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Mini Reviews in Medicinal Chemistry 2020Recently, manipulation of gene expression and switching genes on or off highlight the potential of nucleic acid-based therapies (NA-BTs). Alzheimer's Disease (AD) is a... (Meta-Analysis)
Meta-Analysis
Recently, manipulation of gene expression and switching genes on or off highlight the potential of nucleic acid-based therapies (NA-BTs). Alzheimer's Disease (AD) is a common devastating neurodegenerative disease (NDs) responsible for 60-80% of all cases of dementia and predicted as a main public health concern among aged populations. The aim of this study was to outline the current research in the field of NA-BTs for the treatment of AD disabilities, including strategies to suppress the memory and learning defects, to promote recovery processes, and to reinforce social relationships in these patients. This review was performed via evaluating PubMed reported studies from January 2010 to November 2019. Also, reference lists were checked to find additional studies. All intermediation or complementarity of animal models, case-control and cohort studies, and controlled trials (CTs) on specific NA-BTs to AD were acceptable, although in vitro studies were excluded due to the considerable diversities and heterogeneities. After removing the duplicates according to preferred reporting items for systematic reviews and meta-analyses (PRISMA) instruction, we merged remaining titles across search databases. There are 48 ongoing studies related to the application of nucleic acids in the treatment and diagnosis of AD where more consideration is given to DNA targeting strategies (18 targets for vectors and aptamers), antisense oligonucleotides (10 targets), micro-RNAs mimics (7 targets), antagomiRs (6 targets), small interferences-RNAs (5 targets), as well as mRNAs (2 targets) respectively. All of these targets are grouped into 4 categories according to their role in molecular pathways where amyloid-β (18 targets), neural survival (11 targets), memory and cognition (8 targets), and tau (3 targets) are more targeted pathways, respectively. With recent successes in the systemic delivery of nucleic acids via intravenous injection; it is worth investing in the production of new-generation medicines. There are still several challenges for NA-BTs including, their delivery to the effective modulators, mass production at low cost, sustaining efficacy and minimizing off-target effects. Regarding miRNA-based therapies, given the obvious involvement of miRNAs in numerous facets of brain disease, and the many sophisticated techniques for delivery to the brain, miRNA-based therapies will make new hope for the treatment of neurological diseases such as AD.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Antagomirs; Aptamers, Nucleotide; CRISPR-Cas Systems; Humans; MicroRNAs; Nucleic Acids; Oligonucleotides, Antisense; RNA, Small Interfering
PubMed: 32400332
DOI: 10.2174/1389557520666200513122357 -
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 -
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 -
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 -
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 -
Acta Reumatologica Portuguesa 2019Ultrasound (US) is a relatively cheap, easily available and reliable method to improve the care of rheumatic patients. However, its use in rheumatology practice is very...
INTRODUCTION
Ultrasound (US) is a relatively cheap, easily available and reliable method to improve the care of rheumatic patients. However, its use in rheumatology practice is very heterogeneous and needs to be standardized.
OBJECTIVES
To develop recommendations for the use of US in rheumatic diseases endorsed by the Portuguese Society of Rheumatology.
METHODS
A systematic literature review of the available recommendations on the use of ultrasound in rheumatic diseases was performed and presented in a Portuguese Society of Rheumatology meeting to a subgroup of rheumatologists and rheumatology trainees with special interest in the subject. The most important topics to be addressed were selected and assigned to subgroups for literature review and draft recommendations. Following an iterative process of consensus, the final recommendations were developed, and their level of agreement voted anonymously online. A recommendation was approved when the average level of agreement was ≥ 7.5 in a 10-point Likert scale.
RESULTS
Fourteen recommendations were produced regarding nine rheumatology topics: rheumatoid arthritis, spondyloarthritis, connective tissue diseases, polymyalgia rheumatica, vasculitis, crystal-deposition diseases, soft tissue rheumatism, osteoarthritis and ultrasound-guided procedures.
CONCLUSION
We developed an up-to-date guidance in the form of recommendations for the use of US in nine different areas of rheumatology. As ultrasound is an important imaging modality with increasing use in the rheumatology setting, and there are frequent technological advances in the ultrasound machines and probes, in parallel with continuous associated research, these recommendations should be regularly updated.
Topics: Arthritis, Rheumatoid; Humans; Joint Diseases; Portugal; Rheumatic Diseases; Rheumatology; Ultrasonography
PubMed: 31249273
DOI: No ID Found -
Drugs May 2019Our aim was to assess the efficacy and safety of mipomersen through a systematic review of the literature and a meta-analysis of the available clinical studies. (Meta-Analysis)
Meta-Analysis
AIM
Our aim was to assess the efficacy and safety of mipomersen through a systematic review of the literature and a meta-analysis of the available clinical studies.
METHODS
A systematic literature search in SCOPUS, PubMed Medline, ISI Web of Science and Google Scholar databases was conducted up to January 20, 2019, in order to identify clinical trials assessing the effect of mipomersen on lipoproteins, and the safety profile of mipomersen. Effect sizes for lipid changes were expressed as weighted mean differences (WMD) and 95% confidence intervals (CI). For safety analysis, odd ratios (OR) and 95% CI were calculated using the Mantel-Haenszel method. Data were pooled from 13 clinical studies comprising 49 arms, which included 1053 subjects overall, with 729 in the active-treated arm and 324 in the control arm.
RESULTS
Meta-analysis of data suggested that mipomersen significantly reduced low-density lipoprotein cholesterol (WMD - 1.52, 95% CI - 1.85 to - 1.19; p < 0.001), total cholesterol (WMD - 1.55, 95% CI - 1.97 to - 1.13; p < 0.001), non-high-density lipoprotein cholesterol (non-HDL-C) (WMD - 1.66, 95% CI - 2.06 to - 1.27; p < 0.001), lipoprotein(a) (WMD - 0.99, 95% CI - 1.37 to - 0.62; p < 0.001), apolipoprotein B (WMD - 1.66, 95% CI - 2.04 to - 1.27; p < 0.001), triglycerides (WMD -0.61, 95% CI - 0.76 to - 0.46, p < 0.001), very-low-density lipoprotein cholesterol (WMD - 0.58, 95% CI - 0.73 to - 0.43; p < 0.001) and apolipoprotein A-I (WMD - 0.25, 95% CI - 0.51 to - 0.001; p = 0.049) without affecting HDL-C levels (WMD 0.11, 95% CI - 0.03 to 0.26; p = 0.124). However, treatment with mipomersen was positively associated with an increased risk of discontinuation of treatment (OR 3.02, 95% CI 1.96-4.65; p < 0.001), injection-site reaction (OR 11.41, 95% CI 7.88-16.52; p < 0.001), hepatic steatosis (OR 4.96, 95% CI 1.99-12.39; p = 0.001), hepatic enzymes elevation (OR 3.61, 95% CI 2.09-6.24; p < 0.001) and flu-like symptoms (OR 2.02, 95% CI 1.45-2.81; p < 0.001).
CONCLUSION
Despite favourable effects on the lipid profile, some concerns are reinforced from the safety profile. As a matter of fact, mipomersen therapy is more likely discontinued and associated with increased risk of injection-site reactions, hepatic steatosis, hepatic enzyme elevation, and flu-like symptoms.
Topics: Adolescent; Adult; Aged; Anticholesteremic Agents; Apolipoprotein A-I; Cholesterol, LDL; Fatty Liver; Female; Humans; Lipids; Lipoprotein(a); Male; Middle Aged; Oligonucleotides; Randomized Controlled Trials as Topic; Triglycerides
PubMed: 30989634
DOI: 10.1007/s40265-019-01114-z -
Clinical Pharmacokinetics Oct 2019Enzyme-mediated biotransformation of pharmacological agents is a crucial step in xenobiotic detoxification and drug disposition. Herein, we investigated the metabolism...
Physicochemical Properties, Biotransformation, and Transport Pathways of Established and Newly Approved Medications: A Systematic Review of the Top 200 Most Prescribed Drugs vs. the FDA-Approved Drugs Between 2005 and 2016.
BACKGROUND
Enzyme-mediated biotransformation of pharmacological agents is a crucial step in xenobiotic detoxification and drug disposition. Herein, we investigated the metabolism and physicochemical properties of the top 200 most prescribed drugs (established) as well as drugs approved by the US Food and Drug Administration (FDA) between 2005 and 2016 (newly approved).
OBJECTIVE
Our objective was to capture the changing trends in the routes of administration, physicochemical properties, and prodrug medications, as well as the contributions of drug-metabolizing enzymes and transporters to drug clearance.
METHODS
The University of Washington Drug Interaction Database (DIDB) as well as other online resources (e.g., CenterWatch.com, Drugs.com, DrugBank.ca, and PubChem.ncbi.nlm.nih.gov) was used to collect and stratify the dataset required for exploring the above-mentioned trends.
RESULTS
Analyses revealed that ~ 90% of all drugs in the established and newly approved drug lists were administered systemically (oral or intravenous). Meanwhile, the portion of biologics (molecular weight > 1 kDa) was 15 times greater in the newly approved list than established drugs. Additionally, there was a 4.5-fold increase in the number of compounds with a high calculated partition coefficient (cLogP > 3) and a high total polar surface area (> 75 Å) in the newly approved drug vs. the established category. Further, prodrugs in established or newly approved lists were found to be converted to active compounds via hydrolysis, demethylases, and kinases. The contribution of cytochrome P450 (CYP) 3A4, as the major biotransformation pathway, has increased from 40% in the established drug list to 64% in the newly approved drug list. Moreover, the role of CYP1A2, CYP2C19, and CYP2D6 were decreased as major metabolizing enzymes among the newly approved medications. Among non-CYP major metabolizers, the contribution of alcohol dehydrogenases/aldehyde dehydrogenases (ADH/ALDH) and sulfotransferases decreased in the newly approved drugs compared with the established list. Furthermore, the highest contribution among uptake and efflux transporters was found for Organic Anion Transporting Polypeptide 1B1 (OATP1B1) and P-glycoprotein (P-gp), respectively.
CONCLUSIONS
The higher portion of biologics in the newly approved drugs compared with the established list confirmed the growing demands for protein- and antibody-based therapies. Moreover, the larger number of hydrophilic drugs found in the newly approved list suggests that the probability of toxicity is likely to decrease. With regard to CYP-mediated major metabolism, CYP3A5 showed an increased involvement owing to the identification of unique probe substrates to differentiate CYP3As. Furthermore, the contribution of OATP1B1 and P-gp did not show a significant shift in the newly approved drugs as compared to the established list because of their broad substrate specificity.
Topics: Animals; Biological Transport; Biotransformation; Drug Approval; Humans; Prescription Drugs; United States; United States Food and Drug Administration
PubMed: 30972694
DOI: 10.1007/s40262-019-00750-8 -
Scientific Reports Mar 2019This systematic review assesses the accuracy of molecular diagnostic methods for the detection of pulmonary tuberculosis in studies performed in China, published in...
This systematic review assesses the accuracy of molecular diagnostic methods for the detection of pulmonary tuberculosis in studies performed in China, published in Chinese and English. We searched for studies that assessed the accuracy of molecular diagnostics for pulmonary TB in China in the China National Knowledge Infrastructure, the Wanfang Database, SinoMed, VIP Information, Pubmed, Embase, and the Cochrane Library. For each index test, a summary estimation for sensitivity and specificity was calculated using the bivariate random-effects model. A total of 59 studies were included in our analysis. Loop-mediated isothermal amplifcation (LAMP) assay (six studies; pooled sensitivity 90%, 95% CI 78-95%; specificity 93%, 85-97%), line probe assay (LPA) (one study; 87%, 84-90%; 94%, 92-95%) and polymerase chain reaction (PCR) (FQ-PCR and RT-PCR) (four studies; 90%, 55-99%; 93%, 71-99%) showed good diagnostic performance in the meta-analysis. The highest pooled sensitivity was from Xpert MTB/RIF (20 studies; pooled sensitivity 91%, 95% CI 87-94%). The highest pooled specificity was from cross-priming amplification (CPA) (six studies; pooled specificity 97%, 95-99%). The lowest pooled sensitivity and specificity were from simultaneous amplification and testing (SAT)-TB (three studies; 79%, 66-88%; 72%, 48-88%). In subgroup analysis, molecular diagnostics demonstrated higher sensitivity for pulmonary TB detection in smear-positive specimens. Xpert MTB/RIF, LAMP, LPA, CPA and PCR demonstrated high accuracy overall for pulmonary tuberculosis detection, while SAT-TB had poor performance.
Topics: China; Humans; Molecular Diagnostic Techniques; Mycobacterium tuberculosis; Pathology, Molecular; Predictive Value of Tests; Tuberculosis, Pulmonary
PubMed: 30872692
DOI: 10.1038/s41598-019-41074-8 -
BMJ Open Jan 2019We evaluated the performance of nucleic acid amplification tests (NAATs) using vaginal specimens in comparison to specimens from the cervix or urine in their ability to...
Evaluation of the performance of nucleic acid amplification tests (NAATs) in detection of chlamydia and gonorrhoea infection in vaginal specimens relative to patient infection status: a systematic review.
OBJECTIVE
We evaluated the performance of nucleic acid amplification tests (NAATs) using vaginal specimens in comparison to specimens from the cervix or urine in their ability to detect chlamydia and gonorrhoea infection in women based on patient infection status (PIS).
DESIGN
Systematic review.
DATA SOURCES
EMBASE and Ovid MEDLINE databases were searched through 3 October 2017.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
We included studies that tested samples from the vagina and ≥1 other site (cervix and/or urine) with ≥2 NAATs for chlamydia and ≥2 NAATs or 1 NAAT and culture for gonorrhoea for each site.
DATA EXTRACTION AND SYNTHESIS
Performance is defined as the sensitivity of a NAAT using a specimen site and PIS of the patient. We assessed risk of bias using modified QUADAS-2.
RESULTS
Nine publications met the inclusion criteria (eight for chlamydia; six for gonorrhoea) and were narratively reviewed. Pooled summary estimates were not calculated due to the variable methodology and PIS definitions. Tests performed on vaginal specimens accomplished similar performance to cervical and urine specimens for chlamydia (range of performance estimates: vaginal 65%-100%, cervical 59%-97%, urine 57%-100%) and gonorrhoea (vaginal 64%-100%, cervical 85%-100%, urine 67%-94%). Vaginal specimens were estimated to have a performance >80% for chlamydia and gonorrhoea infections in all but one study.
CONCLUSIONS
Performance of the NAATs for chlamydia and gonorrhoea detection using vaginal specimens was similar to that of cervical and urine specimens relative to PIS. As vaginal samples have a higher acceptability and lower cost, the study can support clinical testing guidelines by providing evidence that vaginal samples are a suitable alternative to traditionally used specimens.
Topics: Chlamydia Infections; Chlamydia trachomatis; Cost-Benefit Analysis; Female; Gonorrhea; Humans; Neisseria gonorrhoeae; Nucleic Acid Amplification Techniques; Sensitivity and Specificity; Vagina
PubMed: 30659036
DOI: 10.1136/bmjopen-2018-022510