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Scientific Reports Mar 2018Antisense oligonucleotide (AON)-based therapies hold promise for a range of neurodegenerative and neuromuscular diseases and have shown benefit in animal models and... (Meta-Analysis)
Meta-Analysis
Antisense oligonucleotide (AON)-based therapies hold promise for a range of neurodegenerative and neuromuscular diseases and have shown benefit in animal models and patients. Success in the clinic is nevertheless still limited, due to unfavourable biodistribution and poor cellular uptake of AONs. Extensive research is currently being conducted into the formulation of AONs to improve delivery, but thus far there is no consensus on which of those strategies will be the most effective. This systematic review was designed to answer in an unbiased manner which delivery strategies most strongly enhance the efficacy of AONs in animal models of heritable neurodegenerative and neuromuscular diseases. In total, 95 primary studies met the predefined inclusion criteria. Study characteristics and data on biodistribution and toxicity were extracted and reporting quality and risk of bias were assessed. Twenty studies were eligible for meta-analysis. We found that even though the use of delivery systems provides an advantage over naked AONs, it is not yet possible to select the most promising strategies. Importantly, standardisation of experimental procedures is warranted in order to reach conclusions about the most efficient delivery strategies. Our best practice guidelines for future experiments serve as a step in that direction.
Topics: Animals; Disease Models, Animal; Drug Delivery Systems; Heredodegenerative Disorders, Nervous System; Neuromuscular Diseases; Oligonucleotides, Antisense
PubMed: 29520012
DOI: 10.1038/s41598-018-22316-7 -
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 -
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 -
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 -
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 -
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 -
Rheumatology (Oxford, England) Dec 2021To investigate the reliability of high frequency ultrasound (HFUS) in measuring skin fibrosis in SSc.
OBJECTIVES
To investigate the reliability of high frequency ultrasound (HFUS) in measuring skin fibrosis in SSc.
METHODS
First, a systematic review (according to PRISMA) was conducted to identify studies that documented HFUS' reliability in SSc as a primary outcome. Then, in an additional pilot study, the inter- and intra-rater reliability of two investigators performing HFUS for dermal thickness (DT) measurements in a standardized manner across all 17 areas of the modified Rodnan Skin Score was evaluated in a group of 59 SSc patients and descriptively in 44 healthy controls (HC). As an external validation, DT measurements by HFUS were performed in a separate group of 30 SSc patients by the same first and another third investigator.
RESULTS
The systematic review retained few (4/1719 unique records) small-scale studies, with mixed study populations (combining SSc and HC). The reported data herein are suggestive of the inter-/intra-rater reliability of HFUS (intra-class correlation coefficient [ICCs] ranging 0.65-0.94/0.55-0.96, respectively). Additionally, in our pilot study, inter-/intra-rater reliability was good-to-excellent in both SSc groups and HC (ICCs ranging 0.70-0.97/0.70-0.98 and 0.65-0.95/0.63-0.96, respectively).
CONCLUSION
The identified small-scale studies were not only combining data from SSc and HC, they were also heterogeneous in terms of technical aspects (probes and frequency), image acquisition methods ([number of] areas assessed) and definitions used for skin thickness, which prevents drawing unequivocal conclusions. Despite these limitations, our standardized pilot study corroborated the findings in literature, paving the way for the applicability of HFUS as a reliable (complementary) tool to quantify skin fibrosis in SSc.
Topics: Adult; Aged; Female; Fibrosis; Humans; Male; Middle Aged; Pilot Projects; Reproducibility of Results; Scleroderma, Systemic; Skin; Ultrasonography
PubMed: 34037710
DOI: 10.1093/rheumatology/keab462 -
Journal of Ovarian Research Mar 2017Mature cystic teratomas are usually found in the ovaries. They are bilateral in 10 to 15% of cases and multiple cystic teratomas may be present in one ovary. The aim of... (Review)
Review
BACKGROUND
Mature cystic teratomas are usually found in the ovaries. They are bilateral in 10 to 15% of cases and multiple cystic teratomas may be present in one ovary. The aim of this study is to clarify if development of mature cystic teratomas of the ovaries in a single host is metachronous or due to autoimplant or recurrence.
CASE PRESENTATION
We report a woman with bilateral mature cystic teratomas of the ovaries. DNA profiles of these teratomas were investigated via short tandem repeat (STR) analysis and methylation statuses were determined via methylation sensitive multiplex ligation-dependent probe amplification methods. The results showed that the cystic teratomas originated from different stages of oogonia or primary oocyte before germinal vesicle stage failure of meiosis I in female gametogenesis. Potentially relevant literature was searched in PubMed database. Cases of bilateral or multiple mature cystic teratomas of the ovaries were analyzed. To date, there has been no reported case of multiple mature cystic teratomas in which clarification of the origin was achieved using molecular genetic methods.
CONCLUSIONS
The results of this case study provide evidence of metachronous development of mature cystic teratomas of the ovaries and may serve as a reference in the management of patients following laparoscopic cystectomy.
Topics: Adult; DNA Copy Number Variations; DNA Methylation; Female; Genetic Loci; Humans; Loss of Heterozygosity; Microsatellite Repeats; Neoplasm Grading; Neoplasms, Second Primary; Ovarian Neoplasms; Sequence Analysis, DNA; Teratoma
PubMed: 28288660
DOI: 10.1186/s13048-017-0313-8 -
The Cochrane Database of Systematic... Mar 2021Tuberculosis is a leading cause of infectious disease-related death and is one of the top 10 causes of death worldwide. The World Health Organization (WHO) recommends... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Tuberculosis is a leading cause of infectious disease-related death and is one of the top 10 causes of death worldwide. The World Health Organization (WHO) recommends the use of specific rapid molecular tests, including Xpert MTB/RIF or Xpert Ultra, as initial diagnostic tests for the detection of tuberculosis and rifampicin resistance in people with signs and symptoms of tuberculosis. However, the WHO estimates that nearly one-third of all active tuberculosis cases go undiagnosed and unreported. We were interested in whether a single test, Xpert MTB/RIF or Xpert Ultra, could be useful as a screening test to close this diagnostic gap and improve tuberculosis case detection.
OBJECTIVES
To estimate the accuracy of Xpert MTB/RIF and Xpert Ultra for screening for pulmonary tuberculosis in adults, irrespective of signs or symptoms of pulmonary tuberculosis in high-risk groups and in the general population. Screening "irrespective of signs or symptoms" refers to screening of people who have not been assessed for the presence of tuberculosis symptoms (e.g. cough). To estimate the accuracy of Xpert MTB/RIF and Xpert Ultra for detecting rifampicin resistance in adults screened for tuberculosis, irrespective of signs and symptoms of pulmonary tuberculosis in high-risk groups and in the general population.
SEARCH METHODS
We searched 12 databases including the Cochrane Infectious Diseases Group Specialized Register, MEDLINE and Embase, on 19 March 2020 without language restrictions. We also reviewed reference lists of included articles and related Cochrane Reviews, and contacted researchers in the field to identify additional studies.
SELECTION CRITERIA
Cross-sectional and cohort studies in which adults (15 years and older) in high-risk groups (e.g. people living with HIV, household contacts of people with tuberculosis) or in the general population were screened for pulmonary tuberculosis using Xpert MTB/RIF or Xpert Ultra. For tuberculosis detection, the reference standard was culture. For rifampicin resistance detection, the reference standards were culture-based drug susceptibility testing and line probe assays.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data using a standardized form and assessed risk of bias and applicability using QUADAS-2. We used a bivariate random-effects model to estimate pooled sensitivity and specificity with 95% credible intervals (CrIs) separately for tuberculosis detection and rifampicin resistance detection. We estimated all models using a Bayesian approach. For tuberculosis detection, we first estimated screening accuracy in distinct high-risk groups, including people living with HIV, household contacts, people residing in prisons, and miners, and then in several high-risk groups combined.
MAIN RESULTS
We included a total of 21 studies: 18 studies (13,114 participants) evaluated Xpert MTB/RIF as a screening test for pulmonary tuberculosis and one study (571 participants) evaluated both Xpert MTB/RIF and Xpert Ultra. Three studies (159 participants) evaluated Xpert MTB/RIF for rifampicin resistance. Fifteen studies (75%) were conducted in high tuberculosis burden and 16 (80%) in high TB/HIV-burden countries. We judged most studies to have low risk of bias in all four QUADAS-2 domains and low concern for applicability. Xpert MTB/RIF and Xpert Ultra as screening tests for pulmonary tuberculosis In people living with HIV (12 studies), Xpert MTB/RIF pooled sensitivity and specificity (95% CrI) were 61.8% (53.6 to 69.9) (602 participants; moderate-certainty evidence) and 98.8% (98.0 to 99.4) (4173 participants; high-certainty evidence). Of 1000 people where 50 have tuberculosis on culture, 40 would be Xpert MTB/RIF-positive; of these, 9 (22%) would not have tuberculosis (false-positives); and 960 would be Xpert MTB/RIF-negative; of these, 19 (2%) would have tuberculosis (false-negatives). In people living with HIV (1 study), Xpert Ultra sensitivity and specificity (95% CI) were 69% (57 to 80) (68 participants; very low-certainty evidence) and 98% (97 to 99) (503 participants; moderate-certainty evidence). Of 1000 people where 50 have tuberculosis on culture, 53 would be Xpert Ultra-positive; of these, 19 (36%) would not have tuberculosis (false-positives); and 947 would be Xpert Ultra-negative; of these, 16 (2%) would have tuberculosis (false-negatives). In non-hospitalized people in high-risk groups (5 studies), Xpert MTB/RIF pooled sensitivity and specificity were 69.4% (47.7 to 86.2) (337 participants, low-certainty evidence) and 98.8% (97.2 to 99.5) (8619 participants, moderate-certainty evidence). Of 1000 people where 10 have tuberculosis on culture, 19 would be Xpert MTB/RIF-positive; of these, 12 (63%) would not have tuberculosis (false-positives); and 981 would be Xpert MTB/RIF-negative; of these, 3 (0%) would have tuberculosis (false-negatives). We did not identify any studies using Xpert MTB/RIF or Xpert Ultra for screening in the general population. Xpert MTB/RIF as a screening test for rifampicin resistance Xpert MTB/RIF sensitivity was 81% and 100% (2 studies, 20 participants; very low-certainty evidence), and specificity was 94% to 100%, (3 studies, 139 participants; moderate-certainty evidence).
AUTHORS' CONCLUSIONS
Of the high-risks groups evaluated, Xpert MTB/RIF applied as a screening test was accurate for tuberculosis in high tuberculosis burden settings. Sensitivity and specificity were similar in people living with HIV and non-hospitalized people in high-risk groups. In people living with HIV, Xpert Ultra sensitivity was slightly higher than that of Xpert MTB/RIF and specificity similar. As there was only one study of Xpert Ultra in this analysis, results should be interpreted with caution. There were no studies that evaluated the tests in people with diabetes mellitus and other groups considered at high-risk for tuberculosis, or in the general population.
Topics: Adult; Antibiotics, Antitubercular; Bacteriological Techniques; Bayes Theorem; Bias; Cohort Studies; Cross-Sectional Studies; Drug Resistance, Bacterial; False Negative Reactions; False Positive Reactions; HIV Infections; Humans; Mycobacterium tuberculosis; Polymerase Chain Reaction; Rifampin; Sensitivity and Specificity; Sputum; Tuberculosis, Pulmonary
PubMed: 33755189
DOI: 10.1002/14651858.CD013694.pub2