1 diabetes (T1D) is an autoimmune disease with a prolonged and variable latent period that culminates in the destruction of pancreatic β-cells and the development... (Review)
Review
Type 1 diabetes (T1D) is an autoimmune disease with a prolonged and variable latent period that culminates in the destruction of pancreatic β-cells and the development of hyperglycemia. There is a need for diagnostic biomarkers to detect more accurately individuals with prediabetes to expedite targeting for prevention and intervention strategies. To assess the current ability to predict the insidious development of T1D, we conducted a comprehensive systematic review for established and prospective predictive markers of T1D using the Medline, OVID, and EMBASE databases. Resulting citations were screened for relevance to subject. Our research generated five major categories of markers that are either currently used or forthcoming: genetic, autoantibody, risk score quantification, cellular immunity, and β-cell function. The current standard used to assess T1D onset or predisposition focuses on autoimmune pathology and disease-associated autoantibodies. Research studies in general go beyond autoantibody screening and assess genetic predisposition, and quantitate risk of developing disease based on additional factors. However, there are few currently used techniques that assess the root of T1D: β-cell destruction. Thus, novel techniques are discussed with the potential to gauge degrees of β-cell stress and failure via protein, RNA, and DNA analyses.
Topics: Autoantibodies; Biomarkers; Diabetes Mellitus, Type 1; Gene Expression Regulation; Genotype; Humans
PubMed: 24662515
DOI: 10.1016/j.trsl.2014.02.004 -
Trends in Ecology & Evolution Dec 2021Epigenetic inheritance is another piece of the puzzle of nongenetic inheritance, although the prevalence, sources, persistence, and phenotypic consequences of heritable... (Review)
Review
Epigenetic inheritance is another piece of the puzzle of nongenetic inheritance, although the prevalence, sources, persistence, and phenotypic consequences of heritable epigenetic marks across taxa remain unclear. We systematically reviewed over 500 studies from the past 5 years to identify trends in the frequency of epigenetic inheritance due to differences in reproductive mode and germline development. Genetic, intrinsic (e.g., disease), and extrinsic (e.g., environmental) factors were identified as sources of epigenetic inheritance, with impacts on phenotype and adaptation depending on environmental predictability. Our review shows that multigenerational persistence of epigenomic patterns is common in both plants and animals, but also highlights many knowledge gaps that remain to be filled. We provide a framework to guide future studies towards understanding the generational persistence and eco-evolutionary significance of epigenomic patterns.
Topics: Animals; DNA Methylation; Epigenesis, Genetic; Epigenomics; Germ Cells; Inheritance Patterns; Phenotype
PubMed: 34489118
DOI: 10.1016/j.tree.2021.08.006 -
Current Medicinal Chemistry Jun 2023Cell-free circulating DNA has been known for many years, but this knowledge has not been beneficial for diagnosis. In this meta-analysis, we examine the diagnostic role...
BACKGROUND
Cell-free circulating DNA has been known for many years, but this knowledge has not been beneficial for diagnosis. In this meta-analysis, we examine the diagnostic role of circulating cell-free DNA in HCC patients to find a reliable biomarker for the early detection of HCC.
MATERIALS AND METHODS
We performed a systematic literature search using Science Direct, Web of Science, PubMed/Medline, Scopus, Google Scholar, and Embase, up to April 1st, 2022. Meta-Disc V.1.4 and Comprehensive Meta-Analysis V.3.3 software calculated the pooled specificity, sensitivity, area under the curve (AUC), diagnostic odds ratio (DOR), positive likelihood ratio (PLR), negative likelihood ratio (NLR) Q*index, and summary receiver-operating characteristic (SROC) for the role of cfDNA as a biomarker for HCC patients. Moreover, the subgroup analyses have been performed based on sample types (serum/plasma) and detection methods (MS-PCR/methylation).
RESULTS
A total of 7 articles (9 studies) included 697 participants (485 cases and 212 controls). The overall pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were 0.706 (95% CI: 0.671 - 0.739), 0.905 (95% CI: 0.865 - 0.937), 6.66 (95% CI: 4.36 - 10.18), 0.287 (95% CI: 0.185 - 0.445), 28.40 (95% CI: 13.01 - 62.0), and 0.93, respectively. We conducted a subgroup analysis of diagnostic value, which showed that the plasma sample had a better diagnostic value compared to the serum.
CONCLUSION
This meta-analysis showed that cfDNA could be a fair biomarker for diagnosing HCC patients.
PubMed: 37349993
DOI: 10.2174/0929867330666230622114235 -
Biomarkers : Biochemical Indicators of... Dec 2023Circulating tumour DNA (ctDNA) has demonstrated robust diagnostic accuracy in several digestive cancers. However, the prognostic role of ctCDNA in gastric cancer (GC)... (Meta-Analysis)
Meta-Analysis
Circulating tumour DNA (ctDNA) has demonstrated robust diagnostic accuracy in several digestive cancers. However, the prognostic role of ctCDNA in gastric cancer (GC) is still controversial. This systematic review and meta-analysis aimed to evaluate the prognostic value of ctDNA in GC. PubMed, Web of Science and Cochrane databases were searched to identify studies reporting the use of ctDNA to predict GC outcome and all relevant studies published until November 2022 were enrolled for our analysis. Data were extracted by two authors independently and statistic analysis was conducted by R program with 'meta' and 'metafor' packages. A total of 34 qualified articles with 5091 subjects were incorporated into our meta-analysis. The corresponding Hazard ratio (HR) of overall survival (OS), disease-free survival (DFS) and progression-free survival (PFS) were 2.74 (95% CI:2.24-3.35), 3.13 (95% CI:2.08-4.72) and 3.04 (95% CI:2.46-3.76), respectively, in GC patients. Blood-based ctDNA assay would be a potential novel biomarker for GC evaluation and prediction. This is the integrated meta-analysis on the association of circulating tumour DNA (ctDNA) and prognosis of gastric cancer (GC) with an increasing number of studies exploring the prognostic value of GC in the last few years, which depicted that the detection of ctDNA could be a promising predictor in GC patients.
Topics: Humans; Prognosis; Circulating Tumor DNA; Stomach Neoplasms; Biomarkers, Tumor; Disease-Free Survival
PubMed: 37036017
DOI: 10.1080/1354750X.2023.2201664 -
Biomarkers in Medicine Feb 2021We aimed to assess the diagnostic performance of circulating cell-free DNA (cfDNA) in hepatocellular carcinoma (HCC). After a systematic literature search bivariate... (Meta-Analysis)
Meta-Analysis
We aimed to assess the diagnostic performance of circulating cell-free DNA (cfDNA) in hepatocellular carcinoma (HCC). After a systematic literature search bivariate linear mixed models were used to integrate sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio. The area under receiver operating characteristics curves of the included studies was used to estimate the diagnostic value. Thirty-eight articles enrolled in quantitative synthesis. In overall analysis the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and area under receiver operating characteristics curves for cfDNA in distinguishing HCC patients from healthy controls were 0.54, 0.90, 5.23, 0.51, 10.27 and 0.82, respectively. This study suggests that cfDNA has a promising diagnostic accuracy in detection of HCC.
Topics: Carcinoma, Hepatocellular; Cell-Free Nucleic Acids; Humans; Liver Neoplasms; ROC Curve
PubMed: 33470842
DOI: 10.2217/bmm-2020-0334