Traditional Screening Tests Research Articles

Prostate cancer screening: Is it time for a new approach? A review article.

Prostate cancer screening has presented a challenge to clinicians. Although the implementation of screening tests such as prostate-specific antigen (PSA) and digital rectal exam (DRE) has had a significant impact on prostate-cancer-specific mortality, these traditional screening tests have a relatively poor positive predictive value of clinically significant prostate cancer (CSPC), leading to unnecessary biopsies and treatment with a host of potential complications. Fortunately, much research has been done to optimize prostate cancer screening. This includes the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, which underwent a secondary analysis to identify an association between PSA level and CSPC, and the IP1-PROSTAGRAM Tri.

Design and optimization of refractive index biosensor for MDA-MB-231 and MCF-7 breast cancer biomarker detection

Breast cancer is the leading malignancy in women and the 2nd widespread cancer globally. Earlier identification of breast cancer can improve treatment outcomes and prevent metastasis beyond the breast. Traditional screening tests are not sensitive enough for early diagnosis and have extended detection periods. Recent studies have explored diversified Breast cancer biosensor techniques, including optical, electrical, electrochemical, and mechanical biosensors. This paper nominates a circlet with a large plus sign refraction indices biosensor for the evaluation of two distinct breast cancer cells namely, MDA-MB-231 and MCF-7. The supreme sensitivity has been viewed as 1714.28 nm/RIU for the MDA-MB-231 and 1714.28 nm/RIU for the MCF-7. The supreme quality factor (QF) value for UC1(usual cell of MDA-MB-231) is 10.52, for CC1(cancer cell of MDA-MB-231) is 11.94, for UC2 (usual cell of MCF-7) is 10.64, and for CC2 (cancer cell of MCF-7) is 12.09. The minimal detection value (DL) for UC1 is 0.1573, CC1 is 0.1360, UC2 is 0.1554, and CC2 is 0.1341. This nominated sensor has the potential to sense breast tumor biomarkers.

Advances in Malaria Testing: Screening and Identification of Carriers from Saliva

Plasmodium is a parasite that can infect red blood cells and cause flu-like symptoms with malaria infection. Traditional diagnostic methods do not include counting or testing for gametocytes, which can reservoir in the liver for long periods of time and recirculate. These carriers may have no symptoms, but they can transmit infection to others or to mosquitos. Currently, no diagnostic tests have been approved to detect Plasmodium gametocytes in either symptomatic or asymptomatic whole blood samples. Therefore, we developed real-time PCR assays to detect active and carrier states of malaria. The first is a traditional screening test that can detect any of the five Plasmodium species that cause malaria infection. The second is a companion test to differentiate and quantitate Plasmodium falciparum and P. vivax gametocytes in samples of whole blood from patients who may be asymptomatic and present negative results from screening tests. The screening test showed amplification of P. falciparum, P. vivax, P. ovale, P. malariae, and P. knowlesi in saliva with an overall detection limit of 565 copies/μL. The gametocyte test showed no cross-reactivity between P. falciparum and P. vivax with a limit of detection of RNA at 1000 copies/μL.

A Pilot Fuzzy System with Virtual Reality for Mild Cognitive Impairment (MCI) Assessment.

Mild cognitive impairment (MCI) is when brain function declines. MCI is the gray area transitioning from normal aging to the AD stage. Currently, the majority of early MCI diagnoses are processed through comprehensive neuropsychological tests. These tests may take the form of interviews, paper-and-pencil tests, or computer-based tests. There may be resistance from the subject if he/she has to undergo many screening tests simultaneously for multiple evaluation information, resulting in execution difficulty. The objectives of this study are to use 3D virtual reality to create an entertaining test scenario integrating the Mini-Cog, SPMSQ, MMSE, SLUMS, CDR, and CASI for middle-aged to older adults, furthermore, to employ fuzzy logic control (FLC) technology to develop a "MCI assessment system" for obtaining some pilot information for MCI assessment. There were 24 middle-aged to older adults aged from 50 to 65 years who participated in the evaluation experiment. The results showed that the MCI assessment system developed in this study is highly correlated with the traditional screening tests, including the Mini-Cog, SPMSQ, MMSE, SLUMS, and CASI. The assessment system can provide an integrated reference score for clinic workers in making judgments. In addition, the distribution of the System Usability Scale (SUS) evaluation scores for the MCI assessment system revealed that 87.5% were grade C (good to use) or above and 29.2% were grade B (extremely good to use) or above. The assessment system received positive feedback from the subjects.

Translation, Adaptation and Validation of the Five-Word Test (Test Delle 5 Parole, T5P) in an Italian Sample: A Rapid Screening for the Assessment of Memory Impairment.

Discriminating between Alzheimer’s disease (AD), mild cognitive impairment (MCI) and functional memory disorders (FMD) can sometimes be difficult because amnesic syndrome can be confused with memory dysfunction due to aging and/or depression. This work aims to translate, adapt and validate the five-word test (FWT) in an Italian sample (Test delle 5 Parole, T5P). FWT is a screening memory task specifically built to discriminate the hippocampal memory deficit—typical of AD and amnesic MCI—from those related to functional disorders. We involved a large number of subjects (n = 264): 60 with AD, 80 with MCI, 46 with FMD, and 78 healthy controls (CTRL). Two traditional screening tests and the T5P were administered to all participants. Results showed an excellent convergent validity of the T5P (p < 0.05). Moreover, the T5P appeared as an effective test able to discriminate between the four conditions, except for FMD and CTRL. In particular, a total score of ≤9 allowed for accurately discriminating subjects with AD + MCI compared to participants with FMD + CTRL with high sensitivity (83.87%) and specificity (76.43%). Overall, the T5P is a simple, rapid and sensible test of the hippocampal memory that is recommended in clinical practice to screen persons with subjective/probable amnesic difficulties and to discriminate between patients with AD or MCI and CTRL.

Ultrasound Guided Measurement of Anterior Neck Tissue for the Prediction of Difficult Airway: A Prospective Observational Study.

To determine that ultrasound (US) measurements of anterior neck soft tissue thickness at hyoid bone, thyrohyoid membrane, and anterior commissure levels can be used to predict difficult laryngoscopy. The present study included 100 patients of age group 18-60 years undergoing elective surgery under general anaesthesia. It was a prospective observational study which included patients with ASA physical status I and II. Excluded patients were with facial and neck deformities, neck trauma, or those undergoing surgery of the larynx, epiglottis and pharynx. Comparison analysis was performed using t-test for continuous variables and chi-square or Fisher exact test for non-continuous variables. Correlation analysis performed using Pearson test. There were 39 out of 100 patients categorised as difficult laryngoscopy. Thickness at hyoid bone (DSHB), thyrohyoid membrane (DSEM) and anterior commissure (DSAC), MMS (modified Mallampati score), and BMI (body mass index) were greater in the difficult laryngoscopy group (p < 0.001). TMD (thyromental distance) was less in the difficult laryngoscopy group (p < 0.001). There was a strong positive correlation between DSEM and DSAC (r = 0.784). Moderate positive correlation was between DSEM and DSHB (r = 0.559), DSEM and MMS(r=0.437). The area under curve (AUC) of DSHB, DSEM, DSAC, TMD and MMS is >0.7. The optimal cut-off values for DSEM, DSHB, DSAC and TMD were 1.34 cm, 0.98 cm, 1.68 cm and 6.59 cm, respectively, in predicting difficult airway. Ultrasound measurement of soft tissue thickness at hyoid bone, thyrohyoid membrane, and anterior commissure of vocal cord are good independent predictors for difficult laryngoscopy. When combined with traditional screening tests it improves the ability to predict difficult laryngoscopy.

The Testamentary Capacity Assessment Tool (TCAT): validation and normative data.

There is an increasing need for objective and standardized assessment of testamentary capacity (TC) in dementia. A new instrument, the Testamentary Capacity Assessment Tool (TCAT), has been recently developed; however, the lack of validation and normative data regarding this cognitive screening test has limited its adoption in forensic and clinical settings. The present study collects normative data for the TCAT and assesses its convergent validity with standardized cognitive tests and the capacity to define what a 'testament' is. The study involved 323 neurologically healthy adults (123 males, 200 females) of different ages (31-93years) and different educational levels (4-25years). The TCAT was administered along with the Beck Depression Inventory-II (BDI-II), the Montreal Cognitive Assessment (MoCA), theMini-Mental State Examination (MMSE), theFrontal Assessment Battery (FAB) and the Testament Definition Scale (TDS). Multiple regression analyses revealed a significant effect for gender, age and education on TCAT scores. Correlation analyses showed significant associations between the TCAT and the MMSE, MoCA, FAB and BDI-II. A positive correlation between the TCAT and TDS was also found, proving good convergent validity of the TCAT with respect to TC. Finally, cut-off scores and Equivalent Scores (ES) were computed. The present study provides normative data for using the TCAT as anadjuvant cognitive screening test in the neuropsychological evaluation of TC. Our findings shall be of interest for theadoption of the TCAT alsoin clinical practice, since it evaluates cognitive functions (e.g., autobiographic memory, Theory of Mind) not measured by traditional screening tests.

Contingent prenatal screening for frequent aneuploidies with cell-free fetal DNA analysis

ObjectiveTo analyze the results of contingent screening for common aneuploidies at our center from June 2017 to June 2019. Materials and methodsTraditional screening tests were performed using a combination of biochemical markers and ultrasound measurements in the first and second trimesters to assess the risk of trisomies 21 (T21), 18 (T18) and 13 (T13). Cell-free DNA (cf-DNA) testing was offered (Harmony test) to pregnant women at high risk (>1/280 for T21 and > 1/150 for T13 and T18) and a normal early morphology scan. In positive cases, prenatal sampling was strongly recommended to confirm the results by gold standard methods (QF-PCR and karyotyping). Newborns' phenotypes were corroborated after birth in all cases. ResultsIn this prospective study, 8153 pregnant women were enrolled, resulting in 390 at high risk according to traditional screening tests. cfDNA testing was offered to 383 women. Traditional screening tests showed a false negative rate of 9.68% for T21. Traditional test sensitivity for T21 was 90.3%, for a false positive rate of 4.17% and a positive predictive value of 7.6%. The positive and negative predictive value for cfDNA testing was 100%. The approach used avoided invasive procedures in 91.3% of women at high risk. The prevalence of chromosomal abnormalities in the population analyzed was 1 in 164, and 1 in 210 for T21. ConclusionsOur results show that offering cf-DNA testing to women at high risk in traditional tests (including those with risks >1 in 50) significantly reduces false positives and, therefore, the number of invasive tests. Extending the use of cf-DNA testing to intermediate risk categories may be cost effective.

Feasibility of a dried blood spot strategy for serological screening and surveillance to monitor elimination of Human African Trypanosomiasis in the Democratic Republic of the Congo.

In recent years, the number of reported Human African Trypanosomiasis (HAT) cases caused by Trypanosoma brucei (T.b.) gambiense has been markedly declining, and the goal of ‘elimination as a public health problem’ is within reach. For the next stage, i.e. interruption of HAT transmission by 2030, intensive screening and surveillance will need to be maintained, but with tools and strategies more efficiently tailored to the very low prevalence. We assessed the sequential use of ELISA and Immune Trypanolysis (ITL) on dried blood spot (DBS) samples as an alternative to the traditional HAT field testing and confirmation approach. A cross-sectional study was conducted in HAT endemic and previously endemic zones in Kongo Central province, and a non-endemic zone in Haut Katanga province in the Democratic Republic of the Congo (DRC). Door-to-door visits were performed to collect dried blood spot (DBS) samples on filter paper. ELISA/T.b. gambiense was conducted followed by ITL for those testing positive by ELISA and in a subset of ELISA negatives. In total, 11,642 participants were enrolled. Of these, 11,535 DBS were collected and stored in appropriate condition for ELISA testing. Ninety-seven DBS samples tested positive on ELISA. In the endemic zone, ELISA positivity was 1.34% (95%CI: 1.04–1.64). In the previously endemic zone and non-endemic zone, ELISA positivity was 0.34% (95% CI: 0.13–0.55) and 0.37% (95% CI: 0.15–0.60) respectively. Among the ELISA positives, only two samples had a positive ITL result, both from the endemic zone. One of those was from a former HAT patient treated in 2008 and the other from an individual who unfortunately had deceased prior to the follow-up visit. Our study showed that a surveillance strategy, based on DBS samples and centralized testing with retracing of patients if needed, is feasible in DRC. ELISA seems well suited as initial test with a similar positivity rate as traditional screening tests, but ITL remains complex. Alternatives for the latter, also analyzable on DBS, should be further explored.

Predicting Alzheimer’s Disease from Spoken and Written Language Using Fusion-Based Stacked Generalization

The importance of automating the diagnosis of Alzheimer disease (AD) towards facilitating its early prediction has long been emphasized, hampered in part by lack of empirical support. Given the evident association of AD with age and the increasing aging population owing to the general well-being of individuals, there have been unprecedented estimated economic complications. Consequently, many recent studies have attempted to employ the language deficiency caused by cognitive decline in automating the diagnostic task via training machine learning (ML) algorithms with linguistic patterns and deficits. In this study, we aim to develop multiple heterogeneous stacked fusion models that harness the advantages of several base learning algorithms to improve the overall generalizability and robustness of AD diagnostic ML models, where we parallelly utilized two different written and spoken-based datasets to train our stacked fusion models. Further, we examined the effect of linking these two datasets to develop a hybrid stacked fusion model that can predict AD from written and spoken languages. Our feature spaces involved two widely used linguistic patterns: lexicosyntactics and character n-gram spaces. We firstly investigated lexicosyntactics of AD alongside healthy controls (HC), where we explored a few new lexicosyntactic features, then optimized the lexicosyntactic feature space by proposing a correlation feature selection technique that eliminates features based on their feature-feature inter-correlations and feature-target correlations according to a certain threshold. Our stacked fusion models establish benchmarks on both datasets with AUC of 98.1% and 99.47% for the spoken and written-based datasets, respectively, and corresponding accuracy and F1 score values around 95% on spoken-based dataset and around 97% on the written-based dataset. Likewise, the hybrid stacked fusion model on linked data presents an optimal performance with 99.2% AUC as well as accuracy and F1 score falling around 97%. In view of the achieved performance and enhanced generalizability of such fusion models over single classifiers, this study suggests replacing the initial traditional screening test with such models that can be embedded into an online format for a fully automated remote diagnosis.

Enhancing Quality of Experience in Malay Language Dyslexia Screening Test

Identifying dyslexia among Malaysian citizens, especially children nowadays is a prominent issue. The usual practice of dyslexia screening tests in the Malaysian school system is by teacher's observation and intervention. However, this is usually time-consuming, less accurate and lacking additional supporting tools. Moreover, dyslexic children enrolling in a normal education system will encounter many problems for the teacher and the children themselves. A Malay language mobile-based application for a dyslexia screening test named Kiddo Disleksia has been developed to solve this issue. However, it has not been tested in terms of Quality of Experience (QoE) as well as usability. Therefore, this research aims to test the QoE level of Kiddo Disleksia and also to compare the traditional dyslexia screening test with Kiddo Disleksia in terms of usability. To test the QoE, several special education teachers are required to rate Kiddo Disleksia using Mean Opinion Score (MOS). Ten children were tested using Kiddo Disleksia and 80% of them recognized as dyslexic. This result also similar with the traditional paper-based screening test. Therefore, the Kiddo Disleksia application is considered reliable for dyslexia screening tests for children. For QoE, the results show that the mean values of MOS are 3.9 and above. Therefore, the quality of experience during dyslexia screening tests can be enhanced using Kiddo Disleksia.

Screening for cancer: the economic, medical, and psychosocial issues.

Despite significant improvements in mortality over the past 20 years, cancer remains the second leading cause of death in the United States. One reason for the improvement in mortality is screening for several common cancers in people at average risk for breast, cervical, colorectal, and prostate cancers, and screening for lung cancer in those with a 20-plus pack-year history. Such screening may result in earlier diagnosis when the cancer is most likely to respond to treatment. However, there are no population-based screening recommendations for the majority of cancers in average-risk patients, most of which are not diagnosed until the later stages. One question is whether earlier diagnosis could not only reduce mortality rates but also reduce medical costs. Screening comes with several potential risks, including false positives and overdiagnosis, both of which can affect patients' mental health, increase morbidity and mortality, and lead to excess spending. Additionally, certain cancers can evade traditional screening tests and lead to false-negative results, which delays cancer detection, treatment, and may affect treatment efficacy. The advent of liquid biopsy tests that could screen for dozens of cancers holds promise for identifying more cancers early. However, the cost, the potential for overdiagnosis and false positives, and a lack of evidence demonstrating clinical utility or an improvement in health outcomes call into question their potential use for widespread screening. Government and managed care organizations will need to consider the risks and benefits of these assays in determining coverage.

Use of procalcitonin and C-reactive protein in the diagnosis of bacterial infection in infants with severe bronchiolitis.

The objective was to evaluate the use of procalcitonin (PCT) and C-reactive protein (CRP) for the diagnosis of bacterial infection in bronchiolitis patients. A prospective, single-centre, descriptive, and comparative observational study was carried out on patients with severe bronchiolitis admitted to the paediatric intensive care unit (PICU), from January 2011 to July 2017. Two cohorts were compared: patients with invasive bacterial infection (IBI) and patients with no bacterial infection (NBI). We included 675 patients, 399 of whom were males (59.1%), with median age of 47 days (IQR 25-100.3). Of them, 181 patients were diagnosed with IBI (26.8%). Seventy-two had sepsis (10.7%), 106 had pneumonia (15.7%), and 41 had a urinary tract infection (6.1%). PCT and CRP values were significantly higher in patients with IBI. ROC curves compared the ability of PCT and CRP to diagnose IBI at admission, 24 h, and 48 h. PCT showed a better AUC for diagnosing IBI, with statistically significant differences at all time points (p < 0.001). The best PCT cut-off for IBI diagnosis at admission was 1.4 ng/mL, with a sensitivity of 69% (95% CI 58.4-74.9) and a specificity of 91% (95% CI 88.1-92.5). Procalcitonin showed a better AUC for diagnosing both sepsis and pneumonia, which makes it an excellent predictor.Conclusion: We present PCT as a novel test in comparison with the traditional CRP screening test to discern which bronchiolitis patients have IBI. We highlight the importance of PCT for the diagnosis of pneumonia and sepsis, as it proved to be more sensitive and specific than CRP, with statistically significant differences. What is Known: • Bronchiolitis should be treated with antibiotics only when a bacterial infection is present. • The rate of antibiotic prescription in severe bronchiolitis is extremely high, so diagnostic tools are needed. What is New: • PCT is a good biomarker to discern which bronchiolitis patients have IBI, specially for pneumonia and sepsis diagnoses. It is more sensitive and specific than CRP, with statistically significant differences. • Implementation of PCT cut-off values may prevent unnecessary antibiotic use.

A Retrospective Analysis Of Different Contingent Screening Models For Fetal Down Syndrome In Southwestern China

To discuss combinations of traditional screening and noninvasive prenatal screening (NIPS) and to compare which traditional screening is the most suitable first-line screening approach to NIPS, pregnant women were recruited in this retrospective observational study. Pregnant women underwent one of four traditional screening tests. The 9 contingent models were combined by high risk cut-offs of 1:50, 1:100, 1:270 and intermediate risk cut-offs of 1:1000, 1:1500, 1:2000. We analyzed cost and performance of various screening models with contingent screening of different risk cut-offs. Compared with other screening tests, combined first-trimester screening (CFTS) had the lowest proportion of high risk (≥1:270) with the highest detection rate (DR) (78.79%) and the lowest proportion of intermediate risk (1:271~1:1000). When intermediate risk was 1:51 ~1:1500, CFTS as first-line screening had the lowest cost with DR of 93.94%. Other screening tests as the first-line screening with intermediate risk of 1:51~1:1000 had the lowest cost, there DR were 90.91%, 84.62%, 91.67%, respectively. Our study demonstrated if only one traditional screening was allowed to screen pregnant women, CFTS was recommended as the first choice. According to local health and economic conditions, adopting appropriate traditional screening with suitable cut-offs as first-line screening will contributed to a cost-effective screening model.

High resolution metagenomic characterization of complex infectomes in paediatric acute respiratory infection

The diversity of pathogens associated with acute respiratory infection (ARI) makes diagnosis challenging. Traditional pathogen screening tests have a limited detection range and provide little additional information. We used total RNA sequencing (“meta-transcriptomics”) to reveal the full spectrum of microbes associated with paediatric ARI. Throat swabs were collected from 48 paediatric ARI patients and 7 healthy controls. Samples were subjected to meta-transcriptomics to determine the presence and abundance of viral, bacterial, and eukaryotic pathogens, and to reveal mixed infections, pathogen genotypes/subtypes, evolutionary origins, epidemiological history, and antimicrobial resistance. We identified 11 RNA viruses, 4 DNA viruses, 4 species of bacteria, and 1 fungus. While most are known to cause ARIs, others, such as echovirus 6, are rarely associated with respiratory disease. Co-infection of viruses and bacteria and of multiple viruses were commonplace (9/48), with one patient harboring 5 different pathogens, and genome sequence data revealed large intra-species diversity. Expressed resistance against eight classes of antibiotic was detected, with those for MLS, Bla, Tet, Phe at relatively high abundance. In summary, we used a simple total RNA sequencing approach to reveal the complex polymicrobial infectome in ARI. This provided comprehensive and clinically informative information relevant to understanding respiratory disease.

Clinical article: screening for trisomy 13 using traditional combined screening versus an ultrasound-based protocol

Aims To compare the screening capability of ultrasonography in detecting trisomy 13 (T13) using a multiparameter sonographic protocol (NT+) with a classical combined screening test (CST) protocol. Methods The project was a prospective, multicenter study based on a nonselected mixed-risk population of women referred for a first-trimester screening examination. Each subject was offered a choice between either the gold standard, traditional combined screening test (CSG arm) or the ultrasound-based screening protocol (USG arm). General and MA-based screening performances were checked. Results The study population comprised 20,887 pregnancies: 12,933 in the CSG arm, including 27 cases of T13, and 7954 in the USG arm, including 30 cases of T13. The DR for T13 was higher in the CSG arm than in the USG arm for all tested cutoff points: 1/50 (88.5 versus 63.3%, respectively), 1/100 (88.5 versus 70%, respectively) and 1/300 (92.3 versus 83.3%, respectively). Using the ROC curves for fixed FPRs of 3 and 5%, the T13 detection rate in our study reached 90 and 93%, respectively, in the USG arm and 92 and 96%, respectively, in the CSG arm. MA influenced the T13 screening performance in the USG arm and reduced the DR in patients <31 years. Such influence was not detected in the CSG arm. Conclusions Classic CST was more effective in detecting T13 than the ultrasound-only approach. However, the recommended cutoff of 1/50 showed unsatisfactory results for both traditional CST and the multiparameter sonographic test we proposed.

Late-Night Salivary Cortisol: Cut-Off Definition and Diagnostic Accuracy for Cushing's Syndrome in a Portuguese Population.

Diagnosis of Cushing's syndrome remains a challenge in clinical endocrinology. Even though late-night salivary cortisolis used as screening tool, individualized cut-off levels for each population must be defined. Three groups of subjects were studied: normal subjects, suspected and proven Cushing's syndrome. Salivarycortisol was measured using an automated electrochemiluminescence assay. The functional sensitivity of the assay is 0.018 μg/dL. Thediagnostic cut-off level was defined by Receiver Operating Characteristic curve and Youden's J index. We studied 127 subjects: 57 healthy volunteers, 39 patients with suspected and 31 with proven Cushing's syndrome. 2.5th- 97.5th percentile of the late-night salivary cortisol concentrations in normal subjects was 0.054 to 0.1827 μg/dL. Receiver OperatingCharacteristic curve analysis showed an area under the curve of 0.9881 (p < 0.0001). A cut-off point of 0.1 μg/dL provided a sensitivityof 96.77% (95% CI 83.3 - 99.92%) and specificity of 91.23% (95% CI 80.7 - 97.09%). There was a significant correlation between latenight salivary cortisol and late-night serum cortisol (R = 0.6977; p < 0.0001) and urinary free cortisol (R = 0.5404; p = 0.0025) in provenCushing's syndrome group. The mean ± SD late-night salivary cortisol concentration in patients with proven Cushing's syndrome (0.6798 ± 0.52 μg/dL) was significantly higher (p < 0.0001). In our population, the late-night salivary cortisol cut-off was 0.1 μg/dL with high sensitivity andspecificity. Late-night salivary cortisol has excellent diagnostic accuracy, making it a highly reliable, noninvasive, screening tool foroutpatient assessment. Given its convenience and diagnostic accuracy, late-night salivary cortisol may be added to other traditionalscreening tests on hypercortisolism.

700: Diagnostic accuracy of Abbott ARCHITECT Syphilis TP chemiluminescent immunoassay in pregnant women

An alternative to a traditional syphilis diagnostic algorithm, the reverse sequence algorithm (treponemal antibody with reflex to rapid plasma reagin (RPR)) utilizes a screening test such as Abbott ARCHITECT Syphilis TP chemiluminescent immunoassay (CIA) to provide objective, rather than subjective, results. We evaluated the diagnostic accuracy of the CIA screen in pregnant women compared to the traditional RPR prior to clinical implementation of the reverse algorithm at our hospital. Prospectively collected blood samples from routine prenatal RPR tests were collected and frozen. Samples were batch-tested with treponemal-specific CIA (index test). Women with reactive (positive) RPR had particle agglutination assay (TPPA, gold standard) available for analysis; for RPR-/CIA+ samples, TPPA was performed. We calculated sensitivity, specificity, predictive value, and false positive rate of the CIA test in pregnant women and evaluated perinatal outcomes of women with reactive CIA. Of 1,605 specimens, 35(2.1%) were RPR+, including 24(69%) CIA+/TPPA+ and 11(31%) CIA-/TPPA- (false positive RPR) (Figure 1). Of 1,570 RPR- specimens, 14(0.9%) were CIA+, including 13(93%) confirmed TPPA+, and 1(7%) TPPA- (false positive CIA). Diagnostic performance of the CIA (with 95% CI) was: sensitivity 100%(90.5-100%), specificity 99.9%(99.6 -100%), positive predictive value 97.4% (86.2-99.9%), and false positive rate 0.06%(0.002-0.4%)(Table 1). Among 37 CIA+/TPPA+ women, 11(30%) had previously treated syphilis, 19(51%) had active infection, and 7(19%) had RPR- status which did not require treatment or investigation by the local health department. There was no difference in age, parity, or race/ethnicity among women with RPR+/CIA+/TPPA+ versus RPR-/CIA+/TPPA+ results. One stillbirth occurred in a woman with early, active RPR+/CIA+/TPPA+ syphilis identified at delivery; no adverse perinatal outcomes occurred among women with RPR-/CIA+/TPPA+ results. Compared with the traditional RPR screening test, the treponemal-specific CIA accurately diagnoses current or past syphilis in pregnancy. While women with RPR+/CIA+/TPPA+ and RPR-/CIA+/TPPA+ results had similar demographic characteristics, the clinical significance of RPR-nonreactive status in pregnancy is unclear: adverse perinatal outcomes were limited to women with untreated, RPR+/CIA+/TPPA+ results in our study.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Structurating Expanded Genetic Carrier Screening: A Longitudinal Analysis of Online News Coverage

Expanded carrier screening (ECS) is a genetic test that is designed to assess the risk of a healthy person passing down a genetic disorder, such as spinal muscular atrophy, to future children. ECS screens for up to several hundred disorders in one test, expanding on traditional carrier screening tests that target one or a few genetic disorders. However, little is known about how this health technology is being presented to the public in media coverage. Accordingly, this study is a qualitative content analysis of online news and information of ECS over a 6-year period, beginning in 2010 when the technology was publicly available. Results indicate that major coverage themes were consistent across the years included, although content within those themes changed over time. Using structuration theory to guide analysis, results reveal that online news and information from 2010 to 2015 structurated ECS as a health technology innovation, an opportunity for business and investment, and a tool for family planning. Results are discussed in terms of implications for future research, for health journalism practice, and for clinical interactions.

Nanoscale flow cytometry of patient plasma for the detection of prostate cancer-associated extracellular vesicles

Introduction Prostate cancer is the predominant cancer in men, affecting one in seven men during their lifetime. Current tests for prostate cancer include the digital rectal exam and the prostate-specific antigen (PSA) test. Extracellular vesicles (EVs) are submicron particles that participate in intercellular cross-talk by releasing cell mediators such as microRNA, carbohydrates and proteins. While they are known to express the broad tetraspanin family of proteins, i.e. CD9/CD63, prostate cancer-derived EVs have also been found to express PSA and six transmembrane epithelial antigen of the prostate (STEAP1). Traditionally, scientists have purified these EVs through ultracentrifugation. Here we propose a tandem purification of patient plasma, followed by nanoscale flow cytometry (A50+) as a novel method to detect tumour-derived EVs. Materials and Methods Plasma was obtained from healthy volunteers, patients with benign prostatic hyperplasia (BPH), and patients with metastatic prostate cancer. CD9, CD63, PSA and STEAP1 were used as primary antibodies for the purification of EVs from neat plasma. To perform the purification in tandem, Protein G immunoprecipitation using CD9 and PSA was carried out first, followed by immunoaffinity purification with biotinylated CD63 and STEAP1. First and second elutions were collected for the enumeration of dual positive events by A50+. Initial histogram overlays and bivariate plots of neat and purified plasma were computed, then exported as comma-separated values for mathematical modelling by MATLAB. Results Strong dual positive EV populations from patient plasma were optimised, demonstrating that the method enriches tumour-derived EVs from neat samples of patient plasma. This was observed for HVs, patients with benign prostatic hyperplasia, and prostate cancer patients with Gleason 4+4. Enrichment in these purified samples was measured by A50+ and demonstrated by overlaying purified and non-purified histoplots by MATLAB. Additional results show that PSA and STEAP1 can be adapted to detect single or dual positive populations of tumour-associated EVs in prostate cancer patients. Discussions and Conclusions This study suggests that tandem purification of tumour-associated EVs and A50+ analysis from plasma of prostate cancer patients can lead to earlier diagnosis and risk stratification, compared to traditional screening tests and aspiration cytology. Future studies will be directed toward optimizing this detection method for markers of other cancer types to achieve better outcomes in cancer detection and prognosis.