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Indian Journal of Ophthalmology Jul 2014To systematically collate and evaluate the evidence from recent SRs of bevacizumab for neo-vascular age related macular degeneration. (Review)
Review
The methodological quality of systematic reviews comparing intravitreal bevacizumab and alternates for neovascular age related macular degeneration: A systematic review of reviews.
OBJECTIVE
To systematically collate and evaluate the evidence from recent SRs of bevacizumab for neo-vascular age related macular degeneration.
MATERIALS AND METHODS
Literature searches were carried out in Medline, Embase, Cochrane databases for all systematic reviews (SRs) on the effectiveness of bevacizumab for neo-vascular age related macular degeneration, published between 2000 and 2013. Titles and abstracts were assessed against the inclusion/exclusion criteria using Joanna Briggs Institute (JBI) study eligibility form. Data was extracted using the JBI data extraction form. The quality of the SRs was assessed using JBI critical appraisal checklist for SRs. Decisions on study eligibility and quality were made by two reviewers; any disagreements were resolved by discussion.
RESULTS
Nine relevant reviews were identified from 30 citations, of which 5 reviews fulfilled the review's inclusion criteria. All 5 reviews showed bevacizumab to be effective for neovascular AMD in the short-term when used alone or in combination with PDT or Pegaptanib. The average quality score of the reviews was 7; 95% confidence interval 6.2 to 7.8 (maximum possible quality score is 10). The selection and publication bias were not addressed in all included reviews. Three-fifth of the reviews had a quality score of 7 or lower, these reviews had some methodological limitations, search strategies were only identified in 2 (40%) reviews, independent study selection and quality assessment of included studies (4 (80%)) were infrequently performed.
CONCLUSION
Overall, the reviews on the effectiveness of intravitreal/systemic bevacizumab for neovascular age-related macular generation (AMD) received good JBI quality scores (mean score = 7.0 points), with a few exceptions. The study also highlights the suboptimal reporting of SRs on this topic. Reviews with poor methodology may limit the validity of the reported results; hence efforts should be made to improve the design, reporting and publication of SRs across all journals.
Topics: Angiogenesis Inhibitors; Aptamers, Nucleotide; Bevacizumab; Humans; Intravitreal Injections; Macular Degeneration; Retinal Neovascularization; Vascular Endothelial Growth Factor A
PubMed: 25116765
DOI: 10.4103/0301-4738.138615 -
Journal of Cardiovascular Development... Jul 2021Familial hypercholesterolemia (FH) lead to significant adverse effects in coronary arteries. Mipomersen is a second-generation antisense oligonucleotide that inhibits... (Review)
Review
Familial hypercholesterolemia (FH) lead to significant adverse effects in coronary arteries. Mipomersen is a second-generation antisense oligonucleotide that inhibits the synthesis of apolipoprotein B-100, an essential component of low density lipoprotein (LDL), and thus decreases the production of LDL. We aimed to determine the effect of mipomersen in patients with FH. We searched Ovid Medline, Ovid EMBASE, WHO ICTRP search portal, ISI database, the reference lists of relevant articles, and also Google Scholar to retrieve articles. All randomized controlled trials (RCTs) comparing patients with FH receiving mipomersen as an add-on and a parallel group receiving a placebo or no intervention were selected. Five studies with more than 500 patients were included. All had low risk of bias. Pooling data showed that mipomersen probably reduces LDL compared with placebo [mean difference: -24.79, 95% CI (-30.15, -19.43)] but with a moderate level of certainty. There was a high level of evidence for injection site reactions [RR = 2.56, CI (1.47-4.44)] and a low level for increased serum alanine transaminase (ALT) > 3 times upper limit of normal (ULN) [RR = 5.19, CI (1.01-26.69)]. A moderate level of evidence in decreasing serum LDL indicates that we are uncertain if this drug provides benefit in any outcome important to patients. Although a low level of evidence for an increase in serum ALT leaves uncertainty about this adverse effect, injection site reactions in 10% or more of patients can be an important concern.
PubMed: 34357325
DOI: 10.3390/jcdd8070082 -
Genes Feb 2023Recently, several studies have highlighted a skewed prevalence of infectious diseases within the African continent. Furthermore, a growing number of studies have... (Review)
Review
Recently, several studies have highlighted a skewed prevalence of infectious diseases within the African continent. Furthermore, a growing number of studies have demonstrated unique genetic variants found within the African genome are one of the contributing factors to the disease severity of infectious diseases within Africa. Understanding the host genetic mechanisms that offer protection against infectious diseases provides an opportunity to develop unique therapeutic interventions. Over the past two decades, several studies have linked the 2'-5'-oligoadenylate synthetase (OAS) family with a range of infectious diseases. More recently, the gene has also been associated with disease severity caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which led to a global pandemic. The OAS family serves as an antiviral factor through the interaction with Ribonuclease-Latent (RNase-L). This review explores the genetic variants observed within the genes and the associations with various viral infections and how previously reported ethnic-specific polymorphisms drive clinical significance. This review provides an overview of genetic association studies with a particular focus on viral diseases affecting individuals of African descent.
Topics: Humans; SARS-CoV-2; COVID-19; Adenine Nucleotides; Oligoribonucleotides
PubMed: 36833454
DOI: 10.3390/genes14020527 -
Frontiers in Neurology 2021We sought to provide an overview of the published and currently ongoing movement disorders clinical trials employing gene therapy, defined as a technology aiming to...
We sought to provide an overview of the published and currently ongoing movement disorders clinical trials employing gene therapy, defined as a technology aiming to modulate the expression of one or more genes to achieve a therapeutic benefit. We systematically reviewed movement disorders gene therapy clinical trials from PubMed and ClinicalTrials.gov using a searching strategy that included Parkinson disease (PD), Huntington disease (HD), amino acid decarboxylase (AADC) deficiency, multiple system atrophy (MSA), progressive supranuclear palsy (PSP), dystonia, tremor, ataxia, and other movement disorders. Data extracted included study characteristics, investigational product, route of administration, safety/tolerability, motor endpoints, and secondary outcomes (i.e., neuroimaging, biomarkers). We identified a total of 46 studies focusing on PD (21 published and nine ongoing), HD (2 published and 5 ongoing), AADC deficiency (4 published and 2 ongoing), MSA (2 ongoing), and PSP (1 ongoing). In PD, intraparenchymal infusion of viral vector-mediated gene therapies demonstrated to be safe and showed promising preliminary data in trials aiming at restoring the synthesis of dopamine, enhancing the production of neurotrophic factors, or modifying the functional interaction between different nodes of the basal ganglia. In HD, monthly intrathecal delivery of an antisense oligonucleotide (ASO) targeting the huntingtin protein (HTT) mRNA proved to be safe and tolerable, and demonstrated a dose-dependent reduction of the cerebrospinal fluid levels of mutated HTT, while a small phase-I study testing implantable capsules of cells engineered to synthesize ciliary neurotrophic factor failed to show consistent drug delivery. In AADC deficiency, gene replacement studies demonstrated to be relatively safe in restoring catecholamine and serotonin synthesis, with promising outcomes. Ongoing movement disorders clinical trials are focusing on a variety of gene therapy approaches including alternative viral vector serotypes, novel recombinant genes, novel delivery techniques, and ASOs for the treatment of HD, MSA, and distinct subtypes of PD (LRRK2 mutation or GBA1 mutation carriers). Initial phase-I and -II studies tested the safety and feasibility of gene therapy in PD, HD, and AADC deficiency. The ongoing generation of clinical trials aims to test the efficacy of these approaches and explore additional applications for gene therapy in movement disorders.
PubMed: 33889127
DOI: 10.3389/fneur.2021.648532 -
Annals of the Rheumatic Diseases Sep 2012Dupuytren's disease (DD) is a common fibroproliferative disorder affecting the palmar fascia, which may lead to permanent contracture of the affected digit. Profiling... (Meta-Analysis)
Meta-Analysis Review
Dupuytren's disease (DD) is a common fibroproliferative disorder affecting the palmar fascia, which may lead to permanent contracture of the affected digit. Profiling studies investigating DD at whole-genomic, transcriptomic and proteomic levels have been carried out, from which large numbers of candidate genes potentially involved in DD have been reported. This review focuses on identifying genes reported by multiple studies or validated by multiple experimental techniques, as well as signalling pathways suggested to contribute to DD. Meta-analysis was also carried out on three microarray datasets. Twenty-one genes were found to be reported as dysregulated in multiple gene expression microarrays, seven of which have been further validated by other experimental methods. Sixty-four genes determined to be dsyregulated by meta-analysis correlate to those reported by published microarray studies. In addition, several pathways have been proposed to be involved in DD by whole-genome or global expression profiling. Further investigation in these genes and pathways, and correlating them to genotypes or environmental factors for DD, may aid in further elucidation of mechanisms involved in DD pathogenesis.
Topics: Dupuytren Contracture; Gene Expression Profiling; Genome; Humans; Oligonucleotide Array Sequence Analysis
PubMed: 22772327
DOI: 10.1136/annrheumdis-2012-201295 -
International Journal of Antimicrobial... Mar 2024Peptide nucleic acids (PNAs) are synthetic molecules that are like DNA/RNA, but with different building blocks. PNAs target and bind to mRNAs and disrupt the function of... (Review)
Review
Peptide nucleic acids (PNAs) are synthetic molecules that are like DNA/RNA, but with different building blocks. PNAs target and bind to mRNAs and disrupt the function of a targeted gene, hence they have been studied as potential antibacterials. The aim of this systematic review was to provide an in-depth analysis of the current status of PNAs as antibacterial agents, define the characteristics of the effective PNA constructs, and address the gap in advancing PNAs to become clinically competent agents. Following the PRISMA model, four electronic databases were searched: Web of Science, PubMed, SciFinder and Scopus. A total of 627 articles published between 1994 and 2023 were found. After screening and a rigorous selection process using explicit inclusion and exclusion criteria, 65 scientific articles were selected, containing 656 minimum inhibitory concentration (MIC) data. The antibacterial activity of PNAs was assessed against 20 bacterial species. The most studied Gram-negative and Gram-positive bacteria were Escherichia coli (n=266) and Staphylococcus aureus (n=53), respectively. In addition, the effect of PNA design, including construct length, binding location, and carrier agents, on antibacterial activity was shown. Finally, antibacterial test models to assess the inhibitory effects of PNAs were examined, emphasising gaps and prospects. This systematic review provides a comprehensive assessment of the potential of PNAs as antibacterial agents and offers valuable insights for researchers and clinicians seeking novel therapeutic strategies in the context of increasing rates of antibiotic-resistant bacteria.
Topics: Anti-Bacterial Agents; Bacteria; Peptide Nucleic Acids; Staphylococcus aureus
PubMed: 38185398
DOI: 10.1016/j.ijantimicag.2024.107083 -
Journal of Molecular and Cellular... Mar 2005Microarray analysis has become a widely available tool for the generation of gene expression data on a genomic scale. Since the studies with similar protocols are... (Review)
Review
Microarray analysis has become a widely available tool for the generation of gene expression data on a genomic scale. Since the studies with similar protocols are growing, it has become necessary to systematically revise the large body of literature to decipher the gene expression data. In this review, we analyzed and critically discussed the database presented from 14 published studies that showed the gene expression profile in heart failure (HF) using microarray as a primary tool. After comparing the diverse database from these studies, we explain the protein translational, matri-cellular, immunological and fibrosis-related mechanisms in HF. In addition to previously annotated genes, we analyzed two differentially expressed expressed sequence tags (ESTs) (KIAA0152 and Suppressor of G(Two) allele of the suppressor of kinetochore protein-1, SGT1) in HF and showed how bio-informatic analysis of ESTs can lead to the identification of novel pathways active in HF. We have also discussed the new publicly accessible tools that link the gene expression data to gene ontogeny (GO) and functionality. Finally, we have systematically revised the chromosomal localization of the genes that are specifically up-regulated in HF. We have thus spotted chromosome 1, 2, 11 and 12 as the chromosomal hotspots of HF. This methodical approach will simplify the existing concepts on the evolution and progression of HF and lead us toward the development of newer diagnostic and therapeutic tools. Although modeled to HF, this approach should be of broader scientific interest to elaborate multiple genes and complex pathways.
Topics: Cell Cycle Proteins; Computational Biology; Databases, Genetic; Expressed Sequence Tags; Extracellular Matrix; Gene Expression Profiling; Heart Failure; Humans; Oligonucleotide Array Sequence Analysis; Peptide Elongation Factors; Quantitative Trait Loci
PubMed: 15733902
DOI: 10.1016/j.yjmcc.2004.12.016 -
Best Practice & Research. Clinical... Apr 2004Endometriosis is a benign but aggressive disease. It occurs when shed endometrium from the female reproductive tract grows at a site outside the uterus. The... (Review)
Review
Endometriosis is a benign but aggressive disease. It occurs when shed endometrium from the female reproductive tract grows at a site outside the uterus. The physiological changes in endometriosis-abnormal tissue growth, invasion, and adhesion phenomena-are similar to those seen in tumorous tissues. Although the etiology of endometriosis is not well understood, the disease is widely accepted to result from the ectopic implantation of refluxed menstrual tissues. In addition, immunologic changes, genetic factors, and environmental factors might also affect a woman's susceptibility to develop endometriosis. Thus far, laparoscopic examination is required to confirm the presence of endometriosis; there is no reliable marker for its diagnosis. Many studies are therefore focusing on identifying markers for the diagnosis and follow-up of endometriosis. This chapter provides a systematic review of these studies, including recent findings from our group on the identification of molecules, in serum and/or endometrium, which are associated with the development of endometriosis at different stages. From this research, we hope to be able to suggest how to approach the potential markers. The identification of highly sensitive and specific markers of endometriosis should facilitate the development of accurate and non-invasive techniques for diagnosis and prognosis.
Topics: Autoantibodies; Biomarkers; Cell Adhesion Molecules; Cytokines; Endometriosis; Endometrium; Female; Genetic Predisposition to Disease; Growth Substances; Humans; Matrix Metalloproteinases; Oligonucleotide Array Sequence Analysis
PubMed: 15157644
DOI: 10.1016/j.bpobgyn.2004.03.003 -
Cells Mar 2023Hereditary cerebellar ataxias (HCAs) are a heterogenous group of neurodegenerative disorders associated with severe disability. Treatment options are limited and overall... (Review)
Review
INTRODUCTION
Hereditary cerebellar ataxias (HCAs) are a heterogenous group of neurodegenerative disorders associated with severe disability. Treatment options are limited and overall restricted to symptomatic approaches, leading to poor prognoses. In recent years, there has been extensive research on gene suppression therapies (GSTs) as a new hope for disease-modifying strategies. In this article, we aim to perform a review of studies investigating the efficacy and safety profile of GSTs in HCAs.
METHODS
A structured PubMed search on GSTs in HCAs from January 1993 up to October 2020 was performed. Inclusion and exclusion criteria were defined, and the selection process was conducted accordingly. The screening process was independently carried out by two authors and was initially based on title and abstract, followed by full-text reading. The risk-of-bias assessment was performed with SYRCLE's tool. A data extraction sheet was created to collect relevant information from each selected article.
RESULTS
The initial search yielded 262 papers, of which 239 were excluded. An additional article was obtained following reference scrutiny, resulting in a total of 24 articles for final analysis. Most studies were not clear on the tools used to assess bias. In SCA1, SCA2, MJD/SCA3 and SCA7, RNA interference (iRNA) and antisense oligonucleotide (ASO) therapies proved to be well tolerated and effective in suppressing mutant proteins, improving neuropathological features and the motor phenotype. In SCA6, the phenotype was improved, but no investigation of adverse effects was performed. In FRDA, only the suppression efficacy of the electroporation of the clustered regularly interspaced short palindromic repeats associated with Cas9 enzyme system (CRISPR-Cas9) system was tested and confirmed.
CONCLUSION
The literature reviewed suggests that GSTs are well tolerated and effective in suppressing the targeted proteins, improving neuropathological features and the motor phenotype . Nonetheless, there is no guarantee that these results are free of bias. Moreover, further investigation is still needed to clarify the GST effect on HCAs such as FRDA, SCA6 and SCA2.
Topics: Animals; Cerebellar Ataxia; Trinucleotide Repeats; Spinocerebellar Degenerations; Proteins
PubMed: 37048110
DOI: 10.3390/cells12071037 -
Medicina (Kaunas, Lithuania) Jun 2022We appreciate Ahmed Sami Aljabali and his colleagues for their interest and comments [...]. (Meta-Analysis)
Meta-Analysis
Reply to Aljabali et al. Comment on "Abbas et al. The Safety and Efficacy of Nusinersen in the Treatment of Spinal Muscular Atrophy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. 2022, , 213".
We appreciate Ahmed Sami Aljabali and his colleagues for their interest and comments [...].
Topics: Humans; Muscular Atrophy, Spinal; Oligonucleotides; Randomized Controlled Trials as Topic
PubMed: 35744055
DOI: 10.3390/medicina58060793