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The Cochrane Database of Systematic... Apr 2020Disease-modifying pharmacological agents for transthyretin (TTR)-related familial amyloid polyneuropathy (FAP) have become available in the last decade, but evidence on...
BACKGROUND
Disease-modifying pharmacological agents for transthyretin (TTR)-related familial amyloid polyneuropathy (FAP) have become available in the last decade, but evidence on their efficacy and safety is limited. This review focuses on disease-modifying pharmacological treatment for TTR-related and other FAPs, encompassing amyloid kinetic stabilisers, amyloid matrix solvents, and amyloid precursor inhibitors.
OBJECTIVES
To assess and compare the efficacy, acceptability, and tolerability of disease-modifying pharmacological agents for familial amyloid polyneuropathies (FAPs).
SEARCH METHODS
On 18 November 2019, we searched the Cochrane Neuromuscular Specialised Register, the Cochrane Central Register of Controlled Trials, MEDLINE, and Embase. We reviewed reference lists of articles and textbooks on peripheral neuropathies. We also contacted experts in the field. We searched clinical trials registries and manufacturers' websites.
SELECTION CRITERIA
We included randomised clinical trials (RCTs) or quasi-RCTs investigating any disease-modifying pharmacological agent in adults with FAPs. Disability due to FAP progression was the primary outcome. Secondary outcomes were severity of peripheral neuropathy, change in modified body mass index (mBMI), quality of life, severity of depression, mortality, and adverse events during the trial.
DATA COLLECTION AND ANALYSIS
We followed standard Cochrane methodology.
MAIN RESULTS
The review included four RCTs involving 655 people with TTR-FAP. The manufacturers of the drugs under investigation funded three of the studies. The trials investigated different drugs versus placebo and we did not conduct a meta-analysis. One RCT compared tafamidis with placebo in early-stage TTR-FAP (128 randomised participants). The trial did not explore our predetermined disability outcome measures. After 18 months, tafamidis might reduce progression of peripheral neuropathy slightly more than placebo (Neuropathy Impairment Score (NIS) in the lower limbs; mean difference (MD) -3.21 points, 95% confidential interval (CI) -5.63 to -0.79; P = 0.009; low-certainty evidence). However, tafamidis might lead to little or no difference in the change of quality of life between groups (Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) total score; MD -4.50 points, 95% CI -11.27 to 2.27; P = 0.19; very low-certainty evidence). No clear between-group difference was found in the numbers of participants who died (risk ratio (RR) 0.65, 95% CI 0.11 to 3.74; P = 0.63; very low-certainty evidence), who dropped out due to adverse events (RR 1.29, 95% CI 0.30 to 5.54; P = 0.73; very low-certainty evidence), or who experienced at least one severe adverse event during the trial (RR 1.16, 95% CI 0.37 to 3.62; P = 0.79; very low-certainty evidence). One RCT compared diflunisal with placebo (130 randomised participants). At month 24, diflunisal might reduce progression of disability (Kumamoto Score; MD -4.90 points, 95% CI -7.89 to -1.91; P = 0.002; low-certainty evidence) and peripheral neuropathy (NIS plus 7 nerve tests; MD -18.10 points, 95% CI -26.03 to -10.17; P < 0.001; low-certainty evidence) more than placebo. After 24 months, changes from baseline in the quality of life measured by the 36-Item Short-Form Health Survey score showed no clear difference between groups for the physical component (MD 6.10 points, 95% CI 2.56 to 9.64; P = 0.001; very low-certainty evidence) and the mental component (MD 4.40 points, 95% CI -0.19 to 8.99; P = 0.063; very low-certainty evidence). There was no clear between-group difference in the number of people who died (RR 0.46, 95% CI 0.15 to 1.41; P = 0.17; very low-certainty evidence), in the number of dropouts due to adverse events (RR 2.06, 95% CI 0.39 to 10.87; P = 0.39; very low-certainty evidence), and in the number of people who experienced at least one severe adverse event (RR 0.77, 95% CI 0.18 to 3.32; P = 0.73; very low-certainty evidence) during the trial. One RCT compared patisiran with placebo (225 randomised participants). After 18 months, patisiran reduced both progression of disability (Rasch-built Overall Disability Scale; least-squares MD 8.90 points, 95% CI 7.00 to 10.80; P < 0.001; moderate-certainty evidence) and peripheral neuropathy (modified NIS plus 7 nerve tests - Alnylam version; least-squares MD -33.99 points, 95% CI -39.86 to -28.13; P < 0.001; moderate-certainty evidence) more than placebo. At month 18, the change in quality of life between groups favoured patisiran (Norfolk QOL-DN total score; least-squares MD -21.10 points, 95% CI -27.20 to -15.00; P < 0.001; low-certainty evidence). There was little or no between-group difference in the number of participants who died (RR 0.61, 95% CI 0.21 to 1.74; P = 0.35; low-certainty evidence), dropped out due to adverse events (RR 0.33, 95% CI 0.13 to 0.82; P = 0.017; low-certainty evidence), or experienced at least one severe adverse event (RR 0.91, 95% CI 0.64 to 1.28; P = 0.58; low-certainty evidence) during the trial. One RCT compared inotersen with placebo (172 randomised participants). The trial did not explore our predetermined disability outcome measures. From baseline to week 66, inotersen reduced progression of peripheral neuropathy more than placebo (modified NIS plus 7 nerve tests - Ionis version; MD -19.73 points, 95% CI -26.50 to -12.96; P < 0.001; moderate-certainty evidence). At week 65, the change in quality of life between groups favoured inotersen (Norfolk QOL-DN total score; MD -10.85 points, 95% CI -17.25 to -4.45; P < 0.001; low-certainty evidence). Inotersen may slightly increase mortality (RR 5.94, 95% CI 0.33 to 105.60; P = 0.22; low-certainty evidence) and occurrence of severe adverse events (RR 1.48, 95% CI 0.85 to 2.57; P = 0.16; low-certainty evidence) compared to placebo. More dropouts due to adverse events were observed in the inotersen than in the placebo group (RR 8.57, 95% CI 1.16 to 63.07; P = 0.035; low-certainty evidence). There were no studies addressing apolipoprotein AI-FAP, gelsolin-FAP, and beta-2-microglobulin-FAP.
AUTHORS' CONCLUSIONS
Evidence on the pharmacological treatment of FAPs from RCTs is limited to TTR-FAP. No studies directly compare disease-modifying pharmacological treatments for TTR-FAP. Results from placebo-controlled trials indicate that tafamidis, diflunisal, patisiran, and inotersen may be beneficial in TTR-FAP, but further investigations are needed. Since direct comparative studies for TTR-FAP will be hampered by sample size and costs required to demonstrate superiority of one drug over another, long-term non-randomised open-label studies monitoring their efficacy and safety are needed.
Topics: Amyloid Neuropathies, Familial; Benzoxazoles; Diflunisal; Disease Progression; Humans; Oligonucleotides; Patient Dropouts; Quality of Life; RNA, Small Interfering; Randomized Controlled Trials as Topic
PubMed: 32311072
DOI: 10.1002/14651858.CD012395.pub2 -
Neuropathology and Applied Neurobiology Jun 2022Codeletion of chromosomal arms 1p and 19q, in conjunction with a mutation in the isocitrate dehydrogenase 1 or 2 gene, is the molecular diagnostic criterion for... (Meta-Analysis)
Meta-Analysis Review
Codeletion of chromosomal arms 1p and 19q, in conjunction with a mutation in the isocitrate dehydrogenase 1 or 2 gene, is the molecular diagnostic criterion for oligodendroglioma, IDH mutant and 1p/19q codeleted. 1p/19q codeletion is a diagnostic marker and allows prognostication and prediction of the best drug response within IDH-mutant tumours. We performed a Cochrane review and simple economic analysis to establish the most sensitive, specific and cost-effective techniques for determining 1p/19q codeletion status. Fluorescent in situ hybridisation (FISH) and polymerase chain reaction (PCR)-based loss of heterozygosity (LOH) test methods were considered as reference standard. Most techniques (FISH, chromogenic in situ hybridisation [CISH], PCR, real-time PCR, multiplex ligation-dependent probe amplification [MLPA], single nucleotide polymorphism [SNP] array, comparative genomic hybridisation [CGH], array CGH, next-generation sequencing [NGS], mass spectrometry and NanoString) showed good sensitivity (few false negatives) for detection of 1p/19q codeletions in glioma, irrespective of whether FISH or PCR-based LOH was used as the reference standard. Both NGS and SNP array had a high specificity (fewer false positives) for 1p/19q codeletion when considered against FISH as the reference standard. Our findings suggest that G banding is not a suitable test for 1p/19q analysis. Within these limits, considering cost per diagnosis and using FISH as a reference, MLPA was marginally more cost-effective than other tests, although these economic analyses were limited by the range of available parameters, time horizon and data from multiple healthcare organisations.
Topics: Brain Neoplasms; Chromosome Aberrations; Chromosomes, Human, Pair 1; Chromosomes, Human, Pair 19; Glioma; Humans; Isocitrate Dehydrogenase; Mutation; Oligodendroglioma
PubMed: 34958131
DOI: 10.1111/nan.12790 -
Pharmacogenomics May 2009Dopamine neurotransmission has been a key player in attempts to identify genetic factors involved in alcohol dependence. The dopamine transporter terminates dopaminergic... (Review)
Review
Dopamine neurotransmission has been a key player in attempts to identify genetic factors involved in alcohol dependence. The dopamine transporter terminates dopaminergic neurotransmission, making the gene encoding the transporter (SLC6A3/DAT1) an attractive candidate in clinical studies on alcohol dependence. We conducted a systematic review of 18 studies examining associations between polymorphisms in DAT1 and alcohol dependence. The DAT1 variable number tandem repeat, the most frequent studied polymorphism in DAT1, did not show a direct association with alcohol dependence in general. Several, but not all, studies found that the DAT1 variable number tandem repeat (9-repeat allele) was associated with alcohol-withdrawal symptoms, such as seizures and delirium tremens. We discuss shortcomings, such as lack of power and disregarding moderating variables, as well as future challenges of gene association studies.
Topics: Alcohol Withdrawal Delirium; Alcoholism; Case-Control Studies; DNA, Complementary; Dopamine Plasma Membrane Transport Proteins; Environment; Family; Female; Genetic Variation; Humans; Male; Minisatellite Repeats; Racial Groups; Risk Factors; Sex Characteristics; Tandem Repeat Sequences
PubMed: 19450132
DOI: 10.2217/pgs.09.24 -
Current Pharmaceutical Biotechnology 2021Cancer is the most devastating disease in the present scenario, killing millions of people every year. Early detection, accurate diagnosis, and timely treatment are...
Cancer is the most devastating disease in the present scenario, killing millions of people every year. Early detection, accurate diagnosis, and timely treatment are considered to be the most effective ways to control this disease. Rapid and efficient detection of cancer at their earliest stage is one of the most significant challenges in cancer detection and cure. Numerous diagnostic modules have been developed to detect cancer cells early. As nucleic acid equivalent to antibodies, aptamers emerge as a new class of molecular probes that can identify cancer-related biomarkers or circulating rare cancer/ tumor cells with very high specificity and sensitivity. The amalgamation of aptamers with the biosensing platforms gave birth to "Aptasensors." The advent of highly sensitive aptasensors has opened up many new promising point-of-care diagnostics for cancer. This comprehensive review focuses on the newly developed aptasensors for cancer diagnostics.
Topics: Aptamers, Nucleotide; Biomarkers, Tumor; Biosensing Techniques; Early Detection of Cancer; Humans; Nanostructures; Neoplasms
PubMed: 32957883
DOI: 10.2174/1389201021999200918152721 -
Briefings in Bioinformatics Jan 2022Since the first report of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019, over 100 million people have been infected by COVID-19, millions...
Since the first report of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019, over 100 million people have been infected by COVID-19, millions of whom have died. In the latest year, a large number of omics data have sprung up and helped researchers broadly study the sequence, chemical structure and function of SARS-CoV-2, as well as molecular abnormal mechanisms of COVID-19 patients. Though some successes have been achieved in these areas, it is necessary to analyze and mine omics data for comprehensively understanding SARS-CoV-2 and COVID-19. Hence, we reviewed the current advantages and limitations of the integration of omics data herein. Firstly, we sorted out the sequence resources and database resources of SARS-CoV-2, including protein chemical structure, potential drug information and research literature resources. Next, we collected omics data of the COVID-19 hosts, including genomics, transcriptomics, microbiology and potential drug information data. And subsequently, based on the integration of omics data, we summarized the existing data analysis methods and the related research results of COVID-19 multi-omics data in recent years. Finally, we put forward SARS-CoV-2 (COVID-19) multi-omics data integration research direction and gave a case study to mine deeper for the disease mechanisms of COVID-19.
Topics: Antiviral Agents; COVID-19; Genomics; Humans; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 34718395
DOI: 10.1093/bib/bbab446 -
Nature Communications Jun 2023Chemical probes have reached a prominent role in biomedical research, but their impact is governed by experimental design. To gain insight into the use of chemical...
Chemical probes have reached a prominent role in biomedical research, but their impact is governed by experimental design. To gain insight into the use of chemical probes, we conducted a systematic review of 662 publications, understood here as primary research articles, employing eight different chemical probes in cell-based research. We summarised (i) concentration(s) at which chemical probes were used in cell-based assays, (ii) inclusion of structurally matched target-inactive control compounds and (iii) orthogonal chemical probes. Here, we show that only 4% of analysed eligible publications used chemical probes within the recommended concentration range and included inactive compounds as well as orthogonal chemical probes. These findings indicate that the best practice with chemical probes is yet to be implemented in biomedical research. To achieve this, we propose 'the rule of two': At least two chemical probes (either orthogonal target-engaging probes, and/or a pair of a chemical probe and matched target-inactive compound) to be employed at recommended concentrations in every study.
Topics: Biomedical Research; Molecular Probes
PubMed: 37270653
DOI: 10.1038/s41467-023-38952-1 -
Sao Paulo Medical Journal = Revista... 2012The age-stratified performance of the oncogenic HPV-DNA (human papillomavirus deoxyribonucleic acid) test for triage of low-grade squamous intraepithelial lesions (LSIL)... (Review)
Review
Colposcopic triage methods for detecting cervical intraepithelial neoplasia grade 3 after cytopathological diagnosis of low-grade squamous intraepithelial lesion: a systematic review on diagnostic tests.
CONTEXT AND OBJECTIVE
The age-stratified performance of the oncogenic HPV-DNA (human papillomavirus deoxyribonucleic acid) test for triage of low-grade squamous intraepithelial lesions (LSIL) requires investigation. The objective of this study was to evaluate and compare the age-stratified performance (cutoff point: 35 years) of oncogenic HPV-DNA testing and repeated cytological tests, for detecting cervical intraepithelial neoplasia grade 3 (CIN3), in order to triage for LSIL.
DESIGN AND SETTING
Systematic review. Studies were identified in nine electronic databases and in the reference lists of the articles retrieved.
METHODS
The eligibility criteria consisted of initial cytological findings of LSIL; subsequent oncogenic HPV-DNA testing and repeated cytological tests; and CIN3 detection. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS) guidelines were used for quality assessment. Qualitative information synthesis was performed.
RESULTS
Out of 7,776 studies, 284 were identified as pertinent and three fulfilled the eligibility criteria. The CIN3 prevalence ranged from 6% to 12%. The HPV-DNA positivity rate ranged from 64% to 83%; sensitivity for CIN3 detection ranged from 95.2% to 100%; and specificity was available in two studies (27% and 52%). The sensitivity of repeated cytological tests, in relation to the threshold for atypical squamous cells of undetermined significance (ASCUS), was available in two studies (33% and 90.8%); and specificity was available in one study (53%).
CONCLUSIONS
Currently, there is no scientific evidence available that would prove that colposcopic triage using oncogenic HPV-DNA testing to detect CIN3 performs better than repeated cytological tests, among women with LSIL aged 35 years and over.
Topics: Adult; Age Factors; Colposcopy; DNA Probes, HPV; Female; Humans; Papillomavirus Infections; Sensitivity and Specificity; Triage; Uterine Cervical Neoplasms; Uterine Cervical Dysplasia
PubMed: 22344359
DOI: 10.1590/s1516-31802012000100008 -
Frontiers in Psychiatry 2021premutation is defined by 55-200 CGG repeats in the Fragile X Mental Retardation 1 () gene. premutation carriers are at risk of developing a neurodegenerative disease...
premutation is defined by 55-200 CGG repeats in the Fragile X Mental Retardation 1 () gene. premutation carriers are at risk of developing a neurodegenerative disease called fragile X-associated tremor/ataxia syndrome (FXTAS) and Fragile X-associated primary ovarian insufficiency (FXPOI) in adulthood. In the last years an increasingly board spectrum of clinical manifestations including psychiatric disorders have been described as occurring at a greater frequency among premutation carriers. Herein, we reviewed the neuroimaging findings reported in relation with psychiatric symptomatology in adult premutation carriers. A structured electronic literature search was conducted on premutation and neuroimaging yielding a total of 3,229 articles examined. Of these, 7 articles were analyzed and are included in this review. The results showed that the main radiological findings among adult premutation carriers presenting neuropsychiatric disorders were found on the amygdala and hippocampus, being the functional abnormalities more consistent and the volumetric changes more inconsistent among studies. From a molecular perspective, CGG repeat size, mRNA and FMRP levels have been investigated in relation with the neuroimaging findings. Based on the published results, FMRP might play a key role in the pathophysiology of the psychiatric symptoms described among premutation carriers. However, additional studies including further probes of brain function and a broader scope of psychiatric symptom measurement are required in order to obtain a comprehensive landscape of the neuropsychiatric phenotype associated with the premutation.
PubMed: 34721105
DOI: 10.3389/fpsyt.2021.728952 -
Molecular and Cellular Probes Feb 2021The newly emerged coronavirus (SARS-CoV-2) continues to infect humans, and no effective treatment has yet been found. Antibody therapy is one way to control infection...
The newly emerged coronavirus (SARS-CoV-2) continues to infect humans, and no effective treatment has yet been found. Antibody therapy is one way to control infection caused by COVID-19. However, the use of classical antibodies raises complex issues. Heavy chain antibodies (HCAbs) are single-domain antibodies derived from the Camelidae family. The variable part of these antibodies (Nanobodies or VHH) has interesting properties such as small size, cost-effective production, and good tissue permeability, causing VHH to be regarded as an antiviral therapeutics. However, the small size of nanobodies may lead to low antigen binding affinity and rapid renal clearance. In this systematic review, the application of nanobodies in the treatment of COVID-19 infection and other similar infections (MERS and SARS) was reviewed.
Topics: Antibodies, Neutralizing; COVID-19; COVID-19 Testing; Humans; SARS-CoV-2; Single-Domain Antibodies
PubMed: 33358936
DOI: 10.1016/j.mcp.2020.101692 -
The International Journal of... Aug 2019To evaluate the accuracy of molecular diagnostics for the detection of drug-resistant tuberculosis (TB) in Chinese patients. Seven databases were searched for eligible... (Comparative Study)
Comparative Study Meta-Analysis
To evaluate the accuracy of molecular diagnostics for the detection of drug-resistant tuberculosis (TB) in Chinese patients. Seven databases were searched for eligible studies that evaluated the accuracy of molecular diagnostics against drug susceptibility testing (DST) for detecting drug resistance. A bivariate random-effects meta-analysis was conducted to pool sensitivity and specificity by the index test and drug resistance type. A total of 159 studies were included. Compared with DST (reference standard), Xpert could diagnose rifampicin (RMP) resistant TB accurately, with a pooled sensitivity and pooled specificity of 92% (95%CI 90-94) and 98% (95%CI 97-98), respectively. Line-probe assays (LPAs) also performed well for RMP resistance, with a pooled sensitivity of 91% (95%CI 88-93) and pooled specificity of 98% (95%CI 96-99), but not for isoniazid (INH) or second-line drugs due to lower sensitivity (<80%). The pooled sensitivity of GeneChip microarrays for RMP, INH and multidrug resistance was 89% (95%CI 86-91), 79% (95%CI 75-82) and 79% (95%CI 73-84), respectively, and the specificities were all >97%. Similarly, the MeltPro TB/STR assay had better sensitivity and specificity for first-line drugs, varying from 87% to 89% and 97% to 98%, respectively, than for second-line drugs. The Xpert assay, LPA, GeneChip assay, and MeltPro assay are credible methods with high accuracy for RMP resistance detection, but they may not be appropriate for other anti-tuberculosis drugs due to low sensitivity.
Topics: Antitubercular Agents; China; Humans; Microbial Sensitivity Tests; Molecular Diagnostic Techniques; Mycobacterium tuberculosis; Sensitivity and Specificity; Tuberculosis, Multidrug-Resistant
PubMed: 31533884
DOI: 10.5588/ijtld.18.0550