A fast and low-cost genotyping method for hepatitis B virus based on pattern recognition in point-of-care settings.
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ABSTRACT:
SUBMITTER: Qiu X
PROVIDER: S-EPMC4910285 | biostudies-other | 2016
REPOSITORIES: biostudies-other
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Project description:Given the scale and rapid spread of the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, or 2019-nCoV), there is an urgent need to identify therapeutics that are effective against COVID-19 before vaccines are available. Since the current rate of SARS-CoV-2 knowledge acquisition via traditional research methods is not sufficient to match the rapid spread of the virus, novel strategies of drug discovery for SARS-CoV-2 infection are required. Structure-based virtual screening for example relies primarily on docking scores and does not take the importance of key residues into consideration, which may lead to a significantly higher incidence rate of false-positive results. Our novel in silico approach, which overcomes these limitations, can be utilized to quickly evaluate FDA-approved drugs for repurposing and combination, as well as designing new chemical agents with therapeutic potential for COVID-19. As a result, anti-HIV or antiviral drugs (lopinavir, tenofovir disoproxil, fosamprenavir and ganciclovir), antiflu drugs (peramivir and zanamivir) and an anti-HCV drug (sofosbuvir) are predicted to bind to 3CLPro in SARS-CoV-2 with therapeutic potential for COVID-19 infection by our new protocol. In addition, we also propose three antidiabetic drugs (acarbose, glyburide and tolazamide) for the potential treatment of COVID-19. Finally, we apply our new virus chemogenomics knowledgebase platform with the integrated machine-learning computing algorithms to identify the potential drug combinations (e.g. remdesivir+chloroquine), which are congruent with ongoing clinical trials. In addition, another 10 compounds from CAS COVID-19 antiviral candidate compounds dataset are also suggested by Molecular Complex Characterizing System with potential treatment for COVID-19. Our work provides a novel strategy for the repurposing and combinations of drugs in the market and for prediction of chemical candidates with anti-COVID-19 potential.
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Project description:In the United States, hepatitis C virus (HCV) infection is most prevalent among adults born from 1945 through 1965, and approximately 50% to 75% of infected adults are unaware of their infection.To estimate the cost-effectiveness of birth-cohort screening.Cost-effectiveness simulation.National Health and Nutrition Examination Survey, U.S. Census, Medicare reimbursement schedule, and published sources.Adults born from 1945 through 1965 with 1 or more visits to a primary care provider annually.Lifetime.Societal, health care.One-time antibody test of 1945-1965 birth cohort.Numbers of cases that were identified and treated and that achieved a sustained viral response; liver disease and death from HCV; medical and productivity costs; quality-adjusted life-years (QALYs); incremental cost-effectiveness ratio (ICER).Compared with the status quo, birth-cohort screening identified 808,580 additional cases of chronic HCV infection at a screening cost of $2874 per case identified. Assuming that birth-cohort screening was followed by pegylated interferon and ribavirin (PEG-IFN+R) for treated patients, screening increased QALYs by 348,800 and costs by $5.5 billion, for an ICER of $15,700 per QALY gained. Assuming that birth-cohort screening was followed by direct-acting antiviral plus PEG-IFN+R treatment for treated patients, screening increased QALYs by 532,200 and costs by $19.0 billion, for an ICER of $35,700 per QALY saved.The ICER of birth-cohort screening was most sensitive to sustained viral response of antiviral therapy, the cost of therapy, the discount rate, and the QALY losses assigned to disease states.Empirical data on screening and direct-acting antiviral treatment in real-world clinical settings are scarce.Birth-cohort screening for HCV in primary care settings was cost-effective.Division of Viral Hepatitis, Centers for Disease Control and Prevention.
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Project description:IntroductionCurrent guidelines by WHO for cervical cancer screening in low- and middle-income countries involves visual inspection with acetic acid (VIA) of the cervix, followed by treatment during the same visit or a subsequent visit with cryotherapy if a suspicious lesion is found. Implementation of these guidelines is hampered by a lack of: trained health workers, reliable technology, and access to screening facilities. A low cost ultra-portable Point of Care Tampon based digital colposcope (POCkeT Colposcope) for use at the community level setting, which has the unique form factor of a tampon, can be inserted into the vagina to capture images of the cervix, which are on par with that of a state of the art colposcope, at a fraction of the cost. A repository of images to be compiled that can be used to empower front line workers to become more effective through virtual dynamic training. By task shifting to the community setting, this technology could potentially provide significantly greater cervical screening access to where the most vulnerable women live. The POCkeT Colposcope's concentric LED ring provides comparable white and green field illumination at a fraction of the electrical power required in commercial colposcopes. Evaluation with standard optical imaging targets to assess the POCkeT Colposcope against the state of the art digital colposcope and other VIAM technologies.ResultsOur POCkeT Colposcope has comparable resolving power, color reproduction accuracy, minimal lens distortion, and illumination when compared to commercially available colposcopes. In vitro and pilot in vivo imaging results are promising with our POCkeT Colposcope capturing comparable quality images to commercial systems.ConclusionThe POCkeT Colposcope is capable of capturing images suitable for cervical lesion analysis. Our portable low cost system could potentially increase access to cervical cancer screening in limited resource settings through task shifting to community health workers.
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Project description:Approximately 170 million people are chronic carriers of hepatitis C virus (HCV). Patients with chronic hepatitis C are currently treated with pegylated interferon and ribavirin (PEG-IFN/RBV). A genome-wide association with PEG-IFN/RBV treatment response and a single nucleotide polymorphism (rs12979860) has been identified near the interleukin 28B gene that encodes interferon-?-3. In this paper, we describe an innovative, fast, and low-cost multiplex polymerase chain reaction with confronting two-pair primers that detects the rs12979860 polymorphism. The assay is internally controlled and does not require the use of restriction endonucleases or special equipment. Moreover, the assay decreases costs, being about 40% cheaper than direct sequencing methods.
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Project description:Monitoring of HIV viral load in patients on combination antiretroviral therapy (ART) is not generally available in resource-limited settings. We examined the cost-effectiveness of qualitative point-of-care viral load tests (POC-VL) in sub-Saharan Africa.Mathematical model based on longitudinal data from the Gugulethu and Khayelitsha township ART programmes in Cape Town, South Africa.Cohorts of patients on ART monitored by POC-VL, CD4 cell count or clinically were simulated. Scenario A considered the more accurate detection of treatment failure with POC-VL only, and scenario B also considered the effect on HIV transmission. Scenario C further assumed that the risk of virologic failure is halved with POC-VL due to improved adherence. We estimated the change in costs per quality-adjusted life-year gained (incremental cost-effectiveness ratios, ICERs) of POC-VL compared with CD4 and clinical monitoring.POC-VL tests with detection limits less than 1000 copies/ml increased costs due to unnecessary switches to second-line ART, without improving survival. Assuming POC-VL unit costs between US$5 and US$20 and detection limits between 1000 and 10,000 copies/ml, the ICER of POC-VL was US$4010-US$9230 compared with clinical and US$5960-US$25540 compared with CD4 cell count monitoring. In Scenario B, the corresponding ICERs were US$2450-US$5830 and US$2230-US$10380. In Scenario C, the ICER ranged between US$960 and US$2500 compared with clinical monitoring and between cost-saving and US$2460 compared with CD4 monitoring.The cost-effectiveness of POC-VL for monitoring ART is improved by a higher detection limit, by taking the reduction in new HIV infections into account and assuming that failure of first-line ART is reduced due to targeted adherence counselling.
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Project description:Loss-of-function CYP2C19 variants are associated with increased cumulative ischemic outcomes warranting CYP2C19 genotyping prior to clopidogrel administration. TAILOR-PCI was an international, multicenter (40 sites), prospective, randomized trial comparing rapid point of care (POC) genotype-guided vs. conventional anti-platelet therapy. The performance of buccal-based rapid CYP2C19 genotyping performed by non-laboratory-trained staff in TAILOR-PCI was assessed. Pre-trial training and evaluation involved rapid genotyping of 373 oral samples, with 99.5% (371/373) concordance with Sanger sequencing. During TAILOR-PCI, 5302 patients undergoing PCI were randomized to POC rapid CYP2C19 *2, *3, and *17 genotyping versus no genotyping. At 12 months post-PCI, TaqMan genotyping determined 99.1% (2,364/2,385) concordance with the POC results, with 90.7-98.8% sensitivity and 99.2-99.6% specificity. In conclusion, non-laboratory personnel can be successfully trained for on-site instrument operation and POC rapid genotyping with analytical accuracy and precision across multiple international centers, thereby supporting POC genotyping in patient-care settings, such as the cardiac catheterization laboratory.Clinical Trial Registration: https://www.clinicalTrials.gov (Identifier: NCT01742117).
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Project description:BackgroundHigh hepatitis C virus (HCV) rates have been reported in young people who inject drugs (PWID). We evaluated the clinical benefit and cost-effectiveness of testing among youth seen in communities with a high overall number of reported HCV cases.MethodsWe developed a decision analytic model to project quality-adjusted life years (QALYs), costs (2016 US$), and incremental cost-effectiveness ratios (ICERs) of 9 strategies for 1-time testing among 15- to 30-year-olds seen at urban community health centers. Strategies differed in 3 ways: targeted vs routine testing, rapid finger stick vs standard venipuncture, and ordered by physician vs by counselor/tester using standing orders. We performed deterministic and probabilistic sensitivity analyses (PSA) to evaluate uncertainty.ResultsCompared to targeted risk-based testing (current standard of care), routine testing increased the lifetime medical cost by $80 and discounted QALYs by 0.0013 per person. Across all strategies, rapid testing provided higher QALYs at a lower cost per QALY gained and was always preferred. Counselor-initiated routine rapid testing was associated with an ICER of $71000/QALY gained. Results were sensitive to offer and result receipt rates. Counselor-initiated routine rapid testing was cost-effective (ICER <$100000/QALY) unless the prevalence of PWID was <0.59%, HCV prevalence among PWID was <16%, reinfection rate was >26 cases per 100 person-years, or reflex confirmatory testing followed all reactive venipuncture diagnostics. In PSA, routine rapid testing was the optimal strategy in 90% of simulations.ConclusionsRoutine rapid HCV testing among 15- to 30-year-olds may be cost-effective when the prevalence of PWID is >0.59%.
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Project description:Cell phones show considerable promise for point-of-care (POC) diagnostic procedures because they are accessible, connected, and computationally powerful. Cell phone image processing methods are being developed for the detection and quantification of a wide range of targets, employing methods from microscopy to fluorescence techniques. However, most of the lab-based biological and biochemical assays still lack a robust and repeatable cell phone analogue. Existing solutions require external smartphone hardware to obtain quantitative results, imposing a design tradeoff between accessibility and accuracy. Here, we develop a cell phone imaging algorithm that enables analysis of assays that would typically be evaluated via spectroscopy. The developed technique uses the saturation parameter of hue-saturation-value color space to enable POC diagnosis. Through the analysis of over 10?000 images, we show that the saturation method consistently outperforms existing algorithms under a wide range of operating field conditions. The performance improvement is also proven analytically via the mathematic relationship between the saturation method and existing techniques. The method presented here is a step forward towards the development of POC diagnostics by reducing the required equipment, improving the limit of detection (LOD), and increasing the precision of quantitative results.
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Project description:Globally, there are approximately 58 million people with chronic hepatitis C virus infection (HCV) but only 20% have been diagnosed. HCV self-testing (HCVST) could reach those who have never been tested and increase uptake of HCV testing services. We compared cost per HCV viraemic diagnosis or cure for HCVST versus facility-based HCV testing services. We used a decision analysis model with a one-year time horizon to examine the key drivers of economic cost per diagnosis or cure following the introduction of HCVST in China (men who have sex with men), Georgia (men 40-49 years), Viet Nam (people who inject drugs, PWID), and Kenya (PWID). HCV antibody (HCVAb) prevalence ranged from 1%-60% across settings. Model parameters in each setting were informed by HCV testing and treatment programmes, HIV self-testing programmes, and expert opinion. In the base case, we assume a reactive HCVST is followed by a facility-based rapid diagnostic test (RDT) and then nucleic acid testing (NAT). We assumed oral-fluid HCVST costs of $5.63/unit ($0.87-$21.43 for facility-based RDT), 62% increase in testing following HCVST introduction, 65% linkage following HCVST, and 10% replacement of facility-based testing with HCVST based on HIV studies. Parameters were varied in sensitivity analysis. Cost per HCV viraemic diagnosis without HCVST ranged from $35 2019 US dollars (Viet Nam) to $361 (Kenya). With HCVST, diagnosis increased resulting in incremental cost per diagnosis of $104 in Viet Nam, $163 in Georgia, $587 in Kenya, and $2,647 in China. Differences were driven by HCVAb prevalence. Switching to blood-based HCVST ($2.25/test), increasing uptake of HCVST and linkage to facility-based care and NAT testing, or proceeding directly to NAT testing following HCVST, reduced the cost per diagnosis. The baseline incremental cost per cure was lowest in Georgia ($1,418), similar in Viet Nam ($2,033), and Kenya ($2,566), and highest in China ($4,956). HCVST increased the number of people tested, diagnosed, and cured, but at higher cost. Introducing HCVST is more cost-effective in populations with high prevalence.
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