scholarly journals Chip-Based Digital PCR Approach Provides A Sensitive and Cost-Effective Single-Day Screening Tool for Common Fetal Aneuploidies—A Proof of Concept Study

2019 ◽  
Vol 20 (21) ◽  
pp. 5486
Author(s):  
Anna Nykel ◽  
Marcin Kaszkowiak ◽  
Wojciech Fendler ◽  
Agnieszka Gach
Keyword(s):  
Clinical Utility ◽  
Screening Tool ◽  
Cost Effective ◽  
Digital Pcr ◽  
Trisomy 13 ◽  
Proof Of Concept ◽  
Rapid Tests ◽  
The Difference ◽  
Clinically Significant ◽  
Fetal Aneuploidies

In the prenatal period, the copy number aberrations of chromosomes 13, 18, 21, X and Y account for over 80% of the clinically significant chromosome abnormalities. Classical cytogenetic analysis is the gold standard in invasive prenatal diagnostics but the long test waiting time affects its clinical utility. Several molecular rapid tests have been developed and employed in clinical practice, however all have substantial drawbacks. The aim of the study was to design and evaluate an optimized tool for rapid molecular detection of fetal aneuploidies. We established a novel single-day method using a chip-based platform, the QuantStudio 3D Digital PCR system. In order to assess the clinical usefulness of our screening test, we analyzed 133 prenatal samples. The difference in distributions of euploid and aneuploid samples identified the ploidy of each of the target chromosomes with high precision. The distribution of the chromosome ratio for euploid and aneuploid samples showed a statistically significant result (p = 0.003 for trisomy 13, p = 0.001 for trisomies 18 and 21, Mann–Whitney U test). Our results suggest that this novel chip-based approach provides a tool for rapid, technically simple, cost-effective screening for common fetal aneuploidies.

scholarly journals Assessment and clinical utility of a non-Next Generation Sequencing based Non-Invasive Prenatal Testing technology

2021 ◽  
Author(s):  
Uzay Gormus ◽  
Alka Chaubey ◽  
Suresh Shenoy ◽  
Yong Wee Wong ◽  
Lee Yin Chan ◽  
...  
Keyword(s):  
Clinical Utility ◽  
Prenatal Testing ◽  
Trisomy 13 ◽  
Rolling Circle Replication ◽  
Rolling Circle ◽  
Non Invasive ◽  
Clinical Laboratories ◽  
Testing Technology ◽  
The Cost ◽  
Fetal Aneuploidies

Background: Rolling circle replication (RCR) is a novel technology that has not been applied to cell-free DNA (cfDNA) testing until recently. Given the cost and simplicity advantages of this technology compared to other platforms currently used in cfDNA analysis, an assessment of RCR in clinical laboratories was performed. Here, we present the first validation study from clinical laboratories utilizing RCR technology. Methods: 831 samples from spontaneously pregnant women carrying a singleton fetus and 25 synthetic samples were analyzed for the fetal risk of Trisomy 21, Trisomy 18 and Trisomy 13 by three laboratories on three continents. All women who provided the samples were followed to birth, where evaluation for fetal aneuploidies was performed using newborn examinations and any suspected aneuploidies were confirmed with karyotyping. Results: The study found rolling circle replication to be a highly viable technology for clinical assessment of fetal aneuploidies with 100% sensitivity for T21 (95% CI:82.35% - 100.00%); 100.00% sensitivity for T18 (71.51% - 100.00%) and 100.00% sensitivity for T13 analyses (66.37% - 100.00%). The specificities were >99% for each trisomies [99.7% (99.01% - 99.97%) for T21; 99.5% (98.62% - 99.85%) for T18; 99.7% (99.03% - 99.97%) for T13], along with a first pass no-call rate of 0.93%. Conclusions: The study showed that using a rolling circle replication-based cfDNA system for the evaluation of the common aneuploidies would provide greater accuracy and clinical utility compared to conventional biochemical screening and comparable results to other reported cfDNA methodologies.

scholarly journals Assessment and Clinical Utility of a Non-Next-Generation Sequencing-Based Non-Invasive Prenatal Testing Technology

2021 ◽  
Vol 43 (2) ◽  
pp. 958-964
Author(s):  
Uzay Gormus ◽  
Alka Chaubey ◽  
Suresh Shenoy ◽  
Yong Wee Wong ◽  
Lee Yin Chan ◽  
...  
Keyword(s):  
Clinical Utility ◽  
Diagnostic Testing ◽  
Prenatal Testing ◽  
Trisomy 13 ◽  
Rolling Circle Replication ◽  
Rolling Circle ◽  
Clinical Laboratories ◽  
Testing Technology ◽  
Post Test ◽  
Fetal Aneuploidies

Background: Rolling-circle replication (RCR) is a novel technology that has not been applied to cell-free DNA (cfDNA) testing until recently. Given the cost and simplicity advantages of this technology compared to other platforms currently used in cfDNA analysis, an assessment of RCR in clinical laboratories was performed. Here, we present the first validation study from clinical laboratories utilizing RCR technology. Methods: 831 samples from spontaneously pregnant women carrying a singleton fetus, and 25 synthetic samples, were analyzed for the fetal risk of trisomy 21 (T21), trisomy 18 (T18) and trisomy 13 (T13), by three laboratories on three continents. All the screen-positive pregnancies were provided post-test genetic counseling and confirmatory diagnostic invasive testing (e.g., amniocentesis). The screen-negative pregnancies were routinely evaluated at birth for fetal aneuploidies, using newborn examinations, and any suspected aneuploidies would have been offered diagnostic testing or confirmed with karyotyping. Results: The study found rolling-circle replication to be a highly viable technology for the clinical assessment of fetal aneuploidies, with 100% sensitivity for T21 (95% CI: 82.35–100.00%); 100.00% sensitivity for T18 (71.51–100.00%); and 100.00% sensitivity for T13 analyses (66.37–100.00%). The specificities were >99% for each trisomy (99.7% (99.01–99.97%) for T21; 99.5% (98.62–99.85%) for T18; 99.7% (99.03–99.97%) for T13), along with a first-pass no-call rate of 0.93%. Conclusions: The study showed that using a rolling-circle replication-based cfDNA system for the evaluation of the common aneuploidies would provide greater accuracy and clinical utility compared to conventional biochemical screening, and it would provide comparable results to other reported cfDNA methodologies.

Investigations into the Clinical Utility of Latex D-Dimer in the Diagnosis of Deep Venous Thrombosis

1993 ◽  
Vol 69 (01) ◽  
pp. 008-011 ◽  
Author(s):  
Cedric J Carter ◽  
D Lynn Doyle ◽  
Nigel Dawson ◽  
Shauna Fowler ◽  
Dana V Devine
Keyword(s):  
Venous Thrombosis ◽  
Deep Venous Thrombosis ◽  
Lower Limb ◽  
Clinical Utility ◽  
Rapid Test ◽  
Fibrin Degradation Product ◽  
Current Form ◽  
Non Invasive ◽  
Clinically Significant ◽  
D Dimer

SummaryThe serial use of non-invasive tests has been shown to be a safe method of managing outpatients who are suspected of having lower limb deep venous thrombosis (DVT). Objective testing has shown that the majority of these outpatients do not have venous thrombosis. A rapid test to exclude DVT in these patients, without the need for expensive and inconvenient serial non-invasive vascular testing, would have practical and economic advantages.Studies measuring the fibrin degradation product D-dimer using enzyme-linked immunoassays (EIA) in patients with veno-graphically proven DVT suggest that it should be possible to exclude this condition by the use of one of the rapid latex bead D-dimer tests.We have examined 190 patients with suspected DVT using both a latex and an EIA D-dimer assay. The latex D-dimer test used in this study was negative in 7 of the 36 proven cases of DVT. This sensitivity of only 80% is not sufficient to allow this type of assay, in its current form, to be used as an exclusion test for DVT. The same plasma samples were tested with an EIA assay. This information was used to mathematically model the effects of selecting a range of D-dimer discriminant cut off points for the diagnosis of DVT. These results indicate that 62% of suspected clinically significant DVT could have this diagnosis excluded, with a 98% sensitivity, if the rapid latex or equivalent D-dimer test could be reformulated to measure less than 185 ng/ml of D-dimer.

Is there a Need for Own Median Calculation in the Second Trimester Biochemical Markers Screening?

2017 ◽  
Vol 68 (5) ◽  
pp. 1070-1072
Author(s):  
Dan Navolan ◽  
Mirela Nicolov ◽  
Simona Vladareanu ◽  
Ioana Ciohat ◽  
Marius Craina ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Gestational Age ◽  
Biochemical Markers ◽  
Biochemical Marker ◽  
Second Trimester ◽  
Established Method ◽  
Crown Rump Length ◽  
The Difference ◽  
Fetal Aneuploidies ◽  
Singleton Pregnancies

Screening of fetal aneuploidies in early pregnancy is a well-established method in the materno-fetal medicine. The aim of our study was to analyze if the medians recommended by the manufacturers are adequate to perform an accurate screening or if there is a need for own laboratory medians calculation in second trimester biochemical marker screening.Sera were collected between 14 wp and 22 wp from 3374 singleton pregnancies. We analyzed three second trimester biochemical markers (AFP, hCG and free Estriol) concentration in all pregnant women and in a subgroup of pregnant women in which gestational age was determined based on crown-rump length. Our results showed that for all biochemical markers the difference between the manufacturer and the own calculated median was lower than 10% excepting the hCG value in the group of pregnant women in which the gestational age was determined on basis of crown-rump-length. Our results show it is recommended to replace the values of the median for hCG measurement with the own laboratory calculated medians. This does not seem to be necessary in the case of AFP and free Estriol measurement.

Clinical utility of Shabda and Sparsha Pareeksha in evaluation of Prakruta and Vaikruta Garbhavastha

2016 ◽  
Vol 1 (2) ◽  
Author(s):  
Priyanka T K ◽  
V.N. K. Usha ◽  
Sucheta Kumari M
Keyword(s):  
Clinical Study ◽  
Clinical Utility ◽  
Neonatal Outcome ◽  
Predictive Accuracy ◽  
Cost Effective ◽  
Well Being ◽  
Prospective Clinical Study ◽  
Clinical Tool ◽  
Accuracy Rate ◽  
Fetal Pathology

Garbha is a conglomeration of biological mass with different strata including consciousness, needs an innovative clinical tool to evaluate its well being, which proves safe, potent, cost-effective and noninvasive. The idea of taking up this study was to sensitively predict the Prakrutavastha or well being w.r.t Garbha-pushti and ongoing Fetal Pathology, Vaikrutavastha w.s.r Garbhavyapads for a sharp interference to get a possible best neonatal outcome. The objective of this study was to calculate the predictive accuracy of evaluation of Garbhaspandanam on external Shabda and Sparsha Pareeksha. A Prospective Clinical study of Garbhaspandanam (FHS and FM) with external Shabda and Sparsha stimulation on maternal abdomen, from 24th week onwards was conducted in a cohort of 30 Singleton Pregnant women at Dept. of Prasuti Tantra and Stri Roga, S.D.M.C.A. Hospital, Udupi. Among the 9 cases in abnormal category, 2 cases had gone for IUD and one case though placed in abnormal category had responded relatively well to Shabda and Sparsha Pareeksha which may be due to the proper antenatal care and intervention given along with the patient’s Vatakara Nidana Parivarjana. Predictive Accuracy Rate on Shabda and Sparsha Pareeksha showed, FHS 70%, FM 76.7%; FHS 73.3%, FM 66.7% respectively. Shabda and Sparshapareeksha can be utilized as the Garbha - chetana - dyodakalakshana and can be performed as a routine antenatal bedside procedure, which can fairly detect the Prakruta and Vaikrutavastha of Garbha w.r.t Pushti. However larger prospective studies are required.

scholarly journals Aptamer-Based Diagnostic Systems for the Rapid Screening of TB at the Point-of-Care

Diagnostics ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1352
Author(s):  
Darius Riziki Martin ◽  
Nicole Remaliah Sibuyi ◽  
Phumuzile Dube ◽  
Adewale Oluwaseun Fadaka ◽  
Ruben Cloete ◽  
...  
Keyword(s):  
Low Income ◽  
Point Of Care ◽  
Health Care Systems ◽  
Cost Effective ◽  
Rapid Screening ◽  
Low Income Countries ◽  
Sputum Smear ◽  
Diagnostic Systems ◽  
Molecular Tests ◽  
Rapid Tests

The transmission of Tuberculosis (TB) is very rapid and the burden it places on health care systems is felt globally. The effective management and prevention of this disease requires that it is detected early. Current TB diagnostic approaches, such as the culture, sputum smear, skin tuberculin, and molecular tests are time-consuming, and some are unaffordable for low-income countries. Rapid tests for disease biomarker detection are mostly based on immunological assays that use antibodies which are costly to produce, have low sensitivity and stability. Aptamers can replace antibodies in these diagnostic tests for the development of new rapid tests that are more cost effective; more stable at high temperatures and therefore have a better shelf life; do not have batch-to-batch variations, and thus more consistently bind to a specific target with similar or higher specificity and selectivity and are therefore more reliable. Advancements in TB research, in particular the application of proteomics to identify TB specific biomarkers, led to the identification of a number of biomarker proteins, that can be used to develop aptamer-based diagnostic assays able to screen individuals at the point-of-care (POC) more efficiently in resource-limited settings.

scholarly journals Possibility of Human Gender Recognition Using Raman Spectra of Teeth

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3983
Author(s):  
Ozren Gamulin ◽  
Marko Škrabić ◽  
Kristina Serec ◽  
Matej Par ◽  
Marija Baković ◽  
...  
Keyword(s):  
Raman Spectra ◽  
Principal Component ◽  
Support Vector ◽  
Gender Recognition ◽  
Proof Of Concept ◽  
Male And Female ◽  
Tooth Type ◽  
Tooth Apex ◽  
The Difference

Gender determination of the human remains can be very challenging, especially in the case of incomplete ones. Herein, we report a proof-of-concept experiment where the possibility of gender recognition using Raman spectroscopy of teeth is investigated. Raman spectra were recorded from male and female molars and premolars on two distinct sites, tooth apex and anatomical neck. Recorded spectra were sorted into suitable datasets and initially analyzed with principal component analysis, which showed a distinction between spectra of male and female teeth. Then, reduced datasets with scores of the first 20 principal components were formed and two classification algorithms, support vector machine and artificial neural networks, were applied to form classification models for gender recognition. The obtained results showed that gender recognition with Raman spectra of teeth is possible but strongly depends both on the tooth type and spectrum recording site. The difference in classification accuracy between different tooth types and recording sites are discussed in terms of the molecular structure difference caused by the influence of masticatory loading or gender-dependent life events.

How the United Kingdom Controls Pharmaceutical Prices and Spending: Learning From Its Experience

2021 ◽  
pp. 002073142199709
Author(s):  
Marc A. Rodwin
Keyword(s):  
United Kingdom ◽  
Cost Effective ◽  
Market Prices ◽  
The United Kingdom ◽  
Generic Market ◽  
Pharmaceutical Spending ◽  
The Difference ◽  
The Government ◽  
Pharmaceutical Prices ◽  
Limit Access

To control costs and improve access, nations can adopt strategies employed in the United Kingdom to control pharmaceutical prices and spending. Current policy evolved from a system created in 1957 that allowed manufacturers to set launch prices, capped manufacturers’ rates of return, and later cut list prices. These policies did not effectively control spending and had limited effects on purchase prices. The United Kingdom currently controls pharmaceutical spending in 4 ways. (a) Since 1999, it has typically paid no more than is cost-effective. (b) Since 2017, for medicines that will have a significant budget impact, National Health Service England seeks discounts from cost-effective prices or seeks to limit access for 2 years to patients with the greatest need. (c) Since 2014, statutes and a voluntary scheme have required branded manufacturers to pay the government rebates to recoup the difference between the global pharmaceutical budget and actual spending. (d) For hospitals, generics and some patented drugs are procured through competitive bidding; community pharmacies are reimbursed through a system that provides an incentive to beat average generic market prices. These policies controlled the growth of spending, with the largest effects following budget controls in 2014. Changes since 2008 have reduced savings, first by paying more than is cost-effective for cancer drugs and then by applying higher cost-effectiveness thresholds for some drugs used to treat cancer and certain other drugs.

scholarly journals NESTROFT—A Cost-Effective Mass Screening Tool for the Detection of β-Thalassemia Carrier Status in Anemic Pregnant Women: A Step Toward Reducing the National Disease Burden

2021 ◽  
Author(s):  
Manasi Gosavi ◽  
Ramesh Chavan ◽  
M. B. Bellad
Keyword(s):  
Pregnant Women ◽  
Effective Mass ◽  
Mass Screening ◽  
Predictive Value ◽  
Screening Tool ◽  
Hematological Parameters ◽  
False Negative ◽  
Cost Effective ◽  
Mean Corpuscular Hemoglobin ◽  
Carrier Status

Abstract Introduction β-Thalassemias are inherited hemoglobinopathies commonly encountered in practice. With chances of a promising cure being rare, the prevention of births with this disorder should assume priority, especially in low-resource countries. This can be achieved by the implementation of a mass screening program that is reliable and, at the same time, cost-effective. Objectives This study focuses on the utility of Naked Eye Single Tube Red Cell Osmotic Fragility Test (NESTROFT) as a mass screening tool to detect thalassemia carriers. Hematological parameters that may predict carrier status were also evaluated. Materials and Methods Hemoglobin estimation was performed on all consented pregnant women. If the patient was found to have hemoglobin < 11 g/dL, the blood sample was subjected to other routine hematological tests along with peripheral smear examination. NESTROFT was performed using 0.36% saline solution. Confirmation was done using high-performance liquid chromatography (HPLC). Statistical Analysis Data obtained were tabulated using version 21 of the Statistical Package for Social Sciences. Means, standard deviations, and percentages were used to describe the sample. Chi-square test and Students’ “t” test were used to identify differences between the groups. Results Of 441 pregnant women enrolled, 206 were found to be anemic. Nineteen (9.2%) of the anemic pregnant women were detected to be carriers of hemoglobinopathies. Among the hematological parameters, mean red blood cell count and reticulocyte count were higher, while mean corpuscular hemoglobin concentration was lower in carriers. Also, carriers were more likely to present with microcytic hypochromic anemia. NESTROFT showed a sensitivity of 84.21%, specificity of 96.25%, a positive predictive value of 69.56%, and a negative predictive value of 98.36%. A false-positive result was seen in 3.74% of the tests, while a false negative result was seen in 15.78% of the tests. Conclusions NESTROFT (0.36%) can be used as a simple and cost-effective mass screening tool for the detection of carrier status. This should be followed by confirmation using HPLC or hemoglobin electrophoresis.

scholarly journals The bowel and beyond: extracolonic findings from CT colonography

2021 ◽  
Author(s):  
Gerard Lambe ◽  
Peter Hughes ◽  
Louise Rice ◽  
Caoimhe McDonnell ◽  
Mark Murphy ◽  
...  
Keyword(s):  
Ct Colonography ◽  
Surgical Intervention ◽  
Potential Significance ◽  
Age And Gender ◽  
Abdominal Aortic ◽  
Life Threatening ◽  
Extracolonic Findings ◽  
The Difference ◽  
Clinically Significant ◽  
And Gender

AbstractCT colonography has emerged as the investigation of choice for suspected colorectal cancer in patients when a colonoscopy in incomplete, is deemed high risk or is declined because of patient preference. Unlike a traditional colonoscopy, it frequently reveals extracolonic as well as colonic findings. Our study aimed to determine the prevalence, characteristics and potential significance of extracolonic findings on CT colonography within our own institution. A retrospective review was performed of 502 patients who underwent CT colonography in our institution between January 1, 2010 and January 4, 2015. Of 502 patients, 60.63% had at least one extracolonic finding. This was close to other similar-sized studies (Kumar et al. Radiology 236(2):519–526, 2005). However, our rate of E4 findings was significantly higher than that reported in larger studies at 5.3%(Pooler et al. AJR 206:313–318, 2016). The difference may be explained by our combination of symptomatic/screening patients or by the age and gender distribution of our population. Our study lends support to the hypothesis that CT colonography may be particularly useful in identifying clinically significant extracolonic findings in symptomatic patients. CT colonography may allow early identification of extracolonic malignancies and life-threatening conditions such as an abdominal aortic aneurysm at a preclinical stage when they are amenable to medical or surgical intervention. However, extracolonic findings may also result in unnecessary investigations for subsequently benign findings.

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