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Journal of Managed Care & Specialty... Apr 2020Funding for this summary was contributed by Arnold Ventures, Commonwealth Fund, California Health Care Foundation, National Institute for Health Care Management (NIHCM),... (Comparative Study)
Comparative Study
Funding for this summary was contributed by Arnold Ventures, Commonwealth Fund, California Health Care Foundation, National Institute for Health Care Management (NIHCM), New England States Consortium Systems Organization, Blue Cross Blue Shield of Massachusetts, Harvard Pilgrim Health Care, Kaiser Foundation Health Plan, and Partners HealthCare to the Institute for Clinical and Economic Review (ICER), an independent organization that evaluates the evidence on the value of health care interventions. ICER's annual policy summit is supported by dues from Aetna, America's Health Insurance Plans, Anthem, Allergan, Alnylam, AstraZeneca, Biogen, Blue Shield of CA, Cambia Health Services, CVS, Editas, Express Scripts, Genentech/Roche, GlaxoSmithKline, Harvard Pilgrim, Health Care Service Corporation, Health Partners, Johnson & Johnson (Janssen), Kaiser Permanente, LEO Pharma, Mallinckrodt, Merck, Novartis, National Pharmaceutical Council, Premera, Prime Therapeutics, Regeneron, Sanofi, Spark Therapeutics, and United Healthcare. Agboola, Fluetsch, Rind, and Pearson are employed by ICER. Lin reports support from ICER during work on this economic model and grants from Mount Zion Health Fund, National Institutes of Health (National Cancer Institute and National Heart, Lung, and Blood Institute), and the Tobacco-Related Diseases Research Program, unrelated to this work. Walton reports support from ICER for work on this economic model and unrelated consulting fees from Baxter.
Topics: Cost-Benefit Analysis; Dystrophin; Exons; Humans; Immunosuppressive Agents; Models, Economic; Morpholinos; Muscular Dystrophy, Duchenne; Oligonucleotides; Oligonucleotides, Antisense; Prednisone; Pregnenediones; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 32223597
DOI: 10.18553/jmcp.2020.26.4.361 -
Danish Medical Journal Aug 20205q spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder caused by insufficient survival motor neuron protein. Untreated SMA involves death or...
INTRODUCTION
5q spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder caused by insufficient survival motor neuron protein. Untreated SMA involves death or permanent respiratory support (type 1), inability to walk (type 2) or ability to walk (type 3). The incidence of SMA is 1 in 7,500 live births, equivalant to eight children being born with SMA in Denmark annually.
METHODS
We undertook a systematic review of the efficacy of nusinersen as SMA treatment. We included randomised controlled trials and cohort studies. Our primary endpoints were survival without permanent respiratory support and change in motor function.
RESULTS
We identified 658 articles and included 13 of these (two randomised controlled trials and 11 cohort studies). Nusinersen increased survival without permanent respiratory support in SMA type 1 and increased motor function development in types 1-3. Nusinersen treatment before symptom onset in children with presymptomatic SMA produced near-normal motor development. So far, nusinersen has only minor safety concerns mostly related to the lumbar puncture.
CONCLUSIONS
Nusinersen increased survival without permanent ventilatory support in children with SMA type 1. Improvements in SMA type 2 and 3 were less evident. Better outcomes were seen in young children with a short disease duration, particularly in children receiving nusinersen before symptom onset. Newborn SMA screening may facilitate presymptomatic treatment with splice modification (nusinersen, risdiplam) or gene implantation therapy (AVXS-101, zolgensma).
Topics: Cohort Studies; Denmark; Female; Humans; Infant; Infant, Newborn; Male; Motor Activity; Muscular Atrophy, Spinal; Oligonucleotides; Randomized Controlled Trials as Topic; Respiration, Artificial; Spinal Muscular Atrophies of Childhood; Treatment Outcome
PubMed: 32800069
DOI: No ID Found -
Experimental Parasitology Dec 2019Studies of the primers that were designed to detect New World Leishmania were systematically reviewed to report the characteristics of each target, detection limit,...
Studies of the primers that were designed to detect New World Leishmania were systematically reviewed to report the characteristics of each target, detection limit, specificity of the primers designed and diagnostic sensibility. The papers identified in the databases PubMed and Web of Science involved 50 studies. Minicircle is the most applied target in molecular research for diagnosis, due to its high sensitivity in detecting Leishmania in different clinical samples, a characteristic that can be partially attributed to the higher number of copies of the minicircle per cell. The other molecular targets shown in this review were less sensitive to diagnostic use because of the lower number of copies of the target gene per cell, but more specific for identification of the subgenus and/or species. The choice of the best target is an important step towards the result of the research. The target allows the design of primers that are specific to the genus, subgenus or a particular species and also imparts sensitivity to the method for diagnosis. The findings of this systematic review provide the advantages and disadvantages of the main molecular targets and primers designed for New World Leishmania, offering information so that the researcher can choose the PCR system best suited to their research need. This is a timely and extremely thorough review of the primers designed for New World Leishmania.
Topics: DNA Primers; DNA, Protozoan; Humans; Leishmania; Leishmaniasis, Cutaneous; Limit of Detection; Polymerase Chain Reaction; Sensitivity and Specificity
PubMed: 31605671
DOI: 10.1016/j.exppara.2019.107773 -
Molecular and Cellular Probes Oct 2020The recently known coronavirus, SARS-CoV-2, has turn into the greatest global health challenge, affecting a large number of societies. The lack of specific treatment and... (Meta-Analysis)
Meta-Analysis
The recently known coronavirus, SARS-CoV-2, has turn into the greatest global health challenge, affecting a large number of societies. The lack of specific treatment and gold-standard diagnostic system has made the situation more complicated. Efforts have led to production of several diagnostic kits that are associated with limitations such as inadequate sensitivity and accuracy. Aptamers as multipotent biological probes could be promising candidates to design sensitive and specific biosensors. Although few studies have introduced specific aptamer types of coronavirus, they may help us select the best approach to obtain specific aptamers for this virus. On the other hand, some of already-introduced aptamers have shown the inhibitory effects on coronavirus that could be applied as therapeutics. The present study has provided a systematic overview on use of aptamer-based biosensors and drugs to diagnose and treat coronavirus.
Topics: Antiviral Agents; Aptamers, Nucleotide; Biosensing Techniques; COVID-19; Coronavirus Infections; Humans; Pandemics; Pneumonia, Viral
PubMed: 32634550
DOI: 10.1016/j.mcp.2020.101636 -
International Journal of Molecular... Aug 2019MiRNAs have been shown to play a crucial role among lung cancer, pulmonary fibrosis, tuberculosis (TBC) infection, and bronchial hypersensitivity, thus including chronic... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
MiRNAs have been shown to play a crucial role among lung cancer, pulmonary fibrosis, tuberculosis (TBC) infection, and bronchial hypersensitivity, thus including chronic obstructive pulmonary disease (COPD) and asthma. The oncogenic effect of several miRNAs has been recently ruled out. In order to act on miRNAs turnover, antagomiRs have been developed.
MATERIALS AND METHODS
The systematic review was conducted under the PRISMA guidelines (registration number is: CRD42019134173). The PubMed database was searched between 1 January 2000 and 30 April 2019 under the following search strategy: (((antagomiR) OR (mirna antagonists) OR (mirna antagonist)) AND ((lung[MeSH Terms]) OR ("lung diseases"[MeSH Terms]))). We included original articles, published in English, whereas exclusion criteria included reviews, meta-analyses, single case reports, and studies published in a language other than English.
RESULTS AND CONCLUSIONS
A total of 68 articles matching the inclusion criteria were retrieved. Overall, the use of antagomiR was seen to be efficient in downregulating the specific miRNA they are conceived for. The usefulness of antagomiRs was demonstrated in humans, animal models, and cell lines. To our best knowledge, this is the first article to encompass evidence regarding miRNAs and their respective antagomiRs in the lung, in order to provide readers a comprehensive review upon major lung disorders.
Topics: Animals; Antagomirs; Biomarkers; Cell Line; Cells, Cultured; Gene Expression Regulation; Humans; Lung Diseases; MicroRNAs; Models, Animal; RNA Interference
PubMed: 31412612
DOI: 10.3390/ijms20163938 -
Current Atherosclerosis Reports May 2020To revise the clinical evidence supporting the use of volanesorsen as new lipid-lowering drug and to assess the efficacy and safety of volanesorsen (ISIS 304801) through... (Meta-Analysis)
Meta-Analysis
PURPOSE OF REVIEW
To revise the clinical evidence supporting the use of volanesorsen as new lipid-lowering drug and to assess the efficacy and safety of volanesorsen (ISIS 304801) through a systematic review of the literature and a meta-analysis of the available phase 2 and phase 3 clinical studies.
RECENT FINDINGS
The meta-analysis of three clinical studies comprising 11 arms (N = l 156 subjects, with 95 in the active-treated arm and 61 in the control one) shows that volanesorsen significantly affects plasma levels of triglycerides (TG) [MD = - 67.90%, 95%CI = - 85.32, - 50.48, P < 0.001], high-density lipoprotein cholesterol (HDL-C) [MD = 40.06%, 95%CI: 32.79, 47.34, P < 0.001], very-low-density lipoprotein cholesterol (VLDL-C) [MD = - 72.90%, 95%CI = - 82.73, - 63.07, P < 0.001], apolipoprotein B (Apo B) [MD = 8%, 95%CI = 2.17, 13.84, P = 0.007], Apo B-48 [MD = - 64.63, 95%CI = - 105.37, - 23.88, P = 0.002], ApoCIII [MD = - 74.83%, 95%CI = - 85.93, - 63.73, P < 0.001], and VLDL ApoCIII [MD = - 83.69%, 95%CI = - 94.08, - 73.29, P < 0.001], without significant impact on LDL-C [MD = 47.01%, 95%CI = - 1.31, 95.33, P = 0.057] levels. Treatment with volanesorsen was associated with an higher risk of injection site reaction (OR = 32.89, 95%CI = 7.97,135,74, P < 0.001) and with an increased risk of upper respiratory tract infections (OR = 10.58, 95%CI = 1.23, 90.93, P < 0.05) when compared to placebo. Volanesorsen has a relevant impact on plasma TG and related parameters without affecting LDL cholesterolemia and is associated with an acceptable safety profile.
Topics: Adult; Aged; Animals; Apolipoprotein C-III; Cholesterol, HDL; Female; Humans; Hypertriglyceridemia; Hypolipidemic Agents; Male; Middle Aged; Oligonucleotides; Triglycerides; Young Adult
PubMed: 32458077
DOI: 10.1007/s11883-020-00836-w -
Journal of Immunology Research 2020Unbiased studies using different genome-wide methods have identified a great number of candidate biomarkers for diagnosis and treatment response in pediatric ulcerative... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Unbiased studies using different genome-wide methods have identified a great number of candidate biomarkers for diagnosis and treatment response in pediatric ulcerative colitis (UC). However, clinical translation has been proven difficult. Here, we hypothesized that one reason could be differences between inflammatory responses in an inflamed gut and in peripheral blood cells.
METHODS
We performed meta-analysis of gene expression microarray data from intestinal biopsies and whole blood cells (WBC) from pediatric patients with UC and healthy controls in order to identify overlapping pathways, predicted upstream regulators, and potential biomarkers.
RESULTS
Analyses of profiling datasets from colonic biopsies showed good agreement between different studies regarding pathways and predicted upstream regulators. The most activated predicted upstream regulators included TNF, which is known to have a key pathogenic and therapeutic role in pediatric UC. Despite this, the expression levels of were increased in neither colonic biopsies nor WBC. A potential explanation was increased expression of , one of the membrane-bound receptors of TNF in the inflamed colon. Further analyses showed a similar pattern of complex relations between the expression levels of the regulators and their receptors. We also found limited overlap between pathways and predicted upstream regulators in colonic biopsies and WBC. An extended search including all differentially expressed genes that overlapped between colonic biopsies and WBC only resulted in identification of three potential biomarkers involved in the regulation of intestinal inflammation. However, two had been previously proposed in adult inflammatory bowel diseases (IBD), namely, MMP9 and PROK2.
CONCLUSIONS
Our findings indicate that biomarker identification in pediatric UC is complicated by the involvement of multiple pathways, each of which includes many different types of genes in the blood or inflamed intestine. Therefore, further studies for identification of combinatorial biomarkers are warranted. Our study may provide candidate biomarkers for such studies.
Topics: Biomarkers; Biopsy; Child; Colitis, Ulcerative; Colon; Gastrointestinal Hormones; Gene Expression Profiling; Humans; Intestinal Mucosa; Matrix Metalloproteinase 9; Neuropeptides; Oligonucleotide Array Sequence Analysis; Receptors, Tumor Necrosis Factor, Type II; Treatment Outcome
PubMed: 32411805
DOI: 10.1155/2020/8279619 -
Clinical Biochemistry Jul 2021Since prostate cancer (PCa) relies on limited diagnosis and therapies, more effective alternatives are needed. Aptamers are versatile tools that may be applied for...
Since prostate cancer (PCa) relies on limited diagnosis and therapies, more effective alternatives are needed. Aptamers are versatile tools that may be applied for better clinical management of PCa patients. This review shows the trends on aptamer-based applications for PCa to understand their future development. We searched articles reporting aptamers applied in PCa on the Pubmed, Scopus and Web of Science databases over the last decade. Almost 80% of the articles used previously selected aptamers in novel approaches. However, cell-SELEX was the most applied technique for the selection of new aptamers allowing their binding to targets in their native configuration. ssDNA aptamers were 24% more common than RNA aptamers. The most studied PCa-specific aptamers were the DNA PSA-specific aptamer PSap4#5 and the PSMA-specific RNA aptamers A10 and A9, being PSA and PSMA the most reported targets. Thus, researchers still prefer the ease of use of DNA aptamers. Blood-based liquid biopsies represented 24% of all samples, being the most promising clinical samples. Especially noteworthy, electro-analytical methods accounted for more than 40% of the diagnostic techniques and treatment approaches with drug delivery systems or transcriptional modifiers were reported in 70% of the articles. Although all these articles showed clinically relevant aptamers for PCa and there are good prospects for their use, the development of all these strategies was in its early stages. Thus, the aptamers are not completely validated and we foresee that the completion of clinical studies will allow the implementation of these aptamer-based technologies in the clinical practice of PCa.
Topics: Animals; Antigens, Surface; Aptamers, Nucleotide; Glutamate Carboxypeptidase II; Humans; Male; Precision Medicine; Prostate-Specific Antigen; Prostatic Neoplasms
PubMed: 33794195
DOI: 10.1016/j.clinbiochem.2021.03.014 -
Acta Neurologica Belgica Dec 2019Recent discovery of nusinersen, an antisense oligonucleotide drug, has provided encouragement for improving treatment of spinal muscular atrophy. No therapeutic options...
Recent discovery of nusinersen, an antisense oligonucleotide drug, has provided encouragement for improving treatment of spinal muscular atrophy. No therapeutic options currently exist for this autosomal recessive motor neuron disorder. Nusinersen is developed for intrathecal use and binds to a specific sequence within the survival motor neuron 2 pre-messenger RNA, modifying the splicing process to promote expression of full-length survival motor neuron protein. We performed a MEDLINE and CENTRAL search to investigate the current evidence for treatment with nusinersen in patients with spinal muscular atrophy. Four papers were withheld, including two phase-3 randomized controlled trials, one phase-2 open-label clinical trial and one phase-1 open-label clinical trial. Outcome measures concerned improvement in motor function and milestones, as well as event-free survival and survival. Results of these trials are hopeful with significant and clinically meaningful improvement due to treatment with intrathecal nusinersen in patients with early- and later-onset spinal muscular atrophy, although this does not restore age-appropriate function. Intrathecal nusinersen has acceptable safety and tolerability. Further trials regarding long-term effects and safety aspects as well as trials including broader spinal muscular atrophy and age categories are required and ongoing.
Topics: Cell Survival; Evidence-Based Medicine; Humans; Motor Neurons; Muscular Atrophy, Spinal; Oligonucleotides; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 31388901
DOI: 10.1007/s13760-019-01199-z -
Journal of Applied Toxicology : JAT Apr 2020Microarray approaches are frequently used experimental tools which have proven their value for example in the characterization of the molecular mode of action of...
Microarray approaches are frequently used experimental tools which have proven their value for example in the characterization of the molecular mode of action of toxicologically relevant compounds. In a regulatory context, omics techniques are still not routinely used, amongst others due to lacking standardization in experimental setup and data processing, and also due to issues with the definition of adversity. In order to exemplarily determine whether consensus transcript biomarker signatures for a certain toxicological endpoint can be derived from published microarray datasets, we here compared transcriptome data from human HepaRG hepatocarcinoma cells treated with different genotoxins, based on re-analyzed datasets extracted from the literature. Comparison of the resulting data show that even with similarly-acting compounds in the same cell line, considerable variation was observed with respect to the numbers and identities of differentially expressed genes. Greater concordance was observed when considering the whole data sets and biological functions associated with the genes affected. The present results highlight difficulties and possibilities in inter-experiment comparisons of omics data and underpin the need for future efforts towards improved standardization to facilitate the use of omics data in risk assessment. Existing omics datasets may nonetheless prove valuable in establishing biological context information essential for the development of adverse outcome pathways.
Topics: Animals; Cell Line, Tumor; Gene Expression Profiling; Genetic Markers; Hepatocytes; Humans; Mutagenicity Tests; Mutagens; Oligonucleotide Array Sequence Analysis; Reproducibility of Results; Risk Assessment; Transcriptome
PubMed: 31845381
DOI: 10.1002/jat.3928